bluuebunny/crossref_metadata_2025_split huggingface dataset:
The deletion polymorphism in the angiotensin-converting enzyme gene is a moderate risk factor for venous thromboembolism
Authors: Czwalinna Andreas , Wermes Cornelia , Eisert Roswith , Scharrer Inge , Ganser Arnold , Ehrenforth Silke , von Depka Mario 
Published: March 2018

SummaryACE displays potent vasoconstrictive effects, attenuation of fibrinolysis, and platelet activation and aggregation, thus possibly promoting venous thromboembolism (VTE). The ACE gene contains an insertion (I) or deletion (D) polymorphism accounting for 50% of the variation in serum ACE concentration. To evaluate the role of the I/D polymorphism in VTE, its prevalence was determined in 931 patients with VTE and 432 blood donors. The prevalence of the DD genotype was 27.6% in patients and 21.3% in controls (OR 1.4; p <0.02). In multivariate analysis there was a trend of the DD genotype to be an independent risk factor (OR 1.4; p = 0.08). No differences in DD genotype prevalence according to exogenous risk factors were found. Coinheritance of FV G1691A, PT G20210A mutation, and PS deficiency with the DD genotype increased the relative risk of VTE. Thus, the ACE DD genotype is a moderate risk factor of hereditary thrombophilia. Exogenous risk factors did not alter the manifestation of VTE among carriers of the DD genotype, whereas coinheritance of the DD genotype with the aforementioned defects increased the risk for VTE considerably.
Quality of life in venous disease
Authors: Vossen Carla , Rosendaal Frits , Cameron Linda , Bovill Edwin , Kaptein Adrian , van Korlaar Inez 
Published: March 2018

SummaryQuality of life (QOL) can be defined as the functional effect of an illness and its consequent therapy upon a patient, as perceived by the patient. Studies on the impact of chronic venous disease on quality of life are scarce compared to quality of life research in other diseases. The purpose of this paper was to describe instruments that assess the quality of life in patients with chronic venous disease and to review the literature on this topic.A computer search of the MedLine database was performed to identify papers; the bibliographies of relevant articles were reviewed to obtain additional papers. Papers were included if they described the development or use of a quality of life instrument for patients with chronic venous disease.A total of 25 papers were identified that fit the inclusion criteria. The studies described in the papers used six different generic instruments and ten disease-specific instruments. Quality of life in chronic venous disease was assessed in 12 studies. Six studies compared different types of treatment for chronic venous disease where QOL was an outcome measure. Despite the wide variety of measures used, results indicate that the quality of life of patients with chronic venous disease is affected in the physical domain mostly with regard to pain, physical functioning and mobility, and that they suffer from negative emotional reactions and social isolation.We feel that QOL should be a standard measure in future studies in patients with chronic venous disease, preferably with a combination of generic and disease-specific measures.
Contraceptive pills induce an improvement in congenital hypoplasminogenemia in two unrelated patients with ligneous conjunctivitis
Authors: Saggiorato Graziella , Pellati Donatella , Casonato Alessandra , Spiezia Luca , Pontara Elena , Gavasso Sabrina , Girolami Antonio , Sartori Maria 
Published: March 2018

SummarySevere type I plasminogen deficiency is the underlying cause of ligneous conjunctivitis, a rare disease characterized by wood-like pseudomembranes developing on the ocular and extraocular mucosa. Two unrelated female patients with ligneous conjunctivitis and moderate hypoplasminogenemia are described. Being of fertile age, they were treated with oral contraceptives, which determined a marked increase in plasminogen levels. Moreover, a palpebral pseudomembrane stopped growing in one patient and disappeared completely in the other while on the estroprogestinic treatment. In patient n.2,who also suffered from von Willebrand’s disease, prior Cushing’s disease induced an increase in both von Willebrand factor and plasminogen levels, which dropped after curative hypophysectomy. Genetic plasminogen study showed a 19Lys>Glu mutation in a heterozygous state in the first proposita and in a homozygous state in the second proband. In addition, both index patients were homozygous for a new intron F-14T>G mutation, which was found to reduce the acceptor splicing site prediction score.In conclusion, oral contraceptive therapy may improve plasminogen deficiency and deserves attention as an alternative therapeutic approach in selected cases of ligneous conjunctivitis with low, but not absent, plasminogen synthesis.
Quality of life and the duration of treatment with vitamin K antagonists in patients with deep venous thrombosis
Authors: Sprangers Mirjam , de Haes Hanneke , Büller Harry , Prins Martin , Locadia Mirjam 
Published: March 2018

