4Objectives Review risks of holding aspirin perioperatively. To learn when / which procedures aspirin should / should not be held.Review POISE-2 methodology.Examine limitations of POISE-2.Provide recommendations on perioperative aspirin management.
5Case 70 y.o. male for primary TKA PMH Meds TIA 5 years prior HTN NIDDM HLDRemote tobaccoMedsASA 81 mg/daySimvastatinMetforminNaproxen prn
6Background 100,000,000 non-cardiac operations /year worldwide. ~ 40% of these patients have / at risk for CV disease.Mangano, Anesthesiology 1990In the U.S., cardiovascular disease (CAD, CVD, PVD):Affects >1/3 adultsLeading cause of morbidity & mortality.Wolff et al, Ann Int Med 2009USPTF Ann Int Med 2009#1 perioperative complication in patients with CV risk factors → M.I.Associated mortality rate of 15 – 25%Peter et al, Thromb Haemost 2011Kumar et al, J Gen Int Med 2001Furthermore, even a mildly elevated troponin postoperatively has been shown to be an independent predictor of increased perioperative morbidity andmortality.
7Aspirin’s Role in CV Disease platelet aggregation inhibitionthrombosis preventionPrimary preventionSecondary preventionKnow aspirin’s indication in these two contextsPrimary prevention = preventing first occurrence of diseaseSecondary prevention = prevention of recurrence
8Aspirin in Secondary Prevention Most recent AHA/ACC/ACCP guidelines:Indefinite rx in virtually all with established CAD or other atherosclerotic disease‘unless absolutely contraindicated’PCI: neuro, cardiac287 study meta-analysis of antiplatelet rx in 135,000 pt’s with CV diseaseAspirin #1 studied rx25% reduction of death from any vascular cause, MI, CVA
9Primary Prevention Unclear in those without risk factors Diabetics 2010 ADA/AHA/ACCFAspirin if increased cardiac risk (10-year risk of cardiac event of >10%).Men > 50 years / women > 60 years & one of the following:Tobacco useHypertensionSignificant cardiovascular disease family historyHypercholesterolemiaAlbuminuriaThe risk-versus-benefit ratio of aspirin therapy for primary prevention, however, is much less clear than for secondary prevention.The Antithrombotic Trialists’ Collaboration has also recently published a meta-analysis of 6 randomized primary prevention trials.They concluded that aspirin reduced the incidence of vascular events (12% proportional reduction or 0.07% per year absolute reduction, P = ), mainly nonfatal myocardial infarction, by a small but statistically significant amount. The largest reduction was for nonfatal myocardial infarction;23% proportional reduction, P < The proportional reductions in the aggregate of all serious vascular events were similar for both men and women. There was no reduction in vascular-related mortality attributed to aspirin use.In addition, they found that aspirin significantly increased the rate of major gastrointestinal bleeding and also increased the risk of hemorrhagic stroke. The authors therefore concluded that aspirin therapy is of uncertain value for primary cardiovascular prevention and that strong consideration must be given tobalancing the reduction in thrombotic events with the risk of major bleeding
12Key Points in Aspirin Pharmacology 2 isoforms of COX: 1 & 2Aspirin irreversibly inactivates COX170x affinity for COX-1 vs COX-2A single dose of 30 mg completely suppresses TXA2 production for 1 week
13Aspirin Mechanism Eur Heart J, Vol 7, May 2005 Key Points in Aspirin Pharmacology2 isoforms of COX: 1 & 2Aspirin irreversibly inactivates COX170x affinity for COX-1 vs COX-2A single dose of 30 mg completely suppresses TXA2 production for 1 weekTXA2 is responsible for activating new platelets, stimulating platelet aggregation, and vasoconstriction—consequently causing thrombosis and hemostasis.Under normal conditions, thrombosis is kept in check by the intact endothelial cell lining that is resistant to interactions with platelets and coagulation factors.When endothelial damage occurs, however, the hemostatic process (including platelet aggregation and activation) is initiated to stop bleeding. If this process becomes exaggerated, excess thrombosis can lead to unwanted vascular occlusion and adverse cardiovascular events.Eur Heart J, Vol 7, May 2005
14Platelets – more than just hemostasis ADP, TXA2Thrombincoagulation cascadeInflammatory mediatorsAtherosclerosisThrombogenicityNeutrophil activationPlatelets role in hemostasis begins by detecting disrupted vascular endothelium and adhering to the newly exposed extracellular matrix.2) Adherent platelets aggregate and release platelet-activation mediators such as ADP and TXA2. TXA2 production is largely catalyzed by COX-1.3) Once activated, platelets generate thrombin and catalyze the coagulation cascade4) Platelets also induce inflammatory leukocytes, which may initiate atherothrombotic plaques promoting undesirable thrombotic events.Platelet granules store many pro- and anti-inflammatory cytokines that have no apparent role in hemostasis5) It is well established that platelets promote atherosclerosis through several mechanisms and the platelet’s role and cell signaling is similar for both maintenance of normal hemostasis and pathologic thrombosis development6) the platelet has been identified as a link between inflammation and thrombogenicity.7) Platelets have been found to express Toll-like receptors to promote neutrophil activation and store antibacterial proteinscalled thrombocidins, both aiding in pathogen protection and killing.
