Thrombosis

Thrombosis

Haemostasis
1. arrest of blood loss from damaged blood vessels-main elements: platelet adhesion & activation, blood coagulation (fibrin formation)
Abnormal function of the haemostatic plug within a blood vessel in the absence of bleeding
1. predisposition:damage to endothelium,poor/turbulant blood flow, Hypercoagulability (genetic/oral contraceptives)
Thrombus
1. Blood clots: forms in static blood in vitro, clots are amorphous & consist of a diffuse fibrin meshwork with random distribution of RBCs & WBCs
2. Thrombi: thrombus forms in vivo, organised aggregates of WBCs & RBCs bound with fibrin, fixed to blood cell wall
  1. many break off & travel as embolus to lodge in small blood vessels-can block vessel causing ischaemia & infarction
3. Arterial thrombus
  1. first step is platelet aggregation induced by:
  2. Collagen-exposed when endothelial cells lining blood vessels are damaged
  3. Thrombin-produced when the blood coagulation cascade is activated
  4. Activated platelets-these produce substances which cause further aggregation (thromboxane A2, 5-HT, platelet activating factor [PAF])
Coagulation cascade
1. soluble fibrinogen converted to insoluble strands of fibrin by thrombin mediated by enzyme cascade involving serine proteases (clotting factors)
2. Vitamin K is required for formation of clotting factors
3. main clotting inhibitor is antithrombin III (neutralises all serine proteases in cascade)
4. Heparin-major cofactor for antithrombin III activity
5. clot lysis mediated by action of plasmin (activated by plasminogen)
Drugs effecting haemostats & thrombosis
1. Anticoagulants
  1. VENOUS THROMBOSIS
  2. prevent formation of thrombi (clots) but won't break down existing ones
    1. heparin-naturally occurring acidic mucopolysaccharide, administered via IV injection=reduces blood clotting by inactivating thrombin via antithrombin
    2. WARFARIN-given orally,interferes with bit K syn (natural coagulation factor)-potential for dangerous drug interactions eg aspirin=increases its effect
2. Antiplatelet drugs
  1. ARTERIAL THROMBOSIS
  2. Aspirin-low doses reduce platelet aggregation by preventing thromboxane A2 formation
  3. Cloridogrel- irreversibly blocks the effects of ADP on platelets
  4. Epoprostenol (synthetic PGIs) given as intravenous infusion-promotes vasodilation, inhibits platelet agg
  5. Endothelial cells: produce substances which prevent adhesion of platelets to endothelial cells (PGI2)
  6. EDRF (endothelium0derived relaxing factor; NO)
  7. Herparin sulphate
3. Thrombolytic drugs
  1. MYOCARDIAL INFARCTION (within 12 hrs) & ACUTE STROKE (within 3 hrs)
  2. can dissolve a thrombus by activating the conversion of plasminogen to plasmin, plasmin then degrades fibrin
  3. Streptokinase: large protein molecule obtained from streptococci cultures. Activates plasminogen
    1. Tissue plasminogen activator (tPA, alteplase); present in endothelial cells. Made recombinantly for drug use
  4. effects can be enhanced by combined administration with low dose aspirin

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	Created by tanitia.dooley about 11 years ago