Case Of Acquired Hemophilia A Research Articles

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.

Acquired Hemophilia A Diagnosed Based on Gross Hematuria: A Case Report and Literature Review

Acquired hemophilia A (AHA) is an acquired bleeding disorder caused by neutralizing antibodies (inhibitors) against Coagulation Factor VIII (FVIII:C), causing sudden hemorrhagic symptoms (i.e., subcutaneous bleeding, intramuscular bleeding, and hematuria). Herein, this study is aimed at presenting a case of AHA diagnosed based on hematuria and reviewing patients who were diagnosed with AHA due to hematuria. A 67‐year‐old woman was referred to Atsugi City Hospital with painless gross hematuria that began 4 weeks before presentation. Contrast‐enhanced computed tomography (eCT) revealed an approximately 2 cm mass in the right renal pelvis, and the patient’s activated partial thromboplastin time (APTT) was elevated (61.4 s). The day after the endoscopic biopsy, the patient was in shock due to a large retroperitoneal hematoma. Although her condition stabilized after intravenous radioembolization, she underwent emergency surgeries several times because of rebleeding within the next 3 weeks. At that time, APTT was more prolonged at 106.4 s, and the FVIII:C level was 2%. Mixing tests showed an upwardly convex curve after 2‐h incubation, indicating the presence of an inhibitor. Factor VIII inhibitor titer was ≥5.1 Bethesda unit (BU)/mL. A combined product of Plasma‐Derived Factors VIIa and X (pd‐FVIIa/FX), as second‐line hemostatic therapy, as well as cyclophosphamide (CYP), were administered after Recombinant Activated Factor VIIa (rFVIIa) had been ineffective. Following this, the Factor VIII inhibitor titer was undetectable, FVIII:C levels were restored, and APTT decreased to within the normal range. Gross hematuria was significantly alleviated. However, the patient died of cytomegalovirus and fungal infections due to prolonged immunosuppressive therapy. Although AHA diagnosed based on hematuria may have a better prognosis than others, there have been occasional cases with severe outcomes. APTT, detected upon initial hematological testing in patients with hematuria, may be a potential indicator of an existing AHA.

Differentiation of Acquired Hemophilia a from Lupus Anticoagulant Using Global Coagulation Assays and Magnesium-Dependent Activated Partial Thromboplastin Time Assay

