Acquired Hemophilia A. Experience Of a Single Center

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4781-4781 ◽  
Author(s):  
Mauricio A Alzate ◽  
Susana S Meschengieser ◽  
Alicia Blanco ◽  
Silvia Grosso ◽  
María A Lazzari ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Initial Symptoms ◽  
Bleeding Episodes ◽  
The Mean ◽  
Inhibitor Titer

Introduction Acquired hemophilia A is a rare and serious autoimmune disease. Morbidity and mortality are associated with advanced age, comorbidities, toxicity of treatment and bleeding severity. Treatment goals are control of the bleeding and eradication of the inhibitor, while treating the underlying condition if it is present. Objective To describe the baseline characteristics of acquired hemophilia A patients and to assess the response to treatment. Patients and Methods Between November 1991 and April 2013, 27 patients were diagnosed with acquired hemophilia A (mean age 59, range 21-86; 18 women - 66%) in the Departamento de Hemostasia y Trombosis. Five patients were lost from follow-up. APTT mixing studies with normal plasma (1:1) and time-temperature dependent effect on the APTT were performed for a-FVIII diagnosis. Whenever possible, inhibitor activity was titrated by Bethesda method at diagnosis (BU/mL). Medical records were reviewed to evaluate the initial symptoms, underlying diseases, treatments and outcome. Results The mean follow-up was 86 weeks (range 1-640). Underlying etiologies included: idiopathic 70.4%, postpartum 14.8%, malignancy 11.1%, autoimmune disease 3.7%. All patients had bleeding at diagnosis. The most frequent sites of bleeding were: muscular 32%, soft tissue 18%, urinary tract 9%, gastrointestinal tract 6%; being from multiple sites in 9%. At diagnosis, the mean value for FVIII was 6% (range 1-40), and inhibitor titer 220 BU/mL (range 2.2-1173). Initial therapeutic scheme included glucocorticoids in 97% of the patients, 13 in monotherapy (mean age 53 years ± 19), 13 with cyclophosphamide (63 years ± 18) (p= ns), and human immunoglobulin in 1 patient. This last patient died after 1 week of diagnosis due to uncontrolled gastrointestinal bleeding (previous to the era of rVIIa). As a second-line therapy, rituximab was used in 3 patients. Sixty-three (63%) patients achieved complete response (CR) (inhibitor titer < 0.6 BU/mL without bleeding episodes), and 23% achieved partial response (PR) (reduction in inhibitor titer > 50% without bleeding episodes), without differences between monotherapy or combined. Overall, women responded more frequently than men (93.3% vs. 71.4%, p= ns). All patients that received rituximab achieved CR. Conclusions In this study, the overall response rate was higher than 80%. In most cases, the disease has a prolonged course like other autoimmune diseases, with remissions and relapses. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Diagnosis and Treatment of Acquired Hemophilia: One Single-Center Experience from PR. China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4250-4250
Author(s):  
Rong-Fu Zhou ◽  
Yueyi Xu ◽  
Wenjin Gao
Keyword(s):  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Coagulation Factor ◽  
Factor Vii ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Coagulation Factor Vii ◽  
Prolonged Aptt ◽  
Inhibitor Titer

Abstract Objective: To deepen the understanding of the clinical manifestations of acquired hemophilia A for timely and correctly treatment. Methods: The clinical data of the acquired hemophilia A patients diagnosed in the hospital from Jan 2006 to Mar 2021 were retrospectively analyzed, and the relevant literature was reviewed. Results: 17 patients with acquired hemophilia A, male: female =10: 7, median age 61 years (19 to 78 years), were diagnosed and treated in the hospital with the median time from the onset to diagnosis 21 days (2 days to 6 months). Six patients had comorbidity, including hepatitis B carrying, chronic myelomonocytic leukemia, diabetes, hypertension and positive autoantibodies, pemphigoid and gastric cancer, respectively. Other 11 patients were healthy before the onset. All patients had large large ecchymosis of skin, and one case was combined with hematuria, and one case with retroperitoneal hematoma. All patients had APTT extension (45s-144.7s) and the prolonged APTT could not be corrected with normal mixed plasma with and without incubation at 37℃ for 2 hours. FVIII activity was 1% - 8.9% and inhibitor titer 2 - 128 Bu/ml. All patients with bleeding were with prothrombin complex/recombinant activated coagulation factor VII, some of them with pd-coagulation factor FVIII preparations. Inhibitors were removed with prednisone acetate (1 case) + chemotherapy (1 case), prednisone acetate / + CTX (11 cases) + chemotherapy (1 case), prednisone acetate/prednisolone + mabthera (2 cases) + CTX (1 case), respectively. The removal time of inhibitor was from 8 days to 4 years. During the treatment process, two patients developed lower extremity venous thrombosis, and one patient was complicated with lung infection. Conclusion: Patients with unexplained bleeding and prolonged APTT should be conducted normal mixed plasma correction test, coagulation factor activity and inhibitor titer examination. After correctly diagnosis, bypass agents /coagulation factor VIII preparations should be given timely for hemostasis, protocol based on glucocorticoid + CTX/mabthera to remove the inhibitor and symptomatic treatment for patients with primary comorbidity disease at the same time. Disclosures No relevant conflicts of interest to declare.

