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Ian A Greer - One of the best experts on this subject based on the ideXlab platform.
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hereditary risk factors for Thrombophilia and probability of venous thromboembolism during pregnancy and the puerperium
Blood, 2016Co-Authors: Andrea Gerhardt, Rudiger E Scharf, Ian A Greer, Rainer B ZotzAbstract:Venous thromboembolism (VTE) is a leading cause of maternal mortality. Few studies have evaluated the individual risk of gestational VTE associated with heritable Thrombophilia, and current recommendations for antenatal thromboprophylaxis in women with severe Thrombophilia such as homozygous factor V Leiden mutation ( FVL ) depend on a positive family history of VTE. To better stratify thromboprophylaxis in pregnancy, we aimed to estimate the individual probability (absolute risk) of gestational VTE associated with Thrombophilia and to see whether these risk factors are independent of a family history of VTE in first-degree relatives. We studied 243 women with the first VTE during pregnancy and the puerperium and 243 age-matched normal women. Baseline incidence of VTE of 1:483 pregnancies in women ≥35 years and 1:741 deliveries in women FVL ; 3.4% (2.2%) for homozygous FVL ; 0.6% (0.4%) for heterozygous prothrombin G20210A; 8.2% (5.5%) for compound heterozygotes for FVL and prothrombin G20210A; 9.0% (6.1%) for antithrombin deficiency; 1.1% (0.7%) for protein C deficiency; and 1.0% (0.7%) for protein S deficiency. These results were independent of a positive family history of VTE. We provide evidence that unselected women with these Thrombophilias have an increased risk of gestational VTE independent of a positive family history of VTE. In contrast to current guidelines, these data suggest that women with high-risk Thrombophilia should be considered for antenatal thromboprophylaxis regardless of family history of VTE.
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antithrombotic treatment for recurrent pregnancy loss
Journal of Thrombosis and Haemostasis, 2011Co-Authors: Ian A GreerAbstract:Summary. Background: Recurrent pregnancy loss (RPL) is a major issue for women’s health. Acquired and heritable Thrombophilias are associated with RPL, this association could reflect a general prothrombotic phenotype rather than a specific Thrombophilia. Antithrombotic intervention has therefore been assessed for RPL. Results: Two large randomised trials with untreated control groups showed no benefit from antithrombotic treatment with LMWH and low dose aspirin in women with RPL. These trials had insufficient power to exclude an effect in women with underlying Thrombophilia, ≥ 3 losses, or late losses. Conclusions: Antithrombotic intervention should not be recommended for unexplained RPL in general. There may be specific groups such as those with an heritable Thrombophilia, or with three or more losses, or second trimester losses that might benefit and where further trials are required. Further there is a need to consider the benefits of LMWH on implantation such as in women undergoing assisted conception therapy.
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oral contraceptives hormone replacement therapy Thrombophilias and risk of venous thromboembolism a systematic review the thrombosis risk and economic assessment of Thrombophilia screening treats study
Thrombosis and Haemostasis, 2005Co-Authors: Lindsay Robertson, Sara Twaddle, Gordon D O Lowe, Peter Clark, Michael Greaves, I D Walker, Peter Langhorne, I Brenkel, L Regan, Ian A GreerAbstract:Combined oral contraceptives,oral hormone replacement therapy and Thrombophilias are recognised risk factors for venous thromboembolism in women.The objective of this study was to assess the risk of thromboembolism among women with Thrombophilia who are taking oral contraceptives or hormone replacement therapy, conducting a systematic review and metaanalysis. Of 201 studies identified, only nine met the inclusion criteria. Seven studies included pre-menopausal women on oral contraceptives and two studies included peri-menopausal women on hormone replacement therapy. For oral contraceptive use, significant associations of the risk of venous thromboembolism were found in women with factor V Leiden (OR 15.62; 95%CI 8.66 to 28.15); deficiencies of antithrombin (OR 12.60; 95%CI 1.37 to 115.79), protein C (OR 6.33; 95%CI 1.68 to 23.87), or protein S (OR 4.88; 95%CI 1.39 to 17.10), elevated levels of factor VIIIc (OR 8.80; 95%CI 4.13 to 18.75); and factor V Leiden and prothrombin G20210A (OR 7.85; 95%CI 1.65 to 37.41). For hormone replacement therapy, a significant association was found in women with factor V Leiden (OR 13.16; 95%CI 4.28 to 40.47).Although limited by the small number of studies, the findings of this study support the presence of interaction between Thrombophilia and venous thromboembolism among women taking oral contraceptives. However, further studies are required to establish with greater confidence the associations of these, and other, Thrombophilias with venous thromboembolism among hormone users.