CONCLUSION Rapid and reliable differentiation between bleeding and thrombotic tendency in cases with prolonged activated partial thromboplastin time (APTT) remains challenging in clinical practice, in particular, distinguishing cases positive for coagulation factor inhibitor or lupus anticoagulant (LA). To differentiate acquired hemophilia A (AHA) from LA using three global coagulation assays: rotational thromboelastometry (ROTEM), thrombin generation assay (TGA), and clot waveform analysis (CWA); also to validate the effectiveness of magnesium-dependent APTT (APTT-Mg) assay. This method uses APTT-Mg and normal APTT using Ca to screen for LA, and APTT-Mg/APTT ratio is smaller in LA. We included patients with prolonged APTT without congenital coagulation factor deficiency who were referred to our department between November 2019 and September 2021. APTT prolongation was defined as >35 s (normal range: 25-35 s) measured routinely with Coagpia APTT-N (Sekisui Medical). The AHA group had a confirmed diagnosis and underwent treatment of AHA. The LA group was divided into LA1 (possible LA) and LA2 (definite LA). LA1 was defined by any of the following conditions: (1) index of circulation anticoagulant ≥15 in the cross-mixing test performed with Coagpia APTT-N; (2) positive dilute Russell's viper venom time (DRVVT) phospholipid neutralization method using Gladipore LA (Medical & Biological Laboratories); (3) positive APTT phospholipid neutralization test using Hemosil SCT (Instrumentation Laboratory); (4) positive for anti-CL antibody; (5) positive for anti-CLβ2GPI antibody; or (6) positive for phosphatidylserine-dependent anti-PT antibody. LA2 was defined by index of circulation anticoagulant >12.4 in the cross-mixing test performed by Thrombocheck APTT-SLA (Sysmex Corporation), or item (2) or (3) above, in accordance with criteria of LA in the International Society of Thrombosis and Haemostasis. LA1 and LA2 did not overlap, because cases that did not meet the conditions of LA2 were treated as LA1, and global coagulation assays were performed in all LA cases. In the global coagulation assays, 12 healthy volunteer samples were tested and regarded as the normal goroup. For the APTT-Mg assay, equal volumes of 25 mmol MgCl 2 and 25 mmol CaCl 2 were used instead of the normally used CaCl 2, and Thrombocheck APTT-SLA was used to measure APTT-Mg, which was then divided by the normal APTT concentration measured with the same APTT reagent. Ten patients in the AHA, 12 in the LA1, and 32 in the LA2 groups were eligible. ROTEM showed that clotting time in the non-activated rotational thromboelastometry assay (NATEM) mode was >3600 s (minimum 1363 s) for AHA, 501 s (IQR: 430-632 s) for LA1, 533 s (IQR: 443-641 s) for LA2, and 500 s (IQR: 429-645 s) for the normal group. TGA showed that peak thrombin concentration was 16 nM (IQR: 13-29 nM) in the AHA group, 242 nM (IQR: 175-273 nM) in the LA1 group, 174 nM (IQR: 129-259 nM) in the LA2 group, and 190 nM (IQR: 125-288 nM) in the normal group. In the CWA, Ad|min1| was 2.1 (IQR: 1.7-3.2) in the AHA group, 8.7 (IQR: 8.0-9.5) in the LA1 group, 6.7 (IQR: 5.8-8.4) in the LA2 group, and 10.3 (IQR: 9.8-10.6) in the normal group. APTT-Mg/APTT was 1.23 (IQR: 1.18-1.29), 1.26 (IQR: 1.23-1.38), and 1.05 (IQR: 0.95-1.20) in the AHA, LA1, and LA2 groups, respectively. ROTEM, TGA, and CWA effectively differentiated between the LA1/2 and AHA groups. Clotting time in non-activated rotational thromboelastometry assay mode (ROTEM) and peak height (TGA) were better at distinguishing high-titer LA cases from LA-positive AHA cases. APTT-Mg/APTT could be suitable for distinguishing AHA from high-titer LA; however, it may not be useful for differentiating AHA from low-titer or suspected LA.

Comprehensive comparison of global coagulation assays to differentiate lupus anticoagulant from acquired hemophilia A in patients with prolonged APTT.

There is no established method for differentiating acquired hemophilia A (AHA) from lupus anticoagulant (LA) positivity because both present with prolonged activated partial thromboplastin time. We compared various parameters of rotational thromboelastometry (ROTEM), thrombin generation assay (TGA), and clot waveform analysis (CWA) in patients with AHA (n = 10) and LA (n = 44). Compared with AHA, possible (n = 12) and definite (n = 32) LA showed significantly shorter clotting time (CT) in NATEM mode of ROTEM (> 3600 vs. 501/533). In TGA, peak height was significantly lower in AHA (16 vs. 242/174nM). In CWA, CT was significantly longer (81 vs. 36/41s) and Ad|min1| was lower (2.1 vs. 8.7/6.7) in AHA. Notably, CT by NATEM and peak height in TGA completely discriminated between AHA and LA, whereas Ad|min1| did not discriminate between them in 4 cases of AHA and 1 of LA. Comparison of 3 patients with both AHA and LA against a patient with only LA and markedly low FVIII activity (3.5%) showed that both CT by NATEM and peak height of TGA precisely classified the former 3 cases as AHA and the latter 1 case as LA, whereas Ad|min1| classified all 4 cases as AHA. ROTEM and TGA can comparably distinguish between AHA and LA.

