MOC-PSSM CME Article: VenousThromboembolism Prophylaxis in PlasticSurgery Patients
Mitchel Seruya, M.D.Stephen B. Baker,
D.D.S., M.D.
Washington, D.C.
Learning Objectives: After studying this article, the participant should be ableto: 1. Understand and appreciate the incidence of venous thromboembolism inplastic surgery. 2. Understand and describe the cause and natural history ofvenous thromboembolism in the setting of plastic surgery. 3. Understand theimportant patient risk factors for venous thromboembolism and perform anindividualized assignment of venous thromboembolism risk. 4. Select a methodof venous thromboembolism prophylaxis based on a patient’s venous throm-boembolism risk assignment and the overall thromboprophylaxis guidelines bythe American College of Chest Physicians.Summary: This Maintenance of Certification module reviews the incidence,cause, and natural history of venous thromboembolism in plastic surgery pa-tients and highlights one algorithm for approaching venous thromboembolismrisk assignment and choice of thromboprophylaxis.
The Maintenance of Certification module series is designed to help the clinician structurehis or her study in specific areas appropriate to his or her clinical practice. This article isprepared to accompany practice-based assessment of preoperative assessment, anesthesia,surgical treatment plan, perioperative management, and outcomes. In this format, theclinician is invited to compare his or her methods of patient assessment and treatment,outcomes, and complications with authoritative, information-based references.
This information base is then used for self-assessment and benchmarking in parts II andIV of the Maintenance of Certification process of the American Board of Plastic Surgery.This article is not intended to be an exhaustive treatise on the subject. Rather, it is designedto serve as a reference point for further in-depth study by review of the reference articlespresented. (Plast. Reconstr. Surg. 122: 1, 2008.)
Venous thromboembolism, a spectrum of dis-ease ranging from deep vein thrombosis topulmonary embolism, is a complication rele-
vant to all practicing plastic surgeons.1–11 In one sur-vey of board-certified plastic surgeons, pulmonaryembolism was found to be the leading cause of deathfollowing liposuction, accounting for 23 percent ofall deaths.12 In a prospective series of office-basedsurgical procedures, 63.6 percent of postoperativedeaths were secondary to thromboembolism.13 Sur-prisingly, however, a recent survey of current mem-bers of the American Society of Plastic Surgeonsfound that only 48.7 percent of surgeons performingface lifts, 43.7 percent of surgeons performing lipo-
suction, and 60.8 percent performing a combinedprocedure use thromboprophylaxis all the time.11
This hesitancy in instituting thromboprophylaxismay be attributable to the belief that there is a lowincidence of venous thromboembolism or to the
Disclosure: Neither of the authors has a financialinterest in any of the products, devices, or drugsmentioned in this article.
The test for the MOC-PSSM CME article “Ve-nous Thromboembolism Prophylaxis in Plas-tic Surgery Patients” by Seruya and Baker isavailable at http://www1.plasticsurgery.org/ebusiness4/onlinecourse/CourseInfo.aspx?Id�13668.
www.PRSJournal.com 1
concern over bleeding complications secondary tochemoprophylaxis.