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superficial vein thrombosis incidence in association with pregnancy and prevalence of thrombophilic defects
Thrombosis and Haemostasis, 1998Co-Authors: M D Mccoll, I D Walker, J E Ramsay, R C Tait, F Mccall, J A Conkie, Matthew J Carty, Ian A GreerAbstract:Superficial venous thrombotic (SVT) events are a feature of thrombophilic abnormalities, particularly those involving the protein C pathway. We have determined the incidence of SVT associated with pregnancy and the early postpartum period in a retrospective study involving 72 000 deliveries. Fourty-nine cases occurring in 47 individuals were recorded, with an overall incidence of 0.68/1000 deliveries (95% CI 0.48-0.88). None had a previous history of deep vein thrombosis or pulmonary embolism. Most events occurred in the early post-partum period (0.54/1000 deliveries). Twenty-four/fourty-seven were screened for established thrombophilic abnormalities, with only 1 abnormality detected (FV Leiden heterozygote). Thrombophilia may play a minor role in the aetiology of SVT associated with pregnancy, although a larger study is required to confirm this.
Roumen G Roussev - One of the best experts on this subject based on the ideXlab platform.
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which thrombophilic gene mutations are risk factors for recurrent pregnancy loss
American Journal of Reproductive Immunology, 2006Co-Authors: Cyle S Goodman, Carolyn B Coulam, Rajasinqam S Jeyendran, Vida A Acosta, Roumen G RoussevAbstract:Problem Thrombophilia has been associated with poor obstetrical outcomes. To determine the association of specific inherited Thrombophilias and recurrent pregnancy loss, 10 thrombophilic genes were investigated. Method of study A total of 550 women with a history of recurrent pregnancy loss had buccal swabs taken for DNA analyses of the following gene mutations: factor V G1691A, factor V H1299R (R2), factor V Y1702C, factor II prothrombin G20210A, factor XIII V34L, β-fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C. The frequencies of these mutations were compared with controls published in the literature. Results When examined individually, PAI-1 4G/5G (P = 0.009), factor XIII V34L (P < 0.0001), and homozygous MTHFR C667T (P < 0.0001) correlated significantly with recurrent pregnancy loss compared with controls. The frequency of the factor V Y1702C mutation was extremely low in patients and controls; thus, this gene was removed from further calculations. The remaining six mutated genes, when analyzed cumulatively, also corresponded with recurrent pregnancy loss (P < 0.0001). Conclusion A panel of thrombogenic gene mutations consisting of factor V G1691A, factor V H1299R (R2), factor II prothrombin G20210A, factor XIII V34L, β-fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), MTHFR C677T, and MTHFR A1298C can identify individuals at risk for recurrent pregnancy loss.
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multiple thrombophilic gene mutations rather than specific gene mutations are risk factors for recurrent miscarriage
American Journal of Reproductive Immunology, 2006Co-Authors: Carolyn B Coulam, Rajasinqam S Jeyendran, L A Fishel, Roumen G RoussevAbstract:Problem Recurrent miscarriage is a heterogeneous condition. While the role of acquired Thrombophilia has been accepted as an etiology of recurrent miscarriage, the contribution of specific inherited thrombophilic genes to this disorder has remained controversial. We compared the prevalence of 10 thrombophilic gene mutations among women with a history of recurrent miscarriages and fertile control women. Method of study A total of 150 women with a history of two or more recurrent pregnancy losses and 20 fertile control women with no history of pregnancy losses had buccal swabs taken for DNA analyses of 10 gene mutations [factor V G1691A, factor V H1299R (R2), factor V Y1702C, factor II prothrombin G20210A, factor XIII V34L, β-fibrinogen −455G>A, PAI-1 4G/5G, HPA1 a/b (L33P), MTHFR C677T, MTHFR A1298C]. The prevalence of these mutations was compared between women experiencing recurrent miscarriage and controls. Results No differences in the frequency of specific gene mutations were detected when women with recurrent miscarriage were compared with control women. However, the prevalence of homozygous mutations and total gene mutations among patients with recurrent miscarriage was significantly higher than among controls. Homozygous mutations were found in 59% of women with a history of recurrent pregnancy loss contrasted to 10% of control women. More than three gene mutations among the 10 genes studied were observed in 68% of women with recurrent miscarriage and 21% of controls. Conclusion Inherited Thrombophilias are associated with recurrent miscarriage. This association is manifest by total number of mutations rather than specific genes involved.
