Chronic Myeloproliferative Disorders and Chronic Myeloid Leukaemia Flashcards
Clonal proliferation of bone marrow stem cells usually leading to excess production of one or more haemopoietic lineage
Chronic myeloproliferative disorders
3 types of chronic myeloproliferative disorders
Polycythaemic vera- RBCs
Esstential thrombocytosis- platelets
Idiopathic myelofibrosis-reactive fibrosis of bone marrow and extramedullary haemopoeisis in the liver and spleen
What percentage of chronic myeloproliferative disorders transform to acute leukaemia
10%
Immature RBCs released into the blood following a bleed
Reticulocytes
Symptoms of polycythaemia vera
Stroke, MI, splenomegaly, gangrene, gout (everytime you breakdown cells, uric acid released into the blood), plethoric face
Lab findings of polycythaemic vera
increased haematocrit
Haematocrit
RBCs relative to plasma
3 types of polycythaemia vera
Primary e.g. PV
Relative e.g. not enough plasma- alcoholics, D&V
Secondary e.g. COPD, altitude, EPO production tumours, renal disease
What is the distinguishing features between primary and secondary polycythaemia
If EPO is high, likely to be secondary
JAK2 mutation, likely to be primary
What is the result of the JAK2 mutation
Erythrocyte replication cycle constantly on
Persistent elevation of peripheral blood platelet count as a result of increased marrow platelet production in the absense of a systemic cause
Thrombocytosis
Clinical features of thrombocytosis
Thrombosis (gangrene, cerebral, coronary arteries) DVT Superficial thrombophlebitis Headaches, visual disturbance Splenomegaly (50%)
Lab findings for essential thrombocytosis
Platelet count >405x109/L
JAK2 mutation in 50%
Hypercellular bone marrow and increased numbers of megakaryocytes
CALR mutation in 45%
What is the effect of the CALR mutation
Cell signalling protein found in myeloid progenitors- may activate cell signal pathways
Treatment for thrombocytosis
Antiplatelet treatment
Interferon- inhibitor of megakaryocytes
Hydroxycarbaminde- decreased DNA synthesis
Prognosis for idiopathic myelofibrosis
5 years- much worse than the others
What are the 3 main characteristics of idiopathic myelofibrosis
Splenomegaly
Extramedullary haematopoiesis
Replacement of bone marrow with fibrosis
Clinical features of idiopathic myelofibrosis
Massive splenomegaly- left hypochondrial pain
Fever, weight loss, pruritis, hepatomegaly and night sweats
Abdominal swelling caused by portal hypertension
CML is characterised by excess production of what cells?
Myeloid cells- neutrophils and granulocytes
Describe the genetic mutation in CML
Leukaemic cells have t(9;22) translocation known as the philadelphia chromosome (BCR-ABL gene fusion forms TK gene that tells cells to proliferate)
Clinical features of CML
Occurs at all ages
Weight loss, night sweats, itching, left hypochondrial pain, gout, splenomegaly
Lab features of CML
Leucocytosis
Treatment for CML
Imatinib (Gleevec) inhibits TK encoded by BCR-ABL gene
B cell clonal lymphoproliferative disease- lymphocytes accumulated in the blood, bone marrow, lymph nodes and spleen
Chronic lymphocytic leukaemia
What age does CLL typically present?
Over 72 yrs
Clinical features of CLL
Lymphadenopathy, night sweats, weight loss due to bone marrow failure, splenomegaly
Hypogammaglobulinaemia-predisposed to infection
Autoimmune haemolytic anaemia
Lab findings of CLL
Increased peripheral blood lymphocytes. Weak expression of IgM
Peripheral blood cytopenias, mostly frequently affecting more than 1 lineage, usually in association with a hypercellular marrow indicating ineffective haemopoiesis
Myelodysplasia
Lab findings for myelodysplasia
Macrocytic anaemia
Neutropenia
Hypercellular bone marrow
