Haematology in systemic disease and intro to haematopathology Flashcards
Pathophsyiolog of leukoerythroblastic anaemia vs haemolytic anaemia
LEB: bone marrow is infiltrated so RBC production problem
Haemolytic anaemia: shortened RBC survival probelm
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?
Erythroblasts (nucleated red blood cells and tear drop red blood cells)
Immature myeloid cells
this is seen in the circulation where it is abnormal (rather than in bone marrow where it is normal)
What are the causes of leucoerythroblastic anaemia?
Suggests bone marrow infiltration
a) Infection: miliary TB/severe fungal infection
b) Malignancy:
i) haemoatological: myelofibrosis/ leukaemia/lymphoma/myeloma/ ii) metastatic Ca
USUALLY A MALIGNANCY INVOLVING BM
**need to do a bone marrow biopsy to distinguish**
(if you see dry tap - myelofibrosis)
What are the laboratory features of haemolytic anaemia?
Broad classification of haemolytic anaemia
Anaemia (though may be compensated)
Reticulocytosis
Unconjugated hyperbilirubinaemia
LDH raised
Reduced haptoglobins
Classification:
a) inherited
b) acquired-
i) immune- infection (eg mycoplasma), malignancy (eg CLL, leukaemia), autoimmune (SLE), idiopathic
ii) non-immune - MAHA, malaria
Which test detects immune haemolytic anaemia?
DAT/Coombs
Recall 2 malignancies that can cause immune haemolytic anaemia?
Lymphoma
CLL
You get antibody formation against RBCs
What type of anaemia is caused by mycoplasma infection?
Immune haemolytic anaemia
**NB NOT non-immune
What are the 2 main causes of non-immune/ Dat neg haemolytic anaemia?
- Malaria
- MAHA - microangiopathic haemolytic anaemia
Recall 2 causes of MAHA
- Underlying adenocarcinoma
- Haemolytic uraemic syndrome
How to distinguish between immune mediated vs MAHA on blood film?
Immune mediated: spherocytes
MAHA: no spherocytes, red cell fragments
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
Reactive neurtophilia will have toxic granulation and vacuoles
Malignant has immature cells + either basophils (indicative of CML) or myeloblasts (indicative of AML)
*rmb in CML you see mature cells while in AML you see immature cells
Causes of eosinophilia
Causes of monocytosis
Causes of lymphocytosis and lymphopenia
–>which is the most common cause of lymphopenia?
HIV is the most common cause of reactive lymphopenia
In which 2 conditions might smear cells appear on the blood film?
CLL
Non-Hodgkins lymphoma
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)
Name 2 primary causes of haemolytic anaemia
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
Recall 2 tests that can determine immunophenotype in blood malignancies, and one use of knowing this info?
Flow cytometry
Immunohistology
Use: working out if T or B lineage, working out if myeloid or lymphoid
Recall 2 tests that can determine cytogenetics in blood malignancies and one use of knowing this info?
Translocations
FISH studies
Use: 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 basic difference between chronic myeloid and acute myeloid neoplasms?
In chronic leukaemia you get increased proliferation of cells but differentiation is normal
In acute leukaemia you get both increased prolfieration and blocked differentiation
generally what type of mutations are involcved in myeloid vs lymphoid malignancies?
Myeloid:
a) proliferation genes eg JAK2, BCR-ABL
b) block differentiation genes eg PML-RARA in APML
Lymphoid:
proliferation+differentiation+
c) mutations in apoptotic genes eg BCL2 and follicular lymphoma
How to differentiate between immature and mature B cell malignancies?
- Immature (e.g. acute b cell lymphoblastic lymphoma)
TDT +ve
surface immunoglobulin negative
CD19 +ve
- Mature (i.e. multiple myeloma)
TDT -ve
Surface Ig positive
CD138 positive
What are the causes of lymphocytosis: mature cells vs immature cells?
1) Mature lymphocytes in peripheral blood:
- Reactive/ atypical lymphocytes
- infectious mononucleosis
- Small lymphocytes and smear cells
- glandular fever or CLL/ NHL
2) Immature lymphoid cells in peripheral blood:
Lymphoblasts - Acute Lymphoblastic Leukaemia- ALL
What marker is indicative of plasma cells?
CD138
