http://www.medscape.com/viewarticle/754332

DabigatranPosesUniqueProblemsinTrauma达比加群成为创伤治疗的一个罕见难题Verylittlecanbedoneforapatienttakingdabigatran(Pradaxa,BoehringerIngelheim)whosuffersatraumaticinjury,andthisnew,potentiallycatastrophicpredicament--lessofanissueinthewarfarinera--underscorestheneedforroutinesurveillanceofneworalanticoagulantstoincludehemorrhagiccomplicationsandtraumadeaths.
创伤性损伤患者服用达比加群(达比加群酯,勃林格殷格翰公司)后就几乎无药可救了.
这一可能是灾难性的新困局—这个问题在华法林时代并不那么突出—突出反映了对新口服抗凝血药进行出血性并发症和创伤性死亡常规监视的必要性.

SosaytwotraumasurgeonsandanemergencyroomphysicianwhoauthoredaresearchletterappearingintheNovember24,2011NewEnglandJournalofMedicine.
Theywritethatthey'verecentlycaredforseveralpatientstakingdabigatranatthetimeoftheirinjury,allofwhomdied[1].
两位创伤外科医生和一位急诊室医师在2011年11月24日《新英格兰内科学杂志》刊登的研究信中如是说.
信中写道,最近,他们照护了几名受伤时服用达比加群的患者,患者都已死亡.
FirstauthorontheletterDrBryanACotton(CenterforTranslationalInjuryResearch,Houston,TX)spokewithheartwirelateFriday,sayingheknowsthathisviews,asatraumasurgeon,"arealittlebitskewed.
"研究信主笔BryanACotton博士(得克萨斯州休斯顿损伤研究翻译中心)星期五晚些时候对Heartwire说,作为一个外科医生,他知道他的观点"有点偏激.
""Wedon'tseeanythingbutcomplicationswiththesepatients,wedon'tseethepeoplewithwonderfulinteractionswithdabigatran.
Allweseeisthebad,butwhenyoudo,it'sahorriblefeeling.
""我们只看到这些病人得了并发症,我们没有看到达比加群产生奇妙作用的人.
我们看到的都是一些坏东西,但是,当你确实看到时,这种感觉很可怕.
"Cottonsays"youkindofrollyoureyeswhenyouhearthatan[incomingtrauma]patientisonCoumadin,thinking'thisisgoingtoincreasetheirrisk,'butatleastyouknowtherearesomethingsyoucando.
.
.
.
Now,withdabigatran,ifIhearapatientisonPradaxa,IgetchestpainmyselfwhenIhearit.
Allofusdo.
"Cotton说,"当你听到一位(新来的创伤)病人正在使用可密定时,你就会眼珠骨碌碌转,觉得'这会增加风险啊',但是,至少你还知道可以采取点办法……如今,有了达比加群,如果我听说有病人正在使用达比加群酯,我听到这个消息时自己都会感觉胸口紧紧的.
我们大家都会这样.
"Cottonandcolleaguespointoutthattraumaisthefourth-leadingcauseofdeathintheUS,reaching40000deathsperyearamongmenandwomenoverage65.
Whilehemorrhagiccomplicationscanalsobecatastrophicinpeopletakingwarfarin,patientsontheolderdrughavetheedgeoverthosetakingneweroralanticoagulantsinanumberofways.
Cotton及其同事指出,创伤是美国第四大死亡原因,每年有40000名65岁以上老人因此丧命.
尽管出血性并发症对华法林使用者来说也可能是灾难性的,但服用旧药的患者在某些方面总要比服用新口服抗凝血药的患者好.

First,thedegreeofwarfarinanticoagulationcanbeeasilyassessed,whereasnosuchtestsexistfordabigatran.
Second,therearestrategiestorapidlyreversetheanticoagulanteffectofwarfarinusingvitaminK,plasmafactorVIIa,andfactorconcentrates,Cottonetalnote.
Bycontrast,coagulopathyismostly"irreversible"inpatientstakingdabigatran.
首先,华法林的抗凝程度容易评价,达比加群则没有这方面的试验;其次,有多种方法,如使用维生素K、血浆因子VIIa、因子浓缩剂等,可以迅速逆转华法林的抗凝效果.
相反,达比加群使用者的凝血病多数是"不可逆的".

"Currently,theonlyreversaloptionfordabigatranisemergencydialysis(assuggestedinasinglelineinthepackageinsert),"Cottonetalwrite.
"Theabilitytoperformrapiddialysisinpatientswithbleedingwhoseconditionisunstableorinthosewithlargeintracranialhemorrhageswillpresentanincrediblechallenge,evenatlevelonetraumacenters.
""眼下,达比加群的唯一逆转方法是紧急透析(包装说明书有此建议),"Cotton等人写道.
"对出血且病情不稳定病人,或颅内大出血病人,快速透析能力就是一个极大的挑战,即使是在一级创伤中心.
"AmongpatientstakingdabigatranseenbyCottonetal,allappearedtohavenormalcoagulationonconventionaltests,butweregrosslyabnormalusingrapidthromboelastography(rTEG).
Onepatientwhosufferedafallanddevelopedneurologicaldeficitsdiedshortlyafteremergencycraniotomy.
"Unfortunately,evenwiththeaidofrTEG,supportivecareisallthatisavailableintheemergencysetting,"theywrite.
在Cottont等人所诊治的达比加群使用者中,他们的凝血常规试验似乎都是正常的,但快速凝血弹性描记检查(rTEG)总体显示异常.
一位患者摔倒后出现神经性缺损,急诊颅骨切开术后不久就死了.
"不幸的是,即使是有rTEG的帮助,急诊室也只有支持疗法而已,"他们写道.

Intheirletter,CottonandcolleaguesurgetheFDAtoconsiderthe"generalizability"ofstudyfindingsfornew,upcomingoralanticoagulants,andtorequiremorepragmatictrials.
"Westronglyurgethathemorrhagiccomplicationsanddeathresultingfromtraumabeincludedaspartoftheroutinesurveillanceofallnewlyapprovedoralanticoagulants,"theyconclude.
在这封信中,Cotton及其同事敦促FDA考虑即将来临的新口服抗凝血药研究结果的"推广"问题,敦促FDA进行更多的实用试验.
"我们强烈敦促将创伤引起的出血性并发症和死亡纳入所有刚批准的口服抗凝血药的常规监视中,"他们在信的最后说.

CottonsaidheinnowayexpectstheRE-LYinvestigatorstogobackandredotheirtrial,buthebelievesreal-worldtraumaeventsshouldbecapturedintrialsofotheranticoagulantsthatarestillongoing.
Healsowantstraumadeaths,whicharenottypicallycapturedinpostmarketingsurveillance,tobeincluded.
Cotton说,他决不指望RE-LY研究人员倒回去重新试验,但是,他认为,现实的创伤事件应该纳入现在仍在进行的其他抗凝血药试验中.
他还要求将目前尚不包括在售后监视范围内的创伤死亡也包括进去.

Infact,CottonsayshewassurprisedandpleasedtogetacallfromBoehringer-Ingelheimafterhisletterwaspublished,askingfordetailsonthethreepatients,suggestingtheyare"takingthisveryseriously.
"Theyalsotoldhimthatthecompanyisactivelyworkingonanantidotetoreversedabigatran'seffects.
事实上,Cotton说,他很惊奇也很高兴信件刊登后接到了勃林格殷格翰公司的电话,询问三位患者的详细情况,建议他们"非常认真地对待此事".
他们还告诉他,公司正积极研制解毒药,以逆转达比加群的效应.