Gili Kenet - One of the best experts on this subject based on the ideXlab platform.
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impact of Thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children a systematic review and meta analysis of observational studies
Circulation, 2010Co-Authors: Gili Kenet, Lisa K Lutkhoff, Manuela Albisetti, Timothy J Bernard, Mariana Bonduel, Leonardo R Brandao, Stephane Chabrier, Anthony K C Chan, Gabrielle Deveber, B FiedlerAbstract:BACKGROUND: The aim of this study was to estimate the impact of Thrombophilia on risk of first childhood stroke through a meta-analysis of published observational studies. METHODS AND RESULTS: A systematic search of electronic databases (Medline via PubMed, EMBASE, OVID, Web of Science, The Cochrane Library) for studies published from 1970 to 2009 was conducted. Data on year of publication, study design, country of origin, number of patients/control subjects, ethnicity, stroke type (arterial ischemic stroke [AIS], cerebral venous sinus thrombosis [CSVT]) were abstracted. Publication bias indicator and heterogeneity across studies were evaluated, and summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Twenty-two of 185 references met inclusion criteria. Thus, 1764 patients (arterial ischemic stroke [AIS], 1526; cerebral sinus venous thrombosis [CSVT], 238) and 2799 control subjects (neonate to 18 years of age) were enrolled. No significant heterogeneity was discerned across studies, and no publication bias was detected. A statistically significant association with first stroke was demonstrated for each Thrombophilia trait evaluated, with no difference found between AIS and CSVT. Summary ORs (fixed-effects model) were as follows: antithrombin deficiency, 7.06 (95% CI, 2.44 to 22.42); protein C deficiency, 8.76 (95% CI, 4.53 to 16.96); protein S deficiency, 3.20 (95% CI, 1.22 to 8.40), factor V G1691A, 3.26 (95% CI, 2.59 to 4.10); factor II G20210A, 2.43 (95% CI, 1.67 to 3.51); MTHFR C677T (AIS), 1.58 (95% CI, 1.20 to 2.08); antiphospholipid antibodies (AIS), 6.95 (95% CI, 3.67 to 13.14); elevated lipoprotein(a), 6.27 (95% CI, 4.52 to 8.69), and combined Thrombophilias, 11.86 (95% CI, 5.93 to 23.73). In the 6 exclusively perinatal AIS studies, summary ORs were as follows: factor V, 3.56 (95% CI, 2.29 to 5.53); and factor II, 2.02 (95% CI, 1.02 to 3.99). CONCLUSIONS: The present meta-analysis indicates that Thrombophilias serve as risk factors for incident stroke. However, the impact of Thrombophilias on outcome and recurrence risk needs to be further investigated.
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factor v leiden and antiphospholipid antibodies in either mothers or infants increase the risk for perinatal arterial ischemic stroke
Stroke, 2009Co-Authors: Michal J Simchen, Gal Goldstein, Aaron Lubetsky, Tzipi Strauss, Eyal Schiff, Gili KenetAbstract:Background and Purpose— The objective was to investigate the role of infant and maternal Thrombophilia in a cohort of mothers and infants presenting with perinatal arterial ischemic stroke. Methods— Forty-seven infants with clinically and radiologically confirmed perinatal arterial ischemic stroke underwent Thrombophilia workup: factor V Leiden (FVL), PII20210A mutation, Methylene-tetrahydrofolate reductase 677T polymorphism, protein C, protein S, antithrombin, FVIII, and antiphospholipid antibodies. Thrombophilia data were available for 23 mother–infant pairs and compared with control populations to evaluate the risk for PAS. Results— Thirty of 47 (64%) infants and 15 of 22 mothers (68%) had evidence of Thrombophilia. In 18 of 23 (78%) mother–infant pairs, there was at least 1 thrombophilic risk factor, but 15 pairs were mismatched in pathology. Among infants, FVL, protein C deficiency, and presence of antiphospholipid antibodies prevailed (OR, 4.2; 95% CI, 1.5–11.3; OR, 12.2; 95% CI, 2.5–59.9; OR, 4.1; ...
