Cancer-Associated Venous Thromboembolic Disease, Version 1.2015

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer.

Abstract

The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease outline strategies for treatment and prevention of venous thromboembolism (VTE) in adult patients with a diagnosis of cancer or for whom cancer is clinically suspected. VTE is a common complication in patients with cancer, which places them at greater risk for morbidity and mortality. Therefore, risk-appropriate prophylaxis is an essential component for the optimal care of inpatients and outpatients with cancer. Critical to meeting this goal is ensuring that patients get the most effective medication in the correct dose. Body weight has a significant impact on blood volume and drug clearance. Because obesity is a common health problem in industrialized societies, cancer care providers are increasingly likely to treat obese patients in their practice. Obesity is a risk factor common to VTE and many cancers, and may also impact the anticoagulant dose needed for safe and effective prophylaxis. These NCCN Guidelines Insights summarize the data supporting new dosing recommendations for VTE prophylaxis in obese patients with cancer.

NCCN: Continuing Education

Accreditation Statement

This activity has been designed to meet the educational needs of physicians, nurses, and pharmacists involved in the management of patients with cancer. There is no fee for this article. The National Comprehensive Cancer Network (NCCN) is accredited by the ACCME to provide continuing medical education for physicians. NCCN designates this journal-based CE activity for a maximum of 1.0 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

NCCN is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center‘s Commission on Accreditation.

NCCN designates this educational activity for a maximum of 1.0 contact hour. Accreditation as a provider refers to recognition of educational activities only; accredited status does not imply endorsement by NCCN or ANCC of any commercial products discussed/displayed in conjunction with the educational activity. Kristina M. Gregory, RN, MSN, OCN, is our nurse planner for this educational activity.

National Comprehensive Cancer Network is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. NCCN designates this continuing education activity for 1.0 contact hour(s) (0.1 CEUs) of continuing education credit in states that recognize ACPE accredited providers. This is a knowledge-based activity. UAN: 0836-0000-15-010-H01-P

All clinicians completing this activity will be issued a certificate of participation. To participate in this journal CE activity: 1) review the learning objectives and author disclosures; 2) study the education content; 3) take the posttest with a 66% minimum passing score and complete the evaluation at http://education.nccn.org/node/73237; and 4) view/print certificate.

Release date: September 18, 2015; Expiration date: September 18, 2016.

Learning Objectives

Upon completion of this activity, participants will be able to:

  • Integrate into professional practice the updates to the NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease

  • Describe the rationale behind the decision-making process for developing the NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease

F1

NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 1.2015

Version 1.2015 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.

Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 13, 9; 10.6004/jnccn.2015.0133

NCCN Categories of Evidence and Consensus

Category 1: Based upon high-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus that the intervention is appropriate.

Category 2B: Based upon lower-level evidence, there is NCCN consensus that the intervention is appropriate.

Category 3: Based upon any level of evidence, there is major NCCN disagreement that the intervention is appropriate.

All recommendations are category 2A unless otherwise noted.

Clinical trials: NCCN believes that the best management for any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Overview

Venous thromboembolism (VTE) is a common and life-threatening condition in patients with cancer.1,2 Results from large retrospective studies (N>10,000) indicate that VTE may occur in up to 19% of patients with cancer, depending on the tumor type.13 The critical need for clinical practice guidelines focusing specifically on VTE in patients with cancer is underscored by studies showing underuse of VTE prophylaxis among these patients,46 despite the strong association between VTE and cancer.711

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Associated Venous Thromboembolic Disease outline strategies to prevent and treat VTE in adult patients with cancer, including medically ill or surgery inpatients and outpatients. These guidelines were developed and are updated annually by the NCCN Cancer-Associated Venous Thromboembolic Disease Panel, an interdisciplinary group of representatives from NCCN Member Institutions, including specialists in hematology and hematology/oncology, surgery and surgical oncology, cardiology, internal medicine, pharmacology, and pharmacy. In the guidelines, VTE is broadly defined to include deep venous thrombosis (DVT), pulmonary embolism (PE), superficial vein thrombosis, and venous thrombosis in other areas of the vasculature. Based on assessment of VTE risk and in the absence of contraindications to anticoagulation, the guidelines recommend pharmacologic prophylaxis for medical and surgical patients with cancer during hospitalization (category 1 recommendation) and in some cases after discharge (see VTE-1 and VTE-2, in the full version of these guidelines at NCCN.org). Obesity is common among patients with cancer and increases the risk of VTE12,13; therefore, these NCCN Guidelines Insights focus on a notable addition to the 2015 NCCN Cancer-Associated Venous Thromboembolic Disease Guidelines: prophylactic anticoagulant dosing for patients with obesity.

Obesity and Cancer

Obesity is considered an epidemic in the United States, affecting at least one-third of the adult population,1214 with rates steadily increasing.1416 High body mass index (BMI) is a risk factor for cancer,1719 and is more prevalent among patients with cancer compared with the general population. Various estimates have been reported for the fraction of cancer cases attributable to obesity, ranging from 3.6% of new cancer cases worldwide to 20% of all cancer cases.20,21 Obesity is strongly associated with certain types of cancer, including 8 recognized by the World Cancer Research Fund: esophageal adenocarcinoma and colorectal, kidney, pancreatic, gallbladder, post-menopausal breast, endometrial, and ovarian cancers.2124 The associations between these cancers and obesity are supported by a vast body of literature, including large meta-analyses showing statistically significant correlations between cancer risk and increasing BMI.30 Primary reports and meta-analyses support that high BMI also increases the risk of aggressive prostate cancer, liver cancer, thyroid cancer, leukemia, malignant melanoma, and non-Hodgkin's lymphoma.19,2531 Oncologists are likely to encounter many obese and overweight patients, and these patients may be particularly difficult to treat, requiring closer monitoring and more interventions. Practitioners need to be aware of key considerations for patients with high BMI when determining treatment choice, dosing, and supportive care.

