Early PPH (within 24 h after surgery) is most commonly the result of technical failure to properly secure the inferior pancreaticoduodenal arteries (IPDAs). One can also see bleeding at any of the three anastomotic suture lines (following PD) and rarely a GDA stump hemorrhage due to failure to properly secure this vessel. If the SMA dissection is performed sharply with direct identification and ligation of the IPDAs at their origin from the SMA, this complication can largely be avoided. Intra-abdominal hemorrhage from poorly secured IPDAs would present as early postoperative intra-abdominal hemorrhage and would require immediate reoperation. Bleeding from the post-PD reconstruction (pancreatic, biliary, or gastric anastomosis) is very uncommon, and the anastomosis of greatest risk is the pancreaticojejunostomy if an invagination anastomosis is performed. With this type of anastomosis, the cut surface of the pancreas is open to the inside of the jejunum and small vessels which are partially cauterized may retract at the time of pancreatic transection only to bleed when the patient is in the recovery room or during the first postoperative night. Hemorrhage from the biliary anastomosis should not occur, and bleeding from the gastrojejunostomy is also very uncommon in the absence of a technical error. Marginal ulceration at the gastrojejunostomy, if it were to occur, presents months or years after the date of surgery. Yekebas et al. presented an analysis of 1669 consecutive pancreatic resections and in their experience, early PPH was due to 3 causes: (1) technical failures in terms of inadequate hemostasis in the operative field always associated with extraluminal PPH (IPDAs being the most common involved vessels); (2) suture line of gastroenteric or one of the enteroenteric anastomoses leading uniformly to intraluminal PPH on the first or second postoperative day; and (3) resection cavity or transection surface of the pancreas resulting in PPH originating from the pancreatico-enteric anastomosis [15].

Late PPH may occur from a gastrointestinal source but more commonly originates from an intra-abdominal site often associated with intra-abdominal infection or abscess formation due to leakage of an anastomosis (most commonly the pancreaticojejunostomy). Intra-abdominal infection is thought to be the major cause of late PPH due to erosion into ligated vessels, most notably the GDA. Bleeding from a disrupted anastomotic suture line can also be caused by intra-abdominal infection and can mimic bleeding from major vessels [7, 8, 16]. Finally, some patients may present with bleeding from the wound after a wound infection but significant hemorrhage from this etiology is uncommon.

The core difference between the etiology of early and late PPH is the association of late PPH with pancreatic fistula and intra-abdominal infection. This finding is consistent throughout the surgical literature which notes an elevated risk of late PPH in patients with pancreatic fistula as well as a near 100 % prevalence of pancreatic fistula in patients who exhibit late arterial bleeding [16, 17]. Surgical reports are consistent in describing a sequence of events at the beginning of which pancreatic fistula causes erosions, pseudoaneurysms, and other vascular irregularities, which eventually result in clinically significant hemorrhage. Clearly, the majority of postoperative pancreatic fistulas do not result in late PPH and the cause of PPH within the population of patients who have a pancreatic leak is likely multifactorial. Extended lymphadenectomy or the need for concomitant adjacent organ resection (resulting in a large retroperitoneal space), soft texture of the pancreatic remnant in the setting of a complete anastomotic disruption, or insufficient drainage of pancreatic fistula (failure to obtain source control) may be the cofactors increasing the risk of fistula-induced vascular injury and PPH [16–18].

Possible pathophysiologic explanations for pancreatic anastomotic leak-associated late PPH include enzymatic digestion of the blood vessel wall by trypsin, elastase, and other pancreatic exocrine enzymes, intra-abdominal infection/abscess with direct involvement of the vessel wall, and/or vascular injury at the time of operation that leads to pseudoaneurysm formation [3]. Most reports and anecdotal clinical observations favor the theory of local sepsis resulting from pancreatic fistula as the main cause of late PPH. Local sepsis may erode the vascular wall and adjacent bowel. This mechanism of injury may result in acute arterial bleeding with or without arterial pseudoaneurysm formation, which typically occurs days to weeks after the operation [19]. There is minimal data regarding the impact of newer energy devices, especially when using them for ligating the IPDAs arising from the SMA; however, anecdotal experiences with such situations have generated reason for caution. Many of us have managed PPH in patients where the use of such energy devices close to arterial structures has been implicated in the etiology of late PPH.

Skeletonization of the hepatic artery and SMA which is performed with PD, and similar dissection of the celiac artery and splenic artery stump associated with distal pancreatectomy make these vessels vulnerable to pseudoaneurysm formation due to local sepsis arising from the pancreatic fistula, anastomotic leakage, or intra-abdominal abscess [20]. In a series reported by Lee et al., of 27 patients with PPH, 26 had an antecedent pancreatic fistula, as shown by drain amylase level and computed tomography (CT) findings. This report confirms the association between late PPH and pancreatic fistula. The onset of the infectious complication ranged from 7 to 13 days but the hemorrhage developed after postoperative day 28 in 9 patients. The high frequency of late-onset (after 4 weeks from the date of operation) hemorrhage in this study led the authors to conclude that PPH can occur more than 4 weeks postoperatively, particularly in patients with pancreatic fistula and/or a complicated initial postoperative course [21].