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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. D-dimer) are more important determinants of recurrence. A case-control study found that testing individuals with a first VTE for thrombophilia did not reduce the incidence of recurrence . There are no randomized or controlled trials assessing the effect of thrombophilia testing on VTE recurrence risk .Studies that support an association of 20210G>A heterozygosity and increased risk for recurrent VTE in adults:In a prospective long-term follow-up study of persons who stopped anticoagulation after treatment for a first VTE, a thrombophilic defect including 20210G>A was associated with a twofold increased recurrence risk .A meta-analysis and a systematic review both concluded that 20210G>A heterozygosity is associated with a modest but statistically significant increased risk for recurrent VTE after a first event (OR = 1.72, OR=1.74, respectively) .Studies that do not support an association of 20210G>A heterozygosity and increased risk for | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. after treatment for a first VTE, a thrombophilic defect including 20210G>A was associated with a twofold increased recurrence risk .A meta-analysis and a systematic review both concluded that 20210G>A heterozygosity is associated with a modest but statistically significant increased risk for recurrent VTE after a first event (OR = 1.72, OR=1.74, respectively) .Studies that do not support an association of 20210G>A heterozygosity and increased risk for recurrent VTE in adults:Multiple retrospective and prospective studies found no significant difference in the rate of recurrent VTE between 20210G>A heterozygotes and individuals without the allele .In a large family study, the incidence of recurrent VTE in relatives with 20210G>A heterozygosity was 7% after two years, 11% after five years, and 25% after ten years, rates similar to those reported in the general population .A systematic review pooling data | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. gt;A heterozygosity and increased risk for recurrent VTE in adults:Multiple retrospective and prospective studies found no significant difference in the rate of recurrent VTE between 20210G>A heterozygotes and individuals without the allele .In a large family study, the incidence of recurrent VTE in relatives with 20210G>A heterozygosity was 7% after two years, 11% after five years, and 25% after ten years, rates similar to those reported in the general population .A systematic review pooling data from nine studies found that 20210G>A heterozygosity is not predictive of recurrent VTE .20210G>A heterozygosity is not associated with an increased risk of recurrent cerebral vein thrombosis .20210G>A heterozygosity is not associated with a higher risk for recurrent VTE during warfarin therapy . Multiple studies showed that the reduction in risk during oral anticoagulation is similar in individuals with and without the allele .Risk for recurrent thrombosis in 20210G | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. general population .A systematic review pooling data from nine studies found that 20210G>A heterozygosity is not predictive of recurrent VTE .20210G>A heterozygosity is not associated with an increased risk of recurrent cerebral vein thrombosis .20210G>A heterozygosity is not associated with a higher risk for recurrent VTE during warfarin therapy . Multiple studies showed that the reduction in risk during oral anticoagulation is similar in individuals with and without the allele .Risk for recurrent thrombosis in 20210G>A homozygotes and in 20210G>A heterozygotes with other risk factorsSummary. The risk for recurrent VTE in 20210G>A homozygotes is not well defined, but presumed to be higher than in 20210G>A heterozygotes. Most studies did not include an adequate number of individuals homozygous for the allele to evaluate the effect on recurrence risk . The available evidence suggests that individuals with multiple thrombophilic defects | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. Risk for recurrent thrombosis in 20210G>A homozygotes and in 20210G>A heterozygotes with other risk factorsSummary. The risk for recurrent VTE in 20210G>A homozygotes is not well defined, but presumed to be higher than in 20210G>A heterozygotes. Most studies did not include an adequate number of individuals homozygous for the allele to evaluate the effect on recurrence risk . The available evidence suggests that individuals with multiple thrombophilic defects have a higher risk for recurrent VTE.Studies that support an increased risk for recurrent thrombosis in 20210G>A homozygotes and in 20210G>A heterozygotes with other risk factors:Individuals who are heterozygous for both the 20210G>A and factor V Leiden alleles (i.e., doubly heterozygous) have a three- to ninefold higher recurrence risk than those with neither allele, and a threefold higher risk than | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. suggests that individuals with multiple thrombophilic defects have a higher risk for recurrent VTE.Studies that support an increased risk for recurrent thrombosis in 20210G>A homozygotes and in 20210G>A heterozygotes with other risk factors:Individuals who are heterozygous for both the 20210G>A and factor V Leiden alleles (i.e., doubly heterozygous) have a three- to ninefold higher recurrence risk than those with neither allele, and a threefold higher risk than individuals heterozygous for the factor V Leiden allele alone .In a prospective study, the annual incidence of recurrent VTE was 12%/year in persons homozygous for the 20210G>A allele or doubly heterozygous for 20210G>A and factor V Leiden, compared to 2.8% in those without either thrombophilia-related allele .A systematic review found that individuals doubly heterozygous for 20210G>A and factor V | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. allele, and a threefold higher risk than individuals heterozygous for the factor V Leiden allele alone .In a prospective study, the annual incidence of recurrent VTE was 12%/year in persons homozygous for the 20210G>A allele or doubly heterozygous for 20210G>A and factor V Leiden, compared to 2.8% in those without either thrombophilia-related allele .A systematic review found that individuals doubly heterozygous for 20210G>A and factor V Leiden had a nearly fivefold increased risk for recurrent VTE .Not all studies found an increased risk for recurrent thrombosis in individuals with multiple thrombophilic alleles:In a family study individuals homozygous for the 20210G>A allele or doubly heterozygous for 20210G>A and factor V Leiden did not have an increased risk for recurrent thrombosis, even when the analysis was restricted to those with a first unprovoked VTE .Risk for recurrent | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. G>A and factor V Leiden had a nearly fivefold increased risk for recurrent VTE .Not all studies found an increased risk for recurrent thrombosis in individuals with multiple thrombophilic alleles:In a family study individuals homozygous for the 20210G>A allele or doubly heterozygous for 20210G>A and factor V Leiden did not have an increased risk for recurrent thrombosis, even when the analysis was restricted to those with a first unprovoked VTE .Risk for recurrent thrombosis in childrenSummary. The risk for recurrent VTE is likely higher in children with an initial spontaneous (unprovoked) event, a strong family history of thrombosis, and multiple thrombophilic defects . Data on the risk for recurrent VTE in children who are 20210G>A heterozygotes are limited and conflicting. Multiple studies were not statistically powered because of small sample size.Studies that support an increased risk for recurrent thrombosis in children who are | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. voked VTE .Risk for recurrent thrombosis in childrenSummary. The risk for recurrent VTE is likely higher in children with an initial spontaneous (unprovoked) event, a strong family history of thrombosis, and multiple thrombophilic defects . Data on the risk for recurrent VTE in children who are 20210G>A heterozygotes are limited and conflicting. Multiple studies were not statistically powered because of small sample size.Studies that support an increased risk for recurrent thrombosis in children who are 20210G>A heterozygotes:In a prospective cohort study, the incidence of recurrent VTE at a median 12 months after the initial event was 58 VTE events/1000 person-years in children with a 20210G>A allele, compared to 11.8/1000 person-years in children without thrombophilia. VTE recurred in 18% of children with 20210G>A compared to 7.6% of controls, suggesting | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. risk for recurrent thrombosis in children who are 20210G>A heterozygotes:In a prospective cohort study, the incidence of recurrent VTE at a median 12 months after the initial event was 58 VTE events/1000 person-years in children with a 20210G>A allele, compared to 11.8/1000 person-years in children without thrombophilia. VTE recurred in 18% of children with 20210G>A compared to 7.6% of controls, suggesting a two- to threefold increase in recurrence risk .In a meta-analysis of 12 observational studies, 20210G>A was associated with a twofold increased risk for recurrent VTE. The risk was increased four- to fivefold in children with multiple thrombophilic defects .Studies that do not support an increased risk for recurrent thrombosis in children who are 20210G>A heterozygotes:In a series of Dutch children with VTE, VTE recurred in 11% | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 7.6% of controls, suggesting a two- to threefold increase in recurrence risk .In a meta-analysis of 12 observational studies, 20210G>A was associated with a twofold increased risk for recurrent VTE. The risk was increased four- to fivefold in children with multiple thrombophilic defects .Studies that do not support an increased risk for recurrent thrombosis in children who are 20210G>A heterozygotes:In a series of Dutch children with VTE, VTE recurred in 11%, none of whom had a 20210G>A allele. The presence of one or more inherited thrombophilic disorders was not an independent risk factor for recurrent VTE .In another study 20210G>A heterozygosity was not found among children with recurrent thrombosis, all of whom had other acquired risk factors .Risk for recurrent thrombosis in pregnant womenSummary. Women with a prior history of VTE have an increased recurrence risk during pregnancy; recurrence | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. with VTE, VTE recurred in 11%, none of whom had a 20210G>A allele. The presence of one or more inherited thrombophilic disorders was not an independent risk factor for recurrent VTE .In another study 20210G>A heterozygosity was not found among children with recurrent thrombosis, all of whom had other acquired risk factors .Risk for recurrent thrombosis in pregnant womenSummary. Women with a prior history of VTE have an increased recurrence risk during pregnancy; recurrence rates range from 0% to 15% among published studies. The risk is higher in women with a prior unprovoked episode or an estrogen-related VTE, and in those with coexisting genetic or acquired risk factors. Note: No studies have specifically evaluated the risk for recurrent VTE in pregnant women with a 20210G>A allele.Analysis of a large in-patient database found that thrombophilia and a prior history of VTE were the strongest risk | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. an increased recurrence risk during pregnancy; recurrence rates range from 0% to 15% among published studies. The risk is higher in women with a prior unprovoked episode or an estrogen-related VTE, and in those with coexisting genetic or acquired risk factors. Note: No studies have specifically evaluated the risk for recurrent VTE in pregnant women with a 20210G>A allele.Analysis of a large in-patient database found that thrombophilia and a prior history of VTE were the strongest risk factors for pregnancy-related VTE, conferring a 52-fold and 25-fold increase in relative risk, respectively .The results of several studies suggest that women with a history of VTE provoked by oral contraceptives or related to pregnancy