Effect of Obesity and Cancer on Risk of VTE

One important consideration for supportive care is that obesity and cancer both increase the risk of VTE. The presence of cancer increases the VTE risk by 4- to 7-fold, and may cause up to 20% of VTE cases.32,33 The association between obesity and VTE is also fairly well established. High BMI (≥35 kg/m2) is included in the calculation of the Khorana score, a metric for assessing risk of VTE in patients with cancer.34 A recent population-based study (N>30,000) in the United States showed that in participants aged 45 years and older, obesity (BMI≥30 kg/m2) was the variable most strongly correlated with VTE.35 Other notably large studies reporting increased rates of VTE in patients with high BMI include a population-based study in Denmark (N>80,000),36 analysis of a cohort (N>15,000) from the Atherosclerosis Risk in Communities study,37 and a prospective study (N>30,000) using the Reasons for Geographic and Racial Differences in Stroke cohort.38 Likewise, obesity rates are higher among patients diagnosed with VTE than in the general population.3941 Interestingly, even among patients with cancer, the risk of VTE may be higher in those who are obese.42 A recently reported analysis of 6,710,066 hospitalizations of US adults found that obesity and metastatic cancer were significantly and independently associated with diagnosis of VTE on hospitalization, indicating that VTE risk would be significantly higher in patients with both conditions (obesity and cancer) relative to those with only one of these risk factors.43

Obesity and Perioperative VTE Risk

In addition to increasing the risk of VTE, high BMI also increases VTE risk in the perioperative setting. Across different types of surgery, including surgery for cancer treatment, BMI correlates with risk of complications, greater blood loss, increased operating times, anastomosis leakage, and longer hospital stays.44,45 A number of analyses, some based on very large patient populations (>2 million shoulder arthroplasties; >20,000 total knee arthroplasties, >26,000 total joint arthroplasties), have shown that obesity increases risk of VTE during orthopedic surgeries.4648 Several large retrospective studies have shown that, for patients undergoing bariatric surgery, the risk of VTE increases with increasing BMI,49,50 a correlation that may be attributed to operating time increasing with BMI.51 Large studies including patients with cancer have shown that obesity is an independent risk factor for portomesenteric VTE in patients receiving major colon and rectal surgery,52 and may increase the risk of VTE associated with central venous catheters or peripherally inserted central catheters used for chemotherapy delivery.5355 The increased risk of perioperative VTE in obese patients means that safe and appropriate VTE prophylaxis may be critical for obese patients with cancer undergoing surgery. Careful determination of the prophylactic anticoagulant dose is especially important in obese patients because of the increased operating times and blood loss.

Adjusting Dosing for Obese Patients

Studies aimed at determining the best approach to dosing in obese patients have produced a variety of results depending on the indication and medication tested.5658 Obesity can potentially affect pharmacokinetics and pharmacodynamics though a variety of physiologic mechanisms, the net result of which could increase or decrease the dose effect. The impact of obesity on the effective dose depends on the agent-specific mechanism of action and pathways of metabolism and elimination. Although for some drugs standard dosing is safe and effective in obese patients, many agents require linear weight-based dose adjustments, and some may require more detailed pharmacokinetic characterization or biomarker measurements to determine the optimal dose for obese patients. One systematic review of chemotherapy dosing indicated that the need for weight-based dose adjustment varies by agent,59 and the ASCO Clinical Practice Guidelines, based on a systematic literature review, recommend weight-based dosing (using actual body weight) for most cytotoxic chemotherapy agents, with a few notable exceptions.60

Weight-Based Anticoagulant Dosing in Patients With High BMI

The development of evidence-based recommendations is hampered by the lack of randomized controlled trials (RCTs) in obese patients comparing standard anticoagulant dosing versus weight-based dosing or higher fixed dosing. However, a number of studies have reported data from obese patients receiving pharmacologic VTE prophylaxis. These reports show that, although patients with high BMI benefit from VTE prophylaxis, VTE rates in patients receiving prophylactic anticoagulation are higher for obese compared with patients with a lower BMI.6166 These data suggest that patients with high BMI may need higher anticoagulant doses to prevent VTE. Indeed, a meta-analysis of bariatric surgery patients receiving prophylactic heparin products (unfractionated heparin [UFH] and low-molecular-weight heparin [LMWH]) showed that weight-adjusted doses were associated with lower VTE rates compared with standard fixed dosing.67

Comparing efficacy of anticoagulant prophylactic dosing regimens can be difficult because reliable measurement of VTE rates requires large sample sizes and long follow-up. Anti–factor Xa (anti-FXa) level, a measure of anticoagulation, has often been used as a surrogate measure of anticoagulant efficacy and safety.68 These data must be interpreted with caution, however, because anti-FXa levels have not been demonstrated conclusively to be associated with clinical events.68

For the 2015 update to the NCCN Guidelines for Cancer-Associated VTE, the panel added dosing recommendations for obese patients receiving prophylaxis with dalteparin, enoxaparin, UFH, and fondaparinux (see VTE-C, page 1081). Appendices 1, 2, 3, and 4 summarize the key studies providing pharmacodynamic, efficacy, and safety data from obese patients receiving these agents for VTE prophylaxis.

Dalteparin

Studies reporting pharmacodynamic, efficacy, or safety data from obese patients treated with prophylactic dalteparin are summarized in Appendix 1. Two RCTs included patients with high BMI treated with prophylactic dalteparin. The Prospective Evaluation of Dalteparin Efficacy for Prevention of VTE in Immobilized Patients (PREVENT) trial compared prophylactic dalteparin with placebo in 3708 medically ill hospitalized patients with at least one VTE risk factor.63 A retrospective subgroup analysis of patients with high BMI (n=1118, most with a BMI of 30.0–34.9 kg/m2) showed that the standard prophylactic dalteparin dosage, 5000 U/d, improved outcomes relative to placebo without increasing bleeding event rates.63 Interestingly, the beneficial effect of dalteparin prophylaxis was apparent across all BMI-based subgroups except for the group with BMI greater than 40 kg/m2, hinting that standard dosing may not be sufficient for morbidly obese patients. Agnelli et al61 reported similar results from their subgroup analysis of an RCT testing VTE prophylaxis with dalteparin (vs fondaparinux) in high-risk patients undergoing abdominal surgery: high BMI was associated with increased VTE rates in both treatment groups, but did not appear correlated with bleeding rates.61 Patients in the dalteparin arm received 2500 U before surgery and 12 hours after surgery, followed by 5000 U once daily; results therefore support that standard dosing may be insufficient for VTE prophylaxis in the obese. In an analysis of 735 patients undergoing bariatric surgery,69 prophylaxis with dalteparin at 2500 U immediately before surgery followed by 5000 U/d (for ≥1 week) provided protection against VTE even after long-term follow-up (0% after ≥6 months), with few patients (<0.5%) having bleeds in the immediate postoperative period. The low VTE rate reported by Magee et al69 may be due to the small number of patients with extreme obesity in the study population, and that only symptomatic VTE was recorded, whereas the previously described RCTs used prospective duplex ultrasound surveillance.61,63

