Acquired Hemophilia A Research Articles

Acquired Hemophilia A: A Narrative Review and Management Approach in the Emicizumab Era

Acquired Hemophilia A (AHA) is a rare bleeding disorder caused by inhibitory autoantibodies to factor VIII (FVIII). The goals of treatment are two-fold, namely immunosuppressive therapy (IST) to eradicate the inhibitor and hemostatic management to control bleeding. Emicizumab, a bispecific antibody that acts as a factor VIIIa (FVIIIa) mimetic, has seen growing use in AHA following its approval for congenital hemophilia A (cHA). This review provides an overview of the epidemiology, pathophysiology, diagnosis, and treatment of AHA. Registry, trial, and case series data are assimilated and summarized with an emphasis on a standardized approach that integrates the use of emicizumab. With recent registry data suggesting the need to focus on immunosuppression-related mortality in AHA, we provide treatment recommendations in an algorithmic format that have become the standard of care at our institution. These recommendations are intended to minimize hemostatic product usage and potential toxicity related to IST, while reducing morbidity and re-hospitalization rates for bleeding. The proposed treatment algorithm, which includes key interventions by phase of therapy, can be readily implemented at centers that have rapid access to plasma FVIII activity using a one-stage assay. A case is presented to illustrate the proposed diagnostic and management considerations.

The in vitro cross-reactivity and blood coagulation potential of recombinant porcine factor VIII in Japanese patients with acquired hemophilia A.

Recombinant porcine factor VIII (rpFVIII) is a hemostatic agent for acquired hemophilia A (AHA). Cross-reaction of auto-antibodies against rpFVIII has been reported, although no data are available in Japanese patients. This study investigated the cross-reactivity and coagulation potential of rpFVIII in plasma samples from Japanese patients with AHA. Cross-reactivity was calculated as the ratio of anti-porcine FVIII inhibitor titer (pFVIII-INH) to human FVIII inhibitor titer. Comprehensive coagulation potential was assessed by clot waveform analysis (CWA) and thrombin generation assay (TGA) in samples spiked with rpFVIII (equivalent to 200 U/kg). Nine of 16 plasma samples (56.3%) had positive pFVIII-INH, with a median cross-reactivity of 1.2%. FVIII activity (FVIII:C) was restored to > 100% in all samples upon spiking with rpFVIII, but was weakly correlated with pFVIII-INH. CWA parameters and most TGA parameters were restored to normal upon spiking with rpFVIII; correlation of these parameters with FVIII:C was similar to that observed in controls. Overall, cross-reactivity to rpFVIII in Japanese patients was similar to that reported in Caucasian patients. Our results suggest that an initial clinical dose of 200 U/kg rpFVIII could restore coagulation potential to normal, and that FVIII:C monitoring after rpFVIII administration may be more informative than pFVIII-INH before administration.

The Role of the Hemostasis and Thrombosis Unit in the Management of the Patients with Acquired Hemophilia.

Acquired hemophilia A (AHA) is a rare autoimmune disease characterised by the presence of autoantibodies against coagulation factor VIII (FVIII), leading to spontaneous haemorrhage in patients without a prior family or personal history of bleeding. This study describes the demographics, diagnosis, underlying disorders, bleeding characteristics, treatment, and outcomes of 41 AHA patients, along with specific case reports. Diagnosis and treatment occurred between 2005 and 2023. The median age at diagnosis was 67.8 years (range 15-93). Among the 41 patients, 10 (24%) were idiopathic, 4 (10%) were postpartum, 18 (44%) had autoimmune diseases, and 9 were diagnosed with cancer. Diagnostic delay exceeded 30 days in 15 out of the 41 cases (36.5%). A total of 38 out of the 41 (93%) patients presented with spontaneous bleeding, with mucocutaneous bleeding being the most common presentation (23/41, 56%). Four patients experienced postpartum bleeding. Clinical remission was achieved in 100% of patients, and no patient died. Haemostatic and Immunosuppressive therapy is essential in AHA, and it should be started as soon as possible in patients with bleeding. However, a significant delay in diagnosis was observed. The absence of mortality is likely attributable to the management of the disease within a specialised Haemostasis and Thrombosis Unit, which offers a clinical ward, a specialised laboratory, and a dedicated ambulatory service. The Italian Society for the Study of Haemostasis and Thrombosis (SISET) is working to secure recognition for this essential role in every hospital.