are at higher risk for recurrent thrombosis during a subsequent pregnancy .A prospective study evaluated the safety of withholding anticoagulation during pregnancy in women with a history of a single VTE. In subgroup analysis, women with a previous spontaneous thromboembolic event and thrombophilia | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. prior history of VTE were the strongest risk factors for pregnancy-related VTE, conferring a 52-fold and 25-fold increase in relative risk, respectively .The results of several studies suggest that women with a history of VTE provoked by oral contraceptives or related to pregnancy are at higher risk for recurrent thrombosis during a subsequent pregnancy .A prospective study evaluated the safety of withholding anticoagulation during pregnancy in women with a history of a single VTE. In subgroup analysis, women with a previous spontaneous thromboembolic event and thrombophilia had the highest recurrence rate during pregnancy (20%, odds ratio of 10) . Women with either inherited or acquired thrombophilia or with a prior unprovoked VTE (but not both) had recurrence rates of 13% and 7.7%, respectively.Pregnancy ComplicationsIt is unlikely that 20210G>A heterozygosity is a major factor contributing to pregnancy loss and other adverse pregnancy outcomes. Although multiple retrospective studies have suggested a modest increased risk of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. a previous spontaneous thromboembolic event and thrombophilia had the highest recurrence rate during pregnancy (20%, odds ratio of 10) . Women with either inherited or acquired thrombophilia or with a prior unprovoked VTE (but not both) had recurrence rates of 13% and 7.7%, respectively.Pregnancy ComplicationsIt is unlikely that 20210G>A heterozygosity is a major factor contributing to pregnancy loss and other adverse pregnancy outcomes. Although multiple retrospective studies have suggested a modest increased risk of fetal loss, most prospective studies have not confirmed an association. The available data suggest that 20210G>A heterozygosity is associated with at most a two- to threefold increased relative risk for pregnancy loss.The association with preeclampsia, fetal growth restriction, and placental abruption is more controversial. A 20210G>A allele is at most one of multiple predisposing factors contributing to these complications. Other genetic and environmental triggers are necessary for the development of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. studies have suggested a modest increased risk of fetal loss, most prospective studies have not confirmed an association. The available data suggest that 20210G>A heterozygosity is associated with at most a two- to threefold increased relative risk for pregnancy loss.The association with preeclampsia, fetal growth restriction, and placental abruption is more controversial. A 20210G>A allele is at most one of multiple predisposing factors contributing to these complications. Other genetic and environmental triggers are necessary for the development of pregnancy complications in women heterozygous and homozygous for the 20210G>A allele.Pregnancy lossSummary. Some (though not all) evidence suggests that 20210G>A heterozygosity increases the risk for fetal loss . However, despite a modest increase in relative risk, the absolute risk for fetal loss is low and the majority of heterozygous women have normal pregnancies.Studies that show an association between unexplained pregnancy loss and a maternal 20210G | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. environmental triggers are necessary for the development of pregnancy complications in women heterozygous and homozygous for the 20210G>A allele.Pregnancy lossSummary. Some (though not all) evidence suggests that 20210G>A heterozygosity increases the risk for fetal loss . However, despite a modest increase in relative risk, the absolute risk for fetal loss is low and the majority of heterozygous women have normal pregnancies.Studies that show an association between unexplained pregnancy loss and a maternal 20210G>A allele:20210G>A heterozygosity was found in 4%-9% of women with recurrent pregnancy loss (the majority in the first trimester), compared with 1%-2% of those with uncomplicated pregnancies, with odds ratios ranging from two to nine .Several case-control studies and three meta-analyses found an increased risk for first trimester pregnancy loss in women with a 20210G>A allele .Several | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. pregnancy loss and a maternal 20210G>A allele:20210G>A heterozygosity was found in 4%-9% of women with recurrent pregnancy loss (the majority in the first trimester), compared with 1%-2% of those with uncomplicated pregnancies, with odds ratios ranging from two to nine .Several case-control studies and three meta-analyses found an increased risk for first trimester pregnancy loss in women with a 20210G>A allele .Several meta-analyses concluded that 20210G>A heterozygosity was associated with a two- to threefold increased risk for recurrent first trimester fetal loss and a nearly ninefold increased risk for non-recurrent second trimester loss .Some evidence suggests that women with prothrombin-related thrombophilia have a higher risk for pregnancy loss in the second and third trimesters. Although late fetal loss may reflect thrombosis of placental vessels, the role of thrombophilic disorders including 20210G& | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. G>A allele .Several meta-analyses concluded that 20210G>A heterozygosity was associated with a two- to threefold increased risk for recurrent first trimester fetal loss and a nearly ninefold increased risk for non-recurrent second trimester loss .Some evidence suggests that women with prothrombin-related thrombophilia have a higher risk for pregnancy loss in the second and third trimesters. Although late fetal loss may reflect thrombosis of placental vessels, the role of thrombophilic disorders including 20210G>A in the complex biologic events predisposing to placental insufficiency is not well defined.An observational study of women with three consecutive miscarriages before ten weeks’ gestation found that 20210G>A heterozygotes had a rate of recurrent early miscarriage similar to that of women without a thromboplhic disorder. However, heterozygous women had a significantly higher rate of late fetal loss during the next pregnancy (8.8% versus 2.3%) .Two | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. thrombophilic disorders including 20210G>A in the complex biologic events predisposing to placental insufficiency is not well defined.An observational study of women with three consecutive miscarriages before ten weeks’ gestation found that 20210G>A heterozygotes had a rate of recurrent early miscarriage similar to that of women without a thromboplhic disorder. However, heterozygous women had a significantly higher rate of late fetal loss during the next pregnancy (8.8% versus 2.3%) .Two studies found 20210G>A heterozygosity in 9%-13% of women with a first unexplained third-trimester loss, compared with 2%-3% of controls suggesting a two- to threefold increase in risk .A meta-analysis found that 20210G>A heterozygosity is associated with a more than threefold higher risk for fetal loss in the second trimester compared to the first trimester. The allele was also associated with a two- to | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. versus 2.3%) .Two studies found 20210G>A heterozygosity in 9%-13% of women with a first unexplained third-trimester loss, compared with 2%-3% of controls suggesting a two- to threefold increase in risk .A meta-analysis found that 20210G>A heterozygosity is associated with a more than threefold higher risk for fetal loss in the second trimester compared to the first trimester. The allele was also associated with a two- to threefold increased risk for third-trimester loss and the risk increased after 24 weeks’ gestation .Studies that found no increased risk for pregnancy loss in women with a 20210G>A allele:Multiple observational and prospective studies found no association between 20210G>A and an increased risk for early or late recurrent pregnancy loss .A family cohort study suggested that 20210G>A has no effect on the outcome of a subsequent pregnancy after | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. was also associated with a two- to threefold increased risk for third-trimester loss and the risk increased after 24 weeks’ gestation .Studies that found no increased risk for pregnancy loss in women with a 20210G>A allele:Multiple observational and prospective studies found no association between 20210G>A and an increased risk for early or late recurrent pregnancy loss .A family cohort study suggested that 20210G>A has no effect on the outcome of a subsequent pregnancy after a first fetal loss. The live birth rate in a second pregnancy was high and similar in women with and without the allele (77% and 76%, respectively) .In a meta-analysis of prospective cohort studies, 20210G>A was not associated with an increased risk for a composite outcome of placental mediated complications including pregnancy loss. However, the analysis was not powered to detect small differences in risk due to the small number of studies reviewed . | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. on the outcome of a subsequent pregnancy after a first fetal loss. The live birth rate in a second pregnancy was high and similar in women with and without the allele (77% and 76%, respectively) .In a meta-analysis of prospective cohort studies, 20210G>A was not associated with an increased risk for a composite outcome of placental mediated complications including pregnancy loss. However, the analysis was not powered to detect small differences in risk due to the small number of studies reviewed .Limited available evidence indicates that paternal thrombophilia, including 20210G>A heterozygosity, is not associated with an increased risk for fetal loss .Other obstetric complicationsAlthough preeclampsia, fetal growth restriction (FGR), and placental abruption may also involve impaired placental perfusion, their association with inherited thrombophilia is controversial. The conflicting results reported in different studies may reflect the varying diagnostic and selection criteria, different ethnic groups, and small number of cases included | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. to the small number of studies reviewed .Limited available evidence indicates that paternal thrombophilia, including 20210G>A heterozygosity, is not associated with an increased risk for fetal loss .Other obstetric complicationsAlthough preeclampsia, fetal growth restriction (FGR), and placental abruption may also involve impaired placental perfusion, their association with inherited thrombophilia is controversial. The conflicting results reported in different studies may reflect the varying diagnostic and selection criteria, different ethnic groups, and small number of cases included . The available evidence does not support an association between 20210G>A heterozygosity and these adverse pregnancy outcomes.Preeclampsia. Preeclampsia is a heterogeneous disorder and it is unlikely that a single thrombophilic variant such as 20210G>A plays a major causal role. The conflicting results of the following studies suggest that 20210G>A heterozygosity does not significantly increase the risk for preeclampsia.Studies showing an increased risk for preeclampsia in women with | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. groups, and small number of cases included . The available evidence does not support an association between 20210G>A heterozygosity and these adverse pregnancy outcomes.Preeclampsia. Preeclampsia is a heterogeneous disorder and it is unlikely that a single thrombophilic variant such as 20210G>A plays a major causal role. The conflicting results of the following studies suggest that 20210G>A heterozygosity does not significantly increase the risk for preeclampsia.Studies showing an increased risk for preeclampsia in women with a 20210G>A allele:Multiple case-control studies found a significantly higher prevalence of 20210G>A in women with preeclampsia (7%-11%) than in women with normal pregnancies (1%-4%), suggesting a two- to sevenfold increase in risk .A recent prospective study found that a 20210G>A allele was associated with threefold higher risk for recurrent preeclampsia which occurred in 50 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. an increased risk for preeclampsia in women with a 20210G>A allele:Multiple case-control studies found a significantly higher prevalence of 20210G>A in women with preeclampsia (7%-11%) than in women with normal pregnancies (1%-4%), suggesting a two- to sevenfold increase in risk .A recent prospective study found that a 20210G>A allele was associated with threefold higher risk for recurrent preeclampsia which occurred in 50% of heterozygous women .A meta-analysis of eight studies found that 20210G>A heterozygosity was associated with a two- to threefold increased risk for preeclampsia .Studies showing no increased risk for preeclampsia in women with a 20210G>A allele:20210G>A heterozygosity did not increase the risk for preeclampsia in multiple studies of unselected women screened during pregnancy . In one study histopathologic features of placental insufficiency were found in 63 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. risk for recurrent preeclampsia which occurred in 50% of heterozygous women .A meta-analysis of eight studies found that 20210G>A heterozygosity was associated with a two- to threefold increased risk for preeclampsia .Studies showing no increased risk for preeclampsia in women with a 20210G>A allele:20210G>A heterozygosity did not increase the risk for preeclampsia in multiple studies of unselected women screened during pregnancy . In one study histopathologic features of placental insufficiency were found in 63% of preeclamptic women, but were not associated with 20210G>A heterozygosity .Two meta-analyses found no significant association between a 20210G>A allele and preeclampsia . The absolute risk for preeclampsia was similar in women with and without a 20210G>A allele (3.5% and 3%, respectively) .Fetal growth restriction (FGR). The data on the risk for FGR associated | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. features of placental insufficiency were found in 63% of preeclamptic women, but were not associated with 20210G>A heterozygosity .Two meta-analyses found no significant association between a 20210G>A allele and preeclampsia . The absolute risk for preeclampsia was similar in women with and without a 20210G>A allele (3.5% and 3%, respectively) .Fetal growth restriction (FGR). The data on the risk for FGR associated with a 20210G>A allele are more limited and also conflicting. There is no consistent association between 20210G>A heterozygosity and FGR.Studies showing an increased risk for FGR in women with a 20210G>A allele:20210G>A heterozygosity was found in 7%-15% of women with pregnancies complicated by FGR, compared with 2%-4% of controls, with | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. data on the risk for FGR associated with a 20210G>A allele are more limited and also conflicting. There is no consistent association between 20210G>A heterozygosity and FGR.Studies showing an increased risk for FGR in women with a 20210G>A allele:20210G>A heterozygosity was found in 7%-15% of women with pregnancies complicated by FGR, compared with 2%-4% of controls, with odds ratios ranging from four to nine .Two meta-analyses found that a 20210G>A allele was associated with a two- to threefold increased risk for FGR .Studies showing no increased risk for FGR in women with a 20210G>A allele:A large case-control study found no significant association between maternal or fetal thrombophilia and FGR. Women heterozygous for the 20210G>A allele had no | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. %-4% of controls, with odds ratios ranging from four to nine .Two meta-analyses found that a 20210G>A allele was associated with a two- to threefold increased risk for FGR .Studies showing no increased risk for FGR in women with a 20210G>A allele:A large case-control study found no significant association between maternal or fetal thrombophilia and FGR. Women heterozygous for the 20210G>A allele had no increase in risk for a pregnancy complicated by FGR compared with unaffected controls .In several prospective studies of unselected pregnant women, a 20210G>A allele did not increase the risk for FGR .A large cohort study and a meta-analysis of 11 case-control studies found no association between a maternal or fetal 20210G>A allele (singly or in combination) and FGR .Placental abruption. The data on the risk | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. G>A allele had no increase in risk for a pregnancy complicated by FGR compared with unaffected controls .In several prospective studies of unselected pregnant women, a 20210G>A allele did not increase the risk for FGR .A large cohort study and a meta-analysis of 11 case-control studies found no association between a maternal or fetal 20210G>A allele (singly or in combination) and FGR .Placental abruption. The data on the risk for placental abruption in women with prothrombin-related thrombophilia are limited and conflicting. A large prospective study and a meta-analysis found that 29210G>A heterozygosity conferred a nine- to12-fold increased risk for placental abruption . In contrast, other prospective studies and a meta-analysis found no association . There is currently no convincing evidence of an association with placental abruption.Factors that Predispose to ThrombosisThe clinical expression of prothrombin thrombophilia | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. abruption. The data on the risk for placental abruption in women with prothrombin-related thrombophilia are limited and conflicting. A large prospective study and a meta-analysis found that 29210G>A heterozygosity conferred a nine- to12-fold increased risk for placental abruption . In contrast, other prospective studies and a meta-analysis found no association . There is currently no convincing evidence of an association with placental abruption.Factors that Predispose to ThrombosisThe clinical expression of prothrombin thrombophilia is influenced by: the number of 20210G>A alleles, coexisting genetic abnormalities, acquired thrombophilic disorders, and circumstantial risk factors.Number of 20210G>A Alleles20210G>A heterozygotes have a relative risk for venous thrombosis that is approximately two- to fivefold increased .20210G>A homozygotes are at higher risk, although the magnitude is not well defined. Whereas 20210G | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. ThrombosisThe clinical expression of prothrombin thrombophilia is influenced by: the number of 20210G>A alleles, coexisting genetic abnormalities, acquired thrombophilic disorders, and circumstantial risk factors.Number of 20210G>A Alleles20210G>A heterozygotes have a relative risk for venous thrombosis that is approximately two- to fivefold increased .20210G>A homozygotes are at higher risk, although the magnitude is not well defined. Whereas 20210G>A homozygotes may develop thrombosis more frequently and at a younger age, the risk is much lower than that associated with homozygous protein C deficiency or homozygous protein S deficiency. Numerous reports of asymptomatic 20210G>A homozygotes emphasize the contribution of other genetic and acquired risk factors to thrombosis .Coexisting Genetic AbnormalitiesAnother inherited thrombophilic disorder is present in 8%-14% of 20210G>A heterozygotes, creating supra-additive effect | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. not well defined. Whereas 20210G>A homozygotes may develop thrombosis more frequently and at a younger age, the risk is much lower than that associated with homozygous protein C deficiency or homozygous protein S deficiency. Numerous reports of asymptomatic 20210G>A homozygotes emphasize the contribution of other genetic and acquired risk factors to thrombosis .Coexisting Genetic AbnormalitiesAnother inherited thrombophilic disorder is present in 8%-14% of 20210G>A heterozygotes, creating supra-additive effect on overall thrombotic risk. Individuals with multiple thrombophilic disorders develop VTE at a younger age and are at higher risk for recurrent thrombosis than those with a single defect .Factor V Leiden. Heterozygosity for a factor V Leiden allele occurs in 20%-40% of symptomatic 20210G>A heterozygotes .Individuals doubly heterozygous for 20210G>A and factor V Leiden have an increased relative risk for VTE, although estimates of the magnitude | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. A heterozygotes, creating supra-additive effect on overall thrombotic risk. Individuals with multiple thrombophilic disorders develop VTE at a younger age and are at higher risk for recurrent thrombosis than those with a single defect .Factor V Leiden. Heterozygosity for a factor V Leiden allele occurs in 20%-40% of symptomatic 20210G>A heterozygotes .Individuals doubly heterozygous for 20210G>A and factor V Leiden have an increased relative risk for VTE, although estimates of the magnitude of risk vary. In one analysis, the risk was increased 20-fold in individuals heterozygous for both alleles, suggesting a multiplicative effect on overall thrombotic risk . A more recent systematic review concluded that double heterozygosity for both thrombophilic alleles confers a more modest sevenfold increase in thrombotic risk . Doubly heterozygous individuals are at a three- to fourfold higher risk than those with a single thrombophilic allele and are more likely to develop thrombosis in unusual locations (e.g | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. for VTE, although estimates of the magnitude of risk vary. In one analysis, the risk was increased 20-fold in individuals heterozygous for both alleles, suggesting a multiplicative effect on overall thrombotic risk . A more recent systematic review concluded that double heterozygosity for both thrombophilic alleles confers a more modest sevenfold increase in thrombotic risk . Doubly heterozygous individuals are at a three- to fourfold higher risk than those with a single thrombophilic allele and are more likely to develop thrombosis in unusual locations (e.g., hepatic, mesenteric, or cerebral veins) .Anticoagulant protein deficiency. In one study of families with thrombophilia, the combination of protein S deficiency and 20210G>A heterozygosity was associated with a nearly 13-fold increased risk for VTE, compared to a fourfold increased risk with 20210G>A heterozygosity alone . In contrast, coinheritance of a 20210G>A allele did not increase the risk for thrombosis | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. thrombosis in unusual locations (e.g., hepatic, mesenteric, or cerebral veins) .Anticoagulant protein deficiency. In one study of families with thrombophilia, the combination of protein S deficiency and 20210G>A heterozygosity was associated with a nearly 13-fold increased risk for VTE, compared to a fourfold increased risk with 20210G>A heterozygosity alone . In contrast, coinheritance of a 20210G>A allele did not increase the risk for thrombosis in a large kindred with protein C deficiency .Other genetic factors. An F2 20210G>A allele may also interact with other genetic factors, such as normal sequence variants in the following two genes, which independently may not predispose to thrombosis:F8, the gene encoding factor XIII. The effect of the F8 Val34Leu variant has been extensively studied with conflicting results . Two meta-analyses found a slight overall protective effect of an | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. allele did not increase the risk for thrombosis in a large kindred with protein C deficiency .Other genetic factors. An F2 20210G>A allele may also interact with other genetic factors, such as normal sequence variants in the following two genes, which independently may not predispose to thrombosis:F8, the gene encoding factor XIII. The effect of the F8 Val34Leu variant has been extensively studied with conflicting results . Two meta-analyses found a slight overall protective effect of an F8 Val34Leu allele against VTE .Note: The F8 variant in exon 2 (NM_000132.3:c.157G>T) encodes a normal protein variant officially designated NP_000123.1:p.Val53Leu (commonly known as Val34Leu, which does