Tuesday, December 18, 2007

Chap 34: Drugs used in coagulation I - basic principles

BLOOD COAGULATION CASCADE
Intruduction
- end products - fibrin formation
- central role - thrombin
- thrombin
  • cleaves peptides from fibrinogen to convert it into fibrin clot
  • activates upstream clotting factors - more thrombin formation, activates factor XIII that stabilises clot
  • platelet activator
  • activates protein C pathway - enhances anticoagulation efx --> no thrombosis causing downstream ischaemia
Initiation of clotting - the tissue factor-VIIa complex
- main initiator = factor VIIa (TF)
- tissue factor

  • transmembrane protein
  • expressed outside vasculature, intravascularly not active
  • exposure to damaged endothelium/blood = binding of factor VIIa + TF = complex --> activation of factor X, IX
- coagulation happens in activated cell surfaces mediated by Ca2+ --> EDTA is a chelator, used in test tubes
- antithrombin (AT) - endogenous anticoagulant --> inactivates IIa, IXa, Xa, XIa, XIIa
- Prot C & S - endogenous anticoagulant --> inactivates Va, VIIIa
- factor V leiden = mutation of factor V = resists inactivation by protein C + S --> thrombophilic

Fibrinolysis
- fibrin digestion by plasmin
- injury --> endothelium releases t-PA --> activates plasminogen to plasmin --> remodels thrombus and limits extension
- t-PA, urokinase, streptokinase - activates fibrinolytic system
- aminocaproic acid - inhibits fibrinolysis
- heparin + oral anticoagulants --> do not affect this pathway

No comments: