Outcomes following pancreatic surgery using three different thromboprophylaxis regimens

Background: Postpancreatectomy haemorrhage (PPH) and venous thromboembolism (VTE) are serious complications following pancreatic surgery. The aim was to assess the timing, occurrence and predictors of PPH and VTE. Methods: Elective pancreatic resections undertaken in a single university hospital between November 2013 and September 2017 were assessed. Three intervals were reviewed, each with a different routine regimen of nadroparin: 2850 units once daily (single dose) administered in hospital only, or 5700 units once daily (double dose) or 2850 units twice daily (split dose) administered in hospital and continued for 6weeks after surgery. Clinically relevant PPH (CR-PPH) was classified according to International Study Group of Pancreatic Surgery criteria. VTE was defined according to a number of key diagnostic criteria within 6weeks of surgery. Cox regression analyses were performed to test the hypotheses that the double-dose group would experience more PPH than the other two groups, the single-dose group would experience more VTE than the other two groups, and the split-dose group would experience the fewest adverse events (PPH or VTE). Results: In total, 240 patients were included, 80 per group. The double-dose group experienced significantly more CR-PPH (hazard ratio (HR) 2.14, 95 per cent c.i. 1.16 to 3.94; P = 0.015). More relaparotomies due to CR-PPH were performed in the double-dose group (16 versus 3.8 per cent; P = 0.002). The single-dose group did not experience more VTE (HR 1.41, 0.43 to 4.62; P = 0.570). The split dose was not associated with fewer adverse events (HR 0.77, 0.41 to 1.46; P = 0.422). Double-dose low molecular weight heparin (LMWH), high BMI and pancreatic fistula were independent predictors of CR-PPH. Conclusion: A double dose of LMWH prophylaxis continued for 6weeks after pancreatic resection was associated with a twofold higher rate of CR-PPH, resulting in four times more relaparotomies. Patients receiving a single daily dose of LMWH in hospital only did not experience a higher rate of VTE.