bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic Evaluation of Von Willebrand Factor/Factor VIII Concentrate (Humate-P®) Prior to Elective Surgery in Patients with Von Willebrand Disease.
Authors: Di Paola Jorge , Gill Joan , Bernstein Jonathan , Leissinger Cindy , Ragni Margaret , Shopnik Rinah , Valentino Leonard , Friedman Carl , Knaub Sigurd 
Published: April 2020

Abstract
The VWF/FVIII concentrate Humate-Pâ (ZLB Behring) was studied in a prospective, uncontrolled, open-label clinical trial in adult and pediatric von Willebrand disease (VWD) patients undergoing elective surgery. During an initial PK phase, a detailed profile of FVIII: C, VWF: RCo, and VWF: Ag levels was obtained for each patient after an infusion of 60 IU/kg VWF: RCo/kg body weight as Humate-P, to guide loading dosing intra- and postoperatively. Forty-one subjects were evaluated for the pharmacokinetic assessment: the median age was 31 years (range 16 to 47 years); 66.7% of subjects were female; 17 had Type 1 VWD, 2 had Type 2A, 4 had Type 2B, 6 had Type 2M, and 13 had Type 3. In the 34 subjects who underwent surgery, the primary endpoint of effective hemostasis (investigator-rated assessment as excellent or good) was achieved in 100% (34/34) of subjects 24 hours after the last infusion. The VWF: RCo PK revealed a median incremental in vivo recovery (IVR) of 2.4% per IU/kg over baseline (range, 1.1% – 4.2%), and an overall median IVR response of 86.7% over baseline (range, 37% – 169%). Median value of Cmax was 159 IU/dL (range 84–334). Median terminal half-life of VWF: RCo was 11.2 hours (range 3.5 to 74.9), median clearance 3.1 ml/kg/h (range, 1.0 to 16.6). The FVIII: C PK revealed a median incremental of 2.7% per IU/kg. A median response of 95.5% (range, 44% – 176%) was achieved 15 minutes after the PK infusion, with values remaining &gt;90% until 4 hours post infusion. At 48 hours post infusion, median levels had decreased to 68% over baseline (range, 17% – 122%). An analysis of the relationship between IVR and dose administered demonstrated the dose linearity of the VWF concentrate within a wide dose range (10–135 IU VWF: RCo/kg b. w.). Using the log-transformed IVR in a repeated measures ANCOVA model, the slope (of log10 IVR vs. dose) was −0.0025 (95% confidence interval: −0.0053 to 0.0004).
Conclusion: The PK results are comparable to PK data from other clinical studies with Humate-Pâ as well as PK data from other VWF-containing products. Dose linearity has been shown over a wide range of dosages. The inter-individual variability observed underlines the importance of performing PK assessments, to guide dosing, prior to surgical interventions.
IVR of all VWF-RCo doses (kg/dL), linear regression with 95% CI of mean IVR of all VWF-RCo doses (kg/dL), linear regression with 95% CI of mean
Is Homozygosity for the MTHFR C677T Mutation a Risk Factor for Miscarriage? — Likely.
Authors: Altomare Ivy , Aledort Louis M. 
Published: April 2020

Abstract
Various hereditary thrombophilias such as activated protein C resistance, the factor V leiden mutation, the prothrombin G20210A mutation, protein S deficiency, hyperhomocysteinemia, or combinations of the above disorders have been linked to pregnancy loss at varying stages of gestation (Robertson L, et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol2006;132(2):171–96; Seligsohn U, et al. Genetic susceptibility to venous thrombosis. N Engl J Med2001;344(16):1222–31). The literature regarding methylenetetrahydrofolate reductase (MTHFR) mutations is confusing. Much of the evidence supporting a causal relationship between MTHFR mutations and early fetal loss comes from individual case reports with little outcome data. Three recent meta-analyses of thrombophilia in pregnancy concluded that although there may be a trend toward higher risk, the relationship between MTHFR mutations and spontaneous abortions is not truly significant (Robertson L, et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol2006;132(2):171–96; Nelen WL, et al. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril2000;74(6):1196–9; Rey E, et al. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet2003;361(9361):901–8). In contrast, a study supporting the role of MTHFR mutations in recurrent unexplained abortions found a 2–3 fold increased risk of early fetal loss among Caucasian females homozygous for the C677T mutation versus normal controls (Nelen WL, et al. Genetic risk factor for unexplained recurrent early pregnancy loss. Lancet1997;350(9081):861). We present 5 patients with this genetic defect who presented consecutively to our clinic for decision making for future pregnancies. Each had strong histories of miscarriages after the 8th week of gestation. The clinical features of these patients are reported in the table below.