A retrospective analysis by Simoneau et al70 showed that dalteparin at 7500 U/d may be an appropriate dose for many obese patients undergoing bariatric surgery: more than 60% had anti-FXa levels within the target range, and none experienced VTE. Bleeding occurred in 2.2% of obese patients, and did not appear correlated with anti-FXa level. Although the data are limited, the NCCN panel recommends considering dalteparin at 7500 U subcutaneous daily for VTE prophylaxis in patients with a BMI of 40 kg/m2 or greater (see VTE-C, page 1081).

Enoxaparin

Several studies have compared prophylactic fixed-dose enoxaparin regimens in obese patients, primarily in the context of bariatric surgery (Appendix 2).65,7174 Scholten et al71 conducted a large retrospective study in patients with extreme obesity receiving enoxaparin before bariatric surgery and then every 12 hours until discharge or ambulation. Results showed that 40 mg twice daily was associated with lower VTE rates during hospitalization and the 6 months following discharge than 30 mg twice daily, without increasing the incidence of bleeding. It is important to note that there was a trend toward higher BMI, higher male/female ratio, longer hospital stay, and longer procedure duration among patients in the 30-mg twice-daily group. The multicenter retrospective PROBE study of patients undergoing bariatric surgery showed that various enoxaparin 40-mg regimens were associated with lower VTE rates compared with the 30-mg regimens but may have increased the risk of severe bleeds.72 A retrospective analysis by Raftopoulos et al65 showed that for bariatric surgery patients receiving 30 mg of enoxaparin twice daily while hospitalized, rates of VTE and major bleeds were significantly reduced by a course of 40-mg once-daily dosing for 10 days after discharge. A large retrospective study by Wang et al66 found that for extremely obese (BMI>40 kg/m2) hospitalized patients, VTE rates were significantly lower with high-dose versus low-dose enoxaparin (40 mg twice daily vs once daily) or UFH.66 Based on review of these findings, the NCCN Cancer-Associated VTE Panel recommends considering more frequent prophylactic enoxaparin dosing for obese patients (BMI≥40 kg/m2): 40 mg every 12 hours (rather than once daily; see VTE-C, page 1081).

Anti-FXa data from multiple studies suggest that higher doses may be needed for effective VTE prophylaxis in obese patients receiving enoxaparin after bariatric surgery (Appendix 2). A prospective study reported by Rowan et al73 showed that increasing the enoxaparin twice-daily dose from 30 to 40 mg increased the percentage of patients with anti-FXa levels within the target range. Nonetheless, therapeutic anti-FXa levels were achieved by fewer than 50% of patients who received 40-mg (twice daily) dosing, a finding corroborated by Steele et al,75 supporting the conclusion that 40 mg every 12 hours may not be sufficient for all obese patients. A prospective study by Simone et al74 showed that increasing enoxaparin from 40 to 60 mg twice daily reduced the proportion of patients with subtherapeutic anti-FXa levels from 44% to 0%, but also increased the proportion of patients with supratherapeutic levels from 0% to 57%. These findings indicate that it may be difficult to identify a fixed twice-daily dose that safely prevents VTE in all obese patients. Indeed, a more recent study by Celik et al76 showed that body weight was an independent predictor of anti-FXa levels in patients receiving enoxaparin at 40 mg twice daily for VTE prophylaxis after bariatric surgery. The 40-mg twice-daily dosage appeared optimal for the subgroup of patients weighing 110 to 150 kg, with 94% of these patients having anti-FXa levels in the target range. Patients with weights above or below this range tended to have anti-FXa levels that were subtherapeutic or supratherapeutic, respectively, indicating that weight-based dosing may be a better approach to achieve anti-FXa levels in the target range.

Several studies have tested weight-based enoxaparin dosing for VTE prophylaxis in obese patients (Appendix 2).64,7779 These studies show that weight-based enoxaparin dosing results in anti-FXa levels that are not correlated with weight or BMI.64,77,79 Moreover, the percentage of patients achieving target anti-FXa levels was higher (>80%) with enoxaparin at 0.5 mg/kg compared with previously published fixed-dose regimens (described earlier).64,78,79 In a prospective study of hospitalized, medically ill patients with extreme obesity (BMI≥40 kg/m2) and at least one VTE risk factor, Freeman et al79 compared 40-mg daily fixed dosing with 2 weight-based daily dosing regimens: 0.4 and 0.5 mg/kg. They showed that 0.5 mg/kg daily resulted in a significantly higher percentage of patients achieving target anti-FXa levels compared with the other 2 regimens. No symptomatic VTE or adverse events were observed, indicating that dose capping was not necessary up to the highest dose tested (130 mg/d). The 2015 NCCN Cancer-Associated VTE Guidelines update does not include weight-based enoxaparin dosing for VTE prophylaxis in obese patients because larger comparative trials are needed to determine whether this dosing regimen translates into lower event rates.

