The Impact of Dalteparin (Fragmin®) on Thrombin Generation in Pregnant Women with Venous Thromboembolism: Significance of the Factor V Leiden Mutation

2001 ◽  
Vol 85 (05) ◽  
pp. 782-786 ◽  
Author(s):  
Edda Eberl ◽  
Ulrich Geisen ◽  
Ralf Grossmann ◽  
Franz Keller ◽  
Schambeck Christian
Keyword(s):  
Venous Thromboembolism ◽  
Pregnant Women ◽  
Thrombin Generation ◽  
Clinical Signs ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Asymptomatic Patients ◽  
The Impact ◽  
Fvl Mutation

SummaryHypercoagulability is observed in patients with inherited thrombophilia, e.g. factor V Leiden (FVL) mutation. Pregnancy represents a hypercoagulable state as well. This study addresses the effects of the FVL mutation on haemostatic activation during pregnancy as indicated by prothrombin fragments (F1+2). 233 pregnant women with no history of venous thromboembolism were studied. Additionally, two patient groups (25 pregnant FVL carriers and 36 pregnant women without thrombophilic diathesis) in whom low molecular weight heparin (dalteparin) was used prophylactically against rethrombosis were investigated.None of the women developed clinical signs of venous thromboembolism during pregnancy or after delivery. Untreated women exhibited substantial hypercoagulability. F1+2 levels were similar in FVL carriers and non-carriers (difference n. s.). After sufficient adjustment for anti-factor Xa activity (≥0.15; ≤0.4 U/mL), heparinized women without any thrombophilic diathesis had significantly lower levels of F1+2 than untreated pregnant women. This was evident only in the first and second trimenon (p <0.01). F1+2 levels in heparinized FVL carriers were quite similar to the levels observed in untreated pregnant women, however. In conclusion, our data support the thesis that in comparison to asymptomatic patients, thrombin generation is exaggerated in symptomatic FVL carriers. Coagulation activation during pregnancy can be reduced by dalteparin.

Effect of FV-Leiden Mutation and Antiphospholipid Syndrome on Thethrombin GenerationTest.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3506-3506
Author(s):  
Ferial Peyvandi ◽  
Wolfgang Miesbach ◽  
Wolfgang Wegert ◽  
Inge Scharrer
Keyword(s):  
Antiphospholipid Syndrome ◽  
Thrombin Generation ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Platelet Poor Plasma ◽  
Time To Peak ◽  
Concentration Peak ◽  
Fvl Mutation

Abstract Introduction: The incidence of Factor V Leiden mutation (Arg 506 Gln) is significantly high in patients with venous and arterial thrombosis. In patients with antiphospholipid syndrome (APS), the FVL mutation may play a major role in the occurrence of thrombosis. The aim of this study was to demonstrate that an increased Endogenous Thrombin Potential (ETP) may be an important mechanism for the thrombotic risk associated with FVL and / or APS and to know if the FVL mutation would increase the risk of thrombosis in patients with APS. Additionally, we tested if fluorometric determination of ETP( area under the curve), thrombin generation velocity (PEAK) and TIME TO PEAK (time from starting to reaching the peak), is suitable to determine changes in haemostatic parameters. Methods and patients: We measured the thrombin generation in 120 patients (67F, 53M) with a median age of 40 year categorized in 3 groups of 40 patients each:(1) either heterozygous or homozygous FVL mutation (14F, 26M of whom 29 were heterozygous and 11 were homozygous) (2) presence of antiphospholipid antibodies (aPL) (20F, 20M) and (3) a combination of both (33F,7M). Three characterizing thrombin generation parameters were measured: ETP, PEAK and TIME TO PEAK. Platelet poor plasma samples (PPP) were derived from citrated blood. In a microtiter plate, we used different concentrations of TF with phospholipids after adding PRP(platelet poor plasma) and buffer. The reaction was started after adding substrate solution. Fluorometer was the Fluoroskan Ascent Type 374. Results: Using four concentrations (Innovin dilutions 1:600, 1:6.000, 1:50.000 and 1:500.000) of TF, the following results (ETP units = relative fluorescence units or RFU; PEAK units: RFU/min; TIME TO PEAK units = min) were obtained for the 3 groups: For all patients TF 1:600 median ETP, PEAK and TIME TO PEAK were taken as 100 % because less dilution gives no further increase resp. decrease in these parameters Patients with aPL: median ETP decreased from 100 % to 36,6 % (lowest TF concentration), PEAK to 34,4 % and TIME TO PEAK increased to 218 %. Patients with FVL median ETP decreased from 100 % to 2,64 % (lowest TF concentration), PEAK to 9 % and TIME TO PEAK increased to 282 %. Patients with aPl and FVL => median ETP decreased from 100 % to 33 % (lowest TF concentration), PEAK to 30,8 % and TIME TO PEAK increased to 143 %. While there was no detectable thrombin generation in aPL patients in low concentration of TF, at the two highest concentrations the thrombin generation was comparable to same concentrations in the haemostatically normal control samples(data not shown). For those affected by FVL and aPL, the threshold of detectable thrombin generation was even shifted to lower concentrations of TF, regarding a “residual activity” of about 33 % for ETP and PEAK, as for patients with FVL. In patients with APS, TF 1:50.000 caused a thrombin generation comparable to TF 1:6.000 in haemostatically normal controls, showing a shift in coagulation factor reactability. In a physiological environment this could indicate a stronger haemostatic reaction to minor vascular lesions in patients affected by factor V Leiden mutation than in those without it. Conclusion: A thrombin generation assay utilizing lower concentrations of TF as coagulation initiating agent could be usefully performed to assess thrombophilic states due to coagulation factor mutations and /or presence of antiphospholipid antibody.

