The Prevalence and Clinical Significance of Inherited Thrombophilic Risk Factors in Patients with Antiphospholipid Syndrome.

Abstract

Antiphospholipid syndrome (APS) is defined as the occurrence of thrombosis and/or recurrent fetal losses in association with the presence of antiphospholipid antibodies (APLA). Although it has been suggested that APLA have a pathogenic role in the thrombotic complications of APS, pathogenicity of APLA has not been conclusively proven. It has been speculated that other inherited or acquired thrombogenic risk factors might influence the development of thrombosis in patients with APS. In the present study, we examined the effect of well known inherited thrombophilic risk factors (inherited protein C (PC), protein S (PS) and antithrombin (AT) deficiencies; factor V Leiden (FVL) G1691A mutation, and prothrombin G20210A mutation) in the development of thrombosis in APS patients. Seventy-three definite APS patients with arterial and venous thrombosis (group 1: APS patients with thrombosis), 29 antiphospholipid antibody-positive patients with first trimester abortus and/or thrombocytopenia and no history of thrombosis (group 2: APLA-positive patients without thrombosis), and 126 healthy controls (group 3) were included into the study. PC, PS, and AT deficiencies were screened with functional assays; the presence of FVL mutation and prothrombin mutation were detected by polymerase chain reaction. PS and AT activities were found to be normal in all groups. Only a single APS patient with thrombosis had been found to have PC deficiency, PC activities were normal in both APLA-positive patients without thrombosis and healthy controls. The frequencies of FVL A allele for APS patients with thrombosis, APLA-positive patients without thrombosis, and healthy controls were 10.4%, 6.8%, and 4.9%, respectively. The frequency of FVL A allele was significantly higher in APS patients with thrombosis compared with healthy controls (10.4% vs 4.9%, p= 0.02 with chi-square test). The frequencies of prothrombin A allele for APS patients with thrombosis, APLA-positive patients without thrombosis and healthy controls were 3.4%, 0%, and 1.3%, respectively. Although the frequency of A allele was higher in APS patients with thrombosis compared with both APLA-positive patients without thrombosis and healthy controls, it was not statistically significant. Our results showed that inherited PC, PS, AT deficiencies, and prothrombin G20210A mutation are not common in patients with APS. FVL G1691A mutation may contribute to the development of thrombosis in a small group of APS patients. This study suggests that the known inherited thrombophilic risk factors are not responsible for the development of thrombosis in the majority of APS patients. Further prospective studies in larger cohorts of patients are needed to delineate the exact role of thrombophilic mutations in the development of thrombosis in APS.