RARE DISEASE
Acquired hemophilia A
Acquired hemophilia A
Acquired hemophilia A
Synonyms: AHA, Acquired F8 deficiency, Acquired factor VIII deficiency
Synonyms: AHA, Acquired F8 deficiency, Acquired factor VIII deficiency
Synonyms: AHA, Acquired F8 deficiency, Acquired factor VIII deficiency
Drug discovery
0
drugs
With orphan designations
Overview
Acquired Hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against factor VIII, leading to impaired coagulation. It presents with spontaneous mucocutaneous or soft-tissue bleeding, often in older adults without prior bleeding history. Diagnosis requires confirmation of factor VIII deficiency and inhibitor detection via Bethesda assay. Management prioritizes bleeding control with bypassing agents (e.g., recombinant FVIIa, aPCC) or recombinant porcine FVIII, followed by immunosuppressive therapy (corticosteroids ± cyclophosphamide/rituximab) for inhibitor eradication [1][2][3][6][12].
Burden
Mortality: Up to 21%, with bleeding complications (3-9%) and immunosuppression-related infections (14%) as leading causes [6][9].
Delayed diagnosis increases morbidity; treatment costs are substantial (e.g., $6M per hospitalization for rpFVIII) [6][14].
Comorbidities (e.g., cardiovascular disease) complicate management in elderly patients [6][12].
Therapies
Hemostasis: Bypassing agents (rFVIIa, aPCC) or recombinant porcine FVIII for acute bleeding; emicizumab considered in refractory cases or contraindications to traditional therapies [1][3][6][12].
Immunosuppression: First-line: corticosteroids ± cyclophosphamide; second-line: rituximab. Remission achieved in ~79% within months [1][3][6][8].
Categories: rare hematological diseases
Research Papers
880 drug discovery papers about Acquired hemophilia A, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
880 drug discovery papers about Acquired hemophilia A, with 3 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-11 | Prepartum Acquired Hemophilia A: Managing a Double Challenge for Mother and Child.
Acquired haemophilia A (AHA) during pregnancy is exceptionally rare and poses significant risks to both mother and fetus, including maternal hemorrhage and neonatal bleeding due to transplacental transfer of factor VIII (FVIII) inhibitors. We report four cases of antenatally diagnosed AHA to provide insights into management and outcomes. All patients received corticosteroids during pregnancy, with individualized peripartum haemostatic strategies using bypassing agents when indicated. Transplacental FVIII inhibitor transfer occurred in three neonates, leading to transient low FVIII levels; only one mild bleeding event was observed, and all infants achieved spontaneous remission within weeks. Postpartum escalation of immunosuppressive therapy, including rituximab, was required in selected mothers to achieve remission. Our series highlights the critical importance of prepartum diagnosis, allowing optimized maternal haemostatic management, avoidance of traumatic delivery, and structured neonatal surveillance to prevent severe bleeding complications.
2026-07-06 | Non-Factor Therapies in Haemophilia: The Era of Factor VIII Mimetics and Targeted Rebalancing Agents.
Non-factor therapies have substantially reshaped the treatment landscape of haemophilia by restoring effective thrombin generation independently of factor replacement. By targeting key regulatory mechanisms of coagulation, these approaches address limitations of conventional therapy, including intravenous administration, fluctuating factor levels, and inhibitor development. Bispecific factor VIII mimetic antibodies enable stable haemostatic protection by functionally substituting the cofactor role of factor VIII, resulting in sustained thrombin amplification with subcutaneous administration. Several years of clinical experience with emicizumab have demonstrated durable efficacy, a favourable safety profile, and broad applicability across patients with haemophilia A with and without inhibitors, establishing factor VIII mimetics as a central component of modern prophylaxis. Next-generation mimetics aim to further optimize potency and haemostatic control. Targeted rebalancing agents enhance coagulation by attenuating endogenous anticoagulants such as tissue factor pathway inhibitor or antithrombin. These approaches provide factor-independent efficacy across haemophilia A and B but introduce distinct safety considerations related to excessive thrombin generation, necessitating dose mitigation and careful monitoring. In acquired haemophilia A, non-factor therapies offer particular advantages by bypassing neutralizing autoantibodies, with prospective data supporting the use of emicizumab for effective bleeding prophylaxis and potential deferral of immunosuppressive therapy in elderly and multimorbid patients. Non-factor therapies enable convenient haemophilia management through subcutaneous administration and sustained haemostatic control. Continued clinical experience will be essential to define the long-term positioning of rebalancing strategies.
2026-07-06 | Mechanism and kinetics study of MG1113, an anti-tissue factor pathway inhibitor antibody promoting hemostasis in hemophilia.
