haemostasis and thrombosis Flashcards
what are the different plasma clotting factors?
- pro-coagulants: prothrombin, F5, F7-F13, fibrinogen
- anti-coagulants: plasminogen, TFPI, Protein C/S, antithrombin
what is the difference between haemostasis and thrombosis?
haemostasis - physiological process
thrombosis - pathophysiological process
what are venous thromboses and where do they form?
- red thrombi
- high fibrin
- forms within blood vessel lumen
what are arterial thromboses? where do they form?
- white thrombi
- high platelets
- thrombus forms within atherosclerotic plaque
what is Virchow’s triad?
- rate of blood flow (slow = no replenishment of anti-coagulant factors)
- consistency of blood (natural imbalance b/ pro and anticoagulation)
- blood vessel wall integrity (damage - exposure to collagen)
what is the 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 drugs target initiation?
anti-coagulants
what drugs target amplification?
anti-platelets
what drugs target propagation?
thrombolytics
what does tissue factor do?
- TF bearing cells activate F10 and F5 forming prothrombinase complex
what is the prothrombinase complex?
- activates F2 (pro-thrombin), forming thrombin
what does antithrombin do?
inactivates F10a and thrombin
name 4 anticoagulant drugs and what they do
- dabigatran: inhibits thrombin (oral)
- rivaroxaban: inhibits F10a (oral)
- heparin: activates antithrombin (IV, SC)
- warfarin: vit K antagonist, Vit K creates F2,7,9,10 (oral)
what are the indications for drug use?
- DVT and PE
- thrombosis during surgery
- atrial fibrillation - prophylactic to strokes
what does thrombin do?
thrombin activates platelets in a +ve feedback effect
describe an activated platelet
- changes shape
- platelets become sticky and attaches other platelets
describe the steps to platelet activation
- thrombin binds to PAR (protease activated receptor)
- PAR activation –> rise in intraceullar Ca
- PAR activation also liberates arachidonic acid, turned into TXA2 by COX
- TXA2 induces expression of G1p2b/3a –> aids platelet activation
- raised Ca –> exocytosis of ADP dense granules
- ADP binds to another platelets P2Y12R –> activates platelets
state the 3 antiplatelet drugs
Clopidogrel - ADP/ P2Y12R antagonist (oral)
Aspirin - irreversible COX1 inhibitor (oral)
Abciximab - GIp2b/3a antagonist (IV, SC)
what are the indications for us of the antiplatelet drugs?
arterial thrombi
- acute coronary syndromes (MI)
- atrial fibrillation: prophylaxis of strokes
what do activated platelets do in propagation?
large scale production of thrombin
what does thrombin do in propagation?
thrombin binds to fibrinogen and converts it to fibrin strands
name a thrombolytic drug and what it does
Alteplase - recombinant tissue-type plasminogen activator (rt-PA)
- oral
- plasminogen analogue
- converts plasminogen to plasmin
- this degrades fibrin and dissolves clot
what are the indications for thrombolytic use?
- stroke = 1st line
- ST elevated MI
what is a DVT?
a red thrombus of deep veins of leg e.g. popliteal vein
what is a DVT caused by?
- stasis of blood
- damage to endothelium
what is a PE?
thrombus detachment
what is the management of DVT/PE?
- reduce levels of anticoagulant factors
- anticoagulants
- e.g. Dabigatran, Rivaroxaban, Heparin, Warfarin
what is a NSTEMI?
Non-ST-Elevated MI
what is a NSTEMI caused by?
caused by white thrombus partially occluded coronary artery - damage to endothelium - platelet aggregation - atheroma formation
what is the management of a NSTEMI?
- reduce lipid formation and platelet aggregation/activation
= antiplatelets
e.g. Clopidogrel, aspirin
what is a STEMI?
ST elevated MI
what is a STEMI caused by?
- white thrombus
- fully occluded coronary artery
- damage to endothelium
- atheroma formation
- platelet aggregation
what is the management of STEMIs?
- reduce lipid formation, platelet aggregation/activation and dissolve thrombus
= antiplatelets, thrombolytics
what is the treatment if a clot is suspected?
thrombolytics
what is the treatment if a clot is suspected to form in future in venous system?
anticoagulants
what is the treatment if a clot if suspected to form in the future in arterial system?
antiplatelets
