PNH and JAK 2 mutation in Pulmonary embolism
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Searching PubMed
"pulmonary embolism" AND "paroxysmal nocturnal hemoglobinuria"
Searching PubMed
"pulmonary embolism" AND JAK2
Searching the Web
British Society Haematology thrombophilia testing PNH JAK2 pulmonary embolism unusual sites guideline
Reading Web Page
https://pubmed.ncbi.nlm.nih.gov/35645034
In a patient with pulmonary embolism (PE), both PNH and JAK2 V617F mutation are acquired hematologic causes of thrombosis, but they are not routine tests for every PE.
| Test | Why it causes thrombosis | When to suspect / test in PE |
|---|---|---|
| PNH flow cytometry | Complement-mediated hemolysis, platelet activation, endothelial dysfunction, and nitric oxide depletion produce a strong prothrombotic state | PE with evidence of hemolysis or marrow failure: cytopenias, raised LDH, low haptoglobin, indirect hyperbilirubinemia, hemoglobinuria, aplastic anemia, unexplained abdominal pain or thrombosis at unusual venous sites |
| JAK2 V617F | Indicates a possible myeloproliferative neoplasm, especially polycythemia vera or essential thrombocythemia, which increases venous and arterial thrombosis risk | PE plus persistent erythrocytosis, thrombocytosis, leukocytosis, splenomegaly, aquagenic pruritus, or prior/recurrent/unusual-site thrombosis |
Key point
- PE at a usual site alone is generally not an indication to screen for PNH or JAK2 mutation.
- Testing becomes appropriate if the PE is unprovoked and there are suggestive blood-count or hemolysis abnormalities, or if there is thrombosis in an unusual site, especially splanchnic veins or cerebral venous sinuses.
- The British Society for Haematology guideline particularly supports JAK2 testing in splanchnic vein thrombosis when there are CBC features suggestive of an MPN. It supports PNH testing when unusual-site thrombosis is accompanied by cytopenia or biochemical evidence of hemolysis. See the BSH thrombophilia-testing guideline.
Practical work-up in PE when these disorders are considered
- Full blood count and peripheral smear
- Hemolysis profile: LDH, bilirubin, haptoglobin, reticulocyte count, urine hemoglobin
- PNH testing: high-sensitivity peripheral-blood flow cytometry, typically FLAER plus CD55/CD59 on granulocytes and monocytes
- MPN testing: JAK2 V617F; if negative but suspicion for MPN remains, hematology may add JAK2 exon 12, CALR, and MPL testing.
Treatment implication
Acute PE is treated with therapeutic anticoagulation as usual. If PNH or an MPN is confirmed, hematology input is needed because the underlying disorder also requires disease-specific treatment, such as complement inhibition for clinically significant PNH or cytoreductive/MPN-directed treatment where indicated. Both PNH and MPN are recognized acquired causes of venous thromboembolism. Goldman-Cecil Medicine, “Myeloproliferative Neoplasms and Paroxysmal Nocturnal Hemoglobinuria,” treatment section.
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