Term
|
Definition
| what factors make up the extrinsic pathway? |
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|
Term
| kininogen->kallikrein->XII(12)->XI (11) -> IX (9)->VIII |
|
Definition
| what factors make up the intrinsic pathway? |
|
|
Term
| X(10) ->V(5)-> thrombin (II)->fibrin (I) -> XIII(13) |
|
Definition
| what factors make up the common pathway? |
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Term
| inactive enzyme precursoer (proenzyme) activation usually involves proteolytic cleavage. |
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Definition
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Term
| stimulatory proteins, factors V and VIII (5 & 8) |
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Definition
| most clotting factors are trypsin-like proteases, but two are not. what are they and which factors? |
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|
Term
| anionic surfaces are exposed (negatively charged) |
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Definition
| injury to the normally anticoagulant endothelial lining of blood vessels makes it procoagulent. what charge change occurs? |
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|
Term
| Hageman factor, binds directly to anionic surfaces "contact activation" it is a zymogen of the intrinsic pathway. this is the "temporary activation" |
|
Definition
| factor XII, what does it do in its initial activation? |
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|
Term
| contact activated factor XII activates prekalekrein. and forms HMWK complex. kallikerin then activates XII by proteolysis. they are "reciprocally autoactivated." this is the "more permanent" activation of factor XII |
|
Definition
| what is the more permanent activation of factor XII and how does it happen? |
|
|
Term
| prekallikrein-high molecular weight kininogen |
|
Definition
| what does the HMWK complex consist of? |
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|
Term
| factor XI (11-plasmathromoplastin antecendent) via proteolysis in the XI-HMWK complex (inrinsic path) |
|
Definition
| factor XIIa activates what? |
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|
Term
| (aka plasma thromboplastin antecedent)activates factor IX (Christmas factor) by proteolysis (intrinsic path) |
|
Definition
|
|
Term
| factor IX(christmas) in presence of VIIIa(anti hemophillic factor A) by proteolysis activates factor X(stuart-prower) (intrinsic path) |
|
Definition
|
|
Term
| it serves as a carrier for factor VIII in circulation (intrinsic) |
|
Definition
| what does von willebrand's factor (vWF) do? |
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|
Term
| factor 3/thromboplastin = a membrane receptor exposed during vascular trauma/injury. (extrinsic path) |
|
Definition
| what is tissue factor(TF) |
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|
Term
| aka proconvertin, binds to TF, and is activated via protein-protein interaction. further activated by factor Xa (feedback) via proteolysis forming factor VIIa. also activated by factor IIa (thrombin) |
|
Definition
|
|
Term
1. binding to TF (thromboplastin exposed in damaged membrane) protein-protein
2. Xa proteolysis -> VIIa
3. factor IIa (thrombin) |
|
Definition
| what 3 ways is proconvertin (factor VII) activated? |
|
|
Term
| VIIa or VII, incomplex with TF -> proteolysis |
|
Definition
| what activates factor X in the extrinsic path? |
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|
Term
| cleaving a hexapeptide (factor VIIa, VII extrinsic or IXa + VIIIa intrinsic) |
|
Definition
| how is factor X activated (both paths) |
|
|
Term
| stuart prower factor -> complexed with Va(accelerin) catalyzes conversion of prothrombin(II) to thrombin(IIa) |
|
Definition
|
|
Term
| thrombin(IIa) catalyzes conversion of fibrinogen (factor I) to fibrin (Ia) forming the soft clot |
|
Definition
|
|
Term
| transglutamidase/fibrin stabilizing factor catalyzes cross-linking of fibrin monomers to yield the hard clot (accompanied by clot retraction) |
|
Definition
| what does factor XIII do? |
|
|
Term
| prothromb. is cut between disulfide bond near gamma-carboxyglutamate, then the n terminal Gla end is chopped off |
|
Definition
| how is prothrombin converted to thrombin? |
