Haematology Myeloproliferative Disorders Flashcards
Myeloproliferative disorders: Description
Clonal haematological disorders characterised by over-production of blood cells and a tendency to transformation to acute leukaemia.
Myeloproliferative disorders: Epi
Generally diseases of middle or older age groups.
Incidence: 2 cases per 100,000
Myeloproliferative disorders: Three related disorders with similar acquired genetic defects (e.g. Janus Kinase Jak-2 mutations)
- Primary polycythaemia
- Essential thrombocythaemia (increased platelets)
- Idiopathic myelofibrosis
Myeloproliferative disorders: Mixed myeloid progenitor
RBC/Platelets/ Neutophil/Monocyte/ Basophil/Eosinophil
Myeloproliferative disorders: Similar disorders
Chronic myeloid leukaemia (CML)
Myeloproliferative disorders: Essential thrombocythaemia
Increased platelet number
Myeloproliferative disorders: Myelofibrosis
Affects stomal calsin BM – scarring and fibrosis in bone marrow
Polycythaemia → Defined by
Defined by the packed cell volume (PCV): a raised PCV of >0.51 in males and >0.48 in females requires further investigation.
Polycythaemia → Measure
The True red cell mass and the plasma volume can be measured.
Involves radionucelotide labelling of red cells and albumen, respectively (less common).
Polycythaemia → The absolute measurements allows
“True” polycythaemia to be distinguished from an “apparent” polycythaemia (decreased plasma volume).
Polycythaemia → Symptos and Signs of Primary Polycythaemia
Hyperviscosity:
Hypervolaemia:
Hypermetabolism:
Hyperviscosity:
Haemostasis (thrombosis – stroke, transient ischaemic attacks, digital ischaemia), haemorrhage, headache
Hypervolaemia:
Plethora, hypertension and splenomegaly
Hypermetabolism:
Pruritis, weight loss, sweats, gout
Polycythaemia → Packed cell volume >0.51 (males)
>0.48 (females) with a raised red cell mass (absolute) definition
Primary polycythaemia
Secondary polycythaemia
Polycythaemia →Packed cell volume >0.51 (males)
>0.48 (females) Normal red cell mass diagnosis
Apparent polycythaemia
Polycythaemia → True polycythaemia
Raised RBC
Plasma volume slightly reduced but overall volume higher
Polycythaemia → Apparent polycythaemia
Overall blood volume is less. Red cell mass normal (Can occur burns, alcohol, smoking)
Differential diagnosis of a true polycythaemia
Primary Polycythaemia
Secondary Polycythaemia
Secondary Polycythaemia
Drive from EPO due to a stimulus.
• Hypoxaemia e.g. chronic lung disease, cyanotic congenital heart disease, sleep apnoea.
• Renal disease e.g. hypernephroma, polycystic kidney disease (cysts causes pressure on cells leading to increased EPO)
• Miscellaneous e.g. hepatomas, cerebellar haemangioma, massive fibroids, high oxygen affinity haemoglobins.
Symptoms and Signs of Primary Polycythaemia
- Facial plethora
- Headache
- Mental clouding
- Pruritis
- Hypertension
- Splenomegaly
- Gout
- Occlusive vascular lesions e.g. stroke, transient ischaemic attacks, digital ischemia
- Bleeding
- Hyper viscosity
Polycythaemia Specialist Investigations
- Serum Erythropoietin → Low in primary polycythaemia
- Jak 2 mutation
- Bone marrow examination
- Abdominnal ultrasound to assess spleen size
Jak 2 mutation
Specific V617F mutation in Jak 2 signal transduction protein linked to erythropoietin receptor. This “activating” mutation promotes proliferation of stem cells.
Identified in 90% of patients with polycythaemia vera and 50% of patients with essential thrombocythaemia and myelofibrosis (30-50%) – permanently switched on – increased RBC.
V617F
Found on cell surface involved in transfer of EPO binding signal to the cell
Bone marrow examination for
Erythroid hyperplasia
Fibrosis (low levels)
Treatment
- Repeated venesections to maintain a PCV of <0.45 (aiming for (slightly lower than normal)
- Hydroxyurea if there is also thrombocytosis (concern increase risk of leukaemia.
