Acquired hemophilia A following choledochal cyst excision - highlighting postoperative bile leak and infection as potential triggers: A case report

Abstract

BACKGROUND

Acquired hemophilia A (AHA) is a rare and potentially fatal bleeding disorder mediated by autoantibodies against coagulation factor VIII (FVIII). Its nonspecific clinical presentation often leads to delayed diagnosis and life-threatening complications. Early recognition and standardized management are crucial for improving outcomes. Secondary AHA following choledochal cyst excision is extremely rare, with no prior reports in the literature. This case report explored the possible etiology, treatment strategies, and disease course of AHA in a patient.

CASE SUMMARY

A 37-year-old woman developed postoperative bile leakage, infection, and recurrent bleeding after laparoscopic choledochal cyst excision with Roux-en-Y hepaticojejunostomy, which was subsequently complicated by AHA. On postoperative day 6, she presented with intra-abdominal hemorrhage. Despite repeated interventions, including exploratory laparotomy and interventional embolization, intermittent active bleeding remained uncontrolled. After multidisciplinary team consultation, she was finally diagnosed with AHA. Treatment included infection control, combined immunosuppressive therapy with corticosteroids and cyclophosphamide, seven plasma exchange sessions, and FVIII replacement therapy. Bleeding was effectively controlled, the intra-abdominal abscess healed, and the patient was discharged after clinical remission was achieved. At the 6-month follow-up, no signs of recurrent bleeding were noted.

CONCLUSION

Prompt FVIII activity and inhibitor testing, along with comprehensive treatment, should be implemented in patients suspicious for AHA.

Key Words: Acquired hemophilia A; Cholangiocystectomy; Postoperative bleeding; Bile leak; Infection; Factor VIII inhibitor; Case report

Core Tip: This report describes the first case of acquired hemophilia A after cholangiocystectomy. Postoperative bile leak with persistent abdominal infection is the key trigger for anti-factor VIII (FVIII) antibody formation. Timely FVIII testing, infection control, immunosuppression, and plasma exchange achieve cure.

INTRODUCTION

Choledochal cyst is a rare congenital condition characterized by cystic dilation of the bile ducts, and it is often associated with an abnormal pancreaticobiliary junction. This condition can lead to biliary stasis, recurrent cholangitis, and increased long-term risks of cholangiocarcinoma. The standard surgical treatment involves complete cyst excision combined with Roux-en-Y hepaticojejunostomy. Common postoperative complications include bile leakage at the anastomosis, anastomotic stricture, cholangitis, intra-abdominal hemorrhage, and abdominal infection[1].

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by the production of specific autoantibodies against coagulation factor VIII (FVIII), resulting in reduced FVIII activity. Clinically, AHA presents as spontaneous or trauma-related bleeding, typically involving soft tissues, muscles, or postoperative sites, with most patients having no prior or family history of bleeding disorders. AHA is frequently associated with autoimmune diseases, malignancies, drug reactions, infections, or inflammatory conditions. Early recognition and timely initiation of immunosuppressive therapy together with appropriate hemostatic agents are essential for improving outcomes in AHA[2-5].

This report describes a case of AHA occurring after choledochal cyst resection and discusses the clinical features, diagnostic approach, and management strategies based on relevant literature, aiming to enhance clinicians’ awareness of and vigilance toward this rare complication. In this case, the patient exhibited bile leakage after surgery, followed by localized infection, which subsequently caused a significant decrease in FVIII activity, ultimately prompting a diagnosis of AHA. Persistent local infection following bile leakage might have activated the immune system and disrupted self-tolerance, potentially promoting the formation of anti-FVIII autoantibodies.

CASE PRESENTATION

Chief complaints

A 37-year-old woman was admitted to our hospital 12 days after common bile duct cyst surgery after experiencing abdominal cavity bleeding for 6 days.