Acquired Postpartum Hemophilia A: About 3 Cases

Introduction: Acquired hemophilia A (AHA) is a rare but severe autoimmune disorder. It is caused by the acquisition of autoantibodies to factor VIII (FVIII). These post-partum autoantibodies account for 7-21% of all cases of AHA and most often develop after the first pregnancy. We report 3 new cases of postpartum-acquired hemophilia A. Observations: Three young women with no prior pathological history presented with a spontaneous and heterogeneous hemorrhagic syndrome, two cases of deep hematomas, and haematuria with ecchymosis in the 3rd patient. The diagnosis was made in all our patients based on plasma FVIII activity <50% and the presence of an FVIII inhibitor. Immunological tests and neoplastic research were negative in all our patients. Hemostatic treatment combined with corticosteroid therapy and immunosuppressive drugs were used for the 3 patients. Conclusion: AHA is a rare disease, and its diagnosis is often underestimated in our population. It is essential to make clinicians aware of this pathology and to be able to evoke it in young patients of childbearing age. A relapse is possible in future pregnancies, so long-term follow-up is recommended.

Cases of acquired hemophilia A following COVID-19 vaccines: Cogent safety signal or possible reporting/detection bias? Preliminary evidence from Tuscany, Italy.

Several case reports of acquired hemophilia A (AHA) following COVID-19 vaccines were recently published. A possible increased incidence of AHA during the COVID-19 vaccination campaign was also suggested. We aimed at generating evidence for the preliminary assessment of the association between AHA and COVID-19 vaccination through an ecological study in one Italian region, Tuscany. An ecological study was performed using the population-based administrative data source of Tuscany. Per each year between 2017 and 2021, we included patients aged 5+ and active into the database as of January 1. Temporal patterns of annual incidence of possible AHA cases and AHA-tested patients were respectively observed. The rates of possible AHA cases per AHA-tested patients were calculated in 2021 and 2017-2019, respectively (calendar year 2020 was excluded because non-representative of the pre-pandemic era). Age-sex standardization was applied. Poisson's 95% confidence intervals (95% CI) were estimated. Statically significant differences were defined as absence of 95% CI overlap. In 2021, standardized incidence of both possible AHA cases (5.6/million subjects/year; 95% CI = 3.4-8.7) and AHA-tested patients (60.7/1000 subjects/year; 95% CI = 60.4-60.9) showed the lowest point estimates, though only the latter was statistically different compared to previous calendar years. The standardized rate of possible AHA cases per AHA-tested patients was 9.2/100000 (95% CI = 5.6-14.3) in 2021 and 12.5/100000 (95% CI = 8.2-18.1) during 2017-2019. These preliminary findings do not support the hypothesis of an increased incidence of AHA cases during the COVID-19 vaccination campaign. However, in 2021, the still ongoing healthcare access restrictions might have contributed to the low incidence of AHA and laboratory tests observed. Therefore, large-scale multi-database studies are warranted.

Acquired hemophilia A following COVID-19 vaccine: a case report

BackgroundIn the literature, reported cases of Acquired hemophilia A (AHA) induced by COVID-19 vaccination occurred after Adenoviral Vector Deoxyribonucleic Acid (DNA)- and SARS-CoV-2 Messenger Ribonucleic acid (mRNA)-Based vaccines. Here, and to the best of our knowledge, we report the first case of AHA occurring after an inactivated Sinovac-coronavac COVID-19 vaccine.Case presentationA 69-year-old Tunisian male patient consulted for severe left leg pain limiting physical mobility due to a 5*6 cm large ecchymosis located at the left inner thigh, having spontaneously appeared 5 days prior consultation and without notion of trauma. The patient had no known personal medical history. He had received the second dose of CoronaVac-SinoVac vaccine 30 days prior to consultation. Further physical examination revealed the presence of two other ecchymoses: one at the inner face of the right forearm, starting at the wrist reaching the elbow and the other at the left flank of the abdomen. Diagnosis of AHA was based on clinical presentation and confirmed with prolonged a PTT, Factor VIII deficiency and the presence of an FVIII inhibitor. The patient was successfully treated with corticosteroids and low dose Rituximab.ConclusionClinicians should consider AHA in front of prolonged aPTT with or without spontaneous bleedings even after inactivated virus COVID-19.