Factor V Leiden Mutation Increases the Risk of Venous Thromboembolism in Cancer Patients – Results From the Vienna Cancer and Thrombosis Study (CATS).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2253-2253
Author(s):  
Ingrid Pabinger ◽  
Cihan Ay ◽  
Daniela Dunkler ◽  
Johannes Thaler ◽  
Eva-Maria Reitter ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Factor V Leiden ◽  
Treatment Modalities ◽  
Individual Risk ◽  
Factor V ◽  
Newly Diagnosed ◽  
Factor V Leiden Mutation ◽  
Increased Risk ◽  
The Impact

Abstract Abstract 2253 Background: Patients with cancer are at an increased risk of venous thromboembolism (VTE). The risk varies markedly in different patient populations and improvement of the prediction of VTE would be of advantage for tailoring thrombosis prophylaxis. Factor V Leiden is the most common genetic risk factor for VTE and the impact of factor V Leiden on cancer-associated thrombosis is not yet fully elucidated. Objective: To study the impact of factor V Leiden on the risk of VTE in cancer patients. Patients and Methods: Nine-hundred-eighty-two patients with newly diagnosed cancer (n=745) or progression of disease after complete or partial remission (n=237) were included in the cancer and thrombosis study (CATS), a prospective observational single centre cohort study at the Medical University Vienna. Patients were followed for a maximum period of 2 years. Blood samples were collected at inclusion and factor V Leiden was determined by genotyping. The main outcome measure was symptomatic or lethal objectively confirmed VTE. All VTE events were adjudicated independently. Results: Of the 982 patients (median age 62 years, interquartile range (IQR) 52–68, 537 men, 445 women) factor V-Leiden was found in 72 (7.3%), 70 had a heterozygous and two a homozygous genotype. Ten of 72 (14%) patients with factor V-Leiden developed VTE, whereas this was the case in 69 of 910 (7.6%) patients without factor V-Leiden. Interestingly, both patients with homozygous factor V Leiden developed VTE. In multivariable analysis that included age, sex, different tumour types, newly diagnosed versus recurrence of disease and the treatment modalities (chemotherapy, radiotherapy and surgery) the hazard ratio (HR) for factor V Leiden was 2.04 (95% confidence interval (CI) 1.04–3.97)). In patients with newly diagnosed tumours the HR for factor V Leiden was 3.7 (95% CI 1.2–12.2) after 30 days. In Kaplan Meier analysis the probability for development of VTE after 6 months was 5.7% in those without and 13% in those with factor V Leiden, after one year the corresponding rates were 7.3% and 15%. Conclusions: Factor V Leiden is a genetically determined and thus disease-independent parameter, which is associated with VTE in cancer patients, especially shortly after cancer diagnosis, and could therefore be used for individual risk assignment. Disclosures: No relevant conflicts of interest to declare.