not count the 19 amino-acid signal sequence) .SERPINE1, the gene encoding PAI1 (plasminogen activator inhibitor | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. found a slight overall protective effect of an F8 Val34Leu allele against VTE .Note: The F8 variant in exon 2 (NM_000132.3:c.157G>T) encodes a normal protein variant officially designated NP_000123.1:p.Val53Leu (commonly known as Val34Leu, which does not count the 19 amino-acid signal sequence) .SERPINE1, the gene encoding PAI1 (plasminogen activator inhibitor type 1). Heterozygosity for the SERPINE1 4G polymorphic allele in combination with 20210G>A heterozygosity was associated with a sixfold increased risk for venous thrombosis. Homozygosity for the SERPINE1 4G polymorphic allele in combination with 20210G>A heterozygosity was associated with a 13-fold increased risk for venous thrombosis . (The risk for 4G/5G was not calculated in this study.)Note: The | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. gene encoding PAI1 (plasminogen activator inhibitor type 1). Heterozygosity for the SERPINE1 4G polymorphic allele in combination with 20210G>A heterozygosity was associated with a sixfold increased risk for venous thrombosis. Homozygosity for the SERPINE1 4G polymorphic allele in combination with 20210G>A heterozygosity was associated with a 13-fold increased risk for venous thrombosis . (The risk for 4G/5G was not calculated in this study.)Note: The SERPINE1 polymorphism commonly referred to as 4G/5G is a missense substitution (NG_013213.1: g.4328G>T;rs114094261) that is -675 nucleotides from the transcription start. The missense substitution results in either four or five G nucleotides in a row; hence, the common designation of 4G or 5G alleles.Family history. A family history of thrombosis affecting | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. in this study.)Note: The SERPINE1 polymorphism commonly referred to as 4G/5G is a missense substitution (NG_013213.1: g.4328G>T;rs114094261) that is -675 nucleotides from the transcription start. The missense substitution results in either four or five G nucleotides in a row; hence, the common designation of 4G or 5G alleles.Family history. A family history of thrombosis affecting at least one first-degree relative is a risk factor for VTE even after identification of an inherited thrombophilic disorder (including 20210A heterozygosity) . A positive family history is associated with a three- to fourfold increased risk for VTE among individuals with a 20210G>A or factor V Leiden allele . The risk is higher when multiple members are affected and thrombosis occurs at a young age.Acquired Thrombophilic DisordersHyperhomocysteinemia may increase the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. history. A family history of thrombosis affecting at least one first-degree relative is a risk factor for VTE even after identification of an inherited thrombophilic disorder (including 20210A heterozygosity) . A positive family history is associated with a three- to fourfold increased risk for VTE among individuals with a 20210G>A or factor V Leiden allele . The risk is higher when multiple members are affected and thrombosis occurs at a young age.Acquired Thrombophilic DisordersHyperhomocysteinemia may increase the thrombotic risk associated with 20210G>A heterozygosity. In one study, the combination of high plasma concentrations of homocysteine (>12 µmol/L) and 20210G>A heterozygosity conferred an estimated 50-fold increase in risk, suggesting a multiplicative effect on overall thrombotic risk .Antiphospholipid antibodies (APLA). The effect of antiphospholipid antibodies on the thrombotic risk associated with a 20210G>A allele is | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. DisordersHyperhomocysteinemia may increase the thrombotic risk associated with 20210G>A heterozygosity. In one study, the combination of high plasma concentrations of homocysteine (>12 µmol/L) and 20210G>A heterozygosity conferred an estimated 50-fold increase in risk, suggesting a multiplicative effect on overall thrombotic risk .Antiphospholipid antibodies (APLA). The effect of antiphospholipid antibodies on the thrombotic risk associated with a 20210G>A allele is not well defined. One study found that the presence of antiphospholipid antibodies was associated with a fourfold increased risk for thromboembolic events in 20210G>A heterozygotes (OR = 4.4) .Malignancy. Whether inherited thrombophilia increases the risk for VTE in persons with cancer is still controversial . Malignancy is associated witha markedly increased risk for VTE, especially during the first few months after diagnosis and in those with distant metastases . Because malignancy is such a strong risk | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 10G>A allele is not well defined. One study found that the presence of antiphospholipid antibodies was associated with a fourfold increased risk for thromboembolic events in 20210G>A heterozygotes (OR = 4.4) .Malignancy. Whether inherited thrombophilia increases the risk for VTE in persons with cancer is still controversial . Malignancy is associated witha markedly increased risk for VTE, especially during the first few months after diagnosis and in those with distant metastases . Because malignancy is such a strong risk factor, it may obscure the effect of mild thrombophilic disorders, including prothrombin thrombophilia. Thrombophilia status was not considered in recent guidelines for prophylaxis and treatment of VTE in patients with cancer .A few small studies found a similar prevalence of 20210G>A heterozygosity in persons with cancer with and without VTE . Other evidence suggests that the 20210G>A allele may increase the risk for malignancy-related VTE.A large population-based | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. . Because malignancy is such a strong risk factor, it may obscure the effect of mild thrombophilic disorders, including prothrombin thrombophilia. Thrombophilia status was not considered in recent guidelines for prophylaxis and treatment of VTE in patients with cancer .A few small studies found a similar prevalence of 20210G>A heterozygosity in persons with cancer with and without VTE . Other evidence suggests that the 20210G>A allele may increase the risk for malignancy-related VTE.A large population-based case-control study found that persons with cancer and 20210G>A heterozygosity had a 17-fold higher risk for VTE than individuals with neither risk factor, and a fourfold higher risk for VTE than those with cancer and without the 20210G>A allele .Individuals with cancer who are heterozygous for factor V Leiden or 20210G>A have a 20-fold higher risk for developing an upper-extremity thrombosis than individuals | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. related VTE.A large population-based case-control study found that persons with cancer and 20210G>A heterozygosity had a 17-fold higher risk for VTE than individuals with neither risk factor, and a fourfold higher risk for VTE than those with cancer and without the 20210G>A allele .Individuals with cancer who are heterozygous for factor V Leiden or 20210G>A have a 20-fold higher risk for developing an upper-extremity thrombosis than individuals with cancer without either thrombophilia-related allele .A meta-analysis found that a 20210G>A allele is associated with a fivefold increased risk for central venous catheter thrombosis in persons with cancer .Circumstantial Risk FactorsOther predisposing factors include: pregnancy, oral contraceptive use, hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), organ transplantation, central venous catheter use, surgery, travel, and minor injury. The 202 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. developing an upper-extremity thrombosis than individuals with cancer without either thrombophilia-related allele .A meta-analysis found that a 20210G>A allele is associated with a fivefold increased risk for central venous catheter thrombosis in persons with cancer .Circumstantial Risk FactorsOther predisposing factors include: pregnancy, oral contraceptive use, hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), organ transplantation, central venous catheter use, surgery, travel, and minor injury. The 20210G>A allele interacts with these environmental risk factors to increase the risk for VTE. At least 50% of thrombotic episodes in individuals with prothrombin-related thrombophilia are provoked by additional predisposing factors, with pregnancy being the most common .Circumstantial risk factors play a major role in VTE in children. In several studies 62%-97% of children with VTE had coexisting circumstantial risk factors, with central venous catheters, malignancy, and congenital | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. travel, and minor injury. The 20210G>A allele interacts with these environmental risk factors to increase the risk for VTE. At least 50% of thrombotic episodes in individuals with prothrombin-related thrombophilia are provoked by additional predisposing factors, with pregnancy being the most common .Circumstantial risk factors play a major role in VTE in children. In several studies 62%-97% of children with VTE had coexisting circumstantial risk factors, with central venous catheters, malignancy, and congenital heart disease among the most frequently reported .Pregnancy. Women with thrombophilia are at higher risk for VTE during pregnancy .In several studies 20210G>A heterozygotes had a three- to 15-fold higher risk for pregnancy-associated VTE than women without the allele .A population based case-control study found that 20210G>A heterozygotes have a 31-fold increased risk of developing VTE during pregnancy or the postpartum period compared with non- | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. central venous catheters, malignancy, and congenital heart disease among the most frequently reported .Pregnancy. Women with thrombophilia are at higher risk for VTE during pregnancy .In several studies 20210G>A heterozygotes had a three- to 15-fold higher risk for pregnancy-associated VTE than women without the allele .A population based case-control study found that 20210G>A heterozygotes have a 31-fold increased risk of developing VTE during pregnancy or the postpartum period compared with non-pregnant women without the allele .A meta-analysis suggested that 20210G>A heterozygotes have a nearly sevenfold higher risk for pregnancy-related VTE than pregnant women without inherited or acquired thrombophilia .Although 20210G>A heterozygosity increases the relative risk for pregnancy-associated VTE, the absolute risk in asymptomatic heterozygotes is low in the absence of other predisposing factors. The highest risk occurs during the first six weeks post partum:Several retrospective studies | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. or the postpartum period compared with non-pregnant women without the allele .A meta-analysis suggested that 20210G>A heterozygotes have a nearly sevenfold higher risk for pregnancy-related VTE than pregnant women without inherited or acquired thrombophilia .Although 20210G>A heterozygosity increases the relative risk for pregnancy-associated VTE, the absolute risk in asymptomatic heterozygotes is low in the absence of other predisposing factors. The highest risk occurs during the first six weeks post partum:Several retrospective studies estimated the probability of VTE in the range of one in 200 to 300 pregnancies . A population study estimated that VTE occurs in approximately one in 111 20210G>A heterozygotes during pregnancy .In a retrospective family study, no VTE events occurred during pregnancy in asymptomatic 20210G>A heterozygotes. Postpartum VTE complicated 1.5% of pregnancies of 20210G>A heterozygotes compared to 0.4% of those in relatives without thromb | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. six weeks post partum:Several retrospective studies estimated the probability of VTE in the range of one in 200 to 300 pregnancies . A population study estimated that VTE occurs in approximately one in 111 20210G>A heterozygotes during pregnancy .In a retrospective family study, no VTE events occurred during pregnancy in asymptomatic 20210G>A heterozygotes. Postpartum VTE complicated 1.5% of pregnancies of 20210G>A