Coagulation

Question 1

Unstable platelet plug formation

Answer 1

Adhesion: Bind collagen via GpIa / VWF via GpIb
Thromboxane + ADP release
Aggregation: GpIIb/IIIa binding

Question 2

Summary of clot formation

Answer 2

Unstable platelet plug formation
Thrombin formed by clotting cascade
Thrombin polymerises fibrinogen to fibrin to stabilise clot

Question 3

Simplified clotting cascade

Answer 3

Clotting cascade = Extrinsic, instrinsic + common pathways

• Extrinsic pathway (7, binds TF)
• Intrinsic pathway (12, 11, 9, 8)
• Common pathway (10, 5, 2)

(Extrinsic and intrinsic pathway act to activate 10, produces small amounts of 2 (thrombin) which then has positive feedback on 8 and 5 production)

Question 4

Simplified clotting pathology

Answer 4

Bleeding time increased = Platelet problem
APTT or PT increased = clotting cascade problem
APTT increased = common or intrinsic (AI) problem (any factor except VII)
PT increased = common or extrinsic (PE) problem
Thrombin time increased = Fibrinogen problem

Question 5

Summary of anti-clotting

Answer 5

Clot removal (fibrinolysis) + 3 clot regulation mechanisms

• Fibrinolysis - tPA converts plasminogen to plasmin. Plasmin cleaves fibrin + destroys clot
• 3 natural regulators = anti-thrombin (mops up thrombin /IIa + excretes by kidney), Protein C/S (IIa negative feedback on itself - binds thrombomodulin - switches from fibrinogen to Protein C cleavage - protein C inactivates factors V and VIII), TFPI (TFPI sneaks in as 4th element of TF-VIIa + Xa complex needed to initiate coagulation cascade

Question 6

Fibrinolysis

Answer 6

TPA cleaves plasminogen to plasmin
Plasmin cleaves fibrin
Dissolves formed clot

Question 7

Natural regulatory mechanisms

Answer 7

Anti-thrombin
Protein C/S
Tissue factor pathway inhibitor (TFPI)

Question 8

Anti-thrombin

Answer 8

Natural regulator of clotting

Mops up thrombin / Xa + excretes from kidney

Question 9

Protein C / S

Answer 9

Natural regulator of clotting
Excess thrombin binds thrombomodulin
Switches from cleaving fibrinogen to protein C
Activated protein C destroys factors 5 and 8

Question 10

Tissue factor pathway inhibitor (TFPI)

Answer 10

Natural regulator of clotting
Triad of TF, VII and X initiates clotting cascade
TFPI sneaks in as 4th element + blocks

Question 11

Single chain glycoprotein synthesised by liver / endothelium

Anti-coagulant

Answer 11

Anti-thrombin III (most common type of Anti-thrombin)

Question 12

Inhibits II, VII, IX and X (vitamin K dependent factors)

Answer 12

Warfarin

Question 13

Potentiates anti-thrombin to mop up more IIa / Xa
Causes osteoporosis + hyperkalaemia
Xa > IIa

Answer 13

Heparin

Question 14

Inhibits IIa or Xa

Answer 14

DOAC (if X in name blocks Xa)

Question 15

Action of aspirin

Answer 15

Anti-platelet
COX1 inhibitor
COX1 converts arachidonic acid to cyclic endoperoxidases TXA2 and PGI2
TXA2 and PGI2 activate platelets

Question 16

Activated by thrombin

Answer 16

V, VIII (positive feedback)

C (negative feedback)

Question 17

Clot formation > clot removal

Answer 17

Thrombosis

Question 18

Clot formation < clot removal

Answer 18

Bleeding disorder

Question 19

VWF

Answer 19

Protects VIII

Binds platelets

Question 20

Most common type of anti-thrombin

Answer 20

Anti-thrombin III