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低分子肝素英文
5/00
MedS
1
Low-Molecular-Weight HeparinandUnfractionated Heparin
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MedS
2
The Coagulation Cascade
Central to the coagulation cascade is the generation of thrombin (factor IIa)
thrombin is generated from prothrombin by the action of activated factor X (Xa)
thrombin then acts on fibrinogen to generate fibrin clot
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MedS
3
Coagulation Cascade
XIIa
XIa
IXa
Intrinsic Pathway
(surface contact)
Xa
Extrinsic Pathway
(tissue factor)
VIIa
Thrombin (IIa)
Thrombin-Fibrin
Clot
aPTT
PT
Heparin / LMWH(AT-III dependent)
Hirudin/Hirulog(direct antithrombin)
Courtesy of VTI
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MedS
4
THROMBOSIS
Collagen XIa
Tissue Factor IXa
Platelet Clumping
Thrombus Formation
Thrombus Growth
HEMOSTASIS
Tissue Factor Collagen
Platelet Aggregation
Platelet-rich
Hemostatic Plug
Xa
Fluid
Thrombin
HEP
HEP HIR
Heparin Inhibits Hemostasis
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MedS
5
The Procoagulant State in Thrombolysis
Amplification
Vascular Injury
Activation of Platelets
And Coagulation
Xa
Thrombin (IIa)
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MedS
6
Low-molecular-weight heparin
UH (mw 3k - 30k) is a heterogeneous mixture of polysacchride chains (glycosaminoglycans)
LMWH (mw 5k) is obtained by alkaline degradation of heparin benzyl ester
LMWH molecules are enriched with short chains with higher anti-Xa:IIa ratio
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7
Mechanism of Action
Both UH and LMWH exert their anticoagulation activity by catalyzing antithrombin (AT or AT III)
catalyzed AT is accelerated in its inactivation of the coagulation enzymes thrombin (factor IIa) and factor Xa.
prolongs aPTT
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8
There are two heparin-cofactors, Antithrombin (AT) and Heparin Co-factor II (HC II).
AT is an effective antithrombin
but HC II is a very weak antithrombin
AT
HC II
++++
- - - -
Interaction of Heparin Co-Factors with Thrombin
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9
AT
HC II
++++
- - - -
Interaction of Heparin Co-Factors with Thrombin
Heparin has a higher affinity for AT than for HC II and there is more AT in plasma than HC II
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MedS
10
AT
Free Thrombin
Antithrombin and Free Thrombin
AT alone does
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