Each woman is Caucasian, and is homozygous for the MTHFR C677T mutation with no other acquired or hereditary thrombophilias. Homocysteine levels were also in normal range for each patient. Our case series of 5 Caucasian women gives support to the theory of a causal relationship between MTHFR mutations and fetal loss. We recommended anticoagulation with low-molecular weight or unfractionated heparin for each patient as a therapeutic intervention to reduce the risk of recurrent abortion in future pregnancies.
A Novel Heterozygous Point Mutation Causing Coagulation Factor XII Deficiency as the Molecular Mechanism of Fatal Thrombosis Event in a Chinese Pedigree.
Authors: Feng Ying , Xu Ye , Pang Ying , Dai Jing , Xie Wei , Zhou Xuhong , Ding Qiulan , Wang Xuefeng 
Published: April 2020

Abstract
Objective: To study on the laboratory diagnosis and molecular mechanism of a pedigree with fatal cerebral thrombosis event caused by hereditary coagulation factor XII deficiency.
Methods: Activated partial thromboplastin time (APTT), prothrombin time (PT), coagulation factor VIII activity (FVIII:C), factor IX activity (FIX:C), factor XI and factor XII activity (FXI:C and FXII:C) were determined in the propositus and the other kindred member for phenotypic analysis. All the 14 exons and their flank sequences of factor XII gene form the propositus were amplified by PCR. The purified PCR products were sequenced directly. After mutation was found, the corresponding gene fragments covering the mutated point from the other member of the kindred were amplified and sequenced.
Results: The APTT of the propositus was significantly elongated (&gt;120 seconds), while her PT was normal. Her FVIII:C,FIX:C and FXI:C were all normal. But her FXII:C was only 1 %, lower than normal. A heterozygous G3774C missense mutation in exon 4 was identified, which has led to the substitution of serine (TCT) 73 for cysteine (TGT). The sequencing results from the pedigree suggested that the other asymptomatic member of the kindred also had the same heterozygous mutation.
Conclusion: The Propositus was diagnosed with inherited coagulation factor XII deficiency. The novel gene mutation found in this pedigree is the molecular mechanism leading to the fatal thrombosis events in the propositus.
Weight Adjusted Low-Dose Warfarin Decreases the Incidence of Thalidomide (T) Associated Venous Thromboembolism (VTE) in Patients (pts) with Multiple Myeloma (MM) and Waldenstroms Macroglobulinemia (WM).
Authors: Miller Kena C. , Manochakian Rami , Padmanabhan Swaminathan , Coignet Jean-Gabriel , Musial Laurie , DePaolo Dawn , Chanan-Khan Asher Alban 
Published: April 2020

