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Anticoagulation and Neuraxial Techniques


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  • 1. Anticoagulation andAnticoagulation and NeuraxialNeuraxial Anesthesia/AnalgesiaAnesthesia/Analgesia Dr. Stelian SerbanDr. Stelian Serban
  • 2. Case Reports of EpiduralCase Reports of Epidural HematomasHematomas on Lovenoxon Lovenox  Prior to ‘94: Vandermuelen - 4/61Prior to ‘94: Vandermuelen - 4/61 casescases  Since ‘94: >45 cases, (IncidenceSince ‘94: >45 cases, (Incidence 1:5000)1:5000)  Dx:Dx:  New onset of LE weakness/numbnessNew onset of LE weakness/numbness  Only aOnly a minorityminority of cases have back painof cases have back pain  Setting:Setting: Almost allAlmost all THA/TKA/Hip fx’sTHA/TKA/Hip fx’s
  • 3. Indications For Antithrombotic TherapyIndications For Antithrombotic Therapy  Venous thromboembolic diseaseVenous thromboembolic disease • Deep venous thrombosis (DVT)Deep venous thrombosis (DVT) • Pulmonary embolism (PE)Pulmonary embolism (PE) • Primary prophylaxis of DVT or PEPrimary prophylaxis of DVT or PE  Arterial thromboembolic diseaseArterial thromboembolic disease • Prosthetic heart valvesProsthetic heart valves • Mitral valve disease, especially with atrial fibrillationMitral valve disease, especially with atrial fibrillation • Congestive cardiomyopathies, especially with atrialCongestive cardiomyopathies, especially with atrial fibrillatiofibrillatio • Atrial fibrillationAtrial fibrillation • Mural cardiac thrombiMural cardiac thrombi • Transient ischemic attacksTransient ischemic attacks • Stroke in evolutionStroke in evolution  Disseminated intravascular coagulationDisseminated intravascular coagulation  Maintenance of patency of vascular grafts, shunts, bypassesMaintenance of patency of vascular grafts, shunts, bypasses
  • 4. Recommended DVT/VTE ProphylaxisRecommended DVT/VTE Prophylaxis Hyers Am J Respir Crit Care 1999Hyers Am J Respir Crit Care 1999 Geerts et al Chest 2001, 2004 Bauer Blood 2002Geerts et al Chest 2001, 2004 Bauer Blood 2002 Risk groupRisk group Recommended prophylaxisRecommended prophylaxis Hip replacementHip replacement Warfarin, LMWH, fondaparinuxWarfarin, LMWH, fondaparinux Knee replacement Warfarin, LMWH, IPC,Knee replacement Warfarin, LMWH, IPC, fondaparinux (Arixtra)fondaparinux (Arixtra) Hip FractureHip Fracture Warfarin, LMWH, fondaparinuxWarfarin, LMWH, fondaparinux Major traumaMajor trauma LMWH, IPCLMWH, IPC Abdominal surgeryAbdominal surgery UFH, LMWH, IPC, warfarin, ESUFH, LMWH, IPC, warfarin, ES Medical PatientsMedical Patients UFH, LMWH, ESUFH, LMWH, ES IPC-Intermittent Pneumatic CompressionIPC-Intermittent Pneumatic Compression ES-Elastic stockingES-Elastic stocking
  • 5. Review of commonly usedReview of commonly used anticoagulantsanticoagulants  Antiplatelet drugs– inhibit plateletAntiplatelet drugs– inhibit platelet functionfunction 1)1) Aspirin(ASA): irreversible inactivatesAspirin(ASA): irreversible inactivates COX, even low-dose aspirin (81) mayCOX, even low-dose aspirin (81) may suppress TXA2 synthesis & PLTsuppress TXA2 synthesis & PLT aggregation, inhibiting 1 hr afteraggregation, inhibiting 1 hr after ingestion, entire lifespan 10 daysingestion, entire lifespan 10 days 2)2) Newer generations: inhibiting ADP-Newer generations: inhibiting ADP- induced PLT aggregation (entire lifespan)induced PLT aggregation (entire lifespan) or PLT GPIIb/IIIa receptor (48 hrs)or PLT GPIIb/IIIa receptor (48 hrs) 3)3) NSAIDs: reversibly and competitivelyNSAIDs: reversibly and competitively inhibit COX, duration is dose-dependentinhibit COX, duration is dose-dependent and half-life of the NSAIDand half-life of the NSAID