17‘Aspirin Withdrawal Syndrome’ Aspirin use is not just an on-off switchComplex relationship between platelet:InhibitionIt must be kept in mind that alternating between platelet inhibition and restoration of platelet function is not a simple “on-off” phenomenon.InhibitionHemostasisInflammationHemostasisInflammation
18Aspirin WithdrawalPlatelet rebound phenomenon in setting of acute aspirin withdrawal.This rebound period is characterized by:Increased thromboxane productionDecreased fibrinolysisLeading to a resultant clinical prothrombotic stateVial et al, Adv Prostaglandin Thromboxane Leukot Res. 1991Beving et al, Blood Coagul Fibrinolysis 1996Fatah et al, Eur Heart J 1996
19Urine metabolites of TXA2 and PGI2 Before, during, and after cessation of a 1-week aspirin regimen.Metabolites (and hence platelet TXA2) rebound to levels beyond that of study controls.Peaked at 7 to 14 days after aspirin withdrawal.
20Measured ‘HHT’ to approximate platelet-TXA2 production 32 pts who stop aspirin-rx 2 weeks before CABG25% of this cohort had 12-HHT levels beyond the normal range 2 weeks after withdrawal.Same investigators, earlier study:12-HHT/TXA2 rebound in healthy subjects after withdrawal of a 1-week aspirin regimen.Dose dependentmore rapid rebound with withdrawal of lower aspirin doses.(12-HHT: a platelet metabolite produced concomitantly in equal amounts to TXA2)12-L-hydroxy-5,8,10-heptadecatrienoic acidIn both studies: observed platelet function rebound.
21Rebound affects more than primary hemostasis Increase fibrin strength after withdrawal.Less fibrinolysis when fibrin strength enhanced.Same authors:demonstrated that patients with more rigid fibrin networks were more prone to CV events.
22Clinically relevant to the Perioperative Period?
23Thrombotic Risks of Aspirin Withdrawal in the Perioperative Period Aspirin is clearly beneficial for secondary prevention.25% RRR in preventing future cardiac or ischemic events.ATC BMJ 2002Tran et al, JAMA 2004Still, typical practice for surgeons and preoperative clinics to council aspirin cessation 7-10 days preoperatively.Collet et al, Int J Cardiol 2000
24Cohort 1358 pts admitted for ACS. Non-user: n=930 (68.%)Prior-users: n=355 (26.1%)Recent withdrawals: n=73 (5.4%)2x increase in death rates of ‘withdrawers’ vs prior users / nonusers.Average time b/w cessation-cardiac event = 11.9 days.Scheduled surgery = 64% cases.Multivariate analysis:Antiplatelet cessationIndependent predictor of both death and major ischemic events.Non-user: no APA >6mo.Prior-users: ‘continued’ aspirin in 3 weeks pre-trialRecent withdrawers: held aspirin within 3 weeks of admissionDespite a similar cardiovascular risk profile, recent withdrawers had higher 30-day rates of death or MI (21.9% versus 12.4%, P0.04)Recent withdrawers of antiplt rx (97% of subjects were aspirin)11.9 days, consistent with the expected time interval for platelet rebound
25Meta-analysis of retrospective studies (1970-2004) n=49590 (14981 on aspirin)CV risks associated with perioperative withdrawal of aspirin vs bleeding risks when continued.
26Mean timing of event after discontinuation of aspirin: Withdrawal preceded:10.2% of acute cardiovascular events.6.1% of lower limb ischemic events.Mean timing of event after discontinuation of aspirin:8.5 days for coronary events.25.8 days for a lower limb event.
