The Incidence of Venous Thromboembolism in Family Members of Patients with Factor V Leiden Mutation and Venous Thrombosis

Middeldorp, Saskia; Henkens, C. M. A.; Koopman, M. M. W.; Pampus, E.C.M. van; Hamulyák, Karly; Meer, Jan van der; Prins, Martin H.; Büller, Harry R.

doi:10.7326/0003-4819-128-1-199801010-00003

Cited by 198 publications

(204 citation statements)

References 19 publications

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“…A similar result was obtained recently in a retrospective family study, 14 in which the estimated annual incidence of VTE in APCR carriers was 0.45%, near that found in our study (0.30%). These figures may explain previous observations 15 that homozygosity for APCR gives a lower risk of thrombosis than homozygosity for PC and PS, which frequently causes severe neonatal thrombosis.…”

Section: Discussionsupporting

confidence: 79%

Risk of Venous Thromboembolism and Clinical Manifestations in Carriers of Antithrombin, Protein C, Protein S Deficiency, or Activated Protein C Resistance

Bucciarelli

Rosendaal

Tripodi

et al. 1999

ATVB

151

105

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Abstract-Deficiencies of antithrombin (AT), protein C (PC) or protein S (PS), and activated protein C resistance (APCR) are very well-established coagulation defects predisposing to venous thromboembolism (VTE). We performed a retrospective cohort family study to assess the risk for VTE in individuals with AT, PC, or PS deficiency, or APCR. Five hundred thirteen relatives from 9 Italian centers were selected from 233 families in which the proband had had at least 1 episode of VTE. We calculated the incidence of VTE in the whole cohort and in the subgroups after stratification by age, sex, and defect. The overall incidence of VTE (per 100 patient-years) in the group of relatives was 0.52. It was 1.07 for AT, 0.54 for PC, 0.50 for PS, 0.30 for APCR, and 0.67 in the group with a double defect. The incidence was associated with age, but not with sex. The mean age at onset was between 30 and 40 years for all the coagulation defects. Women had the peak of incidence in the age range of 21 to 40 years, earlier than men. The lifetime risk for VTE was 4.4 for AT versus APCR, 2.6 for AT versus PS, 2.2 for AT versus PC, 1.9 for PC versus APCR, and 1.6 for PS versus APCR. AT deficiency seems to have a higher risk for VTE than the other genetic defects. There is a relation between age and occurrence of thrombosis for both men and women. The latter had the peak of incidence earlier than the former.

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Section: Discussionsupporting

confidence: 79%

Risk of Venous Thromboembolism and Clinical Manifestations in Carriers of Antithrombin, Protein C, Protein S Deficiency, or Activated Protein C Resistance

Bucciarelli

Rosendaal

Tripodi

et al. 1999

ATVB

151

105

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“…The absolute annual risk for a first episode of venous thrombosis was 0´13% in relatives with the prothrombin gene mutation, 0´19% in those with the factor V Leiden mutation and 0´42% in those with both mutations compared with 0´066% in relatives with neither mutation. The previously reported annual incidence of venous thrombosis in family members with the factor V Leiden mutation varied from 0´28% to 0´45% (Middeldorp et al, 1998;Bucciarelli et al, 1999;Simioni et al, 1999). Perhaps the higher incidence found in previous family studies is due to the fact that, at variance with our study, screening for the prothrombin gene mutation was not carried out, leading to an overestimation of the incidence rate as a result of the presence of both the thrombophilic mutations in some cases.…”

Section: Discussioncontrasting

confidence: 54%

“…Perhaps the higher incidence found in previous family studies is due to the fact that, at variance with our study, screening for the prothrombin gene mutation was not carried out, leading to an overestimation of the incidence rate as a result of the presence of both the thrombophilic mutations in some cases. It has been convincingly demonstrated that heterozygous carriers of the factor V Leiden mutation have an increased risk of venous thrombosis compared with non-carriers, being three-to sevenfold in several population-based case± control studies (Koster et al, 1993;Svensson & Dahlba Èck, 1994;Cattaneo et al, 1998;Margaglione et al, 1998), twofold in a prospective study (Lensen et al, 1996) and three-to fivefold in retrospective family studies Middeldorp et al, 1998;Bucciarelli et al, 1999;Simioni et al, 1999). Because of its more recent discovery, the risk conferred by the G20210A prothrombin gene mutation has been investigated to a lesser extent and not in family studies; the risk estimated in several case±control studies has varied as much as between two-and 12-fold (Poort et al, 1996;Arruda et al, 1997;Margaglione et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…It is likely that such variability is due to the different criteria used to select patients and controls. To date, six family studies on inherited thrombophilia are available (Allaart et al, 1993;Martinelli et al, 1998;Middeldorp et al, 1998;Bucciarelli et al, 1999;Simioni et al, 1999;van Boven et al, 1999), but none of them evaluated the mutation in the prothrombin gene. We chose to investigate 1076 relatives of 335 probands with the prothrombin gene mutation, factor V Leiden or both who were diagnosed in four Italian centres specializing in the diagnosis and treatment of inherited thrombophilia.…”

