The Dreaded Coagulation Cascade Page Tile可怕的凝血级联页面标题.pptVIP

Anticoagulation 101 Neil A. Lachant, MD Chief, Section of Hematology Director, Thrombosis Program Cooper Cancer Institute Professor of Medicine UMDNJ Robert Wood Johnson Medical School Venous ThrombosisMagnitude of the Problem No national data Incidence 1- 2/1,000 300,000 - 600,000 new cases per year increasing as population ages life expectancy 78 years Incidence of VTE Manifestations 2/3 DVT 50- 80% post-phlebitic syndrome 1/3 pulmonary emboli 30% mortality 30,000 – 60,000 deaths per year Mechanisms of Anticoagulation1 Choice of Anticoagulant What are my goals? Pharmacology Side effects What is Heparin? Heterogenous branched glycosoaminoglycan MW 3,000 – 30,000 kd average 15,000 kd 9 – 90 monosaccharides average 45 highly sulfated How Does Heparin Work? Stearic change in AT-III Heparin/AT-III complex inactivate Xa, IIa, IXa, XIa, XIIa Sugars 1 - 5 bind AT-III Other sugars affect pharmacokinetics affect binding properties to coagulation factors cause problems 1/3 of UFH binds to AT-III Low Molecular Weight Heparin Physiology chemical or enzymatic digest of UFH 15 monosaccharides on average MW 5 kD binds AT-III primarily (not IIa or Xa ) anti-Xa/IIa = 3 - 4 (UFH = 1) Metabolism little cell, protein binding consistent renal clearance T1/2 varies with preparation Theoretical Models for Differential Effects of Heparin and LMWH on Thrombin and Factor Xa A 22 yo female presents with an iliofemoral DVT. Her aPTT is 37 sec (nl 32) and she is found to have a lupus anticoagulant. She weighs 55 kg and her creatinine is 0.5 mg/dl. She is started on weight -based UFH. Her aPTT at 4 hrs is 123 s. She could be anticoagulated by all of the following EXCEPT: 1. Decrease UFH with aPTT goal of 1.5-2.5 x her baseline 2. UFH monitoring heparin level 3. UFH correlating heparin level with the aPTT LMWH without monitoring Fondaparinux without monitoring A 22 yo female presents with an iliofemoral DVT. Her aPTT is 37 sec (nl 32) and she is found to have a lupus a