Prevalence and factors associated with high-risk thrombophilia: a single-center cross-sectional study of 3550 patients at a tertiary Thrombosis Centre in Switzerland.

Background Thrombophilia testing remains controversial, with no standardized recommendations across patient populations. Objectives Given the clinical significance of high-risk thrombophilia (homozygous factor V Leiden or prothrombin G20210A mutations, natural anticoagulant deficiencies, and antiphospholipid antibody syndrome [APS]), we aimed to determine its prevalence and the clinical and laboratory factors associated with its diagnosis across diverse patient populations. Methods We conducted a single-center cross-sectional study of 3550 patients tested for thrombophilia at a tertiary thrombosis clinic between 2010 and 2020. Analyses were performed in the entire cohort and by referral indication. Univariate logistic regression was used to calculate the effect measures between clinical and laboratory characteristics of referred patients and high-risk thrombophilia. Results High-risk hereditary thrombophilia and APS were found in 155 (8%) and 67 (3%) tested patients with venous thromboembolism (VTE), in 25 (7%) and 40 (7%) tested patients with unexplained arterial thrombosis, and in 18 (17.2%) and 12 (11%) tested women with pregnancy-related morbidity, respectively. The prevalence of high-risk hereditary thrombophilia and APS was comparable in patients with unprovoked and major risk factor-provoked VTE (5.2% vs 8.2%, P = .1; 3.5% vs 2.8%, P = .9, respectively). A total of 37 (12%) of the tested asymptomatic family members had hereditary high-risk thrombophilia. Patients aged <50 years with VTE, a family history of VTE in a first-degree relative, no comorbidities, and D-dimer > 500 μg/L at the time of thrombophilia testing were more likely to have high-risk hereditary thrombophilia. Conclusion High-risk thrombophilia was mostly prevalent in women with pregnancy-related morbidity. The prevalence of thrombophilia in patients with VTE was comparable, irrespective of VTE risk factors. Several clinical characteristics were associated with high-risk hereditary thrombophilia in patients with VTE.