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Clinical Neurology and Neurosurgery 120 (2014) 49–54

Contents lists available at ScienceDirect

Clinical Neurology and Neurosurgery

journa l homepage: www.e lsev ier .com/ locate /c l ineuro

nfluence of antiplatelet therapy on postoperative recurrence ofhronic subdural hematoma: A multicenter retrospective study in 719atients

asanori Wadaa,∗, Iwao Yamakamib, Yoshinori Higuchic, Mikio Tanakad, Sumio Sudae,unichi Onof, Naokatsu Saekic

Department of Neurosurgery, Chiba Rehabilitation Center, 1-45-2 Hondacho, Midori-ku, Chiba-shi, Chiba 266-0005, JapanDepartment of Neurosurgery, Chiba Central Medical Center, 1835-1 Kasoricho, Wakaba-ku, Chiba 264-0017, JapanDepartment of Neurological Surgery, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-0856, JapanDepartment of Neurosurgery, Sanmu Medical Center, 167 Naruto, Sanmu-shi, Chiba 289-1326, JapanDepartment of Neurosurgery, Kimitsu Chuo Hospital, 1010 Sakurai, Kisarazu-shi, Chiba 292-8535, JapanDepartment of Neurosurgery, Chiba Cardiovascular Center, 575 Tsurumai, Ichihara-shi, Chiba 290-0512, Japan

r t i c l e i n f o

rticle history:eceived 6 August 2013eceived in revised form8 December 2013ccepted 17 February 2014vailable online 24 February 2014

eywords:ntiplatelet agentsematomaubdural

a b s t r a c t

Objective: The present study tested the hypothesis of whether antiplatelet agents (APA) induce chronicsubdural hematoma (CSDH) recurrence via a platelet aggregation inhibitory effect.Method: We examined risk factors for CSDH recurrence, focusing on APA, in 719 consecutive patientswho admitted to three tertiary hospitals and underwent burr-hole craniostomy and irrigation for CSDH.This was a multicenter, retrospective, observational study.Results: Age, sex, history of diabetes mellitus, hypertension, chronic renal failure, alcohol consump-tion habits, consciousness disturbance on admission, or preoperative CT density was not associatedwith recurrence. Subdural drainage was significantly associated with less recurrence. Preoperative oralAPA administration was significantly associated with more recurrence. The recurrence rate of CSDH innon-APA group was 11% if surgery was performed on admission. However, if surgery was performed

ecurrenceisk factors

immediately after discontinuation of oral APA administration, the recurrence rate in APA group signifi-cantly increased to 32% (p value < 0.0001; odds ratio, 3.77; 95% confidence interval, 1.72–8.28). The effectof APA on CSDH recurrence gradually diminished as the number of days until initial surgery, after stoppingAPA, increased.Conclusion: Antiplatelet therapy significantly influences the recurrence of CSDH.

© 2014 Elsevier B.V. All rights reserved.

. Introduction

Chronic subdural hematoma (CSDH) is routinely encounteredy neurosurgeons. There are many different treatment methodsanging from conservative management with oral steroids, twistrill craniostomy [1], craniostomy with or without a closed drain-ge system, and craniotomy with extensive membranectomy. Weave been applying burr-hole craniostomy and irrigation with orithout closed-system subdural drainage as the primary treatment

ethod based on our past experience. We occasionally manage

ases requiring re-operation for CSDH recurrence within a monthfter the initial surgery.

∗ Corresponding author. Tel.: +81 43 291 1831; fax: +81 43 291 1857.E-mail address: wadam6222@yahoo.co.jp (M. Wada).

ttp://dx.doi.org/10.1016/j.clineuro.2014.02.007303-8467/© 2014 Elsevier B.V. All rights reserved.

Risk factors for CSDH recurrence have been examined in sev-eral prior reports. However, few statistically significant risk factorshave been identified [2–11]. Preoperative oral warfarin adminis-tration [2–14] and postoperative drainage [15] have already beensuggested to significantly influence recurrence. To the best of ourknowledge, however, except for the report by Rust et al. [14],antiplatelet agents (APA) have consistently been shown to haveno impact on CSDH recurrence [16–18]. Intuitively, it seems thatpreoperative antiplatelet therapy would affect recurrence, thoughthe evidence remains inconclusive. Thus, we conducted this studyto examine whether APA show associations with CSDH recur-rence.

