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A New Strategy for Identifying the Cause of Cryptogenic Stroke

Simple blood tests could help clinicians determine which patients may need a different treatment approach than the standard of care

Stroke neurologists at Emory Brain Health Center are evaluating a novel blood biomarker profile to help identify the underlying cause of cryptogenic stroke. Their recent clinical study, published in Neurology (May 5, 2020), demonstrates the utility of this biomarker as a diagnostic tool.

Cryptogenic strokes make up about 30-40% of all ischemic strokes. Studies suggest that up to one-third of cryptogenic strokes may be caused by occult atrial fibrillation. Non-cardiac causes such as occult malignancies, paradoxical venous thromboembolism and hypercoagulable states also can cause a cryptogenic stroke. The standard of care for patients with cryptogenic stroke is to prescribe antiplatelet therapy and manage other risk factors for stroke, such as high blood pressure and diabetes. In addition to creating anxiety, the lack of a definitive diagnosis means that standard treatment may not address the patient’s underlying disease state or recurrence risk. The estimated risk of stroke recurrence in these patients is 4-5% a year.

Background, methods and findings

As part of their commitment to identifying patients’ cause of stroke as early as possible, Emory researchers developed the novel “markers of coagulation and hemostatic activation (MOCHA)” profile. The panel includes:

  • Fibrin monomer
  • Prothrombin fragment 1.2
  • Serum D-dimer
  • Thrombin-antithrombin complex

In a 2018 pilot study, the researchers used the MOCHA profile for the first time to identify a subgroup of patients who were at higher risk of having occult atrial fibrillation, a malignancy or recurrent stroke during follow-up, despite receiving standard of care. The 2020 study published in Neurology was a follow-up to that study and focused on whether the MOCHA profile could be used to identify the underlying cause of a cryptogenic stroke.

Study participants included 132 consecutive patients with cryptogenic stroke who met the criteria for an embolic stroke of undetermined source (ESUS) from January 1, 2017, to October 31, 2018. Researchers collected blood samples from each patient at least two weeks after the stroke occurred. Forty percent of the 132 patients had an abnormal MOCHA profile (two or more elevated markers).

The patients received routine clinical care at Emory. Over a median follow-up of 10 months, 23% of patients were diagnosed with the composite outcome of a new diagnosis of atrial fibrillation, a malignancy, venous thromboembolism or a defined hypercoagulable state, such as antiphospholipid antibody syndrome, nephrotic syndrome or von Willebrand factor abnormality.

The patients with an abnormal MOCHA profile had significantly higher rates of the composite outcome than patients with fewer than two abnormal markers (45% vs. 9%). Patients who also had left atrial enlargement were at increased risk for atrial fibrillation. Conversely, none of the 30 patients with normal MOCHA scores and normal left atrial size were diagnosed with any of the composite outcomes.       

Implications for care

“The study holds significant implications for cryptogenic stroke follow-up care,” says principal investigator Fadi Nahab, MD, Stroke Quality Director for Emory Healthcare. “We recommend that all clinicians who manage cryptogenic stroke patients consider obtaining the MOCHA profile and left atrial measurements to help risk-stratify patients as to their most likely cause of stroke,” he explains. “Patients who have four normal MOCHA tests and normal left atrial size are likely to have adequate secondary stroke prevention with antiplatelet therapy alone. But for other patients, test results could prompt clinicians to consider different treatment options.”

For example, patients with an abnormal MOCHA profile may need more extensive diagnostic testing to identify early indications for anticoagulant therapy. Those with an abnormal MOCHA profile and enlarged left atria may need closer surveillance for atrial fibrillation.

“It’s exciting that a simple blood test has so much potential to help patients with cryptogenic stroke,” Dr. Nahab says. “Using this diagnostic tool and left atrial imaging together, we can help identify high-risk disorders early so patients can receive definitive treatment for those concerns, as well as ultimately reducing their stroke risks.”

Looking forward

Dr. Nahab and his colleagues at the Emory Stroke Center are exploring whether cryptogenic stroke patients with an abnormal MOCHA profile who are on anticoagulant therapy are at a lower risk of recurrent stroke. They also hope to study whether using these biomarkers could be useful beyond the realm of stroke care and help potentially identify other patient groups who may be at an increased risk of developing a new malignancy, venous thromboembolism or hypercoagulable state.

For more information about the Emory Stroke Center or to refer a patient, contact us at 404-778-5050 or visit

To read the complete ‘Markers of Coagulation and Hemostatic Activation Aid in Identifying Causes of Cryptogenic Stroke’ research study, click here .

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