Thrombophilia and risk of VTE recurrence according to the age at the time of first VTE manifestation

VASA ◽  
2015 ◽  
Vol 44 (4) ◽  
pp. 313-323 ◽  
Author(s):  
Lea Weingarz ◽  
Marc Schindewolf ◽  
Jan Schwonberg ◽  
Carola Hecking ◽  
Zsuzsanna Wolf ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Cox Proportional Hazards ◽  
First Episode ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Younger Patients ◽  
Risk Of Recurrence ◽  
G20210a Mutation ◽  
Increased Risk ◽  
The Impact

Abstract. Background: Whether screening for thrombophilia is useful for patients after a first episode of venous thromboembolism (VTE) is a controversial issue. However, the impact of thrombophilia on the risk of recurrence may vary depending on the patient’s age at the time of the first VTE. Patients and methods: Of 1221 VTE patients (42 % males) registered in the MAISTHRO (MAin-ISar-THROmbosis) registry, 261 experienced VTE recurrence during a 5-year follow-up after the discontinuation of anticoagulant therapy. Results: Thrombophilia was more common among patients with VTE recurrence than those without (58.6 % vs. 50.3 %; p = 0.017). Stratifying patients by the age at the time of their initial VTE, Cox proportional hazards analyses adjusted for age, sex and the presence or absence of established risk factors revealed a heterozygous prothrombin (PT) G20210A mutation (hazard ratio (HR) 2.65; 95 %-confidence interval (CI) 1.71 - 4.12; p < 0.001), homozygosity/double heterozygosity for the factor V Leiden and/or PT mutation (HR 2.35; 95 %-CI 1.09 - 5.07, p = 0.030), and an antithrombin deficiency (HR 2.12; 95 %-CI 1.12 - 4.10; p = 0.021) to predict recurrent VTE in patients aged 40 years or older, whereas lupus anticoagulants (HR 3.05; 95%-CI 1.40 - 6.66; p = 0.005) increased the risk of recurrence in younger patients. Subgroup analyses revealed an increased risk of recurrence for a heterozygous factor V Leiden mutation only in young females without hormonal treatment whereas the predictive value of a heterozygous PT mutation was restricted to males over the age of 40 years. Conclusions: Our data do not support a preference of younger patients for thrombophilia testing after a first venous thromboembolic event.

High frequency of factor V Leiden in surgical patients with symptomatic venous thromboembolism despite prophylaxis

2007 ◽  
Vol 97 (02) ◽  
pp. 171-175 ◽  
Author(s):  
Mohamed Baba-Ahmed ◽  
Grégoire Le Gal ◽  
Francis Couturaud ◽  
Karine Lacut ◽  
Emmanuel Oger ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Close Association ◽  
Factor V Leiden ◽  
Plaster Cast ◽  
Case Control ◽  
Factor V ◽  
Potential Significance ◽  
Control Study ◽  
Fvl Mutation

SummaryAmong candidate risk factors associated with postoperative venous thromboembolism (VTE), the role of factorV Leiden (FVL) mutation remains unclear. We performed a case-control study to assess the potential significance of FVL mutation in postoperative VTE cases despite prophylaxis. We used data from the ongoing case-control “EDITH” study. We extracted 133VTE cases and 144 controls who had undergone either surgery or had plaster cast in the previous three months. Prophylaxis adequacy with regard to the recommendations published by theAmerican College of Chest Physicians was retrospectively assessed. FVL mutation was present in 20VTE cases and four controls (OR 5.9, 95% CI 2–18). Prophylaxis was judged as adequate in 116 cases (88.5 %) and in 129 controls (87.2 %) (p = 0.66). The frequency of FVL mutation was not different in VTE cases occurring while on adequate prophylaxis and in VTE cases occurring after the end of adequate prophylaxis (p = 0.27). FVL mutation was closely associated with postoperative VTE in patients classified as having received an adequate prophylaxis (8.4; 95% CI, 2.4 to 29). This study shows a close association between the presence of factorV Leiden mutation in symptomaticVTE occurring after surgery despite prophylaxis.