SummaryIn clinical practice, decisions on the duration of treatment with vitamin K antagonists are usually based on the presence of persistent risk factors, the risk of bleeding and centre policy. Little is known about the influence of patients’ experienced quality of life. The objectives of this study were: 1) to explore the course of quality of life in patients with venous thrombosis treated for 3 months versus patients treated for 6 months with vitamin K antagonists; 2) to investigate the factors that were associated with the duration of treatment with vitamin K antagonists. The study sample comprised patients participating in a multi-centre clinical trial. Quality of life was assessed at study entry, after 10-14 days,3 and 6 months in 360 patients. Overall, no dif-ferences in quality of life were found between the 2 patient groups. An interaction effect between group and time was found for physical functioning. Regression analyses indicated that the presence of one or more permanent risk factors, duration of hospitalisation, mobility prior to deep-vein thrombosis and study centre were associated with the duration of treatment with vitamin K antagonists. Interestingly, quality of life was not associated with treatment duration. Since study centre was the most important factor associated with treatment duration, local policy appears to have a great influence on decisions regarding the duration of treatment with vitamin K antagonists.Part of this manuscript has been included in a poster presentation at the International Society for Quality of Life Research in Amsterdam, The Netherlands, November 8, 2001.
Derivation of a Simple Clinical Model to Categorize Patients Probability of Pulmonary Embolism: Increasing the Models Utility with the SimpliRED D-dimer
Authors: Anderson David , Rodger Marc , Ginsberg Jeffrey , Kearon Clive , Gent Michael , Turpie Alexander , Bormanis Janis , Weitz Jeffrey , Chamberlain Michael , Bowie Dennis , Barnes David , Hirsh Jack , Wells Philip 
Published: March 2018

SummaryWe have previously demonstrated that a clinical model can be safely used in a management strategy in patients with suspected pulmonary embolism (PE). We sought to simplify the clinical model and determine a scoring system, that when combined with D-dimer results, would safely exclude PE without the need for other tests, in a large proportion of patients. We used a randomly selected sample of 80% of the patients that participated in a prospective cohort study of patients with suspected PE to perform a logistic regression analysis on 40 clinical variables to create a simple clinical prediction rule. Cut points on the new rule were determined to create two scoring systems. In the first scoring system patients were classified as having low, moderate and high probability of PE with the proportions being similar to those determined in our original study. The second system was designed to create two categories, PE likely and unlikely. The goal in the latter was that PE unlikely patients with a negative D-dimer result would have PE in less than 2% of cases. The proportion of patients with PE in each category was determined overall and according to a positive or negative SimpliRED D-dimer result. After these determinations we applied the models to the remaining 20% of patients as a validation of the results. The following seven variables and assigned scores (in brackets) were included in the clinical prediction rule: Clinical symptoms of DVT (3.0), no alternative diagnosis (3.0), heart rate >100 (1.5), immobilization or surgery in the previous four weeks (1.5), previous DVT/PE (1.5), hemoptysis (1.0) and malignancy (1.0). Patients were considered low probability if the score was <2.0, moderate of the score was 2.0 to 6.0 and high if the score was over 6.0. Pulmonary embolism unlikely was assigned to patients with scores <4.0 and PE likely if the score was >4.0. 7.8% of patients with scores of less than or equal to 4 had PE but if the D-dimer was negative in these patients the rate of PE was only 2.2% (95% CI = 1.0% to 4.0%) in the derivation set and 1.7% in the validation set.Importantly this combination occurred in 46% of our study patients. A score of <2.0 and a negative D-dimer results in a PE rate of 1.5% (95% CI = 0.4% to 3.7%) in the derivation set and 2.7% (95% CI = 0.3% to 9.0%) in the validation set and only occurred in 29% of patients. The combination of a score <4.0 by our simple clinical prediction rule and a negative SimpliRED D-Dimer result may safely exclude PE in a large proportion of patients with suspected PE.
A Novel Approach to the Assessment of Variations in the Human Platelet Count
Authors: James John , Brown Dianne , Whyte Gordon , Dean Mark , Chesterman Colin , Donald Jennifer , Buckley Michael 
Published: March 2018