  • 6. Review of commonly usedReview of commonly used anticoagulantsanticoagulants  Oral anticoagulants (Warfarin)Oral anticoagulants (Warfarin)  Interfering with the Vit. K-dependentInterfering with the Vit. K-dependent coagulation protein, factorscoagulation protein, factors IIII (thrombin),(thrombin), VIIVII,, IXIX, and, and XX  Inhibiting Vit. K reductases, depletes Vit.Inhibiting Vit. K reductases, depletes Vit. KHKH22, and limits carboxylation, and limits carboxylation  PT and INR may not accurately measurePT and INR may not accurately measure true antithrombotic activitytrue antithrombotic activity  A decrease in factorsA decrease in factors IIII andand XX (longer half-(longer half- life) is more important for thelife) is more important for the antithrombotic efficacy of warfarinantithrombotic efficacy of warfarin
  • 7. Review of commonly usedReview of commonly used anticoagulantsanticoagulants  HeparinHeparin  Binding with antithrombinBinding with antithrombin IIIIII, which, which accelerates inactivation of factorsaccelerates inactivation of factors IIII,, IXIX,, XX,, XIXI andand XIIXII  Mixture of polysaccharide chains, MWMixture of polysaccharide chains, MW ranging from 5,000 to 30,000; the length ofranging from 5,000 to 30,000; the length of the heparin chain determines which factorthe heparin chain determines which factor will be inhibitedwill be inhibited  Extensive binding to plasma proteinsExtensive binding to plasma proteins complicated the pharmacokinetics of heparincomplicated the pharmacokinetics of heparin
  • 8. Review of commonly usedReview of commonly used anticoagulantsanticoagulants  LMWH has relatively greater anti-LMWH has relatively greater anti-XaXa activity, more predictableactivity, more predictable bioavailability and longer half-lifebioavailability and longer half-life  PTT doesn’t accurately reflect thePTT doesn’t accurately reflect the degree of anticoagulation, factor Xdegree of anticoagulation, factor X levels don’t correlate with potentiallevels don’t correlate with potential for bleedingfor bleeding
  • 9. Anticoagulant Properties of HeparinAnticoagulant Properties of Heparin 1.1. Inhibits the thrombin-mediatedInhibits the thrombin-mediated conversion of fibrinogen to fibrinconversion of fibrinogen to fibrin 2.2. Inhibits the aggregation of plateletsInhibits the aggregation of platelets by thrombinby thrombin 3.3. Inhibits activation of fibrinInhibits activation of fibrin stabilizing enzymestabilizing enzyme 4.4. Inhibits activated factors XII, XI,Inhibits activated factors XII, XI, IX, X and IIIX, X and II
  • 10. Monitoring of AnticoagulantMonitoring of Anticoagulant TherapyTherapy HeparinHeparin s.q. – no monitoring requireds.q. – no monitoring required (q12H)(q12H) i.v. - partial thromboplastin timei.v. - partial thromboplastin time (P.T.T.)(P.T.T.) *daily or more frequent if PTT*daily or more frequent if PTT variesvaries mechanismmechanism – measures intrinsic pathway– measures intrinsic pathway therapeutic goaltherapeutic goal – 2-2.5 times normal– 2-2.5 times normal
  • 11. Subcutaneous HeparinSubcutaneous Heparin  During administration of subcutaneousDuring administration of subcutaneous heparin, there is no contraindication toheparin, there is no contraindication to neuroaxial techniquesneuroaxial techniques  For patients receiving mini dose heparinFor patients receiving mini dose heparin for ≥ 4 days, reassess platelet count priorfor ≥ 4 days, reassess platelet count prior to neuraxial block or removal of catheterto neuraxial block or removal of catheter  For patients with q8h heparin, PTT andFor patients with q8h heparin, PTT and platelets requiredplatelets required
  • 12. Intravenous HeparinIntravenous Heparin  Indwelling neuraxial catheters should beIndwelling neuraxial catheters should be removed 4 hours after the last heparinremoved 4 hours after the last heparin dose and reevaluation of the patient'sdose and reevaluation of the patient's coagulation status has occurredcoagulation status has occurred  CHECK PTT!!CHECK PTT!!  Re-heparinization should occur 1 h afterRe-heparinization should occur 1 h after catheter removal.catheter removal.
