Haematology

Question 1

How do fibrin degradation products (FDPs) act within the clotting system?

Answer 1

FDPs act to discourage clot formation, one example is D-Dimer.

MOA - competes with procoagulant thrombin

(FDPs are formed from clot break down)

Question 2

How long should coagulation take in an APTT?

Answer 2

42 seconds or less (Intrinsic pathway)

Question 3

How long should coagulation take in an PT?

Answer 3

11 seconds or less

Question 4

The cascade theory of blood clotting is incorrect, why is this?

Answer 4

Only useful for explaining PT and APTT
- The intrinsic and extrinsic pathways actually overlap and affect oneanother! Not exclusive of oneanother.

e.g. total lack of prekallikrein/kallikrein(13) or (12) in the body (Intrinsic pathway; 13, 12, 9, 8) won’t definitely bleed in surgery despite APTT being lengthened, the extrinsic pathway will compensate! But if we have factor 8/9 deficiency we will bleed, the extrinsic pathway won’t compensate for this!

It is only useful for monitoring heparin and warfarin therapy.

Question 5

What is the cell based model of Haemostasis?

Answer 5

In short: the clot only forms in the area affected - a localised response

1. Damage exposes tissue factor bearing cell to the blood and initiates the reaction (it is an Extrinsic pathway-based system)
2. The tissue factor-carrying cells have surfaces that are anticoagulant normally but change to become procoagulant
3. Two phospholipids (PS and PE) exist on the inner surface of the cell membrane - inactive
4. When Flippase and flopase enzymes shuffle these on to the outside surface, the cell becomes active and procoagulant
5. INITIATION: Tissue factor is exposed
6. Binds 7 which Activates 9 and 10
7. 10 Activates 5: A small amount of thrombin is generated
8. Platelets enter the small damaged area and come in to contact with the little bit of thrombin
9. The Same activation as the tissue cells occurs to the platelets: surface phospholipids and therefore procoagulant surface
10. THROMBIN BURST: More platelets join the platelet and generate more thrombin, but only on the single platelet - 9 combines with 8 on the platelet surface and Activates lots of 10
11. CROSS-LINKING/AGGREGATION: Red cells join the clump and then fibrin is laid down by the thrombin catalysation
    - ONLY OCCURS ON THE LOCAL AREA, GROWS OFF THERE -
12. The damaged tissue then releases tissue plasminogen activator to break down the clot

Question 6

Which physiological compounds cause platelet platelet adhesion and activation?

Answer 6

1. Thrombin
2. Adenosine diphosphate (Clopidogrel inhibits ADP receptors for glycoprotein mediation of platelet aggregation and cross linking by fibrin - platelets release ADP to amplify their clotting)
3. Thromboxane A2 (aspirin inhibits COX2 enzyme which prevents thromboxane A2 formation; TXA2 binds platelets and Activates shape change making them procoagulant)

Question 7

Which physiological compounds cause aggregation of platelets?

Answer 7

Fibrinogen

Glycoproteins 2B and 3A

Question 8

How is excessive clot formation prevented by the body?

Answer 8

Serum protease inhibitors - anticoagulants floating in the blood

Initiation and amplification - limited to local area

Healthy endothelium secretes thrombomodulin (TM) - Acts on any thrombin that has spilt over on to healthy areas and creates protein C which cleaves factor 5 and 8, to prevent clot propagation