27Retrospective case–control 309 admissions over 2 years with diagnosis of CVA or TIA & use of long-term aspirin before the index event.Compared to 309 age- and sex- matched controls with a history of CVA or TIA on long-term aspirin and no acute event in previous 6 months.
28Most common reason for aspirin discontinuation: CVA/TIA:13 patients vs 4 controls had discontinued aspirin in previous 4 weeks:4.2% vs 1.3%, P = .03Odds ratio 3.34 (95% CI: 1.07–10.39)Most common reason for aspirin discontinuation:SurgeryMean interval between aspirin d/c and CVA:9.5 days
29One study ( patients) focused on adherence to aspirin therapy in the secondary prevention of CAD, two studies (2594) on aspirin discontinuation in acute CAD, two studies (13 706) on adherence to aspirin therapy before or shortly after coronary artery bypass grafting,and another (2229) on aspirin discontinuation among patients undergoing drug-eluting stenting.Overall, aspirin non-adherence/withdrawal was associated with three-fold higher risk of major adverse cardiac events (OR ¼ 3.14 [1.75–5.61], P ¼ ). This risk was magnified in patients with intracoronary stents, as discontinuation of antiplatelet treatment was associated with an even higher risk of adverse events (OR ¼ [29.90–269.60]).Pooling of the available data showed an average of days (95% CI: 10.25–11.07) between day of discontinuation and thrombotic event.The data indicated that aspirin nonadherence or withdrawal was associated with a threefold higher risk of major cardiac events.Again, the mean time between aspirin withdrawal and thrombotic events was 10 days, which is consistent with the timing of peak thromboxane levels in prior studies.Pooling all these groups yielded a highly significant association between aspirin withdrawal/non-compliance and adverse events (3.14 [1.75–5.61], P for effect=0.0001, P for heterogeneity< , I2=89.8%). Although such meta-analysis may be considered robust as performed according to a random-effect approach, the presence and extent of statistical heterogeneity limits its conclusiveness and leaves it mainly in the hypothesis-generating realm.Moreover, the momentous increase in risk faced by those treated with coronary drug-eluting stents can be easily explained by the highly thrombotic milieau generated by PCI with drug-eluting stent implantation, and its consequent dependence on high-intensity antiplatelet regimens for several months
30Days elapsed between aspirin d/c and thrombotic events: 10.66(95% CI 10.25–11.07)“… further confirms the major detrimental impact of aspirin withdrawal across a large spectrum of subjects at risk for de-novo or recurrent cardiovascular events.”Another notable finding of this work is the homogeneity in intervals reported from the several included studies from aspirin discontinuation to thrombotic events. Indeed, the typical average interval of 10 days appears coherent with pathophysiologic data on half platelet population renewal, and has relevant management implications, as in any case of mandatory physician-supervised aspirin withdrawal, the drug should be reinstituted well before these 10 days have elapsed.
31To date, the only published randomized controlled clinical trial evaluating whether to continue aspirin in the preoperative period was published in 2010 by Oscarsson et al.
32Randomized double blind placebo-controlled. 220 high-risk patients (PCI excluded).Undergoing intermediate- to high- risk noncardiac surgery.Randomized to:daily low-dose aspirin (75mg) or placebo7 days before surgery until 3 days post-procedureAspirin held if needed in placebo groupStudy was undertaken with the primary aim of assessing the incidence of perioperative myocardial damage in patients with or without low-dose aspirin treatment in the perioperative period.Patients on chronic aspirin rx pre-study (n=196; 90% of the study population):Our hypothesis was that low-dose aspirin reduces the incidence of myocardial damage and major adverse cardiac events (MACEs, defined as acute myocardial infarction, severe arrhythmia, cardiac arrest, or cardiovascular death) without increasing bleeding complications.
33Inclusion (one of the following) High-risk surgery CADHeart failureRenal impairmentCVATIAInsulin-dep DMExclusionUnstable CADDecompensated HFShockAspirin allergy< 18 yoHistory of ICH, GIBRx with warfarin, clopidogrel, mtxVascular surgeryHigh-risk surgery(large fluid shifts; known cardiac risk >5%)EsophagealLiverPancreaticIntermediate-risk(cardiac risk 1-5%)Head & neckIntraperitonealIntrathoracicMajor orthoProstateundergoing vascular surgery were excluded since the Vascular Society in Sweden recommends continuation of aspirin in the perioperative period.
