title: Heparin Resistance and Anticoagulation Failure in a Challenging Case of Cerebral Venous Sinus Thrombosis.
abstract: We report a challenging case of cerebral venous sinus thrombosis (multiple etiologic factors) that was complicated by heparin resistance secondary to suspected antithrombin III (ATIII) deficiency. A 20-year-old female previously healthy and currently 8 weeks pregnant presented with worsening headaches, nausea, and decreasing Glasgow Coma Scale/Score (GCS), necessitating mechanical ventilatory support. Imaging showed extensive clots in multiple cerebral venous sinuses including the superior sagittal sinus, transverse, sigmoid, jugular veins, and the straight sinus. She was started on systemic anticoagulation and underwent mechanical clot removal and catheter-directed endovascular thrombolysis with limited success. Complicating the intensive care unit care was the development of heparin resistance, with an inability to reach the target partial thomboplastin time (PTT) of 60 to 80 seconds. At her peak heparin dose, she was receiving >35 000 units/24 h, and her PTT was subtherapeutic at <50 seconds. Deficiency of ATIII was suspected as a possible etiology of her heparin resistance. Fresh frozen plasma was administered for ATIII level repletion. Given her high thrombogenic risk and challenges with conventional anticoagulation regimens, we transitioned to argatroban for systemic anticoagulation. Heparin produces its major anticoagulant effect by inactivating thrombin and factor X through an AT-dependent mechanism. For inhibition of thrombin, heparin must bind to both the coagulation enzyme and the AT. A deficiency of AT leads to a hypercoagulable state and decreased efficacy of heparin that places patients at high risk of thromboembolism. Heparin resistance, especially in the setting of critical illness, should raise the index of suspicion for AT deficiency. Argatroban is an alternate agent for systemic anticoagulation in the setting of heparin resistance.
authors.affiliation: Division of Critical Care, Department of Anesthesiology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Adam B
authors.initials: AB
authors.lastname: King
authors.affiliation: Department of Neurology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Anne E
authors.initials: AE
authors.lastname: O'Duffy
authors.affiliation: Division of Critical Care, Department of Anesthesiology, Vanderbilt University, Nashville, TN, USA.
authors.forename: Avinash B
authors.initials: AB
authors.lastname: Kumar
keywords: cerebrovascular disorders; clinical specialty; hematology; neurocritical care; stroke