While a protocol allowing the effects of warfarin to temporarilybe reversed has been established, it is not possible to reverse theinhibitory effects of APA, underscoring the importance of managingrisks associated with these drugs.

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We herein report risk factors for CSDH recurrence, focusingainly on APA.

. Materials and methods

.1. Study design

We conducted a retrospective observational study using datarom 719 consecutive patients admitted to 3 tertiary hospitals,anmu Medical Center (168 patients), Kimitsu Chuo Hospital (347),nd Chiba Cardiovascular Center (204) in Japan, between January, 1996 and February 1, 2006 and who underwent burr-hole cran-

ostomy and irrigation with or without drainage for CSDH.In general, burr-hole craniostomy and irrigation with or with-

ut drainage is the first choice for surgery for CSDH in aboveentioned hospitals. Twist-drill craniostomy was not adopted.

raniotomy with extensive membranectomy was considered assecond option if burr-hole irrigation failed. The indication for

urgery was symptomatic CSDH proven by CT scan. Presentingymptoms included headaches, confusion, disorientation, drowsi-ess, hemiparesis, ataxia, seizures and aphasia. Patients were

ncluded if they were aged 20 years or older and presented to theepartment of neurosurgery at the 3 above mentioned hospitalsith surgical indication.

Primary outcome was defined as the recurrence rate of CSDH inhe APA and non-APA group. The recurrence rate was defined as theate of re-operation for recurrent CSDH after previous primary burr-ole irrigation with or without drainage. Recurrence was defined ashe development of symptoms attributed to ipsilateral hematomai.e., same side as the initial surgery) proven by CT scan within 3

onthes of the initial surgery. The criteria for re-operation wereases in which the patient’s original neurological deficit increased,ecurred, or worsened, or new neurological deficits appeared, asvidenced by CT scan, necessitating further burr-hole surgery orraniotomy [1,19].

Secondary outcome was defined as contribution of other riskactors to the recurrence rate of CSDH.

Data from patients meeting the following exclusion criteriaere not analyzed:

. Taking warfarin.

. Organized CSDH: Patients who could not be irrigated by the oper-ating surgeon because of old solid clots, for whom drain insertionwas judged unsafe and whose CT showed presence of huge resid-ual CSDH 1 day after surgery.

. Multilocular CSDH: Patients who could not be sufficiently irri-gated by the operating surgeon because of septa, for whom draininsertion was judged unsafe and whose CT showed presence ofhuge residual CSDH 1 day after surgery.

. Thrombocytopenia (i.e., platelet count < 50,000/�L) due to cir-rhosis or thrombocytosis (i.e., platelet count > 2,000,000/�L) dueto leukemia.

CSDH patients who were surgical candidates were immediatelyospitalized. Oral APA administration was discontinued on admis-ion. In principle, the patient was not to resume oral APA for oneonth after surgery.All the data were obtained from medical charts, surgical reports

nd CT reviews.This study was approved by the ethics committee of our hospital.

.2. Patient demographics

We examined 10 factors: age, sex, history of diabetes melli-us (DM), hypertension (HT), chronic renal failure (CRF), alcohol

Neurosurgery 120 (2014) 49–54

consumption habits, consciousness disturbance on admission, pre-operative computed tomography (CT) density (classified into 5types: hypo/iso/high/mixed density and niveau), preoperative oralAPA administration and postoperative drainage. The neurosurgeoncompleted an admission proforma about presenting symptoms andthe 10 conditions mentioned above. DM, HT and CRF were definedby current treatment for the respective conditions. An alcohol con-sumption habit was defined as drinking 1 or more units of liquordaily. Consciousness level <15 on the Glasgow Coma Scale (GCS)was taken to indicate consciousness disturbance. CT studies werereviewed based on the characteristics of the hematoma. The densityof the hematoma was compared to that of the brain parenchyma. AnAPA was defined as an agent that has a platelet aggregation inhibi-tory function as the main effect. The type, dose, and compliance ofAPA were examined. If an APA was discontinued before admission,the duration from cessation to admission was checked.

