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Venous thromboembolism continues tobe problematic in plastic surgery despiteincreased recognition and advancements

in venous thromboembolism prophylaxis. Venous

thromboembolism aects an estimated 33,000plastic surgery patients per year.1 Unortunately,

despite risk-assessment model publicity in theplastic surgery literature,24 the specialty still lagsbehind other medical elds in providing adequatevenous thromboembolism prophylaxis.57

American College o Chest Physicians venousthromboembolism prophylaxis guidelines arebased on the most comprehensive, multispe-cialty, systematic reviews compiled rom over 700

Disclosure: The authors have no fnancial interestin any o the products, devices, or drugs mentionedin this article. The authors have no relevant com-mercial associations or fnancial disclosures relatedto this article.Copyright 2013 by the American Society o Plastic Surgeons

DOI: 10.1097/PRS.0b013e318295870e

Jerrod N. Keith, M.D.Tae W. Chong, M.D.Diwakar Davar, M.D.

Alexander G. Moore, B.S.Alison Morris, M.D., M.S.Michael L. Gimbel, M.D.

Iowa City, Iowa; Dallas, Texas; and

Pittsburgh, Pa.

Background: Venous thromboembolism continues to be problematic despiteincreased recognition and advancements in venous thromboembolism prophy-laxis. Although migration toward preoperative chemoprophylaxis increases,plastic surgeons seem reticent to adopt this practice. This study evaluates pre-operative enoxaparin administration in breast reconstruction patients.Methods: Patients undergoing breast reconstruction perormed by a singlesurgeon over a 5-year period were evaluated retrospectively. The authors in-troduced preoperative chemoprophylaxis with enoxaparin in all breast re-constructions during this time. Prosthetic-based and microsurgical breastreconstructions were examined. Patients were divided into two groups: those

who did and those who did not receive preoperative enoxaparin. The authorsreviewed patient demographics, comorbidities, and complications, ocusing onbleeding complications.Results: Three hundred patients (450 breasts) were included. One hundredty-our patients (244 breasts) underwent reconstruction with tissue expand-ers, and 146 (206 breasts) underwent ree fap reconstructions. One hundredseventy-nine o 300 were given preoperative enoxaparin. Eleven hematomasoccurred, eight (4.5 percent) in the enoxaparin group and three (2.5 percent)without enoxaparin (p =0.399). Blood transusions were given to our patients(2.2 percent) who received enoxaparin and one patient (0.8 percent) whodid not (p = 0.652). Finally, any type o bleeding complication occurred in11 patients (6.1 percent) with enoxaparin and in our (3.3 percent) without(p= 0.419). Larger breasts were more likely to receive enoxaparin (p= 0.011),which did not result in higher bleeding complications.Conclusion: In this retrospective study, the authors ound that preoperativechemoprophylaxis in breast reconstruction was associated with an accept-able rate o postoperative bleeding complications. (Plast. Reconstr. Surg.132: 279, 2013.)CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

From the Department o Surgery, Division o Plastic Surgery,University o Iowa Hospitals and Clinics; the Department oPlastic Surgery, University o Texas Southwestern MedicalCenter; and the Departments o Medicine and Plastic Sur-gery, University o Pittsburgh School o Medicine.Received or publication February 4, 2013; accepted February26, 2013.

The Timing o Preoperative ProphylacticLow-Molecular-Weight Heparin Administration

in Breast Reconstruction

BREAST


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Plastic and Reconstructive Surgery August 2013

reerences.8 Plastic surgery patients are includedor the rst time in the 2012 guidelines. TheAmerican College o Chest Physicians recom-mends chemoprophylaxis or general or abdom-inal-pelvic surgery patients scoring 3 or higheron the Caprini scale. Patients with breast cancerundergoing mastectomy and reconstruction gen-erally all into the high-risk group, with Capriniscores o 5 or greater. Thus, it is advisable thatthese patients receive perioperative mechanicalprophylaxis and chemoprophylaxis. Althoughvenous thromboembolism chemoprophylaxis isrequently administered postoperatively in theeld o plastic surgery, other specialties take amore aggressive approach by administering pro-phylactic anticoagulants preoperatively. Recentstudies in both bariatric surgery patients and gyne-cologic oncology patients support the saety o use

o preoperative chemoprophylaxis in their respec-tive high-risk patient populations.9,10 In addition,in a meta-analysis o 26 studies investigating theadministration o preoperative chemoprophylaxisin cancer patients undergoing nonorthopedic sur-gical procedures, Leonardi et al. ound a threeolddecrease in thromboembolic complication rate.11Although preoperative chemoprophylaxis wouldseem logical, as venous pooling and stasis beginon induction o anesthesia, surgeons are reticentto give preoperative anticoagulants because o theincreased risk o surgical bleeding complications.

