Chapter_24 Prophylaxis Against Venous Thromboembolism

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  • 7/28/2019 Chapter_24 Prophylaxis Against Venous Thromboembolism


    Prophylaxisgai stVenoushromoembolsmIntroductionRisk FactorsMethodsof DVTProphylaxisAnticoagulation nd RegionalAnaesthesiaPulmonary hromboembolismFurtherReading

    INTRODUCTIONPulmonaryembolism s a relatively rare causeof death in the generalpopulation.However, everalperioperativeactorscontributeo the Vlrchow'sriad - venous tasis,abnormalcoagulationand intimal damageof bloodvessels which predisposesovenous hromboembolism.n the absenceof prophylacticmeasures, he reportedincidence f postoperativeatal pulmonaryembolism anges rom 0.1% o 5o/o.Thromboprophylaxis,r DVT prophylaxisas it is more commonlyknown,encompasses seriesof management trategiesaimedat reducing he occurrence fthromboembolichenomena.t shouldbe rememberedhat while prophylaxisagainstpotentiallyatalpulmonary mbolis the maingoal,prophylaxiso preventate sequelaeof extensive eepvein thrombosis swellingof the legs,varicose eils, ulcerationandother rophic changes are also mportant considerations.



  • 7/28/2019 Chapter_24 Prophylaxis Against Venous Thromboembolism



    Theseare someof the terms used o describehis groupof disorders.Venous hromboembolismVTE): a broad term that refers to all aspectsofthrombosisand embolismhat occur n the venoussystem.Deepvenous hrombosis DVT): hrombosiswithin the deep imb veins.Pulmonaryembolism (PE): embolism o the pulmonaryvasculatureof anysubstance uch asblood clots,gas, at, amniotic luid.Pulmonary hromboembolismPTE):embolism o the pulmonaryvasculatureofblood clots or thrombi,usually (80-90%of cases) rom the proximaldeepveinsof the lower limbs andpelvicveins.

    RISKFACTORSSee able 4-1".heseactorsredisposehepatientoperioperativehromboemboli

    Patient factors. Age > 40 years (risk increaseswith age).. Morbidobesity.o Presence f varicoseveins.. Prolongedimmobil2ation.e Previoushistory of thromboembolism.o PregnancS4uerperium,use of oestrogen-containingral contraceptive ills(0cP).Surgical factorso Extensivesurgery asting > 60 minutes.. Pelvic or abdominalsurgeryfor malignancy.o Major orthopaedicower limb surgeryespeciallyhip andknee replacements.Disease conditions. Neoplasm, speciallyabdominal r pelvicmalignancy.r Trauma,especially pinalcord njury and ower imb fractures.. Cardiacdisease:myocardialnfarction,congestive eart failure.. Stroke and ower limb paralysis.o Haematological onditions: olycythaemia,leukaemia,araproteinaemiae.g.,multiple myeloma).. Hypercoagulabletates: antithrombin II deficiency, rotein C and protein Sdeficiency,hrombophilia,antiphospholipid yndrome(especiallyduringpregnancy)andotherrare syndromes.

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    FatalPulmonaryEmbolismHigh RiskMajor surgery npatients> 40 yearswith prior historyof DVT or PEExtensivepeivicorabdominal urgeryfor malignantdiseaseMajor orthopaedicsurgerymajorfractures,multipletrauma

    40-80% 70-20% 5-Ljo/o I-5o/o

    Moderate RiskMajor surgery npatients> 40 yearslasting > 60 minutesI0-40"/o 2-I0o/o l-8o/o 0.1-0.70/o

    Low RiskMinor surgery< 60 minutes npatients< 40 yearswith no additionairisk factors