Anti-FVIII Autoantibodies Share Similar Characteristics In Acquired Hemophilia A Patients With and Without An Associated Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1110-1110
Author(s):  
Joerg Kahle ◽  
Christoph Königs ◽  
Anja Naumann ◽  
Thomas Klingebiel ◽  
John F Healey ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Underlying Disease ◽  
Severe Bleeding ◽  
Bleeding Tendency ◽  
C2 Domain ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Fviii Inhibitor

Abstract Introduction Acquired hemophilia A (AHA) is an autoimmune disease caused by the development of inhibitory autoantibodies against factor VIII (FVIII) resulting in severe hemorrhages. Associated pathologies, such as autoimmune disease, malignancy and pregnancy are observed in approximately 50% of patients. Aim To elucidate the relationship between an underlying disease, the bleeding tendency and patients immunological profile the characteristics of anti-FVIII autoantibodies in AHA patients with (n=6) and without an underlying disease (n=9) were determined. Patients and Methods The median age of this cohort (n=15) was 71 years with two-thirds older than 70 years. Treatment parameters were analysed and patients were classified according to there bleeding tendency into a mild, moderate and severe phenotype. FVIII domain specificity of anti-FVIII autoantibodies was analysed in ELISA by binding to (i) FVIII fragments (heavy (HC) and light chain (LC), A2 and C2 domain) and (ii) single human domain hybrid human/porcine FVIII proteins. The amount of FVIII-specific IgGs was measured by ELISA and their relative contribution to the total amount of anti-FVIII IgG was calculated from standard curves for FVIII-specific IgG1, IgG2, IgG3, and IgG4. Results All but one patient were treated with bypassing agents including activated FVII, activated prothrombin complex concentrate or porcine FVIII. All patients received immunosuppressive treatments. 14/15 achieved initial complete remission with 6 patients experiencing another episode of inhibitors. Characteristics of anti-FVIII autoantibodies in AHA patients with or without an underlying disease were similar: FVIII-specific autoantibodies targeted primarily the FVIII LC with a dominance of epitopes located C2 domain compared to the C1 domain. FVIII-specific antibodies belonged to the subclasses IgG1, IgG2, and IgG4. The individual IgG subclass levels did not correlate with the total amount of anti-FVIII antibodies or inhibitory anti-FVIII antibodies in Bethesda units. IgG1 and 2 vs IgG4 levels did not correlate with bleeding tendency. Patients with a mild bleeding phenotype only recognized the C2 domain, whereas other patients had antibodies against C2 and or other domains. Although lower levels of FVIII activity (FVIII:C) were observed in disease-associated AHA patients with a median FVIII:C of 0.5% (range, 0-6%) compared to 1.5% (range, 0-10%) in idiopathic AHA patients, this difference was not statistically significant. FVIII:C levels and FVIII inhibitor titers at clinical presentation did not correlate to the severity of bleeds: the median FVIII:C level in patients who had strong bleeds was 0.5% (range, 0-10%), moderate bleeds 3.6% (range, 0-6%), and mild bleeds 1.2% (range, 1-6%). The FVIII inhibitor titer at presentation was similar in patients who had mild, moderate and severe bleeding tendency with a median of 35 BU/mL (range, 29-55 BU/mL), 49.5 BU/mL (range, 9-156 BU/mL), and 17.3 BU/mL (range, 2.2-614 BU/mL), respectively. Conclusion The presented data challenges the view from other small cohorts that differential immunological profiles exist between disease-associated and idiopathic AHA patients. Data on the influence of epitopes and IgG subclasses on outcome in AHA patients remains conflicting and needs further study. Disclosures: No relevant conflicts of interest to declare.