APC-RESISTANCE ASSOCIATED WITH FACTOR V LEIDEN GENE MUTATION (GENOTYPE GA): CLINICAL OCCURRENCE IN PREGNANCY

2018 ◽  
Author(s):  
М.Г. Николаева ◽  
А.П. Момот ◽  
Г.В. Сердюк ◽  
В.А. Елыкомов ◽  
К.А. Момот ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Gene Mutation ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Control Group ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Apc Resistance ◽  
Factor Va ◽  
And Control

Цель исследования: изучить связь феномена резистентности фактора Vа к активированному протеину С (АПС-резистентность) при носительстве мутации гена FVL (1691) GA с клинической реализацией во время беременности тромботических событий и гестационных осложнений, таких как преэклампсия, задержка развития плода и невынашивание беременности. Материалы и методы. Проведено проспективное клиническое когортное исследование 1100 беременных. Выделено 2 когорты: основная группа – 500 пациенток с генотипом FVL (1691) GA и группа контроля – 600 женщин с генотипом FVL (1691) GG. Результаты. Медиана нормализованного отношения (НО) АПС-резистентности в контрольной группе у беременных с генотипом FVL (1691) GG колебалась в диапазоне 1,0→0,86. У беременных – носителей генотипа FVL (1691) GA этот показатель был достоверно ниже – 0,55→0,48 (р < 0,05). У пациенток при НО > 0,5 течение беременности было благоприятным. Более выраженная АПС-резистентность (НО ≤ 0,49) ассоциировалась с гестационными осложнениями. Заключение. Полученные данные по АПС-резистентности позволяют относить в группу высокого риска по тромботическим и акушерским осложнениям женщин – носительниц мутации фактора V Лейден (1691) не только с генотипом АА, но и с генотипом GA. AПС-резистентность ≤ 0,49 (по показателю НО) при носительстве мутации фактора V Лейден (1691) GA может рассматриваться как прогностический маркер развития гестационных осложнений с наибольшей точностью при сроке 7-8 недель беременности. Aim: to study during pregnancy the relationship between factor Va resistance to activated protein C (APC-resistance) in carriers of FVL gene mutation (1691) GA with clinical realization of thrombotic events and gestational complications such as preeclampsia, fetal growth retardation and miscarriage. Materials and methods. A prospective clinical cohort study of 1100 pregnant women was performed. Two cohorts were identified: main group – 500 patients with FVL genotype (1691) GA and control group – 600 women with FVL genotype (1691) GG. Results. The median of normalized ratio (NR) of APC resistance in the control group with FVL genotype (1691) GG ranged from 1.0→0.86. In pregnant women – the carriers of FVL genotype (1691) GA this parameter was significantly lower – 0.55→0.48 (р < 0.05). In patients with HO > 0.5 the course of pregnancy was favorable. More expressed APS-resistance (НО ≤ 0,49) was associated with gestational complications. Conclusion. The obtained data on APC-resistance allow to classify women – the carriers of Factor V Leiden (1691) mutation, not only with the AA genotype but also with GA genotype as the group of high risk for thrombotic and obstetric complications. APC resistance ≤ 0.49 (according NR) with the carriage of Factor V Leiden mutation (1691) GA can be considered as a prognostic marker for the development of gestational complications with the greatest accuracy at a period of 7-8 weeks of gestation.

scholarly journals Clinical Utilization and Cost of Thrombophilia Testing in Patients with Venous Thromboembolism

TH Open ◽  
2020 ◽  
Vol 04 (03) ◽  
pp. e153-e162
Author(s):  
Manila Gaddh ◽  
En Cheng ◽  
Maha A.T. Elsebaie ◽  
Imre Bodó
Keyword(s):  
Venous Thromboembolism ◽  
Patient Management ◽  
Clinical Decision Making ◽  
Factor V Leiden ◽  
Direct Costs ◽  
Cost Of Care ◽  
Factor V ◽  
Test Results ◽  
Thrombophilia Testing ◽  
The Impact

Abstract Introduction Testing for inherited and acquired thrombophilias adds to the cost of care of patients with venous thromboembolism (VTE), though results may not influence patient management. Methods This is a single-center, retrospective study conducted at Emory University Hospitals from January to December 2015 to (1) determine the pattern of thrombophilia testing in patients with VTE, (2) study the impact of results of thrombophilia testing on clinical decision-making, and (3) determine the direct costs of thrombophilia testing in patients with VTE. Results Of the 266 eligible patients, 189 (71%) underwent testing; 51 (26.9%) tested positive and the results impacted management in 32 (16.9%) of tested patients. Patient undergoing testing were more likely to be younger than 40 years (30.9 vs. 18.2%), have had prior pregnancy loss (9.0 vs. 0%), or known family history of hypercoagulability (24.9 vs. 10.4%), and were less likely to have had provoked VTE (37 vs. 79.2%). The most common thrombophilias tested were antiphospholipid syndrome (60.1%), factor V Leiden (59.7%), and prothrombin gene mutation (57.5%). Direct costs of thrombophilia testing were $2,364.32 per patient, $12,331.55 to diagnose 1 positive, and $19,653.41 per patient-management affected. Conclusion We noted significant variability in selection of patients and panel of tests, sparse utilization of test results in patient management, but high cost associated with thrombophilia testing in patients with VTE. With guidelines advocating selective use of thrombophilia testing and attention to potential impact of test results in patient management, we propose the need for measures at institutional levels to improve test-ordering practices.

