Langenbeck's Archives of Surgery

, Volume 403, Issue 8, pp 949–957 | Cite as

Risk for hemorrhage after pancreatoduodenectomy with venous resection

  • Dyre KleiveEmail author
  • Mushegh Sahakyan
  • Kjetil Søreide
  • Kristoffer W. Brudvik
  • Pål-Dag Line
  • Ivar P. Gladhaug
  • Knut Jørgen Labori



No consensus exists on the optimal anticoagulation therapy after pancreatoduodenectomy with venous resection (PDVR). The aim of the study was to analyze perioperative outcomes of patients receiving low- vs high-dose anticoagulation therapy and to identify risk factors for postpancreatectomy hemorrhage in patients undergoing PDVR.


Retrospective study of patients undergoing PDVR at a tertiary referral center between January 2006 and April 2017. Patients were investigated according to the dose of postoperative anticoagulation given (low- or high-dose low-molecular-weight heparin). Uni- and multivariate analysis were performed to assess risk factors for postpancreatectomy hemorrhage.


A total of 141 patients underwent PDVR. Low-dose anticoagulation was given to 45 (31.9%) patients. Operative time (428 min vs 398 min, p = 0.025) and the use of interposition grafts (27% vs 11%, P = 0.033) were significantly higher in the high-dose group. There was no difference in the rate of early portal vein thrombosis (4.4% vs 4.2%, p = 0.939) or postpancreatectomy hemorrhage (13.3% vs 16.7%, p = 0.611) between the low- and high-dose groups. On multivariate analysis, serum bilirubin ≥ 200 μmol/L and clinically relevant postoperative fistula were the only factors associated with postpancreatectomy hemorrhage (OR 10.28, 95% CI 3.51–30.07, P < 0.001, and OR 6.39, 95% CI 1.59–25.74, P = 0.009).


Preoperative hyperbilirubinemia and clinically relevant postoperative fistula are risk factors for postpancreatectomy hemorrhage after PDVR. Rates of postpancreatectomy hemorrhage did not differ between patients receiving high- vs low-dose low-molecular-weight heparin.


Pancreatoduodenectomy with venous resection Anticoagulation policy 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was not obtained by all participants. The study was permitted by the hospital review board in accordance with the regional ethical committee.