A Tale of Two Cases: Acquired Hemophilia A and/or Lupus Anticoagulant?

Abstract Distinguishing between acquired hemophilia A (AHA) and lupus anticoagulant (LA) is essential for effective clinical management. This can be challenging due to similarities in laboratory tests and potential interference between their diagnostic tests. Here we present two complex cases. Case 1 is a 69-year-old female with PNH presenting with a subdural hematoma. Prolonged aPTT with no correction on mixing raised clinical suspicion of AHA. Factor VIII activity was low (2%) across three dilutions in the factor assay. A Bethesda assay revealed a low factor VIII inhibitor (1%). LA was negative by DRVVT. Antiphospholipid antibodies (Cardiolipin and Beta-2-Glycoprotein 1) were also negative. Treatment with prednisone and intravenous immunoglobulin was initiated with presumptive diagnosis of AHA. Subsequent samples to check other factor levels uncovered low Factor IX as well. Higher dilutions in factor assays exhibited non-parallelism in Factor IX and VIII, suggesting a non-specific inhibitor. Chromogenic Factor VIII was within the normal range. Another LA test, Staclot-LA was positive. Overall, this case was consistent with LA rather than AHA. The initial ‘positive’ Bethesda assay was attributed to interference by LA. Case 2 is a 20-year-old female with no significant medical history who was admitted elsewhere for a complicated C-section with intraabdominal hemorrhage. She had prolonged aPTT and positive LA by platelet neutralization test there. Upon transfer, the initial assessment confirmed prolonged aPTT and a time-dependent inhibitor pattern in mixing studies. Factor studies revealed significantly diminished factor VIII activity (<1%) using both one-stage clotting and chromogenic assays. A strong factor VIII inhibitor was identified through chromogenic Bethesda assay (126 BU). Non-parallelism was observed in other factors (Factor IX, XI, XII). LA was negative by DRVVT but positive by Staclot-LA. Cardiolipin and beta2-glycoprotein-1 antibodies were negative. The diagnosis of AHA was evident. But is there concurrent LA present? Both Staclot-LA and platelet neutralization tests are PTT-based and susceptible to interference from factor VIII inhibitor. The patient underwent treatment, and factor VIII inhibitor disappeared in 3 months. Staclot-LA also turned negative, suggesting that the initially ‘positive’ LA test was likely a result of interference. In both cases, adopting a holistic approach to differentiate between AHA and LA is beneficial. Relying solely on individual tests may lead to false interpretations, as LA can inhibit FVIII activity assays and produce false positives in the Bethesda assay. It is advisable to include higher dilutions in factor assays and/or chromogenic assays to mitigate interference. The presence of factor VIII inhibitor can also result in false-positive LA results such as Staclot-LA assay. For more reliable results, DRVVT and antibody tests are preferable. If the aPTT-based assay is the sole positive LA test, the presence of LA is suggested when it occurs before and/or after the presence of a factor inhibitor.