mentioning

confidence: 99%

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The risk of venous thromboembolism in family members with mutations in the genes of factor V or prothrombin or both

et al. 2000

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Summary. Factor V Leiden and the G20210A mutation in the prothrombin gene are the most frequent abnormalities associated with venous thromboembolism. It is unknown whether the risks due to the presence of either mutation are of the same magnitude. We compared the prevalence and incidence rate of venous thromboembolism in relatives with either mutation or both. The finding of different rates might influence the strategies for primary prevention of thrombosis in carriers of these mutations. The study population included 1076 relatives of probands with the prothrombin gene mutation, factor V Leiden or both who underwent screening for inherited thrombophilia and were found to be carriers of single mutations or double mutations or who were non-carriers. The prevalence of venous thromboembolism was 5´7% in relatives with the prothrombin gene mutation, 7´8% in those with factor V Leiden, 17´1% in those with both mutations and 2´5% in non-carriers. Annual incidences of thrombosis were 0´13% [95% confidence interval (CI) 0´06±0´24], 0´19% (0´13±0´25), 0´42% (0´15±0´83) and 0´066% (0´03±0´11), respectively, and the relative risk of thrombosis was two times higher in carriers of the prothrombin gene mutation, three times higher in those with factor V Leiden and six times higher in double carriers than in non-carriers. The incidence of venous thromboembolism in carriers of the prothrombin gene mutation is slightly lower than that observed in carriers of factor V Leiden, whereas in carriers of both mutations it is two or three times higher. These findings suggest that lifelong primary anticoagulant prophylaxis of venous thromboembolism is not needed in asymptomatic carriers of single or double mutations. Anticoagulant prophylaxis seems to be indicated only when transient risk factors for thrombosis coexist with mutations.

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“…Systematic reviews are limited by the underlying published studies, the majority of which are retrospective giving an estimate of the magnitude of the increased risk of pregnancy complications which is not reliable and based on the relative risk instead of the absolute risk. Therefore, the expert panel chose to base their evaluation on the results of cohort studies performed in relatives of patients with a particular thrombophilic defect [24][25][26][27][28][29][30][31][32][33]. The overall absolute risk of VTE or obstetric complications is generally low; therefore, there is no clear indication for performing mass screening for thrombophilia.…”

Section: Testing Asymptomatic Women For Thrombophiliamentioning

confidence: 99%

Screening for thrombophilia and antithrombotic prophylaxis in pregnancy: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET)

Lussana

Dentali

Abbate

et al. 2009

Thrombosis Research

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The term thrombophilia describes an increased tendency to develop thrombosis and many laboratory markers with different strengths of association with thrombosis have been identified. The main causes of maternal mortality and morbidity in developed countries is venous thromboembolism (VTE) and obstetric complications. During pregnancy and puerperium the risk for VTE increases due to hemostatic imbalance towards a prothrombotic state, and it is further increased in women carriers of thrombophilia; recent studies have also demonstrated an association between thrombophilia and obstetric complications. These complications are, therefore, considered potentially preventable with the prophylactic administration of anticoagulant drugs, although their efficacy is not proven by data from randomized controlled trials. After a systematic comprehensive literature review and using a rigorous methodology, the expert panel formulated recommendations regarding the usefulness of screening for thrombophilia in pregnancy to identify high-risk women and for the management of antithrombotic prophyalxis. When evidence is lacking, consensus-based recommendations are provided.

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The Incidence of Venous Thromboembolism in Family Members of Patients with Factor V Leiden Mutation and Venous Thrombosis

Cited by 198 publications

References 19 publications

Risk of Venous Thromboembolism and Clinical Manifestations in Carriers of Antithrombin, Protein C, Protein S Deficiency, or Activated Protein C Resistance

Risk of Venous Thromboembolism and Clinical Manifestations in Carriers of Antithrombin, Protein C, Protein S Deficiency, or Activated Protein C Resistance

The risk of venous thromboembolism in family members with mutations in the genes of factor V or prothrombin or both

Screening for thrombophilia and antithrombotic prophylaxis in pregnancy: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET)

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