The purpose o our study was to evaluateour experience with preoperative enoxaparinadministration in breast reconstruction patients.Because o a change in clinical practice, we areable to compare two breast reconstruction patientcohorts; the rst group did not receive preop-erative chemoprophylaxis, whereas the secondgroup did. Specically, we address the questiono whether preoperative enoxaparin is associatedwith an acceptable bleeding complication risk inthis surgical population.

PATIENTS AND METHODSA retrospective review was perormed o all

patients undergoing breast reconstruction per-ormed by a single surgeon over a 5-year periodbetween October o 2006 and April o 2011.The senior surgeon (M.L.G.) gradually incor-porated preoperative chemoprophylaxis in allbreast reconstructions beginning in 2008. Insti-tutional review board approval was obtained toperorm this study. Latissimus dorsi and pedicledabdominal fap reconstructions were not included

because they were so ew that they represented a

very minor subset o our breast reconstructioncohort. All other breast reconstruction patientswere included in the analysis. Types o reconstruc-tions included prosthetic-based reconstructionwith tissue expanders/implants and microsurgicalbreast reconstruction. Patients were divided intotwo groups: those receiving preoperative prophy-lactic enoxaparin and those not receiving preop-erative prophylactic enoxaparin.

We reviewed the ollowing patient demograph-ics and comorbidities: age, BRCAstatus, diabetes,smoking status, coronary artery disease, hyper-tension, chronic obstructive pulmonary disease/asthma, autoimmune disease, prior breast cancer,body mass index, preoperative breast size (by bracup size, dening small as less than a D cup andlarge as D cup or greater), neoadjuvant chemo-therapy, and neoadjuvant radiation therapy. We

collected the ollowing operative and postopera-tive details: tissue expander pocket type (totalmuscle coverage or acellular dermal matrixassisted), acellular dermal matrix dimensions, tis-sue expander size and intraoperative ll volumes,estimated blood loss, antibiotic use and duration,drainage tube duration, and nal expander llvolume. Finally, we collected the ollowing peri-operative complication data: hematoma, seroma,the need or blood transusion, mastectomy fapcomplication, wound healing problem, inection,microvascular thrombosis, ree fap ailure, and

venous thromboembolic events.Hematomas were dened as those requir-

ing procedural interventions such as drainage orreoperation. Any bleeding complications weredened as those patients who encountered post-operative hematomas and/or blood transusions.

Statistical Analysis

Patient characteristics including demographic,comorbidities, body mass index, and operativedetails were summarized and compared betweenpatients receiving enoxaparin and those not receiv-

ing enoxaparin using ttests, Wilcoxon rank-sum,chi-square, or Fishers exact tests where appropri-ate, with a value op< 0.05 considered signicant.Bleeding complications including hematomas,transusion, or any complication were comparedby enoxaparin use using Fishers exact test in thecohort overall and in those having tissue expand-ers or ree faps.

RESULTSThree hundred seventeen patients underwent

breast reconstruction during the study period.


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Three hundred patients (450 breasts) wereincluded in the study, and 17 were excluded basedon type o reconstruction. Patient demographicsare listed in Table 1. Initially, no patients weregiven preoperative chemoprophylaxis. Over time,a change in practice pattern resulted in selected

use, ollowed by uniorm use, o preoperativeenoxaparin (30 mg) subcutaneously within 1 houro incision. Enoxaparin was continued ater sur-gery (40 mg daily or 30 mg twice daily) until thepatient was ambulatory. Mechanical prophylaxiswith sequential compression devices and earlyambulation was used in all patients. Chemopro-phylaxis was discontinued on discharge to home.