Two studies tested BMI-based enoxaparin dosing for VTE prophylaxis,80,81 both in patients undergoing bariatric surgery (Appendix 2). Results from an open-label prospective trial reported by Borkgren-Okonek et al81 showed that postoperative twice-daily enoxaparin dosing based on BMI (40 mg/60 mg for BMI ≤50/>50 kg/m2) resulted in therapeutic anti-FXa levels in most patients (74%) and across the wide range of BMI (36–82 kg/m2) in the sample population. Dosing was adjusted for anti-FXa levels outside the target range, resulting in a low rate of VTE (0.45%) and major bleeding in 2.2% of patients (>1-month follow-up). Singh et al80 conducted a retrospective analysis of patients receiving twice-daily prophylactic enoxaparin doses ranging from 30 to 60 mg across 4 BMI-based subgroups. Remarkably, no symptomatic VTE was observed during the minimum 2-year follow-up. Significant bleeding occurred in 2.9% of patients, but was not correlated with higher doses. Although these studies provide preliminary data indicating that BMI-based dosing may be more effective for obese patients than fixed dosing, further evidence is needed to support this approach. The 2015 NCCN Cancer-Associated VTE Guidelines update therefore does not include BMI-based dosing for prophylactic enoxaparin.

Unfractionated Heparin

Bariatric surgery studies provide most of the data on VTE prophylaxis with UFH in obese patients (Appendix 3).66,82,83 In these studies UFH is usually administered at 5000 U before surgery and/or 2 to 4 times per day after surgery. Several studies have tested higher doses in patients with extreme obesity.66,84,85 Shepherd et al84 reported a prospective series of 245 hospitalized medical and surgical patients, including 25% with a BMI greater than 35 kg/m2 (BMI range, 14–71 kg/m2; weight range, 34–193 kg), administered UFH twice-daily dosing adjusted to achieve therapeutic anti-FXa levels. This approach resulted in doses ranging from 3000 to 19,000 U in the population studied, and the equation that best predicted therapeutic dose included both patient height and weight. The derived equation was then used to determine initial UFH prophylactic dose for patients receiving bariatric surgery (N=700). The resultant VTE rate was notably low (0.4%, all nonfatal), and the bleed rate was similar to that seen in previous standard-dosing studies, even though many patients received doses much higher than 5000 U. The efficacy and safety of higher UFH doses in obese patients was corroborated by low rates of VTE and bleeding reported by Miller and Rovito85 in their retrospective analysis of bariatric surgery patients who received prophylactic UFH every 8 hours at a BMI-dependent dose: 7500 U for BMI greater than 50 kg/m2; 5000 U for BMI of 50 kg/m2 or less. As described earlier, a much larger and more recent study by Wang et al66 showed that using higher UFH/enoxaparin prophylactic dosing (UFH, 7500 U every 8 hours vs 5000 U 2 to 3 times per day; Appendix 2) in hospitalized obese patients (BMI≥40 kg/m2) significantly reduced VTE without increasing bleeding. These data support the NCCN Cancer-Associated VTE Panel's recommendation to consider using 7500 U every 8 hours in obese patients (BMI≥40 kg/m2) receiving UFH for VTE prophylaxis (see VTE-C, page 1081.)

Fondaparinux

Limited data are available regarding fondaparinux dosing for VTE prophylaxis in patients with high BMI, although several studies have used the standard prophylaxis dose (2.5 mg/d) in hospitalized obese patients (Appendix 4).61,86,87 Agnelli et al61 reported results from an RCT in patients at high risk for VTE undergoing abdominal surgery, including more than 300 patients with high BMI (>30 kg/m2 for women, >28.6 kg/m2 for men). They found that a high BMI was associated with an increased risk of VTE, suggesting that extremely obese patients may need higher than standard fondaparinux doses for effective VTE prophylaxis. A more recent retrospective study by Martinez et al87 provides additional evidence that standard fondaparinux VTE prophylaxis doses may be inadequate in obese patients (BMI≥40 kg/m2): only 43% had anti-FXa levels within the therapeutic range, whereas 47% had subtherapeutic levels. Moreover, low anti-FXa was associated with higher BMI within the obese patient population tested. Steele et al75 tested fondaparinux at 5 mg/d for thromboprophylaxis following bariatric surgery and found that this higher dose resulted in a higher proportion of patients (74%) achieving anti-FXa levels in the target range. Moreover, VTE only occurred in 2.2% of patients, and all these events were asymptomatic. This higher fondaparinux dose also had an acceptable safety profile, with only 4% of patients developing minor bleeds. Based on this study, the 2015 NCCN Cancer-Associated VTE Guidelines update recommends considering 5 mg/d in obese patients (BMI≥40 kg/m2) receiving VTE prophylaxis with fondaparinux, acknowledging that supporting data are limited (see VTE-C, page 1081).

Renal Insufficiency and Anticoagulant Dosing in Obese Patients

Chronic kidney disease and renal insufficiency are associated with obesity 8892 and with an increased risk of thromboembolic events.93,94 Renal insufficiency is common in patients with VTE, with 52% having a creatinine clearance (CCr) of less than 90 mL/min.95 In patients treated with anticoagulants, particularly LMWH and fondaparinux, renal insufficiency is associated with anti-FXa levels above the therapeutic range and poorer safety and efficacy outcomes.9699 For the obese with renal dysfunction, the safety of higher than standard prophylactic anticoagulant is unknown: many of the studies excluded patients with severe renal insufficiency (CCr<30 mL/>min; Appendices 1, 2, 3, and 4), and whether any of the obese patients studied had mild or moderate renal insufficiency (CCr, 30–90 mL/min) is unclear. Given the impact of renal insufficiency on clearance of enoxaparin and fondaparinux, we would recommend use of UFH or dalteparin in obese patients with severe renal impairment (CCr<30 mL/min).

Conclusions

Anticoagulant dose adjustments may be critical for optimizing VTE prevention in obese patients with cancer, a population at increased risk for VTE. Based on evidence from the studies described earlier and the consensus of the NCCN panel, the 2015 NCCN Guidelines for Cancer-Associated VTE have been updated to include dose adjustments for obese patients receiving prophylaxis with dalteparin, enoxaparin, UFH, or fondaparinux. The panel agrees that prospective RCTs comparing efficacy and safety of different dosing regimens are needed to further support and optimize anticoagulant dose adjustment in obese patients.

Appendix 1

Dalteparin for VTE Prophylaxis in Obese Patients

T1
Appendix 2

Enoxaparin for VTE Prophylaxis in Obese Patients

T2T2T2
Appendix 3

Unfractionated Heparin for VTE Prophylaxis in Obese Patients

T3
Appendix 4

Fondaparinux for VTE Prophylaxis in Obese Patients

T4

References

  • 1.