History of present illness

On February 23, 2024, the patient underwent laparoscopic excision of a common bile duct cyst, choledochojejunostomy (R-Y anastomosis), and cholecystectomy at an outside hospital. On postoperative day 6, she developed bloody drainage from the abdominal drain, melena, and a progressive decline in hemoglobin levels. The external hospital suspected “postoperative intra-abdominal hemorrhage” and performed emergency laparotomy, exploration of the bile duct, hemostasis, and T-tube drainage after bile-enteric anastomosis. Intraoperatively, active bleeding was identified at the bile-enteric anastomotic site, which was sutured. Postoperatively, she received hemostatic therapy and blood transfusions; however, her hemoglobin level continued to decrease, melena persisted, and ecchymoses appeared in the lower abdomen. For further evaluation and management, the patient was transferred to our department on March 6, 2024.

To clarify the cause of bleeding, celiac arteriography and embolization were performed on March 12, 2024, and prophylactic embolization of the suspected bleeding vessel was performed (Figure 1A and B). Nevertheless, this procedure did not completely control the bleeding. Meanwhile, multiple new subcutaneous ecchymoses appeared in the patient’s lower abdomen and thighs.

Figure 1 Perioperative imaging examinations. A and B: Digital subtraction angiography revealing suspected extravasation of the contrast agent at the transitional area of the first branch of the superior mesenteric artery, gastric right artery, and gastric duodenal artery, and preventive embolization was performed; C: Nuclear magnetic resonance imaging revealing cystic dilation of the extrahepatic bile duct; D and E: Computed tomography (CT) angiography and coronal views highlighting ascites and hematoma in the abdominal cavity; F: Coronal views of CT revealing increased ascites and hematoma in the abdominal cavity; G: Postoperative pathology of the common bile duct cyst suggests a benign epithelial cyst of the bile duct alongside microtissue hyperplasia of the cyst wall and scattered chronic inflammatory cell infiltration, consistent with the diagnosis of bile duct cyst; H: Coronary views of CT indicating the formation of liver abscess and pelvic effusion; I: Coronary views of CT indicating a reduction in the abscess cavity and a decrease in the pus volume of the liver abscess; J: Coronary views of CT indicating that the abscess cavity of the liver abscess has basically healed.

As bleeding persisted despite surgical intervention combined with findings of significant activated partial thromboplastin time (APTT) prolongation that could not be corrected by conventional hemostatic measures, the multidisciplinary team recommended completing a full set of coagulation factor tests after consultation.

History of past illness

She was previously diagnosed with hypertension in 2019, achieving stable blood pressure control via regular treatment with sacubitril/valsartan 0.1 g once daily.

Personal and family history

No significant findings were noted.

Physical examination

The physical examination findings were as follows: Temperature, 36.6 °C; pulse, 106 beats/minute; respiratory rate, 21 breaths/minute; blood pressure, 138/65 mmHg; height, 160 cm; weight, 60 kg; mild pallor because of anemia; slightly distended abdomen; golden-yellow fluid draining from the T-tube; no bloody exudate from the abdominal drain; and subcutaneous bruising observed in the lower abdomen and bilateral thighs. The remaining findings were unremarkable.

Laboratory examinations

After admission, coagulation function was closely monitored. Core indicators included APTT of 58.4 seconds, an FVIII inhibitor titer of 2.08 BU/mL, and elevated D-dimer and fibrin degradation product (FDP) levels (Figure 2 and Table 1).

Figure 2 Timeline of changes in coagulation indices. A-H: Activated partial thromboplastin time (APTT) gradually decreased from 58.4 seconds at the time of admission to 26.8 seconds on April 12, 2024, and the APTT ratio returned to 0.99. Factor VIII (FVIII) activity continuously increased from 0.9% to 138.9% on April 23, 2024. The FVIII inhibitor titer decreased from 2.08 to 0.85 BU/mL and eventually turned negative. D-dimer and fibrin degradation product levels decreased from significantly elevated levels to normal ranges, and the patient’s coagulation function stabilized. FDP: Fibrin degradation product; PT: Prothrombin time; VIII: Factor VIII; APTT: Activated partial thromboplastin time; PT-INR: Prothrombin time-international normalized ratio; TT: Thrombin time.