INCIDENCE OF VENOUSTHROMBOEMBOLISM
Plastic surgery is not immune to the dangers ofvenous thromboembolism, with rates of venousthromboembolism ranging from less than 1 percentto nearly 10 percent, depending on the surgicalprocedure.2,14–18 In a survey of members of the Amer-ican Society for Aesthetic Plastic Surgery, Reinisch etal. reported a 0.49 percent rate of venous thrombo-embolism in face-lift procedures.2 Chen et al. founda 0.57 percent incidence of venous thromboem-bolism in patients undergoing head and neckreconstruction.14 In a series of pedicled transverserectus abdominis myocutaneous flaps for breast re-construction, Erdmann et al. observed a 1.3 percentrate of venous thromboembolism.15 Concerninglarge-volume liposuction procedures, one series re-ported a 1.7 percent incidence of venous thrombo-embolism in patients undergoing 5 liters or more offat aspiration.16 Grazer and Goldwyn cited a 1.9 per-cent incidence of venous thromboembolism in aseries of abdominoplasty patients.17 Belt lipectomyprocedures are associated with the highest rate ofvenous thromboembolism, approximately 9.4 per-cent in a recent study by Aly et al.18
CAUSE OF VENOUSTHROMBOEMBOLISM
As described by the German pathologist Ru-dolf Virchow, venous thrombus formation isdriven by a triad of factors: (1) venous stasis; (2)vascular injury; and (3) hypercoagulability.19 Atleast one part of the triad is necessary to initiatethe coagulation cascade (Fig. 1). During surgery,the combination of general anesthesia, supine po-sitioning, and immobilization promotes venousstasis. Decreased venous return prevents clearanceof activated clotting factors, leading to thrombusaccumulation behind venous valve cusps. Intimaldamage is also a byproduct of surgery, secondaryto venous traction during muscle and tissue re-traction and the vasodilatory effect of anesthesia.At these intimal sites of microscopic injury, plate-lets collect and initiate the coagulation cascade.9
Hypercoagulability can be secondary to inher-ited or acquired coagulation disorders.20,21 Com-mon inherited prothrombotic disorders includefactor V Leiden; prothrombin 20210A; and defi-ciencies of protein C, protein S, and antithrombinIII.20 Factor V Leiden, present in roughly 4 to 6percent of Caucasians, represents the most com-mon genetic prothrombotic defect. The mutated
factor V resists inactivation by activated protein Cand drives unchecked clot formation. Prothrom-bin 20210A, a variant found in 1.7 to 3 percent ofpeople of European descent, results in elevatedprothrombin levels and hypercoagulability. Ac-quired hypercoagulable disorders can stem frompharmacologic interaction or disease sequelaeand include antiphospholipid antibody syn-drome, hyperhomocysteinemia, and cancer.20,21 Incancer, there are multiple mechanisms by whichthe prothrombotic machinery is jump-started.21
Malignancies, such as gastric and pancreatic types,express tissue factor–like material that activatescoagulation. By means of an acute inflammatoryphase reaction, tumor-infiltrating macrophagescan promote thrombus formation through inter-leukin-1 and tumor necrosis factor-� production.Malignancies can also down-regulate endothelialcell anticoagulant activity and stimulate release offibrinogen and factor VIII.
NATURAL HISTORY OF VENOUSTHROMBOEMBOLISM
The natural history of surgery-associated ve-nous thromboembolism events has been well de-scribed by Kearon22 and is summarized below. Upto all three components of Virchow’s triad may bepresent at the time of surgery to promote venousthrombosis, explaining how perhaps 50 percent ofdeep vein thromboses associated with surgery startintraoperatively. Most of these intraoperativedeep vein thromboses begin in the distal veins,specifically, in the calf region. Approximately 50percent of deep vein thromboses formed intraop-eratively may resolve spontaneously within 72hours, with venous thromboprophylaxis facilitat-ing lysis of perioperative deep vein thrombosesand preventing formation of new thrombi. Iso-lated calf deep vein thromboses rarely cause legsymptoms or clinically important pulmonary em-bolisms. Of more concern, approximately 25 per-cent of untreated symptomatic calf deep veinthromboses extend to the proximal veins (at orabove the popliteal vein) within 1 week of presen-tation. The majority of patients with a symptom-atic proximal deep vein thrombosis and withoutchest symptoms have evidence of a pulmonaryembolism on lung scan. The highest risk periodfor fatal postoperative pulmonary embolism oc-curs 3 to 7 days after surgery, with approximately10 percent of symptomatic pulmonary embolismsfatal within 1 hour of first symptoms. Further-more, the risk of symptomatic venous thrombo-embolism is highest within 2 weeks of surgery and
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Fig. 1. Coagulation cascade.
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remains elevated for approximately 2 to 3 months.After a diagnosed pulmonary embolism, 50 per-cent of patients have right ventricular dysfunctionon echocardiography. After a symptomatic deepvein thrombosis, there is an approximately 10 per-cent cumulative incidence of severe postthrom-botic syndrome after 5 years.
