small molecules

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.

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2026-02-02 | Direct oral anticoagulant interference and removal in the factor VIII inhibitor assay.

Direct oral anticoagulants (DOACs) interfere with clot-based assays, including factor (F)VIII testing and the Nijmegen-Bethesda assay, potentially leading to false-positive results for FVIII inhibitors. Misinterpretation of these results carries serious clinical consequences. Activated charcoal-based products, such as DOAC Remove, may restore assay accuracy, but data supporting their use in FVIII inhibitor assays are limited. In this study, we aim to determine DOAC interference in FVIII inhibitor testing and evaluate effectivity of DOAC removal to restore assay reliability. Normal pooled plasma was spiked with therapeutic and supratherapeutic concentrations of apixaban, edoxaban, rivaroxaban, and dabigatran. Plasma pools from persons with acquired hemophilia A were spiked with DOACs and retested with and without DOAC removal treatment to evaluate workflow performance. FVIII inhibitor activity was measured with and without activated charcoal-based DOAC removal to establish DOAC interference and removal efficacy. Spiking experiments with DOACs caused concentration-dependent false-positive FVIII inhibitor results (>0.6 Nijmegen Bethesda Units/mL), with dabigatran showing the strongest interference and apixaban the weakest. DOAC removal substantially reduced or eliminated interference across all drugs. Post-removal FVIII inhibitor values closely matched baseline concentrations in both spiked normal pooled plasma and pooled patient plasma, with most results within ±20% of the assay variability. DOACs significantly interfere with FVIII inhibitor assays, potentially causing clinically significant false-positive results. Activated charcoal-based DOAC removal treatment provides a practical solution to restore assay reliability. These findings support the integration of DOAC removal into anti-FVIII testing protocols for patients on anticoagulant therapy.

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2026-02-01 | Diagnostic Challenges in Acquired Hemophilia A with Concomitant Oral Anticoagulant Use: A Case Series Analysis

Introduction Acquired hemophilia A (AHA) is an uncommon autoimmune bleeding disorder caused by inhibitory autoantibodies directed against coagulation factor VIII (FVIII). Laboratory monitoring of AHA involves serial inhibitor assays to assess treatment response and detect relapse [ 1 ]. The Bethesda assay and its Nijmegen-modified variant quantify residual FVIII activity after incubation of normal plasma with patient plasma, using either a one-stage clotting assay (OSCA) or a chromogenic substrate assay (CSA) [ 2 ]. Both assay formats, however, are susceptible to analytical interference by direct oral anticoagulants (DOACs). In particular, undetected direct factor Xa inhibitors (DFXaIs) may lead to falsely elevated Bethesda titers, potentially misinterpreted as persistent FVIII inhibitors despite clinical remission [ 3 ]. Method Two elderly female patients, aged 86 and 87 years, both with previously treated AHA and confirmed eradication of FVIII autoantibodies, presented during routine follow-up with borderline positive Nijmegen-modified Bethesda assay results (0.7 and 0.8 BU/mL; reference<0.5 BU/mL). Neither patient was under immunosuppressive therapy. Both received apixaban 2.5 mg twice daily—one for secondary prevention after cardioembolic stroke, the other for non-valvular atrial fibrillation. Laboratory testing revealed normal haemostatic screening tests. Liver function tests were within normal limits. Estimated glomerular filtration rate (eGFR) was consistent with moderate-to-severe chronic kidney disease. Haemostatic monitoring included FVIII activity measurement using both OSCA and CSA methods, von Willebrand factor (vWF) activity and antigen, anti-FVIII antibody detection by ELISA, and FVIII inhibitor quantification using the Nijmegen-modified Bethesda assay after heat inactivation. To evaluate possible interference from DOACs, plasma samples were pretreated with DOAC-Remove®​ and the Nijmegen-modified Bethesda assay was repeated. Results After pretreatment with DOAC-Remove®​, FVIII inhibitors were no longer detectable ([ Fig. 1 ]). Apixaban concentrations dropped below the analytical detection limit (<20 ng/mL), confirming effective DOAC removal. Positive control samples containing low-titer FVIII inhibitors demonstrated that DOAC-Remove®​ treatment did not inactivate FVIII autoantibodies, confirming assay validity. Fig. 1 Laboratory results in patients with AHA before and after DOAC-Remove®​ Conclusion Accurate laboratory assessment is essential for the diagnosis and follow-up of AHA. False-positive FVIII inhibitor results due to interference from DFXaIs can lead to misinterpretation of disease persistence and inappropriate clinical management. Anti-FVIII ELISA testing may serve as a complementary approach when DFXaI interference is suspected, but its limited specificity must be considered. Pretreatment of plasma samples with activated charcoal-based adsorbents such as DOAC-Remove®​ or DOAC-Stop®​ offers a simple and effective method to eliminate DFXaI interference in Nijmegen-modified Bethesda assays, thereby enhancing diagnostic reliability in AHA monitoring. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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2025-11-07 | Acquired Factor VIII (FVIII) Deficiency: A Case of Idiopathic Hemorrhage.

