ET is a chronic myeloproliferative neoplasm, a heterogeneous group of diseases involving clonal hematopoietic stem cells that also includes polycythemia vera (PV), idiopathic myelofibrosis and chronic myelogenous leukaemia.4 5
Both PV and ET are characterised by increased sensitivity of haematopoietic cells to their respective primary humoral growth factors: erythroid precursors to erythropoietin in PV and megakaryocytes to thrombopoietin in ET.4
ET is increasingly recognised condition due to introduction of automated platelet counting. Although median age of patients with ET is 60 years, 10–25% of patients are less than 40 years of age and one-third of patients are asymptomatic.1
Janus kinase (JAK) signal transducers and activators of transcription pathway play a central role in initiating signal transduction from haematopoietic growth factor receptors.4 5
ET patients with JAK2 V617F mutation-positive are more sensitive to hydroxyurea.5
The principal causes of morbidity and mortality in ET are thrombosis, haemorrhage and progression to myelofibrosis or acute myelogenous leukaemia.4 5
Patients with ET may present with vasomotor symptoms, for example, TIA, visual disturbances, erythromelalgia, cerebral and myocardial infarction.1
DVT of lower extremities occurs particularly in younger patients with PV or ET.4
Haemostatic complications in ET appear to be multifactorial due to combination of: thrombocytosis, structural and functional abnormalities of platelets and their enhanced interaction with leucocytes and endothelial cells. Additional risk factors for thrombosis are, for example, advanced age, prior history of thrombosis, smoking and hyperlipidaemia.4–6
High-risk patients who should be considered for cytoreductive treatment include: 60 years of age, history of vasomotor symptoms, serious bleeding or thrombosis, and platelet count of 600/mm3
Young patients without symptoms with platelet count of less than 600/mm3
are considered low risk. Haemorrhagic complications are characteristically of ‘platelet type’, involving spontaneous bleeding at superficial sites, for example, skin, mucous membranes and so on. The risk of bleeding increases with extreme thrombocytosis possibly due to the acquired form of von Willebrand.4
The differential diagnoses of ET are RT and PRV, myeloproliferative neoplasms and myelodysplastic syndromes. The causes of RT includes iron deficiency, asplenia, metastatic malignancies, infection or inflammatory process.1 7
These are ruled out as per WHO and PVSG criteria.1–3
Due to potential therapeutic implications Philadelphia chromosome should be tested in ET patients.4
Recent studies in ET patients suggested that, compared to hydroxyurea plus aspirin, anagrelide plus aspirin was associated with an excess rate of arterial thrombosis, major bleeding and myelofibrotic transformation.4 5 8
Aspirin may be highly effective with cytoreductive therapy in PV and ET patients who have thrombotic and vascular complications. However, antiplatelet therapy must be used with caution in ET patients due to risk of serious bleeding when platelet count is more than 1000 × 10/litre.4 8
As patients with ET have near-normal life span4
and the myelosuppressive therapy itself increases risk of transformation to myelofibrosis or acute myelogenous leukaemia, the treatment has to be carefully planned, balancing risks and benefits.
Patients should be advised to stop smoking; avoid using non-steroidal anti-inflammatory drugs, contraceptives; and terminate any hormone replacement therapy.
Various cytoreductive drugs used in ET are hydroxyurea, anagrelide and interferon .4 5 8
We present a case of ET-related AMI in a healthy young man without any coronary artery-associated risk factors.
ECG: ST wave elevation in inferior leads, ventricular ectopic.
- Young patients with no risk factors for coronary events should be assessed thoroughly on the basis of on their clinical history and presentation before ruling out the diagnosis (of AMI).
- Patients with unexplained thrombohaemorrhagic events should have thrombophilia investigation.
- ET is associated with low risk of leukaemic transformation and life-threatening complications; life expectancy is minimally affected. It is important to evaluate the risk factors for thrombohaemorrhagic complications, for example, age, thrombotic event, platelet count and cardiovascular risk factors. Treatment is started, balancing risk and benefits in light of the complications associated with the treatment.
- In patients with established ET, search for congenital or acquired prothrombotic states should be undertaken as they increase the risk of thrombosis among these patients.
- Aspirin should be used cautiously as it may increase risk of bleeding, especially when platelet count is high.