AKT · Haematology/Haemato-oncologylow yield

Myeloproliferative neoplasms & polycythaemia

Clonal overproduction of mature myeloid cells — polycythaemia vera, essential thrombocythaemia, myelofibrosis (JAK2)

Overview

Clonal disorders of the marrow producing too many mature cells of one or more myeloid lineages: polycythaemia vera (red cells, JAK2 V617F), essential thrombocythaemia (platelets), and primary myelofibrosis (marrow fibrosis → cytopenias + massive splenomegaly). The shared hazards are thrombosis (and bleeding) and transformation to acute leukaemia/myelofibrosis. Polycythaemia must be split into true (primary/secondary) vs relative.

Recognise

Polycythaemia vera: raised haematocrit, aquagenic pruritus (itch after a hot bath), facial plethora, erythromelalgia, splenomegaly, thrombosis; JAK2-positive
Essential thrombocythaemia: very high platelets → thrombosis or (paradoxically) bleeding
Primary myelofibrosis: marrow fibrosis → anaemia/cytopenias, MASSIVE splenomegaly, 'tear-drop' poikilocytes and a leucoerythroblastic film

Red flags

Arterial/venous thrombosis (stroke, MI, Budd-Chiari, splanchnic) or major bleeding
Transformation to acute myeloid leukaemia or to myelofibrosis

Differentials & how to tell them apart

Secondary polycythaemiaappropriate EPO rise — chronic hypoxia (COPD, OSA, altitude) or EPO-secreting tumour (renal cell carcinoma); JAK2-negative

Relative (apparent) polycythaemiareduced plasma volume (dehydration, diuretics) — normal red-cell mass

Reactive thrombocytosisinflammation, iron deficiency, post-splenectomy — secondary, not clonal

Investigations

FBC (raised Hb/Hct, platelets, or cytopenias with splenomegaly), blood FILM (tear-drop cells/leucoerythroblastic in myelofibrosis); JAK2 V617F mutation (and CALR/MPL); erythropoietin level + investigate secondary causes for polycythaemia (hypoxia, EPO-secreting tumour); marrow; rule out relative (dehydration) polycythaemia.

Management

PV → venesection + aspirin (+hydroxycarbamide if high-risk); ET → aspirin ± cytoreduction; MF → supportive/JAK inhibitor

1For a raised haematocrit, split TRUE polycythaemia (check JAK2 and EPO) from secondary (hypoxia/EPO-tumour) and relative (dehydration). Polycythaemia vera (JAK2-positive) → venesection to Hct <0.45 + aspirin.Gate: The shared dangers are thrombosis/bleeding and transformation to AML/myelofibrosis; secondary polycythaemia is treated by its cause (hypoxia/tumour), not venesection-as-disease.
2Essential thrombocythaemia → aspirin ± hydroxycarbamide by risk; myelofibrosis → supportive care, JAK inhibitor (ruxolitinib), transplant in selected patients.

Polycythaemia vera: VENESECTION (target Hct <0.45) + aspirin + cardiovascular risk control — reduces thrombosis; hydroxycarbamide for high-risk; treat the itch

Essential thrombocythaemia: aspirin ± cytoreduction (hydroxycarbamide) — reduce thrombotic risk by risk stratification

Myelofibrosis: supportive (transfusion), JAK inhibitor (ruxolitinib), transplant in selected — manage symptomatic splenomegaly and cytopenias

Treat secondary/relative polycythaemia by the cause — oxygen/treat hypoxia; rehydrate relative polycythaemia

Key points

Raised Hct + aquagenic pruritus + plethora + splenomegaly + JAK2 = polycythaemia VERA → venesection (Hct <0.45) + aspirin (± hydroxycarbamide). Split true vs secondary (hypoxia/EPO-tumour — appropriate EPO) vs relative (dehydration). ET = high platelets (thrombosis/bleeding); myelofibrosis = tear-drop cells + massive splenomegaly. All risk thrombosis + leukaemic transformation.

Monitor & prognosis

Counts/haematocrit, thrombosis/bleeding, splenomegaly, transformation; JAK2 status.

Chronic; thrombosis is the main early hazard; risk of transformation to AML/myelofibrosis.

Source: BSH myeloproliferative neoplasms; cross-ref renal (EPO/RCC), respiratory (hypoxia)