2.3. Operative method

In the 3 aforementioned hospitals, essentially the same surgicaltechniques for craniostomy with or without the closed drainagesystem were employed for CSDH. The surgical protocol starts withlocal anesthesia, followed by hematoma evacuation and irrigationwith normal saline through one or two burr holes. We generallyadopted the 1 burr-hole technique. We only adopted the 2 burr-hole technique when the hematoma cavity was large or many septawere expected, making irrigation difficult. For closed system sub-dural drainage, a subdural catheter was connected to a plastic bagfixed on the bed located approximately 10 cm below the patient’sexternal acoustic meatus. Drainage was continued for 24–48 h aftersurgery depending on the amount to be drained [35]. When drainwas removed, the fluid color inside usually became xanthochromic.However, while closed system subdural drainage was performed inprinciple, the surgeon decides whether or not to adopt this methoddepending on the situation.

2.4. CT analysis

CT studies were performed in all patients to confirm the diagno-sis prior to the operation. Routine postoperative CT was performedone day and then again one week after surgery. Neurologicalassessment and CT follow-up were performed for several monthspostoperatively.

2.5. Statistical analysis

Data are given as means ± standard deviation. Results wereanalyzed for statistical significance using the unpaired Student’s t-test. The Pearson’s chi-square test and the Fisher’s exact test wereemployed for univariate analyses and the logistic regression modelfor multivariate analyses. Differences were considered significantif the probability value was <0.05. Statistical analyses were per-formed using IBM SPSS statistical software version 19.0 (IBM JapanLtd., Tokyo, Japan).

3. Results

The trial profile is shown in Fig. 1. A total 719 patients whowere candidates for burr-hole surgery were immediately hospital-ized, and underwent burr-hole irrigation with or without drainage.Meanwhile, 32 patients were excluded: 16 were taking warfarin, 9had organized CSDH (7 were observed after surgery and 2 under-

went craniotomy subsequently), 2 had multilocular CSDH, 4 hadthrombocytopenia due to cirrhosis, and 1 had thrombocytosis dueto leukemia. 6 patients dropped out. Ninety-two patients who tookAPA were classified into 2 groups according to the duration from

M. Wada et al. / Clinical Neurology and Neurosurgery 120 (2014) 49–54 51

CSDH in outpatient settings

Observation

719 Admitted

Indication for surgery (+)Indication for surgery (–)

32 Excluded16 taking warfarin9 organized CSDH

7 observation after surgery2 secondary craniotomy

2 multilocular CSDH4 thrombocytopenia due to cirrhosis1 thrombocytosis due to leukemia

Burr-hole irrigation532 with drainage187 without drainage

92 APA (+) 589 APA (–)

374Surgery

onAdmission

215Delayedsurgery

681 Analyzed

6 Dropped out; 5 died, 1 lost to follow-up

67 Recurrencere-operated 614 No recurrence

34Duration from

APA cessation to surgery

(–)

58Duration from

APA cessation to surgery

(+)

Fig. 1. The trial profile is shown. A total 719 patients who were candidates for burr-hole surgery were immediately hospitalized, and underwent burr-hole irrigation withor without drainage. Meanwhile, 32 patients were excluded and 6 dropped out. Ninety-two patients who took APA were classified into 2 groups according to the durationf e clasu reforea

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of APA taking. There was no significant difference in the distributionof drug, coagulation data between the duration from APA cessationto surgery (−) and (+) groups.

rom APA cessation to initial surgery. The 589 patients who did not take APA wernderwent delayed surgery. Furthermore, 67 patients underwent re-operation. Thegent; CSDH, chronic subdural hematoma.

PA cessation to initial surgery. The duration from APA cessationo surgery (−) group included 34 patients who underwent surgerynd APA cessation on admission. The duration from APA cessationo surgery (+) group included 11 patients who underwent surgeryhile discontinuing APA before admission and 47 patients whonderwent delayed surgery while discontinuing APA on admis-ion. The 589 patients who did not take APA were classified into 2roups: 374 patients who underwent surgery on admission and 215nderwent delayed surgery. Furthermore, 67 patients underwente-operation. Therefore, 681 patients were analyzed for recurrenceactor.

The characteristics of the remaining 681 patients are shown inable 1.

able 1haracteristics of 681 inpatients, including the distribution of APA treatment.

Characteristic n (%) or mean (SD)

DemographicsAge (years) 72.9(11.6)Male/female 454/227

Subdural drainage 517(75.9)APA 92(13.7)

Aspirin (median 100 mg/d) 47(6.8)Ticlopidine (median 200 mg/d) 28(4.0)Ethyl icosapentate 6(0.9)Cilostazol 4(0.6)Beraprost sodium 4(0.6)Dipyridamole 3(0.4)

bbreviation: APA, antiplatelet agent; SD, standard deviation.

sified into 2 groups: 374 patients who underwent surgery on admission and 215, 681 patients were analyzed for recurrence factor. Abbreviations: APA, antiplatelet

Table 2 shows univariate analysis of demographics in 681patients with CSDH. Only rates of DM and HT associated withatherosclerotic disease, i.e. the reason for taking oral APA, differedsignificantly between the APA and non-APA groups. There were nosignificant differences for any of the other factors.

