Chapter 23: Haematology and Transfusion Medicine

Question 1

Define haematopoiesis and where does it occur

Answer 1

• formation of blood cells
• during development occurs in yolk sac, liver, spleen and lastly red bone marrow in all bones
• in childhood, red marrow is replaced by fat yellow marrow

Question 2

What does increased number of circulating reticulocytes (reticulocytosis) reflect?

Answer 2

erythropoeises

Question 3

Describe how red cells are developed from precursors

Answer 3

1. Red blood cell precursor = erythroblast or normoblast
2. These divide and acquire Hb
3. Late normoblast, nucleus condenses and is extruded from cell
4. FIRST NON-NUCLEATED CELL = RETICULOCYTE (but they contain ribosomal material)
5. Reticulocytes lose ribosomal material and mature over 3 days and released into circulation

Question 4

What stimulates proliferation and differentiation of red blood cells

Answer 4

Erythropoietin

Question 5

Describe the composition of haemaglobin

Answer 5

4 globin chains surrounding iron containing haem

2 alpha and 2 non-alpha (beta) chains

Question 6

What does decreased oxygen affinity mean?

Answer 6

Oxygen is released more readily

Important for when you have hypoxic tissues

Question 7

What causes a right shift on the oxygen dissociation curve?

Answer 7

Increase in:
2,3 BPG
H+ 
CO2 
Temp

Decrease in pH

Question 8

What causes a left shift on the oxygen dissociation curve?

Answer 8

Decrease in:
2,3 BPG
H+ 
CO2 
Temp 

Increase in CO
Increase in pH

Question 9

How long do RBC last and how are they cleared?

Answer 9

RBCs last 120 days
Phagocytosed by the reticulo-endothelial system

Amino acids from globin chains are recycled and iron is removed from haem for reuse in haemoglobin synthesis

Question 10

Describe the degradation of the haem structure in RBC

Answer 10

1. Degraded to unconjucated bilirubin
2. conjugated with glucuronic acid in the liver before excreted in bile
3. Conjugated Bilirubin is converted to stercobilin in the small bowel
4. Most of this stercobilin is excreted, some is reabsorbed by kidney as urobilinogen

Question 11

What happens in increased red cell destruction

Answer 11

• Jaundice
• Increased urinary urobilinogen
• decreased haptoglobins (they bind to free RBC)

Question 12

Which is the most common white blood cell in the body

Answer 12

Neutrophils

Question 13

Where do majority of mature neutrophils exist?

Answer 13

bone marrow

Question 14

how many hours do neutrophils spend in the circulation before removal

Answer 14

6-10hrs

Question 15

What 2 system/organ/processess remove neutrophils

Answer 15

1. spleen

2. consumed in inflammatory process/undergo apoptosis

Question 16

Second most common WBC

Answer 16

Eosinophil

Question 17

Which WBC contains granultes and proteins which can intracellularly kill protozoa and hemlinths

Answer 17

Eosinophil

Question 18

Which is the largest WBC

Answer 18

Monocytes

Question 19

Monocytes can migrate and become what cells: (3)

Answer 19

macrophages, Kupffer cells or antigen presenting dendritic cells

Question 20

80% of lymphocytes are ___ cells

Answer 20

T cells

Question 21

Describe the 3 stages of normal haemostasis

Answer 21

Stage 1: Vascular endothelium produces substances (NO, prostacyclin, heparans) to prevent adhesion of platelets and WBC to wall

Stage 2: Endothelium is injured, subendothelial collagen exposed and Tissue Factor (TF) released. Platelets adhere to collagen binding to recepeotr GP1a, causing shape change in platelet shape and adhering to GP1b and GpIIb/IIa to von Willebrand factor and fibrinogen. COAGULATION is activated by Tissue factor extrinsic pathway generating thrombin

Stage 3: Fibrin cot formation: platelets become activated and aggregate, Fibrin formation is supported by platelet membrane. and you get stable fibrin.
Adherent platelets are further activated by many other pathways:
- binding of ADP
- binding of collagen, thrombin, adrenaline
- Cyclo-oxygenase pathway, converts arachidonic acid from platelet membrane into thromboxane A2, which also causes aggregation of platelets

Question 22

Megakaryocytes form what type of cells and where

Answer 22

Platelets, in the bone marrow

Question 23

Platelets circulate for how many days before destruction

Answer 23

8-10 days

Question 24

which lasts longer platelets or neutrophils

Answer 24

PLATELETS

Question 25

Drugs that inhibit platelet formation include: cyco-oxygenase inhibitor ADP mediated inhibitors GPIIb/IIIa inhibitors NAME 1 example of each

