Optimal Timing of Perioperative Chemoprophylaxis in Patients With High Thromboembolic Risk Undergoing Major Abdominal Surgery

Abstract

To determine whether early (before skin closure) versus postoperative chemoprophylaxis affects the incidence of venous thromboembolism (VTE) and bleeding following major abdominal surgery, in a high thromboembolic risk population. Background: Major abdominal surgery incurs both VTE and bleeding risks. Patients with high preoperative VTE risk derive the most benefit from chemoprophylaxis, but carry an increased risk of bleeding. The optimal window for chemoprophylaxis in the perioperative period, whereby both VTE and bleeding risks are minimized, is unknown. Methods: Analysis of pooled data from 5 multicenter studies including only high thromboembolic risk (Caprini score > 4) patients. Clinical VTE was defined as radiographically proven symptomatic disease <30 days postsurgery. Major bleeding was defined as the need for blood transfusion, reintervention, or > 20 g/L fall in hemoglobin. Results: From 5501 cases, chemoprophylaxis was initiated early in 1752 (31.8%) patients and postoperatively in 3749 (68.2%) patients. Baseline characteristics were similar between study groups. The incidence of clinical VTE was not associated with chemoprophylaxis timing [early 0.7% vs. postop 0.7%, odds ratio (OR): 1.11, 95% confidence interval (CI): 0.60-2.15, P = 0.730]. Contrastingly, compared with postoperative chemoprophylaxis, early usage increased the risk of all bleeding (5.1% vs. 2.6%, OR: 2.04, 95% CI: 1.52-2.73, P < 0.001) major bleeding (3.6% vs. 1.8%, OR: 1.99, 95% CI: 1.40-2.81, P < 0.001), and reintervention (2.0% vs. 1.0%, OR: 2.10, 95% CI: 1.32-3.35, P = 0.003). Early chemoprophylaxis independently predicted postoperative bleeding (OR: 1.71, 95% CI: 1.25-2.34, P < 0.001), but not VTE. Conclusions: In high VTE risk patients undergoing major abdominal surgery, chemoprophylaxis commenced postoperatively reduces bleeding risk without affecting clinical VTE risk.

Effect of timing of perioperative chemical thromboprophylaxis on thromboembolic, bleeding, and other complications during and after antireflux surgery: multicentre cohort study

“…The observation that postoperative chemical thromboprophylaxis is associated with a lower risk of bleeding than early usage in antireflux surgery is consistent with studies in gallbladder 9 , liver 17 , ventral hernia 10 , bariatric 18 , breast 19 , hip 20 , and abdominal visceral surgery 8 . Additionally, within major abdominal surgery, subgroup analysis of patients with an inherently high thromboembolic risk also favours postoperative chemical thromboprophylaxis over early usage 21 . These reports, along with findings from two recent meta-analyses, one of randomized trials involving different surgical disciplines 22 , and the other of randomized trials and cohort studies involving major abdominal surgery 23 , demonstrated that postoperative chemical thromboprophylaxis did not diminish protection against VTE.…”

Optimal Timing of Perioperative Chemical Thromboprophylaxis in Elective Major Abdominal Surgery

“…However, these comparisons did not reach statistical significance. Moreover, we recently demonstrated that even in patients with high baseline thromboembolic risk, the timing of perioperative chemoprophylaxis did not impact clinical VTE, but postoperative chemoprophylaxis significantly decreased the risk of bleeding when compared with early chemoprophylaxis 34…”

Towards standardized perioperative chemoprophylaxis in major elective abdominal surgery

“…Therefore, chemoprophylaxis prescription requires balancing the risk of bleeding with thromboembolic protection. Currently, chemoprophylaxis usage is associated with the following issues 3–11 : Guidelines are outdated, unclear or poorly utilized. Compliance is suboptimal, increasing the risk of VTE. The optimal timing of perioperative administration is unclear leading to significant variations in practice. The lack of standardization of chemoprophylaxis may adversely affect bleeding and/or VTE risks. …”

“…The key findings from these studies are summarized below (Table 1): Chemoprophylaxis administered before skin closure (preoperative and intraoperative initiation) offered no additional protection against VTE but increased the risk of major postoperative bleeding, blood transfusion and re‐intervention, compared to postoperative chemoprophylaxis 4,6–10 In patients with the highest baseline VTE risk, postoperative chemoprophylaxis, compared with its administration before skin closure, was still found to offer equivalent VTE protection whilst reducing the risk of postoperative bleeding 9 Chemoprophylaxis can be safely administered at any time within the first 24 h post‐surgery without adversely affecting VTE and bleeding risks 11 …”