Venous Thrombotic Risk in Family Members of Unselected Individuals with Factor V Leiden

2000 ◽  
Vol 83 (06) ◽  
pp. 817-821 ◽  
Author(s):  
R. P. M. Lensen ◽  
R. M. Bertina ◽  
H. de Ronde ◽  
J. P. Vandenbroucke ◽  
F. R. Rosendaal
Keyword(s):  
Risk Factors ◽  
Positive Family History ◽  
Family Members ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
Asymptomatic Carriers ◽  
Kaplan Meier ◽  
Increased Risk

SummaryThe factor V Leiden mutation (FVL) leads to a seven-fold increased risk of venous thromboembolism (VTE). In thrombophilic families, 25% of carriers have experienced thrombosis before the age of 40 years. Aim of our study was to assess the association of FVL with VTE in first-degree family members of unselected symptomatic and asymptomatic carriers of FVL.We tested 197 relatives of consecutive thrombosis patients with FVL and 36 relatives of asymptomatic carriers on the presence of FVL and the occurrence of VTE.The incidence of VTE in relatives with FVL of symptomatic carriers was 0.34%/year. This was similar to the incidence in relatives with FVL of asymptomatic carriers. Kaplan Meier analysis in relatives of symptomatic propositi showed that at the age of 58 years, thrombosisfree survival was reduced to 75% in carriers and 93% in non-carriers (P < 0.05). Carriers of FVL had a three times higher thrombotic risk than non-carriers. In combination with environmental risk factors, FVL clearly adds to the risk of VTE. The thrombotic incidence rate in these unselected relatives with FVL, however, is considerably lower than was seen in carriers of thrombophilic families (1.7%/year). Therefore, special care should be paid to individuals with a positive family history of venous thrombosis while exposed to these risk factors.

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.

Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception

Blood ◽  
2011 ◽  
Vol 118 (8) ◽  
pp. 2055-2061 ◽  
Author(s):  
Elizabeth F. W. van Vlijmen ◽  
Nic J. G. M. Veeger ◽  
Saskia Middeldorp ◽  
Karly Hamulyák ◽  
Martin H. Prins ◽  
...  
Keyword(s):  
Risk Factors ◽  
Oral Contraceptive ◽  
Factor V Leiden ◽  
Informed Choice ◽  
Rational Approach ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
G20210a Mutation

AbstractCurrent guidelines discourage combined oral contraceptive (COC) use in women with hereditary thrombophilic defects. However, qualifying all hereditary thrombophilic defects as similarly strong risk factors might be questioned. Recent studies indicate the risk of venous thromboembolism (VTE) of a factor V Leiden mutation as considerably lower than a deficiency of protein C, protein S, or antithrombin. In a retrospective family cohort, the VTE risk during COC use and pregnancy (including postpartum) was assessed in 798 female relatives with or without a heterozygous, double heterozygous, or homozygous factor V Leiden or prothrombin G20210A mutation. Overall, absolute VTE risk in women with no, single, or combined defects was 0.13 (95% confidence interval 0.08-0.21), 0.35 (0.22-0.53), and 0.94 (0.47-1.67) per 100 person-years, while these were 0.19 (0.07-0.41), 0.49 (0.18-1.07), and 0.86 (0.10-3.11) during COC use, and 0.73 (0.30-1.51), 1.97 (0.94-3.63), and 7.65 (3.08-15.76) during pregnancy. COC use and pregnancy were independent risk factors for VTE, with highest risk during pregnancy postpartum, as demonstrated by adjusted hazard ratios of 16.0 (8.0-32.2) versus 2.2 (1.1-4.0) during COC use. Rather than strictly contraindicating COC use, we advocate that detailed counseling on all contraceptive options, including COCs, addressing the associated risks of both VTE and unintended pregnancy, enabling these women to make an informed choice.