34Secondary endpoints (any with first 30 days postop): Primary endpointPostoperative myocardial damage (TnT)Secondary endpoints (any with first 30 days postop):MACEacute MIcardiac arrestsevere arrhythmiaCV deathCardio-cerebrovascular complicationsMACE or stroke/TIAPerioperative blood loss and major bleedingStudy endpoints
36Myocardial damage and cardio-cerebrovascular complications. Postoperative myocardial damage, defined as a TnT value 0.04 on at least one occasion in the first 48 h after operation period.(MACEs, including acute myocardial infarction, cardiac arrest, severe arrhythmia, orcardiovascular death within the first 30 postoperative days.)Cardiocerebrovascular events: MACE, TIA/stroke, or both. In patients with morethan one event, only one event is included in the outcome variable. Statisticalanalysis was undertaken on an intention-to-treat basis. Patients were assumednot to have had an event when data were missing1.8% of aspirin-treated patients versus 9.0% of placebotreatedpatients had a major adverse cardiac event (P = 0.02) within30 days postoperatively. Aspirin conferred a 7.2% absolute risk reduction,with a RR reduction of 80%, with a number needed to treatof 14 patients. In addition, there was a significantly lower incidenceof perioperative CVA or TIA in the aspirin group.
37Absolute risk reduction = 7.2% [95% CI 1.3–13%] Aspirin use:Absolute risk reduction = 7.2% [95% CI 1.3–13%]NNT = 14 [95% CI 7.6–78]Majority of patients having MACE had it early postop.1 in aspirin group and 8 in the placebo group had MACE within:1st 3 postop days(P=0.02).Patients on chronic aspirin rx pre-study (n=196; 90% of the study population):MACE+ : 10 in placebo vs 1 receiving aspirin(P=0.03).ASA use … for postoperative cardiovascular events within the first 30 days after surgery.There was no MACE in the subgroup of patients who had undergone PCI.ARR=CER (control group’s event rate) – EER (experimental group’s event rate)RRR= ARR/CERNNT= 1/NNTRelative risk reduction = 80% [95% CI 9.2–95%]The relative risk reduction can be more useful than the absolute risk reduction in determining an appropriate treatment plan, because it accounts not only for the effectiveness of a proposed treatment, but also for the relative likelihood of an incident (positive or negative) occurring in the absence of treatment.
39Prospective blinded placebo-control To evaluate risk of recurrent bleeding with low-dose aspirin in pts with actively bleeding peptic ulcers (PU).Eligible:active PU bleed & cont. need for aspirin.Exclusion:Unsuccessful endoscopic hemostasisSensitivity to PPIDual antiplatelet agent neededRandomized post-EGD to aspirin or placebo for 8 weeks.
40The 30-day incidence of recurrent bleeding was 10 The 30-day incidence of recurrent bleeding was 10.3% in the aspirin group versus 5.4% in placebo group, but the all-cause mortality at 8 weeks was significantly lower in the aspirin group than in the placebo (1.3% vs 12.9%, 95% CI for the difference: 3.7%–19.5%).This difference persisted even when they excluded deaths due to gastrointestinal complications.The authors assert that continuous aspirin therapy for secondary prevention, even in the setting of active bleeding PU disease, may reduce mortality rates because of the reduced risk of cardiovascular and cerebral vascular events.Ann Intern Med. 2010;152(1):1-9
4141 studies - 49,590 patients (14,981 on aspirin) 12 retrospective obs., 19 prospective obs., 10 randomizedDental, biopsies, multi-level spine, THA, major vascular/CEA, ENT, neurosurg, and TURP’s.No change in bleeding complications, except:TURP/Prostate proceduresaspirin users: 0.4–5.0 units of red blood cells, VS control patients 0.3–1.7 units
42Randomized double blind placebo-controlled 220 high-risk CAD patientsUndergoing intermediate- to high- risk noncardiac surgery.Randomized to:daily low-dose aspirin or placebo
