自己免疫性後天性凝固因子欠乏症

BACKGROUND Acquired hemophilia A is a rare autoimmune bleeding disorder caused by inhibitory autoantibodies against coagulation factor VIII and is associated with significant morbidity and mortality. Although malignancy-associated acquired hemophilia A is well recognized, its presentation as the initial manifestation of an otherwise clinically subtle indolent B-cell lymphoma, such as splenic marginal zone lymphoma, remains exceedingly uncommon. We report a case highlighting the importance of recognizing acquired factor VIII inhibitors, evaluating for underlying lymphoproliferative disorders, and the potential role of rituximab monotherapy in achieving control of both the inhibitor and the underlying lymphoma. CASE REPORT A 77-year-old man presented with spontaneous bruising and an isolated prolonged activated partial thromboplastin time that failed to correct on mixing studies. Further evaluation demonstrated markedly reduced factor VIII activity, a factor VIII inhibitor, diffuse splenomegaly, and flow cytometry and bone marrow biopsy findings most consistent with splenic marginal zone lymphoma. Treatment with activated prothrombin complex concentrate, corticosteroids, and rituximab resulted in normalization of coagulation parameters, recovery of factor VIII activity, decline in inhibitor titers, resolution of bleeding manifestations, and sustained clinical stability without recurrent bleeding or evidence of lymphoma progression. CONCLUSIONS This case highlights acquired hemophilia A as a rare paraneoplastic manifestation of splenic marginal zone lymphoma and emphasizes the importance of evaluating for an underlying lymphoproliferative disorder in older adults presenting with newly identified factor VIII inhibitors, particularly in the setting of cytopenias or splenomegaly. It also demonstrates that rituximab-based therapy can effectively achieve sustained remission of both the inhibitor and the underlying indolent lymphoma.

INTRODUCTION: Combination therapy with immune checkpoint inhibitors (ICIs) has become the standard pharmacological treatment for renal cell carcinoma; however, careful attention must be paid to immune-related adverse events (irAEs). We report a rare case of acquired autoimmune factor XIII deficiency following ipilimumab plus nivolumab therapy. CASE PRESENTATION: A 75-year-old woman who had previously undergone nephrectomy for left renal cell carcinoma developed pancreatic and pulmonary metastases and was started on combination immunotherapy. Six months after treatment initiation, she presented with bleeding symptoms. Laboratory testing revealed anti-factor XIII autoantibodies, confirming a diagnosis of acquired autoimmune factor XIII deficiency. CONCLUSION: To our knowledge, few reports have described this condition as an irAE. Nonetheless, other irAE-related acquired coagulation factor deficiencies-such as factor V deficiency and acquired hemophilia A-have been reported. These precedents suggest a high likelihood that the current case represents a novel manifestation of irAE.

BACKGROUND: Acquired factor V deficiency is a rare bleeding disorder caused by autoantibodies against factor V, resulting in marked reduction of activity and bleeding tendency. CASE PRESENTATION: We report the case of an 81-year-old man who developed acquired factor V deficiency after total arch replacement and open stent grafting for a thoracic aortic aneurysm. Postoperatively, despite the absence of bleeding tendency, both prothrombin time (PT) and activated partial thromboplastin time (APTT) were markedly prolonged. Factor assays revealed factor V activity <3%, and a factor V inhibitor was detected (1 BU/ml). A cross-mixing test indicated a pattern of factor deficiency, suggesting the involvement of clearance-facilitating antibodies in addition to neutralizing antibodies. DISCUSSION: Acquired factor V deficiency is often associated with surgery, transfusions, or antibiotics. Although rare, it should be considered in patients with unexplained prolongation of PT and APTT. Cross-mixing tests may mimic factor deficiency patterns when clearance-facilitating antibodies are present, requiring careful interpretation. Immunosuppressive therapy including corticosteroids, cyclophosphamide, or rituximab has been reported effective, while bleeding episodes may be managed with plasma or bypassing agents. CONCLUSION: This case emphasizes the importance of considering acquired factor V deficiency in the differential diagnosis of postoperative coagulopathy with unexplained prolongation of PT and APTT.

BACKGROUND: Acquired factor X deficiency (AFXD) is considered a rare but clinically significant cause of coagulation disorders, predominantly associated with systemic AL amyloidosis. Autoimmune-mediated AFXD is very rare, and a clear, well-documented association with Sjögren's syndrome has not yet been reported. CASE PRESENTATION: A 60-year-old woman with hypertension presented with chest pain. Despite normal liver function and absence of monoclonal gammopathy, she was found to have significantly prolonged PT/INR and severe factor X deficiency (3%). During follow-up, she developed symptoms of dry eyes, and autoimmune serology was positive for ANA, anti-SSA, and anti-SSB, meeting the 2016 ACR/EULAR criteria for Sjögren's syndrome. After ruling out alternative causes, she was diagnosed with autoimmune-mediated AFXD. Despite the severe deficiency, she did not present with any significant bleeding symptoms. Prednisone treatment (1 mg/kg/day) led to partial biochemical improvement. CONCLUSION: This report describes the first known association between Sjögren's syndrome and AFXD. Furthermore, the case highlights the importance of considering autoimmune etiologies in cases of unexplained coagulopathy and demonstrates the disconnect between laboratory abnormalities and bleeding phenotypes.

Acquired hemophilia A (AHA) is a rare, potentially life-threatening autoimmune bleeding disorder characterized by the development of inhibitory autoantibodies against factor VIII (FVIII). While most commonly diagnosed in the elderly, AHA can also occur in the postpartum period, where it presents unique diagnostic and therapeutic challenges. This review provides a comprehensive overview of the pathogenesis, clinical features, diagnostic approaches, and current therapeutic strategies for postpartum AHA. We highlight the immunological shifts during pregnancy and the postpartum period that may contribute to the breakdown of immune tolerance and the emergence of FVIII autoantibodies. Key aspects of laboratory diagnosis are outlined, including the role of coagulation screening, mixing studies, and inhibitor assays. We compare the efficacy and safety of established immunosuppressive regimens, with a particular focus on the CyDRi protocol-a combination of cyclophosphamide, dexamethasone, and rituximab-which has demonstrated high rates of complete remission with a favorable toxicity profile. To illustrate clinical application, we describe a case of severe postpartum AHA managed successfully with the CyDRi protocol, followed by an uneventful subsequent pregnancy. With timely diagnosis and appropriately tailored immunosuppressive therapy, postpartum AHA can be effectively treated, and favorable hematologic and reproductive outcomes are achievable.