RISK ASSIGNMENT FOR VENOUSTHROMBOEMBOLISM
Given that up to two-thirds of patients with avenous thromboembolism may appear clinicallysilent,23 leading to a substantial delay in diagnosisand treatment and resulting in significant mor-bidity and mortality, the need for thrombopro-phylaxis is paramount. Because of the elective na-ture of many plastic surgical procedures, it is ofparamount importance that the surgeon allow forappropriate planning and risk-reduction strate-gies. Based on the authors’ preference, choice of
thromboprophylaxis is dependent on venousthromboembolism risk assignment and the 2004American College of Chest Physicians overall rec-ommendations on prophylaxis for surgical pa-tients within each venous thromboembolism riskcategory.21,24
In approaching venous thromboembolismrisk assignment, we advocate an individualized as-sessment of thrombotic risk, as described byBergqvist et al. (Fig. 2).21 This approach takes intoaccount a patient’s unique set of predisposing riskfactors, such as age, history of venous thrombo-embolism, and chronic illness, and any exposingrisk factors, such as type and length of operation.The various risk factors are differentially weightedon the basis of historical incidence data from priorrandomized trials. Tallying a patient’s set of pre-disposing and exposing risk factors yields an over-all risk factor score and assignment to one of fourvenous thromboembolism risk categories (low,
Fig. 2. Venous thromboembolism risk assessment model. Reprinted from Bergqvist etal., “Venous thromboembolism and cancer,” Curr. Probl. Surg. 44: 157, 2007, with permis-sion from Elsevier.
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moderate, high, and highest) as described by theAmerican College of Chest Physicians.24
A number of risk factors with evidence-basedweighting deserve special mention. Borow andGoldson reported a 20 percent incidence of deepvein thrombosis for procedures lasting 1 to 2 hourscompared with a 62.5 percent rate of deep veinthrombosis in operations taking 3 or morehours.25 Given that the incidence of venous throm-boembolism is proportional to surgical duration,operations are scored 1 to 5 depending on thelength of surgery. The above scoring system isespecially applicable in plastic surgery, where pa-tients may undergo lengthy free tissue transferprocedures. Patients with a malignancy have up toa 6-fold increase in the incidence of venous throm-boembolism as compared with those without amalignancy, with the risk of venous thromboem-bolism not disappearing with cancer cure orremission.21 These observations translate into arisk score of 3 for “present cancer” and 2 for a“previous malignancy,” which particularly relatesto patients undergoing reconstructive operationsfor head and neck or breast cancer.
Women on hormonal contraception and re-placement therapy also pose a higher venousthromboembolism risk. Overall observational dataare consistent with a 3- to 6-fold increase in the riskof venous thromboembolism with oral contracep-tive pill use and a 2- to 4-fold increase in risk withhormone replacement therapy.26 Oral contracep-tive pills and hormone replacement therapy bothcontain estrogen, which lowers protein S levelsand promotes thrombosis. The risk of venousthromboembolism is highest within the firstmonth of starting hormonal medications and di-minishes but does not disappear after the firstyear. In this risk assessment model, hormone re-placement therapy or oral contraceptive pill useearns the patient a risk score of 1. Although de-finitive studies on the optimal time of hormonalmedication discontinuation are lacking, we sug-gest discontinuation of hormonal medications atleast 2 weeks before surgery.
VENOUS THROMBOEMBOLISMPROPHYLAXIS
Primary venous thromboprophylaxis is themost useful and cost-effective strategy for reduc-ing the risk of venous thromboembolism in plasticsurgery patients. Diagnostic tests for asymptomaticdeep vein thrombosis screening remain expen-sive, impractical, and inaccurate, and waiting forsymptoms to develop before taking action gambleswith the patient’s long-term health. Choice of
thromboprophylaxis is based on the 2004 Amer-ican College of Chest Physicians overall guidelinesfor each venous thromboembolism risk category24
(Fig. 3). Thromboprophylaxis begins with properpatient positioning on the operating table andearly ambulation postoperatively. Flexion of thepatient’s knees to approximately 5 degrees willmaximize venous return through the poplitealvein. Proper patient positioning and early mobi-lization are sufficient for patients of low venousthromboembolism risk but must be supplementedwith mechanical and/or pharmacologic prophy-laxis for patients with more significant venousthromboembolism risk.
