A case of acquired hemophilia A after pancreaticoduodenectomy for distal cholangiocarcinoma

Abstract

Acquired hemophilia A (AHA) is a rare disease that results from factor VIII inhibitors causing abnormal coagulation, and certain cases may develop after highly invasive surgery. The present case study reports on a 68-year-old male patient who developed AHA after undergoing a subtotal stomach-preserving pancreatoduodenectomy for distal cholangiocarcinoma. The patient experienced complications after surgery, requiring reoperation on postoperative day (PD) 5 due to rupture of the Braun's enterostomy. On PD 6, angiography was performed after bleeding was detected in the jejunal limb, but hemostasis occurred spontaneously during the examination. Bleeding was observed again on PD 8 and direct surgical ligation was performed. On PD 14, bleeding recurred in the jejunal limb and angiography was performed to embolize the periphery of the second jejunal artery. During the procedure, the prothrombin time was normal, but only the activated partial thromboplastin time was prolonged. A close examination of the coagulation system revealed a decrease in factor VIII levels and the presence of factor VIII inhibitors, resulting in the diagnosis of AHA. Administration of steroids was initiated on PD 15 and, in addition to daily blood transfusions, activated prothrombin complex concentrate was administered to achieve hemostasis. The patient was discharged from the intensive care unit on PD 36 but later developed an intractable labial fistula due to suture failure at the gastrojejunostomy site. As the use of factor VIII inhibitors continued despite the administration of steroids, cyclophosphamide (CPA) pulse therapy was added at PD 58. However, CPA was ineffective and the administration of rituximab was initiated on PD 98. After 12 courses of rituximab, the patient tested negative for factor VIII inhibitors on PD 219. On PD 289, labial fistula closure was performed with continuous replacement of factor VIII and the patient was discharged on PD 342.

Keywords: acquired hemophilia A; activated prothrombin complex concentrate; distal cholangiocarcinoma; factor VIII inhibitor; recombinant factor VIII preparation; rituximab; subtotal stomach-preserving pancreaticoduodenectomy; surgery.

Figure 1

Intraoperative image indicating that the bile duct had two holes: The posterior segment branch of the low confluence and the common hepatic duct. CHA, common hepatic artery; GDA, gastroduodenal artery; PV, portal vein; HBD, hepatic bile duct; B6, posterior inferior subsegmental branch of bile duct; B7, posterior superior subsegmental branch of bile duct.

Figure 2

(A) Specimen before additional resection of bile duct, which had two tumors, highlighted by yellow circles (26x18 and 17x14 mm in size, nodular-expanding type). (B) Hematoxylin-eosin stain (scale bar, 1 mm). Histopathologically, both were well-to-moderately differentiated tubular adenocarcinomas.

Figure 3

On postoperative day 8, bleeding reoccurred in the jejunal limb and direct surgical ligation was performed.

Figure 4

On postoperative day 14, bleeding (yellow arrows) recurred in the jejunal limb and an angiography was performed to embolize the periphery of the second jejunal artery.

Figure 5

(A) Course of treatment at the ICU. PT was consistently within the normal range before and after surgery, but the APTT began to prolong after surgery and reached 91.5 secs on PD 12. Acquired hemophilia A was suspected on PD 14 and APCC was administered. The administration of steroids started on PD 15. While at the ICU, APCC was administered for 10 days and a total of 102 units of red blood cells were administered. (B) The long-term therapeutic course is indicated. On PD 58, CPA was administered in addition to steroids, but since factor VIII inhibitors increased, administration of rituximab was started on PD 98. After 12 courses of rituximab, the factor VIII inhibitor finally became negative on PD 219. ICU, intensive care unit; PT, prothrombin time; APTT, activated partial thromboplastin time; APCC, activated prothrombin complex concentrate; CPA, cyclophosphamide; PD, postoperative day; PSL, prednisolone; OPE, operation; RBC, red blood cells; Angio, angiography.

Figure 6

(A) The ruptured gastrojejunostomy suture appeared as a labial fistula (PD 79). (B) Negative pressure wound therapy in a place other than the labial fistula of the wound (PD 79). (C) The incision improved, leaving only a labial fistula (PD 245). (D) The incision was completely closed (PD 342). PD, postoperative day.