We report the case of a 34-year-old female with no prior medical history or known bleeding disorders who presented with a large, spontaneous right arm hematoma developing gradually over 10 days, without preceding trauma. She also had multiple ecchymoses and a history of a right calf hematoma three months earlier, initially misdiagnosed and managed as deep venous thrombosis and later as muscle cramp. Laboratory evaluation revealed anemia (hemoglobin: 9.9 g/dL) and a markedly prolonged activated partial thromboplastin time (aPTT) that failed to correct with mixing studies. Factor VIII activity was severely reduced at 4%, with an inhibitor titer of 3.1 Bethesda units, confirming acquired hemophilia A. Imaging demonstrated an intramuscular hematoma within the biceps. The patient was treated with high-dose intravenous methylprednisolone for three days, a single dose of cyclophosphamide, and transitioned to oral prednisolone and azathioprine. Within 24 hours, her aPTT improved to near-normal, and at one-month follow-up, she demonstrated complete resolution of symptoms, normalized FVIII activity, and no recurrence. This case underscores the importance of prompt recognition and combined laboratory, imaging, and clinical assessment in diagnosing acquired hemophilia, particularly in atypical presentations without mucocutaneous bleeding. Early targeted immunosuppressive therapy can result in rapid inhibitor eradication and favorable outcomes.

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2025-08-26 | P80 | Early rituximab in acquired haemophilia A: two cases report

Background: Acquired hemophilia A (AHA) is a rare event caused by the development of autoantibodies against factor VIII protein (FVIII). Guidelines recommend rituximab or cytotoxic agents as second-line therapy after 3-4 weeks of corticosteroids to eradicate FVIII inhibitor. We present two case reports of early rituximab use in AHA patients.Case 1: A man with myelomonocytic leukemia presented with widespread hematomas. Lab results showed anemia, prolonged aPTT, FVIII activity 0%, and an inhibitor level of 1.9 BU. Initial treatment with Methylprednisolone, APCC and rVIIa had limited response. Early rituximab therapy (375 mg/m2 weekly for 4 weeks) led to progressive hematoma resolution and eliminated the need for transfusions. After 4 weeks, aPTT was 35s, FVIII activity increased to 62%, and the inhibitor level dropped to 0.4 BU. Case 2: A man with metastatic gastric cancer in chemotherapy presented with left gluteal and abdominal swelling, severe anemia, and prolonged aPTT, reduced FVIII levels and the presence of FVIII inhibitor. CT scan showed the presence of muscular hematomas requiring embolization of the left gluteal and superficial left circumflex iliac arteries. Methylprednisolone and rVIIa were initiated with stability for two weeks. New hematomas prompted rituximab therapy, resulting in hematoma resolution, clinical improvement, normalizing aPTT, FVIII activity with FVIII inhibitor complete eradication.Conclusions: Early rituximab use, contrary to guidelines, effectively restored FVIII levels, reduced inhibitors, and resolved hemorrhagic symptoms in AHA patients.

