Diagnosis and Management of Acquired Hemophilia A: A Clinical Analysis from Cho Ray Hospital’s Hematology Department

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Tran, Phuong-Thao T. Le This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5857873/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Acquired hemophilia A (AHA) is a rare autoimmune disorder caused by autoantibodies to coagulation factor VIII. Patients with AHA often bleed spontaneously, severely, difficult to control, and have high treatment costs. Aims: We present a case series of AHA patients treated at the Hematology department in Cho Ray Hospital from May 2019 to June 2023. Methods : This is a retrospective case series report of patients who were diagnosed with AHA. Demographic information, clinical, laboratory characteristics and treatment were described. This is a retrospective case series report of patients who were diagnosed with AHA. It describes demographic information, clinical and laboratory characteristics, and treatment. Results: 29 patients (males, females) were included in the case series. Mean age was 57.1 ± 16.6 years. Median FVIII activity was 2 U/dL (0 – 35). Median inhibitor titer was 30.9 BU (1.5 – 1016.4). Mean hemoglobin levels were 77.5 ± 19.7 g/L. All patients had at least one bleeding episode before being diagnosed with which 21/29 patients were an adverse event. The causes of bleeding were spontaneous (26/29 patients), postoperative (2/29 patients) and after injection (1/29 patient). The common site of bleeding were muscular hematomas (20/29 patients), hematuria (7/29 patients), internal bleeding (3/29 patients) and cerebral hemorrhage (1 patient). The underlying disorders of AHA were idiopathic (22/29 patients), malignancy (4/29 patients) and SLE (3/29 patients). In terms of bleeding treatment, 12 patients received bypass agent including rFVIIa (9 patients) and aPCC (5 patients). The response rate was 91.7%. Thromboembolic events were 0%. All patients received immunosuppressive therapy with corticosteroids alone (19/29 patients), corticosteroids combined with cyclophosphamide (8/29 patients), corticosteroids combined with Rituximab (1/29 patients), and corticosteroids combined with MMF (1 patient). Mean hospitalization period was 12.7 days (5-33 days). 11/29 patients developed secondary infections. 3/29 patients perished in the hospital. Conclusion : From our case series, AHA patients often have severe bleeding, high inhibitor titer, and bypassing agents needed. Although the success rate was high, the cost, hospitalization period, and secondary infection are considered disadvantageous factors. More data is required to find the proper treatment which balances benefits and risks. Acquired hemophilia A Rare Bleeding Disorders bypassing agent Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Acquired hemophilia A (AHA) is a rare disease caused by autoantibodies to factor VIII (FVIII). The autoantibodies to FVIII have the incidence of approximately 1 to 1.5 per million population per year( 1 ). The majority of patients are adults with a median age of 64–78 years( 2 ). The underlying conditions of AHA included autoimmune disorders (systemic lupus erythematosus…), malignancy, pregnancy... However, approximately 50% of patients, AHA is not associated with any medical illnesses (idiopathic AHA)( 1 ). AHA patients usually present with spontaneous bleeding or induced hemorrhage in patients with no previous family or personal history of bleeding and usually exhibit a sudden onset. Bleeding manifestations are also variable, from mild to severe to life-threatening, and mortality may be as high as 22%, especially in elderly patients with other comorbidities( 3 ). Observed clinical bleeding does not relate with FVIII level or inhibitor titer. The hemostatic agents used to control bleeding in AHA are bypassing agents, recombinant activated FVII (rFVIIa) or activated prothrombin complex concentrate (aPCC), or FVIII replacement therapy with concentrates or induction of FVIII release using 1-desamino-8-D-arginine-vasopressin (DDAVP). Because of its rarity, AHA has limited data to support management. Therefore, consensus guidelines on management are largely limited to registries and expert opinion. Until now, clinical data on AHA in VietNam is minimal. So, we conducted this research to clarify the characteristics of AHA patients in the Vietnamese population. Aims We present a case series of AHA patients treated at the Hematology department in Cho Ray Hospital from May 2019 to June 2023. PATIENTS AND METHODS Inclusion criteria the patient who was diagnosed with AHA, confirmed by the Bethesda test with a cut-off of 0.6 Bethesda unit. Exclusion criteria We excluded patients with congenital hemophilia A (with or without FVIII inhibitors). Methods : retrospective, case series report. Demographic information was described. Data for each bleeding episode were entered separately. The characteristics of each new bleeding event were reported: site (CNS, musculoskeletal, retroperitoneal, gastrointestinal, urogenital, skin, none), cause (spontaneous, traumatic, surgical, peripartum or postpartum), severity (severe defined as life-threatening, CNS, hemoglobin (Hb) < 8 g/dL or a drop of more than 2 g/dL). All other bleeding episodes were defined as nonsevere. The hemoglobin level, FVIII level, and inhibitor titer were recorded at presentation and/or at the time of the bleed. The hemostatic therapy used was described by an agent. For patients treated with bypass agents including aPCC and rFVIIa was reported as yes or no. The response to therapy was judged clinically by the physician and was recorded as bleeding resolved with date or bleeding not resolved. We record all bleeding episodes but only analyze the first bleeding episode. Immunosuppressive therapy used was described in 3 groups: steroids alone, steroids combined with cyclophosphamide, and steroids combined with rituximab. Length of hospital stay, cost of treatment, outcome, and complications also be described. The study was approved by the hospital's ethics committee and conducted without any intervention, harm, or interference in the diagnostic and treatment processes carried out by clinical physicians. It adhered to the principles outlined in the Declaration of Helsinki, and all participants provided written informed consent. Retrospective study based on medical records does not affect the patient's diagnosis and treatment process. This study was conducted without any financial support or funding from external agencies. Statistical analysis The data was collected using Epidata. Data analysis was performed by SPSS 20. Data were reported as frequency (percentage) or median. Criteria of diagnosis AHA according to guidance of Ministry of Health ( 4 ) Signs and symptoms Spontaneous bleeding No previous family or personal history of bleeding Laboratory Isolated prolonged aPTT Anticoagulant in the intrinsic pathway (dependent time and temperature) was positive FVIII activity was measured in the local laboratories with level < 40%. FVIII inhibitor titer was determined using the Bethesda method. AHA was defined by the presence of a neutralizing FVIII inhibitor ≥ 0.6 Bethesda units (BU)/mL (lower limit of detection). Normal PT, TT, fibrinogen, and platelet count We conduct diagnostic testing following the flowchart outlined by Tiede et al (Fig. 1 ). Treatment guideline Hemostasis treatment Inhibitor titer ≤ 5 BU Mild bleeding (subcutaneous hemorrhage or muscle hematoma but no functional impairment) - Tranexamic acid at dose of 25 mg/kg 3 to 4 times/day PO or 10 mg/kg 3 to 4 times/day IV. - Desmopressin: 0.3mcg/kg SC or IV. Repeated every 8 to 12 hours if needed. Intermediate and severe bleeding: Increase