Abstract
Introduction: T is an effective antimyeloma therapy. An important and problematic side effect of T is development of VTE. The underlying etiology of T associated VTE remains unknown, though a definite rise in its incidence is recorded when combined with other antimyeloma therapies such as dexamethasone (15%) and doxorubicin (26%). Defining an optimal way to prevent T associated VTE is important to improve patient’s quality of life and safety of T. We prospectively investigated the use of weight-adjusted, low-dose warfarin to decrease the incidence of VTE among pts treated with T based regimens.
Methods: All pts treated with T-based therapies, at our institute were given VTE prophylaxis with 1 vs. 2mg warfarin for actual body weight &lt;70 kg vs. ≥ 70 kg, respectively. Concurrent aspirin or other anticoagulants were not given. Pts with underlying pre-existing hypercoaguable disorders were fully anticoagulated with warfarin and were excluded from this analysis. Warfarin was continued throughout the duration of T therapy.
Results: A total of 80 pts, 60 years (range 43–82), 35M and 45F are included in this analysis. Sixty three had stage III and 14 had ≤ stage II MM while 3 pts had WM. T was given with dex in 58 (72%) with dox in 57(71%) and with bortezomib in 32 (40%). Table 1 outlines the T based regimens used. IgG MM was noted in 39, IgA in 20 and 31 had other types of MM. Median T dose was 200 mg (range 50–300) and the median duration 4 months (range 1–6 months). Thirty two pts received 1mg and 48 received 2mg warfarin. Overall incidence of VTE was 6.25% (n=5). There were no bleeding complications noted with the use of warfarin in this pt population.
Conclusion: Our study demonstrates for the first time that a weight adjusted low-dose warfarin approach in MM pts decreases the incidence of T associated VTE and can be safely instituted in pts treated with this important anti-myeloma therapy. Interestingly, none of the pts who received T with Doxil experienced any episode of VTE.
Regimen No. of Patients Thalidomide Alone 1 Dexamethasone + Thalidomide 28 Bortezomib + Doxil + Thalidomide 24 VAD + Thalidomide 22 Bortezomib + Cyclophosphmaide + Dexamethasone + Thalidomide 5
High Incidence of Venous Thromboembolism in Patients with Lymphoma Receiving Chemotherapy: Assessment of Risk Factors.
Authors: Teegala Shyam , Zhou Xiao , Huen Auris , Ji Yuan , Fayad Luis , Romaguera Jorge Enrique , Hagemeister F.B. , Vadhan-Raj Saroj 
Published: April 2020

Abstract
Background: Venous thromboembolism (VTE) is a significant cause of cancer morbidity and mortality. Lymphoma patients (pts) are at increased risk of VTE, however, the exact incidence and risk factors are unknown.
Methods: Of the 1050 newly referred Lymphoma pts to MDACC in 2003 identified, medical records (MR) of 538 consecutive pts were reviewed for demographics, tumor histology, staging, laboratory values, type of chemotherapy (CT) regimens, risk factors for VTE, incidence of VTE and management over a follow up of 2 years.
Results: 207 out of 538 pts received at least one cycle of CT at MDACC (total CT cycles 1125). The median age was 56 years (range 17–82); there were 81 females and 126 males. Majority of pts (61.8%) were newly diagnosed and the most common histologies were Large Cell Lymphoma (31.88%), followed by Hodgkin’s Disease (16.9%) and Follicular Lymphoma (14.98%). Thirteen out of 207 (6.28%) pts had history of VTE prior to CT and 37 (17.9 %) pts out of 207 had 41 new episodes of VTE; 29 Deep Vein Thrombosis (DVT) (12 upper and 12 lower extremity) and 12 Pulmonary Embolism (PE); 2 pts had both DVT and PE. All VTE episodes were confirmed by imaging except in 3 pts. The mean baseline hemoglobin (Hb) in VTE pts was 12.8 g/dL. The median cycle number for VTE occurrence was cycle 3 with 24/37 (64.86%) pts experiencing VTE by cycle 3 and 6/37 (16.2%) pts had VTE in cycle 1. Two out of the 37 (5.4%) pts had recurrent VTE. Among those with new VTE, 31/37 (83.78%) pts were of age greater than 40, 25/37 (67.56%) pts had BMI &gt; 25, 32/37 (86.4%) pts had aggressive or highly aggressive histology and 29/37 (78.37%) pts had stage 3 or 4 disease. Twenty-three out of 31 (74.2%) pts had received erythropoietin before or during the cycle of VTE. Fourteen of 207 (6.79%) pts were on thromboprophylaxis before the chemotherapy. Only 1 of these 14 pts experienced VTE, approximately 2 months after the discontinuation of prophylaxis. Central venous catheter (CVC) thrombosis occurred in 6/174 (3.44%) patients with CVC. The most common systemic treatment for VTE was Enoxaparin (12/33). By multivariate logistic regression analysis of many of the previously described risk factors and other variables, Doxorubicin and/or Methotrexate based CT regimen was found to be a significant independent risk factor for VTE (OR 5.58, 95%CI 1.62 to 19.13. p = 0.0062).
Conclusion: VTE is a frequent and underestimated complication in Lymphoma pts. These findings underscore the importance of prospective clinical trials of anticoagulation prophylaxis in the high risk patients receiving CT.
Influence of ADP in the Course of Thrombin Receptors Activation.
Authors: Lu Xiaoxu , Wu De Pei , Han Yue , Dai Lan , Sheng Wenhong 
Published: April 2020

