Haemostasis and Thrombosis Flashcards
Give examples of pro-coagulants
Prothrombin, F5, F7-13, fibrinogen
Give examples of anti-coagulants
Plasminogen, TFPI (tissue factor pathway inhibitor), protein S and C, and antithrombin
What’s the difference between venous and arterial thomboses?
Venous - red thrombi with high fibrin. The thrombus forms within blood vessel lumen
Arterial - white thrombi with high platelets. The thrombus forms within atherosclerotic plaque
What is virchow’s triad?
- rate of blood flow
- consistency of blood
- blood vessel wall integrity
What are the different stages of cell based theory of coagulation?
- initiation - small scale production of thrombin
- amplification - large scale production of thrombin on platelet surfaces
- propagation - generation of fibrin strands by thrombin
What molecules target each of the stages of cell based theory of coagulation?
- initiation is targeted by anti-coagulants
- amplification is targeted by anti-platelets
- propagation is targeted by thrombolytics
What happens in the initiation step of coagulation?
Small scale thrombin production where:
- tissue factor bearing cells activate F10 and F5 forming the prothombinase complex
- this prothombinase complex activates F2 (prothrombin) forming thrombin
- antithrombin (AT-III) inactivates F10a and thrombin
What are examples of anticoagulant drugs?
Dabigatran
Rivaroxaban
Heparin
Warfarin
What does Dabigatran do? how is it administered?
Inhibits thrombin
Oral
What does Rivaroxaban do? How is it administered?
inhibits F10a
oral
What does Heparin do? How is it administered?
Activates AT III
IV, SC
What is a low molecular weight version of heparin and how is it administered?
Dalteparin
SC
Why would you use dalteparin instead of heparin?
Dalteparin is a LMW heparin and LMWHs have a more predictable response, a greater bioavailability, and a longer anti-Xa half life than unfractionated heparin
What does warfarin do? How is it administered?
Vitamin K antagonist
Vitamin K creates F2, 7, 9 10
Oral
Why would aspirin have a limited affect on DVTs during long haul flights?
Because they treat ARTERIAL thrombi
What happens in the amplification stage of coagulation?
Large scale production of thrombin:
Thombin activates platelets in a +ve feedback effect
Activated platelets change shape and become ‘sticky’ and attach to other platelets
How are platelets activated in coagulation?
- thrombin binds to the protease activated receptor (PAR)
- PAR activation -> rise in intracellular [Ca2+]
Liberates arachidonic acid which turns into TXA2 by COX enzymes
TXA2 induces expression of Glp2b/3a which aids platelet aggregation - raised [Ca2+] lead to exocytosis of ADP dense granules
- ADP binds to another platelet’s P2Y to activate the platelet
What are examples of antiplatelet drugs?
Clopidogrel
Aspirin
Abciximab
How does clopidogrel work? how is it administered?
ADP/P2Y12R antagonist
Oral
How does aspirin work? How is it administered?
Irreversible COX1 inhibitor
oral
How does abciximab work? How is it administered?
Glp2b/3a antagonist
IV/SC
What are indications for use of anticoagulant drugs?
DVT/Pe
Thrombosis during surgery
Atrial fibrillation - prophylactic to strokes]
VTE
What are indications for use of antiplatelet drugs?
Acute coronary syndromes - MI
Atrial fibrillation - prophylaxis of strokes
ARTERIAL THROMBI
What happens in the propagation step of coagulation?
Thrombin mediated generation of fibrin -
Activated platelets make a large scale production of thrombin
Thrombin then binds to fibrinogen and converts it to fibrin strands
How are pre-formed clots removed using drugs
Use thrombolytics - anticoagulants and antiplatelets won’t remove them
What is an example of a thrombolytic drug and how does it work? How is it administered?
Recombinant tissue type plasminogen activator
(rt-PA)
A plasminogen analogue that converts plasminogen to plasmin and then degrades fibrin and dissolves the clot
Oral
What are indications for thrombolytic use?
Arterial thombi
VTE
Stroke - first line
ST elevated MI
What is a DVT? How is it caused?
A red thrombus of the deep veins of the leg eg a popliteal vein caused by stasis of blood and damage to the endothelium
What is a PE
Thrombus attachment - pulmonary embolism causing a blood clot in the lungs
What are ways to manage a DVT or PE
Reduce levels of anti-coagulant factors using anticoagulants eg dabigatran, rivaroxaban, heparin, warfarin
What are NSTEMI and how are they caused?
Non ST Elevated MI caused by a white thrombus due to a partially occluded coronary artery leading to:
- damage to endothelium
- platelet aggregation
- atheroma formation
How are NSTEMI managed?
reduce the lipid formation and platelet aggregation/activation - antiplatelets eg clopidogrel, aspirin, abciximab
What are STEMI and how are they caused?
ST Elevated MI due to a white thrombus and a fully occluded coronary artery due to:
- damage to endothelium
- atheroma formation
- platelet aggregation
How are STEMI managed?
Reduce lipid formation, platelet aggregation/activation and dissolve thrombus - antiplatelet and thrombolytics
AP - clopidogrel, aspirin, adciximab
TL - alteplase
What are diseases associated with arterial thrombosis?
Brain - stroke
Heart - acute coronary synromes eg AF
Arteries - aortic aneurysm, peripheral arterial disease
What are diseases associated with venous thrombosis?
DVT and PE
What are treatment options of thrombosis if you think there is a clot?
Thrombolytic
What are the treatment options of thrombosis if you suspect a clot in the future in venous system
Anticoagulant
What are treatment options of thrombosis if you suspect a clot in the future in the arterial system
Antiplatelets
