Abstract
BACKGROUND: Pregnancy represents a “physiologic” maternal thrombophilic state, with presumed evolutionary goals of ensuring secure fetal implantation, placental stability, and control of peripartum maternal bleeding. Specific pregnancy-induced maternal changes include increased activated Protein C resistance; decreased active Protein S; increased levels of vitamin K-dependent procoagulants, factor VIII, von Willebrand factor, and fibrinogen; and increased levels of plasminogen activator inhibitor (PAI-1). Superposition of pregnancy upon inherited or acquired thrombophilias may have untoward consequences for both mother and fetus. Venous thromboembolism (the leading cause of maternal morbidity and mortality in pregnancy) is five times more likely to occur in pregnant women than in nonpregnant women of similar age. Placental insufficiency and recurrent fetal loss are strongly associated with inherited and acquired thrombophilia, and antithrombotic interventions with aspirin, unfractionated heparin and low molecular weight heparins (LMWHs) have decreased maternal morbidity and improved fetal outcome. LMWHs offer decreased incidence of bleeding, heparin-induced thrombocytopenia with thrombosis (HITT), and osteoporosis, as well as predictable dosing efficacy. An industry sponsored series of roundtable discussions with US hematology and high-risk obstetrics practitioners revealed that a collective deterrent to use of tinzaparin (the most recently introduced LMWH with favorable pharmacokinetics and once-daily dosing) was the limited amount of published safety and efficacy data in this patient population.
STUDY DESIGN: Fifty pregnancies in women treated with tinzaparin between January 2003, and June 2004, in American maternal/fetal medicine programs for high risk from prior pregnancy-associated VTE, presence of high risk pre-existing thrombophilias, or recurrent fetal loss are undergoing retrospective analysis for maternal and fetal outcomes; safety; and compliance with therapy. A specific identifier-blind data collection tool will capture historical and examination data and diagnostic studies that establish and follow risk as well as tabulate antithrombotic and adjunctive medication/supplement regimens. “Live birth” and “fetal loss” questionnaires will capture maternal and fetal course, complications, anesthesia and delivery decisions, and tissue pathology, as appropriate.
RESULTS: Data analysis will be complete by late November 2004. In the absence of large randomized trials of efficacy and safety, such a study may provide guidelines for safe and effective use of tinzaparin in American high-risk pregnancy.
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