Latent thrombophilic conditions in pregnant and reproductive-age women with an adverse cerebrovascular history and a high risk of acute cerebrovascular events

Aim: to assess the prevalence and pattern of latent thrombophilic conditions in pregnant and reproductive-age women with an adverse cerebrovascular history, as well as in patients at high risk of acute cerebrovascular events (ACVEs) identified using a previously developed prognostic model, based on a comprehensive clinical and hemostasiological analysis.

Materials and Methods. A two-stage observational study was conducted, consisting of sequential retrospective and prospective phases. In the retrospective phase, data from 50 patients with ACVEs that had occurred during pregnancy, in the early postpartum period, or outside gestation were analyzed; 30 clinically healthy pregnant women were included in control group. Based on the retrospective data, a prognostic model for cerebrovascular risk stratification had previously been developed; in the present study, this model was used solely as a tool to identify high-risk patients. In the prospective phase, 45 pregnant and reproductive-age women with ACVEs history or a high risk of their development, as identified by the above model, as well as 30 clinically healthy pregnant women, were examined. All patients underwent an extended clinical and hemostasiological evaluation, including assessing genetic thrombophilia, natural anticoagulant deficiencies, antiphospholipid antibodies (aPL), homocysteine levels, metalloproteinase ADAMTS-13 activity, anti-ADAMTS-13 antibodies, as well as parameters of the vWF/ADAMTS-13 axis.

Results. In the retrospective phase, inherited and acquired forms of thrombophilia were detected significantly more often in patients with ACVEs than in control group, 84.0 % versus 6.7 % cases, respectively. Pattern of cerebrovascular events was featured with ischemic stroke diagnosed in 58.0 % patients, whereas cerebral venous thrombosis – in 42.0 % cases. In prospective group, genetically determined thrombogenic abnormalities were detected in 35.6 % patients, criterial aPLs were detected in 28.9 %, hyperhomocysteinemia – in 15.6 %, reduced ADAMTS-13 activity – in 11.1 %, anti-ADAMTS-13 antibodies – in 26.7 %, and elevated von Willebrand factor levels – in 28.9 %. Combined thrombophilia was identified in 35.6 % patients in the prospective group, suggesting the multifactorial nature of prothrombotic predisposition.

Conclusion. Latent thrombophilic conditions are frequently detected in pregnant and reproductive-age women with ACVEs history, as well as in patients at ACVE high risk, and often have a combined pattern involving both genetically determined and acquired hemostatic disorders. These findings substantiate a need for extended clinical and hemostasiological assessment in this category of patients at the stage of pregnancy planning and during pregnancy to improve risk stratification and individualize prevention of thrombotic complications.

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