The Utility of the Markers of Coagulation and Hemostatic Activation Profile in the Management of Embolic Strokes of Undetermined Source

Abstract

BackgroundPotential causes of embolic stroke of undetermined source (ESUS) include occult malignancy, venous thrombosis (VTE) with paradoxical embolism, and hypercoagulable disorders. Given the association of markers of coagulation and hemostatic activation (MOCHA) with these causes, the objective of this study was to validate the utility of the MOCHA profile in identifying the underlying cause of stroke. MethodsWe prospectively identified ESUS patients from January 1, 2017 to December 1, 2019 who underwent MOCHA profile (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer) testing. Abnormal MOCHA profile was defined as ≥ 2 abnormal markers. New diagnoses of malignancy, VTE, hypercoagulable disorders and recurrent stroke were identified during routine clinical follow-up. ResultsOf 236 ESUS patients, 104 (44%) patients had an abnormal MOCHA profile. In multivariable analyses the number of MOCHA abnormalities was significantly associated with malignancy, VTE, and hypercoagulable disorders (OR 2.59, CI 95% 1.78-3.76, p<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value of an abnormal MOCHA profile for the combined outcome of malignancy, VTE, and hypercoagulability was 96%, 62%, 23%, and 99% respectively. DiscussionThe MOCHA profile was able to identify ESUS patients more likely to have malignancy, VTE, and hypercoagulable disorders during follow-up. Our results show that a normal MOCHA profile in ESUS patients can effectively rule out these potential causes of ESUS.