MechanicalThe 2004 American College of Chest Physi-
cians overall recommendations for surgical pa-tients include the option of mechanical throm-boprophylaxis as stand-alone therapy in bothmoderate and high venous thromboembolism riskgroups and as combination therapy with chemo-prophylaxis in highest venous thromboembolismrisk patients.24 Use of mechanical prophylaxisshould begin before the induction of anesthesia,especially if general anesthesia is used, and con-tinue into the postoperative period until the pa-tient is fully mobile.4 Educating nurses about theimportance of venous thromboembolism prophy-laxis is critical to ensuring compliance with me-chanical methods of prevention. Contraindica-tions for mechanical prophylaxis include severeperipheral arterial disease, congestive heart failure,and acute superficial or deep vein thrombosis.
Mechanical methods of thromboprophylaxis,either “passive” or “active,” have been shown toreduce the risk of deep vein thrombosis in a num-ber of patient groups. “Passive” mechanical throm-boprophylaxis includes graduated compressionstockings, which prevent deep vein thromboses byimproving valve function, reducing distention ofthe vein wall, and increasing venous flow velocitythrough cross-sectional area reduction. In somereports, use of graduated compression stockingsreduced the rate of deep vein thrombosis by ap-proximately 50 to 64 percent in general surgerypatients.27 “Active” mechanical methods of throm-boprophylaxis include intermittent pneumaticcompression devices and venous foot pumps.Deep vein thrombosis prevention is achieved byrelieving venous stasis through increased motionof blood and by stimulating fibrinolytic activitythrough reduction of plasminogen activator-1.28
In a study of face-lift patients, intermittent pneu-
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matic compression devices led to a significant de-crease in the rate of venous thromboembolism ascompared with no thromboprophylaxis (59.2 per-cent versus 4.1 percent, respectively).2 In patientswith contraindications to lower extremity com-pression devices, mechanical prophylaxis can beapplied to the arm, with adequate reduction in theincidence of venous thromboembolism as re-ported by Knight and Dawson.29 The site of activemechanical prophylaxis is not critical, with studiesdemonstrating a decreased incidence of venousthromboembolism with thigh-high, knee-high, orplantar compression devices.2
ChemoprophylaxisThe 2004 American College of Chest Physicians
overall guidelines provide the option of chemopro-phylaxis as stand-alone therapy in moderate, high,and highest venous thromboembolism risk groupsor as combination therapy with mechanical prophy-laxis in highest venous thromboembolism riskpatients.24 Chemoprophylaxis agents include low-dose unfractionated heparin, low-molecular-weightheparin, fondaparinux, and vitamin K antagonists.30
Contraindications to chemoprophylaxis include ac-tive bleeding, heparin-induced thrombocytopenia,worsening renal insufficiency, coagulopathy, recent
Fig. 3. Venous thromboembolism prophylaxis guidelines. Reprinted from Geerts et al., “Pre-vention of venous thromboembolism: The Seventh ACCP Conference on Antithrombotic andThrombolytic Therapy,” Chest 126 (3 Suppl.): 338s, 2004, with permission from Elsevier.
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intracranial surgery, and lumbar tap or epidural an-esthesia within the past 24 hours.
