Extended thromboprophylaxis with low-molecular weight heparin (LMWH) following abdominopelvic cancer surgery

Highlights

• Abdominopelvic cancer surgery has high risk of venous thromboembolism events.

• Evidence shows benefit for extended versus standard duration thromboprophylaxis.

• No increased bleeding or treatment-related deaths were observed.

• Individual risk factors should guide thromboprophylactic duration.

Abstract

Background

Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE). Certain abdominopelvic cancer surgeries are associated with a six to 14-fold increased risk of DVT versus surgeries for benign disease, and extended thromboprophylaxis using perioperative LMWHs may further reduce VTE rates over standard duration administration. This review assesses the value of extended low molecular weight heparin (LMWH) thromboprophylaxis as a recommended strategy after abdominopelvic cancer surgery.

Data sources

Six eligible randomized controlled trials (RCTs), seven meta-analyses (MAs), and five non-randomized cohort studies were identified evaluating extended versus standard thromboprophylaxis following abdominopelvic cancer surgery.

Findings and conclusions

Available evidence showed significantly reduced rates of VTE for extended versus standard LMWH thromboprophylaxis following abdominopelvic cancer surgery, with some studies showing trends toward reduced rates of symptomatic VTE events. Many of these studies showed significantly reduced rates of proximal DVT and some showed trends toward reduced PE, suggesting potentially important clinical benefits.

Introduction

Venous thromboembolism (VTE) is a global health care problem resulting in substantial mortality, morbidity, and increased cost of medical care. VTE includes deep vein thrombosis (DVT; asymptomatic or symptomatic, proximal or distal) and pulmonary embolism (PE), a complication of potentially life-threatening consequence. The yearly age adjusted annual incidence rate of VTE is reported to be from 110 among women and 130 for men per 100,000, representing the third most common circulatory disorder in the West,¹ with reported incidence rates of DVT alone (without PE) and PE (with or without DVT) ranging from 45 to 117 and 29 to 78 per 100,000 person years, respectively.^1,2

Risk factors for VTE include venous stasis, vascular injury, and the induction of hypercoagulable states (Virchow's triad), and patients undergoing major abdominopelvic surgery are exposed to all three of these factors.³ VTE events are 10–100 times more frequent in surgical than medical inpatients,⁴ with asymptomatic DVT rates associated with major abdominopelvic surgery reported to be 15%–40% and fatal PE rates of 0.2%–0.9% in the absence of VTE prophylaxis.^1,5, 6, 7, 8 Cancer is also associated with a hypercoagulable state leading to increased VTE risk,⁹ and the risk of VTE in patients with cancer has been reported to be seven-fold higher than in individuals without malignancy, which can contribute to increased mortality and interfere with cancer therapy.^10,11 Studies have also shown a significant nearly six and 14-fold increased risk of DVT and PE, respectively, in patients receiving gynecologic surgery for cancer compared with those undergoing similar surgeries for benign disease.^12,13 The Caprini score sums individual VTE risk factors for patients undergoing surgery and is one of the most commonly used metrics for defining higher risk patients (score ≥5), which include those ≥41 years old undergoing surgery for either cancer (score ≥5) or for benign disease with additional risk factors (score ≥3).¹⁴ Given the increased VTE risk in these patients, particularly for those undergoing abdominopelvic cancer surgeries, optimal thromboprophylaxis is a subject of great clinical concern.

Standard medical thromboprophylaxis typically consists of unfractionated heparin or low molecular weight heparins (LMWHs) administered during the post-operative period for up to 10 days. This practice is common in patients undergoing abdominopelvic surgery who have VTE risk factors and are not at increased risk for major bleeding complications. VTE risk factors include longer duration of surgery¹⁵ and an increased period of immobilization,¹⁶ as well as increased age, and obesity, among others.17, 18, 19, 20, 21, 22 Standard thromboprophylaxis has been shown to significantly reduce rates of clinical VTE (71%), risk of DVT (72%), and clinical PE (75%) compared with no thromboprophylaxis.⁶ Despite this, two major meta-analyses (MA), show residual VTE rates of 5.6% and 14.3% in patients following standard approaches^3,23 and there is some indication that a hypercoagulable state may persist for up to a month²⁴ with many VTE events (40%) occurring more than 21 days from surgery.²⁵ These data suggest the need for more prolonged prophylaxis.

Extended thromboprophylaxis is typically defined as LMWH use for up to one month following surgery. Evidence from MAs or randomized controlled trials (RCTs) demonstrating significantly improved outcomes for a new therapy compared with standard of care is usually required to support a change in clinical practice.²⁶ Although emerging evidence on extended thromboprophylaxis suggests that this approach is safe and can further reduce VTE rates,^3,11,23 this practice has not been widely adopted.²⁷ The purpose of this review is to assess the risks and benefits of extended LMWH thromboprophylaxis for reducing rates of VTE events following abdominopelvic cancer surgery.