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46613
Thrombosis
Description
Mind Map on Thrombosis, created by tanitia.dooley on 15/04/2013.
Mind Map by
tanitia.dooley
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tanitia.dooley
about 11 years ago
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Resource summary
Thrombosis
Haemostasis
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
predisposition:damage to endothelium,poor/turbulant blood flow, Hypercoagulability (genetic/oral contraceptives)
Thrombus
Blood clots: forms in static blood in vitro, clots are amorphous & consist of a diffuse fibrin meshwork with random distribution of RBCs & WBCs
Thrombi: thrombus forms in vivo, organised aggregates of WBCs & RBCs bound with fibrin, fixed to blood cell wall
many break off & travel as embolus to lodge in small blood vessels-can block vessel causing ischaemia & infarction
Arterial thrombus
first step is platelet aggregation induced by:
Collagen-exposed when endothelial cells lining blood vessels are damaged
Thrombin-produced when the blood coagulation cascade is activated
Activated platelets-these produce substances which cause further aggregation (thromboxane A2, 5-HT, platelet activating factor [PAF])
Coagulation cascade
soluble fibrinogen converted to insoluble strands of fibrin by thrombin mediated by enzyme cascade involving serine proteases (clotting factors)
Vitamin K is required for formation of clotting factors
main clotting inhibitor is antithrombin III (neutralises all serine proteases in cascade)
Heparin-major cofactor for antithrombin III activity
clot lysis mediated by action of plasmin (activated by plasminogen)
Drugs effecting haemostats & thrombosis
Anticoagulants
VENOUS THROMBOSIS
prevent formation of thrombi (clots) but won't break down existing ones
heparin-naturally occurring acidic mucopolysaccharide, administered via IV injection=reduces blood clotting by inactivating thrombin via antithrombin
WARFARIN-given orally,interferes with bit K syn (natural coagulation factor)-potential for dangerous drug interactions eg aspirin=increases its effect
Antiplatelet drugs
ARTERIAL THROMBOSIS
Aspirin-low doses reduce platelet aggregation by preventing thromboxane A2 formation
Cloridogrel- irreversibly blocks the effects of ADP on platelets
Epoprostenol (synthetic PGIs) given as intravenous infusion-promotes vasodilation, inhibits platelet agg
Endothelial cells: produce substances which prevent adhesion of platelets to endothelial cells (PGI2)
EDRF (endothelium0derived relaxing factor; NO)
Herparin sulphate
Thrombolytic drugs
MYOCARDIAL INFARCTION (within 12 hrs) & ACUTE STROKE (within 3 hrs)
can dissolve a thrombus by activating the conversion of plasminogen to plasmin, plasmin then degrades fibrin
Streptokinase: large protein molecule obtained from streptococci cultures. Activates plasminogen
Tissue plasminogen activator (tPA, alteplase); present in endothelial cells. Made recombinantly for drug use
effects can be enhanced by combined administration with low dose aspirin
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