Myeloproliferative Disorders Flashcards
What is a myeloproliferative disorder?
A clonal proliferation of hematopoietic myeloid stem cells in the bone marrow.
These cells have the ability to become RBC, WBC and platelets. So an excess is formed of one of these cell types.
What is polycythaemia?
An excess clonal proliferation of RBC.
What causes relative polycythaemia?
Decreased plasma volume with normal RBC mass.
Acute - Dehydration
Chronic - Obesity, HTN, high alcohol and tobacco intake.
What are the primary causes of absolute polycythaemia?
Primary means the abnormality originates in the bone marrow.
Polycythaemia vera is the condition.
What are the secondary causes of absolute polycythaemia?
Physiological response to hypoxia - Chronic lung disease, high altitude, cyanotic congenital heart disease, heavy smoking
Inappropriate erythropoietin secretion - Renal cell carcinoma, renal artery stenosis
What is absolute polycythaemia?
Increase in the number of erythrocytes
Describe the genetic mutation that causes polycythaemia vera?
Caused by a mutation in Janus Kinase 2 (JAK2) which is a cytoplasmic tyrosine kinase.
This results in a malignant proliferation of clone myeloid progenitor cells which don’t need erythropoietin to avoid apoptosis.
How can polycythaemia vera present?
- Asymptomatic and detected on FBC
- Hyperviscosity symptoms eg headache, dizziness, tinnitus, visual disturbance
- DVT/arterial thrombosis
What are the ‘classic’ polycythaemia vera history signs?
- Itching after a hot bath
- Burning sensation in fingers and toes
- Erythromelalgia (red and hot and burning)
What signs on examination suggest polycythaemia vera?
- Facial plethora
- Splenomegaly
- Signs of DVT
How can PV cause gout?
Increased RBC turnover
What investigations are required for PV?
Bloods - - FBC (raised RCC, haematocrit, packed cell volume) - Sometimes raised WCC and raised platelets - Raised B12 (needed for RBC production) - Reduced serum erythropoietin Bone marrow aspiration - - Hypercellularity - Erythroid hyperplasia Cytogenetics - - Rule out CML (BCR/ABL) vs JAK2 in PV
What is the diagnostic investigation for PV?
Raised red cell mass on Chromium studies and splenomegaly, in the setting of normal pO2 is diagnostic.
What is the treatment for PV?
- Keep the haematocrit <0.45 to reduce risk of thrombosis
Low risk + young = Venesection
High risk + old = Hydroxycarbamide
Everyone = Aspirin 75mg OD
What are the monitoring requirements for PV?
RBC every 3 months
What complications can occur with PV?
- Thrombosis
- Haemorrhage (due to defective platelets)
- Transformation to myelofibrosis
- Transformation to acute leukaemia
What is thrombocythaemia?
Increased platelets count
What is essential thrombocythaemia?
A myeloproliferative neoplasm. It is a clonal proliferation of megakaryocytes leading to persistently raised platelets with abnormal function.
What is the cause of essential thrombocythaemia?
JAK2 mutation
What are the risk factors with essential thrombocythaemia?
- Bleeding
- Arterial or venous thrombosis
- Microvascular occlusion eg headache, atypical chest pain, light headedness, erythromelalgia
What is the treatment for essential thrombocythaemia?
Aspirin 75mg OD
Hydroxycarbamide in high risk patients
Manage any CVD risk factors
What are the causes for reactive thrombocytosis?
- Infection
- Inflammation
- Other tissue injury eg surgery, trauma, burns
- Haemorrhage
- Cancer
- Iron deficiency
What is redistributional thrombocythaemia?
Platelets are redistributed from splenic pool into the bloodstream.
- Post splenectomy
- Hyposplenism
What causes myelofibrosis?
- Hyperplasia of megakaryocytes
- They produce platelet derived growth factor
- This causes intense marrow fibrosis
- Extramedullary haematopoiesis occurs in the spleen and liver
How does myelofibrosis present?
Hypermetabolic symptoms - Night sweats, fever, weight loss
Abdominal discomfort - Splenomegaly
Bone marrow failure - Anaemia, infections, bleeding
What will a blood film show if a patient has myelofibrosis?
Leukoerythroblastic film (nucleated RBC) Teardrop RBC
What investigation is required for diagnosis of myelofibrosis?
Bone marrow biopsy - dry tap aspirate and trephine
What is the treatment for myelofibrosis?
- Marrow support
- Allogeneic stem cell transplant
What is the myeloproliferative disorder that causes a raised WCC?
Chronic myeloid leukaemia