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proteins

2026-07-17 | Acquired hemophilia a induced by clopidogrel

Introduction . Dual antiplatelet therapy (DATT) with aspirin and a platelet P2Y12 receptor inhibitor is one of the main components of treatment and secondary prevention in patients undergoing percutaneous coronary intervention in acute myocardial infarction. Among the side effects of DATT are hemorrhagic complications caused by the antiplatelet effect of the drugs. Less is known about hemorrhagic complications caused by coagulation disorders when taking clopidogrel. Aim : to present a clinical case of acquired hemophilia A, which occurred in a patient as a result of taking clopidogrel. Main findings . A 68-year-old patient received clopidogrel as part of DATT after percutaneous coronary intervention. One month later, he developed a pronounced hemorrhagic syndrome caused by the appearance of antibodies to coagulation factor VIII (FVIII:C 1.5 %, factor VIII inhibitor 61 BU). The elimination of clopidogrel, hemostatic therapy with eptacog alpha (activated) and immunosuppressive therapy with prednisone, cyclophosphamide and rituximab allowed not only to stop the hemorrhagic syndrome, but also to achieve eradication of the inhibitor.

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2026-07-03 | Sequential Use of Recombinant Porcine Factor VIII and Early Emicizumab in Acquired Hemophilia A: A Case Series.

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder requiring prompt hemostatic control and sustained prevention of rebleeding. Recombinant porcine factor VIII (rpFVIII, susoctocog alfa) controls acute bleeding, while emicizumab provides prophylaxis. Real-world data on their sequential use are limited. To describe clinical outcomes of three patients with AHA who received rpFVIII for initial hemostasis followed by early emicizumab. This case series describes three adults with AHA who received 200 U/kg rpFVIII for acute bleeding, early emicizumab loading on Days 2-3 followed by weekly maintenance, and individualized prednisolone. FVIII activity and inhibitor titers were measured using an emicizumab-neutralized assay with anti-idiotype antibodies. Single-dose rpFVIII achieved hemostasis within 24 h in all patients. No breakthrough bleeding, thrombosis, or adverse events occurred. Inhibitor titers decreased under immunosuppression. Two patients showed FVIII recovery by Day 49. One patient with persistently low FVIII activity remained stable on emicizumab. Hemostasis was achieved even in one patient with a baseline inhibitor titer of 105.8 BU/mL. Sequential rpFVIII followed by early emicizumab maintained bleeding control until inhibitor reduction and FVIII recovery occurred. This strategy was feasible and safe in these three patients. Larger studies are needed. The authors have confirmed clinical trial registration is not needed for this submission.

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2026-06-15 | Management of Breakthrough Bleeding During Emicizumab Prophylaxis in Acquired Haemophilia A: Data From the GTH-AHA-EMI Study.

The GTH-AHA-EMI study showed that emicizumab reduces bleeding in patients with acquired haemophilia A (AHA). However, 22 clinically relevant new bleeds (CRNB) occurred in 14 of the 47 study patients, most of which required haemostatic treatment. To describe characteristics, treatment, and outcome of CRNB that occurred during the 12 weeks of haemostatic prophylaxis with emicizumab. Data were extracted from the GTH-AHA-EMI study data base. Further information was collected retrospectively using a standardized questionnaire answered by study investigators. Of the 22 CRNB, 9 and 13 were classified as major and non-major, respectively. 15 bleeds occurred spontaneously, and 20 bleed required treatment. Recombinant factor VIIa was used for treatment in 16 of 20 treated bleeds, recombinant porcine factor VIII was used in three events. Eight patients were admitted to the hospital because of CRNB; extension of hospitalization was reported in 13 patients; 9 were admitted to an intensive care unit; invasive interventions were required in nine patients. Most bleeds were treated successfully; permanent harm from bleeding was reported in two patients. No thromboembolic events or other adverse events were reported. Although emicizumab reduces bleeding in AHA, breakthrough bleeding can still occur, was often severe and required haemostatic treatment. Haemostatic treatment was safe and usually effective. NCT04188639.

