Estrogen levels and thrombophilia—an intervening variable or a confounder?

Abstract

We read with great interest the manuscript of Dulitzky et al. (1) investigating the prevalence of different types of thrombophilia in women suffering from severe ovarian hyperstimulation syndrome (OHSS). We were really surprised about the high frequency of different markers of thrombophilia found in the studied population. These investigators searched for factor V Leiden mutation, the C677T polymorphism in the methylen tetrahydrofolate reductase (MTHFR C677T) gene, protein C deficiency, protein S deficiency, antithrombin deficiency, and presence of circulating lupus anticoagulant or ant icardiolipin antibodies as representatives for antiphospholipid syndrome. The first two thrombophilias are inherited disorders, the antiphospholipid syndrome is acquired, and the rest (protein C, protein S, and antithrombin deficiencies) can be of both origins, but mainly inherited. The two more frequent of the cited thrombophilias are the homozygosity for MTHFR C677T and the factor V Leiden mutation, with an estimated prevalence in the healthy white population of 11% (2) and 4% (3), respectively. The hereditary forms of protein C and protein S deficiencies appeared in 0.3% of the healthy white population each, and the hereditary form of antithrombin deficiency only in 0.04%. Some of these hypercoagulable states present a lower incidence across other different ethnic populations (3). Antiphospholipid antibodies are found among young, apparently healthy control subjects, at a prevalence of 1% to 5% for both anticardiolipin antibodies and lupus anticoagulant antibodies (4).