Hemostasis Flashcards
efficient platelet adhesion to ECM requires what factors?
- vWF (subendothelial ECM)
2. GpIb (platelet)
what links the platelet to the endothelium?
vWF
besides platelets, what else does vWF bind? what is the purpose?
- factor VIII (coagulation factor)
2. prolongs half life, localizes it
where is integrin a2b1 found? what does it do?
- platelet
2. helps adherence to ECM
what causes the dramatic shape change of activated platelets?
Ca2+ signal
what is the role of TXA2 in the blood?
- vasoconstriction
2. platelet activation signals
how is TXA2 made?
- arachadonic acid release upon platelet activation
- arachadonic acid + COX = PG2
- PG2 gives rise to TXA2
what are the roles of ADP in the blood?
- platelet activation
- triggers change in GpIIb - GpIIIa receptor on platelets - allows receptor to bind fibrinogen for initial plug formation
what is the most common bleeding disorder?
vWF disease
how is vWF disease managed?
desmopressin - releases vWF from storage sites in endothelium
what characterizes bernard-soulier syndrome? pathogenesis?
- platelets fail to aggregate in response to stimuli
2. defect in interaction between vWF adn GpIb
what characterizes glanzmann thrombasthenia? pathogenesis?
- platelets fail to aggregate in response to various stimuli
- defect in GpIIb and / or GpIIIa
the coagulation cascade ultimately leads to activation of what compound?
thrombin
the intrinsic and extrinsic pathways converge on the activation of what factor?
factor X (results in activation of thrombin)
what is the key regulator of coagulation?
factor X
partial thromboplastin time test tests which arm of the coagulation cascade?
intrinsic
prothrombin time test tests which arm of the coagulation cascade?
extrinsic
where is factor VIII produced?
endothelium
prothrombin and factors VII, IX, and X contain which modified amino acid residue?
carboxyglutamate
what is the role of caroboxyglutamate?
- chelates Ca2+
- bound Ca2+ binds negatively charged membrane lipids
- clotting factors are active when bound to cell membranes
- restricts clot formation to site of injury
what is responsible for restricting clot formation to the site of injury?
carboxyglutamate
what is required for carboxylase to to convert glutamate to carboxyglutamate?
vitamin K
warfarin inhibits what enzyme? what is the result?
- vitamin k epoxide reductase
2. prevents regeneration of vitamin k
what forms the extrinsic Xase complex?
X + VII + III
what is the role of the Xase complex?
activation of X
what is the role of factor Xa?
slow cleavage of prothrombin to make thrombin
which factors does thrombin activate?
V, fibrinogen, VII, VIII to sustain and accelerate extrinsic pathway
what makes up the prothrombinase complex?
X + Va
what is the role of the prothrombinase complex?
RAPID cleavage of prothrombin to make thrombin
what does the intrinsic Xase complex do?
rapid activation of thrombin
what is the role of transglutaminase?
forms bonds between lysine and glutamine in fibrin monomers - generates hard cross linked clot
hemophilia A is a deficiency in what factor?
VIII
hemophilia B is a deficiency in what factor?
IX
what are the endogenous anticoagulant activities?
- thrombin
- protein C and S
- serpins
- TFPI
what does thrombomodulin do?
- alters thrombin
- thrombin/thrombomodulin activates protein C
- C binds S
- C/S degrades Va and VIIIa - blocks clotting
what is the significance of factor V Leiden?
resistant to cleavage by protein C - hypercoagulation
what do the serpins do?
- inhibit activated forms of coagulation factors
2. binds antithrombin III and heparin
what does TFPI do?
- inhibits VIIa - blocks extrinsic
2. inhibits Xa
what degrades fibrin?
plasmin
what stimulates TPA release?
protein C
what does streptokinase do?
activator of plasminogen - breaks up clots