    KhoranaAAFrancisCWCulakovaE. Thromboembolism in hospitalized neutropenic cancer patients. J Clin Oncol2006;24:484490.

  • 2.

    SallahSWanJYNguyenNP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost2002;87:575579.

    • Search Google Scholar
    • Export Citation
  • 3.

    KhoranaAADalalMLinJConnollyGC. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer2013;119:648655.

    • Search Google Scholar
    • Export Citation
  • 4.

    KakkarAKLevineMPinedoHM. Venous thrombosis in cancer patients: insights from the FRONTLINE survey. Oncologist2003;8:381388.

  • 5.

    CohenATTapsonVFBergmannJF. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet2008;371:387394.

    • Search Google Scholar
    • Export Citation
  • 6.

    TapsonVFDecoususHPiniM. Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients: findings from the International Medical Prevention Registry on Venous Thromboembolism. Chest2007;132:936945.

    • Search Google Scholar
    • Export Citation
  • 7.

    ChewHKWunTHarveyD. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med2006;166:458464.

    • Search Google Scholar
    • Export Citation
  • 8.

    ChewHKWunTHarveyDJ. Incidence of venous thromboembolism and the impact on survival in breast cancer patients. J Clin Oncol2007;25:7076.

    • Search Google Scholar
    • Export Citation
  • 9.

    KudererNMFrancisCWCulakovaE. Venous thromboembolism and all-cause mortality in cancer patients receiving chemotherapy [abstract]. J Clin Oncol2008;26(Suppl 15):Abstract 9521.

    • Search Google Scholar
    • Export Citation
  • 10.

    MartinoMAWilliamsonESiegfriedS. Diagnosing pulmonary embolism: experience with spiral CT pulmonary angiography in gynecologic oncology. Gynecol Oncol2005;98:289293.

    • Search Google Scholar
    • Export Citation
  • 11.

    SorensenHTMellemkjaerLOlsenJHBaronJA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med2000;343:18461850.

  • 12.

    BessesenDH. Update on obesity. J Clin Endocrinol Metab2008;93:20272034.

  • 13.

    OgdenCLCarrollMDKitBKFlegalKM. Prevalence of obesity among adults: United States, 2011–2012. NCHS Data Brief2013:18.

  • 14.

    StevensGASinghGMLuY. National, regional, and global trends in adult overweight and obesity prevalences. Popul Health Metr2012;10:22.

  • 15.

    O'BrienPEDixonJB. The extent of the problem of obesity. Am J Surg2002;184:4S8S.

  • 16.

    NgMFlemingTRobinsonM. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet2014;384:766781.

    • Search Google Scholar
    • Export Citation
  • 17.

    BoeingH. Obesity and cancer—the update 2013. Best Pract Res Clin Endocrinol Metab2013;27:219227.

  • 18.

    KeumNGreenwoodDCLeeDH. Adult weight gain and adiposity-related cancers: a dose-response meta-analysis of prospective observational studies. J Natl Cancer Inst2015;107.

    • Search Google Scholar
    • Export Citation
  • 19.

    RenehanAGTysonMEggerM. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet2008;371:569578.

    • Search Google Scholar
    • Export Citation
  • 20.

    WolinKYCarsonKColditzGA. Obesity and cancer. Oncologist2010;15:556565.

  • 21.

    ArnoldMPandeyaNByrnesG. Global burden of cancer attributable to high body-mass index in 2012: a population-based study. Lancet Oncol2015;16:3646.

    • Search Google Scholar
    • Export Citation
  • 22.

    World Cancer Research Fund/American Institute for Cancer Research. Continuous Update Project Report. Food Nutrition Physical Activity and the Prevention of Ovarian Cancer 2014: AICR; 2014. Available at: http://www.dietandcancerreport.org/cup/cup_resources.php. Accessed August 23 2015.

    • Search Google Scholar
    • Export Citation
  • 23.

    World Cancer Research Fund/American Institute for Cancer Research. Food Nutrition Physical Activity and the Prevention of Cancer: a Global Perspective. Washington DC: AICR; 2007. Available at: http://www.dietandcancerreport.org/cancer_resource_center/er_full_report_english.php. Accessed August 23 2015.

    • Search Google Scholar
    • Export Citation
  • 24.

    CUP team Imperial College London. Continuous update of the epidemiological evidence on food nutrition physical activity and the risk of gallbladder cancer: AICR; 2012. Available at: http://www.dietandcancerreport.org/cancer_resource_center/downloads/cu/CUP_gallbladder_cancer_protocol.pdf. Accessed August 23 2015.

    • Search Google Scholar
    • Export Citation
  • 25.

    AllottEHMaskoEMFreedlandSJ. Obesity and prostate cancer: weighing the evidence. Eur Urol2013;63:800809.

  • 26.

    GolabekTBukowczanJChlostaP. Obesity and prostate cancer incidence and mortality: a systematic review of prospective cohort studies. Urol Int2014;92:714.

    • Search Google Scholar
    • Export Citation
  • 27.

    ChenYWangXWangJ. Excess body weight and the risk of primary liver cancer: an updated meta-analysis of prospective studies. Eur J Cancer2012;48:21372145.

    • Search Google Scholar
    • Export Citation
  • 28.

    DobbinsMDecorbyKChoiBC. The association between obesity and cancer risk: a meta-analysis of observational studies from 1985 to 2011. ISRN Prev Med2013;2013:680536.

    • Search Google Scholar
    • Export Citation
  • 29.

    CastilloJJInghamRRReaganJL. Obesity is associated with increased relative risk of diffuse large B-cell lymphoma: a meta-analysis of observational studies. Clin Lymphoma Myeloma Leuk2014;14:122130.

    • Search Google Scholar
    • Export Citation
  • 30.

    LarssonSCWolkA. Body mass index and risk of non-Hodgkin's and Hodgkin's lymphoma: a meta-analysis of prospective studies. Eur J Cancer2011;47:24222430.

    • Search Google Scholar
    • Export Citation
  • 31.

    KitaharaCMPlatzEAFreemanLE. Obesity and thyroid cancer risk among U.S. men and women: a pooled analysis of five prospective studies. Cancer Epidemiol Biomarkers Prev2011;20:464472.