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perthes disease and the search for genetic associations collagen mutations gaucher s disease and Thrombophilia
Journal of Bone and Joint Surgery-british Volume, 2008Co-Authors: Gili Kenet, E Ezra, S Wientroub, David M Steinberg, Nurit Rosenberg, D Waldman, Shlomo HayekAbstract:The role of heritable thrombophilic risk factors in the pathogenesis of the Perthes' disease is controversial. The clinical and radiological findings of Perthes' disease may be indistinguishable from those of Gaucher's disease, and the most common Jewish N370S Gaucher mutation is threefold greater in patients with Perthes' disease. Familial osteonecrosis of the femoral head is associated with variant mutations of collagen type II (COL2A1 mutations). We therefore studied the potential role of genetic Thrombophilia and the Gaucher and COL2A1 mutations in children with Perthes' disease. Genomic DNA of 119 children with radiologically-confirmed Perthes' disease diagnosed between 1986 and 2005 was analysed for the thrombophilic polymorphisms Factor V Leiden, 677T-MTHFR and FIIG20210A. The results were compared with those of a group of 276 children without Perthes' disease. DNA was also analysed for the Gaucher mutations N370S, G insertion (84GG), L444P, Intron 2 (IVS2+1G>A) and R496H. Enzymic assays confirmed the Gaucher disease status. Collagen (COL2A1) mutations of the 12q13 gene were also analysed. The prevalence of thrombophilic markers was similar among the 119 patients with Perthes' disease and the 276 control subjects. The prevalence of the Gaucher mutation was consistent with Israeli population carriership data and did not confirm an earlier-claimed association with Perthes' disease. All 199 patients were negative for the studied COL2A1 mutations. We found no genetic association between Perthes' disease and either Gaucher's disease or COL2A1 mutations or increased genetic Thrombophilia among our patients compared with the control group. A systematic review of case-control studies suggested that there was a positive association between Perthes' disease and Factor V Leiden. The impact of this association upon the disease, although not consistent across the studies, remains unclear.
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paediatric cerebral sinus vein thrombosis a multi center case controlled study
Thrombosis and Haemostasis, 2004Co-Authors: Gili Kenet, Joseph Kapelushnik, Dalia Waldman, Aharon Lubetsky, Nurit Kornbrut, Abdalla Khalil, Ariel Koren, Baruch Wolach, Aviva Fattal, Hannah TamaryAbstract:The etiology and pathophysiology of cerebral sinus venous thrombosis (CSVT) in the paediatric population is still poorly understood, and the role of thrombophilic risk factors remains to be elucidated. In our multi-center case-controlled study we studied 46 patients with CSVT diagnosed from April 1996 to December 2003, consecutively referred for Thrombophilia work-up. The results of Thrombophilia screen were compared to 112 healthy paediatric controls. Anticoagulant therapy was applied according to treating physicians’ decisions, and all cases were prospectively followed for a median of 4.1 years. Of 46 children, 8 had CSVT diagnosed in the neonatal period and therefore were analyzed separately. The prevalence of single Thrombophilia markers and combinations of thrombophilic risk factors were similar among cases and controls. Among children with CSVT co-morbid systemic illness was present in most patients at diagnosis. Seven out of 8 children with idiopathic CSVT had thrombophilic risk factors as compared to 31/38 patients with co-morbid conditions. Anticoagulation was initiated in most patients, 11/46 patients continued therapy for a total of one year or more post event. Neither clinical presentation nor initial treatment decisions were affected by presence of thrombophilic risk factors in our study group. Thrombophilia prevalence was not increased in children with CSVT as compared to controls, however Thrombophilia was more frequent among children with idiopathic CSVT. Thus, those selected patients would benefit most from Thrombophilia work-up, required for long-term therapy considerations.
Ping Wang - One of the best experts on this subject based on the ideXlab platform.