Thrombotic risk factors in Chinese Budd-Chiari syndrome patients

2013 ◽  
Vol 109 (05) ◽  
pp. 878-884 ◽  
Author(s):  
Chuangye He ◽  
Zhanxin Yin ◽  
Jing Niu ◽  
Ming Bai ◽  
Zhiping Yang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myeloproliferative Neoplasms ◽  
Factor V Leiden ◽  
Jak2 V617f ◽  
Paroxysmal Nocturnal Haemoglobinuria ◽  
Prothrombin G20210a ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
G20210a Mutation

SummaryIn Western countries, thrombotic risk factors for Budd-Chiari syndrome (BCS) are very common, including factor V Leiden mutation, prothrombin G20210A mutation, myeloproliferative neoplasms, paroxysmal nocturnal haemoglobinuria, etc. However, the data regarding thrombotic risk factors in Chinese BCS patients are extremely limited. An observational study was conducted to examine this issue. A total of 246 BCS patients who were consecutively admitted to our department between July 1999 and December 2011 were invited to be examined for thrombotic risk factors. Of these, 169 patients were enrolled. Neither factor V Leiden mutation nor prothrombin G20210A mutation was found in any of 136 patients tested. JAK2 V617F mutation was positive in four of 169 patients tested. Neither MPL W515L/K mutation nor JAK2 exon 12 mutation was found in any of 135 patients tested. Overt myeloproliferative neoplasms were diagnosed in five patients (polycythemia vera, n=3; essential thrombocythemia, n=1; idiopathic myelofibrosis, n=1). Two of them had positive JAK2 V617F mutation. Both CD55 and CD59 deficiencies were found in one of 166 patients tested. This patient had a previous history of paroxysmal nocturnal haemoglobinuria before BCS. Anticardiolipin IgG antibodies were positive or weakly positive in six of 166 patients tested. Hyperhomocysteinaemia was found in 64 of 128 patients tested. 5,10-methylenetetrahydrofolate reductase C677T mutation was found in 96 of 135 patients tested. In conclusion, factor V Leiden mutation, prothrombin G20210A mutation, myeloproliferative neoplasms, and paroxysmal nocturnal haemoglobinuria are very rare in Chinese BCS patients, suggesting that the etiological distribution of BCS might be different between Western countries and China.

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.

Hypofibrinolysis as a Risk Factor for Venous Thrombosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 272-272 ◽  
Author(s):  
Mirjam E. Meltzer ◽  
Carine J.M. Doggen ◽  
Philip G. de Groot ◽  
Frits R. Rosendaal ◽  
Ton Lisman
Keyword(s):  
Risk Factors ◽  
The Netherlands ◽  
Venous Thrombosis ◽  
Factor V Leiden ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
Control Subjects ◽  
Fourth Quartile ◽  
Prothrombin 20210A

Abstract Several genetic and acquired risk factors are known to increase the risk of venous thrombosis (VT). The occurrence of multiple risk factors in a single patient may be associated with a thrombotic risk which exceeds the sum of the individual risks, as is for example seen with oral contraceptive use and factor V Leiden. Previously we have shown that reduced fibrinolytic potential a measured by a plasma-based assay increases the risk of VT. Here, we investigated the thrombotic risk in individuals with hypofibrinolysis overall and in combination with the factor V Leiden and prothrombin 20210A mutation, in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a large population-based case-control study. In the present analyses, 2420 patients with a first episode of deep vein thrombosis of the leg or a pulmonary embolism and 2943 control subjects (partners and randomly selected individuals) between 18 and 70 years were included. Lysis of a tissue factor-induced clot by exogenous tissue-type plasminogen activator was studied by monitoring changes in turbidity during clot formation and subsequent lysis. Using quartiles of clot lysis time (CLT) based on the values found in the control subjects, we found an increase in risk of VT with each increasing quartile of CLT. The odds ratio (OR) (95% confidence interval (CI)) for individuals in the fourth quartile of CLT compared to individuals in the first quartile was 1.8 (1.5–2.1), after adjustment for age and sex. In younger subjects and women these ORs were slightly elevated (table). In individuals with hypofibrinolysis (i.e., the highest quartile of CLT) and without the factor V Leiden mutation an OR of 1.8 (1.5–2.1) was found compared to those without the mutation and with the lowest CLTs (i.e., in the lowest quartile). Individuals with the factor V Leiden mutation with the lowest CLTs had a risk of VT that was 3.6 (2.4–5.4) times increased, compared to those without the mutation and with the lowest CLTs. The risk of VT increased 6.2–fold (4.2–9.2) for individuals in the fourth quartile of CLT with the factor V Leiden mutation compared to people in the first quartile without the mutation. The same analyses for the prothrombin 20210A mutation gave ORs of 1.8 (1.5–2.1) for hypofibrinolysis only, 3.6 (1.4–9.5) for the mutation only, and 3.2 (1.9–5.3) for the combination. Our study confirms the increased risk of VT in individuals with hypofibrinolysis. This risk is especially pronounced in women and younger individuals. The combination of hypofibrinolysis and the factor V Leiden or prothrombin mutation does not appear to enhance the risk of VT. This study was supported by the Netherlands Heart Foundation (NHF) (Grant no. 2005B060 and 98.113) and the Netherlands Organisation for Scientific research (NWO) (Grant no. 912-03-033/2003). Risk of VT for individuals in the fourth quartile (Q4) of CLT overall <49 years >49 years women men * Q1 is reference # cases(Q1/Q4) 452/784 275/285 177/499 261/385 191/398 #controles (Q1/Q4) 733/733 458/248 274/485 430/357 303/376 OR (95% CI)* 1.8 (1.5–2.1) 2.5 (1.9–3.2) 1.7 (1.4–2.2) 2.7 (2.1–3.4) 1.6 (1.3–2.1)