    • Search Google Scholar
    • Export Citation
  • 32.

    BlomJWDoggenCJOsantoSRosendaalFR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA2005;293:715722.

  • 33.

    HeitJAO'FallonWMPettersonTM. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med2002;162:12451248.

    • Search Google Scholar
    • Export Citation
  • 34.

    KhoranaAAKudererNMCulakovaE. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood2008;111:49024907.

    • Search Google Scholar
    • Export Citation
  • 35.

    OlsonNCCushmanMJuddSE. American Heart Association's Life's Simple 7 and risk of venous thromboembolism: the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. J Am Heart Assoc2015;4:e001494.

    • Search Google Scholar
    • Export Citation
  • 36.

    KlovaiteJBennMNordestgaardBG. Obesity as a causal risk factor for deep venous thrombosis: a Mendelian randomization study. J Intern Med2015;277:573584.

    • Search Google Scholar
    • Export Citation
  • 37.

    WattanakitKLutseyPLBellEJ. Association between cardiovascular disease risk factors and occurrence of venous thromboembolism. A time-dependent analysis. Thromb Haemost2012;108:508515.

    • Search Google Scholar
    • Export Citation
  • 38.

    OlsonNCCushmanMLutseyPL. Inflammation markers and incident venous thromboembolism: the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort. J Thromb Haemost2014;12:19932001.

    • Search Google Scholar
    • Export Citation
  • 39.

    WattsJLKuehnlenzDSuloS. Common characteristics of patients diagnosed with upper-extremity venous thromboembolism during hospitalization: a descriptive study. Clin Nurse Spec2015;29:4854.

    • Search Google Scholar
    • Export Citation
  • 40.

    SartoriMMigliaccioLFavarettoE. Two years outcome of isolated distal deep vein thrombosis. Thromb Res2014;134:3640.

  • 41.

    HansenJBFernandezJABorchKH. Activated protein C plasma levels in the fasting and postprandial states among patients with previous unprovoked venous thromboembolism. Thromb Res2012;129:502507.

    • Search Google Scholar
    • Export Citation
  • 42.

    HicksLKCheungMCDingK. Venous thromboembolism and nonsmall cell lung cancer: a pooled analysis of National Cancer Institute of Canada Clinical Trials Group trials. Cancer2009;115:55165525.

    • Search Google Scholar
    • Export Citation
  • 43.

    TsaiJGrantAMBeckmanMG. Determinants of venous thromboembolism among hospitalizations of US adults: a multilevel analysis. PLoS One2015;10:e0123842.

    • Search Google Scholar
    • Export Citation
  • 44.

    WuXSWuWGLiML. Impact of being overweight on the surgical outcomes of patients with gastric cancer: a meta-analysis. World J Gastroenterol2013;19:45964606.

    • Search Google Scholar
    • Export Citation
  • 45.

    ChildsBRNahmNJDolencAJVallierHA. Obesity is associated with more complications and longer hospital stays after orthopaedic trauma[published online ahead of print March 9 2015]. J Orthop Traumain press.

    • Search Google Scholar
    • Export Citation
  • 46.

    SiHBZengYShenB. The influence of body mass index on the outcomes of primary total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc2015;23:18241832.

    • Search Google Scholar
    • Export Citation
  • 47.

    DayJSRamseyMLLauEWilliamsGR. Risk of venous thromboembolism after shoulder arthroplasty in the Medicare population. J Shoulder Elbow Surg2015;24:98105.

    • Search Google Scholar
    • Export Citation
  • 48.

    ParviziJHuangRRaphaelIJ. Symptomatic pulmonary embolus after joint arthroplasty: stratification of risk factors. Clin Orthop Relat Res2014;472:903912.

    • Search Google Scholar
    • Export Citation
  • 49.

    HaskinsINAmdurRSaraniBVaziriK. Congestive heart failure is a risk factor for venous thromboembolism in bariatric surgery[published online ahead of print December 24 2014]. Surg Obes Relat Dis.doi: 10.1016/j.soard.2014.12.020.

    • Search Google Scholar
    • Export Citation
  • 50.

    JamalMHCorcellesRShimizuH. Thromboembolic events in bariatric surgery: a large multi-institutional referral center experience. Surg Endosc2015;29:376380.

    • Search Google Scholar
    • Export Citation
  • 51.

    ChanMMHamzaNAmmoriBJ. Duration of surgery independently influences risk of venous thromboembolism after laparoscopic bariatric surgery. Surg Obes Relat Dis2013;9:8893.

    • Search Google Scholar
    • Export Citation
  • 52.

    RobinsonKAO'DonnellMEPearsonD. Portomesenteric venous thrombosis following major colon and rectal surgery: incidence and risk factors. Surg Endosc2015;29:10711079.

    • Search Google Scholar
    • Export Citation
  • 53.

    LiuYGaoYWeiL. Peripherally inserted central catheter thrombosis incidence and risk factors in cancer patients: a double-center prospective investigation. Ther Clin Risk Manag2015;11:153160.

    • Search Google Scholar
    • Export Citation
  • 54.

    LeungAHealCPereraMPretoriusC. A systematic review of patient-related risk factors for catheter-related thrombosis. J Thromb Thrombolysis2015;40:363373.

    • Search Google Scholar
    • Export Citation
  • 55.

    BlaivasMStefanidisKNanasS. Sonographic and clinical features of upper extremity deep venous thrombosis in critical care patients. Crit Care Res Pract2012;2012:489135.

    • Search Google Scholar
    • Export Citation
  • 56.

    SankaralingamSKimRBPadwalRS. The impact of obesity on the pharmacology of medications used for cardiovascular risk factor control. Can J Cardiol2015;31:167176.

    • Search Google Scholar
    • Export Citation
  • 57.

    VelissarisDKaramouzosVMarangosM. Pharmacokinetic changes and dosing modification of aminoglycosides in critically ill obese patients: a literature review. J Clin Med Res2014;6:227233.

    • Search Google Scholar
    • Export Citation
  • 58.

    Al-DorziHMAl HarbiSAArabiYM. Antibiotic therapy of pneumonia in the obese patient: dosing and delivery. Curr Opin Infect Dis2014;27:165173.