Low-Dose Combined Immunosuppression Results In Rapid Remission In Patients With Acquired Hemophilia A

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3589-3589 ◽  
Author(s):  
Andrea Várkonyi ◽  
Attila Szederjesi ◽  
János Dolgos ◽  
Péter Farkas ◽  
Júlia Galgóczi ◽  
...  
Keyword(s):  
Low Dose ◽  
Hemophilia A ◽  
Bleeding Control ◽  
Off Label Use ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Off Label ◽  
Bypassing Agents ◽  
Inhibitor Titer

Abstract Introduction Acquired hemophilia A (AHA) is a rare severe disorder caused by autoantibodies against FVIII resulting in significant morbidity and mortality up to 20 % in some studies. The two pillars of treatment include acute bleeding control, and immunosuppressive therapy which aims to stop the underlying autoimmune phenomenon. Although critical for long-term disease-free survival, there is currently no consensus for the best immunosuppressive regimen. Most authors use steroids first line, followed by cyclophosphamide and/or rituximab in steroid failures. However, upfront low-dose combined regimens offer the theoretical advantage of reduced steroid-exposure and toxicity as well as increased effectiveness. In the current retrospective analysis, we aim to review our institutional experience with such a regimen. Patients and Methods We identified 16 (7 males and 9 females) AHA patients newly diagnosed between October 2009 and June 2013; all treated with an identical regimen on an institutional protocol. Patient age varied between 53-86 (median 76,4) years. Mean initial inhibitor titer was 30.5 Bethesda units (BU; range 2 - >500). In 4 out of 16 patients (26,7 %) an underlying disease was identified, the remaining 12 cases were considered idiopathic. Low-dose combined immunosuppression consisted of the following regimen: 1000 mg cyclophosphamide on day 1 and 22, 40 mg dexamethasone on day 1, 8, 15 and 22, and 100 mg rituximab on day 1, 8, 15 and 22 (the regimen was termed CyDRi). Simultaneous use of bypassing agents was left to the discretion of the treating physician (8/16 patients, 50 %). All patients received at least 1 cycle of CyDRi. If complete remission (CR, defined as cessation of bleeding and an undetectable FVIII inhibitor in the Bethesda assay) was not achieved, the CyDRi therapy was repeated every 6 weeks until remission. Laboratory follow-up included CBC, routine chemistry and APTT (with a mixing study when prolonged), as well as FVIII levels and the Bethesda assay. Clinical monitoring varied according to the localization of bleeding. Results 50 % of patients presented with severe active bleeding symptoms, and they all received bypassing agents simultaneously with the CyDRi regimen. The remaining 8 patients had a recent history of bleeding but were not actively bleeding at the time of admission, and were given CyDRi without concurrent bypassing agents – none of them had a subsequent episode of bleeding (time to bleeding control = 0; Figure) Bleeding control was also rapidly achieved in the other patients with >90 % of patients free of bleeding within 3 weeks (Figure). CR was achieved in 15/16 patients (93,75 %). The time to CR was short with more than 75% of patients in CR by week 7 (Figure). Toxicity and side effects were infinitesimal compared to commonly used prolonged steroid therapies: One patient acquired pneumonia three weeks after discharge from the hospital, and two patients developed Clostridium difficile colitis during hospitalization. All three patients responded to antibiotic treatment. 8 of 16 patients (50 %) required more than one cycle of CyDRi to achieve a durable CR, either due to slow response or a laboratory relapse (6 and 2 patients, respectively). Two of the 8 patients required a third cycle of CyDRi (one for a very slow response, the other for a second relapse). CyDRi was equally effective in treating relapses. One patient died from a cause deemed unrelated to AHA (elderly patient with a femoral neck fracture). Her inhibitor titer was falling rapidly, but she died before achieving CR. Follow-up of our cohort is median 21 (range 2-45) months. Conclusion The CyDRi low-dose combined immunosuppression produced higher complete remission rates with a remarkably rapid cessation of bleeding and a significantly improved side-effect profile and mortality rate in this retrospective AHA cohort, compared to regimens previously described in the literature. A prospective randomized comparison seems warranted to confirm these results. Disclosures: Off Label Use: Cyclophosphamide, dexamethasone and rituximab are all off label use for the treatment of acquired hemophilia A.