FVIII activity level - Concentrated factor VIII: 20UI/kg every 1 Bethesda unit of inhibitor plus 40 UI/kg/day or 100-200UI/kg/day, IV. - Desmopressin: 0.3mcg/kg, SC or IV. Inhibitor titer > 5 BU or no response with rFVIII Factor VIII bypassing agents: - APCC: bolus injection of 50–100 UI/kg/day repeated every 8 to 12 hours until hemostasis is achieved, up to a maximum of 200 U/kg per day; or - VIIa: bolus injection of 90–120 mcg/kg, repeated every 2 to 3 hours until hemostasis is achieved; or one dose only 270 mcg/kg, if still hemorrhage, repeated after 4 to 6 hours with dose of 90 mcg/kg. Combine with Tranexamic acid at dose of 15–25 mg/kg every 2–3 times/day, do not combine with APCC because of the risk of thrombosis. Inhibitor eradication Administer immunosuppressive therapy as soon as possible after diagnosis. - If FVIII activity level ≥ 1% and inhibitor titer ≤ 20 BU: + First-line: Methylprednisolon or Prednisolon 1mg/kg/day alone for 3–4 weeks. + Second line: if no response, add cyclophosphamid at a dose of 1.5–2mg/kg/day PO for maximum 6 weeks; or Mycophenolate mofetil at a dose of 1g/day for 1 week, after followed by 2g/day; or Rituximab 375mg/m 2 weekly for a maximum of 4 cycles. - If FVIII activity level 20 BU: + First-line: combining corticoid and cyclophosphamid or rituximab for 3–4 weeks. + Second line: If no response, add cyclophosphamid or rituximab whichever was not used during first-line therapy. RESULTS A total of 29 patients were entered into the study between May 2019 and June 2023. The study comprised 15 male (51.7%) and 14 female (48.3%), resulting in a male:female ratio = 1.1:1. The median age at diagnosis was 57.1 ± 16.6 years (Table 1 ). Table 1 Characteristics of sample research Characteristic Value All patient, n 29 Male, n(%) 15 (51.7) Female, n(%) 14 (48.3) Male:female ratio 1.1:1 Age, range 16–82 Mean ± SD 57.1 ± 16.6 All patients had at least one bleeding episode before being diagnosed with which 21/29 patients were an adverse event. The mean hemoglobin levels were 77.5 ± 19.7 g/L. Median FVIII activity was 2 U/dL (0–35). Median inhibitor titer was 30.9 BU (1.5–1016.4) (Table 2 ). Table 2 Laboratory characteristics of AHA patients AHA initial characteristics Value Bleeding as trigger for diagnosis 29 (100) Adverse event, n (%) 21 (72.4) Mean hemoglobin level (g/L) 77.5 ± 19.7 FVIII activity at diagnosis Median (U/dL) 2 Range (U/dL) 0–35 Less than 1 U/dL, n(%) 5 (17.2) 1–5 U/dL, n(%) 17 (58.6) More than 5 U/dL, n(%) 7 (24.1) Inhibitor titer Median (BU) 30.9 Range (BU) 1.5–1016.4 0– 5 BU, n(%) 4 (13.8) > 5 BU, n(%) 25 (86.2) > 20 BU, n(%) 19 (65.5) The causes of bleeding were spontaneous (26/29 patients), postoperative (2/29 patients) and after injection (1/29 patient). The common sites of bleeding were muscular hematomas (20/29 patients), hematuria (7/29 patients), internal bleeding (3/29 patients) and cerebral hemorrhage (1 patient). The underlying disorders of AHA were idiopathic (22/29 patients), malignancy (4/29 patients) and SLE (3/29 patients) (Table 3 ). Table 3 Clinical characteristics of AHA patients Clinical Value Cause of bleeding episodes Spontaneous, n (%) 26 (89.8) Surgery, n (%) 2 (6.8) Injection, n (%) 1 (3.4) Site/type of bleeding Muscular hematomas, n (%) 20 (68.9) Hematuria, n (%) 7 (24.1) Internal bleeding, n (%) 3 (10.3) Cerebral hemorrhage, n (%) 1 (3.4) Underlying disorders Idiopathic 22 (75.9) Malignancy (any type), n (%) 4 (13.8) Autoimmune disease (lupus), n (%) 3 (10.3) In terms of bleeding treatment, 12 patients received bypass agent included rFVIIa (9 patients) and aPCC (5 patients). The response rate was 91.7%. All patients received immunosuppressive therapy with corticosteroids alone (19/29 patients), corticosteroids combined with cyclophosphamide (8/29 patients), corticosteroids combined with Rituximab (1/29 patients), corticosteroids combined with MMF (1 patient) (Table 4 ). Mean hospitalization period was 12.7 days (5–33 days). 11/29 patients developed secondary infections. 3/29 patients perished in the hospital (Table 5 ) Table 4 Treatment and outcome of AHA patients Treatment n, (%) Bypass agent 12 (41.4) rFVIIa 9 (31) aPCC 5 (17.2) Response 11 (91.7) Thromboembolic events 0 (0) Immunosuppressive therapy 29 (100) Corticosteroids alone 19 (65.5) Corticosteroids plus cyclophosphamide 8 (27.6) Corticosteroids plus Rituximab 1 (3.4) Corticosteroids plus MMF 1 (3.4) Mortality 3 (10.3) Infectious complication 11 (37.9) Table 5 Patient's treatment costs Mean Range Patient's treatment costs (VNĐ) 447,130,790 6,435,430–1,570,965,483 Hospitalization time (days) 12,66 5–33 DISCUSSION AHA is a rare disease with an incidence of only 1–1.5 per million population per year( 1 ). During the study period from May 2019 to June 2023, a total of 29 patients matching the criteria were included in the study with a mean age of 57.1 years. Although the youngest age recorded in the study was 16 years old, most patients in the study were middle-aged to older. This is consistent with studies around the world that describe the general characteristics of AHA patients with the average age of disease from 64 to 78 years old ( 2 ). Acute severe hemorrhage often occurs and becomes the clinical feature of this disease, requiring the importance of early diagnosis and prompt treatment. In our series, all patients had onset of the disease with sudden bleeding, of which 21 out of 29 patients were severe at the time of diagnosis. Only 2 patients had bleeding after surgery and 1 had bleeding after injection. The rest of the patients had spontaneous bleeding. The majority of events were severe resulted in clinical acute anemia with mean Hb was 77.5 ± 19.7 g/L. Unlike hereditary hemophilia A, joint hemorrhage is rare. In AHA, the most common hemorrhagic sites are skin hemorrhage, intramuscular hemorrhage, internal hemorrhage (> 50%), hematuria, peritoneal hemorrhage, and other less common sites (< 10%), cerebral hemorrhage is rare ( 1 , 6 ). In our study, most of patients had muscular hematomas (68.9%), the less common was hematuria, internal bleeding and cerebral hemorrhage (Table 3 ). During coagulation cascade, factor VIII acts as a cofactor of factor IX in the activation of factor X on the surface of activated platelets. Proteolysis converts the factor VIII structure from a1-A2-a2-B-a3-A3-C1-C2 into light and heavy chain heterodimers. AHA is caused by the autoantibodies against factor VIII, which is a protein, of the IgG group (mostly IgG1 and IgG4 class). These autoantibodies bind to A2, A3, or C2. A2 and A3 bind factor VIII to factors IXa and X, while C2 binds factor VIII to phospholipids and von Willebrand factor. Autoantibodies in AHA patients are not fixed to complement and therefore do not cause agglutination. These antibodies bind to the active site in a temperature and time dependent manner. However, they do not cause complete inhibition of factor VIII activity, so measuring factor VIII activity has little clinical benefit. In our study, median FVIII activity was 2 U/dL (0–35). Median inhibitor titer was 30.9 BU (1.5–1016.4). Large studies on AHA in the world with large sample sizes have lower median inhibitor titer, however, in terms of width, there are large differences between patients in the same study (Table 6 ). Table 6 Laboratory Characteristics of Patients with Acquired Hemophilia A in Large Registry Studies Our study Delgado( 7 ) Collins( 3 ) EACH2( 1 ) Borg( 8 ) GTH-AH( 9 ) N 29 234 172 501 82 102 Inhibitor titer, median (range) 30.9 (1.5–1016.4) 10 (0,9–32000) 13 (4–38) 12.8 (4.2–42.5) 16.1 (1–2800) 19 (1–1449) The underlying conditions of AHA included autoimmune disorders (systemic lupus erythematosus…), malignancy, pregnancy... However, approximately 50% of patients have AHA is not