Sellar and parasellar tumor removal without discontinuing antithrombotic therapy

Yoshikazu Ogawa MD, PhD1 and Teiji Tominaga MD, PhD2
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  • 1 Department of Neurosurgery, Kohnan Hospital; and
  • | 2 Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
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OBJECT

Treatment with dual antiplatelet agents associated with coronary stenting procedures and long-term anticoagulant therapy is increasingly common, but the treatment carries risks during surgical procedures. Evidence-based recommendations have proposed discontinuation of antithrombotic treatment or introduction of bridging therapy in some procedures less invasive and with lower risk of bleeding. However, neurosurgical procedures without discontinuation of antithrombotic treatment and perioperative management have received little investigation.

METHODS

Between October 2008 and January 2014, 15 consecutive patients (11 males and 4 females; age range 51–75 years [mean 68.2 years]), with sellar and parasellar tumors were treated through the transsphenoidal approach without discontinuation of antithrombotic therapy. Clinical data were compared with another 15 patients, who underwent transsphenoidal surgeries without preoperative antithrombotic therapy.

RESULTS

Gross-total removal of the tumor or total aspiration of the content of Rathke's cleft cyst was achieved in 13 patients, and subtotal removal was achieved in 1 patient with a small remnant in the cavernous sinus. No difference was found in intraoperative bleeding between the antithrombotic agent group and the control group (mean 255 ml vs 215 ml, Mann-Whitney U-test, p = 0.547), and no patient required transfusion. No difference was found in operation time between the antithrombotic agent group and the control group (167.8 minutes vs 150.0 minutes, Mann-Whitney U-test, p = 0.262). All patients were discharged on postoperative Day 12 without neurological deficits.

CONCLUSIONS

The present study suggests that discontinuation of antithrombotic therapy may be unnecessary before the typical transsphenoidal surgery. Large randomized clinical trials at multiple centers are needed to confirm these findings.

ABBREVIATION

PT-INR = prothrombin time; international normalized ratio.

OBJECT

Treatment with dual antiplatelet agents associated with coronary stenting procedures and long-term anticoagulant therapy is increasingly common, but the treatment carries risks during surgical procedures. Evidence-based recommendations have proposed discontinuation of antithrombotic treatment or introduction of bridging therapy in some procedures less invasive and with lower risk of bleeding. However, neurosurgical procedures without discontinuation of antithrombotic treatment and perioperative management have received little investigation.

METHODS

Between October 2008 and January 2014, 15 consecutive patients (11 males and 4 females; age range 51–75 years [mean 68.2 years]), with sellar and parasellar tumors were treated through the transsphenoidal approach without discontinuation of antithrombotic therapy. Clinical data were compared with another 15 patients, who underwent transsphenoidal surgeries without preoperative antithrombotic therapy.

RESULTS

Gross-total removal of the tumor or total aspiration of the content of Rathke's cleft cyst was achieved in 13 patients, and subtotal removal was achieved in 1 patient with a small remnant in the cavernous sinus. No difference was found in intraoperative bleeding between the antithrombotic agent group and the control group (mean 255 ml vs 215 ml, Mann-Whitney U-test, p = 0.547), and no patient required transfusion. No difference was found in operation time between the antithrombotic agent group and the control group (167.8 minutes vs 150.0 minutes, Mann-Whitney U-test, p = 0.262). All patients were discharged on postoperative Day 12 without neurological deficits.

CONCLUSIONS

The present study suggests that discontinuation of antithrombotic therapy may be unnecessary before the typical transsphenoidal surgery. Large randomized clinical trials at multiple centers are needed to confirm these findings.

ABBREVIATION

PT-INR = prothrombin time; international normalized ratio.

Long-term anticoagulant therapy is currently administered to more than 6 million patients for the treatment of atrial fibrillation, deep venous thrombosis, various valve diseases, and malignancy-related syndromes.4,5 In addition, recent advances in coronary stenting procedures have rapidly increased the need for treatment with dual antiplatelet agents.5 However, about 10% of these patients will undergo invasive procedures every year, which will require temporary discontinuation of the antithrombotic therapy or some bridging therapy.4,5,21,28 Evidence-based recommendations have been proposed to deal with this complicated countermeasure in some less invasive procedures with lower risk of bleeding, such as dental procedures or cataract operations.1–3,6–19,21–25,29,30,32–38 However, procedures without discontinuation of antithrombotic treatment have received little attention,39 and the perioperative period in neurosurgical procedures has also been less well studied.20,26,27,31,40–42

The present clinical study retrospectively analyzed a series of transsphenoidal surgeries performed without discontinuation of antithrombotic therapy for comparison with the same number of transsphenoidal surgeries performed in the absence of antithrombotic therapy.

