The prevalence and clinical manifestation of hereditary thrombophilia in Korean patients with unprovoked venous thromboembolisms

Abstract

Background: Hereditary thrombophilia (HT) is a genetic predisposition to thrombosis. Asian mutation spectrum of HT is different from Western ones. We investigated the incidence and clinical characteristics of HT in Korean patients with unprovoked venous thromboembolism (VTE).

Methods: Among 369 consecutive patients with thromboembolic event who underwent thrombophilia tests, we enrolled 222 patients diagnosed with unprovoked VTE. The presence of HT was confirmed by DNA sequencing of the genes that cause deficits in natural anticoagulants (NAs). Median follow-up duration was 40±38 months.

Results: Among the 222 patients with unprovoked VTE, 66 (29.7%) demonstrated decreased NA level, and 33 (14.9%) were finally confirmed to have HT in a genetic molecular test. Antithrombin III deficiency (6.3%) was most frequently detected, followed by protein C deficiency (5.4%), protein S deficiency (1.8%), and dysplasminogenemia (1.4%). The HT group was significantly younger (37 [32-50] vs. 52 [43-65] years; P < 0.001) and had a higher proportion of male (69.7% vs. 47%; P = 0.013), more previous VTE events (57.6% vs. 31.7%; P = 0.004), and a greater family history of VTE (43.8% vs. 1.9%; P < 0.001) than the non-HT group. Age <45 years and a family history of VTE were independent predictors for unprovoked VTE with HT (odds ratio, 9.435 [2.45-36.35]; P = 0.001 and 92.667 [14.95-574.29]; P < 0.001).

Conclusions: About 15% of patients with unprovoked VTE had HT. A positive family history of VTE and age <45 years were independent predictors for unprovoked VTE caused by HT.

Fig 1. Flow diagram of the study population.

VTE, venous thromboembolism; NAs, natural anticoagulants; HT, hereditary thrombophilia; AT, antithrombin III; PC, protein C, PS, protein S; PLG, plasminogen.

Fig 2. Association between recurrence of VTE and anticoagulation in patients with or without hereditary thrombophilia.

N, patients without hereditary thrombophilia; P, patients with hereditary thrombophilia.