associated with any medical illnesses (idiopathic AHA) (Table 7 ). In our study, the underlying disorders of AHA were idiopathic (22/29 patients), malignancy (4/29 patients) and SLE (3/29 patients). Table 7 Underlying disorder of AHA Our study Green ( 10 ) Delgado ( 7 ) Collins ( 3 ) Knoebl EACH2 ( 1 ) Borg (SACHA) ( 8 ) Kessler (HTRS) Tiede (GTH)( 9 ) Time study Before 1981 1985‒2002 2001–2003 2003–2009 2001–2006 2000–2011 2010–2013 Underlying disorder (%) Idiopathic 75.9 46.1 57.7 63.3 51.9 55 44.1 44.1 Malignancy 13.8 6.7 18.4 14.7 11.8 19.5 14.5 14.5 Autoimmune 10.3 18.0 9.4 16.7 11.6 15 18.6 28.3 Post-partum - 7.3 14.5 2.0 8.4 7.3 3.4 3.4 Infection - - - - 3.8 - - - Dermatologic - 4.5 - 3.3 1.4 - - - Drugs - 5.6 - - 3.4 - - - Other - 11.8 - - 11.6 - 38.6 4.8 The International consensus on AHA treatment guidelines was first published in 2009 and updated in 2020 to provide guidelines based on expert experience and research data ( 5 ). The principles of treating AHA patients include managing and preventing bleeding, eradicating inhibitors, and treating underlying conditions. The bypassing agents are the ideal management of patients with a high titer of an inhibitor and have severe bleeding, most commonly rFVIIa and APCC. Our series had 12 patients who needed to be treated with bypass agents (41.1%) with the overall response rate of 91.7% in the first time treated with that. Since the sample size is not large enough, we have not been able to compare the differences between the two agents. In the EACH2 study, hemorrhages were controlled almost successfully with a high response rate of 91.8%, with no difference between rFVIIa (91.8%) and aPCC (93.3%) ( 11 ). Neither rFVIIa nor aPCC has a follow-up test, so the frequency of administration and dose are based on improvements in clinical bleeding symptoms. The international consensus also gives clinical and subclinical indications for appropriate hemostasis and optimal intervals for evaluating bleeding control. Often, specialists require stabilization of hemoglobin levels, the absence of blood transfusions, improvement of clinical and visual hemorrhagic symptoms as appropriate signs of hemostasis. The major deleterious event associated with bypassing agents is thrombosis. Fortunately, the risk of thrombosis is quite low. In a multi-center study (EACH2) that recorded a thrombotic complication of 2.9% in patients using rFVIIa and 4.8% in patients using aPCC ( 11 ). In our study, we did not record any cases of thrombotic complications after using bypass agents. The goal of immunosuppressive therapy is to reduce the risk of bleeding by shortening the time to reach complete response. Auto-recover is seen in some patients who do not receive immunosuppressive treatment but whose outcomes are not predictable ( 5 ). According to current guidelines, immunosuppressive therapy is recommended for all patients diagnosed with AHA ( 12 ). Many of the patients with AHA are elderly, and thus clinicians must carefully consider the toxicities of therapy when choosing a regimen. The first-line immunosuppressive therapy is corticosteroids at a dose of 1 mg/kg/day. A second agent (Rituximab 375 mg/m 2 per week or Cyclophosphamide 1–2 mg/kg per day) is added to treat patients with loss of response to steroids alone. However, recent studies show that the rate of complete remission (CR) is higher when combining the drug (32% CR with steroids alone vs 67.7–83.3% with combination therapy). The international consensus on AHA treatment in 2020 supports the addition of Rituximab or Cyclophosphamide to first-line treatment for patients with > 20 BU inhibitors. The choice between cyclophosphamide and Rituximab depends on the patient's comorbidity. And the elimination of inhibitors is effective with an average of 5–6 weeks of immunosuppression ( 12 ). In our study, all patients started immunosuppressive therapy immediately after diagnosis. The use of the initial drug combination is based on the treatment guidelines of the Ministry of Health and the economic condition of the patient as well as the evaluation of the clinician at the time of diagnosis based on the symptoms and complications of the disease. In 29 patients, 19 patients received corticosteroids alone (65.5%), 8 patients received corticosteroids plus cyclophosphamide 8 (27.6), 1 patient received corticosteroids plus rituximab (3.4) and 1 patient received corticosteroids plus MMF (3.4%). One of the main drawbacks of our study was that we did not have enough data to adequately survey the IST response on all patients after treatment. With less data, we followed up with 4 out of 29 patients who had a complete response after IST. According to studies around the world, about 60–80% of patients will respond to first-line immunotherapy (corticosteroids with or without Rituximab or cyclophosphamide). Relapses are not uncommon during corticosteroid withdrawal, which occurred about 15% of the time in a study in the Netherlands ( 13 ). After the complete cessation of immunotherapy, about 25% of patients relapse with a mean time of 14.7 weeks ( 13 ). So, clinicians should advise patients during immunosuppressive discontinuation on monitoring hemorrhagic markers. Some authors suggest monitoring blood counts, aPTT and/or activated factor VIII levels every 2 weeks during the discontinuation of prednisone and every month for at least 3–6 months ( 2 ). Last but not least, the cost of treatment for AHA patients during severe life-threatening hemorrhages were huge. In our study, the mean cost of treatment was 447,130,790, the largest patient cost up to 1,570,965,483.0 VND. Much of the cost is due to the use of bypass agents. With an average hospital stay of 12.66 (5–33 days), the complication rate is mostly 37.9% secondary infection, further aggravating the severity and cost of treatment. CONCLUSIONS From our case series, AHA patients often have severe bleeding, high inhibitor titer, and bypassing agents needed. Although the success rate was high, the cost, hospitalization period, and secondary infection are considered disadvantageous factors. More data is required to find the proper treatment which balances benefits and risks. Declarations Author Contribution Tung T. Tran, MD, PhD: wrote the main manuscript text Phuong-Thao T. Le, MD: collected, analyzed and processed dataAll authors reviewed the manuscript References Knoebl P, Marco P, Baudo F, Collins P, Huth-Kühne A, Nemes L, et al. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost. 2012;10(4):622–31. Pishko AM, Doshi BS. Acquired Hemophilia A: Current Guidance and Experience from Clinical Practice. J Blood Med. 2022;13:255–65. Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, et al. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007;109(5):1870–7. Sơn NT. Hemophilia A mắc phải. Quyết định số 1832/QĐ-BYT ngày 01/07/2022: Hướng dẫn chẩn đoán và điều trị một số bệnh lý Huyết học. 2022. p. 93–7. Tiede A, Collins P, Knoebl P, Teitel J, Kessler C, Shima M, et al. International recommendations on the diagnosis and treatment of acquired hemophilia A. Haematologica. 2020;105(7):1791–801. Windyga J, Baran B, Odnoczko E, Buczma A, Drews K, Laudanski P, et al. Treatment guidelines for acquired hemophilia A. Ginekol Pol. 2019;90(6):353–64. Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, Villar A. Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol. 2003;121(1):21–35. Borg JY, Guillet B, Le Cam-Duchez V, Goudemand J, Lévesque H. Outcome of acquired haemophilia in France: the prospective SACHA (Surveillance des Auto antiCorps au cours de l'Hémophilie Acquise) registry. Haemophilia. 2013;19(4):564–70. Tiede A, Klamroth R, Scharf RE, Trappe RU, Holstein K, Huth-Kühne A, et al. Prognostic factors for remission of and survival in acquired hemophilia A (AHA): results from the GTH-AH 01/2010 study. Blood. 