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2026-06-01 | APTT dynamics after susoctocog alfa for early diagnostic support in suspected acquired hemophilia A: a case report

Acquired hemophilia A (AHA) requires prompt hemostatic intervention; however, definitive diagnosis may be delayed in resource-limited settings, such as community hospitals, where immediate factor VIII (FVIII) activity and inhibitor assays are unavailable. Susoctocog alfa, a recombinant porcine FVIII, differs from bypassing agents in that its hemostatic effect can be reflected in activated partial thromboplastin time (APTT) measurements.

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2026-05-15 | Successful Perioperative Management of Pregnancy-Related Acquired Hemophilia A Using Only Bypassing Agents: A Case Report.

We report a confirmed case of pregnancy-associated acquired hemophilia A identified during preoperative evaluation for cesarean delivery. Although immunosuppressive therapy is generally recommended to eradicate factor VIII inhibitors, urgent delivery was required because of pregnancy-induced hypertension complicated by nephropathy. Under these circumstances, a cesarean delivery was performed without previous immunosuppressive treatment. Intraoperative hemostasis was well controlled, and both maternal and neonatal outcomes were favorable. This report may assist in clinical decision-making when invasive procedures are required in patients with acquired hemophilia A before therapeutic intervention with immunosuppressive therapy can be initiated.

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antibodies

2026-08-17 | Acquired haemophilia A associated with prostate cancer managed with recombinant activated factor VII and emicizumab.

Acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by neutralising antibodies against factor VIII. We describe an older man with prostate cancer on active surveillance who presented with spontaneous ecchymoses, progressive anaemia and isolated prolongation of activated partial thromboplastin time. Factor VIII activity was severely reduced, and mixing studies and Bethesda assay confirmed a high-titre factor VIII inhibitor. He achieved initial haemostatic control with recombinant-activated factor VII and was transitioned to emicizumab using an accelerated AHA regimen. No corticosteroids were given inpatient. Emicizumab was used for haemostatic prophylaxis while outpatient once-weekly rituximab was planned for inhibitor eradication. This case highlights early recognition, evaluation for associated malignancy and use of emicizumab as prophylaxis that may allow individualised immunosuppression in selected older patients.

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2026-07-17 | Acquired Hemophilia A Revealing Occult Splenic Marginal Zone Lymphoma.

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.

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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.

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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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2026-07-01 | Cost-effectiveness analysis of emicizumab use in hospitalized older individuals with acquired hemophilia A

Acquired hemophilia A (AHA) is a rare, autoimmune disease that leads to a severe bleeding diathesis. The efficacy of emicizumab use in the inpatient management of AHA has been recognized but widespread inpatient use remains limited due to its high cost. To evaluate cost-effectiveness of up-front emicizumab use in the inpatient management of AHA in the US. We built a Markov simulation to examine the cost-effectiveness of administering emicizumab with concurrent recombinant factor VIIa (rFVIIa) versus rFVIIa alone (standard of care, SOC) in older individuals newly diagnosed with AHA and hospitalized for bleeding control. Model outcomes included direct costs (medication use and hospital stay) and utilities associated with bleeding and nonbleeding health states (measured using quality-adjusted life days, QALDs). The analysis was conducted over a 20-day hospitalization horizon with a health system perspective. We conducted deterministic and probabilistic sensitivity analyses (PSA), capturing uncertainty across parameters over 10,000 Monte Carlo simulations. The addition of up-front emicizumab to SOC vs SOC alone yielded lower total direct cost ($248,934 vs. $569,038) and more QALDs (15.92 vs. 14.72). The addition of up-front emicizumab to SOC was the dominant strategy. The duration of daily rFVIIa use had the largest impact on the incremental net monetary benefit. In a PSA, emicizumab was cost-effective in 100% of simulations. The addition of up-front emicizumab to SOC is less costly and more effective, even at current emicizumab pricing. Our results provide strong economic and clinical justification to consider up-front emicizumab use in AHA management.

