Haemostasis and thrombosis Flashcards
Name some procoagulant factors
Prothrombin
Factors V, VII-XIII
Fibrinogen
Name some anticoagulant factors
Plasminogen
TFPI (Tissue factor pathway inhibitor)
Proteins C & S
Antithrombin
What is meant by a red thrombi?
Venous thromboses
High fibrin component
Clot could embolise
Treat using anticoagulants
What is meant by a white thrombi?
Arterial thromboses (thrombus forms within atherosclerotic plaque)
High platelet content
Plaque dislodgement -> ischaemia
Treat using anti platelets
What is virchow’s triad?
- Rate of blood flow: blood flow is slow so there is no replenishment of anticoagulant factors
- Consistency of blood flow: imbalance between anticoagulant and pro coagulation factors
- Blood vessel wall integrity
What do anticoagulants, anti platelets and thrombolytics target in the process of coagulation?
Anticoagulants: Initiation (small scale thrombin production)
Antiplatelets: Amplification
Propagation: thrombolytics
Describe the process of initiation
- Tissue factor cells produce Factor V and 10 (prothrombinase complex)
- Prothrombinase complex activates Factor 2 (prothrombin) -> Factor 2a (thrombin)
- Antithrombin (AT-III) inactivates Factor 10 and Factor 2a
Which drug inhibits Factor IIa?
Dabigatran
Which drug inhibits Factor I0a?
Rivoraxiban
How does heparin work as an anticoagulant?
Activates AT-III (inhibits Factor 10a and 2a)
Low molecular weight heparin activates AT-III but also directly inactivates Factor 10a.
How does warfarin work as an anticoagulant?
Vitamin K antagonist
Vitamin K is needed for making Factors 2, 7, 9 and 10
In what cases would you use anticoagulants?
Venous thromboses:
Deep vein thrombosis and pulmonary embolism
Thrombosis during surgery
Atrial fibrillation-prophylaxis for stroke
Describe the process of amplification
Factor 2a activates platelets
Platelet changes shape, becomes ‘sticky’ and leads to aggregation
Describe the process of platelet activation
Thrombin binds to protease activated receptor (PAR) and stimulates increase in intracellular calcium -> release of ADP from dense granules.
- ADP binds to P2Y[12] receptor involved in platelet activation/aggregation.
- PAR also stimulates COX production from arachidonic acid -> generates Thromboxane A2
- Thromboxane A2 stimulates expression of GpIIb/IIIa integrin receptor on platelet surface for aggregation
What are the drugs used to prevent platelet activation?
Prevent platelet activation/aggregation: Clopidogrel; inhibits P2Y[12] receptor Inhibits production of TXA2: Aspirin-irreversible COX-1 inhibitor, used in high doses Prevent platelet aggregation: Abciximab; inhibits GpIIb/IIIa
When would you use antiplatelet drugs?
In arterial thrombosis:
Acute coronary syndrome-MI
Atrial fibrillation-prophylaxis of stroke
Describe the process of propagation
Large scale thrombin production
Thrombin converse fibrinogen into insoluble fibrin strands
Why are thrombolytics only given in emergency situations?
Only given within 6-8 hours of stroke otherwise they are less effective and the major side effect is bleeding. The patient after this time is more likely to die from bleeding.
Give an example of a thrombolytic drug
Alteplase (IV): converts plasminogen into plasmin. Plasmin is a protease which degrades fibrin.
Recombinant type plasminogen activator
Used in strokes or ST elevated MI