2015;125(7):1091–7. Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost. 1981;45(3):200–3. Baudo F, Collins P, Huth-Kühne A, Lévesque H, Marco P, Nemes L, et al. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood. 2012;120(1):39–46. Kruse-Jarres R, Kempton CL, Baudo F, Collins PW, Knoebl P, Leissinger CA, et al. Acquired hemophilia A: Updated review of evidence and treatment guidance. Am J Hematol. 2017;92(7):695–705. Schep SJ, van Dijk WEM, Beckers EAM, Meijer K, Coppens M, Eikenboom J, et al. Treatment of acquired hemophilia A, a balancing act: results from a 27-year Dutch cohort study. Am J Hematol. 2021;96(1):51–9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5857873","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":408981353,"identity":"ad12f717-de72-41de-80ea-0b3d2b3891e5","order_by":0,"name":"Tung T. Tran","email":"","orcid":"","institution":"Cho Ray Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tung","middleName":"T.","lastName":"Tran","suffix":""},{"id":408981354,"identity":"8d0555da-f402-4272-8f47-0100c85ba708","order_by":1,"name":"Phuong-Thao T. Le","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYBACPiBmhjAZGx98gLAM8GphY2NgbIawmJsNZ5Cohb1NmocoLfK9xx8X1NgwmMs3Nhvbtm3LY2Bv3ibB2HYHjy18ic0zjqUxWLYxNj7ObbtdzMBzrAyo5RkeLTyGzTxshxkMjjE2GwO1JDZI5JhJMJw5TEDLP7CWNmlLkBb5N0Ro4W2DamEE28ID1FKBT0te4mzevjQeg2OJzYY9524Xs/GkFVsk4NHCz3z2wGeebzZyBoePP3zwo+x2Hj/74Y03Phjg1sLAwINEAkECG5jEowFJMVQLXsWjYBSMglEwIgEAt/pNCWcqDeQAAAAASUVORK5CYII=","orcid":"","institution":"Cho Ray Hospital","correspondingAuthor":true,"prefix":"","firstName":"Phuong-Thao","middleName":"T.","lastName":"Le","suffix":""}],"badges":[],"createdAt":"2025-01-19 05:53:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5857873/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5857873/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":75410770,"identity":"833e2c75-9ffb-4efa-837b-8c2238f1038d","added_by":"auto","created_at":"2025-02-04 09:08:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":12505,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-5857873/v1/63d590d8bfeef3f880e4b4c1.png"},{"id":75408728,"identity":"ab22866b-4d37-42a1-a951-b8c05c9971b7","added_by":"auto","created_at":"2025-02-04 09:00:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27822,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-5857873/v1/89554941af2cafb5ee6c211c.png"},{"id":75408729,"identity":"d50288c4-4702-428a-b381-b13df85eb925","added_by":"auto","created_at":"2025-02-04 09:00:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":26398,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-5857873/v1/1f5a178ca42f909f96ba47a8.png"},{"id":75625695,"identity":"b788de9d-5c37-411e-a8b7-a7c927a5dd08","added_by":"auto","created_at":"2025-02-06 12:53:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":737325,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5857873/v1/8b82be6e-92ab-4716-86ee-4eece640703d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Diagnosis and Management of Acquired Hemophilia A: A Clinical Analysis from Cho Ray Hospital’s Hematology Department","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAcquired hemophilia A (AHA) is a rare disease caused by autoantibodies to factor VIII (FVIII). The autoantibodies to FVIII have the incidence of approximately 1 to 1.5 per million population per year(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The majority of patients are adults with a median age of 64\u0026ndash;78 years(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The underlying conditions of AHA included autoimmune disorders (systemic lupus erythematosus\u0026hellip;), malignancy, pregnancy... However, approximately 50% of patients, AHA is not associated with any medical illnesses (idiopathic AHA)(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). AHA patients usually present with spontaneous bleeding or induced hemorrhage in patients with no previous family or personal history of bleeding and usually exhibit a sudden onset. Bleeding manifestations are also variable, from mild to severe to life-threatening, and mortality may be as high as 22%, especially in elderly patients with other comorbidities(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Observed clinical bleeding does not relate with FVIII level or inhibitor titer. The hemostatic agents used to control bleeding in AHA are bypassing agents, recombinant activated FVII (rFVIIa) or activated prothrombin complex concentrate (aPCC), or FVIII replacement therapy with concentrates or induction of FVIII release using 1-desamino-8-D-arginine-vasopressin (DDAVP).\u003c/p\u003e \u003cp\u003eBecause of its rarity, AHA has limited data to support management. Therefore, consensus guidelines on management are largely limited to registries and expert opinion. Until now, clinical data on AHA in VietNam is minimal. So, we conducted this research to clarify the characteristics of AHA patients in the Vietnamese population.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eAims\u003c/strong\u003e \u003cp\u003eWe present a case series of AHA patients treated at the Hematology department in Cho Ray Hospital from May 2019 to June 2023.\u003c/p\u003e \u003c/p\u003e"},{"header":"PATIENTS AND METHODS","content":"\u003cp\u003e \u003cstrong\u003eInclusion criteria\u003c/strong\u003e \u003cp\u003ethe patient who was diagnosed with AHA, confirmed by the Bethesda test with a cut-off of 0.6 Bethesda unit.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eExclusion criteria\u003c/strong\u003e \u003cp\u003eWe excluded patients with congenital hemophilia A (with or without FVIII inhibitors).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eMethods\u003c/b\u003e: retrospective, case series report. Demographic information was described. Data for each bleeding episode were entered separately. The characteristics of each new bleeding event were reported: site (CNS, musculoskeletal, retroperitoneal, gastrointestinal, urogenital, skin, none), cause (spontaneous, traumatic, surgical, peripartum or postpartum), severity (severe defined as life-threatening, CNS, hemoglobin (Hb)\u0026thinsp;\u0026lt;\u0026thinsp;8 g/dL or a drop of more than 2 g/dL). All other bleeding episodes were defined as nonsevere. The hemoglobin level, FVIII level, and inhibitor titer were recorded at presentation and/or at the time of the bleed. The hemostatic therapy used was described by an agent. For patients treated with bypass agents including aPCC and rFVIIa was reported as yes or no. The response to therapy was judged clinically by the physician and was recorded as bleeding resolved with date or bleeding not resolved. We record all bleeding episodes but only analyze the first bleeding episode. Immunosuppressive therapy used was described in 3 groups: steroids alone, steroids combined with cyclophosphamide, and steroids combined with rituximab. Length of hospital stay, cost of treatment, outcome, and complications also be described.\u003c/p\u003e \u003cp\u003eThe study was approved by the hospital's ethics committee and conducted without any intervention, harm, or interference in the diagnostic and treatment processes carried out by clinical physicians. It adhered to the principles outlined in the Declaration of Helsinki, and all participants provided written informed consent. Retrospective study based on medical records does not affect the patient's diagnosis and treatment process. This study was conducted without any financial support or funding from external agencies.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe data was collected using Epidata. Data analysis was performed by SPSS 20. Data were reported as frequency (percentage) or median.