Subcutaneous heparin, in the form of low-dose unfractionated heparin or low-molecular-weight heparin, remains the most-widely usedform of chemoprophylaxis.9 Low-dose unfrac-tionated heparin binds to antithrombin III,leading to inactivation of factors Xa and IIa(thrombin) and disruption of the coagulationcascade. Because of its high affinity for circu-lating plasma proteins and resultant poor bio-availability, low-dose unfractionated heparinrequires more than once-daily dosing.30 The fre-quency of low-dose unfractionated heparin ad-ministration is affected by the level of venousthromboembolism risk, with low-dose unfrac-tionated heparin dosed at 5000 units twice dailyin moderate-risk patients and at 5000 units threetimes daily in high- and highest-risk patients.24
Low-molecular-weight heparin, available asenoxaparin and dalteparin, has become the pre-ferred form of subcutaneous heparin in venousthromboembolism prophylaxis among surgeons.9Similar to low-dose unfractionated heparin, low-molecular-weight heparin mediates its effectsthrough binding with antithrombin III; however,it inhibits thrombin to a lesser degree and factorXa to a greater degree than low-dose unfraction-ated heparin.30 Advantages of low-molecular-weightheparin in comparison with low-dose unfractionatedheparin include increased bioavailability (90 per-cent versus 30 to 40 percent, respectively) leading toonce-daily dosing, superior efficacy in venous throm-boembolism prevention, less bleeding if used atlower but equally efficacious dosages, and decreasedfrequency of heparin-induced thrombocytopenia (0percent versus 2.7 percent, respectively).10,24,30,31 Dos-age of low-molecular-weight heparin is affected bythe level of venous thromboembolism risk. Low-mo-lecular-weight heparin should be dosed at less than3400 units once daily for moderate-risk patients andat greater than 3400 units once daily for high- andhighest-risk patients.24
Fondaparinux, a short-acting synthetic pen-tasaccharide, is a recently approved chemopro-phylaxis agent that indirectly inhibits factor Xa.30
It is usually dosed at 2.5 mg subcutaneously oncedaily. In comparing fondaparinux with low-mo-lecular-weight heparin, studies have found mixedresults. Meta-analysis of three major orthopedicstudies showed a 55.2 percent reduction in venousthromboembolism with a similar rate of bleedingwhen comparing fondaparinux to low-molecular-weight heparin (enoxaparin).30 In contrast, ratesof venous thromboembolism and bleeding were
equivalent for abdominal surgery patients on post-operative fondaparinux versus perioperative low-molecular-weight heparin (dalteparin).32
Oral vitamin K antagonists, such as warfarin,are recommended for highest risk patients and aretitrated to an international normalized ratio goalof 2 to 3.24 Through inhibition of vitamin K–de-pendent clotting factor (II, VII, IX, X) synthesis,vitamin K antagonists disrupt the coagulationcascade.30 Given the delayed onset of action, dailymonitoring, drug-drug interactions, and signifi-cantly lower efficacy in venous thromboembolismprevention in comparison with low-molecular-weight heparin, vitamin K antagonists are not con-sidered a first-line agent in thromboprophylaxis.30
If long-term (3 months of longer) thrombopro-phylaxis is necessary, however, patients may betransitioned from other regimens of chemopro-phylaxis to oral vitamin K antagonists.
Optimal timing of chemoprophylaxis remainscontroversial.10,33 Aggregate evidence from clini-cal research on low-molecular-weight heparin sup-ports the concept that administering the first dose12 hours preoperatively is too early, that giving thefirst dose 12 or more hours postoperatively is prob-ably too late for optimal effectiveness, and thatadministering the first dose 2 hours preoperativelyresults in increased bleeding without improvedefficacy as compared with giving the first dose 6hours postoperatively.33 Additional studies areneeded to compare different times of postopera-tive low-molecular-weight heparin initiation to de-finitively determine the optimal timing of the firstdose. Regarding fondaparinux, a recent study onits use in thromboprophylaxis reported an in-creased rate of bleeding with equivalent efficacy inorthopedic patients receiving a first dose 6 to 8hours postoperatively versus patients receiving afirst dose 24 hours postoperatively.10 In response,some have advocated starting fondaparinux themorning after surgery.
Duration of chemoprophylaxis is a function ofa patient’s venous thromboembolism risk categoryand ambulatory status.9,21 In general, thrombopro-phylaxis should continue until the risk of an acutepostoperative venous thromboembolism has beenmitigated and then until the patient is fullyambulatory.10 The most common practice is tocontinue thromboprophylaxis for 5 to 10 days af-ter surgery.9 Some studies have stressed a month-long duration of thromboprophylaxis for highestvenous thromboembolism risk patients. In a studyof orthopedic hip fracture patients, extended-du-ration (30 to 35 days) low-molecular-weight hep-arin chemoprophylaxis was more effective in ve-
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nous thromboembolism prevention than a 7- to10-day course.10 These findings are not unex-pected, considering that the risk of venous throm-boembolism is highest within the first 2 weeks aftersurgery.22 Additional studies are needed to com-pare the efficacy of various durations of throm-boprophylaxis within different venous thrombo-embolism risk categories.
