Wrong Haemopoiesis Flashcards
(27 cards)
What else can go wrong with haemopoiesis?
Over production caused by myeloproliferative disorders or as a physiological reaction.
What are myeloproliferative disorders?
Essential thrombocytopenia
Polycythemia vera
Myelofibrosis
Chronic Myeloid leukaemia
What are the clinical features of myeloproliferative disorders?
Over production of one or several blood elements with dominance of a transformed clone
Hypercellualar marrow / Marrow fibrosis
Cytogenetic abnormalities Thrombotic and / or haemorrhaging diatheses
Extramedullary haemopoiesis (liver / spleen)
Potential to transform to acute leukaemia
Overlapping clinical features.
Genetic mutation?
Point mutation in one copy of the Janus kinase 2 gene (JAK2) -a cytoplasmic tyrosine kinase on chromosome 9 which causes increased proliferation and survival of haematopoietic precursors. We now have specific drug targeting the aberrant protein
Polycythaemia Vera?
Too many red cells
Diagnostic criteria = High haematocrit or raised red celll mass
JAK2 mutation is present in approx 95% PRV patients
No reactive cause found
Same patients also have high platelets and neutrophils
Median age 60yrs.
Males=Females
Clinical features of PV?
Significant cause of arterial thrombosis
Venous thrombosis
Haemorrhage into the skin / GI tract
Pruritis - itching especially when wet
Splenic discomfort
Gout
In some transformations to myelofibrosis or acute leukaemia
PV management?
Venesection to maintain the Hct to <0.45
Aspiring 75mg unless contraindicated
Manage CVS risk factors
Some drugs to reduce the overproduction of cells should be considered.
Polycythemia?
An increase in circulation red blood cell concentration typified by a persistently raised haematocrit.
Relative = Diatuetic (causes dehydration), clinical dehydration. -normal red cell mass with decreased plasma volume.
Absolute = Primary or Secondary - increased red cell mass
Primary = Polycythaemia Vera
Secondary = Driven by erythropoietin (EPO) production. -
Physiological appropriate in response to tissue hypoxia -
Physiologically inappropriate -Or due to an abnormal high affinity Hb
Physiologically appropriate?
Central Hypoxia
- Chronic lung disease
- R to L shuts
- Training at altitude
- CO poisoning
Renal hypoxia
- Renal artery stenosis
- Polycystic disease
Pathological EPO production?
Hepatocellular carcinoma
Renal cell cancer
Uterine tumours
Phaeochromocytoma
…all produce ectopic EPO
Other causes of EPO in blood?
Doping
Management for Throbocythaemia?
CVS risk factors should be aggressively managed
Aspirin
High risk patients (over 60, platelet >1500 or disease related thrombosis / haemorrhage) : Give hydroxycarbomide to retun platelet to normal range.
Reactive causes of essential thrombocythaemia?
Infection
Inflammation (Imflammatory bowel disease, RA)
Other tissue injury (surgery, trauma, burns)
Haemorrhage
Cancer
Redistribution of platelets
Myelofibrosis
Bone eventually ossifies.
Little space for haematopoiesis so blood count go down
Look like tear drops red cells in fibrotic bone marrow.
Massive splenomegaly and hepatomegaly die to extramedullary haematopoiesis
Clinical features of myelofibrosis?
Patients with advanced disease experience severe constitutional symptoms - fatigue, sweats
The consequences of massive splenomegaly -Pain, Early satiety (full quickly), splenic infarction
Progressive marrow failure requiring transfusions of blood products.
Transformation to leukaemia - Early death
Chronic myeloid leukaemia?
Usually presents with very high WCC, this may be an incidental finding.
Patients may present with symptomatic splenomegaly, hyperviscosity (sticky blood) or bone pain.
Disease of adults v rare in children.
Can get visual disturbance, confusion , tiredness or breathlessness as blood vessels will get clogged up.
Due to philadelphia chromosome (exchange between 9 and 22)
Treatment of CML
Philadelphia chromosome - switch of material between 9 and 22.
Fusion of Abel part of 9 and BCR portion of 22.
This turns on tyrosine kinase which leads to proliferation.
Design drug (Imatinib) that competitively binds so that the substrate cannot bind to kinase site.
This means that tumour cells cannot proliferate.
Median survival has gone form 5 years to 20 years with this drug.
Also no longer need bone marrow transplants in the first 6 months.
Pancytopenia?
Reduction in white cells red cells and platelets
It is caused by reduced production or increased removal.
Increased removal is less likely as the cause.
Increase removal?
Immune destruction - rare to cause pancytopenia
Splenic pooling - Hypersplenism in massive splenomegaly
Haemophagocytosis + chewing up of the cells in the bone marrow (vv rare)
Reduced production?
B12 / Folate deficiency
Bone marrow infiltration by malignancy (blood cancers of other cancers)
Marrow fibrosis
Radiation
Drugs - chemotherapy, antibiotics, anticonvulsants, psychotropic drugs, DMARDs
Viruses - EBV, viral hepatitis, HIV, CMV
Idiopathic aplastic anaemia
Congenital bone marrow failure
Idiopathic aplastic anaemia
It is pancytopenia with a hypocellular bone marrow in the absence of an abnormal infiltrate and with no increase in reticulum (fibrosis)
High death as treatment difficult Screen for viruses and abnormal stuff…
Death is often due to neutropenic infection or bleeding
Platelets?
Key role in Hemostasis to facilitate clot formation initially via a platelet ‘plug’.
Adhesion: to damaged endothelial wall and to vWF (Vin Willebrand Factor)
Activation: change in shape form disk and release granules
Aggregation: clumping together of more platelets to form the plug
Platelets disorders?
Quantative - low (thrombocytopenia
Qualitative - Often normal number but defective function
Thrombocytopenia?
Inherited or Acquired
-Firstly think of drugs!
Decreased platelet production?
Increased platelet consumption?
Increased platelet destruction?