Acute abdomen: an atypical presentation of acquired hemophilia

Acquired hemophilia is a rare but potentially life-threatening disorder characterized by the development of acquired hemophilia A, leading to bleeding complications. Spontaneous, mild-to-life-threatening bleeding in typically elderly individuals without a personal or family history of bleeding is the hallmark of acquired hemophilia A (AHA), a rare autoimmune bleeding illness caused by the formation of auto-antibodies against endogenous factor VIII (FVIII). This hallmark represents our present case, with no obvious history related to the bleeding issue. Prompt detection and treatment of bleeding are essential for the best outcomes. We present a case of a 66-year-old male who had acute-onset severe abdominal pain and with constipation for five days, associated with nausea and loss of appetite. On physical examination, the patient appeared pale, and abdominal examination revealed diffuse tenderness with guarding. Initial evaluation revealed tachycardia and hypotension. Initial abdomen X-rays revealed features suggestive of small bowel obstruction. The patient was stabilized with intravenous fluids, referred to a surgical team, and admitted to the acute bed in the general ward for further management. Keywords: Acquired Hemophilia; Auto-Antibodies; Factor VIII; Intraabdominal Bleeding Citation: Hehsan MR. Acute abdomen: an atypical presentation of acquired hemophilia. Anaesth. pain intensive care 2024;28(5):974−976; DOI: 10.35975/apic.v28i5.2556 Received: March 19, 2024; Reviewed & Accepted: September 08, 2024

Efficacy and safety of recombinant porcine factor VIII in Japanese patients with acquired hemophilia A

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies inhibiting human factor VIII (hFVIII). This phase II/III open-label study evaluated the safety and efficacy of recombinant porcine factor VIII (rpFVIII, susoctocog alfa) in adults with AHA and severe bleeding episodes in Japan (NCT04580407). The initial rpFVIII dose was 200 U/kg, with subsequent doses based on clinical measures including plasma FVIII activity. The primary efficacy endpoint was the proportion of severe bleeding episodes with a positive response to rpFVIII therapy 24 h after treatment initiation. Five patients were eligible for, and completed, rpFVIII treatment (age group: 60s–80s; median hFVIII inhibitor: 52 BU/mL; porcine FVIII [pFVIII] inhibitor: 3/5 patients). The median (range) total dose/patient was 548.4 (198–1803) U/kg with a median 3.0 infusions/patient. All patients responded positively to rpFVIII therapy at 24 h regardless of baseline pFVIII inhibitor status. rpFVIII treatment was well tolerated with no adverse events of special interest such as thromboembolic events or de novo pFVIII inhibitors. This study supports the use of rpFVIII as a novel therapy in the clinical management of patients with AHA in Japan. rpFVIII was approved for treating bleeding episodes in adults with AHA in Japan in 2024.

Severe acquired hemophilia A associated with COVID-19 vaccination: A case report and literature review.

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by an antibody that inhibits coagulation factor VIII activity. More than half of patients with AHA cannot identify underlying disorders. The remaining patients are associated with malignancies, autoimmune diseases, skin diseases, infections, and medications. Here, we present a case of 56-year-old Korean man with underlying hypertension, dyslipidemia, and diabetes mellitus who developed AHA following the second dose of BNT162b2 COVID-19 vaccination. He presented with a large 20 × 30 cm-sized hematoma along the psoas muscle and intracranial hemorrhage, necessitating intensive care with mechanical ventilation and continuous renal replacement therapy. Laboratory testing demonstrated that activated partial thromboplastin time and prothrombin times were 74.7 seconds (normal range 29-43 seconds) and 17.2 seconds (normal range 12.5-14.7 seconds), respectively. Laboratory tests confirmed AHA with undetectable factor VIII activity (<1.5%) and a positive factor VIII antibody with a titer of 8.49 Bethesda units/mL. Recombinant factor VIIa (NovoSeven®) was administered every 2 hours to control the bleeding, alongside immunosuppression with methylprednisolone 1 mg/kg daily and cyclophosphamide 2 mg/kg daily to eliminate the autoantibody. Despite the treatments, the patient developed sepsis and succumbed 14 weeks after admission. This rare case underscores the importance of monitoring for AHA following COVID-19 vaccination. Although the benefits outweigh the risks of vaccination, AHA should be considered in the differential diagnosis of unusual bleeding following the vaccinations. Early diagnosis and management before severe bleeding are critical for successfully controlling life-threatening bleeding.