- Low doe aspirin (if there are no bleeding manifestations) – prevent arterial clots (can’t tolerate other treatments)
- Radioactive phosphorus
Radioactive phosphorus
Single disease controls disorder for 12-18 months but associated with increased risk of leukaemia.
Reserved for elderly frail patients.
Progression and Prognosis
Untreated patients: survival 18 months (clots and myelofibrosis and leukaemia)
Treated patents: survival 10-15 years
In the longer term, 20% of patients transforms to myelofibrosis and about 5% to acute leukaemia (need monitoring)
Essential Thrombocythaemia: Definition
A myeloproliferative disorder characterised by the presence of a persistent thrombocytosis (platelet count >450 x 109/L) increased + 600
Essential Thrombocythaemia: JAk2 mutation
Positive in 50% of cases: useful for diagnosis (not as useful as in polycythaemia)
Essential Thrombocythaemia: Diagnosis
Otherwise, this is a diagnosis of exclusion and other reactive causes of a raised platelet count first need to be considered: e.g. infection, inflammation, malignancy and bleeding (reactive picture).
Essential Thrombocythaemia: Presentation
- 25-50% of patients present with microvascular occlusive events (e.g. burning pain in extremities or digital ischaemia), major vascular occlusive events or haemorrhage (interference with clotting cascade).
- Erythromelalgia in essential – redness and burning the feet and hands
- Livedo reticularis in essential thrombocythaemia.
Essential Thrombocythaemia: Blood film in thrombocythaemia
- Large Platelets (variation in size)
- Iron deficiency
- Hypochrominc RBCs – Iron deficiency
- CHECK THIS
Essential Thrombocythaemia: Bone marrow morphology in essential thrombocytaemia
- Megakaryocytes and abnormal nucleation
* CHECK THIS
Essential Thrombocythaemia: Treatment
- Low dose aspirin (unless history of bleeding)
- Hydroxyurea (carbomide(same thing))
- Anagrelide (younger patients) – chemoagents
Transformatino to myelofibrosis or acute leukaemia may occur in a small minority of patients long term – Primary polycythaemia.
Idiopathic Myelofibrosis: Main Clinical Features
- Bone marrow fibrosis (scar tissue leading to extramedullary)
- Extramedullary haemopoiesis (blood cell production in the liver and spleen)
- Splenomegaly – often massive
- Anaemia with leucoerythroblastic blood picture (precursors to RBC/WBC which you wouldn’t expect to see
- Weight loss, fatigue, bleeding
Idiopathic Myelofibrosis: The Primary Malginant Process involves
Megakaryocytes: generate growth factors such as platelet-derived growth factor which stimulate fibroblast proliferation (stromal cell)
Idiopathic Myelofibrosis:Fibroblast proliferation produce
Produce reticulin and scar bone marrow
1st – proliferation phase
2ndry – Splenomegaly and drop blood counts
Idiopathic Myelofibrosis: X-ay changes
Myelosclerosis
Idiopathic Myelofibrosis:Blood Picture
Leucoerythroblastic blood picture
Idiopathic Myelofibrosis:Bone Marrow histology
Normally – fat cells and organised set of cells.
‘Starry night’
Stranding of cells into other areas – fat spaces
Idiopathic Myelofibrosis: Determine severity of bone marrow histology
Fibrosis criteria to determine severity
Idiopathic Myelofibrosis: Treatment
Blood Transfusions if symptomatic anaemia. Thrombocytopnaenia – symptomatic difficulty w/ splenomegaly therefore increased destruction and therefore not helpful.
Splenectomy to correct anaemia or treat painful enlargement of the spleen.
Idiopathic Myelofibrosis:
Prognosis
2-4 years with death due to haemorrhage, infection or transformation to acute leukaemia → poor
Stem cell transplantation for younger patients (<65 years).
Jak 2 inhibitors for recently licensed: early trials show reduction in splenomegaly and constituitional symptoms and improved survival.