Table 1 Key laboratory values (activated partial thromboplastin time, factor VIII activity, factor VIII inhibitor titer, etc.) at critical time points.

Timeline	APTT (s)	APTT ratio	FVIII activity (%)	FVIII inhibitor (BU/mL)	Hemoglobin (g/L)
Admission	58.4	2.23			75
The day of First embolization	58.3	2.16			69
2 days after First embolization	51.1	1.95			76
The day of Second embolization	53.8	2.05			73
2 days after Second embolization	68	2.52	0.9	2.08	51
The day before Plasma exchange	60.4	2.21	2.2		58
1 day after plasma exchange	49.4	1.55	4.6	0.97	72
8 days after plasma exchange	58	2.03	21.5	0.85	61
The day of last plasma exchange	26.8	0.99			86
Pre-discharge	32.3	1.2			87

APTT: Activated partial thromboplastin time; FVIII: Factor VIII.

Imaging examinations

Postoperative computed tomography (CT) revealed intraperitoneal hematoma and fluid collection, with encapsulated fluid around the liver and near the anastomotic site, suggesting possible bile leakage and intra-abdominal infection. Selected imaging findings during treatment are presented in Figure 1C-F, H-J. Final pathology confirmed a diagnosis of congenital choledochal cyst (Figure 1G).

FINAL DIAGNOSIS

The final diagnosis was AHA following choledochal cyst excision. Other findings included moderate anemia, ascites and pleural effusion, pulmonary infection, electrolyte and metabolic disorders, and stage 1 hypertension.

TREATMENT

Immediately after the definitive diagnosis, comprehensive treatment was initiated. For immunosuppressive therapy, methylprednisolone combined with cyclophosphamide was administered to eliminate FVIII inhibitors. Seven plasma exchange sessions were performed to facilitate the rapid removal of circulating FVIII inhibitors. Because of drug accessibility issues in this case, an alternative regimen of prothrombin complex concentrate combined with cryoprecipitate, fresh frozen plasma, and antifibrinolytic drugs was adopted for hemostatic support. Although this regimen is not optimal, it effectively controlled bleeding under the given conditions. Meanwhile, plasma exchange was actively used as a bridging therapy to rapidly clear antibodies, providing a critical time window for the onset of immunosuppressants. Stepped anti-infection therapy was implemented on the basis of repeated etiological culture results. Meropenem plus vancomycin was administered initially, and the regimen was adjusted to caspofungin combined with meropenem after fungi were isolated from cultures. CT-guided puncture drainage for liver abscess was performed on April 28 and May 11, 2024, which effectively eliminated the source of infection. CT-guided percutaneous catheter drainage of the liver abscess was performed with careful planning. Preprocedural risk assessment was conducted in consultation with the hematology team. To mitigate the high risk of bleeding (FVIII activity < 1%), the patient received one dose of recombinant activated FVII (NovoSeven) before the procedure. The needle path was carefully planned to provide a safe route through the liver parenchyma while avoiding major vessels and bowel loops. No immediate postprocedural bleeding complications were observed, and drainage successfully resolved the abscess. The treatment timeline is illustrated in Figure 3, and the treatment and nursing strategy is presented in Figure 4.

Figure 3 Treatment timeline. CT: Computed tomography.

Figure 4 Treatment strategy and nursing key points chart. A: Individualized treatment strategies for postoperative acquired hemophilia A (AHA); B: Perioperative nursing care for AHA. AHA: Acquired hemophilia A; PCC: Prothrombin complex concentrate; FFP: Fresh frozen plasma; AA: Antifibrinolytic agents; VD: Vasoactive drugs; FVIII: Factor VIII; MDT: Multidisciplinary collaboration; ENS: Enteral nutritional support.

