Myelofibrosis Flashcards
outline the typical presentstion of myelofibrosis
Radiation
Massive splenomegaly
low RBC (normocytic anaemia)
leukoerythroblastosis, low WCC, High plts, poikilocytosis (tear drop - dacrocytes) and dry tap (aspiration) - associated with polycythaemia vera
define myelofibrosis?
Disorder of haematopoietic stem cells characterised by progressive bone marrow fibrosis associated with extramedullary haematopoiesis and splenomegaly
describe the pathogenesis of myelofibrosis?
hyperplasia of megakaryocytes
abnormal megakaryocytes release cytokines like platalet derived growth factor-> stimulate fibroblast proliferation and collagen deposition in bone marrow
results in extramedullary haematopoeisis in liver and spleen-> HEPATOSPLENOMEGALY
Outline the aetiology of myelofibrosis?
primary stem cell defect is unkown
results in increased numbers of abnormal megakaryocytes with stromal proliferation secondary to growth factors released by megakaryocytes
30% of patients have a previous history of polycythaemia rubra vera or essential thrombocythaemia (overproduction of platelets by the bone marrow)
what are the risk factors for myelofibrosis?
age>65
radiation exposure
Hiroshima survivor
industrial solvent exposure (e.g. benzene and other aromatic solvents)
what are the symptoms of myelofibrosis
ASYMPTOMATIC - diagnosed after routine blood count
Dependent on organ/site of involvement, extramedullary hematopoiesis results in hemorrhage, spinal cord compression, focal seizures, ascites, pleural effusion, etc.
Systemic Symptoms (hypermetabolic symptoms)COMMON:
- Weight loss
- Anorexia
- Fever
- Night sweats
- Pruritis
- Abdominal discomfort
UNCOMMON:
- LUQ pain
- Indigestion (due to massive splenomegaly)
- Bleeding
- Bone pain
- Hearing loss
- Gout
- Infections
what are the signs of myelofibrosis on physical examination
SPLENOMEGALY
Hepatomegaly (present in 50-60%)
Portal HT features (UNCOMMON) due to increased splenoportal blood flow => ascites, varices, GI bleeding, hepatic encephalopathy
Pallor, petechiae, haemarthrosis, blood on PR
what are the appopriate investigations for myelofibrosis?
FBC
blood film
bone marrow aspirate
bone marrow biospy
describe GBC in myelofibrosis?
Initially variable Hb, WCC and platelets
Thrombocytosis is more common presentation than thrombocytopenia
Later stages –> anaemia, leukopaenia, thrombocytopaenia
describe the blood film for myelofibrosis?
Leucoerythroblastic changes (red and white cell precursors in the peripheral blood) - metamyelocytes, myelocytes, myeloblasts and nucleated RBCs
‘Tear drop’ poikilocyte red cells – hallmark
describe the bone marrow aspiration result for myelofibrosis
Aspiration usually unsuccessful - ‘dry tap’ (due to fibrosis) -
what is seen in the bone marrow biopsy for myelofibrosis?
Trephine bone marrow biopsy shows;
fibrotic hypercellular marrow, with dense reticulin fibres on silver staining – DIAGNOSTIC