Methods

Between October 2008 and January 2014, 15 consecutive patients (11 males and 4 females; age range 51–75 years [mean 68.2 years]) with sellar and parasellar tumors were treated via a transsphenoidal approach by a single surgeon (Y.O.), accounting for 2.51% of all transsphenoidal operations during the same period. The histological diagnoses were pituitary adenoma (n = 9), Rathke's cleft cyst (n = 4), clival chordoma (n = 1), and biopsy of skull base pachymeningitis (n = 1). Eleven patients were treated with antiplatelet agents and 4 with anticoagulant agents. The prothrombin time–international normalized ratio (PT-INR) was measured preoperatively before administering anticoagulant agents, which verified that all PT-INRs were within the required limits (Table 1). The patients continued to take antithrombotic agents until the morning of surgery, and, after verification of the absence of ischemic and/or hemorrhagic complications on the morning of postoperative Day 1, administration of antithrombotic agents was restarted. All operations were performed via sublabial mucosal incisions, and the closest attention was paid to preserve the arachnoid plane at the top of the lesions in expectation of postprocedural hemostasis by compressive pressure of CSF spaces. Extended transsphenoidal surgeries through the subarachnoid spaces and giant pituitary adenomas with a maximum diameter larger than 40 mm were excluded due to the presumptive high risk of after-bleeding. Clinical data were compared with the data of 15 patients who underwent transsphenoidal surgery without preoperative antithrombotic therapy between December 2013 and January 2014. The surgical policy was explained preoperatively to the patients, and written informed consent was obtained. The overall study design was approved by the ethics committee of Kohnan Hospital. Statistical comparisons used Mini Statmate software (ATMS Co., Ltd.), and p values < 0.05 were regarded as significant.

TABLE 1

Profiles of patients undergoing antithrombotic therapy

Case No.Age (yrs), SexHistologyAntithrombotic AgentReasonRemarks
174, MAtypical adenomaAspirin 100 mgACA stenosisOpening of CS
267, MRathke's cleft cystAspirin 100 mgCoronary stent
375, MPlurihormonal adenomaAspirin 100 mgAnginaOpening of CS
471, FRathke's cleft cystClopidogrel 25 mgMCA stenosis
572, MRathke's cleft cystAspirin 81 mgAMI
675, FAcromegalyPT-INR 1.34Paroxysmal AF
762, MPlurihormonal adenomaAspirin 100 mgAngina
866, MRathke's cleft cystAspirin 100 mgCoronary stent
Ticlopidine 200 mgY graft & FF bypass
967, FGonadotroph cell adenomaCilostazol 200 mgAortic dissection
1072, MMixed GH & PRL adenomaAspirin 100 mgRepeat anginaSuspended clopidogrel
1151, MPachymeningitisPT-INR 2.01AVR, AV block (3)Temporary pacemaker
1269, MPlurihormonal adenomaAspirin 100 mgCoronary stentOpening of CS
1370, MNull cell adenomaAspirin 100 mgAngina
1471, FCorticotroph cell adenomaPT-INR 1.55DVT
1561, MChordomaPT-INR 1.95Paroxysmal AFOpening of CS

ACA = anterior cerebral artery; AF = atrial fibrillation; AMI = acute myocardial infarction; AV = atrioventricular; AVR = aortic valve replacement; CS = cavernous sinus; DVT = deep venous thrombosis; FF = femoral-femoral; GH = growth hormone; MCA = middle cerebral artery; PRL = prolactin; PT-INR = prothrombin time-international normalized ratio.

