Blood, Anaemia and Haemostasis

Question 1

What is anaemia?

Answer 1

A Hb level below that which is normal for age and gender

Question 2

What is the equation for tissue oxygen delivery?

Answer 2

CO x Hb x %saturation of O2 x 1.34

Question 3

What are the clinical signs of anaemia?

Answer 3

Pale, lethargic, failure to thrive, hypoxic, ischaemia, tachycardia (if sudden onset)

Question 4

What are the 3 causes of anaemia?

Answer 4

Failure of production
Increased destruction/loss
Inappropriate production

Question 5

What are the 2 classifications of anaemia?

Answer 5

Regenerative 
- blood loss or breakdown - bone marrow working normally 
- Hb goes down quickly 
Aregenerative 
- bone marrow isn't making enough cells 
- Hb goes down slower

Question 6

How do you determine is a patient needs a transfusion?

Answer 6

• can the patient maintain their HR working at the rate it is until it fails?
• -> need to look at the HR (cardiac compensation)

Question 7

What do hypochromic RBCs indicate?

Answer 7

Pale cells, no haemoglobin

Question 8

What do polychromatic RBCs indicate?

Answer 8

Bluish tinge - immature (prematurely released from the bone marrow)

Question 9

What are the signs of decreased production of red cells?

Answer 9

Reticulocytes and polychromasia

Question 10

What are the signs of increased destruction of red cells?

Answer 10

Jaundice (increased serum bilirubin), haptoglobins (bind free Hb), LDH (picks up bilirubin)

Question 11

Where does haemopoiesis occur and when?

Answer 11

At 6 weeks to 7 months made in the liver and spleen

7 months onwards throughout life made in the bone marrow

Question 12

What is haemostasis?

Answer 12

An interaction of platelets, coagulation factors, coagulation inhibitors, fibrinolytic processes and blood vessels/endothelium
- functions to plug any holes in the system to allow blood to remain in the fluid phase

Question 13

What is primary haemostasis and the timing of it?

Answer 13

Consists of vasoconstriction, platelet adhesion and platelet aggregation
- timing is immediately - seconds to minutes

Question 14

What is secondary haemostasis and the timing of it?

Answer 14

Activation of coagulation factors and the formation of fibrin
- timing is minutes

Question 15

What is fibrinolysis and the timing of it?

Answer 15

Activation of fibrinolysis and the lysis of the clot

- timing is minutes to hours

Question 16

What is Virchow’s triad?

Answer 16

Hypercoagulability, stasis of blood flow and endothelial injury
- lead to thrombosis

Question 17

Describe how the vessel wall contributes to haemostasis?

Answer 17

The vessel wall has an endothelial cell surface which interacts with blood and subcutaneous tissue - it can be antithrombotic or prothrombotic depending on expression of surface molecules

Question 18

How does the process of coagulation start?

Answer 18

Tissue factor is the starter motor –> exposed through endothelial damage, binds to FVII (converted to FVIIa)
- this then activated FX

Question 19

What are the 3 phases of coagulation?

Answer 19

1. Initiation phase
   - initiate a clot
2. Amplification phase
   - make the decision to drive amplification
3. Propagation phase
   - extend the clot to cover the entirety of the hole

Question 20

What is the final step in the coagulation pathway?

Answer 20

Pro-thrombin (II) is converted to thrombin (IIa) via FXa and FVa
Thrombin then converts fibrinogen to fibrin which crosslinks to form a stable fibrin clot (reinforces the platelet plug)

Question 21

What are the actions of thrombin?

Answer 21

It is a controller - essential to convert fibrinogen to fibrin (insoluble clot)

• on/off switch for haemostasis
• binds to thrombomodulin (reduce coagulation)
• activates platelets

Question 22

How is thrombin inactivated?

Answer 22

By binding of thrombomodulin

• APC down regulates the ability to cleave fibrinogen (inhibits FVa and FVIIIa)
• increases plasmin formation

Question 23

How is a clot broken down?

Answer 23

Plasmin activating inhibitor normally inhibits tissue plasminogen (want to keep a clot) but to break it down APC inhibits the plasmin activating inhibitor (so less inhibition of tissue plasminogen) plasminogen –> plasmin –> break down of clot

Question 24

What is the APTT measuring?

Answer 24

The time until conversion of fibrinogen to fibrin

- intrinsic pathway

Question 25

What is PT/INR measuring?

Answer 25

Prothrombin time, assessing the extrinsic pathway of coagulation
- INR is international normalised ratio

Question 26

Describe the cooperativity of haemoglobin

Answer 26

Sigmoidal curve: high affinity to bind O2 in the lungs but once it reaches the tissues it needs to be transferred –> weak binding state at low pO2 and strong binding state at high pO2

Question 27

What is the difference between haemoglobin and myoglobin?

Answer 27

Haemoglobin is a tetramer, myoglobin is a monomer
Myoglobin is in the muscles only
Myoglobin has no cooperativity

Question 28

Which state of Hb is better at binding O2 and why?

Answer 28

Relaxed state (oxy) 
- allosteric interaction --> binding of a ligand at one site affects binding properties at another site

Question 29

How do low pH, 2,3-BPG and CO2 change the affinity of Hb for O2?

Answer 29

Shift the curve to the left and decrease Hb affinity for O2 –> helps release O2 in the tissues

Question 30

What is the difference between foetal Hb and adult Hb?

Answer 30

Foetal Hb binds oxygen with a greater affinity than the mother’s Hb –> gives the foetus access to oxygen carried by the mother’s Hb

Question 31

What are the actions of PGE2?

Answer 31

• relaxes vascular smooth muscle (vasodilator)
• hyperalgesic
• pyrogenic
• angiogenic (wound healing/tumour growth)

Question 32

What are the actions of PGI2? Where is it produced?

Answer 32

Produced by endothelial cells

• reduces platelet activation (ant-thrombotic)
• vasodilator
• protects against coronary artery disease

Question 33

What are the actions of TXA2? Where is it produced?

Answer 33

Produced by platelets

• increases platelet activation
• vasoconstrictor
• promotes coronary artery disease