\u003c/p\u003e \u003cp\u003eCriteria of diagnosis AHA according to guidance of Ministry of Health (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cem\u003eSigns and symptoms\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eSpontaneous bleeding\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNo previous family or personal history of bleeding\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eLaboratory\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eIsolated prolonged aPTT\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eAnticoagulant in the intrinsic pathway (dependent time and temperature) was positive\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eFVIII activity was measured in the local laboratories with level\u0026thinsp;\u0026lt;\u0026thinsp;40%.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eFVIII inhibitor titer was determined using the Bethesda method. AHA was defined by the presence of a neutralizing FVIII inhibitor\u0026thinsp;\u0026ge;\u0026thinsp;0.6 Bethesda units (BU)/mL (lower limit of detection).\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNormal PT, TT, fibrinogen, and platelet count\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eWe conduct diagnostic testing following the flowchart outlined by Tiede et al (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e Treatment guideline\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eHemostasis treatment\u003c/h3\u003e\n\u003cp\u003eInhibitor titer\u0026thinsp;\u0026le;\u0026thinsp;5 BU\u003c/p\u003e \u003cp\u003e \u003cem\u003eMild bleeding (subcutaneous hemorrhage or muscle hematoma but no functional impairment)\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e- Tranexamic acid at dose of 25 mg/kg 3 to 4 times/day PO or 10 mg/kg 3 to 4 times/day IV.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Desmopressin: 0.3mcg/kg SC or IV. Repeated every 8 to 12 hours if needed.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eIntermediate and severe bleeding: Increase FVIII activity level\u003c/em\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e- Concentrated factor VIII: 20UI/kg every 1 Bethesda unit of inhibitor plus 40 UI/kg/day or 100-200UI/kg/day, IV.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- Desmopressin: 0.3mcg/kg, SC or IV.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eInhibitor titer\u0026thinsp;\u0026gt;\u0026thinsp;5 BU or no response with rFVIII\u003c/p\u003e \u003cp\u003eFactor VIII bypassing agents:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e- APCC: bolus injection of 50\u0026ndash;100 UI/kg/day repeated every 8 to 12 hours until hemostasis is achieved, up to a maximum of 200 U/kg per day; or\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e- VIIa: bolus injection of 90\u0026ndash;120 mcg/kg, repeated every 2 to 3 hours until hemostasis is achieved; or one dose only 270 mcg/kg, if still hemorrhage, repeated after 4 to 6 hours with dose of 90 mcg/kg.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eCombine with Tranexamic acid at dose of 15\u0026ndash;25 mg/kg every 2\u0026ndash;3 times/day, do not combine with APCC because of the risk of thrombosis.\u003c/p\u003e\n\u003ch3\u003eInhibitor eradication\u003c/h3\u003e\n\u003cp\u003eAdminister immunosuppressive therapy as soon as possible after diagnosis.\u003c/p\u003e \u003cp\u003e- If FVIII activity level\u0026thinsp;\u0026ge;\u0026thinsp;1% and inhibitor titer\u0026thinsp;\u0026le;\u0026thinsp;20 BU:\u003c/p\u003e \u003cp\u003e+ First-line: Methylprednisolon or Prednisolon 1mg/kg/day alone for 3\u0026ndash;4 weeks.\u003c/p\u003e \u003cp\u003e+ Second line: if no response, add cyclophosphamid at a dose of 1.5\u0026ndash;2mg/kg/day PO for maximum 6 weeks; or Mycophenolate mofetil at a dose of 1g/day for 1 week, after followed by 2g/day; or Rituximab 375mg/m\u003csup\u003e2\u003c/sup\u003e weekly for a maximum of 4 cycles.\u003c/p\u003e \u003cp\u003e- If FVIII activity level\u0026thinsp;\u0026lt;\u0026thinsp;1% or inhibitor titer\u0026thinsp;\u0026gt;\u0026thinsp;20 BU:\u003c/p\u003e \u003cp\u003e+ First-line: combining corticoid and cyclophosphamid or rituximab for 3\u0026ndash;4 weeks.\u003c/p\u003e \u003cp\u003e+ Second line: If no response, add cyclophosphamid or rituximab whichever was not used during first-line therapy.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 29 patients were entered into the study between May 2019 and June 2023. The study comprised 15 male (51.7%) and 14 female (48.3%), resulting in a male:female ratio\u0026thinsp;=\u0026thinsp;1.1:1. The median age at diagnosis was 57.1\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6 years (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of sample research\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAll patient, n\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e29\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (51.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (48.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale:female ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.1:1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, range\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u0026ndash;82\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.1\u0026thinsp;\u0026plusmn;\u0026thinsp;16.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAll patients had at least one bleeding episode before being diagnosed with which 21/29 patients were an adverse event. The mean hemoglobin levels were 77.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.7 g/L. Median FVIII activity was 2 U/dL (0\u0026ndash;35). Median inhibitor titer was 30.9 BU (1.5\u0026ndash;1016.4) (Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory characteristics of AHA patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAHA initial characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBleeding as trigger for diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdverse event, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (72.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean hemoglobin level (g/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFVIII activity at diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (U/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange (U/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u0026ndash;35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLess than 1 U/dL, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;5 U/dL, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (58.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMore than 5 U/dL, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInhibitor titer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (BU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange (BU)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.5\u0026ndash;1016.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash; 5 BU, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (13.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt; 5 BU, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (86.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt; 20 BU, n(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (65.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe causes of bleeding were spontaneous (26/29 patients), postoperative (2/29 patients) and after injection (1/29 patient). The common sites of bleeding were muscular hematomas (20/29 patients), hematuria (7/29 patients), internal bleeding (3/29 patients) and cerebral hemorrhage (1 patient). The underlying disorders of AHA were idiopathic (22/29 patients), malignancy (4/29 patients) and SLE (3/29 patients) (Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of AHA patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCause of bleeding episodes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpontaneous, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26 (89.