Patients underwent tissue expander place-ment (n= 154), with either total muscular cover-age (n= 32) or with the use o acellular dermalmatrix (n= 122). Expanders were lled intraop-

eratively, with an average initial ll volume o 165cc and an average nal ll volume o 460 cc. Jack-son-Pratt drains remained in place or an averageo 13 days. One drain per mastectomy site wasused or total mastectomies, and two drains persite were used or modied radical mastectomies.Microsurgical reconstructions (n = 146 patients,206 breasts) included abdomen-based faps(199 breasts), transverse upper gracilis faps (sixbreasts), and a superior gluteal artery peroratorfap (one breast). There was one ree fap ailure.Although there were no identied deep venous

thromboses in any patients, one ree fap patientwho received preoperative enoxaparin developedan asymptomatic postoperative pulmonary embo-lism ound incidentally on computed tomographyo the abdomen or distention. Table 2 lists proce-dural and enoxaparin results.

The rate o bleeding complications was low. Atotal o 11 hematomas occurred in eight patients(4.5 percent) who received enoxaparin and in

three (2.5 percent) who did not. Blood transu-sions were given in our patients (2.2 percent)who received enoxaparin and in one patient(0.8 percent) who did not. Finally, any type obleeding complication (hematomas plus transu-sions) occurred in 11 patients (6.1 percent) who

received enoxaparin and in our patients (3.3 per-cent) who did not (Table 3).

Because increased complications have beenreported in reconstructions o women with largebreasts,12 breast size was analyzed independentlybased on preoperative bra cup size . First, we exam-ined whether there was bias in giving preoperativeenoxaparin based on bra cup size. No signicantdierence in enoxaparin use was observed betweenthe dierent breast cup size groups (p= 0.097). Wethen grouped the data into small and large breastsize, in which small breasts were dened as less

than D cup and large breasts were D cup or larger(Table 1). We ound that larger breasts were statisti-cally more likely to receive preoperative enoxapa-rin (p = 0.011). However, despite this increased useo enoxaparin, we ound no statistical increase inrates o hematoma ormation, blood transusions,or any bleeding complications between the smalland large breast groups.

There was a trend or patients with hemato-mas to have a somewhat lower body mass index(mean SD body mass index, 23.1 3.5 kg/m2 orhematomas versus 26.0 5.4 kg/m2 or no hema-

toma,p= 0.07). Need or transusion or presenceo any bleeding complication was not related tobody mass index (mean SD body mass index,25.8 5.4 kg/m2 or no transusion versus 28.1 6.8 kg/m2 or transusion,p= 0.36; or any compli-cation, 24.3 5.1 kg/m2 versus 26.0 5.4 kg/m2,p= 0.24).

Because fap reconstructions have inherentlylarger dissected tissue surace areas and thereore

Table 1. Demographic Information, Patient Comorbidities, and Pertinent Patient Characteristics

No Enoxaparin (%) Enoxaparin (%) Total (%) pNo. o patients 121 179 300Mean age, yr 47.8 47.7 0.959Mean BMI 25 26 0.303DM 1 (0.8) 2 (1.1) 3 (1) 0.809HTN 21 (17.3) 24 (13.4) 45 (15) 0.332CAD 3 (2.5) 2 (1.1) 5 (1.7) 0.394Asthma/COPD 6 (5.0) 6 (3.3) 12 (4) 0.553Smoker 19 (15.7) 26 (14.5) 45 (15) 0.749Previous breast cancer 21 (17.3) 36 (20.1) 57 (19) 0.657Neoadjuvant chemotherapy 15 (12.4) 33 (18.4) 48 (16) 0.253Previous irradiation 13 (10.7) 23 (12.8) 36 (12) 1.000Breast size (n= 290)

Small (


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greater potential or bleeding, subset analyses obleeding complication data were perormed orthe two types o reconstruction. No statisticallysignicant dierence in bleeding complicationsexisted between patients who received preopera-tive enoxaparin and patients who did not in eitherthe tissue expander subgroup (Table 4) or the

fap subgroup (Table 5).Finally, we looked at all bleeding compli-

cations based on type o breast reconstructionperormed, to determine whether the type oreconstruction played a role in bleeding compli-cations. There were eight bleeding complications(5.4 percent) in the tissue expander group andseven (4.8 percent) in the ree fap reconstructiongroup. This dierence was not statistically signi-cant (p= 1.00).

