Cerebral Venous Thrombosis During Pregnancy in the Setting of Type I Antithrombin Deficiency: Case Report and Literature Review.

Abstract Abstract 4447 Antithrombin is a serine protease inhibitor that primarily inactivates thrombin and factor Xa as well as multiple other coagulation factors. Hereditary deficiency of antithrombin is associated with a 50%-lifetime risk of venous thrombosis. For women who are antithrombin deficient, each single pregnancy and puerperium also carries a 50% risk of a venous thrombotic complication, with the majority of episodes occurring post-partum. Lower extremity thrombosis is most common but unusual sites such as the central nervous system may also be involved. Although there have been previous reports of successful pregnancy outcomes in antithrombin-deficient women without the use of prophylactic anticoagulation in the form of unfractionated heparin or low molecular weight heparin, current treatment guidelines state that asymptomatic women with hereditary antithrombin deficiency should receive thromboprophylaxis during pregnancy. However, the indications for the use of antithrombin concentrate are less defined and current guidelines do not mandate their use during pregnancy in the absence of an episode of venous thromboembolism. Some authors have advocated that antithrombin should be maintained at adequate levels in women with documented antithrombin deficiency throughout the course of pregnancy and the puerperium, while others have recommended normalization of antithrombin levels during the time of delivery only. The use of plasma-derived antithrombin concentrate is controversial considering its expense as well as issues with the frequency and route of administration (daily intravenous injection) and serial monitoring of antithrombin levels. We present a case of a female with a family history of antithrombin deficiency in multiple first-degree relatives and a documented personal history of Type I antithrombin deficiency who presented with a central nervous system transverse sinus thrombosis in the third trimester of pregnancy despite the use of prophylactic therapeutic doses of low molecular weight heparin since conception. Once the cerebral venous thrombosis was diagnosed, a successful pregnancy outcome was achieved with the combined use of therapeutic anticoagulation and antithrombin concentrate to normalize antithrombin levels. This case further illustrates the highly thrombophilic state that exists in the setting of pregnancy and concomitant antithrombin deficiency and lends further debate to the issue of whether antithrombin concentrate, in addition to anticoagulation, should be routinely administered for venous thromboembolic prophylaxis during pregnancy and puerperium to women with documented antithrombin deficiency. This point may become more relevant as further experience is gained with the use of recombinant human antithrombin. Disclosures: Crowther: BI: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Research Funding; Leo Pharma: Consultancy, Honoraria, Research Funding; Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Artisan Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Webert:Baxter: Research Funding.

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