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInjection, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSite/type of bleeding\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMuscular hematomas, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20 (68.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematuria, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInternal bleeding, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (10.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebral hemorrhage, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUnderlying disorders\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIdiopathic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (75.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignancy (any type), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (13.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutoimmune disease (lupus), n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (10.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn terms of bleeding treatment, 12 patients received bypass agent included rFVIIa (9 patients) and aPCC (5 patients). The response rate was 91.7%. All patients received immunosuppressive therapy with corticosteroids alone (19/29 patients), corticosteroids combined with cyclophosphamide (8/29 patients), corticosteroids combined with Rituximab (1/29 patients), corticosteroids combined with MMF (1 patient) (Table \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Mean hospitalization period was 12.7 days (5\u0026ndash;33 days). 11/29 patients developed secondary infections. 3/29 patients perished in the hospital (Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment and outcome of AHA patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en, (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBypass agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (41.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003erFVIIa\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (31)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eaPCC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eResponse\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (91.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThromboembolic events\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppressive therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroids alone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (65.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroids plus cyclophosphamide\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (27.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroids plus Rituximab\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroids plus MMF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (10.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfectious complication\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (37.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatient's treatment costs\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRange\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient's treatment costs (VNĐ)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e447,130,790\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6,435,430\u0026ndash;1,570,965,483\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization time (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12,66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5\u0026ndash;33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eAHA is a rare disease with an incidence of only 1\u0026ndash;1.5 per million population per year(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). During the study period from May 2019 to June 2023, a total of 29 patients matching the criteria were included in the study with a mean age of 57.1 years. Although the youngest age recorded in the study was 16 years old, most patients in the study were middle-aged to older. This is consistent with studies around the world that describe the general characteristics of AHA patients with the average age of disease from 64 to 78 years old (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAcute severe hemorrhage often occurs and becomes the clinical feature of this disease, requiring the importance of early diagnosis and prompt treatment. In our series, all patients had onset of the disease with sudden bleeding, of which 21 out of 29 patients were severe at the time of diagnosis. Only 2 patients had bleeding after surgery and 1 had bleeding after injection. The rest of the patients had spontaneous bleeding. The majority of events were severe resulted in clinical acute anemia with mean Hb was 77.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.7 g/L. Unlike hereditary hemophilia A, joint hemorrhage is rare. In AHA, the most common hemorrhagic sites are skin hemorrhage, intramuscular hemorrhage, internal hemorrhage (\u0026gt;\u0026thinsp;50%), hematuria, peritoneal hemorrhage, and other less common sites (\u0026lt;\u0026thinsp;10%), cerebral hemorrhage is rare (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In our study, most of patients had muscular hematomas (68.9%), the less common was hematuria, internal bleeding and cerebral hemorrhage (Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDuring coagulation cascade, factor VIII acts as a cofactor of factor IX in the activation of factor X on the surface of activated platelets. Proteolysis converts the factor VIII structure from a1-A2-a2-B-a3-A3-C1-C2 into light and heavy chain heterodimers. AHA is caused by the autoantibodies against factor VIII, which is a protein, of the IgG group (mostly IgG1 and IgG4 class). These autoantibodies bind to A2, A3, or C2. A2 and A3 bind factor VIII to factors IXa and X, while C2 binds factor VIII to phospholipids and von Willebrand factor. Autoantibodies in AHA patients are not fixed to complement and therefore do not cause agglutination. These antibodies bind to the active site in a temperature and time dependent manner. However, they do not cause complete inhibition of factor VIII activity, so measuring factor VIII activity has little clinical benefit. In our study, median FVIII activity was 2 U/dL (0\u0026ndash;35). Median inhibitor titer was 30.9 BU (1.5\u0026ndash;1016.4). Large studies on AHA in the world with large sample sizes have lower median inhibitor titer, however, in terms of width, there are large differences between patients in the same study (Table \u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory Characteristics of Patients with Acquired Hemophilia A in Large Registry Studies\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOur study\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDelgado(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCollins(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEACH2(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBorg(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGTH-AH(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e234\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e172\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e501\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInhibitor titer, median (range)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.9 (1.5\u0026ndash;1016.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (0,9\u0026ndash;32000)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (4\u0026ndash;38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.8 (4.2\u0026ndash;42.