  1. 1.
    Worni M, Castleberry AW, Clary BM, Gloor B, Carvalho E, Jacobs DO, Pietrobon R, Scarborough JE, White RR (2013) Concomitant vascular reconstruction during pancreatectomy for malignant disease: a propensity score-adjusted, population-based trend analysis involving 10,206 patients. JAMA Surg 148:331–338CrossRefGoogle Scholar
  2. 2.
    Tzeng CW, Katz MH, Lee JE et al (2014) Predicting the risks of venous thromboembolism versus post-pancreatectomy haemorrhage: analysis of 13,771 NSQIP patients. HPB (Oxford) 16:373–383CrossRefGoogle Scholar
  3. 3.
    Kleive D, Sahakyan MA, Berstad AE, Verbeke CS, Gladhaug IP, Edwin B, Fosby B, Line PD, Labori KJ (2017) Trends in indications, complications and outcomes for venous resection during pancreatoduodenectomy. Br J Surg 104:1558–1567CrossRefGoogle Scholar
  4. 4.
    Malleo G, Maggino L, Marchegiani G, Feriani G, Esposito A, Landoni L, Casetti L, Paiella S, Baggio E, Lipari G, Capelli P, Scarpa A, Bassi C, Salvia R (2017) Pancreatectomy with venous resection for pT3 head adenocarcinoma: Perioperative outcomes, recurrence pattern and prognostic implications of histologically confirmed vascular infiltration. Pancreatology 17:847–857CrossRefGoogle Scholar
  5. 5.
    Ravikumar R, Sabin C, Abu Hilal M, al-Hilli A, Aroori S, Bond-Smith G, Bramhall S, Coldham C, Hammond J, Hutchins R, Imber C, Preziosi G, Saleh A, Silva M, Simpson J, Spoletini G, Stell D, Terrace J, White S, Wigmore S, Fusai G (2017) Impact of portal vein infiltration and type of venous reconstruction in surgery for borderline resectable pancreatic cancer. Br J Surg 104:1539–1548CrossRefGoogle Scholar
  6. 6.
    Kantor O, Talamonti MS, Wang CH, Roggin KK, Bentrem DJ, Winchester DJ, Prinz RA, Baker MS (2018) The extent of vascular resection is associated with perioperative outcome in patients undergoing pancreaticoduodenectomy. HPB (Oxford) 20:140–146CrossRefGoogle Scholar
  7. 7.
    Chandrasegaram MD, Eslick GD, Lee W, Brooke-Smith ME, Padbury R, Worthley CS, Chen JW, Windsor JA (2014) Anticoagulation policy after venous resection with a pancreatectomy: a systematic review. HPB (Oxford) 16:691–698CrossRefGoogle Scholar
  8. 8.
    von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP (2007) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet (London, England) 370:1453–1457CrossRefGoogle Scholar
  9. 9.
    Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC (2009) Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol 16:1727–1733CrossRefGoogle Scholar
  10. 10.
    National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Pancreatic adenocarcinoma version 2. 2017. Available at:, 2017
  11. 11.
    Balachandran P, Sikora SS, Raghavendra Rao RV, Kumar A, Saxena R, Kapoor VK (2004) Haemorrhagic complications of pancreaticoduodenectomy. ANZ J Surg 74:945–950CrossRefGoogle Scholar
  12. 12.
    Wang WG, Fu L, Babu SR, Wang L, Liang CP, Tian BL (2018) Incidence of and risk factors and reinterventions for post-pancreatoduodenectomy hemorrhage: retrospective analysis. Dig Surg 35:19–27CrossRefGoogle Scholar
  13. 13.
    Dindo D, Demartines N, Clavien PA (2004) Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 240:205–213CrossRefGoogle Scholar
  14. 14.
    Slankamenac K, Nederlof N, Pessaux P, de Jonge J, Wijnhoven BPL, Breitenstein S, Oberkofler CE, Graf R, Puhan MA, Clavien PA (2014) The comprehensive complication index: a novel and more sensitive endpoint for assessing outcome and reducing sample size in randomized controlled trials. Ann Surg 260:757–762 discussion 762-753 CrossRefGoogle Scholar
  15. 15.
    Wente MN, Veit JA, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, Neoptolemos JP, Padbury RT, Sarr MG, Yeo CJ, Büchler MW (2007) Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition. Surgery 142:20–25CrossRefGoogle Scholar
  16. 16.
    Bassi C, Marchegiani G, Dervenis C, Sarr M, Abu Hilal M, Adham M, Allen P, Andersson R, Asbun HJ, Besselink MG, Conlon K, del Chiaro M, Falconi M, Fernandez-Cruz L, Fernandez-del Castillo C, Fingerhut A, Friess H, Gouma DJ, Hackert T, Izbicki J, Lillemoe KD, Neoptolemos JP, Olah A, Schulick R, Shrikhande SV, Takada T, Takaori K, Traverso W, Vollmer CR, Wolfgang CL, Yeo CJ, Salvia R, Buchler M, International Study Group on Pancreatic Surgery (ISGPS) (2017) The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 years after. Surgery 161:584–591CrossRefGoogle Scholar
  17. 17.
    Kleive D, Berstad AE, Sahakyan MA, Verbeke CS, Naper C, Haugvik SP, Gladhaug IP, Line PD, Labori KJ (2018) Portal vein reconstruction using primary anastomosis or venous interposition allograft in pancreatic surgery. J Vasc Surg Venous Lymphat Disord 6:66–74CrossRefGoogle Scholar
  18. 18.
    Kleive D, Berstad AE, Verbeke CS, Haugvik SP, Gladhaug IP, Line PD, Labori KJ (2016) Cold-stored cadaveric venous allograft for superior mesenteric/portal vein reconstruction during pancreatic surgery. HPB (Oxford) 18:615–622CrossRefGoogle Scholar
  19. 19.
    Horsted F, West J, Grainge MJ (2012) Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis. PLoS Med 9:e1001275CrossRefGoogle Scholar
