title: Respective evaluation of the prevalence of haemostasis abnormalities in unexplained primary early recurrent miscarriages. The Nimes Obstetricians and Haematologists (NOHA) Study.
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 hypofibrinolysis was found in 42.6% (38.2-47%) of the patients (reference groups: respectively 0/150, 3/150, 2/150, p < 10(-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.
authors.affiliation: Consultations et Laboratoire d'Hématologie, CHU, Nimes, France.
authors.forename: J C
authors.initials: JC
authors.lastname: Gris
authors.forename: S
authors.initials: S
authors.lastname: Ripart-Neveu
authors.forename: C
authors.initials: C
authors.lastname: Maugard
authors.forename: M L
authors.initials: ML
authors.lastname: Tailland
authors.forename: S
authors.initials: S
authors.lastname: Brun
authors.forename: C
authors.initials: C
authors.lastname: Courtieu
authors.forename: C
authors.initials: C
authors.lastname: Biron
authors.forename: M
authors.initials: M
authors.lastname: Hoffet
authors.forename: B
authors.initials: B
authors.lastname: Hédon
authors.forename: P
authors.initials: P
authors.lastname: Marès
mesh_terms: D000026:Abortion, Habitual / Q000097:blood* / Q000503:physiopathology; D000328:Adult; D000941:Antigens / Q000032:analysis; D005175:Factor XII Deficiency / Q000097:blood / Q000503:physiopathology; D005260:Female; D005342:Fibrinolysis; D006487:Hemostasis; D006801:Humans; D011247:Pregnancy; D011446:Prospective Studies; D014841:von Willebrand Factor / Q000276:immunology
chemical_list: D000941:Antigens; C029417:Von Willebrand antigen; D014841:von Willebrand Factor