Haemostasis & Thrombosis Flashcards
• Explain the steps of cell-based theory of cell coagulation
- Initiation – small scale production of thrombin
• Targeted by ANTI-COAGULANTS - Amplification – large scale production of thrombin (on platelet surfaces)
• Targeted by ANTI-PLATELETS - Propagation – generation of fibrin strands by thrombin.
• Targeted by THROMBOLYTICS
Explain Step 1 of thrombosis - Initial stages
STEP 1 - Initiation (small scale thrombin production):
(1) Tissue factor:
TF-bearing cells activate F10 and F5 forming the prothrombinase complex
(2) Prothrombinase complex:
This actives F2 (pro-thrombin), forming F2a (thrombin)
(3) Antithrombin (AT-III):
AT-III inactivates F10a and F2a (thrombin)
State the anticoagulants that are associated with Step 1: Initiation
(1) Inhibit F2a
= DABIGATRAN (oral)
• F2a inhibitor
(2) Inhibit F10a
= RIVAROXABAN (oral)
• F10a inhibitor
(3) Increase activity of AT-III
= HEPARIN (IV, SC)
• activates AT-III = decrease F2a & F10a
= DALTEPARIN
• low-molecular weight heparin (LMWH)
• activate AT-III = decrease F10a only
(4) Reduce levels of other factors
= WARFARIN (oral)
• Vit.K antagonist
• Vit.K required for F2, 7, 9 & 10 production
Indications for drug use - anticoagulants?
VTE (venous thromboembolism):
- DVT & PE
- Thrombosis during surgery
- Atrial fibrillation - prophylactic to strokes
Why is a LMWH given normally followed by another AC?
LMWH given initially in hospital as quick action
AND then to maintain it, another AC is given
What is a risk if a patient has DVT?
Could go on to develop into a PE which carries a worse risk!
In this case will most likely use Heparin first for maintenance rather than LMWH as faster onset of action
Explain the Risk Factors for DVT & PE
VIRCHOW’S TRIAD
(1) Rate of blood flow:
• Slow = no replenishment of anti-coagulant factors
• SO balance adjusted in favour of coagulation
(2) Consistency of blood:
• Natural imbalance between pro- and anti-coagulation
• e.g. Factor 5 Leiden.
(3) Blood vessel wall integrity:
• e.g. endothelia damage = exposure to collagen (pro-coagulation factors)
Give background to NSTEMI
Non-ST Elevated Myocardial Infarction
‘White’ thrombus
• PARTIALLY occluded coronary artery
• high platelets
Treatment:
• Antiplatelets - reduce lipid formation AND platelet aggregation/activation
• e.g. Clopidogrel, Aspirin, Abciximab
Give background to STEMI
ST Elevated Myocardial Infarction
‘White’ thrombus
• FULLY occluded coronary artery
Treatment:
• Antiplatelets & Thrombolytics - reduce lipid formation, platelet aggregation/activation AND dissolve thrombus
• APs e.g. - Clopidogrel, Aspirin, Abciximab
• TLs e.g. - Alteplase
What are (N)STEMI caused by?
- Damage to endothelium
- Atheroma formation
- Platelet aggregation
Difference between Haemostasis, Thrombosis & Atherosclerosis
Haemostasis:
• physiological process
Thrombosis:
• pathophysiological process
Venous thromboses
• RED THROMBI – high fibrin
• Thrombus forms within blood vessel lumen
Atherosclerosis:
• pathophysiological process
Arterial thromboses
• WHITE THROMBI – high platelets
• Thrombus forms within atherosclerotic plaque.
Explain Step 2 of thrombosis - Amplification
STEP 2 - Amplification (platelet activation & aggregation):
(1) Thrombin:
Thrombin activates platelets in a +VE feedback effect via. F2a
(2) Activated platelet:
Changes shape
Platelets become ‘sticky’ & attaches other platelets
Explain the process of Platelet Activation in Step 2: Amplification
- Thrombin binds to the PAR (Protease Activated Receptor)
- PAR activation –> rise in intracellular [Ca2+]
Also, liberates arachidonic acid (AA) which is turned into TXA2 by COX enzymes.
TXA2 induces expression of Glp2b/3a which aids platelet aggregation - Raised [Ca2+] –> exocytosis of ADP dense granules
- ADP binds to another platelet’s P2Y12R –> activates platelet.
(a) ADP receptors
(b) Cyclo-oxygenase (COX)
(c) Glycoprotein IIb/IIIa receptor (GPIIb/IIIa)
Explain the antiplatelet drugs used and for what
(1) Prevent platelet activation/aggregation
= CLOPIDOGREAL (oral)
• ADP ( & P2Y12R) antagonist
(2) Inhibit production of TXA2
= ASPIRIN (oral)
• irreversible COX-1 inhibitor
• high doses NO MORE effective BUT MORE SEs
(3) Prevent platelet aggregation
= ABCIXIMAB (IV, SC)
• GPIIb/IIIa antagonist
• limited use AND only by specialists
Indications for drug use - antiplatelets?
ARTERIAL THROMBI
- acute coronary syndromes - MI
- atrial fibrillation - prophylaxis of strokes