OUTCOME AND FOLLOW-UP

After comprehensive treatment, the patient’s coagulation function gradually returned to normal. APTT normalization was confirmed on April 12, 2024 (APTT = 26.8 seconds), with the APTT ratio returning to 0.99. FVIII activity increased to 138.9% on April 23, 2024, and the FVIII inhibitor titer decreased to 0.85 BU/mL, eventually turning negative. Hemoglobin levels progressively dropped postoperatively and fluctuated during treatment (Figure 5), and d-dimer and FDP levels gradually returned to their normal ranges. The abdominal cavity and T-tube drainage fluid became clear and golden yellow, the liver abscess healed, and the anemia was corrected.

Figure 5 Trend chart of hemoglobin, procalcitonin, and white blood cell count. A: Hemoglobin; B: Procalcitonin; C: White blood cell count. Hemoglobin levels progressively decreased after surgery, albeit with fluctuation during the diagnosis and treatment process. WBC: White blood cell.

After 6 months of follow-up after discharge, no recurrence of bleeding has occurred, and coagulation function, FVIII activity, and FVIII inhibitor titers have remained continuously normal. The patient has experienced a good quality of life.

DISCUSSION

AHA is a rare bleeding disorder mediated by autoantibodies against FVIII. The annual incidence of AHA is approximately 1.5 per 100000 people. Most studies and clinical observations reported that the triggers of AHA after surgery are mainly nonspecific immune activation or stress responses triggered by surgical trauma[6-8]. However, the severe and persistent infection caused by bile leakage in this patient after surgery suggested the involvement of a more direct and crucial factor that induces FVIII autoantibodies. The patient exhibited signs of bile leakage at the beginning of the clinical course that rapidly evolved into abdominal infection, bacteremia, and an eventual liver abscess. This series of events constituted a persistent and intense immune system activation signal, thereby creating conditions for the occurrence and development of AHA. Analyzing the characteristics of the disease, the possible causes for the occurrence of AHA in this patient include four aspects.

Repeated bleeding and consumption of coagulation factors

Six days after surgery, this patient began to experience abdominal bleeding, hematochezia, and progressive decreases in hemoglobin levels. Abdominal bleeding persisted despite surgical interventions such as exploratory laparotomy and arterial embolization. Long-term and repeated active bleeding led to significant loss and consumption of coagulation factors. Moreover, it has been reported that bleeding activates the coagulation-inflammation feedback loop, thereby exposing self-antigen epitopes and promoting antibody production[9]. Some studies have also noted that large amounts of red blood cells, plasma, and cryoprecipitate transfusions can further induce immune system activation and increase the risk of antibody formation[5]. This patient received multiple blood transfusions and coagulation factor replacement treatments because of repeated bleeding, which might have further amplified the abnormal immune response and formed a vicious cycle of “bleeding-immune activation-increased difficulty in stopping bleeding”.

Infection-induced inflammatory response

This patient was clearly diagnosed with postoperative bile leakage, which subsequently triggered abdominal infection. Imaging and pathology clearly revealed the presence of abdominal effusion and liver abscess. Throughout the disease course, the patient experienced fever and significantly elevated infection indicator levels, and the efficacy of anti-infection treatment was in line with the control of bleeding. This strongly suggests that the abdominal infection caused by bile leakage was closely related to the occurrence of AHA in this patient. When the infection focus is not completely cleared, the efficacy of immunosuppression and plasma exchange is often difficult to maintain. Conversely, after drainage of the abscess and stepwise anti-infection treatment, the FVIII inhibitor titer rapidly turned negative, clinically validating the key role of infection.

Postoperative stress and hepatic impairment

Surgical trauma, anesthesia, blood loss, and infection jointly constitute a strong stress state, leading to excessive activation of the hypothalamic-pituitary-adrenal axis and the release of large amounts of cortisol and catecholamines. Although glucocorticoids can inhibit the immune response, chronic or repeated stress induces the upregulation of inflammatory factors and promotes the production of autoantibodies[7]. At the same time, this patient was in a weakened state because of abdominal infection, abscess formation, and repeated bleeding. The FVIII synthesis capacity of the liver was significantly decreased. Additionally, liver dysfunction can reduce the clearance of autoantibody-antigen complexes, further amplifying the immune-damaging effect. Therefore, postoperative liver protection treatment and close monitoring of liver function indicators play key roles in preventing the occurrence and development of AHA.