    • Search Google Scholar
    • Export Citation
  • 59.

    HallRG2ndJeanGWSiglerMShahS. Dosing considerations for obese patients receiving cancer chemotherapeutic agents. Ann Pharmacother2013;47:16661674.

    • Search Google Scholar
    • Export Citation
  • 60.

    GriggsJJManguPBAndersonH. Appropriate chemotherapy dosing for obese adult patients with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol2012;30:15531561.

    • Search Google Scholar
    • Export Citation
  • 61.

    AgnelliGBergqvistDCohenAT. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg2005;92:12121220.

    • Search Google Scholar
    • Export Citation
  • 62.

    FrederiksenSGHedenbroJLNorgrenL. Enoxaparin effect depends on body-weight and current doses may be inadequate in obese patients. Br J Surg2003;90:547548.

    • Search Google Scholar
    • Export Citation
  • 63.

    KucherNLeizoroviczAVaitkusPT. Efficacy and safety of fixed low-dose dalteparin in preventing venous thromboembolism among obese or elderly hospitalized patients: a subgroup analysis of the PREVENT trial. Arch Intern Med2005;165:341345.

    • Search Google Scholar
    • Export Citation
  • 64.

    BickfordAMajercikSBledsoeJ. Weight-based enoxaparin dosing for venous thromboembolism prophylaxis in the obese trauma patient. Am J Surg2013;206:847851discussion 851–842.

    • Search Google Scholar
    • Export Citation
  • 65.

    RaftopoulosIMartindaleCCroninASteinbergJ. The effect of extended post-discharge chemical thromboprophylaxis on venous thromboembolism rates after bariatric surgery: a prospective comparison trial. Surg Endosc2008;22:23842391.

    • Search Google Scholar
    • Export Citation
  • 66.

    WangTFMilliganPEWongCA. Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients. Thromb Haemost2014;111:8893.

    • Search Google Scholar
    • Export Citation
  • 67.

    IkesakaRDellucALe GalGCarrierM. Efficacy and safety of weight-adjusted heparin prophylaxis for the prevention of acute venous thromboembolism among obese patients undergoing bariatric surgery: a systematic review and meta-analysis. Thromb Res2014;133:682687.

    • Search Google Scholar
    • Export Citation
  • 68.

    VandiverJWRitzLILalamaJT. Chemical prophylaxis to prevent venous thromboembolism in morbid obesity: literature review and dosing recommendations[published online ahead of print May 17 2015]. J Thromb Thrombolysisin press.

    • Search Google Scholar
    • Export Citation
  • 69.

    MageeCJBarryJJavedS. Extended thromboprophylaxis reduces incidence of postoperative venous thromboembolism in laparoscopic bariatric surgery. Surg Obes Relat Dis2010;6:322325.

    • Search Google Scholar
    • Export Citation
  • 70.

    SimoneauMDVachonAPicardF. Effect of prophylactic dalteparin on anti-factor Xa levels in morbidly obese patients after bariatric surgery. Obes Surg2010;20:487491.

    • Search Google Scholar
    • Export Citation
  • 71.

    ScholtenDJHoedemaRMScholtenSE. A comparison of two different prophylactic dose regimens of low molecular weight heparin in bariatric surgery. Obes Surg2002;12:1924.

    • Search Google Scholar
    • Export Citation
  • 72.

    HamadGGChobanPS. Enoxaparin for thromboprophylaxis in morbidly obese patients undergoing bariatric surgery: findings of the prophylaxis against VTE outcomes in bariatric surgery patients receiving enoxaparin (PROBE) study. Obes Surg2005;15:13681374.

    • Search Google Scholar
    • Export Citation
  • 73.

    RowanBOKuhlDALeeMD. Anti-Xa levels in bariatric surgery patients receiving prophylactic enoxaparin. Obes Surg2008;18:162166.

  • 74.

    SimoneEPMadanAKTichanskyDS. Comparison of two low-molecular-weight heparin dosing regimens for patients undergoing laparoscopic bariatric surgery. Surg Endosc2008;22:23922395.

    • Search Google Scholar
    • Export Citation
  • 75.

    SteeleKECannerJProkopowiczG. The EFFORT trial: preoperative enoxaparin versus postoperative fondaparinux for thromboprophylaxis in bariatric surgical patients: a randomized double-blind pilot trial. Surg Obes Relat Dis2015;11:672683.

    • Search Google Scholar
    • Export Citation
  • 76.

    CelikFHuitemaADHooijbergJH. Fixed-dose enoxaparin after bariatric surgery: the influence of body weight on peak anti-xa levels. Obes Surg2015;25:628634.

    • Search Google Scholar
    • Export Citation
  • 77.

    RondinaMTWheelerMRodgersGM. Weight-based dosing of enoxaparin for VTE prophylaxis in morbidly obese, medically-Ill patients. Thromb Res2010;125:220223.

    • Search Google Scholar
    • Export Citation
  • 78.

    LudwigKPSimonsHJMoneM. Implementation of an enoxaparin protocol for venous thromboembolism prophylaxis in obese surgical intensive care unit patients. Ann Pharmacother2011;45:13561362.

    • Search Google Scholar
    • Export Citation
  • 79.

    FreemanAHornerTPendletonRCRondinaMT. Prospective comparison of three enoxaparin dosing regimens to achieve target anti-factor Xa levels in hospitalized, medically ill patients with extreme obesity. Am J Hematol2012;87:740743.

    • Search Google Scholar
    • Export Citation
  • 80.

    SinghKPodolskyERUmS. Evaluating the safety and efficacy of BMI-based preoperative administration of low-molecular-weight heparin in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg2012;22:4751.

    • Search Google Scholar
    • Export Citation
  • 81.

    Borkgren-OkonekMJHartRWPantanoJE. Enoxaparin thromboprophylaxis in gastric bypass patients: extended duration, dose stratification, and antifactor Xa activity. Surg Obes Relat Dis2008;4:625631.

    • Search Google Scholar
    • Export Citation
  • 82.