DISCUSSIONBreast cancer patients constitute a high-risk

population or the development o periopera-tive venous thromboembolic complications. Riskactors in this population include underlyingmalignancy, presence o central venous cath-eters, hormone-modulating medications, che-motherapy, and, commonly, increased age.13,14 Inaddition, breast reconstruction involves operativetimes greater than 45 minutes, another risk ac-tor or venous thromboembolism. Leonardi etal. perormed a systematic review o deep venousthrombosis prophylaxis in cancer patients. Theyreviewed nonorthopedic surgery patients withcancer rom 26 retrospective controlled trialsencompassing 7639 patients. Most studies in thereview gave the rst chemoprophylactic dose 2hours preoperatively, whereas some gave a dose

the night beore. The overall deep venous throm-bosis rate was 12.7 percent or pharmacologic pro-phylaxis compared with 35.2 percent in controls.Furthermore, the combination o heparin andmechanical prophylaxis decreased the rate to 5percent in this high-risk population. Importantly,discontinuation o high-dose (>5000 units threetimes daily) heparin prophylaxis occurred in only3 percent o patients secondary to bleeding.11,15The results rom the current study corroboratethe acceptably low bleeding risk with preoperativechemoprophylaxis.

Many surgical specialties are exploring theuse o preoperative low-molecular-weight hepa-rin or venous thromboembolism prophylaxis.Martino et al. retrospectively reviewed 122 gyne-cologic cancer patients, hal o whom were givenpreoperative low-molecular-weight heparin and

pneumatic compression devices. They ound nodierence in bleeding, transusion requirements,operative time, or hospital stay.9 Furthermore,Singh et al. used body mass indexbased pre-operative dosing in obese patients undergoingRoux-en-Y gastric bypass surgery. Some o these170 patients received a dose as high as 60 mg oenoxaparin preoperatively. They also ound thisregimen to be sae and eective in their high-riskpatient population, reporting no clinically signi-cant deep venous thrombosis or pulmonary embo-lism events during a 2-year ollow-up.10 Hate et

al. examined the relationship between body con-touring surgery and enoxaparin administration.They compared enoxaparin treatment timing, 2hours preoperatively versus intraoperatively orimmediately postoperatively. There was no statisti-cally signicant dierence in bleeding requiringtransusions, intraoperative blood loss, or venousthromboembolic events.16

In the breast reconstruction literature, Liao etal. perormed a multicenter study o 679 patientsundergoing transverse rectus abdominis muscu-locutaneous (TRAM) and ree TRAM fap opera-

tions. The ound venous thromboembolism rateswith and without postoperative chemoprophylaxiso 0.8 and 1.4 percent, respectively, and hema-toma rates o 1 and 0.5 percent, respectively.17Ashjian et al. compared postoperative aspirin

Table 2. Type of Reconstruction as Related to Use ofPreoperative Enoxaparin Chemoprophylaxis

NoEnoxaparin Enoxaparin Total

Tissue expander 64 90 154(244 breasts)

Free fap 57 89 146(206 breasts)

Total 121 179 300*

*p= 0.761.

Table 3. Bleeding Complications as Related to Use of Preoperative Enoxaparin Chemoprophylaxis

No Enoxaparin (%) Enoxaparin (%) Total (%) p

No. o patients 121 179 300Hematoma 3 (2.5) 8 (4.5) 11 (3.7) 0.399Blood transusion 1 (0.8) 4 (2.2) 5 (1.7) 0.652Any bleeding complication 4 (3.3) 11 (6.1) 15 (5.0) 0.419