SummaryThis is the first report of a method to assess the significance of numerical changes in the platelet count based upon a result exceeding the normal intra-individual variation in platelet numbers. Serial platelet counts from 3,789 subjects were analysed to determine the intra-individual variation in platelet numbers. A platelet count difference of 98 × 109/L in males was found to represent a change that would occur by chance in less than 1 in 1,000 platelet count determinations. Tables to determine the significance of platelet number variations, given N previous observations, are provided at two probability levels. The repeatability of the platelet count was calculated as 0.871 (males) and 0.849 (females) indicating that the heritability of platelet count is high and that the platelet count is predominantly genetically determined. A seasonal variation in platelet count was found with a ‘winter’ versus ‘summer’ difference of 5.10 × 109/L (males) and 5.82 × 109/L (females).
A Comparison of the Safety and Efficacy of Oral Antiocoagulation for the Treatment of Venous Thromboembolic Disease in Patients with or without Malignancy
Authors: Legnani Cristina , Lee Agnes , Manotti Cesare , Hirsh Jack , D’Angelo Armando , Pengo Vittorio , Moia Marco , Coccheri Sergio , Palareti Gualtiero 
Published: March 2018

SummaryThe optimal long-term treatment of acute venous thromboembolism (VTE) in patients with malignancy remains undefined. In particular, based on current evidence, it is uncertain whether secondary prophylaxis using standard intensity oral anticoagulant therapy is associated with higher risks of bleeding and recurrent thrombosis in patients with cancer than in those without cancer. This study compared the outcome of anticoagulation courses in 95 patients with malignancy with those of 733 patients without malignancy. All patients were participants in a large, nation-wide population study and were prospectively followed from the initiation of their oral anticoagulant therapy.Based on 744 patient-years of treatment and follow-up, the rates of major (5.4% vs 0.9%), minor (16.2% vs 3.6%) and total (21.6% vs 4.5%) bleeding were statistically significantly higher in cancer patients compared with patients without cancer. Bleeding was also a more frequent cause of early anticoagulation withdrawal in patients with malignancy (4.2% vs. 0.7%; p <0.01; RR 6.2 (95%CI 1.95-19.4). There was a trend towards a higher rate of thrombotic complications in cancer patients (6.8% vs. 2.5%; p = 0.058; RR 2.5 [CI 0.96-6.5]) but this did not achieve statistical significance. In the group of patients with cancer, the bleeding rate was high across the different INR categories and was independent of the temporally associated International Normalized Ratio (INR). In contrast, the bleeding rate was increased only with INR values greater than 4.5 in the group of patients without cancer. The rate of thrombotic events was significantly higher in both cohorts when the INR was less than 2.0.In conclusion, patients with malignancy treated with oral anticoagulants have a higher rate of bleeding and possibly an increased risk of recurrent thrombosis compared with patients without malignancy. Safer and more effective anticoagulant therapy is needed for this challenging group of patients.
The VITA Project: Heritability of Resistance to Activated Protein C
Authors: Tosetto Alberto , Castaman Giancarlo , Cappellari Antonio , Rodeghiero Francesco 
Published: March 2018

SummaryResistance to activated protein C (APC) is a risk factor for venous thromboembolism also in absence of the FV Leiden mutation. To evaluate the influence of genetic factors on APC resistance, we evaluated the heritability of the APC resistance phenotype in 1,519 sib-parent pairs randomly selected from the VITA Project. After adjustment for known influencing factors, a high heritability coefficient (0.58) was observed and parental response to APC was the single most important factor in predicting the corresponding phenotype in sibs. In 32 parentsib pairs in which phenotypic resistance to APC unrelated to FV Leiden was present in both parents and sibs, no additional mutation on the 306-aminoacid residue of FV (FV Cambridge and FV Hong Kong) was found. In these 32 parent-sib pairs, FVIII:C and vWf:Ag levels were not significantly increased and there was no excess prevalence of the R2 allele of exon 13 of FV gene. This study suggests that the response to APC is significantly influenced by genetic factors also at a population level, but the responsible mechanisms are still undefined.
The HR2 Haplotype of Factor V Is not Associated with the Risk of Myocardial Infarction
Authors: Doggen Carine , de Visser Marieke , Vos Hans , Bertina Rogier , Cats Volkert , Rosendaal Frits 
Published: March 2018