    < 10o/o < 7o/o 0.2o/" < 0.07o/o


    tnUf" Z+-f . ni.t of postoperativeenoushromboembolism

    I Risk I Vein I Vein I PulmonaryI PulmonaryI| Category | ThrombosisI ThrombosisI EmbolismI EmbolismI| nruiorsurgeryin| +o-soN I to-zoN I s-tooto I t-su" II I Icor I | | I| | |; disease I | | |ll ur4or ursery," "'. , .l| .rcu" | .t ' I o.zu, | .o.orl| . 60minutesn Y'ln'n""*. | | I I I

    Th. combined estrogen-progesteroneontraceptive ill (combinedOCP) s recognizedto be associated ith an ncreasen thromboticcomplications, hile progesterone-onlypreparations onot predisposeo DVT.Postmenopausalormone eplacementegimenscontainmuch ess oestrogenhan the contraceptive ills and do not increase he riskD\/ t- - ' - '

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    In the absence f additional isk factors, }ere is insufficientevidenceo supportroutinecessation f combinedOCPn suchpatients.Nofurtherprophylaxis s requiredin heatthywomenundergoingminorprocedures. n the otherhand, f the patienthasadditional isk factor(s), t is advisableo stop the pill before he scheduled urgeryand adviseher on aiternative meansof contraception.The patient shouldreceiveperioperativeDVT prophylaxisaccordingo guidelines'

    METHODSFDVTPROPHYLAXISThere re lreebroadmethodsopreventostoperativehromboembolism'

    Pharnracological. Heparin: nfractionatedr "standard" eparin SH),ow molecularweightheparin LMWH).. Oralanticoagulantsuchaswarfarin.. Dextran: extran 0,dextran 0.. 0thers:antiplateletgents, ntithromboticgents'Mechauical. Graduatedompressiontockings.o Intermittent neumaticompressionevice'. Electrical alfstimulation.o Activeandpassiveeg exercises.. Earlymobilization ndambulation.fuiaest}etic technique. Regionalnaesthesia,pecificallyentralneuraxial lockade.

    HeparinHeparins ahiglly anionic olysaccharideroducedythemastcellsof animalsusuallyderivedrombovineungandbovine rporcinentestine.It activates lasma ntithrombinII that n turnblockshe enzymaticctivityoftheactivated lotting actors primarilyXa,butalso Ia, IXa,XIa,XIIa andplasmin).

    StandardeparinThis s amixtureof inearpo$saccharideoleculesfvariable hainengths ndmolecular eights 5,000-36,000altons), ith a meanmolecular eightof12,000-15,000.

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    The mostwidely used egime s low-doseSCheparin5,000U 8-12 hourly.Prophylaxisvdth SHis simple and effective,but suffers from these.. Large interpatient variability in anticoagulantresponsedueto differences n

    bioavailability andprotein binding.o Increase n haemorrhagrc omplications,such as wound haematoma, ftersurgery.. Risk ofheparin-inducedhrombocytopaenic yndrone (HITS) n 3o/o fpatients.o Risk of osteoporosis.It is not recommendedn surgicalprocedures e.g.,ophthalmicsurgery neuro-surgery) where control of haemostasiss vital.

    weightheparinThis is preparedby chemicalor enzymaticdepolymerization f heparinmolecules.The averagemolecularweight of the LMWH s in the rangeof 4,00H,500 Daltons.Compared ith SH, LMWH has:o Greater antithromboticpotency.. Longerplasmahalf-life (4-6 hourscomparedwlthyr-Ihour in SH), furtherprolonged n patientswith renal tailure.. Longerduration of action;hence onger dosing nterval (oncedaily dose s

    acceptable).. Greater than90o/obioavailability after SC njection.o Predictableand reproducibleanticoagulant esponse;hencerequiresnolaboratory testing.. Residualanticoagulanteffect only partially reversedby protamine.. Less immunogenic,with lower incidence of HITS and fewer bleedingcomplications.Recommendedose:SCenoxaparin G4:0mg daily,or SCdalteparin2,500U daily.Antiplatelet or anticoagulantmedicationsadministeredn combinationwith LMWHmay ncreasehe risk of haemorrhage.