Acquired hemophilia successfully treated with recombinant factor VIIa: A case report

Acquired Hemophilia A (AHA) is a disorder characterized by the impaired clotting ability of the blood, primarily resulting from a deficiency in factor VIII, a crucial clotting protein. It is an infrequent disorder that affects a minority of individuals. This condition can pose a life-threatening risk, with reported mortality rates reaching as high as 22%. The diagnosis of AHA is challenging owing to its non-specific presentation and low prevalence rate. The primary objectives of treatment for AHA encompass the cessation and prevention of bleeding episodes, eradication of the inhibitor, and management of the underlying disease in secondary cases. This case report summarizes the successful treatment of a patient with AHA and major bleeding with the repeated use of prednisolone, recombinant factor VIIa, and rituximab.

Acquired Hemophilia A (AHA): A Rare Bleeding Disorder In a Tertiary Care Hospital In Dhaka, Bangladesh

Acquired Hemophilia A (AHA) is a rare bleeding disorder. This results from autoantibodies to factor VIII (FVIII) that neutralizes the ability of factor VIII. This causes potentially severe bleeding episodes that carries a high risk of morbidity and mortality. Acquired Hemophilia usually occurs over 60 years of age or in postpartum period and associated with other autoimmune conditions. The diagnosis should be suspected when patients with new onset of bleeding without prior personal or family history of bleeding. The hallmark of this condition is mucocutaneous bleeding leading to ecchymosis, malena, hematoma, hematuria and spontaneous oozing from wounds. Management should uphold both hemostatic therapies to minimize bleeding and immune modulation strategies to re-establish immune tolerance to factor VIII. Here we present an older male case of such Acquired Hemophilia A without history of previous anticoagulant therapy as well as family history or personal history of bleeding episodes. The patient has got hemiarthroplasty with prosthesis with bone cementing due to fracture neck of femur. After 10th post-operative day he was diagnosed with clot retention in catheter in-situ and oozing from wound site after 12th post-operative day. His laboratory reports showed prolongation of Prothrombin Time (PT) and Activated Partial Prothrombin Time (APTT). His factor VIII was very low level and factor VIII inhibitor showed the time depended inhibitor presence. Thus diagnosed as Acquired Hemophilia A (AHA), the rare case in Bangladesh. He was managed with medications that resulted in normalization of factor VIII level. J MEDICINE 2024; 25: 173-175

Retrospective study of the clinical manifestations and efficacy of immunotherapy for patients with acquired hemophilia A.

Raising awareness of acquired hemophilia A (AHA) and early diagnosis is critical to reduce the associated mortality rate. We aimed to characterize acquired hemophilia in Chinese patients and evaluate the effectiveness of immunotherapy. The clinical characteristics, laboratory test data, therapeutic approaches, and outcomes of 20 patients with AHA who were admitted to Xi'an Central Hospital between January 2012 and December 2020 were retrospectively studied. Nine of the patients (45%) were treated by single glucocorticoid administration; three (15%) with cyclophosphamide (CP) in combination with a glucocorticoid; four individuals (20%) received a combination therapy of rituximab with CP and glucocorticoid or rituximab with CP, vincristine, and a glucocorticoid; three (15%) by injection of human immunoglobulin in combination with a glucocorticoid; and one (5%) with CP alone. Six patients (30%) achieved total remission and 11 (55%) partial remission (PR), but three (15%) did not enter remission, indicating an objective response rate of 85%. Combination therapy with rituximab or intravenous human immunoglobulin achieves superior results in some patients with AHA. Immunosuppression and the administration of coagulation factors can rapidly control the disease and are efficacious, but >50% of patients only achieved PR. These findings suggest that the complete elimination of inhibitors requires prolonged immunosuppression therapy.

Acquired haemophilia A in Finland: A nationwide study of incidence, treatment and outcomes.