heterozygotes compared to 0.4% of those in relatives without thrombophilia .In two prospective cohort studies of unselected pregnant women, no VTE events occurred during pregnancy or the postpartum period in 20210G>A heterozygotes .Women homozygous for 20210G>A or doubly heterozygous for 20210G>A and factor V Leiden have a higher risk for pregnancy-associated VTE:The risk for pregnancy-associated VTE was increased 26-fold in 20210G>A homozygotes in one study | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 4% of those in relatives without thrombophilia .In two prospective cohort studies of unselected pregnant women, no VTE events occurred during pregnancy or the postpartum period in 20210G>A heterozygotes .Women homozygous for 20210G>A or doubly heterozygous for 20210G>A and factor V Leiden have a higher risk for pregnancy-associated VTE:The risk for pregnancy-associated VTE was increased 26-fold in 20210G>A homozygotes in one study .The risk for pregnancy-associated VTE was increased 15-fold in 20210G>A heterozygotes, ninefold in those heterozygous for factor V Leiden, and greater than 100-fold in women who were doubly heterozygous for 20210G>A and factor V Leiden .VTE complicated 17.8% of pregnancies in women doubly heterozygous for 20210G>A and factor V Leiden, compared to 6.2% | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. >A homozygotes in one study .The risk for pregnancy-associated VTE was increased 15-fold in 20210G>A heterozygotes, ninefold in those heterozygous for factor V Leiden, and greater than 100-fold in women who were doubly heterozygous for 20210G>A and factor V Leiden .VTE complicated 17.8% of pregnancies in women doubly heterozygous for 20210G>A and factor V Leiden, compared to 6.2% of those in women heterozygous for the 20210G>A allele alone, suggesting that the combination confers a nearly threefold greater risk than 20210G>A heterozygosity alone .The absolute risk for pregnancy-associated VTE in 20210G>A homozygotes and women doubly heterozygous for 20210G>A and factor V Leiden is less well defined:Women doubly heterozygous for 20210G>A and factor V Le | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. iden, compared to 6.2% of those in women heterozygous for the 20210G>A allele alone, suggesting that the combination confers a nearly threefold greater risk than 20210G>A heterozygosity alone .The absolute risk for pregnancy-associated VTE in 20210G>A homozygotes and women doubly heterozygous for 20210G>A and factor V Leiden is less well defined:Women doubly heterozygous for 20210G>A and factor V Leiden have a higher risk for VTE in the range of 1/20 to 1/125 pregnancies . The estimated absolute risk in 20210G>A homozygotes is approximately 1/40 pregnancies .A family study found a low risk for pregnancy-associated VTE in asymptomatic doubly heterozygous women. No VTE events occurred during pregnancy; postpartum VTE complicated 1.8% of pregnancies .In a large family cohort of women who were heterozygous, doubly heterozygous or homozygous for factor | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. >A and factor V Leiden have a higher risk for VTE in the range of 1/20 to 1/125 pregnancies . The estimated absolute risk in 20210G>A homozygotes is approximately 1/40 pregnancies .A family study found a low risk for pregnancy-associated VTE in asymptomatic doubly heterozygous women. No VTE events occurred during pregnancy; postpartum VTE complicated 1.8% of pregnancies .In a large family cohort of women who were heterozygous, doubly heterozygous or homozygous for factor V Leiden or 20210G>A, the absolute risk for pregnancy associated VTE with women with no, a single, or combined defects was 0.73, 1.97, and 7.65 per 100 pregnancy years, respectively .Oral contraceptive use. The use of oral contraceptives substantially increases the risk for VTE in women heterozygous for the F2 20210G>A allele. The risk for thrombosis is much higher during the first year of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. heterozygous, doubly heterozygous or homozygous for factor V Leiden or 20210G>A, the absolute risk for pregnancy associated VTE with women with no, a single, or combined defects was 0.73, 1.97, and 7.65 per 100 pregnancy years, respectively .Oral contraceptive use. The use of oral contraceptives substantially increases the risk for VTE in women heterozygous for the F2 20210G>A allele. The risk for thrombosis is much higher during the first year of oral contraceptive use than during subsequent years .Oral contraceptive use alone and 20210G>A heterozygosity alone are associated with a two- to fourfold and two- to threefold increased risk for VTE, respectively. However, the relative risk for VTE is increased 16- to 59-fold in 20210G>A heterozygotes who use contraceptives, indicating a supra-additive effect .The risk for VTE is also markedly increased in oral contraceptive users who are doubly | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. is much higher during the first year of oral contraceptive use than during subsequent years .Oral contraceptive use alone and 20210G>A heterozygosity alone are associated with a two- to fourfold and two- to threefold increased risk for VTE, respectively. However, the relative risk for VTE is increased 16- to 59-fold in 20210G>A heterozygotes who use contraceptives, indicating a supra-additive effect .The risk for VTE is also markedly increased in oral contraceptive users who are doubly heterozygous for 20210G>A and factor V Leiden, with reported odds ratios ranging from 17 to 110 . Although no studies have estimated the thrombotic risk associated with oral contraceptives in 20210G>A homozygotes, the risk is likely to be substantially higher than in women who are heterozygous.Despite the marked increase in relative risk, the absolute incidence of VTE may still be low because of the low baseline risk in young healthy women.In a | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. increased in oral contraceptive users who are doubly heterozygous for 20210G>A and factor V Leiden, with reported odds ratios ranging from 17 to 110 . Although no studies have estimated the thrombotic risk associated with oral contraceptives in 20210G>A homozygotes, the risk is likely to be substantially higher than in women who are heterozygous.Despite the marked increase in relative risk, the absolute incidence of VTE may still be low because of the low baseline risk in young healthy women.In a recent family study that assessed the risk of a first VTE during OCP use in women heterozygous, doubly heterozygous, or homozygous for factor V Leiden or 20210G>A, the incidence of VTE in women with a single defect or combined defects was 0.35 and 0.94 per 100 person-years, respectively .In another family study the absolute incidence of VTE among women with a 20210G>A allele who used oral contraceptives | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. risk in young healthy women.In a recent family study that assessed the risk of a first VTE during OCP use in women heterozygous, doubly heterozygous, or homozygous for factor V Leiden or 20210G>A, the incidence of VTE in women with a single defect or combined defects was 0.35 and 0.94 per 100 person-years, respectively .In another family study the absolute incidence of VTE among women with a 20210G>A allele who used oral contraceptives was 0.2%/years of use .A prospective family study found that none of the 84 asymptomatic women with a 20210G>A allele who used oral contraceptives developed VTE during a total of 84 years of use .Other contraceptives. The risk for VTE associated with transdermal and vaginal ring contraception is at least as high as the risk for VTE associated with oral contraceptives . The thrombotic risk of these newer forms of contraception in 20210G> | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. gt;A allele who used oral contraceptives was 0.2%/years of use .A prospective family study found that none of the 84 asymptomatic women with a 20210G>A allele who used oral contraceptives developed VTE during a total of 84 years of use .Other contraceptives. The risk for VTE associated with transdermal and vaginal ring contraception is at least as high as the risk for VTE associated with oral contraceptives . The thrombotic risk of these newer forms of contraception in 20210G>A heterozygotes has not been studied, but is likely to be higher than in women without thrombophilia. Unopposed progestin contraception is associated with a much lower risk for thrombosis than estrogen-containing contraception. A retrospective study found that oral progestin alone did not increase the risk for VTE in high-risk women with a history of thrombosis and/or thrombophilia including a small group of 20210G>A heterozygotes and women doubly heterozygous for 20210 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. contraception in 20210G>A heterozygotes has not been studied, but is likely to be higher than in women without thrombophilia. Unopposed progestin contraception is associated with a much lower risk for thrombosis than estrogen-containing contraception. A retrospective study found that oral progestin alone did not increase the risk for VTE in high-risk women with a history of thrombosis and/or thrombophilia including a small group of 20210G>A heterozygotes and women doubly heterozygous for 20210G>A and factor V Leiden . However, no prospective studies confirm the safety of progestin-alone contraception in 20210G>A heterozygotes.Hormone replacement therapy (HRT). Oral HRT is associated with a two- to fourfold increase in relative risk for VTE in healthy postmenopausal users of HRT compared to non-users . The risk increases with higher estrogen doses and may differ with the particular estrogen and progestin components .Limited data suggest that women | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. heterozygotes and women doubly heterozygous for 20210G>A and factor V Leiden . However, no prospective studies confirm the safety of progestin-alone contraception in 20210G>A heterozygotes.Hormone replacement therapy (HRT). Oral HRT is associated with a two- to fourfold increase in relative risk for VTE in healthy postmenopausal users of HRT compared to non-users . The risk increases with higher estrogen doses and may differ with the particular estrogen and progestin components .Limited data suggest that women heterozygous for a 20210G> allele who use HRT have a significantly increased thrombotic risk:A case-control study found that women with a 20210G>A allele or a factor V Leiden allele who used oral estrogen replacement had a 25-fold increased risk for VTE compared with non-users without either thrombophilic allele .The risk of VTE in postmenopausal HRT users with either a 20210G>A or a factor V | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. progestin components .Limited data suggest that women heterozygous for a 20210G> allele who use HRT have a significantly increased thrombotic risk:A case-control study found that women with a 20210G>A allele or a factor V Leiden allele who used oral estrogen replacement had a 25-fold increased risk for VTE compared with non-users without either thrombophilic allele .The risk of VTE in postmenopausal HRT users with either a 20210G>A or a factor V Leiden allele was threefold higher than the risk in HRT users without thrombophilia .The risk for VTE may differ with the type of hormonal content. In one study, the risk for VTE was fivefold higher with conjugated equine estrogen use than with esterified estrogen use among women with a 20210G>A allele or factor V Leiden allele .A meta-analysis found that women with either a 20210G>A allele or a factor V Le | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. >A or a factor V Leiden allele was threefold higher than the risk in HRT users without thrombophilia .The risk for VTE may differ with the type of hormonal content. In one study, the risk for VTE was fivefold higher with conjugated equine estrogen use than with esterified estrogen use among women with a 20210G>A allele or factor V Leiden allele .A meta-analysis found that women with either a 20210G>A allele or a factor V Leiden allele who used oral estrogen had an eightfold increased venous thrombotic risk .Transdermal hormone replacement therapy. The available evidence suggests that transdermally administered