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Markers of coagulation and hemostatic activation aid in identifying causes of cryptogenic stroke
Fadi Nahab1, Vera Sharashidze2, Michael Liu2
1From the Departments of Neurology (F.N., V.S., M.L., P.R., S.E.J., F.M., S.B., N.B., T.B., L.H., K.M., S.R.), Pediatrics (F.N.), Pathology (A.D.), and Cardiology (M.H.), Emory University, Atlanta, GA fnahab@emory.edu.
Insights
Markers of coagulation and hemostatic activation (MOCHA) identify patients with cryptogenic stroke who are more likely to develop malignancy, venous thromboembolism, or hypercoagulable states. This profile aids in evaluating underlying causes of stroke.
Area of Science:
- Cardiology
- Hematology
- Neurology
Background:
- Cryptogenic stroke, or stroke of unknown origin, presents a diagnostic challenge.
- Identifying underlying causes is crucial for effective secondary prevention strategies.
Purpose of the Study:
- To evaluate the utility of the Markers of Coagulation and Hemostatic Activation (MOCHA) profile in identifying causes of cryptogenic stroke.
- To determine if MOCHA markers can predict subsequent diagnoses of malignancy, venous thromboembolism (VTE), or other hypercoagulable states (HS) in patients with embolic stroke of undetermined source (ESUS).
Main Methods:
- Serum MOCHA profiles (D-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer) were obtained from 132 patients meeting ESUS criteria.
- Patients were monitored for new diagnoses of atrial fibrillation (AF), malignancy, VTE, or HS during follow-up.
- An abnormal MOCHA profile was defined as two or more elevated markers.
Main Results:
- In a median follow-up of 10 months, 23% of patients were diagnosed with AF, malignancy, VTE, or HS.
- Patients with an abnormal MOCHA profile (40%) were significantly more likely to be diagnosed with malignancy (21% vs 0%), VTE (9% vs 0%), or HS (11% vs 0%) compared to those with normal MOCHA.
- No significant difference in new AF diagnoses was observed between groups (8% vs 9%).
- A combination of normal MOCHA and normal left atrial size demonstrated 100% sensitivity for ruling out prespecified endpoints.
Conclusions:
- The MOCHA profile effectively identifies patients with cryptogenic stroke at higher risk for malignancy, VTE, or HS.
- MOCHA testing may serve as a valuable tool for guiding the etiological evaluation of cryptogenic stroke.
- Normal MOCHA combined with normal left atrial size can reliably exclude key secondary causes of stroke.
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 < 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.
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