Acquired hemophilia A (AHA) due to anti-SARS-CoV-2 vaccination: A systematic review.

Vaccination against SARS-CoV2 has been the largest vaccination campaign over the past two decades. The aim of this study is to qualitatively assess the reported cases of acquired hemophilia A (AHA) that developed after COVID-19 vaccination to further elaborate on incidence, presentation, treatment, and outcomes.We queried Medline (PubMed), Google Scholar, and Embase databases to find reported cases of AHA after COVID-19 vaccines. We found 14 studies (19 cases) for this descriptive analysis. Most patients were elderly (mean age 73 years) and males (n = 12) with multiple comorbidities. All cases developed after mRNA vaccines - BNT162b2 Pfizer-BioNTech (n= 13) and mRNA-1273 Moderna (n = 6). All except one patient were treated, with the most common therapy being a combination of steroids, immunosuppression, and rFVIII (n= 13). Two patients died due to acute respiratory distress, and gall bladder rupture with persistent bleeding, respectively. While evaluating a patient with bleeding diathesis after COVID-19 vaccination, AHA should be kept in the differential diagnosis. Given the low incidence, we believe that the benefit of vaccination still outweighs the risk of disease acquisition.

Acquired Hemophilia in an Elderly Patient with Non-Small Cell Lung Cancer: a Case Report

Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. We report here a case of AHA that occurred in the Department of Medicina D’Urgenza in Sant’Andrea Hospital in a patient with previous diagnosis of NSLC. The aim of this article is to allow a more comprehensive knowledge of AHA that both for the rarity and the poor literature is underdiagnosed; for all these reasons, it is important that different specialists, like emergency specialists, experts in internal medicine, hematologists, and oncologists, acquire a more complete knowledge of the clinical and laboratory features of this disease, allowing an early diagnosis crucial for the evolution of the coagulopathy.

Management of Acquired Hemophilia

Acquired hemophilia A (AHA) is a rare autoimmune condition characterized by spontaneous antibodies formation against coagulation factor VIII (FVIII). In the United Arab Emirates (UAE), the treatment paradigm of AHA varies, leading to heterogeneous patient outcomes. Because AHA cases often present to clinical practitioners with insufficient experience in the disease, diagnosis is sometimes delayed. This document aims to provide recommendations to clinical practitioners in the UAE to bridge the gap of heterogeneous practice in the clinical management of AHA. Structured literature searches in PubMed and Google Scholar with a three-stage Delphi method were conducted. Evidence suggests that prolonged activated partial thromboplastin time before surgery or coupled with acute or recent onset of bleeding is a hallmark of AHA. Treatment using bypassing agents is recommended in AHA patients with bleeding. Corticosteroids and rituximab with (out) a cytotoxic agent represent the first-line treatment in patients with FVIII: C <1 IU/dL. Second-line therapy involves agents not utilized in the first round of treatment. Thromboprophylaxis is recommended if FVIII: C has returned to normal levels. These recommendations are intended to improve the clinical practice and awareness of this disorder among hematologists and nonhematologists in the UAE and provide practical diagnosis and treatment advice.

