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Abstract

Introduction: Hypofibrinogenemia after treatment with systemic recombinant tissue plasminogen activator (rtPA) is reported in up to 60% of patients treated for acute myocardial infarction, appears to be dose-dependent, and may increase bleeding risk. Conversely, hypofibrinogenemia and abnormal INR are poorly described after rtPA for acute ischemic stroke (AIS), and routine monitoring of fibrinogen and INR after rtPA administration is not recommended. Hypothesis: We hypothesize that systemic rtPA for treatment of AIS is associated with hypofibrinogenemia, an abnormal INR, and an increased bleeding risk. Methods: An index case involving an 87 year old male with AIS treated with rtPA prompted this investigation. An INR 9 hours post rtPA was 4.2 with an associated fibrinogen <35 mg/dL. Our stroke database was queried to identify the incidence and significance of hypofibrinogenemia and abnormal INR after rtPA. All patients in this case series received systemic rtPA for AIS from October 1, 2009 to June 30, 2012. Those with a baseline INR prior to rtPA and an INR and/or fibrinogen measured within 24 hours after rtPA were included. Data are reported as median (interquartile range). Results: 57 patients received rtPA for AIS, of whom 15 (26%) met inclusion criteria. The rtPA dose was 0.88 mg/kg (0.81-0.91 mg/kg). Baseline INR was 1.1 (1.0-1.2) and was normal in 100%. Repeat INR within 24 hours of rtPA was 1.2 (1.1-1.3), but was abnormal (1.4 and 4.2) in 2/15 (13%). Fibrinogen was measured in 7 patients, and was low (<35 and 61 mg/dL) in the same 2 patients with an elevated INR. Cerebral hemorrhagic conversion occurred in 3 (20%) of the 15 patients; all 3 had a normal INR, 2 had a normal fibrinogen, and fibrinogen was unmeasured in one. No patient developed systemic hemorrhage. In-hospital deaths occurred in 2 (13%); the fibrinogen was normal in one and unmeasured in the other. Conclusions: Hypofibrinogenemia and abnormal INR after the administration of systemic rtPA for AIS occurred in 13% (95% CI, 4 to 38%) in our small retrospective case series, and was of uncertain significance. Further evaluation of this topic, and correlation with bleeding risk in a larger cohort, is warranted.