The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis

Abstract In a prospective cohort study, we assessed the incidence of spontaneous and risk period–related venous thromboembolism (VTE) in asymptomatic family members of patients who experienced VTE and had the factor V Leiden mutation. In all, 561 family members of 131 probands were included, 313 of whom were carriers (299 heterozygous and 14 homozygous) and 248 of whom were noncarriers of the factor V Leiden mutation. Average follow-up was 4 years (range, 4 months-6 years). There were 1255 and 984 observation-years of follow-up in carriers and noncarriers, respectively. Eight episodes of VTE occurred in heterozygous carriers, resulting in an annual incidence of 0.67% (95% confidence interval [CI], 0.29-1.33). Two events occurred in the absence of associated risk factors, determining an annual incidence of spontaneous VTE of 0.17% (95% CI, 0.02-0.6). Only one VTE (risk period–related) occurred in noncarriers, with an annual incidence of 0.1% (95% CI, 0.003-0.56). Relative risk for VTE in heterozygous carriers compared with noncarriers of the factor V Leiden mutation was 6.6 (95% CI, 1.1-39.8). Risk period–related VTE occurred with an incidence of 18% and 5% per risk period in heterozygous carriers and in noncarriers, respectively. Thus, the low rate of VTE in asymptomatic family members carrying the mutation did not justify continuous anticoagulant prophylaxis. Screening families of symptomatic probands with the factor V Leiden mutation has the potential to identify those asymptomatic carriers who might benefit from thromboprophylaxis during risk periods.

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Bewertung des Rezidivthrombose-risikos venöser Thromboembolien

Hämostaseologie ◽

10.5482/ha-1144 ◽

2011 ◽

Vol 31 (01) ◽

pp. 07-12 ◽

Cited By ~ 4

Author(s):

E. Lindhoff-Last

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Venous Thrombosis ◽

Factor V Leiden ◽

Recurrence Risk ◽

Factor V ◽

Recurrence Rates ◽

Factor V Leiden Mutation ◽

Symptomatic Pulmonary Embolism ◽

Recurrent Venous Thromboembolism

SummaryRecurrent venous thromboembolism is associated with increased mortality in 5–9% of the patients. On the other hand prolonged anticoagulation can increase the bleeding risk which can also be responsible for an increased mortality. Therefore, it is necessary to validate the recurrence risk of venous thromboembolism on an individual basis.In this review the most relevant risk factors for recurrent venous thromboembolism are analyzed. Spontaneous thrombosis is associated with significantly increased recurrence rates in comparison to risk associated venous thrombosis. In addition, a positive D-dimer result after stop of anticoagulation, an increased amount of residual thrombus in proximal veins analyzed by compression sonography, a proximal localization of thrombosis, symptomatic pulmonary embolism and male sex are clinically relevant risk factors for increased recurrence rates. While mild thrombophilic defects like heterozygous factor V Leiden mutation are not associated with a clinically relevant recurrence risk, inherited inhibitor deficiencies and the anti-phospholipid-syndrome are known to be responsible for an increased recurrence rate of venous thromboembolism. A new recurrence risk-score (RR-Score) for individual judgement of patients with a first spontaneous venous thrombosis is introduced.

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Long-term, low-dose warfarin among venous thrombosis patients with and without factor V Leiden mutation: rationale and design for the Prevention of Recurrent Venous Thromboembolism (PREVENT) trial

Vascular Medicine ◽

10.1191/135886398668337204 ◽

1998 ◽

Vol 3 (1) ◽

pp. 67-73 ◽

Cited By ~ 5

Author(s):

P.M. Ridker

Keyword(s):

Venous Thromboembolism ◽

Venous Thrombosis ◽

Low Dose ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation ◽

Dose Warfarin ◽

Recurrent Venous Thromboembolism ◽

Prevent Trial

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Should the factor V Leiden mutation be screened among ethnic Malays with venous thrombosis?