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versus low-molecular-weight heparin ater reefap surgery and ound hematoma rates o 2.3and 2.9 percent and pulmonary embolism rateso 1.2 and 1.6 percent, respectively.18 Our pre-operative enoxaparin group hematoma rate (3.7percent) was within the published norm o 0.5 to5.7 percent.15,17,19 Importantly, the current study isnot designed to determine a dierence in venousthromboembolism between those receiving and

those not receiving preoperative enoxaparin.The timing o chemoprophylaxis is the keyissue. The critical thrombosis period begins at sur-gery and can continue beyond hospitalization.20One must weigh the risk o bleeding complica-tions with early prophylaxis administration againstthe risk o venous thromboembolism.20 Pannucciet al. studied autogenous breast reconstructionand venous thromboembolism, nding an over-all venous thromboembolism rate o 2.2 percent.However, only 11.8 percent o the total patient pop-ulation received any orm o pharmacologic pro-

phylaxis. O these patients, three o 20 who receivedpostoperative chemoprophylaxis developed venousthromboembolism, whereas none was seen in thosepatients receiving preoperative prophylaxis.21

In a study by Kim et al., two groups o patientsundergoing immediate pedicled TRAM fap breastreconstruction were compared, with one groupreceiving no chemoprophylaxis and the otherreceiving 7 days o enoxaparin starting 1 hourpreoperatively. They ound no dierence in trans-usion rates, hematomas, or seromas. However,there was a signicant dierence in asymptomaticpulmonary embolism, 16.7 percent in the groupwithout chemoprophylaxis versus 0 percent inthe group receiving preoperative and postopera-tive chemoprophylaxis.19 The current study identi-ed one patient who developed an asymptomatic,

incidentally ound pulmonary embolism ater reefap breast reconstruction. This low rate may stemrom the act that our patients are studied (chestcomputed tomographic angiography or lowerextremity duplex sonography) only i symptomatic.It is well accepted that many venous thromboem-bolisms are asymptomatic and oten not discoveredwithout routine imaging o high-risk patients.22

Overall, our study compares avorably with the

reported literature, as the venous thromboembo-lism rates were very low and complication rateswere within the acceptable range. It was inter-esting to note the increased use o enoxaparinin patients with larger breast size. This may havebeen attributable to some biased use o enoxapa-rin because o perceived increased venous throm-boembolism risks in patients who were viewed ashaving a larger body habitus. However, or thepurposes o this study, it is more important to notethat the increased use o preoperative enoxapa-rin in patients with large breasts did not result in

increased bleeding complications.We did notice a trend toward increased bleed-ing complications in those patients receivingenoxaparin. The current study has 80 percentpower to detect a ourold dierence in bleedingcomplications. Although a larger study might haveound the bleeding complication rate dierenceobserved in our study to be statistically signicant,the authors eel that a relatively small increase inreadily treatable bleeding complications is out-weighed by the potential benets o decreasedvenous thromboembolism complications dem-onstrated in the current surgical literature. Ourstudy is also limited by its retrospective nature.This study is not intended or powered to dem-onstrate the benet o chemoprophylaxis in pre-venting venous thromboembolism complications,

Table 4. Bleeding Complications as Related to Use of Preoperative Enoxaparin Chemoprophylaxis in the TissueExpanderOnly Group

No Enoxaparin (%) Enoxaparin (%) Total (%)

No. o patients 58 90 148Hematoma 2 (3.4) 5 (5.6) 7 (4.7)Transusion 0 2 (2.2) 2 (1.4)Any bleeding complication 2 (3.4) 6 (6.7) 8 (5.4)

Table 5. Bleeding Complications as Related to Use of Preoperative Enoxaparin Chemoprophylaxis in the FreeFlapOnly Group

No Enoxaparin (%) Enoxaparin (%) Total (%)

No. o patients 58 89 146Hematoma 1 (1.7) 3 (3.4) 4 (2.7)Transusion 1 (1.7) 2 (2.2) 3 (2.0)Any bleeding complication 2 (3.4) 5 (5.6) 7 (4.8)


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as multiple other studies have already establishedthis point. However, it does show that the bleed-ing complication rates with preoperative chemo-prophylaxis were within the acceptable range inprosthesis-based and microsurgical autologoustissuebased breast reconstruction.

CONCLUSIONSTo date, this is the largest study looking at

preoperative chemoprophylaxis in breast recon-struction. Preoperative enoxaparin was ound tobe acceptable to use in our patient populationundergoing prosthesis-based and microsurgicalbreast reconstruction.

Michael L. Gimbel, M.D.5750 Centre Avenue, Suite 180

Pittsburgh, Pa. 15206

[email protected]

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mailto:[email protected]:[email protected]

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