Abstract
Objective In order to compare the functions of ADP in platelet aggregation and platelet membrane surface glycoproteins expression after thrombin receptors activation, then to investigate the role of ADP in thrombin signal transmission.
Methods Peptide SFLLRN (PAR1-AP, TRAP) and AYPGKF(PAR4-AP)were used for stimulating platelet at different time points (0~30minute) in 12 normal subjects, then the alterations of platelet aggregation and GPIbα, P-selectin were analyzed in the involvement of ADP inhibitor, ApyraseVII, which was observed by aggregometer and flowcytometry respectively.
Results Either PAR1 or PAR4 peptide can lead to platelet activation, inducing absolute platelet aggregation, together with a persistent increase of P-selectin and reversible interlisation of GPIb. Platelet aggregation was partly inhibited by ApyraseVII and showed a reversible curve upon PAR1 activation, and no change upon PAR4 activation. In addition, ApyraseVII accelerated the return of GPIb to platelet surface in PAR1 pathway, produced weak effect on GPIbα internalisation, … ltogether with little effect on GPIb alteration in PAR4 pathway. Meanwhile, no change of P-selectin was obtained in the involvement of Apyrase for both peptides.
Conclusion All the results confirm a critical role of ADP in thrombin signal transmission through the process of PAR1 pathway. ADP induces platelet aggregation and slows down the restoration of GPIb to platelet surface.
Timing and Safety of Postpartum Enoxparin.
Authors: Freedman Rachel A. , Zwicker Jeffrey , Bauer Kenneth Alan 
Published: April 2020

Abstract
The appropriate time to restart anticoagulation in the postpartum period is not known. Both the American College of Obstetrics and Gynecology as well as American College of Chest Physicians (ACCP) have issued guidelines regarding the use of anticoagulants during pregnancy but neither have generated recommendations regarding the timing of the first dose of low-molecular-weight heparin (LMWH) in the postpartum period. The incidence of postpartum hemorrhage was assessed in a retrospective cohort study of 95 women treated with enoxaparin and compared with 303 consecutive deliveries where anticoagulation was not administered. The rate of severe postpartum hemorrhage did not differ significantly for women treated with peripartum enoxaparin versus a control group of women undergoing vaginal delivery (3.6% versus 1.4%, P=0.72) or cesarean section (5.1% versus 3.4%, P=0.98). There were no severe postpartum hemorrhages following the re-initiation of enoxaparin postpartum. In 75% of vaginal deliveries and 49% of cesarean sections, enoxaparin was restarted within 24 hours. Two incisional hematomas were observed in the group of women who received enoxaparin within 24 hours following cesarean section. We conclude that severe postpartum hemorrhage is an infrequent complication following the administration of enoxaparin postpartum. In support of current clinical practice, enoxaparin can be safely administered 0 to 24 hours following vaginal delivery and 12 to 36 hours following cesarean section.
Anti-Platelet Properties of Salivary Secretions of the Avian Leech.
Authors: Wakeman Lisa J. , Munro Roger C. , Al-Ismail Saad 
Published: April 2020