CONCLUSIONSGiven the devastating morbidity and mortality
associated with venous thromboembolism and theinaccuracy and expense of screening modalities,venous thromboembolism prevention should bethe goal in plastic surgery patients. We recom-mend an individualized assessment of thromboticrisk, based on a patient’s set of predisposing andexposing risk factors. Patients are stratified intolow, moderate, high, or highest venous thrombo-embolism risk, depending on the total risk factorscore. Based on the 2004 American College ofChest Physicians overall guidelines for surgical pa-tients, a thromboprophylaxis regimen is selectedfor the appropriate venous thromboembolism riskcategory. Proper patient positioning and early am-bulation are recommended for low venous throm-boembolism risk patients. Either mechanical pro-phylaxis or chemoprophylaxis may be used inmoderate or high venous thromboembolism riskpatients. Chemoprophylaxis is necessary as stand-alone or as combination therapy with mechanicalprophylaxis in highest venous thromboembolismrisk patients. Optimal timing and duration of che-moprophylaxis is controversial and warrants fur-ther clinical trials.
Stephen B. Baker, D.D.S., M.D.Georgetown University Hospital
ACKNOWLEDGMENTSThe authors gratefully acknowledge Steven P. Davi-
son, D.D.S., M.D., Mark L. Venturi, M.D., ChristopherE. Attinger, M.D., and Scott L. Spear, M.D., for theirprior contribution on the topic of venous thromboembo-lism in the plastic surgery patient.
REFERENCES1. McDevitt, N. B. Deep vein thrombosis prophylaxis: American
Society of Plastic and Reconstructive Surgeons. Plast. Recon-str. Surg. 104: 1923, 1999.
2. Reinisch, J. F., Bresnick, S. D., Walker, J. W. T., and Rosso,R. F. Deep venous thrombosis and pulmonary embolus after
face lift: A study of incidence and prophylaxis. Plast. Reconstr.Surg. 107: 1570, 2001.
3. Rohrich, R. J., and Rios, J. L. Venous thromboembolism incosmetic plastic surgery: Maximizing patient safety. Plast.Reconstr. Surg. 112: 871, 2003.
4. Davison, S. P., Venturi, M. L., Attinger, C. E., Baker, S. B., andSpear, S. L. Prevention of venous thromboembolism in theplastic surgery patient. Plast. Reconstr. Surg. 114: 43e, 2004.
5. Most, D., Kozlow, J., Heller, J., and Shermak, M. A. Throm-boembolism in plastic surgery. Plast. Reconstr. Surg. 115: 20e,2005.
6. The Doctors Company. Deep venous thrombosis and pul-monary embolism in plastic surgery office procedures. Avail-able at: http://www.thedoctors.com. Accessed November28, 2007.
7. Conroy, F. J., Thornton, D. J. A., Mather, J., Srinivasan, J., andHart, N. B. Thromboembolic prophylaxis in plastic surgery:A 12-year follow up in the UK. J. Plast. Reconstr. Aesthet. Surg.59: 510, 2006.
8. Newall, G., Ruiz-Razura, A., Mentz, H. A., Patronella, C. K.,Ibarra, F. R., and Zarak, A. A retrospective study on the useof a low-molecular weight heparin for thromboembolismprophylaxis in large-volume liposuction and body contour-ing procedures. Aesthetic Plast. Surg. 30: 86, 2006.
9. Young, V. L., and Watson, M. E. The need for venous throm-boembolism (VTE) prophylaxis in plastic surgery. AestheticSurg. J. 26: 157, 2006.
10. Green, D. VTE prophylaxis in aesthetic surgery patients.Aesthetic Surg. J. 26: 317, 2006.
11. Broughton, G., II, Rios, J. L., Rohrich, R. J., and Brown, S. A.Deep venous thrombosis prophylaxis practice and treatmentstrategies among plastic surgeons: Survey results. Plast. Re-constr. Surg. 119: 157, 2007.
12. Grazer, F. M., and de Jong, R. H. Fatal outcomes from lipo-suction: Census survey of cosmetic surgeons. Plast. Reconstr.Surg. 105: 436, 2000.
13. Clayman, M. A., and Caffee, H. H. Office surgery safety andthe Florida moratoria. Ann. Plast. Surg. 56: 78, 2006.
14. Chen, C. M., Disa, J. J., and Mehrara, B. J. The incidence ofvenous thromboembolism in head and neck reconstruction.Presented at the 24th Annual Meeting of the NortheasternSociety of Plastic Surgeons, Bermuda, October 3–7, 2007.