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amaurosis fugax caused by heritable Thrombophilia hypofibrinolysis in cases without carotid atherosclerosis thromboprophylaxis prevents subsequent transient monocular partial blindness
Clinical and Applied Thrombosis-Hemostasis, 2007Co-Authors: Charles J Glueck, Karl C. Golnik, Ping WangAbstract:Nineteen patients (age 60 ± 14) with amaurosis fugax associated with heritable Thrombophilia-hypofibrinolysis without ipsilateral atherosclerotic carotid plaque or other causes of amaurosis fugax were studied. Our hypothesis was that case-specific thromboprophylaxis would prevent subsequent amaurosis fugax episodes. Prospective treatment data were available for 13 cases. Thrombophilic disorders included high Factors VIII and XI, G20210A prothrombin heterozygosity, low proteins C and S, MTHFR mutations, and the PL A1/A2 mutation. Hypofibrinolytic disorders included plasminogen activator inhibitor-1 4G4G, and high lipoprotein (a). Treatments included Coumadin; Lovenox, folic acid-vitamin B6-vitamin B12, discontinuation of estrogens-selective estrogen receptor modulators, Glucophage, and aspirin, as appropriate. Usually within 1 month on therapy, patients became asymptomatic and have remained asymptomatic for ≥ 1 year on therapy, without adverse treatment side effects. When amaurosis fugax occurs without car...
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61 amaurosis fugax caused by Thrombophilia hypofibrinolysis in cases without carotid atherosclerosis therapy with coumadin lovenox or folic acid b6 b12 prevents subsequent transient monocular partial blindness
Journal of Investigative Medicine, 2005Co-Authors: Charles J Glueck, L Sieve, Dawit Aregawi, Ping WangAbstract:In 8 men and 9 women, age 60 ± 14, all white) without carotid atherosclerosis, whose amaurosis fugax was caused by Thrombophilia-hypofibrinolysis, we hypothesized that case-specific intervention for coagulation disorders (Coumadin-Lovenox or folic acid [5 mg]-B6 [100 mg]-B12 [2000 μg]) would prevent subsequent episodes of transient monocular partial or total blindness. PCR measures of Thrombophilia (V Leiden, prothrombin, MTHFR, platelet glycoprotein PL A1/A2 mutations) and hypofibrinolysis (plasminogen activator inhibitor-1 4G4G mutation) were compared in 17 cases vs 276 healthy controls, 145 male, 131 female, 240 white, 32 black, 4 other. MTHFR C677T homozygosity or C677T-A1298C compound heterozygosity was more common in cases (7/16 [44%]) than controls (35/276 [13%]), Fisher9s p = .003. Serologic measures of Thrombophilia (proteins C, antithrombin III, free S, homocysteine, anticardiolipin antibody IgG and IgM, lupus anticoagulant, Factor VIII, Factor XI) and hypofibrinolysis (plasminogen activator inhibitor-1 [PAI-Fx], Lp[a]) were compared in the 17 cases vs 78 healthy adults. High (> 150%) Factor VIII was more common in cases (4/16 [25%]) than controls (5/72 [7%]), Fisher9s p = .053. All 17 cases had ≥ 1 thrombophilic-hypofibrinolytic disorder, with the most common being MTHFR C677T homozygosity or C677T-A1298C compound heterozygosity (7 cases), 4G4G homozygosity (5 cases), high Factor VIII (4 cases), lupus anticoagulant (4 cases), the platelet PL A1/A2 mutation (4 cases), low free protein S (2 cases), high PAI-Fx (2 cases), V Leiden heterozygosity (1 case), prothrombin gene mutation (1 case), and protein C deficiency (1 case). In 4 cases on Coumadin for 3, 5, 11, and 84 months, in 1 case for 8 months of pregnancy on Lovenox, and in 4 cases on folic acid-B6-B12 for 2, 3, 10, and 13 months, amaurosis fugax disappeared, usually within 1 month of starting therapy. Amaurosis fugax stopped in 2 cases when exogenous estrogens-SERMS were discontinued, stopped in 1 case on aspirin alone, and stopped spontaneously in 1 case. When amaurosis fugax occurs in the absence of carotid artery atherosclerosis, Thrombophilia and/or hypofibrinolysis are nearly universal, reversible pathoetiologies.
Jan Van Der Meer - One of the best experts on this subject based on the ideXlab platform.