|
|
Term
| 10 gamma-carboxy-glutamyl residues (gla) |
|
Definition
| what is at the n-terminal region of prothrombin? |
|
|
Term
| serine proteases chymotrypsin and elastase |
|
Definition
| what are the 2 chains of thrombin?? |
|
|
Term
|
Definition
| what is the catalytic triad? |
|
|
Term
| Arg-Gly bond in substrate (fibrinogen) -similar to trypsin |
|
Definition
| what bond is cleaved by thrombin? |
|
|
Term
| it is removed from circulation by the liver stimulating de novo synth of Gla proteins and secretion of these proteins into cirulation |
|
Definition
| what happens to activated prothrombin? |
|
|
Term
1. I -> Ia
2. V -> Va
3. VII
4. VIII
5. XIII |
|
Definition
| what are the 5 major roles of thrombin? (things activated by it) |
|
|
Term
| acidic residues: Asp, Glu, tyrosine-o-sulfate |
|
Definition
| what are fibrinopeptides comprised of? |
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|
Term
|
Definition
| what is the arrangement of fibrin monomers? |
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|
Term
| cross linking of lys, and Gln catalyzed by factor XIIIa (transglutamidase) |
|
Definition
| what converts soft -> hard clots? |
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|
Term
|
Definition
| what kind of bond forms between lys and glu? |
|
|
Term
| redox cofactor - catalyzes formation of Gla residues in blood clotting factors II, VII, IX, X and proteins C and S |
|
Definition
| what is the role of vitamin K in Gla proteins? |
|
|
Term
|
Definition
| what factors are bound by calcium? |
|
|
Term
| vitamin K dependent carboxylase |
|
Definition
| what enzyme converts glutamine to gamma-carboxyglutamate? (Glu->Gla) |
|
|
Term
| vit K epoxide and vit K reductase |
|
Definition
| what 2 enzymes participate in the 2 step reduction of vitamin K |
|
|
Term
|
Definition
| draw the vit K dependent carboxylase reaction |
|
|
Term
| dithiol dependent vit K epoxide reductase and vit K reductase |
|
Definition
| converts vit K epoxide back to Vit KH2 |
|
|
Term
| it is a vit K analog that prevents clotting in vivo by inhibiting the reductases |
|
Definition
| what does warfarin/coumadin/dicoumarol do? |
|
|
Term
| thrombin/throbomodulin are activated, Va and VIIIa are inactivated |
|
Definition
| what activates protein C and S and what do they in turn inactivate? |
|
|
Term
| serine protease inhibitor ex: antithrombin III |
|
Definition
|
|
Term
| prevents clotting by assisting antithrombin III in binding to clotting factors, by a factor of about 9,000 for factor IIa, and 17,000 for Xa |
|
Definition
|
|
Term
1. inactivation of Va and VIIIa by protein C
2. Inhibition of thrombin by antithrombin III
3. inhibition of extrinsic pathway by LACl
4. protein Z and ZPI |
|
Definition
| what are the 4 ways coagulation is regulated? |
|
|
Term
| lipoprotein associated coagulation inhibitor aka TF pathway inhibitor (TFPI) or anticonvertin. binds to TF-VIIa-Ca-Xa complex and inhibits factors VIIa and Xa |
|
Definition
|
|
Term
ZPI + PZ = inhibits Xa
ZPI - PZ = inhibits XIa |
|
Definition
| What does ZPI (z dependent protease inhibitor) + or - Protein Z do? |
|
|
Term
| major form of hemophilia, facotr VIII deficient, x linked recessive |
|
Definition
|
|
Term
| minor form of hemophilia, x linked recessive, factor IX deficiency |
|
Definition
|
|
Term
1. adhesion and aggregation at sites of vessel injury
2. phospholipid surface for binding clotting factors |
|
Definition
| 2 main roles of platelets: |
|
|
Term
|
Definition
| what do platelets adhere to? |
|
|
Term
| release of ADP and thromboxane A2 |
|
Definition
| what promotes platelet aggregation? |
|
|
Term
| helps aggregation and forming the plug. binds to receptors GP Ib/IX, and GP IIb/IIIa |
|
Definition
| vWF's role in platelet aggregation |
|
|
Term
bernard-soulier disease -GP Ib/IX
glanzmann's thromboastenia -GP IIb/IIIa
von Willebrand's disease - vWf |
|
Definition
| what are the 3 bleeding tendency diseases and what is deficient? |
|
|
Term
fribrolysis via plasmin
TPA(tissue plasminogen activator) bound to fibrin converts plasminogen to plasmin, causing the fibrin clot to break into soluble fibrin fragments |
|
Definition
| how do blood clots dissolve? |
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