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cell therapies

2026-08-12 | Successful management of acquired hemophilia A with life-threatening bleeding and MRSA bacteremia in a hemodialysis patient: importance of a multimodal approach

Abstract Background Acquired hemophilia A (AHA) is a rare and fatal bleeding disorder. AHA in patients undergoing hemodialysis (HD) often leads to impaired hemostasis, necessitating temporary catheters that increase the risk of catheter-related infection. This complication hinders the use of immunosuppressive therapy, often resulting in treatment failure. We herein report the case of AHA in a patient undergoing HD with life-threatening bleeding and MRSA bacteremia, which was successfully managed with a multimodal approach. Case presentation A 64-year-old Japanese man had undergone HD owing to diabetic nephropathy and was admitted to our hospital with a massive hematoma in the left iliopsoas muscle and poor hemostasis at the vascular access site. Hemoglobin (Hb) had dropped to 5.0 g/dL despite daily blood transfusions, and activated partial thromboplastin time was alone prolonged around 60.0 s. Transcatheter arterial embolization (TAE) was performed owing to difficulty in hemostasis. After the diagnosis of AHA was made, 60 mg/day of prednisolone and bypassing agents were introduced. Additional plasma exchange (PE) was performed and rituximab was also administered. Factor VIII (FVIII) inhibitor decreased from 91.0 to 32.0 Bethesda Units (B.U)/mL, and hemostasis was achieved temporarily. Despite a decreasing trend, the FVIII inhibitor titer persisted at a high range. Hb decreased to 5.7 g/dL, and blood transfusions were needed again. Thus, a second TAE and a third PE were performed. After that, FVIII inhibitor improved to 7.0 B.U/mL, and hemostasis was fully achieved. Notably, a temporary dialysis catheter led to methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, necessitating careful PSL tapering. At 6 months after discharge, the patient had not experienced any relapse. Conclusions AHA in patients undergoing HD often leads to difficulty in hemostasis during HD, necessitating temporary catheters that almost induce catheter-related infection. This complication hinders the use of immunosuppressive therapy, sometimes resulting in treatment failure. Given the specific clinical setting of AHA in patients undergoing HD, achieving rapid bleeding control and preparing for impending infections are paramount, which necessitates a well-designed multimodal approach including immunosuppressive therapy and PP (plasmapheresis). This instructive case offers a potential framework for managing similar high-risk patients.

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2026-03-25 | Hemorrhagic Shock and Massive Abdominal Wall Hematoma After Cesarean Section in a Patient with Peripartum Acquired Hemophilia A:A Case Report.

Acquired Hemophilia A (AHA), a rare bleeding disorder caused by autoimmune suppression of coagulation factor VIII(FVIII), has a low incidence in perinatal women but carries significant risks of severe hemorrhage. The lack of consensus guidelines and limited clinical data from developing countries underscore the importance of this case report. Consequently, this report informs clinical practice and expands the evidence base for the treatment of AHA. This case describes an extensive abdominal wall hematoma and hemorrhagic shock following a cesarean section in a patient. The condition was successfully managed through comprehensive interventions, including shock resuscitation, endovascular embolization, pharmacological hemostatic therapy, removal of circulating immune complexes, and immunosuppressive therapy. AHA usually causes acute bleeding, and early identification and removal of acquired inhibitors are the main treatment methods. In such cases, endovascular embolization is an effective procedure to control bleeding.

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2025-12-22 | Laparoscopic Cholecystectomy for Acute Cholecystitis in a Patient with Acquired Hemophilia A: A Case Report of Perioperative Hemostatic Management with Plasma Exchange.