43Two patients (2%) in the aspirin group versus none in the placebo group (p=0.24) had bleeding which necessitated reoperation in the perioperative period.Both had urologic procedures (TURP, open prostatectomy).There were no significant differences in the amount of:Intraoperative EBL (aspirin 300 mL vs placebo 300 mL, p=0.61)postoperative bleeding between the 2 groupssurgeon’s assessment of intraoperative bleedingNo statistically significant differences between the groups:CrystalloidsPacked red blood cellsPlasma
44Dermatologic Chu et al, J Am Acad Dermatol 2011 Alcalay et al, Dermatol Surg 2004Reviewed bleeding complications: biopsies, excisions, and Mohs procedures while on aspirinNo significant events; do not stop aspirinCook-Norris et al, J Am Acad Dermatol 2011Retrospective analysis, 220 patients, 363 procedures on DUAL anti-platelet rx (aspirin + clopidogrel)There were significant wound-related complicationsnone life-threateningAttributed majority of problems to combination or the clopidogrel
45Rosenbaum et al, Ann Vasc Surg 2010 VascularRosenbaum et al, Ann Vasc Surg 2010Retrospective review of various antiplatelet regimes in CEA260 patients, 171 continued aspirin perioperativelyNeck hematoma – no differenceOther bleeding complications – no differenceBurdess et al, Ann Surg 2010Prospective; lower extremity vascularAll on aspirin ± clopidogrelNo statistical difference in major or minor bleeding on dual APAAspirin alone did not impact bleeding-related issuesBurdess:
46Vascular - Lindblad et al, Stroke 1993 Vascular surgeons blinded to aspirin use in CEA:Could not differentiate patients on aspirin from patients off aspirin just from bleeding behavior
47Urologic - Renal transplantation Eng et al, Clin Transplant 2011Retrospective59 on aspirin preop vs 213 no anti-platelet agentNo significant differences in:Transfusion requirementsChange in hemoglobinHospital LOS(5.1% vs 1.4% for no preoperative therapy, RR = 3.61, P = 0.12).Because of the limited number of patients, the 95% CI for the RR was very wide (0.84–15.21).
48Urologic – Prostate Surgery - 1 Aspirin may cause significant bleeding complications in TURP procedures.vascular bedendogenous urokinase2 studies from 1990’s:Increased bleeding and need for significant more blood products in TURP patients on aspirin.Wierod et al, Scand J Urol Nephrol 1998Thurston et al, Br J Urol 1993
49Urologic – Prostate Surgery - 2 Ala-Opas et al, Scand J Urol Nephrol 1996Chronic - 250mg/dayTURPNo greater EBL than nonusersaspirin users: 358 mL vs nonusers: 478 mLNielsen : RECENT study
50Urologic – Prostate Surgery - 3 Nielsen et al, Scand J Urol Nephrol 2000Prospective, randomized, double-blind, placebo-controlled.150 mg continued perioperatively.Intraop blood loss:no differencePostop blood loss:aspirin group (n=26) significantly higher vs placebo (n=27)median 284ml vs median 144ml, P=0.011No significant differences in:Foley catheter removalLOSTransfusion requirementsTheir group recommended holding aspirin for 10 days preoperatively.
51General / Trauma Surgery Ferraris et al, Surg Gyn Obst 1983Small (n=52) observational study‘Unplanned’ appendectomy & cholecystectomyNo impact on bleeding-related complicationsNo additional need for transfusion
52General / Trauma Surgery Ott et al, J Trauma 2010Retrospective, 212 patients adm to L-1 trauma center (excluding head injuries)67 on aspirin, clopidogrel, warfarin, or comboTotal LOS - increased11.5 days vs 8.8 days, P = 0.04ICU LOS – no difference4.7 days vs 3.9 days, P = 0.5Injury Severity Score – no difference21.4 vs 21.0, P = 0.76Mortality – no difference13.4% users vs 9.7% nonusers, P = 0.41.Although this study was not on patients undergoing an elective surgical procedure, it is germane to the trauma surgical population.