Inherited Prethrombotic Disorders and Infectious Purpura

1996 ◽  
Vol 75 (06) ◽  
pp. 899-901 ◽  
Author(s):  
Rudi G J Westendorp ◽  
Pieter H Reitsma ◽  
Rogier M Bertina
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Disease Course ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk ◽  
C Protein ◽  
Severity Of The Disease

SummaryPatients with severe meningococcal infection are characterized by extensive microvascular thrombosis, consumption coagulopathy and secondary hemorrhages. The contribution of the inherited prethrombotic disorders to the severity of the disease course is not established yet. Here, we report on the levels of protein C, protein S, antithrombin and the presence of the factor V Leiden mutation (R506Q) in 50 patients with meningococcal disease, as determined 6 to 58 months after hospital discharge. In addition, we recalled the parents of 16 deceased patients to screen for the mutation in factor V, an abnormality which results in resistance to activated protein C. Among the patients, the prevalence of the genetic risk factors for thrombosis was not higher than expected on the basis of their prevalence in the general population. Moreover, the prevalence of the factor V Leiden mutation was not increased among the parents of the deceased patients. The individual plasma levels of protein C, protein S, and antithrombin did not differ between the patients with or without severe purpura. The present data constitute circumstantial evidence that primary defects in the natural anticoagulant systems do not play a major role in the severity of the disease course. Screening of patients with infectious purpura for inherited thrombotic risk factors is therefore not indicated.

The contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus

Blood ◽  
2004 ◽  
Vol 104 (1) ◽  
pp. 143-148 ◽  
Author(s):  
Jan-Leendert P. Brouwer ◽  
Marc Bijl ◽  
Nic J. G. M. Veeger ◽  
Hanneke C. Kluin-Nelemans ◽  
Jan van der Meer
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Factor V Leiden ◽  
Factor V ◽  
Systemic Lupus ◽  
Thrombotic Risk ◽  
Arterial Thromboembolism ◽  
Increased Risk ◽  
Prothrombin Mutation

Abstract Systemic lupus erythematosus (SLE) is associated with an increased risk of venous (VTE) and arterial thromboembolism (ATE). Lupus anticoagulant (LA) and anticardiolipin antibodies (ACAs) are established risk factors. We assessed the contribution of deficiencies of antithrombin, protein C, total protein S, factor V Leiden, the prothrombin G20210A mutation and APC resistance, either alone or in various combinations with LA and/or ACAs, to the thrombotic risk in a cohort of 144 consecutive patients with SLE. Median follow-up was 12.7 years. VTE had occurred in 10% and ATE in 11% of patients. LA,ACAs, factor V Leiden, and the prothrombin mutation were identified as risk factors for VTE. Annual incidences of VTE were 2.01 (0.74-4.37) in patients with one of these disorders and 3.05 (0.63-8.93) in patients with 2 disorders. The risk of VTE was 20- and 30-fold higher, respectively, compared with the normal population. In contrast with LA and ACAs, thrombophilic disorders did not influence the risk of ATE. In conclusion, factor V Leiden and the prothrombin mutation contribute to the risk of VTE in patients with SLE, and potentiate this risk when one of these thrombophilic defects are combined with LA and/or ACAs.