Improved Prognosis of Acquired Hemophilia A: A 10-Year-Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4348-4348 ◽  
Author(s):  
Rudiger E. Scharf ◽  
Barbara Bomke ◽  
Holger Seidel ◽  
Roya Gheisari ◽  
Marie Antonia Scharf ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Respiratory Diseases ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Treatment Algorithm ◽  
Factor Vii ◽  
Laboratory Evaluation ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Life Threatening

Abstract Abstract 4348 Background: Acquired hemophilia A (AHA) is a rare but significant hemostatic disorder caused by inhibitory autoantibodies against coagulation factor VIII (FVIII:C). The annual incidence of AHA is low with about 1 to 4 cases per million individuals. However, the mortality rate due to severe hemorrhages and comorbidity is high reaching 22% in several series. In the past, only a few patients were reported in whom an association of AHA with respiratory disorders was observed. Patients, Methods, and Study Protocol: We have performed a monocenter study on 35 consecutive patients with AHA A who were referred for diagnosis and treatment to the Düsseldorf Hemophilia Comprehensive Care Center between March 2001 and June 2011. The cohort included 24 males (age: 44–86 years) and 11 females (age: 20–83 years). For laboratory evaluation, a standardized staged protocol of APTT, FVIII:C activity and concentration, mixing studies with patient and normal plasma, and quantitation of inhibitor titers (Nijmegen modification of the Bethesda assay) was used. Diagnostic work-up for any underlying disease was performed according to a standardized protocol of clinical examinations and imaging procedures (including X-ray examination of thorax, sonography of abdomen, retroperitoneum and thyreoidea and, whenever indicated, computerized tomography of thorax, abdomen, or pelvis). Therapy was performed according to a treatment algorithm consisting of (a) acute antihemorrhagic therapy (irrespective of residual FVIII:C activity and inhibitor titer), (b) immediate immunosuppression (individually tailored to the patients’ risks with regard to age and comorbidity), and, if life-threatening bleedings persisted, (c) inhibitor elimination by immunoadsorption or plasmapheresis, and (d) concomitant immunotolerance regimens. Predefined clinical endpoints were control of bleeding, eradication of the inhibitor, complete or partial remission (CR, PR), relapse, or early death (< 30 days). CR was defined as no inhibitor detectable, FVIII:C activity > 80%, and withdrawal of immunosuppressive therapy. Results: In 21 (60%) of the 35 patients with AHA, an underlying disorder was identified, including 9 patients with respiratory diseases (26%), 8 patients with autoimmune disorders (23%), 3 with malignancies, and one with postpartum state, while in 14 patients (40%) AHA remained idiopathic. Upon admission, 16 of the 35 patients presented with life-threatening hemorrhages. In 13 of these 16 patients, control of bleeding was achieved by high doses of recombinant activated factor VII (rFVIIa; 90–120 μ g/kg every 2–3 h), while 3 patients required combined FVIII bypassing agents (rFVIIa plus bolus injections of activated prothrombin complex concentrates, aPCC; 100 IU/kg every 8–12 h). In the other 19 patients, bleeding also subsided in response to rFVIIa. Concurrent immunosuppression with prednisone alone (2 mg/kg/day) was performed in 11 patients, while 24 patients received cyclophosphamide (2 mg/kg/day) sequentially in combination with prednisone. In 5 patients in whom this first-line immunosuppression failed, 4 doses of rituximab (375 mg/m2) were administered as second-line therapy. Of the 35 patients, 13 required extracorporeal inhibitor elimination procedures due to persisting life-threatening bleeds. Exchange plasmapheresis was performed in 4, daily large-volume immunoadsorption (Ig-Therasorb) for up to 4 weeks in 9 patients. In 3 of them, immune tolerance was concomitantly induced by exogenous FVIII (100 IU/kg/day). Of the 35 patients in total, 28 individuals achieved CR (80%), 3 had PR, one relapsed, and 3 died within 30 days (one of acute myocardial infarction while on antihemorrhagic treatment, one of sepsis while on immunosuppression due to active AHA, one of lung bleeding in assocociation with pre-existing pulmonary sarcoidosis). Conclusions: This monocenter study demonstrates that control of life-threatening bleeding, eradication of the inhibitor, and induction of immune tolerance to FVIII have clearly improved the clinical outcome of AHA. Our data also suggest a shift in underlying disorders associated with AHA, whereby, in comparison to published studies, a relative increase in the proportion of patients with respiratory diseases is observed. Large controlled multicenter studies are required to confirm these findings. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Treatment of Acquired Hemophilia a with Rituximab and Emicizumab

