Summary.  Background: Lupus anticoagulant (LA) is a strong risk factor of thrombosis. However, a subgroup of patients positive for LA is unaffected by thrombosis and currently no predictive markers are available to identify patients positive for LA at increased risk for thrombosis. Objective: The aim of the study was to investigate whether anti‐beta‐2‐glycoprotein I (anti‐β2GPI) or anticardiolipin antibodies (ACA) are associated with an increased risk of thrombosis in patients persistently positive for LA. Patients and methods: A cohort of 87 consecutive patients persistently positive for LA was investigated, 55 with and 32 without a history of thrombosis. Immunoglobulin G (IgG) and M (IgM) antibodies against β2GPI and cardiolipin were determined by enzyme‐linked immunoassay. Results: Patients positive for LA with thrombosis had significantly higher levels of anti‐β2GPI IgG (median 16.7 standard units, interquartile range 3.0–75.2, P = 0.002) and of ACA IgG (41.1 IgG phospholipid units per mL, 8.9–109.0, P = 0.002) than those without thrombosis (2.6, 1.4–7.9 and 9.7, 4.6–22.1, respectively). Levels of anti‐β2GPI IgM and ACA IgM did not differ significantly between LA patients with and without thrombosis (P = 0.25 and 0.12, respectively). Elevated anti‐β2GPI IgG was associated with an increased risk for thrombosis (OR = 4.0, 95% CI 1.2–13.1), especially for venous thromboembolism (OR = 5.2, 95% CI 1.5–18.0). Conclusions: Increased levels of anti‐β2GPI IgG were associated with thrombosis. We conclude that anti‐β2GPI IgG levels above normal predict an increased risk of thrombosis in patients persistently positive for LA.

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Summary. Background: Limited data exist on the clinical manifestations of homozygous factor (F)V:G1691A mutation (FV Leiden) and the impact of environmental and genetic risk factors. Objectives: To assess the contribution of these factors on the thrombophilic phenotype. Patients and methods: In a retrospective multicenter cohort study 165 individuals with homozygous FV:G1691A mutation, of whom 129 had previous venous thromboembolism (VTE), were included. To study the role of environmental risk factors, patients were compared by the use of a standardized questionnaire to 165 sex-and agematched individuals (reference group A); of these, two had previous VTE. To assess the role of genetic risk factors, factor (F)II:G20210A and MTHFR:C677T were determined in individuals homozygous for FV:G1691A and in 177 healthy individuals without previous VTE (reference group B). Results: The first VTE occurred significantly earlier in women (median age 25 years) than men (35.5 years). In 81% of women and 29% of men an environmental risk factor was present before first VTE. Oral contraceptives increased the risk of thrombosis 4-fold [odds ratio (OR) 4.0, 95% confidence interval (CI) 1.7, 10.4] in women with homozygous FV:G1691A. Postoperative and post-traumatic VTE as first manifestation occurred in 13% and 15% of surgical/traumatic events in patients and in 0.7% and 1.8% in reference group A, respectively (OR 19.7, 95% CI 2.5, 154 and OR 9.2, 95% CI 1.1, 79.4). Heterozygous FII:G20210A was more prevalent in symptomatic patients (11.7%) compared with reference group B (2.8%, OR 4.6, 95% CI 1.6, 13.2). The prevalence of homozygous MTHFR:C677T genotype was similar in patients and reference group B. Conclusions: Our study supports the concept of thrombophilia as a multifactorial disorder. The knowledge of coexisting factors predisposing to VTE is useful for medical advice for primary and secondary prophylaxis in these patients.