PO112 | REFRAMING THE ENIGMA: ACQUIRED HEMOPHILIA A AS A HARBINGER OF HHV-8–ASSOCIATED MULTICENTRIC CASTLEMAN DISEASE

M. Palladino¹, G. Gammaitoni¹, C. Santoro², M. Muscaritoli¹ | ¹Medicina Interna e Nutrizione Clinica-Dip. Medicina Traslazionale e di Precisione; ²Ematologia- Dip. Medicina Traslazionale e di Precisione, Umberto I Roma, Italy

Background. Acquired hemophilia A (AHA) is a rare, potentially fatal autoimmune coagulopathy caused by inhibitory autoantibodies targeting factor VIII (FVIII). Its incidence is approximately 1 case per million annually, predominantly affecting older adults, with a smaller peak in postpartum women. Clinically, AHA presents with spontaneous bleeding—typically involving soft tissues, mucosae, or internal organs—in patients without a personal or familial bleeding history. A defining laboratory feature is isolated prolongation of activated partial thromboplastin time (aPTT), uncorrected by mixing studies. In nearly 50% of cases, AHA is associated with underlying conditions, including malignancies, autoimmune disorders, infections, dermatologic diseases, and pregnancy; the remainder are idiopathic. Mortality ranges from 10% to 30%, primarily due to hemorrhagic complications. Castleman disease (CD) is a heterogeneous group of non-clonal lymphoproliferative disorders characterized by lymphadenopathy and systemic inflammation. Multicentric Castleman disease (MCD) represents a systemic and aggressive form, frequently associated with human herpesvirus-8 (HHV-8), particularly in immunocompromised individuals. HHV-8–driven MCD is mediated by dysregulated cytokine production, notably interleukin-6, and may coexist with Kaposi’s sarcoma. The association between AHA and MCD is exceedingly rare and diagnostically challenging.
Case Report. A 69-year-old man presented with right lower limb pain and spontaneous hematomas. Deep vein thrombosis was excluded. Laboratory findings revealed normocytic anemia and prolonged aPTT (69.5 s). Coagulation studies showed markedly reduced FVIII activity (3.5%) and FVIII inhibitors (3.5 BU), confirming AHA. Treatment with corticosteroids and activated prothrombin complex concentrate (FEIBA, 4000 IU twice daily) led to clinical improvement, with gradual FVIII recovery and declining inhibitor titer (Figure 1). Imaging revealed multiple hemorrhagic sites (bilateral subdural, adrenal, and thigh hematomas), splenomegaly (16 cm), and diffuse lymphadenopathy. Further evaluation demonstrated elevated chromogranin A and biclonal gammopathy (IgG-kappa and IgG-lambda). Bone marrow biopsy was inconclusive. Virological testing identified active cytomegalovirus and HHV-8 infection, prompting antiviral therapy. Owing to worsening cytopenias and splenomegaly, lymph node excision was performed, establishing HHV-8–positive MCD with microscopic Kaposi’s sarcoma. Rituximab was initiated to address both the lymphoproliferative disorder and secondary autoimmune coagulopathy, resulting in progressive clinical stabilization.
Conclusions. This case underscores a rare association between AHA and HHV-8–associated MCD with Kaposi’s sarcoma. AHA should be suspected in patients with unexplained bleeding and isolated aPTT prolongation. Thorough evaluation for underlying conditions is essential, particularly in the presence of systemic features such as lymphadenopathy or splenomegaly. A multidisciplinary approach is critical for accurate diagnosis and optimal management. Prompt hemostatic treatment combined with immunosuppression and targeted therapy of the underlying disorder is essential to improve outcomes. This report highlights the importance of recognizing secondary causes of AHA and contributes to the limited literature on its association with HHV-8–related lymphoproliferative disease.