Delayed diagnosis: Lack of FVIII activity monitoring

The early diagnosis of AHA relies on vigilance for isolated APTT prolongation and timely detection of FVIII activity and FVIII inhibitor titers. In this patient, APTT was significantly prolonged after surgery, but the comprehensive coagulation factor examination and subsequent diagnosis were delayed. Concerning potential explanations, postoperative bleeding is often initially attributed to mechanical causes such as anastomotic leakage and vascular injury, and the preferred remedial methods are exploratory laparotomy and interventional embolization. In addition, many clinicians are not aware that APTT prolongation cannot be corrected by conventional hemostatic measures under such conditions. Finally, subcutaneous ecchymosis (nonsurgical area bleeding) was not linked to acquired coagulation disorders. This diagnostic delay leads to unnecessary invasive procedures and causes patients to miss the best opportunity for early immunosuppressive treatment. This case serves as a warning that, rather than repeatedly attempting surgical hemostasis, FVIII activity should be assessed as soon as possible in patients who experience persistent bleeding after surgery alongside isolated APTT prolongation and ineffective surgical intervention. Furthermore, the diagnostic delay in this case highlights an important learning point for radiologists and interventionalists. A significant discrepancy was observed between the CT findings, which showed a large, expanding hematoma, and the digital subtraction angiography findings, which revealed only equivocal extravasation. This discordance, together with an isolated prolonged APTT, should have raised suspicion of a systemic coagulopathy such as AHA rather than prompting repeated embolization. Radiologists should proactively correlate imaging findings with laboratory data and recommend hematology consultation when such a discrepancy is identified.

The diagnostic process involved the systematic exclusion of other potential causes of bleeding. Given the postoperative context, mechanical causes such as anastomotic leakage, vascular injury, and pseudoaneurysm rupture were initially suspected but were ruled out by exploratory laparotomy and angiography. Disseminated intravascular coagulation was considered but excluded based on the absence of significant thrombocytopenia, prolonged prothrombin time (PT), and decreased fibrinogen levels. Because the patient had no history of bleeding disorders, inherited hemophilia A was considered unlikely. Other acquired coagulopathies, such as vitamin K deficiency and anticoagulant overdose, were also excluded based on a normal PT and a review of the patient’s medication history. The combination of isolated APTT prolongation, refractory bleeding, and subsequent detection of a FVIII inhibitor confirmed the diagnosis of AHA.

CONCLUSION

Postoperative AHA following total cystectomy of the common bile duct is an extremely rare but dangerous condition, potentially associated with substantial morbidity and mortality. This case suggests that postoperative bile leakage leading to abdominal infection, persistent bleeding, systemic stress, and liver function impairment results in the occurrence and development of AHA, and delayed diagnosis results in further aggravation of the condition. Clinicians should be highly vigilant for patients with isolated APTT prolongation after surgery and bleeding that cannot be controlled by surgical means and should promptly test FVIII activity and inhibitor titers. Once diagnosed, a comprehensive treatment strategy based on infection source control, immunosuppressive therapy as the core, and plasma exchange should be implemented as soon as possible. In cases in which direct FVIII supplementation is not possible, alternative hemostasis regimens such as prothrombin complex combined with cryoprecipitate, fresh frozen plasma, and anti-fibrinolytic drugs can be used to improve the patient’s prognosis. As a single case report, the findings of this study are not generalizable and cannot definitively establish causality. The rarity of this condition limits the feasibility of large-scale studies, and further research is needed to elucidate the precise pathophysiological mechanisms linking bile leakage, infection, and AHA.