The majority of women with gynecologic cancer will undergo surgery for their disease. Deep vein thrombosis and pulmonary embolism, or venous thromboembolic events are common, serious complications. The rate of pulmonary embolism in women with gynecologic malignancy may be as high as 6.8%, with the case fatality rate being 11%-12%. Hence, one key strategy to lower the rate of fatal pulmonary embolism depends on proper prophylaxis for deep vein thrombosis prevention.
Factors associated with the development of venous thromboembolic events (VTE) include prior VTE, malignancy, older age, African American race, prolonged operative time, and prior radiation therapy (Obstet. Gynecol. 1987;69:146-50). The risk of pulmonary embolism (PE) in women undergoing gynecologic surgery is quadrupled in the presence of malignancy (Obstet. Gynecol. 2006;107:666-71) and these patients are twice as likely to die from a VTE, compared with matched controls (Gynecol. Oncol. 2007;106:439-45). In addition, cancer patients are typically older and have longer and more complex surgeries. Furthermore, the presence of a pelvic mass further contributes to venous stasis (Obstet. Gynecol. 2012;119:155-67).
Other risk factors associated with the development of VTE include hormone replacement therapy, oral contraceptives, use of tamoxifen, and inherited thrombophilias. The most common is factor V Leiden deficiency, affecting up to 20% of patients with VTE. Affected heterozygotes have a 3- to 8-fold increased risk of VTE, whereas homozygotes have a 50- to 80-fold increased risk (Blood 1995;85:1504-8).
Depending on additional risk factors, both the American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin and guidelines published by the American College of Chest Physicians (ACCP) place women with gynecologic cancers into "high" or "highest" risk categories (Obstet. Gynecol. 2007;110:429-40; Chest 2012;141:e227S-77S).
Currently, thromboprophylaxis regimens include mechanical and pharmacologic methods. Mechanical devices include graduated compression stockings and intermittent pneumatic compression, which reduce venous stasis and may promote endogenous fibrinolysis. Pharmacologic prophylaxis includes unfractionated heparin (UFH) and low-molecular weight heparin (LMWH). Prospective controlled trials have shown that UFH reduces VTE in patients with gynecologic cancer. Trials comparing LMWH with UFH have demonstrated equivalent efficacy and similar bleeding complications. The recommended prophylactic dose for LMWH is 40 mg subcutaneous injection daily. However, this dose may need to be adjusted in morbidly obese patients (body mass index greater than 40 kg/m2) as well as in women with abnormal renal clearance. UFH should be administered as a dose of 5,000 units subcutaneously three times daily. Intermittent pneumatic compression also has been shown to reduce the incidence of VTE in this patient population.
A combined regimen of pharmacologic and mechanical prophylaxis may improve efficacy, especially in the highest-risk patients, such as women with gynecologic cancer. Although limited data exist to support this approach in gynecology patients, studies from other surgical disciplines suggest benefit from a combined regimen. With regards to addressing the timing of initiation, a large retrospective trial of patients undergoing hysterectomy for benign indications concluded that postoperative rather than preoperative administration of UFH or LMWH may reduce the risk of bleeding complications without apparent risk of increased VTE (Acta. Obstet. Gynecol. Scand. 2008;87:1039-47).
In summary, the majority of gynecologic oncology patients are considered to be at the highest risk for developing VTE. For this group of women, double prophylaxis with either UFH or LMWH, and a mechanical method (intermittent pneumatic compression) are recommended in the perioperative setting. In addition, ACCP further recommends that these patients receive extended postoperative prophylaxis with LMWH for 4 weeks. Further evidence is needed to determine acceptable timing for initiation of therapy in order to find a balance between adequate thromboprophylaxis and bleeding complications.
Dr. Roque is a fellow in the gynecologic oncology program at the University of North Carolina at Chapel Hill. Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology and a professor in the division of gynecologic oncology at the university. Dr. Roque and Dr. Clarke-Pearson said they had no relevant disclosures. Scan this QR code or go to obgynnews.com to view similar columns.