HEPARININDUCEDTHROMBOCYTOPENIAUniversityofheparininduced血小板減少大學PPT學習教案

1、會計學1HEPARININDUCEDTHROMBOCYTOPENIAUniversityofheparininduced血小血小板減少大學板減少大學第1頁/共51頁第2頁/共51頁Blood 2012; 119: 2209第3頁/共51頁Presenting with thrombosis (n=65)Presenting with no thrombosis (n=62)Total (n=127)Age67 10.766.7 12.367.0 11.4Male/Female27/3833/2960/67SURGICAL PTS513384 (66.1%) Orthopedic251540 C

2、ardiovascular10919 Oncology7613 General628 Neurosurgery314MEDICAL PTS142943 (33.9%) Cardiac61016 DVT or PE4711 Other41216Warkentin and Kelton, Am J Med 1996;101:502第4頁/共51頁Type of thrombosisPts presenting with thrombosis (n=65)Pts presenting with only thrombocytopenia (n=62)VENOUS (n=78)5424 DVT (n=

3、61)4021 New3521 Progression40 Recurrence10PE (n=32)266 New255 Recurrence11ARTERIAL (n=18)126 Limb72 Myocardial infarct31 Thrombotic stroke23Other (n=3)12 Sudden death01 Adrenal hemorrhage11 NO THROMBOSIS (n=30)NA30第5頁/共51頁Am J Med 1996;101:502Over 50% of patients presenting with “isolated HIT” had a

4、 subsequent thrombotic episode within 30 daysSubstitution of warfarin for heparin after the onset of thrombocytopenia did not prevent thrombosis 第6頁/共51頁Warkentin et al, NEJM 1995;332:1330第7頁/共51頁Warkentin et al, NEJM 1995;332:1330Odds ratio for thrombosis 37 times higher in HIT pts第8頁/共51頁All cases

5、 in patients receiving UFH as prophylaxisHIT associated with 40-fold increase in risk of thrombosisGirolami et al, Blood 2003;101:2955第9頁/共51頁Prandoni et al, Blood 2005;106:3049(29% vs 2.4%)第10頁/共51頁Lubenow, N. et al. Blood 2010;115:1797-1803第11頁/共51頁Warkentin et al, NEJM 1995;332:1330第12頁/共51頁*Wark

6、entin et al, NEJM 1995;332:1330*Thrombotic episode第13頁/共51頁Warkentin and Kelton, NEJM 2001;344:1286第14頁/共51頁Warkentin and Kelton, NEJM 2001;344:1286第15頁/共51頁Warkentin et al, NEJM 1995;332:1330第16頁/共51頁days11 patients re-treated with heparin: all had clinical deterioration and worsening thrombocytope

7、nia3 patients diedAnn Intern Med 2002;136:210第17頁/共51頁第18頁/共51頁Platelet membraneFC receptorFabFCAntibody binding to platelet FC receptor activates platelet41PF4Activated plateletsecretes PF42HeparinPF4 binds heparin3Antibody binds heparin-PF4 complex第19頁/共51頁Warkentin, Brit J Haematol 2003;121:5351.

8、Heparin-PF4 complexes stimulate antibody production2.Ag-Ab complex binds to and activates platelets, monocytesSize of immune complex is critical, varies with PF4 and heparin concentrationsInhibited by high heparin concentrations3.Activated platelets release procoagulant microparticles4.Activated mon

9、ocytes produce tissue factor5.Antibodies may cross-react with PF4 bound to endothelial cell heparan sulfate vessel wall injury6.Some HIT antibodies can activate platelets in the absence of heparin第20頁/共51頁Blood 2007;110:4253Low heparin:PF4 ratio small complexesHigh heparin:PF4 ratio small complexes1

10、:1 heparin:PF4 large complexesCharge of complexesHeparin conc第21頁/共51頁Blood 2007;110:4253J Thromb Haemost 2012;10:1446第22頁/共51頁J Thromb Haemost 2005;3:2168第23頁/共51頁第24頁/共51頁第25頁/共51頁1.Median platelet nadir 55K2.15% had nadir 150K (diagnosed because platelet count fell more than 50% or because of cli

11、nical events)3.The severity of thrombocytopenia did not predict thrombotic eventsWarkentin, Brit J Haematol 2003;121:535第26頁/共51頁Blood 2012;119:2209第27頁/共51頁Score% Testing positive534%第28頁/共51頁第29頁/共51頁SRA and EIA positiveSRA and EIA negativeEIA positive, SRA negativeAm J Hematol 2007;82:1037第30頁/共5

12、1頁Warkentin, Brit J Haematol 2003;121:535 第31頁/共51頁J Thrombos Haemost 2004;2:2133-7OD values in HIT vs HITT patientsThrombosis-free survival vs OD第32頁/共51頁第33頁/共51頁第34頁/共51頁 (Refludan)Recombinant form of leech anticoagulantClearance mainly renal (avoid in renal failure); halflife normally 80 minAnti

13、body formation may cause drug accumulation or anaphylaxis (rare) (Novastan)Synthetic arginine derivativeClearance mainly hepatic (can use in renal failure); halflife 40-50 minBoth given by continuous iv infusion, monitoring aPTTCoagulopathic patients (long baseline aPTT) difficult to monitorNo antid

14、ote for either drug第35頁/共51頁% with:Lepirudin treated patientsControlspNew thrombosis4.414.9.02Limb amputation3.30.24Death14.321.3.094Combined end point19.829.8.028第36頁/共51頁Cumulative incidence of death, thromboembolism or limb amputationCumulative incidence of major bleedingJ Thromb Haemost 2005; 3:

15、2428第37頁/共51頁J Thromb Haemost 2005; 3:2428第38頁/共51頁第39頁/共51頁Chest 2006;129:1407第40頁/共51頁第41頁/共51頁(Arixtra) Rare reports of fondaparinux-associated HIT (NEJM 2007; 356:2653)第42頁/共51頁ReferenceNNew thrombosisMajor BleedingKuo & KovacsThromb Haemost 200550/50/5Lobo et alThromb Haemost 200770/70/7Grouzi et alClin Appl Thromb Haemost 2009240/240/24Pooled Data360/360/36Warkentin, Hematol Oncol Clin N Am 2010; 24:755第43頁/共51頁第44頁/共51頁