Abstract
Introduction
Haematophages, animals evolved to a bloodsucking lifestyle as their exclusive mode of feeding secrete compounds capable of arresting haemostasis in the host. It is clear that exploitation of host haemostasis is an absolute requirement for the survival of these species. Since the discovery and with the subsequent characterisation and engineering of Hirudin a potent thrombin inhibitor from the European medicinal leech Hirudo medicinalis, attention has been focused on the potential anticoagulant and platelet aggregation inhibitors derived from an array of different species of leech from both the Rhynchobdellid and Arhynchobdellid orders. Haematophagous leeches of the genus Theromyzon sp. of the Rhynchobdellid order, also termed duck leeches, feed directly on the nasal passages, trachea and nictating membranes of migratory birds. We present the novel observation of inhibition of aggregation of human platelets by the salivary secretion extracts of the avian leech Theromyzon tessulatum.
Methods
Twelve adult leeches of the species T. tessulatum (total weight 2.828g) were anaesthetised with ethanol vapour. The leeches were severed at the anterior end and a homogenate produced containing salivary gland secretions. The posterior two thirds of the leeches were treated identically to serve as control material. Platelet rich plasma (PRP) was prepared from blood from a normal individual (free from known platelet modifying medicines) mixed 9:1 (v:v) with 0.105 M trisodium citrate in siliconised glass vacutainers. Platelet numbers were adjusted with autologous platelet poor plasma (PPP) to obtain concentrations of approximately 300 × 109/L. Leech extracts (anterior or posterior control) were added to PRP at a ratio of 1:4. Aggregation studies were performed using thrombin (10units/ml), collagen 10μg/ml, Ristocetin (1.5mg/ml) and ADP (5μm/ml).
Results
Data from this study shows that platelet aggregation was completely inhibited when stimulated by thrombin, collagen and ADP and partially inhibited (40%) on the addition of ristocetin.
Conclusion
Our observations contradict the belief that the anti-thrombocyte properties of this species of haematophagous leech are restricted to duck thrombocytes. We suggest the presence of one or more inhibitory molecules acting by various mechanisms including inhibition of vWF and platelet integrin mediated collagen interactions, inhibition of ristocetin mediated vWF and platelet GPIb receptor binding and salivary secretion derived apyrase inhibition of arachidonic acid mediated platelet aggregation.
These findings provide conclusive evidence that this blood sucking bird leech has the ability to overcome thrombocyte function in higher vertebrates.
Is Age Related Fibrinogen Affected by Warfarin?.
Authors: Munro Roger C. , Wakeman Lisa J. , Al-Ismail Saad 
Published: April 2020