Results

Gross-total removal of the tumor or total aspiration of the content of the Rathke's cleft cyst was achieved in 13 patients, and subtotal removal was achieved in 1 patient with a small remnant in the cavernous sinus. Aggressive removal was suspended in 1 patient because intraoperative histological examination had revealed pachymeningitis. Head CT scanning performed the morning of postoperative Day 1 revealed that most cavities of the sellae were occupied with CSF, so-called empty sellae. No patient experienced massive abnormal bleeding throughout the hospital course. Comparison of the antithrombotic agent group and the control group found no difference in preoperative tumor volume (antithrombotic agent group vs control: 2.45 ml vs 3.18 ml, p = 0.48), but patients were older in the antithrombotic agent group (63.32 years vs 57.73 years, p = 0.029). Opening of the ipsilateral cavernous sinus occurred in 4 patients in the antithrombotic agent group, but hemostasis was achieved in all patients with common techniques, such as compression with cotton flakes and/or point-by-point coagulation. In the antithrombotic agent group, bleeding varied from 100 ml to 485 ml (mean 255 ml), and no patient required transfusion, even after open cavernous sinus surgeries. Comparison of the antithrombotic agent group and the control group found no difference in intraoperative bleeding (255 ml vs 215 ml, Mann-Whitney U-test, p = 0.547). Operation time varied in the antithrombotic agent group from 114 minutes to 241 minutes (mean 167.8 minutes). Comparison of the antithrombotic agent group and the control group found no difference in operation time (167.8 minutes vs 150.0 minutes, Mann-Whitney U-test, p = 0.262) (Tables 2 and 3). All patients were discharged on postoperative Day 12 without neurological deficits.

TABLE 2

Results of surgery with antithrombotic therapy

Case No.HistologyVol (ml)Blood Loss (ml)Operation Time (mins)Removal Rate (%)
1Atypical adenoma1.89130164100
2Rathke's cleft cyst0.86230114100
3Plurihormonal adenoma1.16125149100
4Rathke's cleft cyst0.94485162100
5Rathke's cleft cyst0.09100137100
6Acromegaly3.04150127100
7Plurihormonal adenoma4.39290228100
8Rathke's cleft cyst0.5125123100
9Gonadotroph cell adenoma0.6300144100
10Mixed GH & PRL adenoma5.46460171100
11Pachymeningitis115241Biopsy
12Plurihormonal adenoma9.0142523796
13Null cell adenoma2.89205131100
14Corticotroph cell adenoma0.01290195100
15Chordoma3.4400194100
TABLE 3

Results of surgery without antithrombotic therapy

Case No.Age (yrs), SexPathologyVol (ml)Blood Loss (ml)Operation Time (mins)Removal Rate (%)
1628, FLactotroph cell adenoma0.05135156100
1754, FAcromegaly4.8224519998
1858, MNonfunctioning1.89185147100
1946, MPlurihormonal adenoma3.56150164100
2071, FPlurihormonal adenoma2.28163157100
2141, MPituitary apoplexy2.57134119100
2265, FPlurihormonal adenoma0.91353145100
2366, MPlurihormonal adenoma3.23345120100
2456, FPlurihormonal adenoma0.84180123100
2562, FMixed GH & PRL adenoma0.32100119100
2670, MPlurihormonal adenoma5.86350191100
2781, MPlurihormonal adenoma3.63120155100
2881, MSomatotroph cell adenoma11.0253519095
2955, FPlurihormonal adenoma6.55135148100
3032, FPlurihormonal adenoma0.19100116100

Discussion

The risk of thrombosis has been estimated for some systemic diseases or conditions.4,5,28 Recent venous thrombosis (within 1 month), repeated arteriovenous thrombophilia, and mitral valve disease carry higher risks of thrombosis, whereas old venous thrombosis (> 3 months) and nonvalvular atrial fibrillation involve lower risks of thrombosis.21 Invasive procedures also involve the risk of bleeding in patients receiving antithrombotic therapy. Orthopedic hip procedures and colon polypectomy have higher risks of bleeding, whereas dental procedures, cataract surgery, dermatological procedures, and surgery for carpal tunnel syndrome have lower risks of bleeding.4 The factors of thrombogenesis and fibrinolysis have been specifically considered in some invasive procedures, resulting in evidence-based recommendations for discontinuation of antithrombotic therapy or introduction of bridging therapy.4,5,21,28 A large randomized study was reported recently in patients receiving or not receiving aspirin therapy who underwent noncardiac surgery. The study revealed that there was not an increase in cardiac or cerebrovascular events in the patients who discontinued the antiplatelet therapy compared with those who did not, although there was a slight increase in the amount of hemorrhage in the group that stayed on antiplatelet therapy.12 However, in this study more than two-thirds of the patients had received bridging anticoagulant therapy, so the true result with or without discontinuation of antiplatelet therapy in perioperative period remains unsolved.

