低分子肝素英文

1、5/98MedSlides1 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 5/98MedSlides2 Coagulation Cascade XIIa XIa IX

2、a 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 5/98MedSlides3 THROMBOSIS Collagen XIa Tissue Factor IXa Platelet Clumping Thrombus Form

3、ation Thrombus Growth HEMOSTASIS Tissue Factor 337:447-452 5/98MedSlides22 1.0 mg/kg q 12 h 30 days Enox Hep Incidence of death, MI, angina 14 d 16.6% 19.8% p=.019 30 d 19.8% 23.3% p=.016 Minor bleeding 30 d 13.8% 8.8% p.001 Major bleeding 30 d 6.5% 7.0% NS Death alone 14 d 2.2% 2.3% NS 30 d 2.9% 3.

4、6% NS 5/98MedSlides23 43 days 5/98MedSlides24 TIMI 11B LMWH in Unstable Angina 4,021 pts with acute coronary syndrome Two treatment groups: UFH: 70 U/kg bolus 15 u/kg/hr iv LMWH: 30 mg bolus 1 mg/kg s.q. bid Primary endpoint (death, MI, urgent revascularization) 48-72 hr26% 14 days15%p0.03 Circulati

5、on 1999; 100:1593-1601 5/98MedSlides25 Meta-Analysis ESSENCE and TIMI 11B Primary endpoint Death / MI / Urgent Revscularization Odds ratioRisk Reductionp-val Day 8 0.7121%0.02 Day 14 0.7921%0.0005 Day 43 0.8020%0.0006 European Society of Cardiology - August 1998 5/98MedSlides26 Primary Endpoint : Da

6、y 43 Death/MI/Urgent Revasc 00 22 44 66 88 1010 1212 1414 1616 1818 2020 004488121216162020242428283232363640404444 P=0.048 RRR 12 % P=0.048P=0.048 RRR 12 %RRR 12 % UFHUFH UFH ENOXENOX ENOX 19.7 %19.7 %19.7 % 17.3 %17.3 %17.3 % % DaysDaysDays 5/98MedSlides27 Difference Between Lovenox and Heparin Lo

7、venoxHeparin Half-life (hr) 4.5 dose-dependent Anti-Xa:IIa 14:1 1:1 Molecular wt (avg) 4,500 15,000 Time to peak activity 3-5 2-4 Dosing units mg IU 4/00MedSlides28 Enoxaparin in DVT Prophylaxis DOSAGEDURATION in patients undergoing30 mg q12h SCaverage duration: 7 to 10 days hip-replacement surgeryi

8、nitiate 12-24h postopup to 14 days 40 mg qd SC initiated 12h (3) preop extended prophylaxis in40 mg qd SC3 weeks post discharge hip replacement in patients undergoing30 mg q12h SCaverage duration: 7 to 10 days knee-replacement surginitiate 12-24h postop in patients undergoing40 mg qd SCaverage durat

9、ion: 7 to 10 days abdominal surgeryinitiate 2h preop 4/00MedSlides29 Enoxaparin in Treatment of in acute DVT with or without PE DOSAGEDURATION For patients who can be1 mg q12h SCcontinue LOVENOX for a treated at home for acute initiate warfarin sodiumminimal of 5 days and until DVT without PEtherapy

10、 when appropriatea therapeutic oral anticoagulant (usually within 72h ofeffect has been achieved (INR Lovenox administration)2.0 to 3.0). average duration: 7 days For hospitalized patients 1.5 mg/kg qd SC at the with acute DVT with or same time every day or without PE1 mg/kg q12h SC 4/00MedSlides30

11、Enoxaparin for UA and non-Q MI DOSAGEDURATION For the prevention of1 mg/kg q12h SCminimum 2 days; usual duration ischemic complicationswith oral aspirin therapyof therapy: 2 to 8 days of unstable angina and(100 to 325 mg once daily) non-Q-wave myocardial infarction (MI) when concurrently administere

12、d with aspirin 5/98MedSlides31 Economic Assessment of LMWH vs UFH Results from the ESSENCE Trail enoxaparin heparin Need for coronary angioplasty (initial)15%20% p=.04 coronary angioplasty (30d)18%22% p=.08 diagnostic cath (30d)57%63% p=.04 Initial hospitalization mean drug cost in U.S.*$155$80 mean

13、 total cost of care$11,857$12,620 mean duration of treatment 2.3 days mutidose vial enoxaparin - 1 mg/kg at $0.38/mg Circulation 1998;97:1702-1707 5/98MedSlides32 References Low-molecular weight heparins. Weitz JI. N Eng J Med 1997;337:688-698. Biochemistry and pharmacology of low molecular weight heparin. Rosenberg RD. Semin Hematol 1997;34(suppl 4):2-8. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionaed heparin. Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS