Atypical Postoperative Bleeding as a First Manifestation of Acquired Hemophilia A: A Case Report

Abstract

Acquired hemophilia A (AHA) is a rare autoimmune coagulopathy disorder characterized by the development of inhibitory autoantibodies against coagulation factor VIII. It often presents with spontaneous or post-procedural bleeding in individuals without prior bleeding history and requires prompt recognition and management. We report the case of a 70-year-old male who developed life-threatening hemorrhagic complications following pancreaticoduodenectomy. Re-laparotomy revealed dehiscence of the pancreaticojejunostomy, which was resected, and a temporary Wirsungostomy was created. The patient was admitted to the Intensive Care Unit (ICU) with progressive anemia, subcutaneous hematomas, and recurrent gastrointestinal bleeding. Laboratory tests revealed isolated activated partial thromboplastin time (aPTT) prolongation, lack of correction in the mixing study, reduced factor VIII activity (15.3%), and the presence of an inhibitor (0.7 Bethesda Units; BU). Based on the above, acquired hemophilia A was diagnosed. Treatment included recombinant activated factor VII (rFVIIa) for 6 days and corticosteroid therapy with methylprednisolone. Clinical improvement and nearcomplete remission were achieved, with normalization of aPTT, restoration of factor VIII activity (99.6%), and persistence of only trace inhibitor levels. This case highlights the diagnostic complexity of atypical postoperative bleeding, underscoring the need for a broad differential diagnosis and a high index of suspicion for rare disorders like acquired hemophilia A to ensure timely, life-saving intervention.

Introduction

Acquired hemophilia A (AHA) is a rare but potentially life-threatening coagulopathy disorder caused by autoantibodies that inhibit coagulation factor VIII (FVIII). Its incidence is estimated at approximately 1.5 cases per million population per year.^{1 -3} Unlike congenital hemophilia, AHA typically affects older adults and occurs in individuals with no prior history of bleeding disorders. ⁴

According to data from the European Acquired Haemophilia Registry (EACH2), the median age at diagnosis exceeds 70 years, with approximately 50% of cases classified as idiopathic. The remaining cases are associated with underlying conditions such as malignancies, autoimmune diseases, the postpartum period, or drug exposure. ²

The clinical presentation of AHA is variable, ranging from mild mucocutaneous bleeding to severe spontaneous hemorrhages.^{1,5 -7} Due to its rarity and nonspecific symptoms, AHA is frequently underdiagnosed or misdiagnosed, leading to delays in appropriate treatment. ⁸

Early recognition and initiation of targeted therapy are essential to control bleeding and eliminate the inhibitor. In this report, we present a case of AHA diagnosed in a patient following pancreatic surgery, with an atypical presentation and significant clinical implications.

Case Presentation

About 70-year-old male had undergone pancreaticoduodenectomy for pancreatic cancer and subsequently required re-laparotomy due to an anastomotic leak at the pancreaticojejunostomy site. During the procedure, the anastomosis was taken down, and the main pancreatic duct (Wirsung’s duct) was exteriorized through the abdominal wall using a drain, resulting in the creation of a temporary pancreatic duct stoma (Wirsungostomy).

Five days later, the patient was admitted to the intensive care unit (ICU) postoperatively. The presence of extensive subcutaneous hematomas, progressive anemia, and a recurrent episode of gastrointestinal bleeding involving both the upper and lower tracts raised suspicion of a coagulation disorder. Abdominal contrast-enhanced CT revealed new intra-abdominal hematomas, without evidence of active surgical bleeding. This supported the suspicion of a systemic coagulation disorder rather than a technical surgical complication. aPTT was consistently prolonged, remaining around 50 seconds.

Upon further history taking, the patient disclosed a 1-year history of easy bruising and prolonged bleeding episodes, which he had not reported initially. He also recalled that a previously performed endoscopic retrograde cholangiopancreatography (ERCP), conducted as part of the diagnostic workup for pancreatic cancer, had been complicated by post-procedural bleeding. After ruling out a heparin effect, the differential diagnosis was extended to consider an underlying coagulopathy. Based on isolated aPTT prolongation (Figure 1), lack of correction in the mixing study, reduced factor VIII activity (15.3%), and the presence of a factor VIII inhibitor (0.7 BU), a diagnosis of acquired hemophilia A was confirmed.

