Block 4 - Haematology

Front 1

Which cells do myeloblast differentiate into?

Back 1

* Myelobast --> promyelocytes --> basophils, neutrophils, eosinophils
* Myeloblast --> monoblast --> monocytes

Front 2

What 3 types of blast cells does the common myeloid progenitor differentiate into?

Back 2

* Megakaryoblast (--> platelets)
* Proerythroblast (--> RBCs)
* Myelobast

Front 3

What are the main symptoms and signs of anaemia?

Back 3

* Tiredness
* Headache
* Dizziness
* SOB
* Cardiac: palpitations, chest pain, postural hypotension
* Pallor

Front 4

* What are haematocrit, MCH, and MCHC?

Back 4

* Haematocrit = % of whole blood made up of RBCs

* MCH = mean corpuscular haemoglobin = average amount of Hb per RBC

* MCHC = mean corpuscular haemoglobin concentration = average concentration of Hb in RBCs

Front 5

* What are causes of non-megaloblastic macrocytic anaemia?

Back 5

* Liver disease
* Alcohol
* Reticulocytosis
* Bone marrow disorders
* Pregnancy
* Hypothyroidism

Front 6

What are the roles of the following proteins:
* Ferritin?
* Ferroportin?
* Hepcidin?
* Transferrin?

Back 6

* Ferritin: binds Fe in cells to prevent Fe toxicity

* Ferroportin: transports Fe out of cells

* Hepcidin: produced by liver, inhibits ferroportin

* Transferrin: carries Fe in blood to erythyroid precursors

Front 7

What are clinical & lab signs of Fe deficiency?

Back 7

* Microcytic anaemia
* Koilonychia
* Atrophy of tongue papillae (glossitis)
* Pica, RLS
* Pencil cells, target cells

Front 8

What is the most useful test for Fe deficiency?

Back 8

* ↓Ferritin

(but can be falsely raised by acute inflammation, masking ↓iron)

Front 9

What lab test differentiates anaemia of iron deficiency and anaemia of chronic disease?

Back 9

Soluble transferrin receptor assay

(Transferrin ↑ in Fe deficiency, ↓ in chronic disease)

Front 10

Where are folic acid and vitamin B12 absorbed?

Back 10

* Folic acid: jejunum
* B12: terminal ileum

Front 11

What is the role of haptoglobin?

Back 11

* Produced by liver
* Binds free Hb in blood
* ↓free haptoglobin in intravascular haemolysis

Front 12

What specific parts of the nervous system are affected by Vitamin B12 deficiency?

Back 12

* Myelin synthesis (PNS & CNS)
* Dorsal columns of spinal cord
* Corticospinal tract of spinal cord

Front 13

What surface markers are typically expressed on B cells in CLL?

Back 13

* B cell markers (CD19, 22, 10) + CD5 (normally a T cell marker)

Front 14

What is the Coombs (direct antiglobulin) test?

Back 14

* Add anti-human globulin to RBCs
* Agglutination --> presence of antibodies against RBCs

Front 15

What are common opportunistic infections? (4)

Back 15

* Pneumocystis carinii pneumonia (PCP)
* Cryptococcal meningitis
* Candidiasis
* CMV infection

Front 16

What is the Philadelphia chromosome and what disease is it associated with?

Back 16

* ABL oncogene on chromosome 9 translocated to BCR on chromosome 22
* Resulting chromosome 22 is "Philadelphia chromosome"
* BCR-ABL present in 95% of CML

Front 17

* What is the main pharmacological treatment for Philadelphia chromosome CML?

Back 17

Imatinib (Glivec)

Inhibits tyrosine kinase encoded by BCR-ABL

Reduces rate of transformation to AML or ALL

Front 18

What clotting factors are involved in the extrinsic (initiating) pathway?

Back 18

Tissue factor (III) + VII

Front 19

What clotting factors are involved in the intrinsic pathway?

Back 19

XII, XII, IX, VIII

(IX activates X. VIII is a cofactor for IXa in the presence of calcium and phospholipid.)

Front 20

What clotting factors are involved in the common pathway?

Back 20

X, V, II (thrombin), fibrin, XIII (cross-links fibrin)

(Xa + Va +calcium + phospholipid activate II)

Front 21

What are normal values for PT and aPTT?

Back 21

Pt: 10-12 s
aPTT: 25-35 s

Front 22

Vitamin K together with which enzyme is required for synthesis of Vitamin K-dependent clotting factors?

Back 22

gamma-carboxylase

Front 23

What are the functions of thrombin?

Back 23

* Converts fibrinogen --> fibrin
* Initiates platelet activation
* Activates factors V, VIII, IX (amplification)
* Activates endothelium & leukocytes
* Activates plasmin

Front 24

What are some of the factors contained inside platelet granules?

Back 24

* vWF
* Fibrinogen
* ADP
* Ca2+
* Serotonin

Front 25

What are the 2 main roles of vWF?

Back 25

* Facilitates adhesion of platelets to subendothelial matrix (via Gp1b)

* Stabilizes factor VIII in circulation

Front 26

What is the half-life of factors VII and VIII in circulation?

Back 26

* VII: 4-6 hours
* VIII: 12-18 hours

Front 27

Why does warfarin have an initial pro-coagulatory effect?

Back 27

Half life of Protein C (12-16 hours) is less than half life of II, IX, and X

Front 28

What are the main types of haemaglobin?

Back 28

* HbA: α2β2 (> 95% in adults)

* HbA2: α2δ2 (2% in adults, ↑in β-thal)

* HbF: α2γ2 (foetus, adults with β-thal major)

* Hb Bart: γ4 (α-thal, babies)
* HbH: β4 (α-thal w/ 3 deletions, adults)

Front 29

On what chromosomes are the genes for α- and β-globin?

Back 29

α-globin: chromosome 16
β-globin: chromosome 11

Front 30

What is Virchow's triad?

Back 30

* Endothelial damage
* Abnormal blood flow
* Hypercoaguability

Front 31

What is the effect of the Factor V Leiden mutation?

Back 31

Makes Factor V resistant to cleavage by Protein C

Front 32

What is the mechanism of action of heparin?

Back 32

* Enhances antithrombin activity
* Also antagonizes Factor Xa

Front 33

How does the mechanism of action of low molecular weight heparin differ from unfractionated heparin?

Back 33

* Main effect is on Xa, not IIa

(Advantages: ↑half-life, ↑bioavailability, ↓risk HIT)

Front 34

What is the antidote to heparin?

Back 34

Protamine sulphate

Front 35

Which worm is the most common worm in children?

Back 35

* Enterobius vermicularis ("pin worm")

(Causes itchy bum)

Front 36

Which malaria species has a development cycle of 72 hours (rather than 48)?

Back 36

P. malariae

Front 37

What is the most common haematological abnormality during pregnancy?

Back 37

Anaemia (usually due to Fe deficiency)

Front 38

How does the coagulation state change during pregnancy?

Back 38

↑↑ in coagulation factors & vWF

(thromboembolism is a significant risk in pregnancy and post partum)

Front 39

What factors favor iron absorption in the gut?

Back 39

* Inorganic Fe
* Fe in ferrous form (Fe2+)
* Acidic pH
* Vitamin C

Front 40

How long should anticoagulation treatment be provided following a DVT?

Back 40

6 weeks if a clear reversible predisposing factor

Minimum 3 months otherwise