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

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

Acquired hemophilia A following COVID-19 vaccination – The importance of prompt diagnosis: A case report

Acquired hemophilia A (AHA) is a rare coagulopathy characterized by hemorrhagic manifestations. It has been linked to various conditions, including autoimmune disorders, drugs, tumors, lymphoproliferative disorders, and infections. We present a case of AHA in a 71-year-old male patient with cutaneous hematoma occurring 8 days after vaccination for COVID-19. This report aims to highlight the risk of FVIII inhibitor development following an immune stimulus, thus improving our knowledge regarding possible vaccination-related adverse events. Furthermore, we underline how the potential risk of not recognizing disease manifestations promptly, together with specific coagulation alterations, could significantly affect the patient's outcome. Adequate management plans and the diffusion of shared guidelines are of fundamental importance in order to prevent the development of life-threatening complications and initiate appropriate treatment as soon as possible. Data AvailabilityAll data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

Examination of the effect of immunosuppressive therapy on acquired hemophilia A in elderly patients with bloodstream infections

Acquired hemophilia A (AHA) is an acquired autoantibody (inhibitor) against blood coagulation factor VIII (FVIII) that significantly reduces FVIII activity and causes a bleeding tendency. Immune acquired coagulation factor deficiency. The peak age of onset is in the 70s. In Japan, which has an aging society, the number of reports has recently been increasing, and it should be noted that AHA is a bleeding disease that can occur in the elderly. Examined 5 cases of AHA that were experienced in our hospital. The FVIII inhibitor level, APTT, underlying disease, treatment history, and outcome were retrospectively examined using medical records. The age of onset was 76-93 years. At the time of diagnosis, the Hb (mg/dL) value was 6.1-10.3, the APTT was 75.6-203.2 seconds, the FVIII inhibitor value (BU/mL) was 18-686, and the platelet count was within the normal range in all cases. Bleeding control was possible using a bypass hemostatic agent in 4 patients. All patients underwent immunosuppressive therapy. Two patients were discharged alive and 3 patients died. The cause of death was infectious disease in all cases. The total prednisolone-equivalent dose of the deceased patients was 1,240-3,206 mg; one patient was treated with cyclophosphamide and was treated with dexamethasone. Long-term immunosuppressive therapy is expected to increase the risk of infection in elderly patients. The risk assessment of AHA treatment-related bloodstream infections is insufficient, and it will be necessary to accumulate data and consider appropriate assessments and countermeasures.

Acquired Hemophilia A: A Rare Presentation with Buccal Bleeding: A Case Report

Introduction: Acquired Hemophilia A (AHA) is a rare but potentially lifethreatening bleeding disorder characterized by autoantibodies for coagulation factor VIII. Awareness of AHA different presentations may save patients’ lives. However, there is diverse presentation of AHA reported in medical literature. Aim: To report AHA case with rare presentation of buccal bleeding and raise awareness of a such condition. Case: We reported a case of AHA in a patient with chronic medical condition that presented with buccal mucosal bleed. Despite referral to multiple medical specialties and multiple reviews, the diagnosis was not picked up until the patient had heavy vaginal bleeding and was admitted in tertiary center. The patient was treated eventually and recovered. Conclusion: AHA could present with buccal mucosa bleeding. It is important to remember this diagnosis when treating a chronically ill and symptomatic patient. An early diagnosis could reduce patient’s suffering and medical investigations. The treatment is possible with blood transfusion, steroids, DDAVP, activated factor VII and immunosuppressant.