Factor V Leiden mutation and pregnancy-related venous thromboembolism: What is the exact risk?

2006 ◽  
Vol 96 (07) ◽  
pp. 14-18 ◽  
Author(s):  
Jean-Francois Schved ◽  
Jean-Pierre Daures ◽  
Christine Biron-Andreani
Keyword(s):  
Venous Thromboembolism ◽  
Meta Analysis ◽  
Random Effect ◽  
Factor V Leiden ◽  
Significant Heterogeneity ◽  
Average Risk ◽  
Factor V ◽  
Case Control Studies ◽  
Factor V Leiden Mutation ◽  
Statistical Heterogeneity

SummaryThe magnitude of the association of factor V Leiden mutation with pregnancy-related venous thrombosis remains unclear. Our objective was to undertake a systematic review and a meta-analysis of the literature to estimate precisely the association of factor V Leiden mutation with the risk of first,or recurrent,pregnancy-related venous thromboembolism. Studies published before October 2005 were identified by Medline®. Using both fixed and random effect models, odds ratios (OR) with accompanying 95% confidential intervals (CI) were calculated for the factor V Leiden mutation and the clinical end-point (Yusuf-Peto adaptation of the Mantel-Haenszel, DerSimonian and Laird method).We identified 13 studies including 7 cohorts and 6 case control studies relating to factor V Leiden and pregnancy-related venous thrombosis.The results from the cohorts showe a pooled OR of 4.46 (95% CI,1.82–10.94;7,879 pooled women), with no evidence of statistical heterogeneity (p=0.36), for the risk of a first venous thromboembolism during pregnancy or the postpartum period associated with the factor V Leiden mutation.Case-control studies revealed a higher risk ( OR 8.6,95% CI, 5.85–12.63; 1,524 pooled women) with significant heterogeneity (p<0.005). Because of insufficient data, an analysis for the risk of recurrence could not be performed. Our findings emphasize the fact that limited data are available on this topic.This meta-analysis provides clinicians with an estimate of the average risk of a first thrombosis occurring during pregnancy in women carrying the factor V Leiden to assist the management of such women.

Factor V Leiden (G1691A) and Prothrombin Gene G20210A Mutations as Potential Risk Factors for Venous Thromboembolism after Total Hip or Total Knee Replacement Surgery

2002 ◽  
Vol 87 (04) ◽  
pp. 580-585 ◽  
Author(s):  
G. Larson ◽  
T. L. Lindahl ◽  
C. Andersson ◽  
L. Frison ◽  
D. Gustafsson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Factor V Leiden ◽  
Composite Endpoint ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
G20210a Mutation ◽  
Symptomatic Pulmonary Embolism ◽  
Increased Risk ◽  
Prothrombin Gene

SummaryPatients (n = 1600) from 12 European countries, scheduled for elective orthopaedic hip or knee surgery, were screened for Factor V Leiden and prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations, respectively. All patients underwent prophylactic treatment with one of four doses of melagatran and ximelagatran or dalteparin, starting pre-operatively. Bilateral ascending venography was performed on study day 8-11. The patients were subsequently treated according to local routines and followed for 4-6 weeks postoperatively. The composite endpoint of screened deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE) during prophylaxis did not differ significantly between patients with or without these mutations. Symptomatic venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was significantly over-represented among patients with the prothrombin gene G20210A mutation (p = 0.0002). A tendency towards increased risk of VTE was found with the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over-represented in both the Factor V Leiden and prothrombin gene G20210A mutated patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the patients with these genetic risk factors will not suffer a VTE event, a general pre-operative genotyping is, in our opinion, of questionable value.

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