    BecattiniCAgnelliGManinaG. Venous thromboembolism after laparoscopic bariatric surgery for morbid obesity: clinical burden and prevention. Surg Obes Relat Dis2012;8:108115.

    • Search Google Scholar
    • Export Citation
  • 83.

    StrohCBirkDFlade-KutheR. Evidence of thromboembolism prophylaxis in bariatric surgery-results of a quality assurance trial in bariatric surgery in Germany from 2005 to 2007 and review of the literature. Obes Surg2009;19:928936.

    • Search Google Scholar
    • Export Citation
  • 84.

    ShepherdMFRosboroughTKSchwartzML. Heparin thromboprophylaxis in gastric bypass surgery. Obes Surg2003;13:249253.

  • 85.

    MillerMTRovitoPF. An approach to venous thromboembolism prophylaxis in laparoscopic Roux-en-Y gastric bypass surgery. Obes Surg2004;14:731737.

    • Search Google Scholar
    • Export Citation
  • 86.

    TurpieAGBauerKAErikssonBILassenMR. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med2002;162:18331840.

    • Search Google Scholar
    • Export Citation
  • 87.

    MartinezLBurnettABorregoM. Effect of fondaparinux prophylaxis on anti-factor Xa concentrations in patients with morbid obesity. Am J Health Syst Pharm2011;68:17161722.

    • Search Google Scholar
    • Export Citation
  • 88.

    LiYChenYLiuX. Metabolic syndrome and chronic kidney disease in a Southern Chinese population. Nephrology (Carlton)2014;19:325331.

  • 89.

    LinBShaoLLuoQ. Prevalence of chronic kidney disease and its association with metabolic diseases: a cross-sectional survey in Zhejiang province, Eastern China. BMC Nephrol2014;15:36.

    • Search Google Scholar
    • Export Citation
  • 90.

    KhajehdehiPMalekmakanLPakfetratM. Prevalence of chronic kidney disease and its contributing risk factors in southern Iran: a cross-sectional adult population-based study. Iran J Kidney Dis2014;8:109115.

    • Search Google Scholar
    • Export Citation
  • 91.

    McMahonGMPreisSRHwangSJFoxCS. Mid-adulthood risk factor profiles for CKD. J Am Soc Nephrol2014;25:26332641.

  • 92.

    TsujimotoTSairenchiTIsoH. The dose-response relationship between body mass index and the risk of incident stage >/=3 chronic kidney disease in a general japanese population: the Ibaraki prefectural health study (IPHS). J Epidemiol2014;24:444451.

    • Search Google Scholar
    • Export Citation
  • 93.

    ZengWTSunXTTangK. Risk of thromboembolic events in atrial fibrillation with chronic kidney disease. Stroke2015;46:157163.

  • 94.

    BauerALimpergerVNowak-GottlU. End-stage renal disease and thrombophilia. Hamostaseologie2015;35.

  • 95.

    CookLMKahnSRGoodwinJKovacsMJ. Frequency of renal impairment, advanced age, obesity and cancer in venous thromboembolism patients in clinical practice. J Thromb Haemost2007;5:937941.

    • Search Google Scholar
    • Export Citation
  • 96.

    NutescuEASpinlerSAWittkowskyADagerWE. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother2009;43:10641083.

    • Search Google Scholar
    • Export Citation
  • 97.

    DealENHollandsJMRineyJN. Evaluation of therapeutic anticoagulation with enoxaparin and associated anti-Xa monitoring in patients with morbid obesity: a case series. J Thromb Thrombolysis2011;32:188194.

    • Search Google Scholar
    • Export Citation
  • 98.

    GerlachATPickworthKKSethSK. Enoxaparin and bleeding complications: a review in patients with and without renal insufficiency. Pharmacotherapy2000;20:771775.

    • Search Google Scholar
    • Export Citation
  • 99.

    HoffmannPKellerF. Increased major bleeding risk in patients with kidney dysfunction receiving enoxaparin: a meta-analysis. Eur J Clin Pharmacol2012;68:757765.

    • Search Google Scholar
    • Export Citation
  • 100.

    KothariSNLambertPJMathiasonMA. Best Poster Award. A comparison of thromboembolic and bleeding events following laparoscopic gastric bypass in patients treated with prophylactic regimens of unfractionated heparin or enoxaparin. Am J Surg2007;194:709711.

    • Search Google Scholar
    • Export Citation
  • 101.

    BrasileiroALMirandaFJrEttingerJE. Incidence of lower limbs deep vein thrombosis after open and laparoscopic gastric bypass: a prospective study. Obes Surg2008;18:5257.

    • Search Google Scholar
    • Export Citation
  • 102.

    KhoursheedMAl-BaderIAl-AsfarF. Therapeutic effect of low-molecular weight heparin and incidence of lower limb deep venous thrombosis and pulmonary embolism after laparoscopic bariatric surgery. Surg Laparosc Endosc Percutan Tech2013;23:491493.

    • Search Google Scholar
    • Export Citation
  • 103.

    Escalante-TattersfieldTTuckerOFajnwaksP. Incidence of deep vein thrombosis in morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass. Surg Obes Relat Dis2008;4:126130.

    • Search Google Scholar
    • Export Citation
  • 104.

    SchauerPRIkramuddinSGourashW. Outcomes after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Ann Surg2000;232:515529.

  • 105.

    HigaKDHoTBooneKB. Laparoscopic Roux-en-Y gastric bypass: technique and 3-year follow-up. J Laparoendosc Adv Surg Tech A2001;11:377382.

    • Search Google Scholar
    • Export Citation
  • 106.

    PrystowskyJBMoraschMDEskandariMK. Prospective analysis of the incidence of deep venous thrombosis in bariatric surgery patients. Surgery2005;138:759763; discussion 763–755.

    • Search Google Scholar
    • Export Citation
  • 107.

    McCulloughPAGallagherMJDejongAT. Cardiorespiratory fitness and short-term complications after bariatric surgery. Chest2006;130:517525.

    • Search Google Scholar
    • Export Citation
  • 108.

    VaziriKBhanotPHungnessES. Retrievable inferior vena cava filters in high-risk patients undergoing bariatric surgery. Surg Endosc2009;23:22032207.

    • Search Google Scholar
    • Export Citation

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