Thrombosis Research ◽

10.1016/j.thromres.2009.08.002 ◽

2010 ◽

Vol 125 (5) ◽

pp. 471-472 ◽

Cited By ~ 1

Author(s):

H.J. Ng ◽

E.S. Koay ◽

A. Abdul Ghafar ◽

L.C. Lim ◽

L.H. Lee

Keyword(s):

Venous Thrombosis ◽

Factor V Leiden ◽

Factor V ◽

Factor V Leiden Mutation

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Combined Factor V Leiden (R506Q) and prothrombin G20210A genotyping in young patients presenting with deep venous thrombosis

Phlebology The Journal of Venous Disease ◽

10.1258/026835506775971171 ◽

2006 ◽

Vol 21 (1) ◽

pp. 24-27 ◽

Cited By ~ 2

Author(s):

A Mansilha ◽

F Araújo ◽

M Severo ◽

S M Sampaio ◽

T Toledo ◽

...

Keyword(s):

Risk Factor ◽

Young People ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Young Patients ◽

Factor V Leiden ◽

First Episode ◽

Control Group ◽

Factor V ◽

Factor V Leiden Mutation

Objective: To evaluate the association between the Factor V Leiden (FV R506Q) and prothrombin gene (FII G20210A) mutations and deep venous thrombosis (DVT) in young people. Methods: Blood samples were drawn from 199 subjects: 100 healthy controls and 99 unselected patients, with an objectively documented first episode of DVT under 40 years old. DNA analysis was performed using the polymerase chain reaction. Results: The mean age in the patient cohort was 27 years (range 16–40) and 68 (68.7%) were women. Patient prevalences were 20.6% and 10.1% for FV R506Q and FII G20210A, respectively. In the control group, carrier frequencies were 2% and 5%, respectively. We found an increased overall relative risk of DVT with statistical significance for FV R506Q carriers (OR: 12.8; 95% CI: 2.9–56.7; P < 0.001), but not for FII G20210A mutation (OR: 2.1; 95% CI: 0.7–6.5; P = 0.19). Conclusions: Our results suggest a possible increase in DVT risk for the young G20210A allele carriers, which can be more expressed in the presence of a circumstantial risk factor. There is extremely strong evidence that the Factor V Leiden mutation is an important risk factor in the development of a first episode of DVT in young people.

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Incidence of Venous Thromboembolism in Families with Inherited Thrombophilia

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614442 ◽

1999 ◽

Vol 81 (02) ◽

pp. 198-202 ◽

Cited By ~ 210

Author(s):

Paolo Simioni ◽

Bernd-Jan Sanson ◽

Daniela Tormene ◽

Philip Friederich ◽

Bruno Girolami ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Oral Contraceptive ◽

Contraceptive Use ◽

Post Partum ◽

Family Members ◽

Factor V Leiden ◽

Factor V ◽

Relative Risks ◽

Oral Contraceptive Use

SummaryThe risk of spontaneous or risk-period related venous thromboembolism in family members of symptomatic carriers of antithrombin (AT), protein C (PC) or protein S (PS) defects, as well as of the Factor V Leiden mutation is still undefined. We performed a retrospective cohort study in family members (n = 793) of unselected patients with a documented venous thromboembolism and one of these deficiencies to make an estimate of this risk. The annual incidences of total and spontaneous venous thromboembolic events in carriers of AT, PC or PS defects (n = 181) were 1.01% and 0.40%, respectively, as compared to 0.10% and 0.04% in non-carriers, respectively (relative risks both 10.6). In carriers of Factor V Leiden (n = 224), the annual incidences of total and spontaneous venous thromboembolism were 0.28% and 0.11%, respectively, as compared to 0.09% and 0.04% in non-carriers, respectively (relative risks 2.8 and 2.5). Additional risk factors (immobilisation, surgery and trauma; oral contraceptive use; and pregnancy/ post-partum) increased the risk of thrombosis in carriers of AT, PC and PS defects as compared to non-carriers (relative risks 8.3, 6.4 and 8.2, respectively). Oral contraceptive use and pregnancy/ post-partum period increased the risk of thrombosis in carriers of Factor V Leiden to 3.3-fold and 4.2-fold, respectively, whereas other risk factors had only a minor effect.These data lend some support to the practice of screening family members of symptomatic carriers of a AT, PC and PS deficiency. For family members of symptomatic carriers of Factor V Leiden, screening does not seem to be justified except for women in fertile age.

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