Myeloproliferative disorders Flashcards
Myeloproliferative neoplasms are associated with acquired mutations of genes that encode tyrosine kinases or kinase-associated proteins such as?
- primarily JAK2
- CALR
- MPL (the receptor for thrombopoietin)
Polycythaemia is defined as?
an increase in the Hb concentration above the upper limit of normal for the patient’s age and sex
what is absolute polycythaemia?
or erythrocytosis, red cell mass (volume) is raised greater than 125% of that expected for body mass and gender
note: the plasma volume is normal
what is relative polycythaemia/ pseudopolycythaemia?
the red cell volume is normal but the plasma volume is reduced
If the haematocrit is higher than 0.60 there will always be a raised red cell mass and absolute polycythaemia. T or F.
True
which features indicate that erythrocytosis is likely?
A Hb >185 g/L or haematocrit >0.52 in men or
Hb >165 g/L or haematocrit >0.48 in women, indicates that erythrocytosis is likely
what are the types of absolute polycythaemia?
- primary polycythaemia (includes both rare congenital causes of polycythaemia related to genetic changes in oxygen sensing or erythropoietin signalling, and the more common acquired myeloproliferative neoplasm polycythaemia vera)
- secondary polycythaemia (the bone marrow is driven by an increase in erythropoietin as a result of factors such as smoking, sleep apnoea or altitude)
what is polycythaemia vera?
in PV, the increase in red cell volume is caused by clonal malignancy of a marrow stem cell
note: 95% of patients have the JAK2 V617F mutation
what is the WHO major criteria for diagnosing PV?
- Hb > 16.5 g/dl in men; > 16 g/dl in women or
PCV > 0.49 in men; > 0.48 in women or
Increased red cell mass - JAK2 mutation
- bone marrow biopsy revealing hypercellularity with trilineage growth
what’s the WHO minor criterion for diagnosing PV?
low serum erythropoietin
Diagnosis of PV requires meeting how many criteria?
Diagnosis of PV requires meeting either all three major criteria, or the first two major criteria and the minor criterion
Criteria #2 (BM) is not required in diagnosis if?
Criteria #2 (BM) not required if Hb > 18.5 g/dl / PCV > 0.55 in men; Hb >16.5 g/dl / PCV > 0.49 in women and JAK 2 present and EPO levels low.
PV is usually a disease of older people and has an equal sex incidence. T or F?
True
what are the clinical features of PV?
- Headaches, dyspnoea, blurred vision and night sweats.
- Generalised pruritus, characteristically after a hot bath or shower
- Plethoric appearance: ruddy cyanosis, conjunctival suffusion and retinal venous engorgement.
- Splenomegaly in 75% of patients
- haemorrhage or thrombosis
- gout
what are the lab findings of PV?
- haemoglobin, haematocrit and red cell count are increased. The total red cell volume is increased.
- neutrophil and basophils may increase
- platelet count may increase
- A JAK2 mutation is present in the bone marrow and peripheral blood granulocytes in over 95% of patients.
- The bone marrow is hypercellular with trilineage growth- trephine biopsy
- Serum erythropoietin is low.
- Plasma urate is often increased; the serum LDH is normal or slightly raised.
- Circulating erythroid progenitors are increased
- chromosome abnormalities are found in the minority
TP53 and RUNX1 mutations predict for transformation to what?
AML
how is PV treated?
- venesection- to reduce haematocrit <0.45
- hydroxycarbamide (hydroxyurea)
- Jak inhibitors (ruxolitinib)
- α-interferon
- low-dose aspirin
- ACE inhibitors
- radioactive phosphorus
- allopurinol
what is the aim of treatment for PV?
The haematocrit should be strictly maintained below 0.45 and the platelet count below 600 and ideally below 400×10^9/L
what is essential thrombocythaemia (ET)?
in this condition there is a sustained increase in the platelet count due to megakaryocyte proliferation and overproduction of platelets
The haematocrit is normal and the Philadelphia chromosome or BCR-ABL1 rearrangement is present in ET. T or F.
False
the Ph chromosome is absent in ET
What is the central diagnostic feature in ET?
A persisting platelet count of greater than 450 × 10^9/L is the central diagnostic feature
What is the major criteria for diagnosis of ET?
what is the minor criteria for diagnosis of ET?
what are the clinical and laboratory findings?
what are causes of a raised platelet count other than any myeloproliferative disorder?
- haemorrhage, trauma, post-op
- chronic iron deficiency
- malignancy
- chronic infections
- connective tissue diseases (eg. rheumatoid arthritis)
- post-splenectomy
what classifies a high-risk patient with ET?
Patients at high risk include those over 60 years of age, and/or with previous thrombosis and/or with platelet count >1500 × 109/L
how is a low risk patient with ET treated?
with low dose aspirin at 75 mg/day
how is a high risk patient with ET treated?
with hydroxycarbamide
what is primary myelofibrosis (PMF)?
progressive generalised reactive fibrosis of the BM in association with megakaryocytic atypic and proliferation with the development of haemopoiesis in the spleen and liver
what are the clinical features in PMF?
- insidious onset in older people
- symptoms of anaemia
- massive splenomegaly- with abdominal discomfort, pain or indigestion
- hyper metabolic symptoms- weight loss, anorexia, fever and night sweats
- bleeding problems, bone pain or gout (minority)
what are the lab findings in PMF?
- normochromic anaemia, but normal or increased Hb may be found
- white cell and platelet counts are high in early disease but decrease in late disease
- leucoerythroblastic blood film- tear drop poikilocytes/red cells; nucleated red cells in peripheral blood; immature granulocytes
- BM trephine biopsy- fibrotic, hypercellular
- increased megakaryocytes in BM
- high serum urate and high LDH levels
- JAK2 mutation in 50% of pts
- osteosclerosis in some patients
what is the treatment for PMF?
- blood transfusions + regular folic acid therapy
- ruxolitinib
- hydroxycarbamide (hydroxyurea)
- splenectomy
- allopurinol
- allogenic SCT
what is mastocytosis?
what are the symptoms of mastocytosis?
how is mastocytosis treated?