    Theseare colloid solutions comprisingglucosepolymerswith mean molecularweightsof 40,000(Dextran40) or 70,000fDextran70).They causea relative haemodilution, educeplatelet aggregation,mprovebloodflow andfacilitate clot breakdownby increasing ibrino$sis. As a result, Dextran

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    40 is frequentlyused n microvascular urgery o promotemicrocirculationandimprovegraft survival.Dextran 70 shows imited efficacy n preventionof DVT following generalsurgerybut appearsmoreeffectivefollowing hip surgery.problemsof dextran nclude cost, fluid overload, isk of allergic reactionsandpossibilityof precipitatingacuterenal failure.

    Mechanical ethodsElastic compression tockings are used in low risk cases,while electrical calfstimulationand ntermittentpneumatic eg compression re used n moderateo highrisk cases.Regardless f the risks, all patientswould benefit from early ambulationand eg exercises.The mechanicalmethodshavean advantageoveranticoagulantssince hey arenotassociatedwith an increasedisk of intra- or postoperative aemorrhage. hey areusefulin surgicalprocedures ophthalmicsurgery neurosurgery)whereanticoagulants recontraindicated.

    ANTICOAGULATIONNDREGIONALNAESTHESIAComparedo generalanaesthesia,egionalanaesthesias associatedwith a reductionin the incidenceof DVT and pulmonaryemboiismn patients undergoingotal hip orknee eplacements.Mechanismsostulated o explain hebeneficialeffectsof regionalanaesthesianclude hese.

    Sympatheticblockadewith reduction n vascularresistancemaxtmizes enousblood low andpreventsvenousstasis.Improved low characteristicsdue to reducedbloodviscosityas a result ofhaemodilutionrom fluid preloading.Inhibition of plateletaggregation.Facilitationof earlierandpain-freemobilizationn the postoperative eriod.

    However,hepracticeof regionalanaesthesian patients eceivinganticoagulationemainsan areaofcontroversy.ariousguidelines ndrecommendationsavebeenproposed ydifferentanaestheticorganizattons.requentupdatesarerequiredasneweranticoagulanttherapiesare advocatedandanticoagulantdrugsare introduced nto the market.

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    24 PROPHYLAXISAGAINSTVENOUSTHROIMBOEMBOLISM85In patients at risk, single-shotspinal techniqueswithout catheter or aiterna-tive regionai echniques, uch as peripheralnerveblocks,shouldbe considered.TabIe24-2 summarizeshe safetyprecautionswhenusingcentral neuraxialblockade

    in -thepresence f anticoagulants.Table 2b2. Safetyprecautions or centrai neuraxialblockade n the presenceofalticoagulants

    recommendationsnclude hese.Careshouldbe takento minimize raumaduringperformance f the centralneur-axial block. Adopt a midline approachand use fine pencil-pointspinal needle

    ProphyLacticMeasure Safety PrecautionsStandardheparin (SH) Performblock before irst doseor at least4 hoursafter last dose.Low molecularweight heparin Performblock before irst iose or at leastL0-12 hoursafter last dcse.Antiplateletdrug. Aspirinandothernon-steroidalantiinflammatoryrugs(NSAIDs). Ticlopidine,lopidogrel

    No specificprecaution or low doseaspirintherapy (30-300mg daily) or NSAIDs.Ticlopidine,clopidogrel: ite blockbeforefirst doseor 7-I0 davsaJter ast dose.Preoperativeherapeuticanticoagulationr coagulopathy Block absolutelycontraindicated.lntraoperativeanticoagulation Delay heparinization or t hour afterinsertionof block. Usesmallestdoseofheparinneededor the therapeuticgoal.Postoperativeanticoagulation Removalof epiduralcatheter. For SH:at least 2-4 hours after the lastdose,and t hour before he next dose.

