Hemostasis and Thrombosis Flashcards
thrombosis
inappropriate activation of normal clotting processes in uninjured vessels or thrombotic occlusion after minor injury
hemorrhage
defects in hemostatic plug formation
steps of clot formation
- neurogenic vasoconstriction in response to injury
- platelets recruited to injury. adhere to subendothelial matrix and are activated
3 phospholipid membrane forms upon which clot forms
4 thrombus formation
function of epithelial cells
maintain blood fluidity
regulate vessel tone- promote vasodilation
prevent aggreation
how do epithelial cells maintain blood fluidity
prevent interaction with adhesive proteins like collagent, tissue factor
secretes heparin like molecules
modulates fibrinolysis
tissue factor
membrane protein in smooth muscle, fibroblasts, macrophages, etc.
recognized as nonself trigger for coagulation
platlets
formed by megakaryocytes
dense bodies: ADP, ATP, serotonin, calcium
a-granule: VWF, Factor 5, factor 4, fibrinogen
the three As
platelet heomostasis
adhesion to subendothelium mediated by vWF
activation
aggregation- fibrinogen cross links, phospholipids exposed, and mechanical contraction
concept of antiplatelet therapy
prevents diseases like ischemic heart disease, CAD
aspirin- blocks COX1 in platlets
NSAIDS- blocks COX1
Plavix- blocks ADP receptor
Reopro: block GPIIb/IIIa
vonwillebrand factor
made and stored in endothelial cells and a-granules of platelets
constituitively secreted, and secreted by activation
vonwillebrand functions
adhesion- conformational change
aggregation- binds GPIIb/IIIa
factor 8- protects from cleavage and giudes to site of hemorrhage
which coagulation enzymes are vitamin k dependent?
factors 2, 7, 9, and 10
intrinsic pathway
factor 12 -> 12 a 12a activates 11 -> 11a 11a activates 9 -> 9a 9a in the presence of 8a and Ca 10 -> 10a 10a in the presence of 5a and Ca activates 2 -> 2a 2a in the presence of Ca activates fibrinogen to fibrin fibrin in the presence of 13 = crosslinked fibrin = clot
extrinsic pathway
TF and factor 7a activate
10 -> 10a
10a in the presence of 5a and Ca activates
2 -> 2a
2a in the presence of Ca activates
fibrinogen to fibrin
fibrin in the presence of 13 = crosslinked fibrin = clot
in vivo pathway
when TF comes in contact w/ 7a, activates
9 -> 9a
9a in the presence of 8a activates
10 -> 10a
10a in the presence of 5a and Ca activates
2 -> 2a
2a in the presence of Ca activates
fibrinogen to fibrin
fibrin in the presence of 13 = crosslinked fibrin = clot
thrombin master conductor activates
factor 9a, 8 to become 8a, 5 to become 5a, platelets, fibrinolysis, and fibrin
what does 13 do?
stabilizes clot by crosslinking lysine and glutamine side chain in the fibrin polymers
quaternary complex
enzyme + cofactor assembled on phospholipid surface by calcium ions
improves efficiency of clotting
mechanisms for localized clots
anticoagulate systems to prevent clotting of entire vascular tree
endothelial derived (heparin like), thrombomodulin, tissue plasminogen, etc)
coumadin
vitamin K antagonist, decreases factors 2 7 9 10
heparin
inhibits factor 10
t-PA, urokinase, streptokinase
fibrinolytic agents to lyse clot
anticoagulant mechanisms
antithrombin system
protein c system
fibrinolytic system
antithrombin
in presence of heparin like molecules, under goes conformational change that acts on thrombin and prevents it from acting further
protein c system
thrombomodulin- endothelial bound protein binds protein C (vit K dependent). protein S is a cofactor of protein C
protein C inactivates 5 and 8
fibrinolytic system
plasminogen (t-PA- tissue type, protein bound; u-PA- urokinase type, made in kidney, free in plasma)- converted to plasmin
cleaves fibrin
plasminogen activator inhibitr
inactivates excess plasminogen
secreted by endothelial cells
alpha-2-antiplasmin
inactivates excess plasmin
secreted by endothelial cells