  • 13. Low-Molecular Weight Heparin (LMWH)Low-Molecular Weight Heparin (LMWH)  Monitoring of anti-Xa level is notMonitoring of anti-Xa level is not recommended as it is not predictive of therecommended as it is not predictive of the risk of bleeding.risk of bleeding.  Antiplatelet or oral anticoagulant medicationsAntiplatelet or oral anticoagulant medications administered in combination with LMWH mayadministered in combination with LMWH may increase the risk of spinal hematoma.increase the risk of spinal hematoma.  Traumatic needle or catheter placement mayTraumatic needle or catheter placement may signify an increased risk of spinal hematomasignify an increased risk of spinal hematoma and initiation of LMWH therapy in this settingand initiation of LMWH therapy in this setting should be delayed for 24 hours.should be delayed for 24 hours.
  • 14. Low-Molecular Weight Heparin (LMWH)Low-Molecular Weight Heparin (LMWH) Twice daily dosingTwice daily dosing  The first dose of LMWH should be started noThe first dose of LMWH should be started no earlier than 24 hours postoperatively andearlier than 24 hours postoperatively and surgical hemostasis has been achieved.surgical hemostasis has been achieved.  Indwelling catheters should be removed prior toIndwelling catheters should be removed prior to initiation of LMWH thromboprophylaxis.initiation of LMWH thromboprophylaxis.  If a continuous technique is selected, theIf a continuous technique is selected, the epidural catheter may be left indwellingepidural catheter may be left indwelling overnight and removed the following day, withovernight and removed the following day, with initiation of LMWH occurring at least two hoursinitiation of LMWH occurring at least two hours after catheter removal.after catheter removal.
  • 15. WarfarinWarfarin  In patient’s receiving chronicIn patient’s receiving chronic anticoagulation, warfarin should beanticoagulation, warfarin should be discontinued at least 4-5 days beforediscontinued at least 4-5 days before procedure.procedure.  The PT/INR should be evaluated prior toThe PT/INR should be evaluated prior to any neuroaxial technique.any neuroaxial technique.  In patients with an epidural receiving lowIn patients with an epidural receiving low dose warfarin therapy, the PT/INR shoulddose warfarin therapy, the PT/INR should be monitored on a daily basis, andbe monitored on a daily basis, and checked before catheter removal.checked before catheter removal.
  • 16. WarfarinWarfarin  Indwelling catheters can be removed whenIndwelling catheters can be removed when the INR is less 1.4the INR is less 1.4  In patient’s with an INR >3, the warfarinIn patient’s with an INR >3, the warfarin dose should be held or decreased.dose should be held or decreased. • No removal of neuraxial catheters in patientsNo removal of neuraxial catheters in patients with therapeutic levels of anticoagulation.with therapeutic levels of anticoagulation.  Neurologic testing should be performedNeurologic testing should be performed routinely during epidural analgesia androutinely during epidural analgesia and should be continued after cathetershould be continued after catheter removal for at least 24 hours.removal for at least 24 hours.
