Clotting Flashcards
Glycoproteins provide phospholipid surface for platelets to stick to. Describe 3 glycoproteins that facilitate this step and what they bind to [3]
What other component of the blood assists in platelet adhesion?
Gp 1a/2a + 6 bind directly to exposed collagen
GP 1b bind to vWF, indirectly to collagen
GP 2b/3a bind to Fibrinogen
VWF assists inplatelt adhesion
After a platelet plug is formed, we then form a fibrin clot. What causes this? [2]
Whats the difference between primary hemostatic plug and definitive hemostasis [2]
Activation of coagulation factors by physiological activator e.g. Tissue Factor
These activate each other in a cascade like dominos.
When the primary hemostatic plug forms, its still a weak clot - only fibrinogen adheres
Definitive hemostasis is when fibrin forms
What are the final steps in the coagulation cascade
Prothrombin cleaved to Thrombin
Its then cleaves Fibrinogen to Fibrin which forms the clot
Describe 3 natural anti-coagulants and their function
Overall function: confine clot formation
TFPI - switches off factors 7a and 10a
Proteins C + S - Switch off 5 and 8a, reducing thrombin production
Anti-thrombin - Switches of 5, 8 , 9, 10, 11, thrombin
What triggers fibrinolysis?
[3]
Endothelial cells releasing plasminogen activators (t-PA, u-PA)
What do Tissue Plasminogen Activators do?
They cleave plasminogen into plasmin allowing fibrinolysis to occur
What do we test for in a D-dimer? [1]
Fibrin Degradation Products
Anti-thrombotic drugs include antiplatelets and anticoagulants.
Anti-platelets act in 3 pathways. Give examples of each.
- Target adhering Gylcoproteins eg Abciximab
- Target surface receptors eg Clopidogrel, prasugrel, Ticagrelor
- Inhibition of COX pathway preventing AA> TXA2, prevents platelet aggregation eg aspirin
Warfarin is a common anti-coagulant what does it do? [3]
- Inhibits epoxide reductase, prevents reduction of vitamin K (Vitamin K antagonist)
- Prevents coagulation cascade
- Reduces conc of various clotting factors inc 2, 7, 9, 10 and prothrombin
Other anti-coagulants include heparins and DOACs, what are their MOAs? Give 2 examples of DOACs
Heparins inhibit thrombin
Direct Oral AntiCoagulants:
1) Rivaroxaban inhibits factor Xa
2) Dabigatran inhibits thrombin
Endothelium produces a variety of substances in a physiological state in a blood vessel. What are these substances that cause endothelium to act as a non-stick pan? [5]
Heparans TFPI - tissue factor pathway inhibitor Thrombomodulin Prostacyclin NO
Vessel damage results in platelet adhesion: 3 steps
Describe the last 2 steps
Platelets adhere, activate and aggregate
Platelet activation - platelets release ADP, thromboxane A2 and serotonin which attract more platelets causing…
Platelet aggregation - platelet plug formation
What inhibits t-PA and u-PA? [2]
What inactivates plasmin [3]
Describe TAFI
Regulators:
Inhibitors of plasminogen t-PA and u-PA: PAI-1 and PAI-2
Inhibitors of plasmin - alpha2-antiplasmin, alpha2-macroglobulin
Thrombin activatable fibrinolysis inhibitor (TAFI) which modifies fibrin to make it more resistant to t-PA
Warfarin
Indications [3]
Side effects
Indications
- VTE
- AF
- Mechanical heart valves
SE
- Hemorrhage
- Teratogenic
- Skin necrosis
- Purple toes
How does skin necrosis occur as a side effect in warfarin?
How can it be avoided?
synthesis of protein C reduced at first when started causing temporary pro-coagulant state (normally avoided by concurrent heparin administration) so thrombosis across venules leads to skin necrosis