Answer 25

1. Aspirin 2. clopidogrel, prasugrel, ticagrelor 3. abciximab, tirofiban

Question 26

What are the two pathways by which coagulation occurs

Answer 26

Extrinsic (tissue factor) pathway | Intrinsic pathway

Question 27

All clotting factors are produced by the ______ except Factor __ which is produced by____

Answer 27

liver | Factor V, produced by platelets and endothelial cells

Question 28

Which factors need post-translational carboxylation and the enzyme which does is, is dependent on which vitamin __

Answer 28

Factor II, VII, IX, X (tv channels) Vitamin k

Question 29

Vitamin K is converted to an epoxide in the post translational carboxylation of the VitK dependent clotting factors. However it must be reduced to its active form by a reductase enzyme. Warfarin inhibits which part of this process?

Answer 29

The reductase is inhibited by warfarin

Question 30

In which disorders do you see microcytosis ?

Answer 30

Iron deficiency anaemia Thalassaemia Sideroblastic anaemia

Question 31

If a person is Vitamin B12 or folate def, or has liver disease (alcoholic), or has hypothyrodism or on certain drugs e.g. trimethoprin, methotrexate, what do we expect the red cell appearance to be

Answer 31

macrocytosis (increased average cell size)

Question 32

Prothrombin Time (PT) assess which pathway

Answer 32

Tissue Factor (extrinsic) pathway

Question 33

Intrinsic pathway is assessed by which coagulation screening test

Answer 33

Activated partial thromboplastin time (APPT)

Question 34

If both PT and APTT are prolonged what does this indicate

Answer 34

deficiency or inhibition of the final common pathway (Factor X, V, prothrombin and fibronogen)

Question 35

Why do we use the international normalised ratio (INR)

Answer 35

To assess the theraputic effect of coumarin anticoagulants (e.g. warfarin)

Question 36

Measurement of plasma levels of Fibrin degraded d-dimers are useful in what situation

Answer 36

in excluding the diagnosis of active venous thrombosis

Question 37

Thrombophillia is defined as

Answer 37

Abnormal propensity to develop clots

Question 38

What investigations would you order for a person who presents with Venous thrombosis <45 years, has recurrent VTEs, family history of unprovoked or recurrent thrombosis, combined arterial and venous thrombosis OR a venous thrombosis at an unsual site e.g. cerebral, hepatic vein, portal vein

Answer 38

this person has suspected thrombophillia Order: 1. Full Blood count + antithrombin levels, protein C, protein S, antiphospholipid antibodies 2. Genetic testing Factor V Leiden, Prothrombin G20210A, JAK2 VG17F mutation, CALR mutation 3. Flow cytometry to screen for GPI-linked surface proteins

Question 39

Anaemia is defined as:

Answer 39

The state in which level of haemoglobin in the blood is below the reference range appropriate for age and sex

Question 40

Two broad reasons for anaemia

Answer 40

1. Decreased or ineffective marrow production (lack of iron, vit B12, folate, invasion of malignant cells, renal failure) 2. Normal marrow production but increased removal of cells (blood loss, haemolysis, hypersplenism)

Question 41

When should someone with a high haematocrit be investigated

Answer 41

for more than 2 months >0.6 males >0.56 females

Question 42

Explain what true vs relative/low polycythemia means

Answer 42

True = excess red cells (called polycythemia rubra vera) Relative/low = due to decreased plasma volume (therefore gives the appearance that there is more RBC)

Question 43

4 causes of polycythemia

Answer 43

increase in bone marrow activity (myeloproliferation) increased EPO in chronic hypoxaemia inappropriate secretion of EPO (renal disease or tumours) Athletes injecting EPO

Question 44

High altitude, and cardiorespiratory disease can cause tissue hypoxia causing high production of ______ and resulting in _____

Answer 44

erythropoietin and resulting in polycythemia

Question 45

Polycythemia rubra vera is also considered what type of disorder

Answer 45

Myeloproliferative disorder

Question 46

Patient presents with erythrocytosis with raised Haematocrit, normal red cell mass, reduced plasma volume and also has HTN, Smokes, drinks alcohol and uses diuretics

Answer 46

Secondary polycythemia called: | "Gaisböck’s syndrome"

Question 47

Over 90% of cases with polycythaemia rubra vera (PRV) have which mutation

Answer 47

JAK - 2 V617F

Question 48

Reduction in total number of WBC is called **can be all types of WBC or an individual cell in isolation

Answer 48

Leucopenia

Question 49

Neutropenia is defined as

Answer 49

reduction in neutrophil count <1.5 x 10^9