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prevalence of parental thrombophilic defects after fetal death and relation to cause
Obstetrics & Gynecology, 2010Co-Authors: Fleurisca J Korteweg, Nic J G M Veeger, Jan Jaap H M Erwich, Nienke Folkeringa, Albertus Timmer, Joke M Ravise, J P Holm, Jan Van Der MeerAbstract:OBJECTIVE: To estimate whether parental thrombophilic defects after fetal death, either acquired or inherited, were more prevalent than in the normal population and to estimate associations between these thrombophilic defects and different fetal death causes. METHODS: In a multicenter, prospective cohort study of 750 fetal deaths, we tested couples for antithrombin, protein C, total and free protein S, and von Willebrand factor (vWF) plasma levels. Mothers' values were compared with reference values in gestational age-matched healthy pregnant women, and fathers were compared with healthy men. Prevalence of factor V Leiden, prothrombin G20210A mutation, and lupus anticoagulant were compared with the normal population. A panel classified death cause. RESULTS: More women with fetal death had decreased antithrombin (16.8%, P <.001) and protein C (4.0%, P = .03) and increased vWF (15.5%, P <.001) plasma levels than healthy pregnant women (2.5%). However, compared with normal ranges in the nonpregnant population, we only observed more women with increased vWF (12.4%, P <.001). More fathers had decreased free protein S (6.3%, P <.001) and elevated vWF (12.1%, P <.001) than healthy men (2.5%). Prevalence of inherited Thrombophilias was not higher in couples with fetal death than in the population. Neither inherited nor acquired maternal or paternal thrombophilic defects were associated with the main cause of death. Of placental causes, abruption and infarction were associated with acquired maternal defects. CONCLUSION: Except for vWF and paternal free protein S, acquired and inherited thrombophilic defects were not more prevalent after fetal death. Routine Thrombophilia testing after fetal death is not advised.
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risk of recurrent venous thrombosis in homozygous carriers and double heterozygous carriers of factor v leiden and prothrombin g20210a
Circulation, 2010Co-Authors: Willem M Lijfering, S Middeldorp, Nic J G M Veeger, Karly Hamulyak, Martin H Prins, Harry R Buller, Jan Van Der MeerAbstract:Background— Homozygous or double heterozygous factor V Leiden and/or prothrombin G20210A is a rare inherited thrombophilic trait. Whether individuals with this genetic background have an increased risk of recurrent venous thrombosis is uncertain. Methods and Results— A case-control design within a large cohort of families with Thrombophilia was chosen to calculate the risk of recurrent venous thrombosis in individuals with homozygosity or double heterozygosity of factor V Leiden and/or prothrombin G20210A. Cases were individuals with recurrent venous thrombosis, and controls were those with only 1 venous thrombosis. The cohort consisted of 788 individuals with venous thrombosis; 357 had factor V Leiden, 137 had prothrombin G20210A, 27 had factor V Leiden and/or prothrombin G20210A homozygosity, and 49 had double heterozygosity for both mutations. We identified 325 cases with recurrent venous thrombosis and 463 controls with only 1 venous thrombosis. Compared with noncarriers, crude odds ratio for recurren...
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selective testing for Thrombophilia in patients with first venous thrombosis results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives
Blood, 2009Co-Authors: Willem M Lijfering, S Middeldorp, Nic J G M Veeger, Karly Hamulyak, Martin H Prins, Harry R Buller, Janleendert P Brouwer, Ivan Bank, Michiel Coppens, Jan Van Der MeerAbstract:Thrombophilia screening is controversial. In a retrospective family cohort, where probands had thrombosis and a thrombophilic defect, 2479 relatives were tested for Thrombophilia. In antithrombin-, protein C-, and protein S-deficient relatives, annual incidences of venous thrombosis were 1.77% (95% CI, 1.14-2.60), 1.52% (95% CI, 1.06-2.11), and 1.90% (95% CI, 1.32-2.64), respectively, at a median age of 29 years and a positive family history of more than 20% symptomatic relatives. In relatives with factor V (FV) Leiden, prothrombin 20210G>A, or high FVIII levels, these were 0.49% (95% CI, 0.39-0.60), 0.34% (95% CI, 0.22-0.49), and 0.49% (95% CI, 0.41-0.51), respectively. High FIX, FXI, and TAFI, and hyperhomocysteinemia were not independent risk factors. Annual incidence of major bleeding in antithrombin-, protein C-, or protein S-deficient relatives on anticoagulants was 0.29% (95% CI, 0.03-1.04). Cumulative recurrence rates in relatives with antithrombin, protein C, or protein S deficiency were 19% at 2 years, 40% at 5 years, and 55% at 10 years. In relatives with FV Leiden, prothrombin 20210G>A, or high levels FVIII, these were 7%, 11%, and 25%, respectively. Considering its clinical implications, Thrombophilia testing should address hereditary deficiencies of antithrombin, protein C, and protein S in patients with first venous thrombosis at young age and/or a strong family history of venous thrombosis.
