Term
Functions of the circulating components of hemostasis
-role of von Willebrand factor |
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Definition
Endothelial injury exposes thrombogenic subendothelial ECM, faciliating platelet adherence and activation --> platelet shape change, release of secretory granules
Aggregation, collagen fibers, hemostatic plug
Primary hemostasis
-mediated primarily by vWf (produced in endothelial cells and megakaryocytes)
Platelet adhesion = "platelet plug"
mediated via interactions with vWf |
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Term
| Functions of the tissue components of hemostasis |
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Definition
Tissue factor is exposed at the site of injury
- factor III aka thromboplastin
Acts in conjunction with factor VII to initiate coagulation cascade
--> thrombin generation
cleaves circulating fibrinogen --> fibrin
secondary hemostasis - coag factors |
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Term
| Actions of the components of the fibrinolytic systems |
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Definition
Antithrombotic
Endothelial cells synthesize tissue-type plasminogen activator (t-PA), cleaves plasminogen --> plasmin, which cleaves fibrin to degrade thrombi |
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Term
Actions of the factors controlling blood coagulation
-antithrombosis
-prothrombosis |
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Definition
Antiplatelet: PGI2, NO, ADPase
Anticoagulant: heparin-like molecules, thrombomodulin (activates Protein C, inactivates Va & VIIIa), tissue factor pathway inhibitor, antithrombin-III
Fibrinolytic: t-PA
Platelet: platelets interact with vWf
Procoagulant: in response to cytokines or bacterial endotoxin, endothelial cells make tissue factor, activates extrinsic pathway; augments IXa & Xa
Antifibrinolytic: activated EC secrete inhibitors of plasminogen activator, limit fibrinolysis, favor thrombosis |
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Term
| Tests used to monitor blood coagulation |
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Definition
Bleeding time: most general test of *platelet function*
Prothrombin time (PT): measures the function of *extrinsic pathway,* also a good indicator of prognosis for pts with hepatocellular disease
-factors III, VII, X, V, II, I
Partial thromboplastin time (PTT): measures the function of *intrinsic pathway*
-factors III, XII, XI, IX, VIII, X, V, II, I |
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Term
Actions of the most commonly used agents to control blood coagulation
-to reduce clotting
-to facilitate clotting |
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Definition
REDUCE CLOTTING:
Anticoagulants: heparin, coumadin, Ca++ chelators
-heparin combines with AT-III, then inhibits thrombin activity
-coumadin is a vit K antagonist (II, XII, IX, X)
Antiplatelet: aspirin
Thrombolytics: t-PA, streptoK, uroK
FACILITATE CLOTTING:
Replacement factors: VIII (Hemophilia A), IX (Hemophilia B), XI (Hemophilia C)
Plasminogen inhibitors: aminocaproic acid |
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Term
| The final three steps of blood coagulation |
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Definition
1. Prothrombin activator is formed (factor Xa, Ca++, PF3, factor V)
2. Prothrombin --> thrombin
3. Thrombin facilitates the joining of fibrinogen into a fibrin mesh
-(I) --> fibrin
-fibrin, along with Ca++, VIII --> VIIIa
-VIIIa stabilizes polymer |
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Term
PLATELETS
-adhesion
-secretion
-aggregation |
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Definition
"Platelet plug," vWf, bridges GP Ib and collagen
"release rxn"
granules release ADP, Ca++, vasoactive substances
production of phospholipid complex (for binding Ca++) and shape change
Platelet-platelet adherence promoted by ADP, TxA2, thrombin
Results in reversible "primary plug"
Thrombin converts fibrinogen to fibrin, "glues" platelets together, stabilized by VIIIa
Platelet contraction creates irreversible secondary plug |
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Term
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Definition
The function of most of the coagulation factors
Highly specific
Prothrombin, X, IX, trypsinogen |
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Term
What are the four regulators of fibrin formation?
What is the action, effect of each? |
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Definition
Tissue factor pathway inhibitor (TFPI):
-inhibits VIIa (tissue factor)
-inhibits thrombin formation
SERINE PROTEASE INHIBITORS
-neutralize thrombin & factor Xa
-inhibit thrombin formation & activity
PROTEIN C
-proteolysis (not limited) of Va & VIIa
-inhibits thrombin formation
FIBRINOLYTIC SYSTEM
-proteolysis (not limited) of fibrin
-removes excess fibrin clot |
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Term
Regulation of excess coag: fibrinolytic system
Function of the fibrinolytic system
Why is circulating plasmin usually not in detectable quantities? |
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Definition
tPA converts plasminogen --> plasmin (limited proteolysis)
-tPA req's fibrin as cofactor
-tx with tPA --> blood can flow; can counteract acute MI
*Plasmin* degrades fibrin clots & fibrinogen by non-limited proteolysis (req's fibrin!)
Urokinase and streptokinase, like tPA, activate plasminogen (but don't require fibrin as cofactor)
-aminocaproic acid inhibits uroK
"brakes" the clotting system
causes the dissolution of fibrin
cleans up fibrin debris
anti plasminogen activators are normally present in plasma
in some pathologic states, fibrinolytic crisis may develop |
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Term
What activates thrombin?
What's the last step of the coagulation cascade? |
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Definition
Prothrombin activator
-Xa
-Ca++
-PF3
-Va
Factor XIII - solidifies fibrin clot
-factor XIII is activated by fibrin in the presence of Ca++ |
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Term
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Definition
tissue destruction, sepsis, endothelial injury => release of tissue factor
tissue factor, platelet aggregation => widespread microvascular thrombosis
--> consumption of clotting factors, platelets -> bleeding
--> vascular occlusion -> microangiopathic hemolytic anemia, ischemic tissue damage
--> plasmin activation
-> proteolysis of clotting factors -> bleeding
-> fibrinolysis -> FSPs -> inhibition of thrombin, platelet aggregation, fibrin polymerization |
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