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Session 4
Bleeding Disorders (Hemophila, thrombophilia etc...)
22
Medical
Graduate
02/18/2011

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Cards

Term
Primary hemostasis
Definition
-platelet plug formation
-damaged endothelial cells interact with platelets via von Willebrand's factor
Term
von Willebrand Factor
Definition
-large glycoprtn
-mediates platelet adhesion to exposed extracellular matrix when the endothelial lining of the blood vessel is damaged (in plasma and extracellular matrix)
-adhered platelets become activated by agents (thrombin and thromboxane) increased the calcium concentration of platelet
Term
Secondary Hemostasis
Definition
-Formation of cross-linked fibrin clot through a series of proteolytically activated enzymes (clotting factors)
-initiated by activated platelets and factors released from dammed tissue
-takes place on surface of aggregated, activated platelets (initially and most efficiently)
Term
4 Major players of clot formation:
Definition
1. Endothelial Cells: (inhibit blood clotting, produce prostacyclin which is an inhibitor of platelet adhesion and aggregation b/c when endothelium is in tact, don't want clot formation)
2. Subendothelial Tissue: (not normally exposed or in contact w/blood, platelets and clotting factors bind to this tissue)
3. Platelets: (release protons and vasoactive amines after binding to the subendothelial tissue, clotting Factors before active on the surface of these activated platelets
4. CF: (plasma protons which create a protelolytic cascade which ends with the production of insoluble fibrin from soluble fibrinogen)
Term
Fibrin
Definition
-aggregation of platelets alone isn't enough to seal large injury
-fibrin is not normally found in blood but its precursor (fibrinogen) is present and when cleaved by protease thrombin = fibrin
Term
Thrombin
Definition
FINISH
Term
Cross linking is catalyzed by:
Definition
Transglutaminase, Factor 13
Term
Thrombin & Where VIT K enters
Definition
-formation lmtd to side to injury.
-activated from prothrombin from Factor Xa
-rxn = thrombin and inactive fragment
-inactive fragment contains 10 residues of gamma-carboxyglutamate (these are produced by hepatocytes by a rxn req VIT K)
Term
Can factor X be activated by intrinsic and extrinsic pathways?
Definition
YES
Term
Extrinsic pathway has 1 factor...
Definition
Factor VIIa (active only in presence of tissue factor, a membrane glycoprtn exposed after injury of blood vessel)
Term
Does the intrinsic pathway req a (+) charged surface to activate?
Definition
NO, requires (-)
Term
CLassic example of extrinsic pathway?
Definition
stab wound
Term
Not a gross vascular damage from outside, might be a microtear or plaque causing issues, what is it?
Definition
example of intrinsic pathway
Term
Contact Phase Activation
Definition
*initiating rxn of the intrinsic pathway
-REQ 2 proteases: 1. kallikrein and 2. factor XIIa
-also REQ

FINISH
Term
Which steps req Ca
Definition
prothrombin-->thrombin
x-->xa
IX--IXa

more??
Term
Antithrombin III
Definition
*most IMP inhibitor of clotting
*activated by heparin
*most proteases of the intrinsic and extrinsic pathways are inhibited by ATIII and heparin
Term
Plasmin
Definition
-degrades fibrin clot
-from inactive precursor plasminogen which binds fibrin clot with high affinity
-fibrin complex can be activated by tissue type plasminogen activator (tPA)
* a serine protease that also binds to fibrin

FINISH
Term
Plasminogen activated by
Definition
tPA
1. urokinase
2. streptokinase (activates allosterically without proteolytic cleavage)
*with acute MI within an hour
Term
Clotting can be inhibited by removal of what ions?
Definition
Ca
Term
Which factors are Vit K dependent?
Definition
Factor 2, 7, 10
Term
Assess blood clotting
Definition
1. bleeding time
2. aPTT
3. PT
Term
What test measure heparin and coumadin efficacy?
Definition
aPTT will be used to measure the efficacy of heparin (intrinsic and common)
PT measure the efficacy of coumadin (extrinsic and common)
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