Very few clinical studies have considered perioperative management of neurosurgical patients receiving antithrombotic therapy except for antiplatelet therapies incorporated in intravascular treatments.20,26,27,31,42 Temporary discontinuation of antithrombotic therapy or introduction of bridging therapy is rarely mentioned in cases of internal carotid artery dissection,40 as is placement of cutaneousventricular drainage for patients after intravascular treatment.41 However, these cases do not provide a high level of medical evidence.

The present cohort study was performed at a single institution and by a single surgeon. The protocol was simple, as neither discontinuation of antithrombotic therapy nor introduction of bridging therapy was required. Therefore, the treatment and control groups were easily compared. However, the true implications cannot be fully clarified, and validation of this protocol is limited only to extraarachnoid, typical transsphenoidal surgeries. Large randomized clinical trials at multiple centers are essential to recommend standardization of this management for patients receiving antithrombotic therapy. Although patients receiving antithrombotic therapy should only undergo transsphenoidal surgery when absolutely necessary, various types of procedures should be investigated to establish a high level of medical evidence about this increasing problem in the neurosurgical field.

Conclusions

Transsphenoidal surgeries were performed in 15 patients without discontinuation of antithrombotic therapy. No patient required transfusion, and intraoperative bleeding, operation time, and tumor removal rate showed no significant differences between these patients and the control group. The present study suggests that discontinuation of antithrombotic therapy may be unnecessary before the typical transsphenoidal surgery. Large randomized clinical trials are needed to establish validation of this procedure.

Author Contributions

Conception and design: Ogawa. Acquisition of data: Ogawa. Analysis and interpretation of data: Ogawa. Drafting the article: Ogawa. Critically revising the article: both authors. Reviewed submitted version of manuscript: Tominaga. Approved the final version of the manuscript on behalf of both authors: Ogawa. Statistical analysis: Ogawa. Administrative/technical/material support: Ogawa. Study supervision: Tominaga.

References

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    Cannon PD, & Dharmar VT: Minor oral surgical procedures in patients on oral anticoagulants—a controlled study. Aust Dent J 48:115118, 2003

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    Carrel TP, , Klingenmann W, , Mohacsi PJ, , Berdat P, & Althaus U: Perioperative bleeding and thromboembolic risk during non-cardiac surgery in patients with mechanical prosthetic heart valves: an institutional review. J Heart Valve Dis 8:392398, 1999

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    • Export Citation
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  • 1

    Ah-Weng A, , Natarajan S, , Velangi S, & Langtry JA: Preoperative monitoring of warfarin in cutaneous surgery. Br J Dermatol 149:386389, 2003

    • Search Google Scholar
    • Export Citation
  • 2

    Alam M, & Goldberg LH: Serious adverse vascular events associated with perioperative interruption of antiplatelet and anticoagulant therapy. Dermatol Surg 28:992998, 2002

    • Search Google Scholar
    • Export Citation
  • 3

    Alcalay J: Cutaneous surgery in patients receiving warfarin therapy. Dermatol Surg 27:756758, 2001

  • 4

    Armstrong MJ, , Gronseth G, , Anderson DC, , Biller J, , Cucchiara B, & Dafer R, et al.: Summary of evidence-based guideline: periprocedural management of antithrombotic medications in patients with ischemic cerebrovascular disease: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 80:20652069, 2013

    • Search Google Scholar
    • Export Citation
  • 5

    Baron TH, , Kamath PS, & McBane RD: Management of antithrombotic therapy in patients undergoing invasive procedures. N Engl J Med 368:21132124, 2013

    • Search Google Scholar
    • Export Citation
  • 6

    Billingsley EM, & Maloney ME: Intraoperative and postoperative bleeding problem in patients taking warfarin, aspirin, and nonsteroidal anti-inflammatory agents. A prospective study. Dermatol Surg 23:381383, 1997

    • Search Google Scholar
    • Export Citation
  • 7

    Cannon PD, & Dharmar VT: Minor oral surgical procedures in patients on oral anticoagulants—a controlled study. Aust Dent J 48:115118, 2003

    • Search Google Scholar
    • Export Citation
  • 8

    Carrel TP, , Klingenmann W, , Mohacsi PJ, , Berdat P, & Althaus U: Perioperative bleeding and thromboembolic risk during non-cardiac surgery in patients with mechanical prosthetic heart valves: an institutional review. J Heart Valve Dis 8:392398, 1999