estrogen has minimal or no effect on thrombotic risk .Multiple retrospective studies and a meta-analysis found that current use of low- or high-dose transdermal estrogen replacement with or without a progestin did not increase the risk for VTE. In contrast, oral HRT was associated with a two- to fourfold increase in thrombotic risk .There | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. ;A allele or a factor V Leiden allele who used oral estrogen had an eightfold increased venous thrombotic risk .Transdermal hormone replacement therapy. The available evidence suggests that transdermally administered estrogen has minimal or no effect on thrombotic risk .Multiple retrospective studies and a meta-analysis found that current use of low- or high-dose transdermal estrogen replacement with or without a progestin did not increase the risk for VTE. In contrast, oral HRT was associated with a two- to fourfold increase in thrombotic risk .There is also evidence that transdermal estrogen is associated with a lower thrombotic risk than oral estrogen in women with inherited thrombophilic disorders such as prothrombin-related thrombophilia .Women with a 20210G>A allele using transdermal estrogen had a risk similar to that of non-users with the allele. Among women with a 20210G>A allele the use of oral estrogen was associated with a fourfold higher risk for VTE than transdermal estrogen . However, no | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. to fourfold increase in thrombotic risk .There is also evidence that transdermal estrogen is associated with a lower thrombotic risk than oral estrogen in women with inherited thrombophilic disorders such as prothrombin-related thrombophilia .Women with a 20210G>A allele using transdermal estrogen had a risk similar to that of non-users with the allele. Among women with a 20210G>A allele the use of oral estrogen was associated with a fourfold higher risk for VTE than transdermal estrogen . However, no prospective randomized trials have confirmed the safety of transdermal HRT in women with inherited or acquired thrombophilia and/or prior VTE.Selective estrogen receptor modulators (SERMs). Limited data suggest that SERMs such as tamoxifen and raloxifene are associated with a twofold increased risk for VTE, similar to the risk for HRT . The thrombotic risk associated with tamoxifen was higher than raloxifene in trials for primary prevention of breast cancer . 20210G>A heterozygosity did not | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. VTE than transdermal estrogen . However, no prospective randomized trials have confirmed the safety of transdermal HRT in women with inherited or acquired thrombophilia and/or prior VTE.Selective estrogen receptor modulators (SERMs). Limited data suggest that SERMs such as tamoxifen and raloxifene are associated with a twofold increased risk for VTE, similar to the risk for HRT . The thrombotic risk associated with tamoxifen was higher than raloxifene in trials for primary prevention of breast cancer . 20210G>A heterozygosity did not increase the risk for arterial or venous thromboembolism in high-risk healthy women using tamoxifen for breast cancer prevention . However, both studies were limited by the small number of cases included. The risk for VTE in women heterozygous for a 20210G>A allele who use SERMs is uncertain but likely higher than that associated with SERM use alone.Obesity. Obesity (BMI>30 kg/m2) is associated with a two- to threefold increased | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. G>A heterozygosity did not increase the risk for arterial or venous thromboembolism in high-risk healthy women using tamoxifen for breast cancer prevention . However, both studies were limited by the small number of cases included. The risk for VTE in women heterozygous for a 20210G>A allele who use SERMs is uncertain but likely higher than that associated with SERM use alone.Obesity. Obesity (BMI>30 kg/m2) is associated with a two- to threefold increased risk for VTE. Obese women with a 20210 G>A allele have a nearly sevenfold higher risk for VTE than women with neither risk factor. Overweight women (BMI ≥25 and <30 kg/m2) with the allele have a fivefold increased thrombotic risk .Organ transplantation. It is unclear whether 20210G>A heterozygosity contributes to thrombotic and other complications after organ transplantation .A 20210G>A allele was | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. associated with a two- to threefold increased risk for VTE. Obese women with a 20210 G>A allele have a nearly sevenfold higher risk for VTE than women with neither risk factor. Overweight women (BMI ≥25 and <30 kg/m2) with the allele have a fivefold increased thrombotic risk .Organ transplantation. It is unclear whether 20210G>A heterozygosity contributes to thrombotic and other complications after organ transplantation .A 20210G>A allele was associated with a trend toward a threefold increased risk for thromboembolic complications after renal transplantation which did not reach statistical significance due to the small number of recipients with the allele .20210G>A heterozygosity was identified in 14% of liver allografts complicated by hepatic artery thrombosis, but not in recipient peripheral blood leukocytes . However, a recent study found no association with hepatic vascular thrombosis after liver transplantation Central venous catheters. An indwelling central venous catheter is the strongest risk factor for | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 10G>A allele was associated with a trend toward a threefold increased risk for thromboembolic complications after renal transplantation which did not reach statistical significance due to the small number of recipients with the allele .20210G>A heterozygosity was identified in 14% of liver allografts complicated by hepatic artery thrombosis, but not in recipient peripheral blood leukocytes . However, a recent study found no association with hepatic vascular thrombosis after liver transplantation Central venous catheters. An indwelling central venous catheter is the strongest risk factor for upper-extremity thrombosis, contributing to up to one third of occurrences . The data on the contribution of a 20210G>A allele to catheter-related thrombosis are conflicting:20210G>A heterozygotes had a two- to threefold increased risk for central venous catheter-related thrombosis .Two other studies reported a low prevalence of the allele in persons with catheter-related thrombosis, similar to controls or the general population .Surgery. It is still | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. venous catheter is the strongest risk factor for upper-extremity thrombosis, contributing to up to one third of occurrences . The data on the contribution of a 20210G>A allele to catheter-related thrombosis are conflicting:20210G>A heterozygotes had a two- to threefold increased risk for central venous catheter-related thrombosis .Two other studies reported a low prevalence of the allele in persons with catheter-related thrombosis, similar to controls or the general population .Surgery. It is still unclear to what extent the F2 20210G>A allele adds to the overall thrombotic risk in individuals undergoing surgery. Any excess risk conferred by 20210G>A heterozygosity is likely small in comparison to the thrombotic risk associated with surgery:Individuals with a 20210G>A allele or a factor V leiden allele undergoing surgery had a nearly 13-fold increased risk for upper-extremity DVT during a postoperative period of up to three | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. general population .Surgery. It is still unclear to what extent the F2 20210G>A allele adds to the overall thrombotic risk in individuals undergoing surgery. Any excess risk conferred by 20210G>A heterozygosity is likely small in comparison to the thrombotic risk associated with surgery:Individuals with a 20210G>A allele or a factor V leiden allele undergoing surgery had a nearly 13-fold increased risk for upper-extremity DVT during a postoperative period of up to three months .In a large prospective trial, a 20210G>A allele was a risk factor for symptomatic VTE after total hip or knee arthroplasty, conferring a tenfold increase in risk. The allele was associated with a sixfold increased risk for symptomatic postoperative pulmonary embolism .In contrast, several other studies found no association between a 20210 G>A allele and the risk for VTE after orthopedic surgery .Travel. Some evidence suggests that 20210G | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. during a postoperative period of up to three months .In a large prospective trial, a 20210G>A allele was a risk factor for symptomatic VTE after total hip or knee arthroplasty, conferring a tenfold increase in risk. The allele was associated with a sixfold increased risk for symptomatic postoperative pulmonary embolism .In contrast, several other studies found no association between a 20210 G>A allele and the risk for VTE after orthopedic surgery .Travel. Some evidence suggests that 20210G>A heterozygotes are more likely to develop VTE after travel. One study found that air travel was a mild risk factor for a first VTE (OR = 2). However, the combination of air travel and any type of thrombophilia (including 20210G>A heterozygosity) was associated with a 17-fold increase in risk, indicating a multiplicative interaction between the two risk factors .Minor injury. Minor leg injuries are associated with a | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. . Some evidence suggests that 20210G>A heterozygotes are more likely to develop VTE after travel. One study found that air travel was a mild risk factor for a first VTE (OR = 2). However, the combination of air travel and any type of thrombophilia (including 20210G>A heterozygosity) was associated with a 17-fold increase in risk, indicating a multiplicative interaction between the two risk factors .Minor injury. Minor leg injuries are associated with a fivefold increased risk for VTE. The risk is particularly high after muscle or ligament rupture. Individuals with a 20210G>A allele and a minor leg injury had a nine- to 30-fold higher thrombotic risk than those without these risk factors .Thrombosis NOT Convincingly Associated with Prothrombin-Related ThrombophiliaArterial thrombosis in adults. The role of prothrombin-related thrombophilia in arterial disease is controversial, with conflicting results from different studies. The available evidence indicates | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. . Minor leg injuries are associated with a fivefold increased risk for VTE. The risk is particularly high after muscle or ligament rupture. Individuals with a 20210G>A allele and a minor leg injury had a nine- to 30-fold higher thrombotic risk than those without these risk factors .Thrombosis NOT Convincingly Associated with Prothrombin-Related ThrombophiliaArterial thrombosis in adults. The role of prothrombin-related thrombophilia in arterial disease is controversial, with conflicting results from different studies. The available evidence indicates that the 20210G>A allele is not a major risk factor for arterial thrombosis. The majority of myocardial infarctions (MIs) and strokes occur in the presence of established cardiovascular risk factors including hypertension, hyperlipidemia, diabetes mellitus, and smoking. The contribution of a single thrombophilic allele to these complex diseases is likely small.Most studies of unselected or elderly adult populations found no significant association between the presence of one or two 20210G>A | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. from different studies. The available evidence indicates that the 20210G>A allele is not a major risk factor for arterial thrombosis. The majority of myocardial infarctions (MIs) and strokes occur in the presence of established cardiovascular risk factors including hypertension, hyperlipidemia, diabetes mellitus, and smoking. The contribution of a single thrombophilic allele to these complex diseases is likely small.Most studies of unselected or elderly adult populations found no significant association between the presence of one or two 20210G>A alleles and myocardial infarction or stroke .Other studies also found no increase in the annual