Acquired hemophilia A (AHA) is a rare but potentially life-threatening bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII). Surgery in patients with AHA is challenging because of the substantial risk of severe perioperative hemorrhage. However, no consensus has been reached on the optimal perioperative hemostatic strategies, especially for urgent surgical settings that require rapid correction of coagulation function, because of the rarity of this condition. A 79-year-old woman was diagnosed with AHA and received immunosuppressive therapy (prednisolone and cyclophosphamide) and hemostatic treatment (activated prothrombin complex concentrate). She developed acute cholecystitis on day 23. However, surgery was initially contraindicated due to inadequate coagulation control, persistently prolonged activated partial thromboplastin time, low FVIII activity, and high FVIII inhibitor titer. Antibiotic therapy was initiated, and endoscopic nasobiliary gallbladder drainage was attempted on day 26. However, the procedure was unsuccessful. The worsening abdominal pain on day 27 prompted further interventions. Plasma exchange (PE) was performed to rapidly reduce the FVIII inhibitor titers and correct the coagulation status before laparoscopic cholecystectomy. The coagulation parameters markedly improved after 3 PE sessions, as evidenced by the shortened activated partial thromboplastin time, increased FVIII activity, and significant reduction in FVIII inhibitor titers. This enabled a safe laparoscopic cholecystectomy with minimal intraoperative blood loss on day 30. No additional PE was required, and the patient was discharged uneventfully on POD 16. The FVIII inhibitor was eliminated within 2 months, and immunosuppressive therapy was discontinued 4 months after surgery. The patient has been in remission to date. This case highlights the potential utility of PE as a bridging strategy to achieve rapid hemostatic correction in patients with AHA requiring urgent surgery, especially those with high-titer FVIII inhibitors. Immunosuppressive therapy and bypassing agents remain the cornerstones of AHA management. However, PE may be an effective adjunct treatment option for refractory cases or in time-constrained settings. This report provides valuable insights into individualized multidisciplinary approaches that may facilitate safe surgical intervention in patients with AHA.

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2025-03-08 | Anti-CD19 CAR-T cell therapy for acquired hemophilia A

Acquired hemophilia A (AHA) is a rare autoimmune disorder caused by development of antibodies against clotting factor VIII (FVIII). It is characterized by severe spontaneous bleeding and prolonged bleeding after injury, often life-threatening. The therapeutic approach includes hemostatic medication (bypassing agents and recombinant porcine FVIII) to stop acute bleeding, and immunosuppressive therapy (IST) to eradicate autoantibody formation and induce remission [ 1 ]. Recently, the bispecific antibody emicizumab was introduced to prevent bleeding until remission of AHA [ 2 ]. Approximately 60–80% of patients reach complete remission (CR) over a variable period of weeks to months with established IST regimens. However, resistance to IST can pose a significant clinical challenge, as bleeding symptoms often persist, leading to continued need for hemostatic medications, intractable breakthrough bleeding, and an increased risk of death.

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2025-03-04 | [Post-traumatic acquired hemophilia A: a case report and literature review].

Acquired Hemophilia A is an acquired bleeding disorder characterized by reduced FⅧ activity due to the presence of autoantibodies against anticoagulant factor Ⅷ in the circulation. Laboratory tests are typically characterized by prolonged isolated activated partial thromboplastin time (APTT). Clinically, it often manifests as severe bleeding, and 50% of AHA patients can identify the cause. This article reports on a patient with post-traumatic AHA who rapidly improved after antibody removal and bypass replacement therapy, followed by wound healing following surgical intervention. A review of relevant literature is also conducted to enhance clinicians' awareness of AHA, which presents with normal coagulation initially and gradually develops into prolonged APTT accompanied by bleeding manifestations, aiming for early diagnosis and timely treatment.

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other

2024-09-28 | Biological Barriers for Drug Delivery and Development of Innovative Therapeutic Approaches in HIV, Pancreatic Cancer, and Hemophilia A/B.