Targeting tissue factor pathway inhibitor (TFPI) is an emerging hemostatic rebalancing strategy for hemophilia. MG1113 is a humanized monoclonal antibody designed to specifically bind the Kunitz domain (KD)2 of TFPI. This study elucidated the detailed pharmacologic mechanism of action and the preclinical hemostatic efficacy of MG1113. In vivo efficacy was evaluated using an acquired hemophilia A (HA) cynomolgus monkey model. In vitro chromogenic assays, factor (F)Xa generation, and clot waveform analysis were performed in human factor-deficient plasmas to assess the dynamics of coagulation. Additionally, a cell-based system using EA.hy926 endothelial cells was established to examine the dual neutralization of TFPI isoforms. In acquired HA monkeys, a single dose of MG1113 (3 mg/kg) reduced free TFPI levels by 98.8%, shortened the modified prothrombin time and restored thrombin peak height to ∼78% of normal levels. Mechanistically, MG1113 successfully prevented TFPI-mediated inhibition of the extrinsic tenase complex-specifically in the presence of FXa-despite targeting only KD2. MG1113 restored the FXa amplification loop and simultaneously neutralized both plasma-derived TFPI-α and cell-surface TFPI-β. However, despite sufficiently restoring FXa generation, clot waveform analysis revealed that MG1113 exhibited a broader, less intense, and more prolonged coagulation profile compared with the rapid burst characteristic of factor replacement therapy. MG1113 effectively restores hemostasis by blocking the TFPI/FXa interaction. By systematically lowering the threshold for tissue factor-mediated initiation, MG1113 facilitates physiological restoration of hemostasis. This mechanistic profile-combined with gradual clot kinetics and the advantages of a monoclonal antibody-makes MG1113 suited for routine prophylaxis.
2026-07-11 | Prepartum Acquired Hemophilia A: Managing a Double Challenge for Mother and Child.
Acquired haemophilia A (AHA) during pregnancy is exceptionally rare and poses significant risks to both mother and fetus, including maternal hemorrhage and neonatal bleeding due to transplacental transfer of factor VIII (FVIII) inhibitors. We report four cases of antenatally diagnosed AHA to provide insights into management and outcomes. All patients received corticosteroids during pregnancy, with individualized peripartum haemostatic strategies using bypassing agents when indicated. Transplacental FVIII inhibitor transfer occurred in three neonates, leading to transient low FVIII levels; only one mild bleeding event was observed, and all infants achieved spontaneous remission within weeks. Postpartum escalation of immunosuppressive therapy, including rituximab, was required in selected mothers to achieve remission. Our series highlights the critical importance of prepartum diagnosis, allowing optimized maternal haemostatic management, avoidance of traumatic delivery, and structured neonatal surveillance to prevent severe bleeding complications.
2026-07-06 | Non-Factor Therapies in Haemophilia: The Era of Factor VIII Mimetics and Targeted Rebalancing Agents.
Non-factor therapies have substantially reshaped the treatment landscape of haemophilia by restoring effective thrombin generation independently of factor replacement. By targeting key regulatory mechanisms of coagulation, these approaches address limitations of conventional therapy, including intravenous administration, fluctuating factor levels, and inhibitor development. Bispecific factor VIII mimetic antibodies enable stable haemostatic protection by functionally substituting the cofactor role of factor VIII, resulting in sustained thrombin amplification with subcutaneous administration. Several years of clinical experience with emicizumab have demonstrated durable efficacy, a favourable safety profile, and broad applicability across patients with haemophilia A with and without inhibitors, establishing factor VIII mimetics as a central component of modern prophylaxis. Next-generation mimetics aim to further optimize potency and haemostatic control. Targeted rebalancing agents enhance coagulation by attenuating endogenous anticoagulants such as tissue factor pathway inhibitor or antithrombin. These approaches provide factor-independent efficacy across haemophilia A and B but introduce distinct safety considerations related to excessive thrombin generation, necessitating dose mitigation and careful monitoring. In acquired haemophilia A, non-factor therapies offer particular advantages by bypassing neutralizing autoantibodies, with prospective data supporting the use of emicizumab for effective bleeding prophylaxis and potential deferral of immunosuppressive therapy in elderly and multimorbid patients. Non-factor therapies enable convenient haemophilia management through subcutaneous administration and sustained haemostatic control. Continued clinical experience will be essential to define the long-term positioning of rebalancing strategies.
2026-07-06 | Mechanism and kinetics study of MG1113, an anti-tissue factor pathway inhibitor antibody promoting hemostasis in hemophilia.
Targeting tissue factor pathway inhibitor (TFPI) is an emerging hemostatic rebalancing strategy for hemophilia. MG1113 is a humanized monoclonal antibody designed to specifically bind the Kunitz domain (KD)2 of TFPI. This study elucidated the detailed pharmacologic mechanism of action and the preclinical hemostatic efficacy of MG1113. In vivo efficacy was evaluated using an acquired hemophilia A (HA) cynomolgus monkey model. In vitro chromogenic assays, factor (F)Xa generation, and clot waveform analysis were performed in human factor-deficient plasmas to assess the dynamics of coagulation. Additionally, a cell-based system using EA.hy926 endothelial cells was established to examine the dual neutralization of TFPI isoforms. In acquired HA monkeys, a single dose of MG1113 (3 mg/kg) reduced free TFPI levels by 98.8%, shortened the modified prothrombin time and restored thrombin peak height to ∼78% of normal levels. Mechanistically, MG1113 successfully prevented TFPI-mediated inhibition of the extrinsic tenase complex-specifically in the presence of FXa-despite targeting only KD2. MG1113 restored the FXa amplification loop and simultaneously neutralized both plasma-derived TFPI-α and cell-surface TFPI-β. However, despite sufficiently restoring FXa generation, clot waveform analysis revealed that MG1113 exhibited a broader, less intense, and more prolonged coagulation profile compared with the rapid burst characteristic of factor replacement therapy. MG1113 effectively restores hemostasis by blocking the TFPI/FXa interaction. By systematically lowering the threshold for tissue factor-mediated initiation, MG1113 facilitates physiological restoration of hemostasis. This mechanistic profile-combined with gradual clot kinetics and the advantages of a monoclonal antibody-makes MG1113 suited for routine prophylaxis.
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0 orphan drug designations.
0 orphan drug designations.
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