Figure 1.

Diagnostic approach to isolated prolonged aPTT.

In accordance with current recommendations, bypassing therapy with recombinant activated factor VII (rFVIIa) was initiated at a dose of 90 mcg/kg every 3 hours. In parallel, corticosteroid therapy with methylprednisolone at 1.5 mg/kg/day was started to achieve inhibitor eradication (Table 1). After 2 days of treatment, the dosing interval was gradually extended. However, the patient subsequently passed a bloody stool, prompting a return to the original 3-hour dosing interval. In total, rFVIIa was administered for 6 days, after which it was successfully discontinued. No further bleeding episodes or anemia were observed.

Table 1.

Recommended hemostatic and immunosuppressive treatment strategies for acquired Hemophilia A.

Treatment of acquired hemophilia A
Immunosupressive therapy – inhibitor eradication	Hemostatic therapy – initiate treatment if clinically relevant
FVIII ⩾ 1% and FVIII inhibitor ⩽ 20 BU/ml	Bypassing agents
• Steroids [Prednisolone or prednisone – 1 mg/kg/day for 3-4 wk (max 4-6 wk)]	• rFVIIa – 90 μg/kg every 2-3 h • aPCC – 50-100 U/kg every 8-12 h (max 200 U/kg/day)
• If not responding add	Porcine factor VIII
• RTX – 375 mg/ m² weekly for maximum of four cycles  OR • CTX b – 1.5-2 mg/kg/day for 6 wk OR MMF b – 1 g/day for 1 wk, followed by 2 g/day	If anti-porcine titer low or undetectable (exclude if an anti-rpFVIII inhibitor titer > 20 BU) • rpFVIII – 200 U/kg followed by tailored dosing to maintain trough levels > 50% of FVIII activity
• FVIII < 1% or FVIII inhibitor > 20 BU/ml	Other options
• Steroids a  + • RTX a  OR • CTXa,b OR MMFa,b	• hFVIII – 50 to 100 U/kg followed by tailored dosing only if bypassing agents or rpFVIII are unavailable or ineffective and the inhibitor titer is low
• If not responding add
• RTX a  OR • CTX a OR MMF a

Abbreviations: RTX, rituximab; CTX, cyclophoshamide; MMF, mycophenolate mofetil; rFVIIa, recominant factor VIIa; aPCC, activated protrombin complex concentrate; rpFVIII, recombinant porcine factor VIII; hFVIII, human factor VIII.

a

Dosage as above.

b

Do not use in pregnancy or during breastfeeding.

Follow-up laboratory tests revealed normalization of aPTT, factor VIII activity of 99.6%, and an inhibitor level at the limit of detection, indicating near-complete remission. The patient was discharged from the ICU in stable condition, transferred back to the surgical ward, and subsequently discharged home 60 days after admission (Figure 2).

Figure 2.

Timeline of the patient’s hospitalization.

Discussion

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by the development of autoantibodies against factor VIII. It typically occurs in elderly patients and can be associated with malignancies, autoimmune diseases, or occur idiopathically. The clinical presentation is often nonspecific, and the absence of a prior history of bleeding can delay diagnosis. Unlike congenital hemophilia, AHA typically presents with spontaneous subcutaneous, muscular, or gastrointestinal bleeding, whereas joint involvement is uncommon.

Diagnosis relies on laboratory findings, primarily the presence of isolated prolongation of activated partial thromboplastin time (aPTT), lack of correction in the mixing study, reduced factor VIII activity, and detection of FVIII inhibitors. In this case, persistent aPTT elevation, combined with mucocutaneous bleeding and a history of post-procedural hemorrhage, raised the suspicion of an acquired coagulation disorder.