Combined Factor V Leiden and Prothrombin Genotyping in Patients Presenting With Thromboembolic Episodes

2001 ◽  
Vol 125 (1) ◽  
pp. 105-111
Author(s):  
John A. Friedline ◽  
Ejaz Ahmad ◽  
Diana Garcia ◽  
Deborah Blue ◽  
Noel Ceniza ◽  
...  
Keyword(s):  
Risk Factors ◽  
Factor V Leiden ◽  
Genetic Defects ◽  
Factor V ◽  
Thrombotic Risk ◽  
Additional Risk ◽  
Mutation Carriers ◽  
First Case ◽  
Increased Risk ◽  
Prothrombin Mutation

Abstract Background.—Several genetic defects are associated with increased risk of venous thrombosis. The factor V Leiden (FVL) and prothrombin G20210A mutations are the most frequent causes of inherited thrombophilia. Objectives.—To evaluate combined genotyping for these 2 mutations in patients presenting with thromboembolic episodes and to correlate genotypic findings with clinical characteristics. Results.—Blood specimens were collected from 401 patients presenting with thromboembolic disease between January 1998 and September 1998, and genotyping for both FVL and prothrombin mutations was performed. Thirty-two patients (8%) were heterozygous for FVL, 4 (1%) were homozygous for FVL, and 20 (5%) were heterozygous for the prothrombin mutation. Two cases (0.5%) were identified with combined FVL and prothrombin mutations. The most common clinical presentation was lower-extremity deep vein thrombosis with or without pulmonary embolism. Arterial events were rare. The thromboembolic episodes were often precipitated by additional risk factors. Recurrent disease was found in 73.9% of FVL carriers and 52.9% of prothrombin mutation carriers; 52% of the patients with FVL and 50% of prothrombin mutation carriers had a first thrombotic episode before age 45 years. The 2 cases with combined genetic defects demonstrate amplified thrombotic risk. In the first case this was effected in thrombosis at a young age, and recurrence of thrombotic events even in the absence of precipitating factors. A complex interplay between genetic and additional risk factors was seen in the second case. Conclusions.—Identification of both FVL and prothrombin mutations is important in the overall assessment and management of patients with thrombophilia. Detection of these mutations can identify patients at high risk and help evaluate the interaction of genetic and acquired risk factors.

scholarly journals Factor V Leiden and other coagulation factor mutations affecting thrombotic risk

1997 ◽  
Vol 43 (9) ◽  
pp. 1678-1683 ◽  
Author(s):  
Rogier M Bertina
Keyword(s):  
Risk Factors ◽  
Protein C ◽  
Dna Analysis ◽  
Factor V Leiden ◽  
Coagulation Factor ◽  
Laboratory Diagnosis ◽  
Factor V ◽  
Single Mutation ◽  
Factor V Leiden Mutation ◽  
Thrombotic Risk

Abstract Five genetic defects have been established as risk factors for venous thrombosis. Three are protein C, protein S, and antithrombin deficiencies, defects in the anticoagulant pathways of blood coagulation. Together they can be found in ∼15% of families with inherited thrombophilia. Their laboratory diagnosis is hampered by the large genetic heterogeneity of these defects. The other two genetic risk factors, resistance to activated protein C associated with the factor V Leiden mutation and increased prothrombin associated with the prothrombin 20210 A allele, are much more prevalent and together can be found in 63% of the thrombophilia families. Because both defects are caused by a single mutation, DNA analysis is the basis of their laboratory diagnosis.

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.

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