Acquired haemophilia A (AHA) is a bleeding disorder caused by autoantibody development against factor VIII (FVIII). Studies on AHA have mainly focused on patients treated at specialist centres. To determine the incidence, clinical characteristics and outcomes of AHA in an unselected population-based patient cohort from Finland. This retrospective observational cohort comprised all cases diagnosed with AHA in Finland between 2006 and 2019. Patients were identified by the two central laboratories performing FVIII antibody testing in Finland, the Finnish Red Cross Blood Service and HUSLAB. Clinical details were collected from all hospitals and healthcare units where patients were treated. This study was performed in conjunction with the AHA in the Nordics study. The median incidence of AHA was 0.65 per million per year (range 0.19-1.27). Fifty-five patients were identified, with a median age of 76 years and an even sex ratio (51% women). When diagnosed, all had bleeding symptoms with severe bleeds in 92%. First-line immunosuppressive treatment regimens included steroid monotherapy in 31% of cases, steroids and a cytotoxic agent in 51% and a rituximab-based regimen in 16%. Clinical remission was achieved in 71% of cases, and 15% had relapses. Mortality was 13% for bleeds and 9% for treatment-related infections. Overall survival was 64% for 1 year and 56% for 2 years after diagnosis. In a nationwide population-based cohort study, we discovered a lower incidence of AHA than previously reported. Mortality among patients with AHA was high, calling for the consideration of updated treatment strategies.

Acquired Hemophilia A after SARS-CoV-2 Immunization: A Narrative Review of a Rare Side Effect.

Acquired hemophilia A (AHA) is a rare bleeding disorder (1.4 per million inhabitants per year) caused by neutralizing antibodies against factor VIII. Although uncommon, these autoantibodies can cause a high rate of morbidity and mortality. Several conditions are linked with AHA; based on an EACH2 study, 3.8% of AHA could be connected to infection. In the last four years, most humans have contracted the SARS-CoV-2 infection or have been vaccinated against it. Whether or not COVID-19 immunization might induce AHA remains controversial. This review aims to evaluate the evidence about this possible association. Overall, 18 manuscripts (2 case series and 16 case reports) were included. The anti-SARS-CoV-2 vaccination, as also happens with other vaccines, may stimulate an autoimmune response. However, older individuals with various comorbidities are both at risk of developing AHA and of COVID-19-related morbidity and mortality. Therefore, the COVID-19 vaccine must always be administered because the benefits still outweigh the risks. Yet, we should consider the rare possibility that the activation of an immunological response through vaccination may result in AHA. Detailed registries and prospective studies would be necessary to analyze this post-vaccine acquired bleeding disorder, looking for possible markers and underlying risk factors for developing the disease in association with vaccination.

First-line immunosuppressive therapies for acquired hemophilia A: A 25-year cohort experience and network meta-analysis

Acquired hemophilia A (AHA) presents a significant bleeding risk. Management involves bleeding control and immunosuppressive therapy (IST) to eliminate inhibitors. This study, encompassing a retrospective cohort of 76 newly diagnosed AHA patients (1997–2022), evaluated IST outcomes such as complete remission (CR), relapse, and mortality rates, alongside influencing factors. Supplementing these findings, a systematic review and network meta-analysis compared CR and relapse rates across ISTs, sourcing from Embase, Scopus, and ScienceDirect up to November 2023. In our cohort, demarcated by a 20 Bethesda-unit titer threshold, cyclophosphamide plus prednisolone (CP; n = 64) was the predominant initial IST. Lower inhibitor levels significantly correlated with higher CR rates (86.8 % vs 62.2 %; P = .014) and showed an odds ratio of 0.26 for CR (P = .021). Median relapse-free survival (RFS) extended to 37.13 months, significantly enhanced by CP (hazard ratio, 0.24; 95 % confidence interval, 0.10–0.60; P = .002). Our network meta-analysis, including 1476 CR and 636 relapse patients, indicated CP and rituximab-based ISTs significantly outperformed steroid monotherapy in terms of CR and lower relapse rates (risk differences of 0.15 and −0.13/−0.15, respectively; P < .05), without significant differences between CP and rituximab. Moreover, adding rituximab to the front-line treatment did not produce superior outcomes compared to the CP regimen alone, positioning CP as a viable first-line choice, particularly where rituximab is less accessible. The consideration of IST toxicity remains critical in treatment decisions.