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.1 (1\u0026ndash;2800)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19 (1\u0026ndash;1449)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe underlying conditions of AHA included autoimmune disorders (systemic lupus erythematosus\u0026hellip;), malignancy, pregnancy... However, approximately 50% of patients have AHA is not associated with any medical illnesses (idiopathic AHA) (Table \u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). In our study, the underlying disorders of AHA were idiopathic (22/29 patients), malignancy (4/29 patients) and SLE (3/29 patients).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnderlying disorder of AHA\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOur study\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eGreen (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDelgado (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCollins (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eKnoebl EACH2 (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eBorg (SACHA) (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eKessler (HTRS)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTiede (GTH)(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime study\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBefore 1981\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1985‒2002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2001\u0026ndash;2003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2003\u0026ndash;2009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2001\u0026ndash;2006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2000\u0026ndash;2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2010\u0026ndash;2013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eUnderlying disorder (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIdiopathic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e57.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e63.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e44.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e44.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignancy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e14.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAutoimmune\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e28.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-partum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.8\u003c/p\u003e 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colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e38.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe International consensus on AHA treatment guidelines was first published in 2009 and updated in 2020 to provide guidelines based on expert experience and research data (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The principles of treating AHA patients include managing and preventing bleeding, eradicating inhibitors, and treating underlying conditions. The bypassing agents are the ideal management of patients with a high titer of an inhibitor and have severe bleeding, most commonly rFVIIa and APCC. Our series had 12 patients who needed to be treated with bypass agents (41.1%) with the overall response rate of 91.7% in the first time treated with that. Since the sample size is not large enough, we have not been able to compare the differences between the two agents. In the EACH2 study, hemorrhages were controlled almost successfully with a high response rate of 91.8%, with no difference between rFVIIa (91.8%) and aPCC (93.3%) (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Neither rFVIIa nor aPCC has a follow-up test, so the frequency of administration and dose are based on improvements in clinical bleeding symptoms. The international consensus also gives clinical and subclinical indications for appropriate hemostasis and optimal intervals for evaluating bleeding control. Often, specialists require stabilization of hemoglobin levels, the absence of blood transfusions, improvement of clinical and visual hemorrhagic symptoms as appropriate signs of hemostasis. The major deleterious event associated with bypassing agents is thrombosis. Fortunately, the risk of thrombosis is quite low. In a multi-center study (EACH2) that recorded a thrombotic complication of 2.9% in patients using rFVIIa and 4.8% in patients using aPCC (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). In our study, we did not record any cases of thrombotic complications after using bypass agents.\u003c/p\u003e \u003cp\u003eThe goal of immunosuppressive therapy is to reduce the risk of bleeding by shortening the time to reach complete response. Auto-recover is seen in some patients who do not receive immunosuppressive treatment but whose outcomes are not predictable (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). According to current guidelines, immunosuppressive therapy is recommended for all patients diagnosed with AHA (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Many of the patients with AHA are elderly, and thus clinicians must carefully consider the toxicities of therapy when choosing a regimen. The first-line immunosuppressive therapy is corticosteroids at a dose of 1 mg/kg/day. A second agent (Rituximab 375 mg/m\u003csup\u003e2\u003c/sup\u003e per week or Cyclophosphamide 1\u0026ndash;2 mg/kg per day) is added to treat patients with loss of response to steroids alone. However, recent studies show that the rate of complete remission (CR) is higher when combining the drug (32% CR with steroids alone vs 67.7\u0026ndash;83.3% with combination therapy). The international consensus on AHA treatment in 2020 supports the addition of Rituximab or Cyclophosphamide to first-line treatment for patients with \u0026gt;\u0026thinsp;20 BU inhibitors. The choice between cyclophosphamide and Rituximab depends on the patient's comorbidity. And the elimination of inhibitors is effective with an average of 5\u0026ndash;6 weeks of immunosuppression (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). In our study, all patients started immunosuppressive therapy immediately after diagnosis. The use of the initial drug combination is based on the treatment guidelines of the Ministry of Health and the economic condition of the patient as well as the evaluation of the clinician at the time of diagnosis based on the symptoms and complications of the disease. In 29 patients, 19 patients received corticosteroids alone (65.5%), 8 patients received corticosteroids plus cyclophosphamide 8 (27.6), 1 patient received corticosteroids plus rituximab (3.4) and 1 patient received corticosteroids plus MMF (3.4%). One of the main drawbacks of our study was that we did not have enough data to adequately survey the IST response on all patients after treatment. With less data, we followed up with 4 out of 29 patients who had a complete response after IST. According to studies around the world, about 60\u0026ndash;80% of patients will respond to first-line immunotherapy (corticosteroids with or without Rituximab or cyclophosphamide). Relapses are not uncommon during corticosteroid withdrawal, which occurred about 15% of the time in a study in the Netherlands (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). After the complete cessation of immunotherapy, about 25% of patients relapse with a mean time of 14.7 weeks (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). So, clinicians should advise patients during immunosuppressive discontinuation on monitoring hemorrhagic markers. Some authors suggest monitoring blood counts, aPTT and/or activated factor VIII levels every 2 weeks during the discontinuation of prednisone and every month for at least 3\u0026ndash;6 months (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eLast but not least, the cost of treatment for AHA patients during severe life-threatening hemorrhages were huge. In our study, the mean cost of treatment was 447,130,790, the largest patient cost up to 1,570,965,483.0 VND. Much of the cost is due to the use of bypass agents. With an average hospital stay of 12.66 (5\u0026ndash;33 days), the complication rate is mostly 37.9% secondary infection, further aggravating the severity and cost of treatment.