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 18-19
Author(s):  
Evan C. Chen ◽  
William J. Gibson ◽  
Paula Temoczko ◽  
Nathan T. Connell ◽  
Robert Handin ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Case Series ◽  
High Dose ◽  
Recurrent Bleeding ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Private Company ◽  
Fviii Inhibitor ◽  
Fviii Activity

Background Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies that inhibit coagulation factor VIII (FVIII). The disorder is understudied given its rarity and there are no randomized prospective trials to guide therapy. In practice, treatment involves attaining hemostasis and eliminating the FVIII inhibitor, typically with high-dose steroids (1 mg/kg daily) and either cyclophosphamide or rituximab. However, current approaches carry risk of significant adverse events and delayed or inadequate responses. Emicizumab is a bispecific antibody that targets coagulation factors IXa and X to recapitulate the function of endogenous FVIII. We present a case series of patients with acquired hemophilia A who were successfully treated with a regimen consisting of rituximab and emicizumab. Methods We identified patients &gt;18 years who were diagnosed with acquired hemophilia A and received treatment with rituximab and emicizumab at Brigham and Women's Hospital between 2019 and 2020. We performed a retrospective chart review. Data collected included the patients' clinical presentation, laboratory studies (including coagulation testing, FVIII activity, and FVIII inhibitor titer), and treatments received (including systemic therapies, recombinant factor VIIa [rFVIIa], red blood cell [RBC] transfusions, and vascular embolization). We recorded the time to normalization of the activated partial thromboplastin time (aPTT) and chromogenic FVIII activity following emicizumab and rituximab initiation, respectively. Activated prothrombin complex concentrate was avoided given the use of emicizumab. Results We identified 8 patients with acquired hemophilia A who received treatment with emicizumab and rituximab. The median patient age was 81 (range 47-93). All patients sought medical attention for extensive ecchymoses or bleeding and were found to have prolonged aPTT leading to FVIII inhibitor identification (Table 1). The median inhibitor titer was 18 Bethesda units (range 9.2-107.5). Patients concurrently received 4 weekly doses of rituximab 375mg/m2 and 4 weekly loading doses of emicizumab 3mg/kg. Patient (Pt) #1 continued emicizumab 3mg/kg every two weeks to complete three months of treatment. Pts #2, #3, and #8 received high-dose prednisone (1mg/kg) at the start of treatment for a range of 10-14 days. Pt #8 received 7 additional days of prednisone for an initial aPTT of 60.7 seconds before starting emicizumab and rituximab; she had no clinical response when treated with prednisone alone. Pts #2, #5, and #7 required vascular embolization. 7 patients (Pts #2 through #8) had aPTT retested within 1 week of starting emicizumab, and the aPTT for these patients normalized within 10 days of starting emicizumab (i.e. after only 1-2 doses; Figure 1). Except for Pt #5 who had recurrent hematuria from a persistent anatomic bladder defect that eventually required prostatic artery embolization, patients did not require rFVIIa or RBC transfusions for more than 7 days after starting emicizumab. Except for Pt #5 who required 28 doses of rFVIIa and 3 units of RBC transfusions after starting emicizumab, the median number of rFVIIa doses and RBC units given to the remaining 7 patients was zero (range 0-6 doses) and zero (range 0-4 units), respectively. Pts #2 and #3 had chromogenic FVIII levels obtained &gt;30 days after starting rituximab with improvement in FVIII activity to 29% (day 71) and 86% (day 91), respectively. During a median follow-up of 102 days, no patients experienced recurrent bleeding. However, Pt #3 exhibited a slowly increasing aPTT that reached 46.3 seconds on day 233 of follow-up without symptoms; further diagnostic testing is pending. Conclusion Our case series demonstrates that the combination of rituximab and emicizumab can be an effective and safe regimen for the treatment of acquired hemophilia A. No thrombotic events or thrombotic microangiopathy occurred. Treatment with weekly emicizumab led to aPTT normalization after 1-2 doses and facilitated hemostasis, as reflected by a median usage of zero rFVIIA doses and zero RBC transfusions after starting emicizumab when excluding one patient with hematuria from an anatomic defect. This compares favorably to historical reports. While no patient has had recurrent bleeding, additional chromogenic FVIII activity testing for patients is needed to confirm long-term normalization of FVIII activity. Disclosures Gibson: Ampressa therapeutics: Current equity holder in private company; nference: Consultancy, Current equity holder in private company; ImmPACT-Bio: Consultancy; Boston Clinical Research Institute: Consultancy. Parnes:Bayer: Consultancy; I-Mab: Consultancy; Sunovion: Consultancy; UniQure: Consultancy; Sigilon: Consultancy; Shire/Takeda: Consultancy, Research Funding; Genentech: Research Funding; Geron: Current equity holder in publicly-traded company. OffLabel Disclosure: Emicizumab is used off-label in our case series for the treatment of acquired hemophilia A.