SummaryThe HR2 haplotype of the factor V gene, which contains the histidine to arginine substitution at position 1299, has been reported to be associated with reduced factor V levels. Because high factor V levels have been found to be associated with an increased risk of myocardial infarction, we examined how the presence of the R2 allele affected the risk of myocardial infarction in the case-control “Study of Myocardial Infarctions Leiden”.Among 560 men with a first myocardial infarction before the age of 70 years, 9.5% were heterozygous carriers of the R2 allele. The control group consisted of 646 men, in which 9.9% were heterozygous and 0.2% homozygous carriers of the R2 allele. The risk of myocardial infarction in the presence of the R2 allele was not increased (odds ratio, 0.9; 95% confidence interval 0.6 to 1.4). Exclusion of factor V Leiden carriers did not change this result. The risk was 4.4-fold increased for smokers who carried the R2 allele compared to non-smoking noncarriers. No synergy was found between metabolic risk factors and the presence of the R2 allele.We conclude that the risk of myocardial infarction for men in the presence of the R2 allele of the His1299Arg polymorphism is neither increased nor decreased.
The Procoagulant State of the VX-2 Tumor in Rabbit Lung In Vivo
Authors: Ross Bonnie , Bardossy Leslie , Southward Suzanne , DeReske Marnie , Richardson Mary , Blajchman Morris , Hatton Mark 
Published: March 2018

SummaryDuring their growth, many malignant solid tumors elicit a hemostatic response in the host. In this report, the fluxes of various rabbit plasma hemostatic proteins into pulmonary VX-2 tumors have been measured in vivo. VX-2 cells were contained within a small rabbit plasma clot which was injected intravenously into rabbits. At 28 d, each rabbit was injected intravenously with two radiolabeled (131I, 125I) proteins selected from fibrinogen, prothrombin, antithrombin-α, heparin cofactor II, or plasminogen-I or -II. After allowing the labeled proteins to circulate for 10-200 min, each rabbit was perfused with Krebs-Henseleit solution and the lungs excised. Solid tumors were isolated, weighed and measured for radioactivity content. A mean of 14 tumors/pair of lungs with a mean tumor weight of 0.3 g was obtained. Radioactivity per g of tumor was related to radioactivity/ml of blood at exsanguination for each protein at each time interval. Maximum flux rates were calculated (as pmol/g of tumor/min): Fibrinogen, 65.0; prothrombin, 53.0; antithrombin-α, 24.1; HCII, 17.2; plasminogen-II, 5.0; and plasminogen-I, 3.2. Using immunocytochemical staining, fibrin(ogen) was distributed heterogeneously within the VX-2 tumor, appearing largely in the perinodular region and in the necrotic core. From the net fluxes of these proteins, the profile of chronic hemostasis associated with the VX-2 tumor was shown to differ markedly from the hemostatic response that occurs after an acute vascular injury.
The Identification of Polymorphisms in the Coding Region of the Apolipoprotein (a) Gene
Authors: Leus Frank , Bouma Bonno , van Rijn Herman , Prins Janke 
Published: March 2018

