BCR-ABL1-negative myeloproliferative neoplasm (MPN) characterized by a sustained elevation of platelet number with a tendency for thrombosis and haemorrhage.
- M/C myeloproliferative neoplasm
- Median age at diagnosis: 65-70 years
- M/C driver mutation: JAK2V617F (~99% PV, 55% ET, and 65% PMF)
Myeloproliferative neoplasms (MPN):
Driver mutation distributions in ET and PMF (similar):
- JAK2V617F mutated (50–65%)
- CALR mutated (15–30%)
- MPL mutated (4–8%)
- Triple-negative (10–20%): Do not express any one of the 3 mutations
Clinical presentation is dominated by a predisposition to vascular occlusive events and haemorrhages.
- Splenomegaly (M/C physical finding, mild compared to other myeloproliferative neoplasms)
Vascular occlusive events: major thrombotic events involving the cerebrovascular, coronary and peripheral arterial circulation
- Deep vein thrombosis: Potentially life-threatening due to risk of
- Pulmonary embolism
- Hepatic (Budd Chiari syndrome) or portal thrombosis
- Platelet-mediated transient occlusive thrombosis in the end-arterial circulation:
- Aspirin-sensitive erythromelalgia
Neurological manifestations (due to vascular occlusive events):
- Headache (M/C neurological manifestation)
- Visual disturbances:
- Attacks of diplopia
- Sudden reversible attacks of blurred vision
Aspirin-sensitive erythromelalgia (characteristic microvascular disturbance in ET):
- Burning painful and ulcerative toes, often accompanied by a warm, red or violet colored congested limb extremity
- The ischemic attacks of digital arteries may subsequently progress towards small zones of limited necrosis or even peripheral gangrene with palpable arterial pulsations.
Hemorrhagic manifestations: Often limited to recurrent skin manifestations:
- Bruising, subcutaneous hematomas, ecchymoses, and epistaxis or gum bleeding.
- Petechiae never seen.
The bleeding diathesis is not due to impaired platelet function but rather to an acquired Von Willebrand’s disease caused by proteolytic reduction of Von Willebrand Factor (VWF) multimers. There is an inverse relationship between VWF levels and platelet counts.
- First-trimester spontaneous abortions (⅓ cases)
- Recurrent fetal loss
Thrombosis (20% cases):
- Cerebral vessels → ischemic attack or stroke
- Coronary arteries → Acute coronary syndrome
- Hepatic vein → Budd-Chiari syndrome
Haemorrhage (10% cases)
- Placental abruption
- Intrauterine growth retardation
Bone marrow biopsy:
- Clustered enlarged megakaryocytes with matured cytoplasm containing multilobulated nuclei
- Prefibrotic PMF
- Masked polycythemia vera
- Chronic myeloid leukaemia
- Refractory anaemia with ring sideroblasts