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Objective  To test the hypothesis that markers of coagulation and hemostatic activation (MOCHA) help identify causes of cryptogenic stroke, we obtained serum measurements on 132 patients and followed them up to identify causes of stroke.    Methods  Consecutive patients with cryptogenic stroke who met embolic stroke of undetermined source (ESUS) criteria from January 1, 2017, to October 31, 2018, underwent outpatient cardiac monitoring and the MOCHA profile (serum D-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer) obtained ≥2 weeks after the index stroke; abnormal MOCHA profile was defined as ≥2 elevated markers. Prespecified endpoints monitored during routine clinical visits included new atrial fibrillation (AF), malignancy, venous thromboembolism (VTE), or other defined hypercoagulable states (HS).    Results  Overall, 132 patients with ESUS (mean age 64 ± 15 years, 61% female, 51% nonwhite) met study criteria. During a median follow-up of 10 (interquartile range 7–14) months, AF, malignancy, VTE, or HS was identified in 31 (23%) patients; the 53 (40%) patients with ESUS with abnormal MOCHA were significantly more likely than patients with normal levels to have subsequent new diagnoses of malignancy (21% vs 0%,  p  &lt; 0.001), VTE (9% vs 0%,  p  = 0.009), or HS (11% vs 0%,  p  = 0.004) but not AF (8% vs 9%,  p  = 0.79). The combination of 4 normal MOCHA and normal left atrial size (n = 30) had 100% sensitivity for ruling out the prespecified endpoints.    Conclusion  The MOCHA profile identified patients with cryptogenic stroke more likely to have new malignancy, VTE, or HS during short-term follow-up and may be useful in direct evaluation for underlying causes of cryptogenic stroke.

Markers of coagulation and hemostatic activation aid in identifying causes of cryptogenic stroke