10. When Haemopoiesis Goes Wrong

Question 1

What can go wrong with haemopoiesis?

Answer 1

Overproduction of cells

Other caused by myeloproliferative disorders or as a physiological reaction

Question 2

What are myeloproliferative disorders?

Answer 2

Essential thrombocythaemia
Polycythaemia Vera
Myelofibrosis
Chronic myeloid leukaemia

All involve dysregulation at the mutlipotent haematopoietic stem cell

Question 3

What are the clinical features of myeloproliferative disorders?

Answer 3

Overproduction of one or several blood elements with dominance of a transformed clone
Hypercellular marrow/marrow fibrosis
Cytogenetic abnormalities
Thrombotic and/or haemorrhagic diatheses
Extramedullary haemopoiesis
Potential to transform to acute leukaemia

Question 4

What causes myeloproliferative disorders?

Answer 4

Specific point mutation in one copy of Janus kinase 2 gene
A cytoplasmic tyrosine kinase on chromosome 9 whic causes increased proliferation and survival of haematopoietic precursors

Question 5

What is polycythaemia Vera?

Answer 5

High haematocrit (>0.52 in men, >0.48 in women) or raised red cell mass (more concentrated blood)
Some have high platelets and neutrophils 
Male=female

Question 6

What are the clinical features of polycythaemia Vera?

Answer 6

Significant cause of arterial thrombosis
Venous thrombosis 
Haemorrhage into skin or GI tract 
Pruritis 
Splenic discomfort, splenomegaly
Gout

Question 7

What is the management for polycythaemia Vera?

Answer 7

Venesection to maintain lower haematocrit
Aspirin to reduce platelets
Manage CVS risk factors
Drugs to reduce overproduction of cells

Question 8

What is polycythaemia?

Answer 8

An increase in circulating red cell concentration typified by a persistently raised haematocrit
Can be: relative (normal red cell mass with decreased plasma volume) or absolute (increased red cell mass)

Question 9

What is secondary polycythaemia?

Answer 9

Driven by erythropoietin EPO production
Physiologically appropriate in response to tissue hypoxia - chronic lung disease, R to L shunts, training at altitude, CO poisoning or renal hypoxia
Physiologically inappropriate - hepatocellular carcinoma, renal cell cancer, uterine tumours

Question 10

What is essential thrombocythaemia?

Answer 10

Excess platelets in blood
Large and dark excess megakaryocytes in bone marrow
Thrombotic events

Question 11

What is the management of essential thrombocythaemia?

Answer 11

CVS risk factors should be aggressively managed
Aspirin
Return platelet count to normal range with drug such as hydroxycarbomide

Question 12

What is myelofibrosis?

Answer 12

Cause of massive splenomegaly and/or hepatomegaly due to extramedullary haematopoiesis
Heavily fibrotic marrow, little space for haemopoiesis
Blood film shows red cells looking like tear drops
Canal haemopoietic stem cell proliferation

In all cases progressive pancytopenia due to bone marrow fibrosis and hypersplenism

Question 13

What are the clinical features of myelofibrosis?

Answer 13

Patients with advanced disease experience severe constitutional symptoms - fatigue, sweats
Consequences of splenomegaly (pain, early satiety, splenic infarction)
Progressive marrow failure requiring transfusions
Transformation to leukaemia
Early death

Question 14

How does chronic myeloid leukaemia usually present?

Answer 14

Very high WCC
May preset with symptomatic splenomegaly, hyperviscosity or bone pain
Blood film and marrow will show excess of all myeloid series from blast through to fully mature neutrophils

Question 15

What is pancytopenia?

Answer 15

Reduction in white cells, red cells and platelets

Question 16

How does pancytopenia happen?

Answer 16

Reduce production (most common)
Or increased removal - immune destruction, splenic pooling, haemophagocytosis

Question 17

What can caused reduced production of blood cells and therefore pancytopenia?

Answer 17

B12/folate deficiency 
Bone marrow infiltration by malignancy
Marrow fibrosis
Radiation
Drugs
Viruses
Idiopathic aplastic anaemia
Congenital bone marrow failure

Question 18

What is aplastic anaemia?

Answer 18

Pancytopenia with a hypocellular bone marrow in the absence of. Abnormal infiltrate and with no increase in reticulin (fibrosis)
Mortality is high

Question 19

What are the roles of platelets?

Answer 19

Key role in haemostasis to facilitate clot formation, initially via a platelet ‘plug’:

• adhesion to damaged endothelial wall and to vWF
• activation: change in shape form disc and release of granules
• aggregation: clumping together of more platelets to form the plug

Question 20

What are the platelet disorders?

Answer 20

Quantitative - low (thrombocytopenia)

Qualitative - often normal number but defective function

Question 21

What acquired reasons can cause thrombocytopenia?

Answer 21

Decreased platelet production
Increased platelet consumption
Increased platelet destruction

Question 22

What are the consequences of severe thrombocytopenia?

Answer 22

Generally not symptomatic until platelet count below 30 (usually 150-400)
Easy bruising
Petechiae, prupura 
Mucosal bleeding
Sever bleeding after trauma
Intracranial haemorrhage

Question 23

What are the disorders of platelet function?

Answer 23

Hereditary (rare) - Bernard soulier syndrome, Glanzmann’s thrombasthenia
Acquired (common) - aspirin/NSAIDS/clopidogrel, uraemia, hypergammaglobulinaemia, myeloproliferative disorders