Prospective Evaluation of the Prevalence of Haemostasis Abnormalities in Unexplained Primary Early Recurrent Miscarriages

Abstract

The prevalence of haemostasis abnormalities was evaluated in 500 consecutive women with unexplained primary recurrent miscarriages. Two matched reference groups with no antecedent of miscarriage were studied: 100 healthy mothers and 50 childless women. In the prospective part of the study, we found 9.4% of the patients (95% C.I.: 6.8-12%) with an isolated factor XII deficiency, 7.4% of the patients (5.0-9.8%) with primary antiphopholipid antibodies, 47% of the patients (42.6-51.4%) with an insufficient response to the venous occlusion test and an isolated hypofibri- nolysis was found in 42.6% (38.2-47%) of the patients (reference groups: respectively 0/150, 3/150, 2/150, 2/150, pclO’³). Willebrand disease, fibrinogen deficiency, antithrombin, protein C or protein S deficiencies were not more frequent in recurrent aborters than in members of the reference groups. In the retrospective part of the study, cases of plasma resistance to activated protein C were not abnormally frequent. Patients had higher Willebrand factor antigen (vWF), tissue-type plasminogen activator antigen (t-PA), plasminogen activator inhibitor activity (PAI) and D-dimers (D-Di) than the reference women. Values of vWF, t-PA, PAI and D-Di were altogether correlated but were not related to C-reactive protein concentrations. Among patients, those with an antiphospholipid syndrome and those with an insufficient response to the venous occlusion test had higher vWF, t-PA, PAI and D-Di values than the patients with none of the haemostasis-related abnormalities. Thus, factor XII deficiency and hypofibrinolysis (mainly high PAI) are the most frequent haemostasis-related abnormalities found in unexplained primary recurrent aborters. In patients with antiphospholipid antibodies or hypofibrinolysis, there is a non-inflammatory ongoing chronic elevation of markers of endothelial stimulation associated with coagulation activation. This should allow to define subgroups of patients for future therapeutic trials.