Haematology 6 - Haematology in systemic disease and intro to haematopathology

Question 1

What disease is characterised by primary raised erythrocytes?

Answer 1

Polycythaemia vera

Question 2

What disease is characterised by a secondary reduction in erythrocytes?

Answer 2

Auto-immune haemolytic anaemia

Question 3

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

Answer 3

Haemophilia B

Question 4

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

Answer 4

Factor IX Padua

Question 5

How can haemophilia B be treated using gene therapy?

Answer 5

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

Question 6

Which disease is caused by an acquired mutation in JAK2?

Answer 6

Polycythaemia vera

Question 7

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

Answer 7

PNH paroxysmal nocturnal haemoglobinuria

Question 8

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

Answer 8

An inflammatory process

may cause thrombosis (high F8)

Question 9

How can haemophilia be acquired? (Rather than genetic)

Answer 9

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

Question 10

Recall 2 secondary causes of raised erythrocytes?

Answer 10

Altitude
EPO-secreting tumour

Question 11

Recall 3 secondary causes of reduced erythrocytes

Answer 11

Bone marrow inflitration
Deficiency (B12/Fe)
Haemolytic anaemia

Question 12

What is the most likely cause of iron deficiency anaemia?

Answer 12

Bleeding (until proven otherwise!)

Question 13

How is iron deficiency anaemia diagnosed?

Answer 13

microcytic hypochromic anaemia

Low ferritin and transferrin saturation

High TIBC

Question 14

What does an excess level of protein C lead to?

Answer 14

pro-thrombotic

Question 15

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

Answer 15

Gastric
Renal
Bladder

Question 16

What are the morphological features of leuco-erythroblastic anaemia?

Answer 16

Erythroblasts (nucleated red blood cells and tear drop red blood cells)
Immature myeloid cells

Question 17

What are the causes of leucoerythroblastic anaemia?

Answer 17

BM INFILTRATION

Malignancy: myelofibrosis/ leukaemia/lymphoma/myeloma/ metastatic Ca

Infection: miliary TB/severe fungal infection

Question 18

What are the laboratory features of haemolytic anaemia?

Answer 18

Anaemia (though may be compensated)

Reticulocytosis

Unconjugated hyperbilirubinaemia

LDH raised (RBC breakdown)

Reduced haptoglobins

Question 19

Causes of inherited haemolytic anaemia

Answer 19

Membrane – hereditary spherocytosis

Cytoplasm/enzyme – G6PD deficiency

Haemoglobin – SCD (structural) or thalassemia (quantitative)

Question 20

Which test detects immune haemolytic anaemia?

Answer 20

DAT/Coombs

Question 21

Causes of acquired haemolytic anaemia (immune mediated)

Answer 21

malignancy (lymphoma/CLL)

autoimmune (SLE)

infection (mycoplasma)

idiopathic

Question 22

What would you see on blood film of someone with immune mediated haemolytic anaemia?

Answer 22

spherocytes (not hereditary spherocytosis)

Question 23

Causes of acquired haemolytic anaemia (non immune mediated)

Answer 23

infection - malaria

microangiopathic anaemi

Question 24

Recall 2 malignancies that can cause immune haemolytic anaemia?

Answer 24

Lymphoma
CLL

Question 25

What type of anaemia is caused by mycoplasma infection?

Answer 25

Immune haemolytic anaemia

Question 26

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

Answer 26

1. Malaria 2. MAHA - microangiopathic haemolytic anaemia

Question 27

Recall 2 causes of MAHA

Answer 27

1. Underlying adenocarcinoma 2. Haemolytic uraemic syndrome

Question 28

causes of anaemia of chronic disease

Answer 28

- chronic infection (TB, osteomyelitis) - vasculitis - rheumatoid arthritis - malignancy

Question 29

Ferritin in ACD

Answer 29

high - Fe sequestered in macrophages to deprive invading bacteria of fe

Question 30

How can CLL and AML be distinguished on blood film?

Answer 30

CLL has mature cells, AML has immature cells

Question 31

What is the main cause of neutrophilia?

Answer 31

Pyogenic infection Other Corticosteroids Underlying neoplasia Tissue inflammation → colitis or pancreatitis Myeloproliferative or leukemic disorders

Question 32

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

Answer 32

Reactive neutrophilia has a limit (they won't be sky high) No immature cells in reactive neutrophilia Malignant has immature cells + either basophils (indicative of CML) or myeloblasts (indicative of AML)

Question 33

Which infections do not cause neutrophilia?

Answer 33

Brucella Typhoid Viral infections

Question 34

Causes of reactive eosinophilia

Answer 34

Parasitic infection Allergic - asthma, rheumatoid, polyarteritis, pulmonary eosinophilia Underlying neoplasms → Hodgkin’s, T-cell NHL Drugs → reaction erythema multiforme

Question 35

Cause of chronic eosinophilic leukaemia

Answer 35

Eosinophils part of clone FIP1L1-PDGFRa fusion gene

Question 36

causes of monocytosis

Answer 36

rare - chronic infections and primary haem disorders * TB, brucella, typhoid * Viral, CMV, varicella zoster * Sarcoidosis * Chronic myelomonocytic leukaemia (CMML, myelodysplastic syndrome)

Question 37

causes of reactive lymphocytosis

Answer 37

EBV, CMV, Toxoplasma Infectious hepatitis, rubella, herpes infections Autoimmune disorder Sarcoidosis

Question 38

What is the most common cause of a reactive lymphopaenia?

Answer 38

HIV also Auto immune disorders Inherited immune deficiency syndromes Drugs (chemotherapy)

Question 39

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

Answer 39

CLL Non-Hodgkins lymphoma

Question 40

Name 2 primary causes of haemolytic anaemia

Answer 40

Any of: Hereditary spherocytosis G6PD deficiency Sickle cell Thalassaemia

Question 41

How can DIC cause MAHA?

Answer 41

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 42

How is B cell clonality determined?

Answer 42

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

Question 43

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

Answer 43

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

Question 44

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

Answer 44

Translocations FISH studies Use: Philadelphia chromosome identification

Question 45

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

Answer 45

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

Question 46

Acute vs chronic leukaemia

Answer 46

chronic = ↑ proliferation, normal differntiation acute = ↑ proliferation, blocked differntiation

Question 47

causes of reduced platelets

Answer 47

BM infiltration or deficiency disease (B12 deficiency) shortened survival (ITP/TTP)

Question 48

What would you see on blood film in MAHA?

Answer 48

RBC fragments thrombocytopoenia

Question 49

Which CD markers are present in B cell ALL?

Answer 49

TdT +ve (immature cells; used in VDJ rearrangement) CD19 +ve (B cell lineage) Surface Ig **-ve**

Question 50

Which CD markers are present in MM?

Answer 50

TdT -ve - normal Surface Ig +ve - normal CD138 **+ve**

Question 51

What does the BCL2 mutation lead to in follicular lymphoma?

Answer 51

anti-apoptotic - prolong cell survival