Chronic myeoproliferative disorders and chronic myeloid leukaemia. Flashcards
define chronic myeloproliferative disorders.
long term myeloid lineage cells hyper proliferate.
what blood cancer can chronic myeloproliferative disorders progress too
leukaemia
what cells are contained within stem cells
erythrocytes
Granulocytes (neutrophil, eosinophil and basophil)
Megakaryocytes (platelets)
define polycythaemia vera
increased RBC, +/- neutrophils and platelets.
deine essential thrombocthaemia
increased platelets
define myelofibrosis
proliferation of an abnormal clone of hematopoietic stem cells in the bone marrow and other sites results in fibrosis, or the replacement of the marrow with scar tissue
3 myleoprolifertive disorders
myelofibrosis
polycathaemia vera
essential thrombocythaemia.
symptoms of polycythaemia vera
Insidious, itching, plethoric face, headache, general malaise, tinnitus, peptic ulcer, gout-uric acid crystals, gangrene of the toes, plethora, gangrene, engorged retinal veins, spleenomegaly.
how is polycathaemia vera diagnosed
Persistent increased Hb/hct (haemoatocrit) >0.5
what is the difference between relative and absolute polycathemia.
relative is where RBC appear high in comparison to plasma which has decreased in volume happens in dehydrated e.g. alcoholic)
absolute is where the level of RBC is down.
what is the difference between primary and secondary polycythaemia.
primary is in the bone marrow, secondary is due to another factor such as living in high altitudes,
what is the first line of tests if you suspect polycythaemia.
FBC
Ferritin
EPO level
UE/LFT
what is the only primary cause of polycythaemia
polycythaemia vera
what are the secondary causes of polycythaemia.
central hypoxic process renal disease -EPO drug associated- androgen preparations Congenital- high oxygen affinity, erthythrpoeitien receptor mediated. Idiopathic erythrocytosis
what are the second line tests for polycthaemia
CXR-chest xray
ABG
USS-abdomen for spleenomegaly.
EPO Normal- JAK2 mutation, Bone marrow examination, EXON 12 mutation.
what change takes place in the JAK2 mutation.
G-to-T mutation at nucleotide 1849
Phenylalanine for valine at 617 in protein (V617F)
how does the JAK2 mutation cause myeloproliferative disorders
EPO binds to receptor with JAK2 and phosphorylation causes DNA replication, but with mutation receptor in activated without EPO.
Treatment for polycythaemia vera
venesection (remove RBC) aim to get haemocrit 0.45.
Aspirin.
causes of reactive (secondary) thrombocytosis
surgery, infection, inflammation, malignancy, iron deficiency, hyposplenism, haemolysis, drug induced (steroids or adrenaline, TPO), rebound post chemo
what are the first line investigations of thrombocytosis
- FBC and film
- Ferritin
- CRP
- CXR
- ESR
what are the second line investigations for thrombocytosis
- JAK2
- CALR
- ? Bone marrow biopsy
- Extensive search for secondary cause
what is CALR
• cell signalling protein produced in ER (endoplasmic Reticulin) and found in myeloid progenitors.
treatment for thrombocytosis
Aspirin 75mg daily- inhibits platelets.
Cytoreduction (only if High risk)
what is cytorecustion (used in thrombocytosis treatment)
Hydroxycarbamide- antifolate- reduced DNA synthesis.
Clinical presentation of myelofibrosis.
pancytopenia- deficney in all 3 blood cell types
fever, night sweats and weight loss.
spleenomegaly is a complication of which 2 of the 3 myeloproliferative disorders
polycathemia and myelofibrosis
what are the first line investigations for myelofibrosis
FBC and film
how is myelofibrosis diagnosed
blood film, bone marrow results, JAK mutation and CALR mutation.
how do you measure spleen size
from mid clavicular line at the costal margin to the furthest margin at which the spleen can be felt.
causes of spleenomegaly
Cancer Hameatological -myelofibrosis. Infection Congestion-liver/portal disease Autoimmune Glycogen storage disorders Other- amyloid.
Treatment for myelofibrosis
Supportive care- EPO injections. Anaemic (blood transfusion), platelets transfused.
JAK2 Inhibitors- helps shrink spleen.
Bone marrow Transplant
which of the 3 myeloporliferative disorders has poor prognosis
myelofibrosis
what are the clinical features of chronic myeloid leukaemia
leukocytosis- lots of WBC.
anaemia.
splenomegaly.
symptoms of chronic myeloid leukaemia
- Abdominal discomfort:Splenomegaly
- Abdominal pain: Splenic infarction
- Fatigue: Anaemia, catabolic state
- Venous occlusion: Retinal vein, DVT, priapism (continuous erection cause infract)
- Gout- Hyperuricaemia
treatment for chronic myeloid leukaemia.
chronic and acute phase
chronic phase- Low dose oral cytotoxic drugs (busulphan, hydroxycarbamide).
Acute transformation- intensive chemotherapy
Allogenic bone marrow transplant
What common translocation increases the chance of developing chronic myeloid leukaemia
- ABL- chromosome 9
- BCR- chromosome 22
- Translocation results in these 2 sitting next to each other- oncogene, which codes for tyrosine kinase tells cells to hyperprolifearte, which causes anaemia.
which drug inhibits the Philadelphia chromosome
• Gleevac (imantinib)- block the active site in the bcr-abl tyrosine kinase.
BCR-ABL mutations confer resistance to which drug used to treat chronic myeloid leukaemia
-Imatinib.
what are the 2 phases of chronic myeloid leukaemia
chronic
acute transformation.
