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Heghine Khachatryan: Hematologic Causes of Cryptogenic Stroke
Mar 16, 2026, 14:51

Heghine Khachatryan: Hematologic Causes of Cryptogenic Stroke

Heghine Khachatryan, Editor-in-Chief of Hemostasis Today, Head of Hemophilia and Thrombosis Center at Yeolyan Hematology and Oncology Center, shared a post on LinkedIn:

Cryptogenic Stroke: When the Cause May Be Hematologic

Despite comprehensive evaluation, approximately twenty to thirty percent of ischemic strokes remain classified as cryptogenic.

In a meaningful proportion of these patients, the underlying mechanism may lie within the hemostatic or hematologic system.

A targeted diagnostic approach is therefore essential.

Before initiating extensive thrombophilia testing, clinicians should first complete the standard evaluation for ischemic stroke, including:

  • Brain imaging
  • Vascular imaging
  • ECG and cardiac rhythm monitoring
  • Echocardiography when indicated

Once common causes have been excluded, hematologic investigation becomes particularly relevant in selected patients, especially when the following features are present:

  • Young age
  • Recurrent stroke or unexplained thrombosis
  • Multifocal or atypical infarct patterns
  • Family history of thrombosis or early stroke
  • Abnormalities on CBC (thrombocytosis, erythrocytosis, hemolysis)
  • Clinical suspicion of malignancy or autoimmune disease

Practical first-line hematologic testing may include:

  • Complete blood count and peripheral smear
  • Antiphospholipid antibody panel
  • Homocysteine level

Further testing should be guided by clinical phenotype.

For example:

  • Antiphospholipid syndrome remains one of the most important immune-mediated causes of arterial thrombosis.
  • Myeloproliferative neoplasms associated with JAK2 mutations may present with arterial events, including stroke.
  • Rare disorders such as Paroxysmal nocturnal hemoglobinuria should be considered in patients with hemolysis or cytopenias.
  • Malignancy-related hypercoagulability, including Trousseau syndrome, may also manifest as cryptogenic stroke.

Importantly, inherited thrombophilia panels should not be ordered indiscriminately.

Testing for conditions such as Factor V Leiden mutation or Prothrombin G20210A mutation is generally reserved for carefully selected cases.

Clinical takeaway

A targeted hematologic evaluation—rather than routine broad thrombophilia screening- can help identify occult prothrombotic states that may otherwise remain undetected in patients with cryptogenic stroke.

Recognizing these mechanisms is critical for improving secondary prevention strategies and long-term patient outcomes.”

Heghine Khachatryan: Hematologic Causes of Cryptogenic Stroke

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