incidence of stroke, transient ischemic attack (TIA), or MI associated with a 20210G>A allele . In a prospective study the annual incidence of a first arterial cardiovascular event was 0.56% in family members with the allele compared to 0.73% in those without the allele . The annual incidence of ischemic stroke or TIA was also similar in family members with | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. two 20210G>A alleles and myocardial infarction or stroke .Other studies also found no increase in the annual incidence of stroke, transient ischemic attack (TIA), or MI associated with a 20210G>A allele . In a prospective study the annual incidence of a first arterial cardiovascular event was 0.56% in family members with the allele compared to 0.73% in those without the allele . The annual incidence of ischemic stroke or TIA was also similar in family members with and without the allele (0.33% and 0.23%, respectively).The results of several meta-analyses suggest at most a weak association with ischemic stroke (pooled OR = 1.4) , and myocardial infarction (per allele relative risk = 1.31) .The risk for arterial thrombosis in 20210G>A homozygotes is unknown, as very few homozygous individuals have been included in published studies.Myocardial infarction (MI). | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. TIA was also similar in family members with and without the allele (0.33% and 0.23%, respectively).The results of several meta-analyses suggest at most a weak association with ischemic stroke (pooled OR = 1.4) , and myocardial infarction (per allele relative risk = 1.31) .The risk for arterial thrombosis in 20210G>A homozygotes is unknown, as very few homozygous individuals have been included in published studies.Myocardial infarction (MI). Although a 20210G>A allele is not a major risk factor for ischemic heart disease, it may contribute to the risk for MI in selected populations. 20210G>A heterozygosity increased the risk for MI 43-fold in women younger than age 50 years with traditional cardiovascular risk factors, particularly smoking . The risk may also be increased in heterozygous postmenopausal women who use HRT .Stroke in adults. Although 20210G>A is | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. studies.Myocardial infarction (MI). Although a 20210G>A allele is not a major risk factor for ischemic heart disease, it may contribute to the risk for MI in selected populations. 20210G>A heterozygosity increased the risk for MI 43-fold in women younger than age 50 years with traditional cardiovascular risk factors, particularly smoking . The risk may also be increased in heterozygous postmenopausal women who use HRT .Stroke in adults. Although 20210G>A is not a general risk factor for stroke, it may contribute to the risk for stroke in selected populations: In two case-control studies, 20210G>A heterozygosity conferred a fourfold increased risk for ischemic stroke in individuals younger than age 50 years without established cardiovascular risk factors .Arterial thromboembolism may also occur "paradoxically" through a patent foramen ovale (PFO) in the heart of individuals with venous thrombosis. A meta-analysis concluded that a 20210G | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 20210G>A is not a general risk factor for stroke, it may contribute to the risk for stroke in selected populations: In two case-control studies, 20210G>A heterozygosity conferred a fourfold increased risk for ischemic stroke in individuals younger than age 50 years without established cardiovascular risk factors .Arterial thromboembolism may also occur "paradoxically" through a patent foramen ovale (PFO) in the heart of individuals with venous thrombosis. A meta-analysis concluded that a 20210G>A allele was significantly associated with PFO-related stroke in comparison with controls (OR = 3.85) and persons with non-PFO associated stroke (OR = 2.31) .Stroke in children. Arterial ischemic stroke in children usually occurs in the setting of multiple predisposing factors . Data on the association of thrombophilia with ischemic stroke are conflicting and mostly limited to small case series and case-control studies. Stroke accounted for 21% of thrombotic events | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. -analysis concluded that a 20210G>A allele was significantly associated with PFO-related stroke in comparison with controls (OR = 3.85) and persons with non-PFO associated stroke (OR = 2.31) .Stroke in children. Arterial ischemic stroke in children usually occurs in the setting of multiple predisposing factors . Data on the association of thrombophilia with ischemic stroke are conflicting and mostly limited to small case series and case-control studies. Stroke accounted for 21% of thrombotic events in a highly selected group of symptomatic children with a 20210G>A allele. Children younger than age two years had a significantly higher rate of arterial thrombosis than older children in whom venous thrombosis was far more common . A meta-analysis of 13 studies found that children with a 20210G>A allele had a twofold increased risk for a first stroke. The risk was increased nearly 19-fold in children with multiple thrombophilic defects . However | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. Stroke accounted for 21% of thrombotic events in a highly selected group of symptomatic children with a 20210G>A allele. Children younger than age two years had a significantly higher rate of arterial thrombosis than older children in whom venous thrombosis was far more common . A meta-analysis of 13 studies found that children with a 20210G>A allele had a twofold increased risk for a first stroke. The risk was increased nearly 19-fold in children with multiple thrombophilic defects . However, several other small studies and a smaller meta-analysis found no significant association between 20210G>A heterozygostiy and first ischemic stroke in children .Genotype-Phenotype CorrelationsHomozygotes for the 20210G>A allele have a greater risk for thrombosis than do heterozygotes for the 20210G>A allele, although the magnitude of risk is not well defined.The clinical course of an acute thrombotic episode is not more | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. children with multiple thrombophilic defects . However, several other small studies and a smaller meta-analysis found no significant association between 20210G>A heterozygostiy and first ischemic stroke in children .Genotype-Phenotype CorrelationsHomozygotes for the 20210G>A allele have a greater risk for thrombosis than do heterozygotes for the 20210G>A allele, although the magnitude of risk is not well defined.The clinical course of an acute thrombotic episode is not more severe or resistant to anticoagulation in 20210G>A homozygotes than in 20210G>A heterozygotes.PrevalenceF2
20210G>A heterozygosity is the second most common inherited thrombophilia after factor V Leiden. The prevalence of 20210G>A heterozygosity varies by population.20210G>A heterozygosity occurs in 1.7%-3% of the general US and European populations. The highest heterozygosity | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. of an acute thrombotic episode is not more severe or resistant to anticoagulation in 20210G>A homozygotes than in 20210G>A heterozygotes.PrevalenceF2
20210G>A heterozygosity is the second most common inherited thrombophilia after factor V Leiden. The prevalence of 20210G>A heterozygosity varies by population.20210G>A heterozygosity occurs in 1.7%-3% of the general US and European populations. The highest heterozygosity rate is found in Europe; the allele is extremely rare in Asian, African, and Native American populations. Within Europe the prevalence varies from 3% in southern Europe to 1.7% in northern countries .In the US, the prevalence of 20210G>A heterozygosity is 2%-5% in whites, 2.2% in Hispanic whites, and 0%- 0.6% in African Americans, reflecting the world distribution of the allele | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. US and European populations. The highest heterozygosity rate is found in Europe; the allele is extremely rare in Asian, African, and Native American populations. Within Europe the prevalence varies from 3% in southern Europe to 1.7% in northern countries .In the US, the prevalence of 20210G>A heterozygosity is 2%-5% in whites, 2.2% in Hispanic whites, and 0%- 0.6% in African Americans, reflecting the world distribution of the allele .A study of a multiracial American population found 20210G>A heterozygosity in 8.2% of white and 1.1% of African American persons with VTE. The allele was not detected in the African American control population .Among adults with VTE, 20210G>A heterozygosity is present in 6%-14% of those with a first VTE, and 18%-21% of those with a personal or family | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. , reflecting the world distribution of the allele .A study of a multiracial American population found 20210G>A heterozygosity in 8.2% of white and 1.1% of African American persons with VTE. The allele was not detected in the African American control population .Among adults with VTE, 20210G>A heterozygosity is present in 6%-14% of those with a first VTE, and 18%-21% of those with a personal or family history of recurrent VTE . A prospective study identified 20210G>A heterozygosity in 3.7% of children with a first spontaneous VTE .The prevalence of 20210G>A homozygosity is approximately one in 10,000. 20210G>A homozygosity is found in 1.8%-4.5% of individuals with a history of VTE .Double heterozygosity for the 20210G>A and factor | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. % of those with a personal or family history of recurrent VTE . A prospective study identified 20210G>A heterozygosity in 3.7% of children with a first spontaneous VTE .The prevalence of 20210G>A homozygosity is approximately one in 10,000. 20210G>A homozygosity is found in 1.8%-4.5% of individuals with a history of VTE .Double heterozygosity for the 20210G>A and factor V Leiden alleles occurs in approximately one in 1000 individuals in the general population and is found in 1%-5% of persons with VTE .Differential DiagnosisThe differential diagnosis of venous thromboembolism (VTE) includes several other inherited and acquired thrombophilic disorders. Because these disorders are not clinically distinguishable, laboratory testing is required for diagnosis in each case. (See also Management, Evaluations Following Initial Diagnosis.)InheritedFactor V Leiden refers to the specific G-to- | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 10G>A and factor V Leiden alleles occurs in approximately one in 1000 individuals in the general population and is found in 1%-5% of persons with VTE .Differential DiagnosisThe differential diagnosis of venous thromboembolism (VTE) includes several other inherited and acquired thrombophilic disorders. Because these disorders are not clinically distinguishable, laboratory testing is required for diagnosis in each case. (See also Management, Evaluations Following Initial Diagnosis.)InheritedFactor V Leiden refers to the specific G-to-A substitution in F5 that predicts a single amino-acid replacement (Arg506Gln) that destroys a cleavage site for activated protein C. The resulting impaired anticoagulant response to activated protein C results in increased thrombin generation and a prothrombotic state . Factor V Leiden heterozygosity is found in 3%-8% of the general population and 15%-20% of individuals with a first VTE. Factor V Leiden heterozygosity is identified in 20% | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. refers to the specific G-to-A substitution in F5 that predicts a single amino-acid replacement (Arg506Gln) that destroys a cleavage site for activated protein C. The resulting impaired anticoagulant response to activated protein C results in increased thrombin generation and a prothrombotic state . Factor V Leiden heterozygosity is found in 3%-8% of the general population and 15%-20% of individuals with a first VTE. Factor V Leiden heterozygosity is identified in 20%-40% of symptomatic 20210G>A heterozygotes with VTE .A specific single nucleotide variant (SNV) (677C>T) in MTHFR, encoding methylenetetrahydrofolate reductase, results in a variant thermolabile enzyme with reduced activity for the remethylation of homocysteine. Homozygosity for 677C>T (also known as C677T) occurs in 10%-20% of the general | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. Leiden heterozygosity is identified in 20%-40% of symptomatic 20210G>A heterozygotes with VTE .A specific single nucleotide variant (SNV) (677C>T) in MTHFR, encoding methylenetetrahydrofolate reductase, results in a variant thermolabile enzyme with reduced activity for the remethylation of homocysteine. Homozygosity for 677C>T (also known as C677T) occurs in 10%-20% of the general population and predisposes to mild hyperhomocysteinemia in the setting of suboptimal folate stores. The MTHFR variant does not confer an increased risk for VTE . The official designation for this MTHFR variant is NM_005957.4:c.665C>T, NP_005948.3:p.Ala222Val, or rs1801133.Inherited deficiencies of the natural anticoagulant proteins C, S, and antithrombin are approximately | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. 