HAEMATOLOGY - MYELOPROLIFERATIVE NEOPLASMS Flashcards
What are myeloproliferative neoplasms?
Proliferation of bone marrow cells from the myeloid lineage (RBC, Plt, neutrophils, basophils, mast cells and eosinophils)
What are the different myeloproliferative neoplasms?
Polycthemia Vera - RBC
Essential thrombocythemia - Plt
CML - granulocytes
Primary myelofibrosis - bone marrow fibrosis
Chronic eosinophilia leukaemia
Systemic mastocytosis
What is polycythemia?
A myeloproliferative disorder where there is excess proliferation of RBCs
What are the different types of secondary polycythaemia?
A relative polycythemia results from decreased plasma volume but normal RBC mass e.g. dehydration, diuretics
Appropriate absolute polycythaemia - physiological response to any cause of chronic hypoxia where we get low O2 sats causing increased EPO production so RBC mass increases but plasma volume remains the same
Inappropriate absolute polycythaemia - pathological overproduction of EPO e.g. renal cell carcinoma, hepatocellular carcinoma, pheochromocytoma etc . EPO levels and RBC mass are increased but plasma volume is normal
What is polycythemia Vera
Primary polycythaemia
The malignant proliferation of a clone derived from a single pluripotent stem cell.
Caused by a mutation in JAK2 in 95% of cases
There is excess proliferation in RBCs, WBCs and platelets leading to hyperviscocity and thrombosis
Outline the pathophysiology of polycythemia Vera
JAK2 is found on haematopoietic stem cells and, when activated by EPO, causes the cell to divide and produce blood cells
In polycythemia Vera, JAK2 is always on due to a mutation so the cell binds even in the absence of EPO
= massive RBC production
As these keep proliferating they will eventually become the predominant haematopoeitic stem cells in the bone marrow
In time these cells start to die out and cause fibrosis of the bone marrow. Eventually it can’t produce blood cells leading to anaemia, thrombocytopenia and leukopenia. = spent phase (now its secondary myelofibrosis)
How is polycythemia treated?
Venesection
Chemotherapy with hydroxyurea in those who don’t tolerate Venepuncture
JAK2 inhibitor ruxolitinib
Low dose aspirin
Anagrelide - inhibits megakaryocyte differentiation
Avoiding very hot baths to prevent pruritis
Allopurinol to block uric acid production
Why is uric acid high in polycythemia Vera?
occur due to the high turnover of red blood cells, which results in higher-than-normal uric acid production
What proportion of polycythemia Vera cases progress to myelofibrosis?
12-21% of cases
What proportion of polycythemia Vera cases progress into AML?
5%
What can polycythemia Vera develop into?
Myelofibrosis and AML
What is essential thrombocythemia?
A myeloproliferative neoplasm characterised by a persistently raised platelet count. Patients usually have normal Hb levels, but mild anaemia may occur
Whats the pathophysiology of essential thrombocythemia?
A mutation in JAK2 gene so that its always on and cases haematopoetic cells to divide even in the absence TPO stimulation (50%)
There can also be a mutation in the thrombopoetin receptor (25%) or chaperone protein calreticulin too (25%)
What can essential thrombocythemia develop into?
Myelofibrosis and acute leukaemia
How does essential thrombocythaemia present?
Thrombotic complications
Erythromelalgia
Splenomegaly
Also:
Fatigue, headache, dizziness, nausea, tinnitus. Numbness in hands and feet
Predisposed to bleeding
How is essential thrombocythaemia diagnosed?
Increased Plt count
Bone marrow biopsy - increased megakaryocytes and genetic mutations e.g. JAK2 or CalR
There must also be no alternative diagnosis and the absence of any indicator of reactive thrombocytosis
What is thrombocytosis? What are the 2 subtypes?
a disorder in which your body produces too many platelets.
It’s called reactive thrombocytosis or secondary thrombocytosis when the cause is an underlying condition, such as an infection
How is essential thrombocythaemia managed?
Low dose aspirin to rescue thrombotic risk
Hydroxyurea for cytoreduction
Interferon-Alfa is also effective used for young patients or pregnancy women
What can cause secondary thrombocytosis?
Those who have had splenectomy’s
Autoimmune rheumatic disorders
Malignancy
Acute bleeding and blood loss
Infections
Iron deficiency
Haemolytic anaemia
What is myelofibrosis?
A debilitating myeloproliferative neoplasm characterised by clonal proliferation of stem cells and abnormal myeloid cells in the bone, liver, spleen etc
What are the 2 types of myelofibrosis?
Primary - idiopathic (myeloproliferative neoplasm)
Secondary - arises secondary to other things e.g. leukaemia, autoimmune diseases, toxins, glycogen storage disease
Whats the pathophysiology of myelofibrosis?
50% had a JAK2 mutation and 25% have CalR mutation
These both lead to hyperplasia of abnormal megakaryocytes which release fibroblast stimulating factors such as platelet derived growth factors. This increases fibrosis in the bone marrow by excessive collagen deposition which replaces haematopoetic stem cells leading to anaemia
What are WBC and Plt counts like in myelofibrosis?
Variable from normal to low depending on the extent of bone marrow fibrosis
What are the symptoms of myelofibrosis?
Cytokines released into the blood cause fever, weight loss and decreased appetite
Fatigue and SOB - anaemia
Bleeding and bruising - thrombocytopenia
Fullness or pain in upper abdomen because of hepatosplenomegaly - can cause Loss of appetite and weight loss - extramedullary haematopoeisis
Gout
Pruritis
Severe pain related to respiration may indicate perisplenitis secondary to splenic infarction