Biological barriers remain a major obstacle for the development of innovative therapeutics. Depending on a disease's pathophysiology, the involved tissues, cell populations, and cellular components, drugs often have to overcome several biological barriers to reach their target cells and become effective in a specific cellular compartment. Human biological barriers are incredibly diverse and include multiple layers of protection and obstruction. Importantly, biological barriers are not only found at the organ/tissue level, but also include cellular structures such as the outer plasma membrane, the endolysosomal machinery, and the nuclear envelope. Nowadays, clinicians have access to a broad arsenal of therapeutics ranging from chemically synthesized small molecules, biologicals including recombinant proteins (such as monoclonal antibodies and hormones), nucleic-acid-based therapeutics, and antibody-drug conjugates (ADCs), to modern viral-vector-mediated gene therapy. In the past decade, the therapeutic landscape has been changing rapidly, giving rise to a multitude of innovative therapy approaches. In 2018, the FDA approval of patisiran paved the way for small interfering RNAs (siRNAs) to become a novel class of nucleic-acid-based therapeutics, which-upon effective drug delivery to their target cells-allow to elegantly regulate the post-transcriptional gene expression. The recent approvals of valoctocogene roxaparvovec and etranacogene dezaparvovec for the treatment of hemophilia A and B, respectively, mark the breakthrough of viral-vector-based gene therapy as a new tool to cure disease. A multitude of highly innovative medicines and drug delivery methods including mRNA-based cancer vaccines and exosome-targeted therapy is on the verge of entering the market and changing the treatment landscape for a broad range of conditions. In this review, we provide insights into three different disease entities, which are clinically, scientifically, and socioeconomically impactful and have given rise to many technological advancements: acquired immunodeficiency syndrome (AIDS) as a predominant infectious disease, pancreatic carcinoma as one of the most lethal solid cancers, and hemophilia A/B as a hereditary genetic disorder. Our primary objective is to highlight the overarching principles of biological barriers that can be identified across different disease areas. Our second goal is to showcase which therapeutic approaches designed to cross disease-specific biological barriers have been promising in effectively treating disease. In this context, we will exemplify how the right selection of the drug category and delivery vehicle, mode of administration, and therapeutic target(s) can help overcome various biological barriers to prevent, treat, and cure disease.

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2024-03-06 | A CROSS-SECTIONAL STUDY ON THE PREVALENCE OF HEMOPHILIA IN DISTRICT LARKANA

An inherited bleeding problem is hemophilia. Recombinant clotting factor VIII or factor IX and immunosuppressive drugs are used to treat hemophilia A or B to stop the development of alloantibodies and inhibitors. Treatment of hemophilia is a problem due to the formation of inhibitors to these factors. Patients with inhibitors are treated with activated recombinant factor VII and plasma-derived activated prothrombin complex concentrate. Treatment differs depending on the circumstance since bleeding is more likely to occur in cases of pregnancy, surgery, and cancer. The major topic of this study was to assess healthy persons' awareness of hemophilia and their familiarity with this condition from birth. 30 people from rural Sindh participated in a cross-sectional, random study. All participants were asked regular questions about their awareness of the illness, and SPSS software was used to analyze the data. There is currently no long-term or permanent treatment for hemophilia. Hemophilia may be temporarily cured by factor replacement. The direction of gene therapy or stem cell treatment, both of which are under development, may lead to a permanent cure. Previous research has shown that gene therapy seldom succeeds in curing patients for many months without the requirement for recombinant factor replenishment. To obtain a long-lasting and permanent cure for hemophilia, more adjustments to the treatment plan are necessary.

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2023-12-15 | HEMOPHILIA: DIAGNOSIS AND INNOVATIVE MANAGEMENT.