    . For LMWH: at least 12 hours after thelast dose, and 2 hours before he nextdose.

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    286 MANUALOFANAESTHESIA(26Gor smaller) or subarachnoid lock.Do not insert the epiduralcatheter ur-ther than 3-4 cm into the epiduralspace o minimize he risk of inadvertent as-cular trauma.If the neuraxialblock is technicallydifficult or if bleedingoccursduring epiduralneedleor catheter nsertion, he procedureshouldbe abandoned nd analternative anaesthetic echniqueutilized. Although controversial,appearanceof blood in the needle and/orcatheterdoesnot mandatecancellationof theplannedsurgery.Frequentpostoperativemonitoring of the neurologicstatus isimportant, andfurther anticoagulation houldbe withheld for 6 hours (heparin)or 24 hours (LMWH).Short-actingocal anaesthetic houldbe used or surgery o allow assessment fneurologicstatus n the immediatepostoperative eriod.For postoperative nalgesia, se opioid-onlysolutions (e.9.,pethidine)or dilutelocal anaestheticwith opioidsolutions (e.g.,0.7o/oopivacainewith fentanyl)soas not to masksignsand symptomsof spinalcord or nerve oot compression.Monitor the patientcioselyand regularly or neurologicsequelae. high degreeof suspicions required.Suspect pinalhaematoman anypafientwith new onsetof back pain or of neurologicaldeficits,such as motor weaknessprogressingoflaccidparalysis,numbness, ndbowel or bladderdysfunction.Note that clinicalsymptomsmay developat any momentwith an indwelling epiduralcatheterandup to several daysafter its removal.Early investigationand urgent surgical evacuationof haematoma y meansofdecompressiveaminectomy s important, as recovery s unlikely if surgery sdelayedor more than 8-12 hours from the onsetof initial s5rmptoms.

    Before he introductionand widespreadusage of LMWII, the reported ncidenceofclinicallysignificant spinalhaematoman patientsundergoing entralneuraxialblockadeappearedo be low in both normal patients and those receivinganticoagulantDVTprophylaxis.Casesof spontaneous pinalhaematoma nrelated o centralneuraxialblockadehavealso beenreported.Until 1994, the rare casesof epiduralhaematomafollowing a spinal or epiduralanaesthetic ad identifiablecauses either a positivehistory of traumatic or technically difficult blocks, or someform of perioperativeanticoagulantreatment eceivedby the patient.Following he introductionof LMWH into clinical practice,case eportsof spinalhaematomaollowing LMWHhaveappearedn the literature at disconcertingly egularinteruals.This is especiallyso in the UnitedStates,where the dosesof LMWH are

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    comparativelyargerand dose ntervals shorter.Thiswas attributed n part to the failweto understand he pharmacological ifferences etweenstandardheparinand LMWH,specifically he longerdurationof action of LMWH and the need o time the insertionand removalof epiduralcathetersaccording o recommendations. venthough theincidenceof spinal haematoma as since reducedafter the Europeandosagerecommendationsere adopted, t remainsan importantproblemand a clinicaldilemmafor the anaesthesiologist.Herbalmedications,or examplegarlic, grngkoor ginseng,maybe associated ithincreased erioperative leedingespeciallywhen ombined ith othermedicationshatinhibit plateletaggregation. ven hough he use of herbalmedications lonedoesnotcreatea levelof risk that will interferewith the performance f neuraxialblocks,oneshouldbe aware of their potentialeffectson haemostasis.Oneshould also remember hat the margin of safety decreasesn elderly ordebilitatedpatients, those with liver diseaseor on a combinationof anticoagulantdrugs.The decision o performcentralneuraxialblockadeand the timing of catheterremoval n suchpatientsshouldbe madeon an individual basis,weighing he risk ofspinal haematomaagainst the benefits of regional anaesthesiaor eachparticularpatient.

