Myeloproliferative Neoplasms Flashcards
are myeloproliferative disorders and neoplasms the same thing
disorders old term, neoplasms new term
what is the difference between polycythaemia rubra vera and PV
PRV old term
what does ‘myelo’ mean
bone marrow lineage- granulocyte, red cells, platelets
what are myeloproliferative neoplasms
clonal haemopoietic stem cell disorders with increased production of one/ more types of haemopietic cells
what is maturation of cells like in MPN
preserved (unlike acute leukaemias)
what are the subtyprs of MPN
BCR-ABL1 +ve
-CML (overproduction of granulocytes, philadelphia chromosome)
BCR-ABL1 -ve
- essential thrombocythaemia (over production of platelets)
- primary myelofibrosis
- polycythaemia vera (overproduction of red cells)
when should you consider MPN as a diagnosis IMPORTANT
when there is no reactive explanation for: high granulocyte count \+/- high red cell/ Hb \+/- high platelet count \+/- eosinophilia/ basophilia
splenomegaly
thrombosis in an unusual place
what are the features of chronic myeloid leukaemia
proliferation of myeloid cells:
- granulocytes + precursors
- other lineages (platelets)
chronic phase with intact maturation followed by an accelerated phase and finally a blast crisis with maturation defect
fatal without stem cell/ bone marrow transplant in the chronic phase
what are the clinical features of CML
asymptomatic
splenomegaly
hypermetabolic symptoms
gout
problems due to hyperleucocytosis: priapism
what are the lab features of CML
normal/ low Hb
leucocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia
thrombocytosis
(compared to reactive will have higher WBC, neutrophils, eosinophils and basophils. Will have lower monocytes and lymphocytes)
what is the hallmark of CML
the philadelphia chromosome
what is BCR-ABL1
the chiameric gene that results from the philadelphia chromosome (CML)
what is the gene product of BCR-ABL1
tyrosine kinase
this causes abnormal phosphorylation = haematological change in CML
what drugs work in CML
tyrosin kinase inhibitors e.g. Imatinib
what features are common to all MPN
Asymptomatic
Increased cellular turnover (gout, fatigue, weight loss, sweats)
Symptoms/signs due to splenomegaly
Marrow failure (fibrosis or leukaemic transformation:lower with PRV and ET)
Thrombosis (arterial or venous including TIA, MI, abdominal vessel thrombosis, claudication, erythromelalgia)
what is polycythaemia vera
high Hb/ haematocrit accompanied by erythrocytosis (a true increase in red cell mass)
can have excessive production of other lineages
what must you differentiate PV from IMPORTANT
secondary polcythaemia (chronic hypoxia, smoking, erythropoietin secreting tumour)
pseudopolycythaemia (dehydration, diuretic therapy, obesity)
what are the clinical features specific to PV
headache
fatigue
itch (aquagenic puritis)
what viscosity is raised in PV
blood viscosity NOT plasma viscosity (why you get HAs)
how do you investigate polcythaemia
Hx (exclude secondary polycythaemia) exam (splenomegaly?) FBC blood film JAK2 MUTATION STATUS IMPORTANT (JAK2 analysis)
look for secondary/pseudo causes: CXR, O2 sats/ ABGs. drug Hx
infrequent tests: erythropoietin levels, bone marrow biopsy
what is JAK2
a kinase
how many of patients with PV have a JAK2 mutation
95%
what does a JAK2 mutation (substitution) cause
loss of auto-inhibition
activation of erythropoiesis in the absence of a ligand
what test forms part of the initial screening for PV
JAK2 mutation analysis
what is the treatment for PV
venesect to haematocrit <0.45
aspirin
cytotoxic oral chemo (hydroxycarbamide)
what is essential thrmobocythaemia
uncontrolled production of abnormal platelets
causes abnormal platelet function:
- thombosis
- at high levels causes bleeding due to acquired VWF disease
what are the clinical features specific to ET
bleeding
vasoocclusive complications
how does ET compare to reactive thrombocytosis
Hb, platelets, RBCs, haematocrit, eosinophils and basophils higher
wbc and neutrophils lower
how is ET diagnosed
EXCLUDE REACTIVE THROMBOCYTOSIS (blood loss, inflammation, malignancy, iron deficiency)
exclude CML
JAK2 mutation in 50-60%, CALR in 25%, MPL in 5%, 10-20% triple negative
characteristic bone marrow appearances
what is the treatment for ET
anti-platelets (aspirin)
cytoreductive therapy: hydroxycarbamide, anafrelide, interferon alpha
what is myelofibrosis
hyperplasia of megakaryocytes which produce platelet-derived growth factor= intense marrow fibrosis and haematopoiesisin the spleen and liver
what causes myelofibrosis
idiopathic
post-polycythmaeia/ essential thrombocythaemia
what are the features of idiopathic myelofibrosis
marrow failure
bone marrow fibrosis
extramedullary haematopoiesis (liver and spleen)
LEUKOERYTHROBLASTIC FILM APPEARANCES IMPORTANT
tearsrop shaped RBCs in peripheral blood
what are the clinical features of myelofibrosis
marrow failure: anaemia, bleeding, infection
splenomegaly (LUQ pain, comps e.g. portal hypertension)
hypercatabolism
how is myelofibrosis diagnosed
blood film: tear drop shaped RBCs and leucoerythoblastic
dry aspirate
fibrosis on trephine biopsy
JAK2, CALR, MPL mutations
what can cause a leucoerythroblastic film IMPORTANT
(immature cells and teardrop RBCs)
reactive (sepsis)
marrow infiltration
myelofibrosis
what is the treatment for myelofibrosis
supportive care (blood transfusion, platelets, antibiotics) allogenic stem cell transplantation (select few patients) splenectomy (controversial) JAK2 inhibitors (improve spleen size and constitutional symptoms)
are reactive causes or MPN more common
reactive causes
summaries the reactive causes resulting in increased cells
Granulocytes
- Infection: eg pyogenic bacteria causing neutrophilia
- Physiological eg post-surgery, steroids
Platelets
- Infection
- Iron deficiency
- Malignancy
- Blood loss
Red cells
- Dehydration (diuretics): pseudopolycythaemia
- Secondary polycythaemia (eg hypoxia-induced)
how can you tell the difference between reactive changes an MPN
Hx and exam
reactive changes unlikely to be associated with the comps of MPN
