Haematology 6 - Haematology in systemic disease and intro to haematopathology Flashcards
What disease is characterised by primary raised erythrocytes?
Polycythaemia vera
What disease is characterised by a secondary reduction in erythrocytes?
Auto-immune haemolytic anaemia
Which disease is caused by a genetic deficiency of factor IX?
Haemophilia B
Which disease is caused by a genetic excess of factor IX?
Factor IX Padua
Which disease is caused by a genetic deficiency of erythrocytes?
Sickle cell disease/ HbS (beta globin gene mutation)
How can haemophilia B be treated using gene therapy?
Factor IX Padua gene can be put into adenoviruses as a vector, to cause factor IX production
Which disease is caused by an acquired mutation in JAK2?
Polycythaemia vera
Which disease is caused by an acquired mutation in PIG A?
PNH paroxysmal nocturnal haemoglobinuria
What is a raised factor VIII likely to be secondary to?
An inflammatory process
How can haemophilia be acquired? (Rather than genetic)
Auto-immune disorder common in elderly - body produces autoantibodies directed against factor VIII
Recall 2 secondary causes of raised erythrocytes?
Altitude
EPO-secreting tumour
Recall 3 secondary causes of reduced erythrocytes
Bone marrow inflitration
Deficiency (B12/Fe)
Haemolytic anaemia
What is the most likely cause of iron deficiency anaemia?
Bleeding (until proven otherwise!)
How is iron deficiency anaemia diagnosed?
Ferritin and transferrin saturation: both would be low
Recall 3 types of cancer that may present first with an iron deficiency anaemia?
Gastric
Renal
Bladder
What are the morphological features of leuco-erythroblastic anaemia?
Immature bone marrow blood cells in peripheral blood
Erythroblasts (nucleated red blood cells and tear drop red blood cells)
Immature myeloid cells
What are the causes of leucoerythroblastic anaemia?
Infection: miliary TB/severe fungal infection
Malignancy: myelofibrosis/ leukaemia/lymphoma/myeloma/metastatic non-haematological Ca
USUALLY A MALIGNANCY INVOLVING BONE MARROW
What are the laboratory features of haemolytic anaemia?
Anaemia (though may be compensated)
Reticulocytosis
Unconjugated hyperbilirubinaemia
LDH raised
Reduced haptoglobins
Which test detects immune haemolytic anaemia (an acquired cause)?
DAT/Coombs
DAT +’ve and presence of spherocytes -> immune haemolytic anaemia
Recall 2 malignancies that can cause immune haemolytic anaemia?
Lymphoma
CLL
What type of anaemia is caused by mycoplasma infection?
Immune haemolytic anaemia
What are the 2 main causes of non-immune/ Dat neg haemolytic anaemia?
- Malaria (no immune mechanism - just toxic breakdown by the parasite)
- MAHA - microangiopathic haemolytic anaemia (reticulocytes will be raised)
Recall 2 causes of MAHA
- Underlying adenocarcinoma
2. Haemolytic uraemic syndrome
How can CLL and AML be distinguished on blood film?
CLL has mature cells, AML has immature cells
What is the main cause of neutrophilia?
Pyogenic infection
How do you distinguish a reactive neutrophilia vs a malignant one?
Reactive neutrophilia has a limit (they won’t be sky high)
No immature cells in reactive neutrophilia
Malignant hasimmature cells + either basophils and myelocytes (indicative of CML) or myeloblasts (indicative of AML)
What is the most common cause of a reactive lymphopaenia?
HIV
In which 2 conditions might smear cells appear on the blood film?
CLL
Non-Hodgkins lymphoma
Name primary causes of haemolytic anaemia
Always a problem with the red cells themselves whereas secondary causes will be due to defects of the environment
Any of: Hereditary spherocytosis G6PD deficiency Sickle cell Thalassaemia
How can DIC cause MAHA?
Procoagulant factors released
In places where blood moves slowly (eg small vasculature) there is platelet deposition and fibrinogen is converted to fibrin
Red cells pushed through fibrin web and fragmented
How is B cell clonality determined?
Look for light chain restriction - the ratio of kappa and lambda (60:40 would be reactive, 99:1 would be malignant)
Useful to look at if unsure about glandular fever vs mature lymphocyte malignancy
Recall 2 tests that can determine immunophenotype in blood malignancies, and one use of knowing this info?
Flow cytometry (liquid tumour)
Immunohistology (solid tumour)
Use: working out if T or B lineage, working out if myeloid or lymphoid - by seeing if they express markers from that lineage
Recall 2 tests that can determine cytogenetics in blood malignancies and one use of knowing this info?
Translocations FISH studies (interphase FISH or metaphase FISH) Use: looking for chromosomal markers e.g. Philadelphia chromosome identification
Recall 2 tests that can determine molecular genetics in blood malignancies and one use of knowing this info?
PCR
Pyro sequencing
Use: Detect JAK2 mutation, or BCR ABL cDNA
What is the difference between primary and secondary disorders?
Primary = issue with bone marrow production - haematological.
These can be germ-line mutations or acquired/somatic mutations later in life.
Secondary = systemic issue which affects blood components but bone marrow production is fine