Table 3 shows univariate analysis of demographics in 92 patients

Table 2Univariate analysis of demographics in 681 patients with CSDH.

Demographics APA (+) APA (−) p Value

No. of patients 92 589Age 78.1 72.1 NSM/F ratio 61/31 395/194 NSDM 21(23%) 67(11%) 0.04HT 42(46%) 196(33%) 0.01CRF 2(2%) 5(1%) NSAlcohol 15(16%) 147(25%) NSGCS score < 15 43(47%) 181(31%) NSCT density

Hypo density 64(70%) 371(63%) NSIso density 6(7%) 73(12%) NSHigh density 1(1%) 14(2%) NSMixed density 15(16%) 95(16%) NSNiveau 6(6%) 36(6%) NS

Drainage 76(83%) 441(75%) NS

Abbreviations: APA, antiplatelet agent; CRF, chronic renal failure; CT, computedtomography; DM, diabetes mellitus; GCS, Glasgow coma scale; HT, hypertension;NS, not significant.

52 M. Wada et al. / Clinical Neurology and Neurosurgery 120 (2014) 49–54

Table 3Univariate analysis of demographics in 92 patients of APA taking.

Demographics Duration from APAcessation to surgery (−)

Duration from APAcessation to surgery (+)

p Value

No. of patients 34 58APA

Aspirin 18(53%) 29(50%) NSTiclopidine 7(21%) 20(34%) NSCilostazol 1(3%) 3(9%) NS

PT–INR 1.15 1.19 NSAPTT (s) 29.4 29.7 NS

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SDH

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Duration from APA cessation to initial surgery (day)

APA taking (+)

APA taking (–)

Fig. 2. shows the influence of surgical delay on CSDH recurrence. If the initial surgerywas performed without delay after discontinuing oral APA, the CSDH recurrence ratewas significantly higher. Regardless of the presence or absence of APA administra-tion, the recurrence rate gradually decreased as the number of days until surgery

TM

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bbreviations: APA, antiplatelet agent; NS, not significant; PT–INR, prothrombinime–International normalized ratio; APTT, activated partial thromboplastin time.

Table 4 shows the multivariate analyses of factors related toSDH recurrence. Because surgical timing was judged by each neu-osurgeon, this would introduce bias. We tried to distinguish APAnd the time of surgery. Therefore, we compared the groups takingPA with surgery and APA cessation on admission, and not takingPA with surgery on admission. There was no significant difference

n age, sex, history of DM, HT, CRF, alcohol consumption habits,onsciousness disturbance on admission, or preoperative CT den-ity between these two groups. APA treatment was significantlyssociated with more recurrence and subdural drainage was sig-ificantly associated with less recurrence (p value, 0.004, 0.005;dds ratio [OR], 3.59, 0.41; 95% confidence interval [CI], 1.50–8.61,.22–0.76, respectively).

Then, we compared all patients taking and not taking APA toesolve the multicollinearity between APA and surgical timing inultivariate analysis. There was also no significant difference in

ge, sex, history of DM, HT, CRF, alcohol consumption habits, con-ciousness disturbance on admission, or preoperative CT densityetween these two groups. Subdural drainage was significantlyssociated with less recurrent CSDH (p value, 0.002; OR, 0.38; 95%

I, 0.21–0.70). Although APA treatment and immediate surgeryxhibited tendencies toward association with more recurrence, thessociation was not significant (p value, 0.06, 0.05; OR, 1.99, 2.04;5% CI, 0.96–4.10, 1.01–4.16, respectively).

able 4ultivariate analyses of factors related to CSDH recurrence.