    PULMONARYHROMOEMBOLISMApproximately 75% of patients who present with clinically suspectedvenoustlrombosis or pulmonaryembolismdo not have theseconditions.0bjective testingis necessa4y hen either s suspected, ecause linical diagnosisalone s inaccurate,and consequencesf misdiagnosis re serious.Failure to diagnose ulmonaryembolism s associatedwith high mortality, while incorrect diagnosissubjectsthe patient to the risks of unnecessaryanticoagulant herapy. Tests available forDVT are compressionultrasonographyof the femoral and popliteal veins andcontrast venography,while radionuclide ung imaging (ventilation-perfusion can),contrast-enhancedpiral CT and pulmonaryangrography re tests for diagnosisofpulmonaryhromboembolismPTE).PIE maypresent o the anaesthesiologists a catastrophic vent n the intra- orpostoperative eriod.At the other end of the spectrum,symptomsof minor PIE areusually subtle, non-specific nd self-limiting,and some casesmay evenpassundiagnosed.hemanifestation f s5rmptomsepends n a varietyof factors, ncludingthe degree f tlrombosis, he presence nd degree f collateralvesselsand he severityof inflammation.

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    ClinicalManifestationsPresentationmay be that of:

    Uncomplicated mboluswith dyspnoea.Pulmonarynfarctionslmdrome$leuritic pain and/orhaemoptysis).Circulatorycollapseor syncope.

    Signsand symptomsCommon(> 5oo/o ases)' Apprehension.. Dyspnoea,achypnoea, ough, ales.. Tachycardia, hestpain (pleuriticor angina-like),oud pulmonicheart sound.Less common(L0-40o/ocases)o HaemoPtysis,ow grade ever,cyanosis.. Diaphoresis, yncope, lteredmentalstatus.. Signsof elevatedCVP,clinical DVT.Rare (< L0% cases). Wheezing, bdominal ain.. Disseminatedntravascularcoagulation.

    InvestigationsABG. This typically showshypoxaemiaand/othypocarbia.. However. normalPa0, n ABG doesnot rule out diagnosis f I{lE.ECG. ECG s normal n 30o/o f patientswith PTE.. ChangesncludeST-Twaveabnormalitiesandrhythm disturbancen the form

    of atrial or ventricular ectopicbeats,and atrial tachycardia.. Changesn the right heart with right atrial strain, right bundlebranch blockand axisdeviationgiverise to the classicalpictureof SrQ,T, (Swave n leadI, Qwave and nvertedT wave n leadIII)'cxR. Changes renon-specific; telectasis ndpulmonary arench5rmalbnormalityaremost common.. Others ncludeelevationof hemidiaphragm, leural effusion,"knuckle sign"(pulmonaryartery apers abruptly) andpulmonary nfarction.

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    PlasmaD-dimerr Theseare generatedwhen fibrin is degraded y the endogenousibrinolyticsystem.. Elevated evelsof plasmaD-dimermay suggestpresence f PTE but thesearenot specific o PTE alone.However, negativeD-dimerassayusuallymeansthe diagnosisof PTE canbe excluded.Ventilation-p erfirsion scan. V/Q scan s the most usefulnon-invasivemethod or diagnosisof PTE; a normalperfusionscanexcludes he diagnosis ndfurther tests areunnecessary.o However,V/Q scans are less likely to be helpfui in patients with COPD,cardiorespiratory iseaseor history of pulmonaryembolism.Helical ("spiral") CT scan:. It allowsfor directvisualizationof emboliwithin the pulmonatyafiery,aswellas any abnormalitiesn the parenchyma hat mayprovidea different aetiologrfor the patient'ssymptoms.. Sensitivitywith helical CT scanning angesbetween57o/o nd 100%,whilespecificity angesbetween78o/o nd700o/o.Pulmonary angiographyo This is regardedas the "gold standard" or the diagnosisof PTE but is invasive,

    difficult to performand nterpret,andassociated ith a mortality rate of.0.5o/o.. Angtography houldbe employed nly in patientswhere he diagnosis annotbe established y less nvasivemeans.

    ptionsare basedonwhether he patient s haemodynamicallytableandanticoagulations advisable. hereare also supportivemeasuresnto specific herapy, isted below.

    measuresO4ygenherapy and ventilatory support.Volume esuscitation.Use of vasoactivedrugs: notropes (dopamine, obutamine), asodilatorsfhydralazine) s indicated.