SummaryLipoprotein (a) [Lp(a)] is a quantitative genetic trait in human plasma and elevated levels represent a major inherited risk factor for the development of atherosclerotic disease. In our search for sequence polymorphisms in the coding region of the apolipoprotein(a) [apo(a)] gene that may affect the Lp(a) concentration, four new polymorphic sites were identified. These include two coinciding polymorphisms with an allele frequency of 38% located at amino acid positions 87 and 101 (Leu87,101 →Val) in the interkringle region of kringle IV (K.IV) type 7 and two polymorphisms located in K.IV type 7 (Arg60 →Ser) and in K.IV type 10 (Tyr2 →Phe) both with estimated allele frequencies of about 1%.The linkage between the newly identified K.IV type 7 Leu87,101 →Val polymorphism and earlier described polymorphic sites in the non-coding and coding regions of the apo(a) gene, its distribution over the apo(a) isoform sizes and its possible influence on the Lp(a) concentration was analysed in 201 healthy unrelated Caucasians. The earlier described polymorphic sites included in this study were the variable number of a TTTTA pentanucleotide repeat (7-11 PNR) starting at -1231 bp, the -772 bp G/A polymorphism, the +93 bp C/T polymorphism and the +121 bp G/A polymorphism in the non-coding region, and the K.IV type 8 Thr12/Pro polymorphism and the K.IV type 10 Thr66/Met polymorphism in the coding region of the apo(a) gene.Linkage disequilibria were observed between the polymorphic sites in the 5’ non-coding region and the sites in K.IV type 7 and 8 in the coding region of the apo(a) gene, confirming that the expansion of the variable number of K.IV type 2 repeats results from intrachromosomal recombinational events. The distribution over the apo(a) isoform sizes of the K.IV type 7 Val87,101 subtype was not significantly different from that of the K.IV type 7 Leu87,101 wild-type, suggesting a relative ancient mutational event. No influence of the K.IV type 7 Leu87,101 →Val polymorphism on the Lp(a) level was observed. In fact, of all the polymorphic sites studied, only the +121 A subtype could be associated with an increased, and the K.IV type 8 Pro12 and the 10 PNR subtypes with a reduced, Lp(a) concentration corrected for apo(a) isoform size (p <0.05).
A Longitudinal Study of the Factor VII Rise during Pregnancy
Authors: Wright D. , Thomson J. M. , Sidebotham A. , Hirst C. F. , Hirsch P. , Poller L. 
Published: March 2018

SummaryA longitudinal study of 21 pregnant women has been undertaken using a variety of factor VII assays, including factor VIIa, to investigate the increase of factor VIIc. All assays demonstrated significant rises (p <0.001), most marked for factor VIIa (82%) and factor VIIc rabbit (81%). Smaller rises were seen for factor VIIc bovine (50%) and VII antigen (40%). Three indirect measures of activity state, factor VIIc rabbit:antigen, bovine:antigen and bovine:rabbit, provided conflicting data. Factor VIIa:antigen showed a significant increase of 36% (p <0.001). Within individual pregnancies the change in factor VIIc rabbit and antigen correlated with maternal weight gain (p <0.05). Two activity state measures, bovine:rabbit and bovine:antigen, showed negative correlation with birthweight. The increases in both zymogen and in activity state appear to contribute to the factor VIIc rise. The extent of this rise appears to be influenced by maternal weight gain. Increased factor VII activation is associated with reduced foetal growth.
The Influence of a Serine Protease Inhibitor, Nafamostat Mesilate, on Plasma Coagulation, and Platelet Activation during Experimental Extracorporeal Life Support (ECLS)
Authors: Skogby Maria , Friberg Lars Göran , Tengborn Lilian , Wadenvik Hans , Mellgren Karin 
Published: March 2018

SummaryIntroduction: During extracorporeal circulation the contact between blood and the artificial surface of the circuit induces several changes in the hemostatic system. The objective of the present study was to assess the effect of a serine protease inhibitor – Nafamostat mesilate (FUT-175) – on coagulation and on platelets during experimental extracorpo-real circulation. Methods: Two identical Extra Corporeal Life Support (ECLS) circuits were primed with fresh, heparinized human blood and circulated for 24 h. FUT-175 was added to one of the paired circuits and the other was used as a control. The following FUT-175 concentrations were employed: (1) 7.1 mg/l/h, (2) 14.2 mg/l/h, (3) 14.2 mg/l/h + 85.5 mg given as an initial bolus, (4) 28.5 mg/l/h + 171 mg given as an initial bolus. Blood samples were collected from the circuits before the start of the perfusion and at 0.5, 1, 3, 12, and 24 h of perfusion, and analysed for platelet count, plasma betathromboglobulin ( -TG), platelet membrane glycoprotein (GP) Ib and GPIIb/IIIa expression, thrombin/ antithrombin III complex (TAT), prothrombin fragment 1+2 (F1+2), fibrinogen, D-dimer, and plasminogen activator inhibitor 1 activity (PAI-1). Results: Significantly higher platelet membrane GPIb expression and lower plasma -thromboglobulin levels were observed in the circuits holding FUT-175, suggesting a lower degree of platelet activation. Also, a reduced activation of the coagulation system was observed in the “FUT-circuits”, as reflected by the levels of F1+2 and TAT, and the PAI-1 activity that was rapidly inactivated. Conclusion: FUT-175 reduces the activation of platelets and plasma coagulation in an in vitro ECLS model.