Target patients APA taking APA not takSurgery and APAcessation on admission

Surgery on

No. of patients 34 374Recurrence (%) 11(32%) 42(11%)

Demographics Multivariate analysis

p Value ORc 95% CI

Agea 0.32 1.46 0.69–3.06M/F ratio 0.2 0.63 0.31–1.28DM 0.92 1.05 0.43–2.52HT 0.86 1.06 0.55–2.03CRF 1 0 0Alcohol 0.14 0.54 0.24–1.23GCS < 15 0.25 1.45 0.77–2.71CT density

Hypo density 0.71 1.26 0.39–4.07Iso density 0.21 2.32 0.63–8.59High density 0.99 0 0Mixed density 0.35 0.49 0.11–2.21Niveau Control

APA taking 0.004 3.59 1.50–8.61With Drainage 0.005 0.41 0.22–0.76Immediate surgeryb

a Classified as <70 or ≥70 years old.b Immediate surgery means no duration from APA cassation to surgery for the patientsc OR < 1 means less recurrence.

bbreviations: APA, antiplatelet agent; CI, confidence interval; CRF, chronic renal failurellitus; GCS, Glasgow coma scale; HT, hypertension; OR, odds ratio.

increased. If the surgery was delayed for more than 3 days, there was no CSDH recur-rence. Abbreviations: APA, antiplatelet agent; CSDH, chronic subdural hematoma.

Table 5 presents information about the oral APA taken by thestudy subjects. The recurrence rate of CSDH in non-APA groupwas 11% if surgery was performed on admission. However, if thepatients underwent surgery and APA cessation on admission, therecurrence rate in APA group significantly increased to 32% (pvalue < 0.0001; OR, 3.77; 95% CI, 1.50–8.28).

In many cases, the surgeon opted to delay surgery for about oneweek after APA discontinuation. If we include these patients amongthose taking APA, the recurrence rate with APA would be 14%. Thisis not significantly different from the 9% recurrence rate of thosenot taking APA (p value, 0.14; OR, 1.63; 95% CI, 0.85–3.12).

As shown in Fig. 2, regardless of APA administration, the recur-rence rate gradually decreased as the number of days until surgeryincreased. If the operation was delayed for more than 3 days, there

was no CSDH recurrence.

During the period of waiting for surgery after APA discon-tinuation, 3 patients required emergency surgery due to acute

ing APA taking APA not takingadmission Over all Over all

92 58913(14%) 54(9%)

Multivariate analysis

p Value OR 95% CI

0.31 1.39 0.74–2.640.2 0.67 0.37–1.230.7 1.16 0.55–2.430.71 1.11 0.64–1.931 0 00.28 0.68 0.34–1.360.58 1.17 0.67–2.03

0.58 0.76 0.29–2.010.79 1.17 0.38–3.580.9 0.86 0.09–8.270.18 0.43 0.12–1.47Control0.06 1.99 0.96–4.100.002 0.38 0.21–0.700.05 2.04 1.01–4.16

with APA, and surgery on admission for the patients without APA.

e; CSDH, chronic subdural hematoma; CT, computed tomography; DM, diabetes

M. Wada et al. / Clinical Neurology and Neurosurgery 120 (2014) 49–54 53

Table 5The influences of delaying surgery and APA on CSDH recurrence.

Duration from APAcessation to surgery

APA taking (+) APA taking (−) Univariate analysis

No. of patients Recurrence (%) No. of patients Recurrence (%) p Value OR 95% CI

0 34 11(32%) 374 42(11%) < 0.0001 3.77 1.77–8.281 10 1(10%) 153 9(6%)2 9 1(11%) 31 3(10%)3 4 0 16 04 1 0 6 05 4 0 1 06 6 0 2 07 4 0 2 08–13 days 16 0 3 0≥14 days 4 0 1 0

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bbreviations: APA, antiplatelet agent; CI, confidence interval; CSDH, chronic subdu

eurological deterioration. The operations were performed twoays after APA discontinuation in all 3 patients.

. Discussion

.1. Purpose of the study

Many large-scale clinical studies focusing on the preventiveffects of antiplatelet therapy on vascular disorders have been con-ucted over the past decade. Accordingly, the frequency of APA useas been increasing [17,20,21]. Therefore, the risk of severe bleed-

ng events due to APA has been recognized [22]. The association ofPA administration with the occurrence of CSDH has already beeneported [23,24]. While few studies have suggested APA to influ-nce CSDH recurrence, many reports have shown warfarin to affectecurrence [2,12–14,25].

Thus, we hypothesized that APA may induce recurrence via alatelet aggregation inhibitory effect.