10%-20% of the general population and predisposes to mild hyperhomocysteinemia in the setting of suboptimal folate stores. The MTHFR variant does not confer an increased risk for VTE . The official designation for this MTHFR variant is NM_005957.4:c.665C>T, NP_005948.3:p.Ala222Val, or rs1801133.Inherited deficiencies of the natural anticoagulant proteins C, S, and antithrombin are approximately tenfold less common than F2 20210G>A heterozygosity with a combined prevalence of less than 1% of the population. Anticoagulant protein deficiencies are found in 1%-3% of individuals with a first VTE.Elevated levels of lipoprotein(a) are associated with premature atherosclerosis and may also be a risk factor for venous thrombosis.Hereditary dysfibrinogenemias are rare and infrequently cause thrombophilia and thrombosis.See Thrombophilia: OMIM | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. C, S, and antithrombin are approximately tenfold less common than F2 20210G>A heterozygosity with a combined prevalence of less than 1% of the population. Anticoagulant protein deficiencies are found in 1%-3% of individuals with a first VTE.Elevated levels of lipoprotein(a) are associated with premature atherosclerosis and may also be a risk factor for venous thrombosis.Hereditary dysfibrinogenemias are rare and infrequently cause thrombophilia and thrombosis.See Thrombophilia: OMIM Phenotypic Series, to view genes associated with this phenotype in OMIM.AcquiredHigh plasma concentration of homocysteine is present in 10% of individuals with a first VTE. In early studies a high plasma concentration of homocysteine was associated with a twofold increased relative risk for VTE; however, more recent data indicate that a high homocysteine level is a much weaker risk factor for VTE than previously reported . It was not associated with an increased thrombotic risk in children . The plasma concentration of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. thrombosis.See Thrombophilia: OMIM Phenotypic Series, to view genes associated with this phenotype in OMIM.AcquiredHigh plasma concentration of homocysteine is present in 10% of individuals with a first VTE. In early studies a high plasma concentration of homocysteine was associated with a twofold increased relative risk for VTE; however, more recent data indicate that a high homocysteine level is a much weaker risk factor for VTE than previously reported . It was not associated with an increased thrombotic risk in children . The plasma concentration of homocysteine reflects genetic as well as environmental factors.Antiphospholipid antibodies comprise a heterogeneous group of autoantibodies directed against proteins bound to phospholipid. Anticardiolipin antibodies and the related anti-beta2 glycoprotein 1 antibodies are detected by solid phase immunoassays. Lupus inhibitors are autoantibodies that interfere with phospholipid-dependent clotting assays. Persistent high titer lupus inhibitors are more strongly associated with arterial and venous thromboembolism than other antiphospholipid antibodies . Recent evidence indicates that "triple positivity" for all three types of antiphospholipid antibodies confers | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. risk in children . The plasma concentration of homocysteine reflects genetic as well as environmental factors.Antiphospholipid antibodies comprise a heterogeneous group of autoantibodies directed against proteins bound to phospholipid. Anticardiolipin antibodies and the related anti-beta2 glycoprotein 1 antibodies are detected by solid phase immunoassays. Lupus inhibitors are autoantibodies that interfere with phospholipid-dependent clotting assays. Persistent high titer lupus inhibitors are more strongly associated with arterial and venous thromboembolism than other antiphospholipid antibodies . Recent evidence indicates that "triple positivity" for all three types of antiphospholipid antibodies confers the highest risk of thrombosis and pregnancy complications .An elevated factor VIII level greater than 150% of normal is associated with a four- to fivefold increased risk for a first VTE and also significantly increases the risk for recurrent thrombosis . Familial clustering of high factor VIII levels occurs although the relative contribution from genetic factors to persistently elevated levels is still unknown. No specific F8 benign variants have been associated with elevaled plasma factor VIII levels .An elevated plasma level of factor IX | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. for all three types of antiphospholipid antibodies confers the highest risk of thrombosis and pregnancy complications .An elevated factor VIII level greater than 150% of normal is associated with a four- to fivefold increased risk for a first VTE and also significantly increases the risk for recurrent thrombosis . Familial clustering of high factor VIII levels occurs although the relative contribution from genetic factors to persistently elevated levels is still unknown. No specific F8 benign variants have been associated with elevaled plasma factor VIII levels .An elevated plasma level of factor IX and factor XI is each associated with a twofold increased risk for VTE .Elevated plasma levels of both factor VIII and factor IX are associated with an eightfold increased risk for VTE .An elevated plasma prothrombin level greater than 110% -115% of normal is associated with a twofold increased risk for VTE in the absence of F2 20210G>A . The combination of oral contraceptives and high levels of prothrombin and factor V or factor XI had a supra-additive | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. .An elevated plasma level of factor IX and factor XI is each associated with a twofold increased risk for VTE .Elevated plasma levels of both factor VIII and factor IX are associated with an eightfold increased risk for VTE .An elevated plasma prothrombin level greater than 110% -115% of normal is associated with a twofold increased risk for VTE in the absence of F2 20210G>A . The combination of oral contraceptives and high levels of prothrombin and factor V or factor XI had a supra-additive effect on thrombotic risk, with odds ratios ranging from ten to 13 .OtherAlthough thrombosis has been reported in association with defects or deficiencies of other coagulation and fibrinolytic proteins, including heparin cofactor II, PAI-1, tissue factor pathway inhibitor, thrombin activatable fibrinolysis inhibitor (TAFI), and protein Z, a causal association has not been established .Other genetic risk factors for thrombosis under investigation include a fibrinogen gamma chain variant (10034T), genetic | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. or factor XI had a supra-additive effect on thrombotic risk, with odds ratios ranging from ten to 13 .OtherAlthough thrombosis has been reported in association with defects or deficiencies of other coagulation and fibrinolytic proteins, including heparin cofactor II, PAI-1, tissue factor pathway inhibitor, thrombin activatable fibrinolysis inhibitor (TAFI), and protein Z, a causal association has not been established .Other genetic risk factors for thrombosis under investigation include a fibrinogen gamma chain variant (10034T), genetic variants in the protein C promoter region, and several single-nucleotide polymorphisms (SNPs) in coagulation proteins . Genome-wide association analysis has also been used to identify novel susceptibility genes for venous thrombosis .Several global markers of coagulation such as measurement of thrombin generation show promise in identifying individuals at high risk for thrombosis .Testing for these potential risk factors is not routinely recommended and in many cases, assays are not commercially available.ManagementEvaluations Following Initial DiagnosisBecause of the | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. variant (10034T), genetic variants in the protein C promoter region, and several single-nucleotide polymorphisms (SNPs) in coagulation proteins . Genome-wide association analysis has also been used to identify novel susceptibility genes for venous thrombosis .Several global markers of coagulation such as measurement of thrombin generation show promise in identifying individuals at high risk for thrombosis .Testing for these potential risk factors is not routinely recommended and in many cases, assays are not commercially available.ManagementEvaluations Following Initial DiagnosisBecause of the increased incidence of a second thrombophilic defect among symptomatic individuals with inherited thrombophilia , individuals heterozygous or homozygous for the F2
20210G>A allele should be tested for other inherited and acquired thrombophilic disorders in order to evaluate the risk for thrombosis. Testing should include:An activated protein C resistance or DNA assay for factor V Leiden;Serologic assays for anticardiolipin antibodies and anti-beta 2 glycoprotein 1 antibodies;Multiple phospholipid-dependent coagulation assays for | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. ations Following Initial DiagnosisBecause of the increased incidence of a second thrombophilic defect among symptomatic individuals with inherited thrombophilia , individuals heterozygous or homozygous for the F2
20210G>A allele should be tested for other inherited and acquired thrombophilic disorders in order to evaluate the risk for thrombosis. Testing should include:An activated protein C resistance or DNA assay for factor V Leiden;Serologic assays for anticardiolipin antibodies and anti-beta 2 glycoprotein 1 antibodies;Multiple phospholipid-dependent coagulation assays for a lupus inhibitor.Note: Testing for antiphospholipid antibodies should include assays for all three antibodies (anticardiolipin antibodies, anti-beta2 glycoprotein 1 antibodies, and lupus inhibitors) since only 50% of individuals with the antiphospholipid antibody syndrome have more than one type of antibody.Evaluation of high-risk individuals (i.e., those with a history of recurrent VTE especially at a young age, or those with strong family history of VTE at a young age), | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK1148/ | m1y45qR | Prothrombin-Related Thrombophilia | C1867596 | 31,754 | prothrombin-related thrombophilia. ;Multiple phospholipid-dependent coagulation assays for a lupus inhibitor.Note: Testing for antiphospholipid antibodies should include assays for all three antibodies (anticardiolipin antibodies, anti-beta2 glycoprotein 1 antibodies, and lupus inhibitors) since only 50% of individuals with the antiphospholipid antibody syndrome have more than one type of antibody.Evaluation of high-risk individuals (i.e., those with a history of recurrent VTE especially at a young age, or those with strong family history of VTE at a young age), should also include assays of:Protein C activity;Antithrombin activity;Protein S activity or free protein S antigen.Note: In an evaluation for thrombophilia: (1) Measurement of plasma concentration of homocysteine is no longer recommended because no data support the use of vitamin supplementation or modification of the duration of anticoagulation in individuals with hyperhomocysteinemia and a history of VTE ; (2) there is no clinical rationale for DNA testing for MTHFR variants; and (3) routine | [
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