Haematology in systemic disease and intro to haematopathology

Question 1

Pathophsyiolog of leukoerythroblastic anaemia vs haemolytic anaemia

Answer 1

LEB: bone marrow is infiltrated so RBC production problem

Haemolytic anaemia: shortened RBC survival probelm

Question 2

What disease is characterised by primary raised erythrocytes?

Answer 2

Polycythaemia vera

Question 3

What disease is characterised by a secondary reduction in erythrocytes?

Answer 3

Auto-immune haemolytic anaemia

Question 4

Which disease is caused by a genetic deficiency of factor IX?

Answer 4

Haemophilia B

Question 5

Which disease is caused by a genetic excess of factor IX?

Answer 5

Factor IX Padua

Question 6

Which disease is caused by a genetic deficiency of erythrocytes?

Answer 6

Sickle cell disease/ HbS (beta globin gene mutation)

Question 7

How can haemophilia B be treated using gene therapy?

Answer 7

Factor IX Padua gene can be put into adenoviruses as a vector, to cause factor IX production

Question 8

Which disease is caused by an acquired mutation in JAK2?

Answer 8

Polycythaemia vera

Question 9

Which disease is caused by an acquired mutation in PIG A?

Answer 9

PNH paroxysmal nocturnal haemoglobinuria

Question 10

What is a raised factor VIII likely to be secondary to?

Answer 10

An inflammatory process

Question 11

How can haemophilia be acquired? (Rather than genetic)

Answer 11

Auto-immune disorder common in elderly - body produces autoantibodies directed against factor VIII

Question 12

Recall 2 secondary causes of raised erythrocytes?

Answer 12

Altitude
EPO-secreting tumour

Question 13

Recall 3 secondary causes of reduced erythrocytes

Answer 13

Bone marrow inflitration
Deficiency (B12/Fe)
Haemolytic anaemia

Question 14

What is the most likely cause of iron deficiency anaemia?

Answer 14

Bleeding (until proven otherwise!)

Question 15

How is iron deficiency anaemia diagnosed?

Answer 15

Ferritin and transferrin saturation: both would be low

Question 16

Recall 3 types of cancer that may present first with an iron deficiency anaemia?

Answer 16

Gastric
Renal
Bladder

Question 17

What are the morphological features of leuco-erythroblastic anaemia?

Answer 17

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)

Question 18

What are the causes of leucoerythroblastic anaemia?

Answer 18

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)

Question 19

What are the laboratory features of haemolytic anaemia?

Broad classification of haemolytic anaemia

Answer 19

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

Question 20

Which test detects immune haemolytic anaemia?

Answer 20

DAT/Coombs

Question 21

Recall 2 malignancies that can cause immune haemolytic anaemia?

Answer 21

Lymphoma
CLL

You get antibody formation against RBCs

Question 22

What type of anaemia is caused by mycoplasma infection?

Answer 22

Immune haemolytic anaemia

**NB NOT non-immune

Question 23

What are the 2 main causes of non-immune/ Dat neg haemolytic anaemia?

Answer 23

1. Malaria
2. MAHA - microangiopathic haemolytic anaemia

Question 24

Recall 2 causes of MAHA

Answer 24

1. Underlying adenocarcinoma
2. Haemolytic uraemic syndrome

Question 25

How to distinguish between immune mediated vs MAHA on blood film?

Answer 25

Immune mediated: spherocytes MAHA: no spherocytes, red cell fragments

Question 26

How can CLL and AML be distinguished on blood film?

Answer 26

CLL has mature cells, AML has immature cells

Question 27

What is the main cause of neutrophilia?

Answer 27

Pyogenic infection

Question 28

How do you distinguish a reactive neutrophilia vs a malignant one?

Answer 28

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

Question 29

Causes of eosinophilia

Answer 29

Question 30

Causes of monocytosis

Answer 30

Question 31

Causes of lymphocytosis and lymphopenia --\>which is the most common cause of lymphopenia?

Answer 31

HIV is the most common cause of reactive lymphopenia

Question 32

In which 2 conditions might smear cells appear on the blood film?

Answer 32

CLL Non-Hodgkins lymphoma

Question 33

How is B cell clonality determined?

Answer 33

Look for light chain restriction - the ratio of kappa and lambda (60:40 would be reactive, 99:1 would be malignant)

Question 34

Name 2 primary causes of haemolytic anaemia

Answer 34

Any of: Hereditary spherocytosis G6PD deficiency Sickle cell Thalassaemia

Question 35

How can DIC cause MAHA?

Answer 35

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

Question 36

Recall 2 tests that can determine immunophenotype in blood malignancies, and one use of knowing this info?

Answer 36

Flow cytometry Immunohistology Use: working out if T or B lineage, working out if myeloid or lymphoid

Question 37

Recall 2 tests that can determine cytogenetics in blood malignancies and one use of knowing this info?

Answer 37

Translocations FISH studies Use: Philadelphia chromosome identification

Question 38

Recall 2 tests that can determine molecular genetics in blood malignancies and one use of knowing this info?

Answer 38

PCR Pyro sequencing Use: Detect JAK2 mutation, or BCR ABL cDNA

Question 39

What is the basic difference between chronic myeloid and acute myeloid neoplasms?

Answer 39

In chronic leukaemia you get increased proliferation of cells but differentiation is normal In acute leukaemia you get both increased prolfieration and blocked differentiation

Question 40

generally what type of mutations are involcved in myeloid vs lymphoid malignancies?

Answer 40

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

Question 41

How to differentiate between immature and mature B cell malignancies?

Answer 41

1. Immature (e.g. acute b cell lymphoblastic lymphoma) TDT +ve surface immunoglobulin negative CD19 +ve 2. Mature (i.e. multiple myeloma) TDT -ve Surface Ig positive CD138 positive

Question 43

What are the causes of lymphocytosis: mature cells vs immature cells?

Answer 43

**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

Question 44

What marker is indicative of plasma cells?

Answer 44

CD138