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    2. Specifictlerapya. HaemodynamicallytablepatientsStandardheParin

    . This is the standard reatment or hemodynamically tablepatientwithvenous lromboembolism'. It is administered n the form of continuous ntravenous nfusion butrequires requent aboratorymonitoringand dose itration.Oral anticoagulant warfarino Warfarin is administered n conjunctionwith heparinwith a 48-houroverlap,as it takes 3-5 daysfor the antithromboticeffect to work.Fondaparinux. This is a synthetic antithrombotic agentwith specificanti-FactorXaactivitY.. It is administeredn a fixed dose,oncedailySC njection,andrequireslessfrequent aboratorymonitoringcomparedo standardheparin.Low molecularweight heParin. LMWH is givensubcutaneouslyn either a weight-basedormula (fortreatment)or a fixed dose(forprophylaxis)'. It has the benefit of not requiring laboratorymonitoring,and n many

    studiesLMWH hasbeenshown o be superior o standardheparin nterms of bleedingcomPlications.b. HaemodynamicallynstablepatientsThrombolytictheraPY. This therap54singstreptokinase r recombinantissueplasminogenactivator (rtPA), s indicated or haemodynamicallynstablepatientswith acutePIE.. Themajor imitation of thrombolytic reatment s an increased isk and

    incidenceof severebleedingcomparedwith heparin.. Somedatashowa decreasen recurrentpulmonaryembolismn rtPApatientscomparedwith heparin-alone atients.Surgicalmeasures. These are used for haemodynamicaliy nstablepatients withcontraindicationsor thrombolysis.. These ncludepulmonaryembolectomy ith cardiopulmonaryypass,transvenous atheterembolectomy,r placement f inferior venacavafilter.

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    FURTHEREADING1. Hyers TM. Management f venous hromboembolism: ast,present,and future.Arch Intern Med 2003:163:759-68.2. WhittleJ, JohnsonP,LocalioAR. Anticoagulationherapy n patientswith venousthromboembolicisease. Gen nt Med 1998;13:373-8.3. Wheatley T, Veitch PS. Recent advancesn prophylaxisagainst deep veintlrombosis. Br J Anaesth 1997;78118-20.4. 'ffalker CPR,RoystonD. Thrombingenerafion nd ts inhibition:A reviewof thescientificbasisand mechanism f action of anticoagulantherapies.Br JAnaesth2002;88:848-63.5. HoriockerTT,HeitJA.Lowmolecularweightheparin: harmacology,erioperativeprophylaxis egimen,andguidetinesor regionalanestheticmanagement. nesthAnalg 1997;85:874-85.6. White RH. Low-molecular-weighteparins:Are they all the same?Br J Haem2003;721,:12-20.7. HorlockerTT, et al. Regionalanesthesian the anticoagulated atient:Definingthe risks. RegAnesth PainMed 2003;28:172-97.8. T$ba M. European ractice guidelines:Thromboembolismrophylaxisandregional

    anesthesia.Reg Anesth Pain Med 7998;23:178-82.9. Litz RJ,Hubler M, Kock T, AlbrechtM. Spinat-epiduralematomaollowing epiduralanesthesia n the presenceof antiplatelet and heparin therapy.Anesthesiologr2001;95:1031-3.10. GoldhaberSZ. Pulmonaryembolism.N EnglJ Med 7998;339:93-104.