ПРИОБРЕТЕННАЯ ГЕМОФИЛИЯ А В РЕАЛИЯХ СОВРЕМЕННОЙ МЕДИЦИНЫ: ОПЫТ КЛИНИЧЕСКОЙ ПРАКТИКИ

Abstract. Introduction. Acquired hemophilia A is a rare form of severe coagulopathy with an autoimmune mechanism of development. It occurs due to the formation of circulating inhibitory factor VIII (FVIII) antibodies, which leads to impaired activation of factor X and the occurrence of spontaneous bleeding in patients without previous hemostasis system pathology. In about a half of the cases, FVIII autoantibodies appear in patients without any comorbidities. It should be noted that the average age of patients was 74 years at the time of diagnosis. However, the occurrence of the disease in young women is rare and may be associated with pregnancy and childbirth. Given the rarity of this disease, the management of these patients is a challenging clinical problem. Aim. To describe a clinical case of diagnosis and treatment of a patient with the inhibitor form of acquired hemophilia A (AHA). Materials and Methods. A 38–year–old female patient had acute hemorrhagic syndrome of the hematoma type, manifested by large hematomas in different areas of the body. During the patient’s stay in the hospital, standard lab tests were made, the test results were evaluated over time, and instrumental diagnostics was performed. Results and Discussion. The typical hematoma type of bleeding detected during diagnosing, prolongation of coagulation parameters, presence of factor VIII inhibitor (605 BU), and a decrease in factor VIII level down to 0.5%) verified the AHA diagnosis. Methods of substitution, immunosuppressive therapy, and monoclonal antibodies were successfully used to treat AHA in this patient. The patient is followed up by a hematologist at the place of residence. Hematomas did not recur. Conclusions. This clinical observation demonstrates the peculiarities of the course, diagnostic algorithm, and management of patients with AHA without any concomitant pathology, with a history of only prolonged postpartum uterine bleeding, and with no autoimmune or malignant diseases.

Extensive ecchymosis and retroperitoneal hemorrhage due to acquired hemophilia-A following influenza vaccination: A case report.

Acquired hemophilia-A (AHA) is a rare but potentially life-threatening impaired coagulation disorder characterized by the development of autoantibodies against clotting factor VIII. Only a few case reports have been experienced with influenza vaccine-triggered AHA. Here, we report a case of severe hemorrhagic disorder due to AHA following influenza vaccine, which was successfully treated. The patient presented to the emergency department because of several severe, progressively worsening bruises after receiving the influenza vaccination. Consequently, the patient required intubation due to nasal-oral bleeding, which compromised the airway, and retroperitoneal hemorrhage with shock also developed. AHA was confirmed through a coagulation factor assay, including coagulation activity and antibody testing, which is possibly triggered by influenza vaccination. Low-dose cyclophosphamide and hydrocortisone were prescribed until activated partial thromboplastin time showed normal levels. Coagulation factor VIIa was administered, and aggressive blood transfusion was carried out concurrently to address the blood loss. The upper airway bleeding subsided and bleeding tendencies had been corrected to normal. The patient was smoothly weaned from the ventilator and recovered from critical illness. She was then discharged on the 19th day. The activated partial thromboplastin time mixing test can be performed immediately to establish the initial differential diagnosis and treatment plan for severe coagulopathy. AHA may be triggered by vaccination, with the hypothesis of activation of autoantibodies and molecular mimicry; this mechanism should be further studied.

Genetics and Epigenetics in Acquired Hemophilia A: From Bench to Bedside.

Acquired hemophilia A (AHA) is a bleeding disorder characterized by the immunological inhibition of factor VIII (FVIII) of the hemostatic pathway leading to hemorrhagic events. Different domains of FVIII are the target of autoantibodies (mainly immunoglobulin (Ig) G) leading to the deficiency of FVIII. Several factors have been associated with the activation of the auto-immunity towards FVIII. Emerging evidence implicates CD4+ T cell activation in mediating this autoimmune response, with their involvement like that observed in congenital hemophilia A. Several genes such as HLA II DRB*16, DQB1*0502, and CTLA-4 + 49 are responsible for the pathogenesis of AHA. Epigenetic modifications and mainly long-coding RNAS (lncRNAs) are potentially contributing to the pathogenesis of AHA. The treatment approach of AHA includes the management of acute bleeding events and the administration of immunosuppressive medications. This review aimed to summarize the published data on the genetics and epigenetics of AHA. The severity and the mortality of this disease are creating an emerging need for further research in the field of the genetics and epigenetics of acquired hemorrhagic disorder.