scholarly journals Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry

Blood ◽  
2012 ◽  
Vol 120 (1) ◽  
pp. 39-46 ◽  
Author(s):  
Francesco Baudo ◽  
Peter Collins ◽  
Angela Huth-Kühne ◽  
Hervé Lévesque ◽  
Pascual Marco ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Hemostatic Agent ◽  
Symptomatic Therapy ◽  
Bleeding Control ◽  
First Line ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Acquired Haemophilia ◽  
Bleeding Episodes ◽  
Bypassing Agents

AbstractAcquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).

Acquired Factor VIII Inhibitors: Pathophysiology and Treatment

Hematology ◽  
2006 ◽  
Vol 2006 (1) ◽  
pp. 432-437 ◽  
Author(s):  
Alice D. Ma ◽  
Daniel Carrizosa
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Morbidity And Mortality ◽  
Prior History ◽  
Significant Morbidity ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Congenital Deficiency ◽  
History Of ◽  
Bleeding Episodes

Abstract Hemophilia A is classically caused by a congenital deficiency of factor VIII, but an acquired form due to inhibitors to factor VIII (FVIII) typically presents later in life. Patients who develop such acquired factor VIII inhibitors may present with catastrophic bleeding episodes, despite having no prior history of a bleeding disorder. Though the disorder is rare, it is known to cause significant morbidity and mortality. This review will focus on what is currently known about acquired hemophilia A, its pathogenesis, its associated etiologies, and its treatment.

scholarly journals Orihime Study: Real World Treatment Patterns and Clinical Outcomes of 338 Patients with Acquired Hemophilia a from a Japanese Health Claims Database

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1042-1042
Author(s):  
Yoshiyuki Ogawa ◽  
Kagehiro Amano ◽  
Yukari Matsuo-Tezuka ◽  
Norihiro Okada ◽  
Yoichi Murakami ◽  
...  
Keyword(s):  
Research Funding ◽  
Hemophilia A ◽  
Disease Diagnosis ◽  
Health Claims ◽  
Acquired Hemophilia A ◽  
Acquired Hemophilia ◽  
Claims Database ◽  
Chugai Pharmaceutical ◽  
Hemostatic Therapy ◽  
The Mean

