Anticlotting systems

Question 1

hypercoagulability definition and causes

Answer 1

three different mechanisms to limit and prevent spread of clot formation
defects in these natural mechanisms may lead to high risk of clotting

Question 2

first anticoagulent mechanism - when it acts, what it uses, its consequences

Answer 2

acts during initiation process of clotting
uses plasma protein: tissue factor pathway inhibitor (TFPI)
TFPI is secreted by endothelial cells
TFPI binds to tissue factor-factor VIIa complexes and inhibits their ability to generate factor Xa
-> extrinsic pathway can only produce small amounts of thrombin

Question 3

second anticoagulent mechanism - what it’s triggered by, substances, consequences

Answer 3

triggered by thrombin binding to endothelial cell receptor: thrombomodulin
eliminates procoagulent effects and causes thrombin to pind plasma protein C
activated protein C w/ another plasma protein inactivates factors VIIIa and Va

Question 4

third anticoagulent mechanism - substance used, binding, consequences

Answer 4

plasma protein: antithrombin III inactivates thrombin and other clotting factors
antithrombin III activity is enhanced when binding to heparin - substance on surface of endothelial cells
prevents spread of clot by inactivating clotting factors carried away from site by flowing blood

Question 5

procoagulent actions of thrombin

Answer 5

cleaves fibrinogen to fibrin
activates clotting factors XI, VIII, V and XIII
activates platelets

Question 6

anticoagulent actions of thrombin

Answer 6

binds to thrombomodulin
activates protein C
protein C inactivates VIIIa and Va

Question 7

fibrinolytic system function

Answer 7

dissolves a clot after it’s formed

Question 8

fibrinolytic system mechanism

Answer 8

plasma proenzyme: plasminogen activated to enzyme plasmin by plasminogen activators
plasmin digests fibrin and dissolves clot

Question 9

example of a plasminogen activator

Answer 9

tissue plasminogen activator (t-PA)
secreted by endothelial cells
weak enzyme in absence of fibrin
last of anticlotting functions exerted by endothelial cells

Question 10

t-PA and fibrin

Answer 10

plasminogen and t-PA bind to fibrin and become incorporated in clot
fibrin increases ability of t-PA to to catalyse plasminogen to plasmin