Acquired hemophilia A in a case of purple urine bag syndrome

The rare hemorrhagic disorder known as acquired hemophilia A (AHA) is brought on by the spontaneous development of autoantibodies against coagulation factor VIII (FVIII). It may be secondary to autoimmune diseases or cancers, or it may be idiopathic. Less than 10% of cases may have an infection as a secondary cause. We present the case of a 90-year-old anemic woman who was admitted to the hospital. She contracted a urinary tract infection (UTI) while in the hospital, and her urine took on a distinct purple hue. She had poor hemorrhagic manifestations and a prolonged partial thromboplastin time. After ruling out autoimmune and neoplastic causes, we diagnosed AHA as a result of a UTI caused by Enterococcus faecalis.

A rare case of acquired hemophilia A

Acquired hemophilia A (AHA) is a rare bleeding disorder characterized by IgG autoantibodies directed against circulating coagulation factor (F) VIII neutralizing its coagulant function. The usual clinical presentation of AHA is spontaneous or provoked bleeding in a person with a negative personal or family history of a coagulopathy and can lead life threatening bleeding especially in older patients. Here we report a case of 54-year-old male patient presenting with blood and passage of clots in urine. He was treated with recombinant factor VII and VIII with steroid as eradication therapy. Underlying cause remained unclear in this case.

Innovative Therapies for Acquired Hemophilia A.

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder which can be life-threatening. AHA is due to autoantibodies against coagulation factor VIII. Disease onset may be idiopathic (approximately half of the cases) or triggered by autoimmune disorders, cancers, drugs, infections, or pregnancy. Besides treating the underlying disorder, specific AHA treatments include management of bleeding and inhibitor eradication. Various first-line and second-line hemostatic and immunosuppressive agents are currently available for the management of AHA. Recently, the hemostatic drug emicizumab and the immunosuppressive drug rituximab have been the object of intense research from investigators as innovative promising therapies for AHA. This narrative review will be focused on the current status of the clinical use of these two off-label therapeutic agents in AHA.

Case Report: Acquired hemophilia A following COVID-19 vaccine

Background: In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified and has subsequently been responsible for immense morbidity and mortality. This resulted in the development of vaccines in record time, potentially posing safety issues. Several cases of acquired hemophilia A (AHA) following coronavirus disease 2019 (COVID-19) vaccines have been described in the literature. AHA is a rare autoimmune disease due to the production of IgG autoantibodies to coagulation FVIII that burdens high morbidity and mortality. It is presumed mainly on identifying an increased activated partial thromboplastin time (aPTT), even without bleeding and is confirmed by determining a FVIII inhibitor. To the best of our knowledge, this is the first report of AHA after inactivated virus COVID-19 treated with low dose rituximab (RTX). Lower RTX doses may lead to shorter infusion duration, lower risk of adverse events and lower costs. Case presentation: We report a case of AHA occurring in a 69-year-old man 60 days after an inactivated Sinovac-coronavac COVID-19 vaccine. Diagnosis of AHA was based on clinical presentation and confirmed with prolonged activated partial thromboplastin time, Factor VIII deficiency and the presence of an FVIII inhibitor. Follow-up showed a significant clinical and biological improvement, aPTT was normalized as of 18 days of treatment with corticosteroids along with low dose rituximab. Conclusions: In the literature, the reported cases of AHA following COVID-19 vaccination occurred after Adenoviral Vector DNA- and SARS-CoV-2 mRNA-based COVID-19 vaccines. Here, AHA was presented following inactivated virus COVID-19 vaccine. AHA treated with low dose rituximab can limit occurrence of side effects and the cost of treatment.