  • 17. Antiplatelet MedicationsAntiplatelet Medications  NSAIDs,NSAIDs,  Thienopyridine derivativesThienopyridine derivatives • Ticlopidine and ClopidogrelTiclopidine and Clopidogrel  Platelet GP IIb/IIIa antagonistsPlatelet GP IIb/IIIa antagonists • Abciximab, Eptifibatide and TirofibanAbciximab, Eptifibatide and Tirofiban
  • 18. Antiplatelet MedicationsAntiplatelet Medications  NSAIDs do not represent added significantNSAIDs do not represent added significant risk for the development of spinalrisk for the development of spinal hematoma in patients having epidural orhematoma in patients having epidural or spinal anesthesia.spinal anesthesia.  The actual risk of spinal hematoma withThe actual risk of spinal hematoma with ticlopidine and clopidogrel and the GPticlopidine and clopidogrel and the GP IIb/IIIa antagonists is unknownIIb/IIIa antagonists is unknown • The suggested time interval betweenThe suggested time interval between discontinuation of thienopyridine therapy anddiscontinuation of thienopyridine therapy and neuraxial blockade is 14 days for ticlopidineneuraxial blockade is 14 days for ticlopidine and 7 days for clopidogrel.and 7 days for clopidogrel.
  • 19. Plavix/ClopidogrelPlavix/Clopidogrel Ticlid/TiclopidineTiclid/Ticlopidine  Plavix has fewer side effects thanPlavix has fewer side effects than TiclidTiclid  Inhibits platelets (via ADP binding)Inhibits platelets (via ADP binding)  long t1/2long t1/2  Plavix: wait 7d till CNBPlavix: wait 7d till CNB  Ticlid: wait 14d(!) till CNBTiclid: wait 14d(!) till CNB
  • 20. Plavix testPlavix test Population Frequency of Cytochrome P450 (CYP) 2C19 Metabolizer Types Poor (no or low enzyme levels) Intermediate (reduced enzyme levels) Extensive (normal enzyme levels) CYP2C19 3-21% 24-36% 43-73%
  • 21. Arixtra/FondaparinuxArixtra/Fondaparinux  Inhibits Xa via ATIIIInhibits Xa via ATIII binding sitebinding site  Inhibits plateletsInhibits platelets  Long t1/2 (>20hrs)Long t1/2 (>20hrs)  Avoid CNB!!!!!Avoid CNB!!!!!  Actual risk unknownActual risk unknown  Start 6-8 h afterStart 6-8 h after surgerysurgery  If given wait 36 h (2If given wait 36 h (2 T1/2s)T1/2s)
  • 22. Direct Factor Xa inhibitorsDirect Factor Xa inhibitors  DabigatranDabigatran  RivaroxabanRivaroxaban  ApixabanApixaban
  • 23. Antithrombin medicationsAntithrombin medications  ArgatrobanArgatroban  LepirudinLepirudin  DesirudinDesirudin  BivalirudinBivalirudin  All inhibit both free and clot-boundAll inhibit both free and clot-bound thrombinthrombin  No existing reversal agents available atNo existing reversal agents available at this timethis time  No neuraxial techniques advised!No neuraxial techniques advised!
  • 24. Herbal medicationsHerbal medications  No evidence re: direct relationship withNo evidence re: direct relationship with neuraxial cathsneuraxial caths  Caution with concomitant clot formingCaution with concomitant clot forming inhibitorsinhibitors  Gingko biloba associated withGingko biloba associated with subdural/subarachnoid hemorrhagesubdural/subarachnoid hemorrhage  Ginkgo, garlic, gingseng, cranberryGinkgo, garlic, gingseng, cranberry decreases warfarin metab.decreases warfarin metab.  St. John’s wort increases warfarin metab.St. John’s wort increases warfarin metab.
  • 25. ““All areAll are anticoagulatedanticoagulated untiluntil provenproven otherwise”otherwise”