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eFrom our case series, AHA patients often have severe bleeding, high inhibitor titer, and bypassing agents needed. Although the success rate was high, the cost, hospitalization period, and secondary infection are considered disadvantageous factors. More data is required to find the proper treatment which balances benefits and risks.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eTung T. Tran, MD, PhD: wrote the main manuscript text Phuong-Thao T. Le, MD: collected, analyzed and processed dataAll authors reviewed the manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKnoebl P, Marco P, Baudo F, Collins P, Huth-K\u0026uuml;hne A, Nemes L, et al. Demographic and clinical data in acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2). J Thromb Haemost. 2012;10(4):622\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePishko AM, Doshi BS. Acquired Hemophilia A: Current Guidance and Experience from Clinical Practice. J Blood Med. 2022;13:255\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, et al. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation. Blood. 2007;109(5):1870\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSơn NT. Hemophilia A mắc phải. Quyết định số 1832/QĐ-BYT ng\u0026agrave;y 01/07/2022: Hướng dẫn chẩn đo\u0026aacute;n v\u0026agrave; điều trị một số bệnh l\u0026yacute; Huyết học. 2022. p. 93\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTiede A, Collins P, Knoebl P, Teitel J, Kessler C, Shima M, et al. International recommendations on the diagnosis and treatment of acquired hemophilia A. Haematologica. 2020;105(7):1791\u0026ndash;801.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWindyga J, Baran B, Odnoczko E, Buczma A, Drews K, Laudanski P, et al. Treatment guidelines for acquired hemophilia A. Ginekol Pol. 2019;90(6):353\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDelgado J, Jimenez-Yuste V, Hernandez-Navarro F, Villar A. Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol. 2003;121(1):21\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBorg JY, Guillet B, Le Cam-Duchez V, Goudemand J, L\u0026eacute;vesque H. Outcome of acquired haemophilia in France: the prospective SACHA (Surveillance des Auto antiCorps au cours de l'H\u0026eacute;mophilie Acquise) registry. Haemophilia. 2013;19(4):564\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTiede A, Klamroth R, Scharf RE, Trappe RU, Holstein K, Huth-K\u0026uuml;hne A, et al. Prognostic factors for remission of and survival in acquired hemophilia A (AHA): results from the GTH-AH 01/2010 study. Blood. 2015;125(7):1091\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGreen D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost. 1981;45(3):200\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBaudo F, Collins P, Huth-K\u0026uuml;hne A, L\u0026eacute;vesque H, Marco P, Nemes L, et al. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood. 2012;120(1):39\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKruse-Jarres R, Kempton CL, Baudo F, Collins PW, Knoebl P, Leissinger CA, et al. Acquired hemophilia A: Updated review of evidence and treatment guidance. Am J Hematol. 2017;92(7):695\u0026ndash;705.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchep SJ, van Dijk WEM, Beckers EAM, Meijer K, Coppens M, Eikenboom J, et al. Treatment of acquired hemophilia A, a balancing act: results from a 27-year Dutch cohort study. Am J Hematol. 2021;96(1):51\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Acquired hemophilia A, Rare Bleeding Disorders, bypassing agent","lastPublishedDoi":"10.21203/rs.3.rs-5857873/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5857873/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcquired hemophilia A (AHA) is a rare autoimmune disorder caused by autoantibodies to coagulation factor VIII. Patients with AHA often bleed spontaneously, severely, difficult to control, and have high treatment costs.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAims:\u003c/strong\u003eWe present a case series of AHA patients treated at the Hematology department in Cho Ray Hospital from May 2019 to June 2023.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis is a retrospective case series report of patients who were diagnosed with AHA. Demographic information, clinical, laboratory characteristics and treatment were described.\u003c/p\u003e\n\u003cp\u003eThis is a retrospective case series report of patients who were diagnosed with AHA. It describes demographic information, clinical and laboratory characteristics, and treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e29 patients (males, females) were included in the case series. Mean age was 57.1 ± 16.6 years. Median FVIII activity was 2 U/dL (0 – 35). Median inhibitor titer was 30.9 BU (1.5 – 1016.4). Mean hemoglobin levels were 77.5 ± 19.7 g/L. All patients had at least one bleeding episode before being diagnosed with which 21/29 patients were an adverse event. The causes of bleeding were spontaneous (26/29 patients), postoperative (2/29 patients) and after injection (1/29 patient). The common site of bleeding were muscular hematomas (20/29 patients), hematuria (7/29 patients), internal bleeding (3/29 patients) and cerebral hemorrhage (1 patient). The underlying disorders of AHA were idiopathic (22/29 patients), malignancy (4/29 patients) and SLE (3/29 patients). In terms of bleeding treatment, 12 patients received bypass agent including rFVIIa (9 patients) and aPCC (5 patients). The response rate was 91.7%. Thromboembolic events were 0%. All patients received immunosuppressive therapy with corticosteroids alone (19/29 patients), corticosteroids combined with cyclophosphamide (8/29 patients), corticosteroids combined with Rituximab (1/29 patients), and corticosteroids combined with MMF (1 patient). Mean hospitalization period was 12.7 days (5-33 days). 11/29 patients developed secondary infections. 3/29 patients perished in the hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eFrom our case series, AHA patients often have severe bleeding, high inhibitor titer, and bypassing agents needed. Although the success rate was high, the cost, hospitalization period, and secondary infection are considered disadvantageous factors. More data is required to find the proper treatment which balances benefits and risks.\u003c/p\u003e","manuscriptTitle":"Diagnosis and Management of Acquired Hemophilia A: A Clinical Analysis from Cho Ray Hospital’s Hematology Department","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-02-04 09:00:49","doi":"10.21203/rs.3.rs-5857873/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5c8826a1-cd7c-4f36-8a47-fa4e56e91f08","owner":[],"postedDate":"February 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-06T12:53:22+00:00","versionOfRecord":[],"versionCreatedAt":"2025-02-04 09:00:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5857873","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5857873","identity":"rs-5857873","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}