Hemophilia is an acquired,X-linked,passive disorder caused by an insufficiency of utilitarian plasma clotting factor VIII (FVIII). In a critical number of cases, the disorder results from a novo mutation. It rarely manifests as an acquired autoimmune process.Research facility thinks about for suspected hemophilia include a total blood cell tally,coagulation ponders, and an FVIII assay. In patients with an established diagnosis of hemophilia, periodic research facility evaluations include screening for the presence of FVIII inhibitors and screening for transfusion-related or transmissible illnesses such as hepatitis and HIV contamination. Estimation of FVIII levels is critical for observing FVIII substitution treatment. Treatment of hemophilia includes prophylaxis, treatment of bleeding episodes, and induction of immune tolerance.Intended for the treatment and rehabilitation of the patients who are taking factor inhibitors and patients have hemophilic synovitis. Treatment for hemophiliacs should ideally be provided by a Hemophilia Day Care center.We discuss innovative management for the prevention of hemophilia through gene therapy,non-replacement therapy,EHL recombinant concentration,etc.we discuss the data from our studies and emerging results from other gene therapy trials in both hemophilia A and B. This analysis will provide evidence and information on the feasibility and data quality/completeness of the hemophilia database to assess the impact of innovative management on hemophilia outcomes in developing countries.We used a statistical method to analyze the data of adult and pediatric patients who come to hemophilia day care center for taking treatment.The data analysis was performed by the data collected monthly at the hemophilia day care center.

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2022-12-15 | Acute-type acquired hemophilia A after COVID-19 mRNA vaccine administration: A new disease entity?

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder. Various autoimmune diseases, including AHA, have been reported to occur after the administration of mRNA COVID-19 vaccines. However, the characteristics of these AHA cases remain unclear. We report a case in which AHA arose in a young patient after the administration of an mRNA COVID-19 vaccine, but improved rapidly. The patient's factor VIII (FVIII) inhibitor titer spontaneously decreased to less than half of that seen at diagnosis. One week after the initial immunosuppressive therapy, the FVIII inhibitor had disappeared. Our case suggests that AHA that arises in young patients after COVID-19 vaccination may resolve spontaneously, and the levels of FVIII inhibitors may decrease more rapidly in such cases than in idiopathic AHA. Unlike for immune thrombocytopenic purpura (ITP), no acute type of AHA has been recognized. This case suggests that just as there is an acute type of ITP that develops in children/after vaccination, there may be an acute type of AHA that arises in young patients that receive mRNA COVID-19 vaccines.

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2020-09-09 | High-level protein production in erythroid cells derived from in vivo transduced hematopoietic stem cells.

We developed an in vivo hematopoietic stem cell (HSC) transduction approach that involves HSC mobilization from the bone marrow into the peripheral bloodstream and the IV injection of an integrating, helper-dependent adenovirus (HDAd5/35++) vector system. HDAd5/35++ vectors target human CD46, a receptor that is abundantly expressed on primitive HSCs. Transgene integration is achieved by a hyperactive Sleeping Beauty transposase (SB100x) and transgene marking in peripheral blood cells can be increased by in vivo selection. Here we directed transgene expression to HSC-derived erythroid cells using β-globin regulatory elements. We hypothesized that the abundance and systemic distribution of erythroid cells can be harnessed for high-level production of therapeutic proteins. We first demonstrated that our approach allowed for sustained, erythroid-lineage specific GFP expression and accumulation of GFP protein in erythrocytes. Furthermore, after in vivo HSC transduction/selection in hCD46-transgenic mice, we demonstrated stable supraphysiological plasma concentrations of a bioengineered human factor VIII, termed ET3. High-level ET3 production in erythroid cells did not affect erythropoiesis. A phenotypic correction of bleeding was observed after in vivo HSC transduction of hCD46+/+/F8-/- hemophilia A mice despite high plasma anti-ET3 antibody titers. This suggests that ET3 levels were high enough to provide sufficient noninhibited ET3 systemically and/or locally (in blood clots) to control bleeding. In addition to its relevance for hemophilia A gene therapy, our approach has implications for the therapy of other inherited or acquired diseases that require high levels of therapeutic proteins in the blood circulation.

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