Thrombocytosis

Thrombocytosis is a platelet count over 450 x 10^9/L. Most cases (80 to 90 percent) are reactive (secondary), with a low risk of thrombosis, while a minority are due to a myeloproliferative neoplasm (essential thrombocythaemia) with a higher risk of thrombosis and bleeding.

• Reactive causes: iron deficiency (very common), infection, inflammation (rheumatoid arthritis, inflammatory bowel disease, vasculitis, giant cell arteritis, tuberculosis), malignancy, tissue damage (surgery, trauma, burns), acute blood loss, haemolysis, asplenia or hyposplenism (sickle cell disease), recovery from thrombocytopenia (rebound), drugs (adrenaline, vincristine, steroids, all-trans retinoic acid), and exercise.
• Clonal causes: essential thrombocythaemia (JAK2 V617F in 60 percent, CALR in 20 to 25 percent, MPL in 3 to 5 percent), polycythaemia vera, primary myelofibrosis, chronic myeloid leukaemia, and myelodysplastic syndrome with 5q deletion.
• Counts over 1000 x 10^9/L are more often reactive than clonal, but acquired von Willebrand syndrome and bleeding can occur at counts over 1000.

• Most patients have no symptoms.
• Essential thrombocythaemia: microvascular symptoms (headache, dizziness, visual disturbance, erythromelalgia with burning pain and redness of hands and feet, tingling, transient ischaemic attacks), arterial and venous thrombosis (including splanchnic vein thrombosis), bleeding, splenomegaly, pruritus, and pregnancy loss.
• Reactive: symptoms and signs of the cause (infection, inflammation, cancer, anaemia, bleeding).
• History: fever, weight loss, bleeding, iron deficiency symptoms, previous splenectomy, smoking, thrombosis, cardiovascular risk factors, family history of myeloproliferative disease, and drugs.
• Examination: spleen size, signs of infection or inflammation, pallor, evidence of arterial and venous thrombosis.

• Repeat the FBC after 2 to 4 weeks and review the film: giant or abnormal platelets, nucleated red cells, leucoerythroblastic changes, basophilia, and neutrophilia.
• First tests: ferritin, CRP and ESR, liver function, renal function, lactate dehydrogenase, urate, blood glucose, and in selected patients a chest X-ray and abdominal ultrasound for spleen size and occult cancer.
• If reactive causes are excluded or the count persists over 450 for 3 months, or there is thrombosis, splenomegaly, or unexplained high count (over 600): JAK2 V617F mutation test, then CALR and MPL; BCR-ABL1 PCR to exclude chronic myeloid leukaemia; bone marrow biopsy to confirm essential thrombocythaemia and exclude myelofibrosis and myelodysplasia.
• Reactive thrombocytosis: platelets rarely exceed 1000, the film is normal, and the count falls when the cause is treated.
• Risk stratification of essential thrombocythaemia: age over 60, previous thrombosis, JAK2 mutation, and cardiovascular risk factors.

Reactive thrombocytosis

• Treat the cause (iron replacement with ferrous sulfate 200 mg daily or alternate days, treatment of infection, inflammation, or cancer); no antiplatelet drugs or cytoreduction are needed, since thrombotic risk is not raised except in high risk situations (post-splenectomy with other risk factors, major surgery, immobility).
• Venous thromboprophylaxis according to the usual risk of the clinical situation; aspirin 75 mg daily after splenectomy only when other vascular risk factors are present.
• Recheck FBC in 4 to 8 weeks after treating the cause; refer if the count persists.

Essential thrombocythaemia (haematology)

• Cardiovascular risk control: stop smoking, treat hypertension, diabetes and hyperlipidaemia, weight control, and exercise.
• Aspirin 75 to 100 mg orally once daily for all with microvascular symptoms, JAK2 or CALR mutation, or cardiovascular risk factors (omit if platelets exceed 1000 x 10^9/L until acquired von Willebrand syndrome is excluded; twice daily may be used in some cases).
• Cytoreduction for high risk disease (age over 60, previous thrombosis, platelets over 1500 x 10^9/L, or bleeding): hydroxycarbamide 15 mg/kg/day orally (start 500 mg twice daily, adjust to keep platelets under 400 and neutrophils over 1.0 x 10^9/L); monitor FBC every 2 weeks for 2 months, then every 3 months; side effects include cytopenias, mouth ulcers, skin ulcers, and skin cancers (sun protection and annual skin examination).
• Second line: interferon alfa (pegylated interferon 45 to 90 micrograms weekly) for young patients and pregnancy, anagrelide 0.5 mg twice daily increasing to 1 mg twice daily (headache, palpitations, fluid retention; avoid in heart disease), or ruxolitinib in selected cases.
• Treat venous thrombosis with anticoagulation (rivaroxaban 15 mg twice daily for 21 days then 20 mg daily, or apixaban 10 mg twice daily for 7 days then 5 mg twice daily) with a specialist plan for duration.
• Lifelong follow up every 3 to 6 months with FBC; monitor for progression to myelofibrosis or acute leukaemia.

Special groups

• Pregnancy: aspirin 75 mg daily and low molecular weight heparin (enoxaparin 40 mg daily) for high risk women with previous thrombosis or pregnancy loss; interferon alfa for cytoreduction; avoid hydroxycarbamide and anagrelide.
• Young patients: interferon is favoured because of long term risks of hydroxycarbamide.