Myeloproliferative Disorders

 

• Definition and types

  • Clonal expansion of haematopoietic myeloid stem cells in marrow, classified by cell type that proliferates. Also known as myeloproliferative neoplasms, though whether not they are 'cancer' is ambiguous.
  • Types: polycythaemia vera (↑RBC), essential thrombocytosis (↑PLT), myelofibrosis (↑fibroblast activity), chronic myeloid leukaemia (CML) (↑WBC).
  • Myelodysplastic syndrome is a potential complication of all. Involves the proliferation of abnormal myeloid cells (vs. normal cells in myeloproliferative disease) and can progress to acute myeloid leukaemia.
  • Rarer types are mastocytosis and chronic neutrophilic or eosinophilic leukaemia.

• Polycythaemia vera

  Aka polycythaemia rubra vera, primary proliferative polycythaemia.

  Pathophysiology

  • ↑RBC, also ↑WBC and ↑platelets.
  • JAK2 somatic mutation present in 95%.

  Signs and symptoms

  • Can be asymptomatic.
  • Thrombosis (e.g. stroke, MI, PE) or haemorrhage (e.g. GI).
  • Headache, dizziness.
  • Skin: itch (may be triggered by hot water), plethora (facial redness), erythromelalgia (burning in fingers/toes).
  • Splenomegaly
  • Gout

  Diagnosis

  • FBC (Hct >0.52 in men or >0.48 in women) and blood film.
  • JAK2 mutation testing.
  • If ↑Hct but JAK2 -ve, polycythemia vera (as opposed to secondary polycythaemia) is suggested by ↑red cell mass, normal PaO2 on ABG, ↓EPO, splenomegaly on abdo US, and/or abnormal bone marrow biopsy.

  Management

  • Venesection: twice weekly (replaced by normal saline), until Hct <45%.
  • Aspirin
  • Cytoreductive therapy if venesection is ineffective or intolerable. Interferon if age <40, hydroxycarbamide (hydroxyurea) if age ≥40, or anagrelide 2nd line.

• Essential thrombocytosis

  Aka primary thrombocytosis, primary thrombocythaemia.

  Definition and epidemiology

  • ↑Platelets, which can be >1000 K/μL, and abnormal platelet function
  • Commoner in women.

  Signs and symptoms

  • Can be asymptomatic.
  • Bleeding, commonly GI.
  • Arterial and venous thrombosis.
  • Headache, dizziness.
  • Chest pain.
  • Skin: erythromelalgia, livedo reticularis.
  • Splenomegaly

  Management

  • Aspirin, unless young, asymptomatic, and very low risk.
  • Cytoreduction if very high risk: hydroxycarbamide (hydroxyurea), an antimetabolite which inhibits cell proliferation, or anagrelide, a transcription factor inhibitor which decreases platelet production.
  • Plateletpheresis if there is thrombosis or bleeding.

• Myelofibrosis

  Pathophysiology

  • Clonal proliferation of a multipotent haematopoietic myeloid stem cell, leading to abnormal cell production, excess cytokine release, neoangiogenesis, and extramedullary haematopoiesis.
  • Leads to bone marrow fibrosis, as well as accumulation in other sites (myeloid metaplasia), mainly the liver and spleen.
  • Can be primary (PMF), or secondary to various causes including haematological malignancy, infection (HIV, TB), and SLE.

  Signs and symptoms

  • Can be asymptomatic.
  • Constitutional symptoms.
  • Massive splenomegaly ± hepatomegaly. May lead to abdominal discomfort and early satiety.

  Investigations

  • FBC
  • Blood film: leukoerythroblastosis (myelocytes and myeloblasts) and teardrop cells.
  • Bone marrow aspiration (can't aspirate, 'dry tap') and bone marrow biopsy (fibrosis).

  Management

  • Folic acid.
  • Allopurinol if there is hyperuricaemia.
  • Bone marrow transplant if symptomatic. Ruxolitinib if unsuitable for transplant.

  Complications and prognosis

  Median survival is 5 years if untreated. Causes of death:

  • Bone marrow failure.
  • Acute leukaemia.
  • Pulmonary or portal hypertension.
  • Heart failure.