.2. Interpretation of the results

If surgery is performed immediately, or soon, after discontin-ation of oral APA, the recurrence rate rises significantly. Theecurrence rate showed a gradual decrease as the number of daysntil surgery increased. If the surgery was delayed for more thandays, there was no CSDH recurrence. This is thought to reflect

he effects of attenuating blood APA levels and the regeneration oflatelets. Platelets have a life-span of approximately one week, andccordingly are produced daily. Even if only 20% of the total plateletopulation has normal cyclooxygenase activity, normal plate-

et aggregation is maintained. Furukawa et al. reported plateletggregation to be extremely enhanced one day after discontinu-ng oral aspirin and that the normal range was restored 3 daysfter discontinuation [26,27]. This is consistent with our presentesults.

In order to avoid severe complications, including acute fatalemorrhage, burr-hole surgery is delayed for approximately oneeek after discontinuing oral APA in many cases. If we include theseatients in whom surgery is delayed among those taking APA, there

s no significant difference in the CSDH recurrence rate between theroups with and without APA administration.

If we operate immediately and do not employ postoperative

rainage for patients taking APA, the total odds ratio would be.59/0.41 = 8.76, indicating a 8-fold increase in the risk of CSDHecurrence. Like warfarin, APA is an important risk factor for CSDHecurrence.

54(9%) 0.14 1.63 0.85–3.12

matoma; OR, odds ratio.

4.3. Mechanisms of recurrence

A gradual increase in CSDH has been recognized in clinicalpractice. Anticoagulant components of the hematoma itself [28,29]and oozing from numerous sinusoids of the outer membrane[30,31] are important mechanistic factors.

APA and other anticoagulants are considered to influence both ofthe aforementioned mechanistic factors. The anticoagulant effect ofwarfarin can be rapidly reversed prior to surgery. Since it is not pos-sible to reverse the inhibitory effect of APA on platelet aggregation,we cannot maintain normal platelet aggregation in the absence of aplatelet transfusion. Thus, even if anticoagulant components of thehematoma are replaced with saline by employing irrigation, ooz-ing from neovascular sinusoids is likely to be induced by APA. Onthe other hand, drainage may prevent CSDH recurrence probablydue to continuous evacuation of the anticoagulant components ofthe residual hematoma itself and via the promotion of brain tissueexpansion [15].

4.4. Future directions

It has been suggested that re-operation is the simplest manage-ment strategy, because the risk of fatal CSDH recurrence is low.However, unnecessary repeat surgery should be avoided from theviewpoints of patient burden and cost containment.

We can significantly reduce the effect of APA by delaying the ini-tial surgery just one day. In fact, surgery should be delayed at least3 days for patients taking oral APA, whenever possible. In addi-tion, guidelines for management of anticoagulant and antiplatelettherapy in cardiovascular disease in Japan include the followingrecommendations: if the operation is to be performed in a regionin which postoperative bleeding is difficult to control, the surgeryshould be delayed for at least 3, 7 and 14 days after discontinuationof oral cilostazol, aspirin and ticlopidine, respectively [32,33].

On the other hand, 3 of our patients experienced neurologicalsymptom deterioration while waiting for surgery. All 3 underwentemergency operations two days after discontinuing APA. Thus, neu-rosurgeons must remain vigilant regarding the most appropriatetiming of surgery.

4.5. Limitations

First, the concept that large individual differences exist in theantiplatelet properties of APA has been established recently. Plate-

let functions in patients in whom the inhibitory effect of APA onthese functions is low, the so-called poor responders, were notmeasured in this study [34]. This issue warrants further study inthe future.

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4 M. Wada et al. / Clinical Neurolog

Secondary, clopidogrel was not taken into consideration in thistudy, as it came on to the Japanese market in May 2006. Ourata were collected until January 2006. The use of clopidogrel hasecome common over the recent years. However, we would likeo highlight the generalizability of our findings. In addition, weonsider that the result of this study, the increased risk of CSDHecurrence, is probably similar with clopidogrel, as its antiplateletroperty is much higher than that of aspirin [35]. This issue alsoeeds to be investigated further.

Third, a limitation of this study is its retrospective nature. There-ore, further prospective studies are required to confirm the presentndings.

. Conclusion

Antiplatelet therapy significantly influences the recurrence ofSDH. We can, however, achieve major reductions in the impact ofPA by delaying the initial surgery just one day. It is optimal for

he operation to be delayed at least 3 days after discontinuationf oral APA to prevent recurrence, but with careful attention toeurological deterioration requiring emergency intervention.

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