    • Search Google Scholar
    • Export Citation
  • 9

    Carter K, & Miller KM: Phacoemulsification and lens implantation in patients treated with aspirin or warfarin. J Cataract Refract Surg 24:13611364, 1998

    • Search Google Scholar
    • Export Citation
  • 10

    Custer PL, & Trinkaus KM: Hemorrhagic complications of oculoplastic surgery. Ophthal Plast Reconstr Surg 18:409415, 2002

  • 11

    Devani P, , Lavery KM, & Howell CJ: Dental extractions in patients on warfarin: is alteration of anticoagulant regime necessary?. Br J Oral Maxillofac Surg 36:107111, 1998

    • Search Google Scholar
    • Export Citation
  • 12

    Devereaux PJ, , Mrkobrada M, , Sessler DI, , Leslie K, , Alonso-Coello P, & Kurz A, et al.: Aspirin in patients undergoing non-cardiac surgery. N Engl J Med 370:14941503, 2014

    • Search Google Scholar
    • Export Citation
  • 13

    Dunn AS, & Turpie AG: Perioperative management of patients receiving oral anticoagulants: a systematic review. Arch Intern Med 163:901908, 2003

    • Search Google Scholar
    • Export Citation
  • 14

    Evans IL, , Sayers MS, , Gibbons AJ, , Price G, , Snooks H, & Sugar AW: Can warfarin be continued during dental extraction? Results of a randomized controlled trial. Br J Oral Maxillofac Surg 40:248252, 2002

    • Search Google Scholar
    • Export Citation
  • 15

    Gainey SP, , Robertson DM, , Fay W, & Ilstrup D: Ocular surgery on patients receiving long-term warfarin therapy. Am J Ophthalmol 108:142146, 1989

    • Search Google Scholar
    • Export Citation
  • 16

    Hall DL, , Steen WH Jr, , Drummond JW, & Byrd WA: Anticoagulants and cataract surgery. Ophthalmic Surg 19:221222, 1988

  • 17

    Kallio H, , Paloheimo M, & Maunuksela EL: Haemorrhage and risk factors associated with retrobulbar/peribulbar block: a prospective study in 1383 patients. Br J Anaesth 85:708711, 2000

    • Search Google Scholar
    • Export Citation
  • 18

    Katholi RE, , Nolan SP, & McGuire LB: Living with prosthetic heart valves. Subsequent noncardiac operations and the risk of thromboembolism or hemorrhage. Am Heart J 92:162167, 1976

    • Search Google Scholar
    • Export Citation
  • 19

    Katz J, , Feldman MA, , Bass EB, , Lubomski LH, , Tielsch JM, & Petty BG, et al.: Risks and benefits of anticoagulant and antiplatelet medication use before cataract surgery. Ophthalmology 110:17841788, 2003

    • Search Google Scholar
    • Export Citation
  • 20

    Kim DJ, , Suh SH, , Kim BM, , Kim DI, , Huh SK, & Lee JW: Hemorrhagic complications related to the stent-remodeled coil embolization of intracranial aneurysms. Neurosurgery 67:7379, 2010

    • Search Google Scholar
    • Export Citation
  • 21

    Lip GYH, , Durrani OM, , Roldan V, , Lip PL, , Marin F, & Reuser TQ: Peri-operative management of ophthalmic patients taking antithrombotic therapy. Int J Clin Pract 65:361371, 2011

    • Search Google Scholar
    • Export Citation
  • 22

    McCormack P, , Simcock PR, & Tullo AB: Management of the anticoagulated patient for ophthalmic surgery. Eye (Lond) 7:749750, 1993

  • 23

    McMahan LB: Anticoagulants and cataract surgery. J Cataract Refract Surg 14:569571, 1988

  • 24

    Morris A, & Elder MJ: Warfarin therapy and cataract surgery. Clin Experiment Ophthalmol 28:419422, 2000

  • 25

    Narendran N, & Williamson TH: The effects of aspirin and warfarin therapy on haemorrhage in vitreoretinal surgery. Acta Ophthalmol Scand 81:3840, 2003

    • Search Google Scholar
    • Export Citation
  • 26

    Niemi T, & Armstrong E: Thromboprophylactic management in the neurosurgical patient with high risk for both thrombosis and intracranial bleeding. Curr Opin Anaesthesiol 23:558563, 2010

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