According to international recommendations the management of bleeding in acquired hemophilia A should be guided primarily by the clinical severity of bleeding, rather than by factor VIII activity levels or inhibitor titers.^7,9 This approach is particularly relevant in our case, where the patient exhibited a relatively low inhibitor level (0.7 BU; Figures 3 and 4) but developed significant bleeding complications necessitating intensive care admission. ¹⁰

Figure 3.

Measurement of factor VIII inhibitor (Bethesda assay).

Figure 4.

Relationship between residual factor VIII activity and Bethesda Units.

In addition to recombinant activated factor VII (rFVIIa), other therapeutic options include activated prothrombin complex concentrate (aPCC, commercially available as FEIBA) and recombinant porcine factor VIII (rpFVIII). ¹¹ The choice of agent depends on factors such as availability, bleeding site, prior treatment response, and thrombotic risk. Both rFVIIa and aPCC are considered first-line bypassing agents, while rpFVIII offers a targeted approach when precise factor VIII monitoring is desired and cross-reactivity with inhibitors is minimal.^1,7,12

Furthermore, emicizumab, a bispecific monoclonal antibody that mimics activated factor VIII function, has recently emerged as a promising agent in the management of AHA. An early report from a multicenter study suggests potential benefits in the control of bleeding. ¹³ However, future studies will be required to confirm safety and efficacy of emicizumab in this setting.

Therapeutic goals in AHA include control of acute bleeding and eradication of the inhibitor. Bypassing agents, such as recombinant activated factor VII (rFVIIa), are effective in managing bleeding episodes, while immunosuppressive therapy is used to eliminate the autoantibody.^5,7 After calculating the equivalence between oral prednisone and intravenous methylprednisolone, the multidisciplinary team decided to administer intravenous methylprednisolone in an individualized dose, taking into account the patient’s ongoing respiratory concerns. Other immunosuppressive agents, such as cyclophosphamide or rituximab, were not introduced due to the patient’s postoperative condition and the presence of infection. At that time, he was receiving broad-spectrum antibiotics for intraabdominal bacterial growth and had elevated inflammatory markers, as well as HRCT findings of ground-glass opacities. Given these considerations, corticosteroids alone were initiated, which led to clinical improvement, and therefore additional immunosuppressants were not required. In this case, treatment with rFVIIa and methylprednisolone resulted in rapid stabilization of the patient’s condition and near-complete remission, as reflected by normalization of aPTT, near-physiological FVIII activity, and only trace inhibitor levels.

The patient was followed for 75 days during hospitalization. Factor VIII inhibitor became undetectable and aPTT normalized. The patient was discharged on steroids and was subsequently reviewed in follow-up clinic 6 months later, with no relapse of bleeding. We hypothesize that, since the malignant tissue had been surgically removed, there was no ongoing trigger to promote antibody formation.

This case highlights the clinical challenge of diagnosing acquired hemophilia A and the importance of maintaining a high index of suspicion in atypical bleeding scenarios. Timely diagnosis and coordinated multidisciplinary management are essential to optimize outcomes in patients with this rare condition.

The strengths of this case include a broad and systematic differential diagnosis, laboratory confirmation of the specific antibody, prompt initiation of appropriate therapy, and an almost immediate therapeutic response. However, this report also has certain limitations. It describes an exceptionally rare phenomenon, and the clinical course was influenced not only by the hematologic disorder itself but also by surgical factors and the transfusion of blood components, which complicated the clinical picture. Therefore, the management described here does not fully reflect the typical approach used in patients with hemophilia.

Conclusion

Acquired hemophilia A is a rare but serious bleeding disorder that may present with nonspecific symptoms and no prior history of coagulopathy. Persistent, unexplained aPTT prolongation should prompt early diagnostic evaluation, even in surgical oncology patients. Timely recognition and appropriate treatment can significantly reduce morbidity and prevent life-threatening complications. This case underscores the importance of considering acquired bleeding disorders in patients with atypical hemorrhagic events and abnormal coagulation profiles.