Epidemiology and Management of Acquired Hemophilia A in a Single Hospital System

Introduction: Acquired Hemophilia A (AHA) is an uncommon autoimmune disease that occurs when autoantibodies form against intrinsic factor VIII. Cases are typically identified due to isolated prolongation of the partial thromboplastin time (PTT) or unexplained bleeding diathesis, prompting further evaluation with PTT mixing studies and the Bethesda assay. AHA is historically associated with a high mortality rate; however, when appropriately diagnosed and treated, modern mortality from acute bleeding is approximately 4.5% (Knoebl et al Journal of Thrombosis and Haemostasis 2012). This study aims to explore the epidemiology, management, and outcomes in cases of AHA found within our hospital system to guide future care.Methods: The study design involves identifying all diagnosed cases of AHA within our hospital system using diagnosis codes and use of specific laboratory tests. The study design was presented to the University of Illinois College of Medicine at Peoria Internal Review Board and granted exempt status. 1,931 patients were identified, of which 6 patients met criteria for diagnosis of AHA.Results: The initial analysis reveals that the study population had a median age of 79.5 years old (high: 90; low: 61). All the patients presented with bleeding symptoms and 5 of 6 had major bleeding requiring transfusion. 5 of the 6 patients also developed soft tissue bleeding with hematoma or hemarthrosis. Underlying diagnosis of cancer was the suspected etiology in 4 of 6 cases. The median initial Bethesda assay value was 106.5 Bethesda units (high: 180; low: 33) and the median initial factor VIII activity assay result was less than 1%. The median PTT mixing study result was 51.5 seconds (high: 66.7; low: 44). In 3 of the 6 cases, patient survival was less than 1 year from onset of bleeding symptoms. 1 patient died prior to initiation of a bypassing agent. All the remaining patients were treated with the bypassing agent recombinant factor VIIA (NovoSeven ®). 2 of those 5 cases required management with a second line bypassing agent and in both cases porcine recombinant factor VIII (Obizur ®) was used and successfully achieved hemostasis. Remission with complete eradication of the acquired factor inhibitor was achieved in 4 of 5 cases receiving a bypassing agent with subsequent immunosuppressive therapy. Prednisone was used in all cases, with two using a second immunosuppressant (cyclophosphamide and rituximab). Of the 4 patients achieving remission, all eventually had recurrence of bleeding. Only 1 patient is still alive and none of the other patients survived to 5 years from initial presentation. 4 of those 5 patients died from direct complications of bleeding.Conclusions: Despite having access to electronic patient data from one of the largest hospital systems in Illinois, only 6 diagnoses were confirmed. We suspect that AHA is significantly underdiagnosed and that many patients developing factor inhibitors die before a full workup can be performed. The EACH2 registry changed how we view AHA; however, that analysis of that database must continue to be supported by population data from centers not included in that study (Knoebl et al Journal of Thrombosis and Haemostasis 2012). Furthermore, analysis of outcomes with newer bypassing agents and more sophisticated use of these agents is ongoing. We plan to publish the full results of our study, including a cost-benefit analysis of these 6 cases. We hope that our patient data can be compounded with other recent studies to help to shape future management decisions and guidelines. DisclosuresNo relevant conflicts of interest to declare.

Clinical Outcomes of Acquired Factor VIII Inhibitors in Cancer Population: A Systematic Review

Background: In cancer patients, the development of autoantibodies against coagulation factors is a rare but a life-threatening bleeding disorder. Acquired hemophilia A (AHA) is the most common subset of the disorder and is caused by the inhibitory antibodies against coagulation factor VIII (FVIII) activity which can cause significant bleeding diathesis in those patients. Therefore, a prompt diagnosis is necessary for management of controlling the suppression of the inhibitor and the bleeding diathesis.Aims: We conducted a systematic review to study the occurrence of FVIII inhibitors in cancer patients, particularly their clinical outcomes and treatment responses.Methods: We performed an electronic search through March 31, 2017 with search terms “acquired hemophilia factor VIII inhibitor and cancer”, “acquired hemophilia A” in PUBMED and EMBASE. Manuscripts with unavailable details, other coagulation factor inhibitors, hereditary cases and in other languages were excluded. The primary endpoint was measuring clinical response to treatments as defined by reduction of at least 50% in the baseline FVIII inhibitor level. Secondary endpoints were identifying early (defined a time to response ≤ 1.5 months from the initiation of therapy) vs. late responders to treatments and overall survival (OS) between responders and non-responders.Results:47 cases of AHA associated with malignancies were analyzed. Several cancer and hemophilia characteristics were compared between treatment responders and non-responders. Findings include 68% males, median age 70 (58-74), hematologic vs. solid malignancy of 62% vs. 38%, median FVII inhibitor level 14 BU/mL. The most common therapy used to eradicate the inhibitor was immunosuppressive therapy; differences in treatment modalities did not result in significant differences between responders and non-responders (Table 1). Treatment responders have lower median FVII inhibitor level as compared to non-responders (12 vs. 41 BU/mL; p = 0.027). There was equal number of cases for early and late responders. Median OS for responders was 41 months with 95 % CI [10.7-71.3] vs. 2 months for non-responders with 95% CI [1.3-2.7].Conclusion:The amount of inhibitor overall seems to be the best predictor of clinical outcomes in AHA patients regardless of the type of therapy used and the type of malignancy. Earlier detection of FVIII inhibitors could lead to earlier interventions with suppression therapy, potentially improving outcomes. Larger studies are needed to confirm our findings. [Display omitted] DisclosuresRojas Hernandez:Daichii Sankyo: Research Funding. Oo:Daichii Sankyo: Research Funding.

