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.

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.

scholarly journals Risk Factor Profiles in Patients with Different Clinical Manifestations of Venous Thromboembolism: A Focus on the Factor V Leiden Mutation

1996 ◽  
Vol 76 (04) ◽  
pp. 510-513 ◽  
Author(s):  
Bert Manten ◽  
Rudi G J Westendorp ◽  
Ted Koster ◽  
Pieter H Reitsma ◽  
Frits R Rosendaal
Keyword(s):  
Pulmonary Embolism ◽  
Deep Vein Thrombosis ◽  
Venous Thromboembolism ◽  
Clinical Manifestations ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Deep Vein

Summary Background. Patients with venous thromboembolic disease may present with different clinical manifestations. Factor V Leiden mutation leading to resistance to activated protein C is associated with a sevenfold increased risk for presenting with deep-vein thrombosis. It is not yet established whether carriers of the mutation have a similarly increased risk for manifesting with pulmonary embolism. Methods. From an Anticoagulation Clinic monitoring coumarin therapy, a consecutive series of patients with a first thromboembolic event (objectively proven by current radiological methods) were enrolled. All patients were interviewed and blood was drawn for geno-typing. From the hospital charts and the personal interview, information was obtained on acquired risk factors and the signs and symptoms on hospital admission. Results. 45 patients presented with symptoms of pulmonary embolism only, 211 had only symptoms of deep-vein thrombosis whereas 23 had clinical features of both. In about half of the patients acquired risk factors for venous thromboembolism were present which did not differ between the three groups of patients. Recent surgery had been performed more often in patients presenting with pulmonary embolism than in other patients (33.3% vs. 18.5%, p <0,05). Factor V Leiden was present in 9% of the patients presenting with pulmonary embolism (relative risk: 3.3 95% Cl: 1.0-10.6) and 17% of the patients presenting with deep-vein thrombosis (relative risk: 6.9 95% Cl: 3.6-12.8). The prevalence of factor V Leiden was intermediate in patients with both clinical characteristics. Conclusion. These data suggest that patients with venous thromboembolism have different clinical presentation depending on the risk factor profile. Factor V Leiden may preferentially lead to manifest deep-vein thrombosis. Differences in structure of venous thrombi could underlie differences in embolic tendency.

Third Generation Oral Contraceptives and Heritable Thrombophilia as Risk Factors of Non-fatal Venous Thromboembolism

1998 ◽  
Vol 79 (01) ◽  
pp. 28-31 ◽  
Author(s):  
Birthe Søgaard Andersen ◽  
Jørn Olsen ◽  
Gunnar Lauge Nielsen ◽  
Flemming Hald Steffensen ◽  
Henrik Toft Sørensen ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Oral Contraceptives ◽  
Factor V Leiden ◽  
Factor V ◽  
Third Generation ◽  
Confounding By Indication ◽  
Antithrombin Deficiency ◽  
Factor V Leiden Mutation ◽  
Increased Risk

SummaryThird generation oral contraceptives (OCs) are apparently stronger risk factors for venous thromboembolism (VTE) than other OCs, however, the increased risk may be due to confounding by indication related to differences in prescription behaviour.We estimated the risk of VTE associated with use of OCs with and without the presence of Factor V Leiden mutation, protein C-, protein S- or antithrombin deficiency.Sixty-seven cases with VTE were compared with 134 controls. The risk of VTE in the presence of thrombophilia was of the same magnitude for third generation OC users as for users of other OCs; OR: 52.5 (95% CI: 3.7-738.1) and OR: 63.3 (95% CI: 6.2-648.4), respectively.It is unlikely that confounding by indication entirely explains the risk of VTE associated with third generation OCs since the combined effect exceeds what could be explained if this source of error was the only determinant of the association.

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.

Homozygous and double heterozygous Factor V Leiden and Factor II G20210A genotypes predispose infants to thromboembolism but are not associated with an increase of foetal loss

2003 ◽  
Vol 90 (10) ◽  
pp. 628-635 ◽  
Author(s):  
Patrick Hundsdoerfer ◽  
Barbara Vetter ◽  
Brigitte Stöver ◽  
Christian Bassir ◽  
Tristess Scholz ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Individual Risk ◽  
Factor V ◽  
Thromboembolic Events ◽  
Foetal Loss ◽  
Asymptomatic Children ◽  
Factor Ii ◽  
The Individual ◽  
The Impact

SummaryProspective and controlled data about the individual risk profile in asymptomatic children with homozygous or double heterozygous risk genotypes for Factor V Leiden (FVL) and factor II (FII) G20210A are currently unavailable. The systematic and prospective observational study presented here was designed to determine the impact of the homozygous and double heterozygous FVL and FII G20210A genotypes on the prenatal and postnatal risk profiles of affected children. Risk infants and heterozygous controls were identified by screening of 85,304 neonates. Follow-up included the comparison of prenatal and postnatal development, ultrasonography of brain and kidneys, and a panel of independent determinants of thrombophilia. The numbers of identified or expected FVL homozygotes and double heterozygotes did not differ significantly (FVL: 116 ver-sus 91, p=0.08; FVL/FII: 94 versus 76, p=0.17), indicating the absence of a prenatal disadvantage. A prenatal advantage was suggested in FII homozygotes, whose identified number far exceeded the expected (19 versus 4, p=0.002). Clinical and/or imaging abnormalities indicated spontaneous thromboembolic events in 4 of 129 risk infants (3%) but in none of the 178 controls (p=0.02). Physical and neurological development was normal in both groups during the first 2 years of life. The risk genotypes appear to confer a significant predisposition for spontaneous thromboembolic events in infancy without impeding development within the first two years of life. Foetal risk genotypes do not cause an increased foetal loss rate. Moreover, homozygous FII G20210A appears to be associated with a prenatal advantage.

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.

Is APC Resistance a Risk Factor for Venous Thromboembolism in Patients over 70 Years?

2002 ◽  
Vol 88 (10) ◽  
pp. 587-591 ◽  
Author(s):  
Karine Lacut ◽  
Grégoire Le Gal ◽  
Patrick Van Dreden ◽  
Luc Bressollette ◽  
Pierre-Yves Scarabin ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Dna Analysis ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Apc Resistance ◽  
Increased Risk ◽  
History Of

SummaryActivated protein C (APC) resistance is the most common risk factor for venous thromboembolism (VTE). Previous studies mostly analysed patients under 70 years and reported a four-to sevenfold increased risk. This case-control study included consecutive patients referred for a clinical suspicion VTE to our medical unit: 621 patients with a well-documented diagnosis (cases) and 406 patients for which the diagnosis was ruled out and who had no personal history of VTE (controls). APC resistance related to factor V Leiden was defined by either a positive DNA analysis or a positive STA® Staclot APC-R assay. Under 70 years, APC resistance was associated with a threefold increased risk of VTE (odds ratio 3.2, 95% CI, 1.7 to 6.0), whereas in patients over 70 years, it appeared to be no longer a strong risk factor (odds ratio 0.8, 95% CI, 0.4 to 1.7). Age appeared as an effectmeasure modifier with a significant interaction (p = 0.005). Our data suggest that APC resistance is not a risk factor for VTE in elderly.

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