15. Erdmann, D., Sundin, B. M., Moquin, K. J., Young, H., andGeorgiade, G. S. Delay in unipedicled TRAM flap recon-struction of the breast: A review of 76 consecutive cases. Plast.Reconstr. Surg. 110: 762, 2002.
16. Albin, R., and de Campo, T. Large-volume liposuction in 181patients. Aesthetic Plast. Surg. 23: 5, 1999.
17. Grazer, F. M., and Goldwyn, R. M. Abdominoplasty assessedby survey, with emphasis on complications. Plast. Reconstr.Surg. 59: 513, 1977.
18. Aly, A. S., Cram, A. E., Chao, M., Pang, J., and McKeon, M.Belt lipectomy for circumferential truncal excess: The Uni-versity of Iowa experience. Plast. Reconstr. Surg. 111: 398,2003.
19. Virchow, R. L. K. Gesammelte abhandlungen zur wissenschaftli-chen Medizin. Frankfurt: Medinger Sohn & Co, 1856. P. 285
20. Anderson, F. A., Jr., and Spencer, F. A. Risk factors forvenous thromboembolism. Circulation 107: i9, 2003.
21. Bergqvist, D., Caprini, J. A., Dotsenko, O., Kakkar, A. K.,Mishra, R. G., and Wakefield, T. W. Venous thromboembo-lism and cancer. Curr. Probl. Surg. 44: 157, 2007.
22. Kearon, C. Natural history of venous thromboembolism. Cir-culation 107: i22, 2003.
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23. Poponick, J., and Bosker, G. The current challenge ofvenous thromboembolism (VTE) in the hospitalized pa-tient: Optimizing recognition, evaluation, and prophy-laxis of deep venous thrombosis (DVT) and pulmonaryembolism (PE). Part I: Patient identification, risk factorassessment, and diagnostic strategies. Hosp. Med. ConsensusRep. Available at: www.clinicalconsensusreports.com. Ac-cessed November 28, 2007.
24. Geerts, W. H., Pineo, G. H., Heit, J. A., et al. Prevention ofvenous thromboembolism: The Seventh ACCP Conferenceon Antithrombotic and Thrombolytic Therapy. Chest 126(3 Suppl.): 338s, 2004.
25. Borow, M., and Goldson, H. Postoperative venous thrombo-sis: Evaluation of five methods of treatment. Am. J. Surg. 141:245, 1981.
26. Gomes, M. P., and Deitcher, S. R. Risk of venous thrombo-embolic disease associated with hormonal contraceptive andhormone replacement therapy: A clinical review. Arch. Intern.Med. 164: 1965, 2004.
27. Agu, O., Hamilton, G., and Baker, D. Graduated compres-sion stockings in the prevention of venous thromboembo-lism. Br. J. Surg. 86: 992, 1999.
28. Comerota, A. J., Chouhan, V., Harada, R. N., et al. The fibrino-lytic effects of intermittent sequential calf compression: Mech-anism of enhanced fibrinolysis. Ann. Surg. 226: 306, 1997.
29. Knight, M. T., and Dawson, R. Effect of intermittent com-pression of the arms on deep venous thrombosis in the legs.Lancet 2: 1265, 1976.
30. Andersen, J. C. Advances in anticoagulation therapy: Therole of selective inhibitors of factor Xa and thrombin inthromboprophylaxis after major orthopedic surgery. Semin.Thromb. Hemost. 30: 609, 2004.
31. Warkentin, T. E., Levine, M. N., Hirsh, J., et al. Heparin-induced thrombocytopenia in patients treated with low-mo-lecular-weight heparin or unfractionated heparin. N. Engl.J. Med. 332: 1330, 1995.
32. Agnelli, G., Bergqvist, D., Cohen, A. T., Gallus, A. S., andGent, M. Randomized clinical trial of postoperative fondapa-rinux versus perioperative dalteparin for prevention ofthromboembolism in high-risk abdominal surgery. Br.J. Surg. 92: 1212, 2005.
33. Raskob, G. E., and Hirsh, J. Controversies in timing ofthe first dose of anticoagulant prophylaxis against venousthromboembolism after major orthopedic surgery. Chest 124:379, 2003.
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