Hemostatic therapy as a management strategy for acquired hemophilia: what does the future hold?

ABSTRACT Introduction: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies that bind and inactivate factor VIII (FVIII), predisposing to a potentially life-threatening bleeding. Areas covered: The main epidemiological, clinical, laboratory and therapeutic features of AHA are critically discussed. In particular, we focus on the hemostatic management of AHA patients analyzing the currently available treatment options and showing the latest data on the innovative hemostatic agents still under investigation. Authors searched the Medline and PubMed electronic databases for publication on AHA in the last twenty years. Expert opinion: While a rapid recognition of suspected cases of AHA is essential to make a correct diagnosis and appropriately and timely treat the hemorrhagic manifestations, the multidisciplinary approach to this challenging, rare and life-threatening bleeding disorder is of equal importance to improve patients’ outcome. Although promising, the safety and efficacy of the clinical use of emicizumab in AHA needs to be validated by trials including an adequate number of patients, before registering the drug also for this indication.

Acquired hemophilia A presenting as progressive intra-abdominal hemorrhage, muscle hemorrhage and hemothorax postpartum: A case report and literature review.

Acquired hemophilia A (AHA) is a rare antibody-mediated condition in which autoantibodies form against a coagulation factor, most commonly factor VIII (FVIII), causing severe coagulopathy. Here the present report presents a case of AHA in a 35-year-old postpartum woman with continuous polyserous bloody effusions who was admitted to the First Affiliated Hospital of Zhejiang Chinese Medical University (Hangzhou, China) in October 2017 without a history of trauma, anticoagulation treatment or coagulopathy. At presentation, the patient's hemoglobin level was low (70 g/l; normal range: 115–150 g/l) g/l, blood pressure was 89/58 mmHg (normal range, 90–140/60–90 mmHg), and activated partial thromboplastin time was 68.4 sec (normal range: 25.0–36.0 sec), with a normal international normalized ratio (0.94; normal range, 0.8–1.2). The reaction time in thrombography was prolonged (35.8 min; normal range: 5–10 min), coagulation FVIII had markedly decreased activity (12.6%; normal range, 60–150%), and FVIII inhibitor had a high titer [7.4 Bethesda units (BU)/ml; normal range, 0–0.6 BU/ml]. Notably, the patient's autoantibody level was markedly higher than normal (1:320; normal range: <1:100). The patient was successfully treated with bleeding control, eradication of FVIII inhibitor, and treatment of the underlying disease. To the best of our knowledge, this is the first case of AHA with polyserous bloody effusions in a patient with an autoimmune disorder during the postpartum period. Reports of such rare cases will aid the characterization of disease pathogenesis, which may in turn lead to the recognition and timely treatment of this rare disorder.