  20. 20.
    Akl EA, Terrenato I, Barba M, Sperati F, Muti P, Schünemann HJ (2008) Extended perioperative thromboprophylaxis in patients with cancer. A systematic review. Thromb Haemost 100:1176–1180CrossRefGoogle Scholar
  21. 21.
    Bergqvist D, Agnelli G, Cohen AT, Eldor A, Nilsson PE, le Moigne-Amrani A, Dietrich-Neto F, ENOXACAN II Investigators (2002) Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med 346:975–980CrossRefGoogle Scholar
  22. 22.
    Farge D, Debourdeau P, Beckers M et al (2013) International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost 11:56–70CrossRefGoogle Scholar
  23. 23.
    Rasmussen MS, Jorgensen LN, Wille-Jorgensen P et al (2006) Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study. J Thromb Haemost 4:2384–2390CrossRefGoogle Scholar
  24. 24.
    Fagarasanu A, Alotaibi GS, Hrimiuc R, Lee AYY, Wu C (2016) Role of extended thromboprophylaxis after abdominal and pelvic surgery in cancer patients: a systematic review and meta-analysis. Ann Surg Oncol 23:1422–1430CrossRefGoogle Scholar
  25. 25.
    Bergqvist D, Burmark US, Flordal PA, Frisell J, Hallböökr T, Hedberg M, Horn A, Kelty E, Kvitting P, Lindhagen A, Ljungström KG, Mätzsch T, Risberg B, Syk I, Törngren S, Wellander E, Örtenwall P (1995) Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 XaI units in 2070 patients. Br J Surg 82:496–501CrossRefGoogle Scholar
  26. 26.
    Glebova NO, Hicks CW, Piazza KM, Abularrage CJ, Cameron AM, Schulick RD, Wolfgang CL, Black JH III (2015) Technical risk factors for portal vein reconstruction thrombosis in pancreatic resection. J Vasc Surg 62:424–433CrossRefGoogle Scholar
  27. 27.
    Murakami Y, Satoi S, Motoi F, Sho M, Kawai M, Matsumoto I, Honda G, the Multicentre Study Group of Pancreatobiliary Surgery (MSG-PBS) (2015) Portal or superior mesenteric vein resection in pancreatoduodenectomy for pancreatic head carcinoma. Br J Surg 102:837–846CrossRefGoogle Scholar
  28. 28.
    Ravikumar R, Sabin C, Abu Hilal M, Bramhall S, White S, Wigmore S, Imber CJ, Fusai G, UK Vascular Resection in Pancreatic Cancer Study Group (2014) Portal vein resection in borderline resectable pancreatic cancer: a United Kingdom multicenter study. J Am Coll Surg 218:401–411CrossRefGoogle Scholar
  29. 29.
    Dua MM, Tran TB, Klausner J, Hwa KJ, Poultsides GA, Norton JA, Visser BC (2015) Pancreatectomy with vein reconstruction: technique matters. HPB (Oxford) 17:824–831CrossRefGoogle Scholar
  30. 30.
    Diamond T, Rowlands BJ (1991) Endotoxaemia in obstructive jaundice. HPB (Oxford) 4:81–94Google Scholar
  31. 31.
    Kloek JJ, Heger M, van der Gaag NA, Beuers U, van Gulik TM, Gouma DJ, Levi M (2010) Effect of preoperative biliary drainage on coagulation and fibrinolysis in severe obstructive cholestasis. J Clin Gastroenterol 44:646–652CrossRefGoogle Scholar
  32. 32.
    Scheufele F, Schorn S, Demir IE, Sargut M, Tieftrunk E, Calavrezos L, Jäger C, Friess H, Ceyhan GO (2017) Preoperative biliary stenting versus operation first in jaundiced patients due to malignant lesions in the pancreatic head: a meta-analysis of current literature. Surgery 161:939–950CrossRefGoogle Scholar
  33. 33.
    van der Gaag NA, Rauws EA, van Eijck CH et al (2010) Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med 362:129–137CrossRefGoogle Scholar
  34. 34.
    Grutzmann R, Ruckert F, Hippe-Davies N et al (2012) Evaluation of the International Study Group of Pancreatic Surgery definition of post-pancreatectomy hemorrhage in a high-volume center. Surgery 151:612–620CrossRefGoogle Scholar
  35. 35.
    Sanjay P, Fawzi A, Fulke JL, Kulli C, Tait IS, Zealley IA, Polignano FM (2010) Late post pancreatectomy haemorrhage. Risk factors and modern management. JOP 11:220–225Google Scholar
  36. 36.
    Callery MP, Pratt WB, Kent TS, Chaikof EL, Vollmer CM Jr (2013) A prospectively validated clinical risk score accurately predicts pancreatic fistula after pancreatoduodenectomy. J. Am. Coll. Surg 216:1–14CrossRefGoogle Scholar
  37. 37.
    Miller BC, Christein JD, Behrman SW, Drebin JA, Pratt WB, Callery MP, Vollmer CM (2014) A multi-institutional external validation of the fistula risk score for pancreatoduodenectomy. J Gastrointest Surg 18:172–179 discussion 179-180 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Hepato-Pancreato-Biliary SurgeryOslo University Hospital, RikshospitaletOsloNorway
  2. 2.Institute of Clinical MedicineUniversity of OsloOsloNorway
  3. 3.Department of Surgery N1Yerevan State Medical University after M. HeratsiYerevanArmenia
  4. 4.The Intervention CenterOslo University Hospital, RikshospitaletOsloNorway
  5. 5.Department of Gastrointestinal SurgeryStavanger University HospitalStavangerNorway
  6. 6.Clinical SurgeryRoyal Infirmary of Edinburgh and University of EdinburghEdinburghUK
  7. 7.Department of Clinical MedicineUniversity of BergenBergenNorway
  8. 8.Institute of Transplantation MedicineOslo University Hospital, RikshospitaletOsloNorway

Personalised recommendations