53Orthopedic Surgery - Hip fracture / Femoral neck fractures Thaler et al, J Trauma 2010Used PFA in 98 patients on chronic aspirin rx64 (65%) had true impaired platelet functionMortality, major bleeding, red blood cell requirement, and drainage blood loss did not correlate with platelet aggregation inhibitor intake or platelet function.collagen/epinephrine closure time (CEPI-CT) has been shown to reflect platelet inhibition by aspirin and clopidogrel
54NeurosurgeryMeningioma with neuro sx’s dx’ed 3 months after placement of DES: dual APAEmbolization, admitted/telemetry, plavix stopped / ASA continued / bridged with eptifibatide (Integrillin) until 8 hours preop.no unusual surgical bleeding was noted. The patient was discharged on postoperative day 3 withsatisfactory recovery
56POISE-2 Evaluation of the effect of ‘low-dose’ aspirin vs placebo Non-cardiac surgeryJuly Dec 2013135 hospitals / 23 countriesPrimary endpoint:30-day composite risk of death & nonfatal MIRandomized, controlled multicenter trial conducted from
57POISE-2 - MethodsInitiation - 200mg ASA just before surgery & continued 100mg for 30-days post-op. Continuation (daily ASA use pre-op for 4/6 weeks) - stopped aspirin for at least 3 days pre-op - ‘placebo group’ to preop ASA dose after 7-days - ‘aspirin group’ restarted with 100mg postopContinuation group: prior users of aspirinInitiation group: not prior users of aspirinThe 30-day follow-up was complete for 99.9% of the patients
58200 mg preop >>>100 mg/d x 30 days post-opNo aspirin 3 days preop >>>200 mg preop >>>100 mg/d postop x 7 days >>>Usual dose for balanceNo aspirinNo aspirin 3 days preop >>>Placebo x 7 days postop >>>Usual dose for balance
61Problem 1 – High-risk Population? Participants requiring aspirin for either primary or secondary prevention made up no more than 36.3% of all pts assigned to aspirin groupIt is unclear from risk criteria whether any addt’l pts met AHA guidelines for aspirinAlso, unclear how many CS pts were taking aspirin for a guideline recommendation
62Problem 2 – Placebo Group really Placebo? 2821 IS patients received no aspirin during study period2191 CS returned to usual aspirin dose within 7 daysHence, 44% (2191 / ( )) of Placebo Group was actually on aspirin for 23 of 30 day follow-up
64Bleeding – 1/7 ‘Safety Outcomes’ Major bleedA major bleed was defined as a bleeding event that was not specified under life- threateningbleeding and resulted in any one of the following:1. a hemoglobin ≤70 g/L and the patient received a transfusion of ≥2 units of red blood cells;2. a hemoglobin drop of ≥50 g/L and the patient received a transfusion of ≥2 units of red bloodcells;3. the patient received a transfusion of ≥4 units of red blood cells within a 24 hour period;4. any one of the following interventions (i.e., embolization, superficial vascular repair, nasalpacking); or5. retroperitoneal, intraspinal, or intraocular (confirmed clinically or on imaging) bleeding.
66* the second composite outcome was a composite of mortality, nonfatal myocardial infarction, cardiac revascularization procedure,nonfatal pulmonary embolism, or nonfatal deep venous thrombosis.Major bleedA major bleed was defined as a bleeding event that was not specified under life- threateningbleeding and resulted in any one of the following:1. a hemoglobin ≤70 g/L and the patient received a transfusion of ≥2 units of red blood cells;2. a hemoglobin drop of ≥50 g/L and the patient received a transfusion of ≥2 units of red bloodcells;3. the patient received a transfusion of ≥4 units of red blood cells within a 24 hour period;4. any one of the following interventions (i.e., embolization, superficial vascular repair, nasalpacking); or5. retroperitoneal, intraspinal, or intraocular (confirmed clinically or on imaging) bleeding.
68POISE-2 IssuesOnly ~1/3 aspirin-patients were on appropriate indications.4-4.5% in each group received therapeutic anti-coagulant.1.2% in each group received P2Y12 inhibitors.Safety of aspirin withdrawal in pts with prior percutaneous coronary interventions not fully elucidated.Placebo (?) vs aspirin.
72SummaryTemporary cessation of aspirin rx should only be considered for procedures:risk of bleeding > > risk of a major adverse CV event2 major groups of procedures to consider when contemplating aspirin cessation:1) Additional / excessive EBL would lead to worse outcomes:intracranial surgeryspinal canal proceduresposterior chamber eye surgerymiddle ear surgerypossibly prostate surgeryKorinth M, Acta Neurochir 2006Chassot et al, BJA 2007Korinth et al, Eur Spine 20072) Procedures in which an increase in surgical blood loss to have minimal consequences:no change in transfusion requirements or no increase in major morbidity or mortality.Samana et al, Can J Anes 2002However, it is important to note that most of the information on the risks of continuing aspirin in the perioperative period is observational and retrospective.- weighing the increased risk of bleeding with aspirin continuation versus the thrombotic risk associated with aspirin cessation.The perioperative management of aspirin should be based on an optimal risk–benefit assessment