Abstract Introduction: Acquired hemophilia A (AHA) is a rare disorder characterized by severe, spontaneous bleeding caused by autoantibodies against factor (F)VIII (inhibitors). It is known that onset of AHA is triggered by malignancy, autoimmune disease, dermatological disease, and pregnancy/delivery. As the standard therapy, immunosuppressive therapy (IST) should be started immediately to eliminate inhibitors and hemostatic therapy is also necessary in case of bleeding. Many patients require prolonged bed rest because of the bleeding risk; therefore, it is difficult to determine the best time to start rehabilitation. Additionally, the early deaths and high thrombotic rates are frequently reported in AHA. Since it is a rare disorder, the actual situation has not been fully clarified. This study was to describe the epidemiology and clinical practice of AHA in the real world using a large health claims database in Japan. Methods: This was a retrospective observational study using a health claims database provided by Medical Data Vision Co., Ltd. The data period was Apr. 2008-Mar. 2020. Patients who met all of the following criteria were included; patients with disease diagnosis of AHA; patients were hospitalized on the day of AHA diagnosis; and patients had immunosuppressants on/after the date of the first hospitalization. The first date of hospitalization was set as an Index date. Patients with disease diagnosis code of antiphospholipid syndrome, lupus anticoagulant, acquired factor XIII deficiency, acquired von Willebrand disease, or acquired factor V deficiency were excluded. Treatment/procedure patterns (IST, hemostatic therapy, and rehabilitation) and clinical outcome (Activities of Daily Living [ADL], death, and thromboembolism in the hospitalization) in AHA patients were investigated. Results: The study population of 338 patients (214 males: 124 females) was with the mean age of 75.7 (21-96) years. A total of 105 patients (pts) (31.1%) had concurrent diseases, including malignancy (61 pts, 18.0%), autoimmune diseases (40 pts, 11.8%), and dermatological diseases (18 pts, 5.3%). In bypassing agent use (153 pts, 45.3%), recombinant activated factor VII (rFVIIa) was the most frequently used (129 pts, 38.2%) followed by activated prothrombin complex concentrate (aPCC) (36 pts, 10.7%), and plasma-derived factor VIIa and factor X (FVIIa/FX) (14 pts, 4.1%). FVIII agent uses (8 pts) were very few. Median duration of treatment for bypassing agents ranged from 2.5 (FVIIa/FX) to 6.0 (aPCC) days. Steroids alone were used predominantly in the first line for immunosuppression (292 pts, 86.4 %) and oral prednisolone was the most frequently used. The category of rehabilitation most commonly implemented in AHA patients was disuse syndrome (104 pts, 30.8%) followed by locomotor (73 pts, 21.6%) and cerebrovascular (49 pts, 14.5%). Median time (days) from Index date to initiating rehabilitation was 16.5 for disuse syndrome, 23.0 for locomotor, 19.0 for cerebrovascular. In the total ADL scores (Barthel Index) in 196 patients with all 10 items, the proportions of patients with less than 70 points were high at both initial admission and final discharge (47.4% and 38.8%, respectively). The median number of times and length of hospitalization were 1.0 time and 62.0 days, respectively. Of evaluable population (328 pts), thromboembolism during hospitalization was recorded in 15 patients, by type of which disseminated intravascular coagulation (10 pts, 3.0%) was the most frequently recorded. Acute coronary syndrome (3 pts, 0.9%), pulmonary embolism and other (1 pt, 0.3%, each) were fewly recorded. The proportion of deaths during hospitalization was 18.6% (63 pts). Table 1 shows study result summary. Conclusions: This was the first study in a large AHA population using a health claims database in Japan. From an epidemiological point of view, the number of male patients was slightly larger and the mean age was slightly higher compared to the demographics in previous reports. The possible reason is regional variance or data source, whereas, the treatment patterns and the proportion of deaths during hospitalization are mostly aligned with the previous studies. Also this was the first report publishing the data on ADL and rehabilitation in AHA patients. The results showed that it took median 2-3 weeks to start rehabilitation. Further development of treatment strategies to enable early start of rehabilitation is awaited. Figure 1 Figure 1. Disclosures Ogawa: Chugai Pharmaceutical Co., Ltd.: Consultancy. Amano: Chugai Pharmaceutical Co., Ltd.: Consultancy, Speakers Bureau; KM Biologics Co., Ltd.: Research Funding, Speakers Bureau; Bioverativ Inc.: Speakers Bureau; Bayer AG: Speakers Bureau; Shire Plc: Speakers Bureau; Takeda Pharmaceutical Co., Ltd.: Speakers Bureau; Sanofi S.A.: Speakers Bureau; Novo Nordisk A/S: Speakers Bureau; CSL Behring: Speakers Bureau; Pfizer Inc.: Speakers Bureau; Japan Blood Products Organization: Speakers Bureau. Matsuo-Tezuka: Chugai Pharmaceutical Co., Ltd.: Current Employment. Okada: Chugai Pharmaceutical Co., Ltd.: Current Employment. Murakami: Chugai Pharmaceutical Co., Ltd.: Current Employment. Nakamura: Chugai Pharmaceutical Co., Ltd.: Current Employment. Yamaguchi-Suita: Chugai Pharmaceutical Co., Ltd: Current Employment. Nogami: Chugai Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda Pharmaceutical Co., Ltd.: Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding, Speakers Bureau; Novo Nordisk A/S: Honoraria, Research Funding, Speakers Bureau; Bayer AG: Honoraria, Research Funding, Speakers Bureau; Sanofi S.A.: Honoraria, Research Funding, Speakers Bureau; KM Biologics Co., Ltd.: Honoraria, Research Funding, Speakers Bureau. OffLabel Disclosure: Data on the uses of cyclophosphamide, cyclosporin A, and rituximab for acquired hemophilia may be included in the poster presentation. However, with regard to these drugs, treatments for other diseases may also be included because this study was conducted with a secondary use of a health claims database. Off-label drug use is explained in the poster.

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