Abstract
Introduction: There is published evidence which indicates that advancing age may be associated with higher plasma concentrations of fibrinogen. There is also evidence that derived fibrinogen values are significantly higher than Clauss measurements and that this discrepancy is greater in patients receiving warfarin. The purpose of this study was to determine whether age related derived fibrinogen levels are similar in both warfarin and non-warfarin groups.
Methods: Venous samples were collected into siliconised glass B-D Vacutainers containing tri-sodium citrate (Ref: 367691) from 1000 patients receiving long term warfarin treatment and an equal number of age-matched patients not receiving warfarin. Genders were equally represented in both groups. Patients in both groups were categorized into 5 years age bands as follows: &lt;40 n=23: 40–44 n=20: 45–49 n=43; 50–54 n=74: 55–59 n=113: 60–64 n=155: 65–69 n=178: 70–74 n=191: 75–79 n=124; 80–84 n=56: 85–89 n=23. Derived fibrinogen was measured in each patient on an ACL300R coagulometer (I L) within 1 hour of collection using IL PT-FIB HS Plus reagent and following the manufacturer’s protocol. Appropriate CLSI guidelines were followed throughout. A normal probability plot of the data was performed to confirm that it did not deviate too much from the normal distribution.
Results: The T-test for independent samples using the separate variance estimate showed that there was a statistically significant difference in the mean fibrinogen between patients on warfarin and those not on warfarin (p&lt;0.05) in each group except for the last (85–89 years). There was a statistically significant difference (ANOVA) in the fibrinogen levels of patients of different age in both warfarinised and non-warfarinised groups (p&lt;0.05). The modified least significance procedure in the ANOVA test showed that in the non-warfarin group, most of significant difference in fibrinogen between the different age groups is contributed by the difference between patients under 50 years of age. In the non-warfarin group, it requires an age gap of at least 20 years for the difference in fibrinogen to be statistically significant but in the warfarin group, it only requires an age gap of ten years (p&lt;0.05). Both Linear Regression and Cross Tabulation indicate that the relationship between fibrinogen and age does not vary whether or not the patient is on warfarin. These also show that the effect of age on fibrinogen is not affected by warfarin treatment.
Conclusion: Differences or correlations detected in this analysis are of statistical significance but not necessarily clinically significant. Placing age and warfarin treatment in the same model shows that variations in fibrinogen have to be explained by other factors (e.g. technical) not included in the study as only 12% of the error in predicting fibrinogen levels can be reduced by knowing both the age and status of warfarin treatment in individual patients.
High Incidence of Venous Thromboembolism (VTE) in Patients with Cancer Hospitalized at a University Hospital in Chile. Efficacy of Pharmacological Thromboprophylaxis.
Authors: Conte Guillermo F. , Figueroa Gaston L. , Altmann Arie D. , Donaire Luisa A. 
Published: April 2020

Abstract
Inpatients are at increased risk of VTE due to multiple factors. Cancer diagnosis is an important risk factor determined through prospective studies. The aims of this study are to know the incidence of VTE in cancer patients hospitalized due to acute medical conditions and describe the use of pharmacological thromboprophylaxis and its efficacy.
Methods: Retrospective analysis of cancer patients admitted to the University of Chile Clinical Hospital due to acute medical conditions between 2003 and 2004. Exclusion criteria: VTE diagnosed at admission, oral anticoagulant therapy at admission, age &lt;18 years, admission to Intensive Care Unit (ICU). It was necessary to confirm VTE diagnosis by ultrasonography or angio-CT scan.
Results: Data of 366 patients was retrieved. The cancer origin was: gastric (38%), lung (19%), colorectal (15%), breast (10%), hepatocarcinoma (5%), others (13%). Seventy-seven percent of the cases presented an advanced disease (stage TNM III-IV). The main diagnoses at admission were: pneumonia (17%), vomits/dehydratation (16%), urinary tract infection (7%), decompensated diabetes mellitus (7%), digestive hemorrhage (7%). In 125 cases (34%) no type of pharmacological thromboprophylaxis was used; unfractionated heparin was used in 120 (33%) (5000 U sc c/8–12 hr) and low-molecular-weight heparin (dalteparin or enoxaparin) in 121 (33%). The VTE incidence was 3% (11 cases). In patients who did not receive thromboprophylaxis, the VTE incidence was 6.4% (8/125) versus 1.2% (3/241) in those who were administered heparin or LMWH (Odds Ratio=0.18 CI 95% 0.05–0.65). The group of patients who did not receive thromboprophylaxis was younger (median 60 vs. 65 years), had a higher frequency of thrombocytopenia (&lt;150.000; 39% vs. 15%) and hypoprothrombinemia (INR&gt;1.5; 35% vs. 14%), and a lower frequency of recent oncologic surgery (3% vs.19%).
Conclusions: Cancer patients with acute medical conditions showed a high incidence of symptomatic VTE (3% in this series). One third of patients were not administered pharmacological thromboprophylaxis. The use of thromboprophylaxis in these high-risk patients was associated to a significative reduction of the VTE frequency.