Acquired hemophilia with thrombosis in a cancer patient

: Acquired hemophilia A (AHA) which presents with spontaneous severe intramuscular, mucosal and/or subcutaneous bleeding is a rare bleeding disorder. Even 50% of AHA patients are defined as idiopathic; 10% of cases are related with malignancy. Here, we present a case of AHA in a 43-year-old lady who was diagnosed with malignancy and venous thromboembolism on vena cava 2 years ago. To the best of our knowledge, this is the first report in literature presented with both acquired hemophilia and thrombosis associated with malignancy. A routine workup for malignancy like solid tumors, lymphoproliferative, or myeloproliferative diseases should be performed and followed up for a long time despite clinical improvement for individuals presented with AHA. Moreover, because of warfarin treatment, the diagnosis may be difficult and delayed. Clinicans should rule out AHA in patients who are on warfarin treatment and have abnormal coagulation tests.

Intractable Lower GI Bleeding due to Acquired Hemophilia A in a Patient With Rectal Cancer

Introduction: Acquired hemophilia A (AHA) is a rare bleeding disorder with an estimated incidence of 1-2/million/year. It is caused by production of auto-antibodies which inhibit the coagulant activity of factor VIII. It can be idiopathic or associated with postpartum status, autoimmune disorders, infection and malignancy. We present a case of intractable GI bleeding due to AHA as a paraneoplastic manifestation in a patient with rectal cancer. Case report: An 87 year old male presented with new onset lower GI bleed and easy bruising. A colonoscopy with biopsies diagnosed rectal adenocarcinoma. CT angiogram was then performed due to persistent bleeding and showed extravasation of contrast at the rectal mass. Prolonged activated thromboplastin time (aPTT) of 76 sec was noted, with normal platelets and INR. Further work-up revealed a positive mixing study, severe Factor VIII activity deficiency, and a positive Factor VIII inhibitor. The diagnosis of Acquired Hemophilia A was established. Efforts were made to control the bleeding with recombinant activated factor VII, Factor VIII Inhibitor Bypassing Agent, and Methylprednisolone. The rectum also underwent packing, followed by radiation. Ultimately, due to continued rectal bleeding, he underwent lower anterior resection with end-colostomy. Following surgery, he had surgical wound bleeding requiring multiple abdominal washouts and packing. Hospital course was further complicated by multi-organ failure and family decided to withdraw care.Figure: Angiography shows the gastroduodenal artery before (Fig 1a) and after (Fig 1b) angioembolization.Figure: CT imaging done the day after angioembolization of the gastroduodenal artery showed hypodense non-enhancing areas in the head and uncinate process of pancreas with acute necrotic collections consistent with acute pancreatitis (Fig 2a). The common bile duct (CBD) was not dilated (Fig 2b), however interval CT imaging 3 months later showed significant CBD dilatation (Fig 2c).Figure: EUS (Fig 3a) noted a dilated CBD and distal CBD stricture with no accompanying biliary wall thickening or mass. Contrast hold-up was noted at the distal CBD during ERCP (Fig 3b). Subsequent attempts to cross the CBD stricture during attempted internalization of the percutaneous transhepatic biliary drain were unsuccessful (Fig 3c).Discussion: Acquired hemophilia A is a rare disease that may cause life-threatening GI bleeding. A paraneoplastic phenomenon is reported in approximately 10% of AHA cases. The most common solid cancer associated with AHA is prostate cancer with rare reports of rectal cancer. Time to diagnosis is critical due to the difficulties in treating this disease and its high mortality. Diagnosis is made in a patient with prolonged aPTT not corrected with mixing study and demonstrating: 1) reduced FVIII level and 2) detectable FVIII inhibitor. Treatment includes hemostasis and suppression of inhibitor production. Hemostasis should be attempted with a bypassing agent such as recombinant activated factor VII (rFVIIa) or Factor VIII Inhibitor Bypassing Agent (FEIBA). Immunosuppression options include use of corticosteroids alone or corticosteroids combined with cyclophosphamide. Rituximab has been also been found to be successful as a second line treatment option.Figure: CT angiogram showing luminal extravasation of contrast.Table: Table. Lab Results