Acquired Hemophilia A Research Articles

United States Post-Marketing Safety (PMS) Study of rpFVIII in Patients with Acquired Hemophilia A: Preliminary Data

Introduction: Acquired hemophilia A (AHA) is a rare autoimmune disorder characterized by development of neutralizing autoantibodies to circulating factor VIII (FVIII). Obizur® is a recombinant, B-domain deleted, porcine-sequence FVIII (rpFVIII) with low cross-reactivity to anti-human-FVIII antibodies for the treatment of AHA. The objective of this study is to collect data assessing the safety, safety-related factors, utilization, and effectiveness of rpFVIII in real-world clinical practice.Methods: This is a multi-center, non-controlled, open-label, non-interventional Post-Marketing Safety (PMS) surveillance study conducted in the United States for AHA patients treated with rpFVIII. This is a prospective and retrospective data will a target enrollment of 40 patients. Statistical analyses will be conducted and include, specifically but not exclusively, descriptive statistics.Results: A second, preliminary, unplanned data read-out was conducted on March 31, 2017, on 19 patients (11 males and 8 females) from 11 centers in the US. Complete demographic data was available for 15 patients and they had a median age of 73 years (range: 54-81) and the median weight was 85.1 kg (range: 43.7-159.3). The mean lag time of AHA diagnosis was 13.2 days (range: 16 [pt with no bleed at the diagnosis] -127) and the median was 6 days. The mean days from bleeding onset to first Obizur infusion was 98.1 (range: 3-581) with a median of 19 days. The first bleeding episode was spontaneous in 10/19 (52.6%) and described as located in other, 42.1%, while 7/19 (36.8%) of patients experienced bleeds described as deep (musculoskeletal, retroperitoneal). The bleed characteristics of 14 patients with sufficient data are described in Table 1. The loading dose of rpFVIII administered ranged from 50 to 300 U/kg (mean 125.5 U/kg) to treat the bleeds, which significantly differs from the initial dose of 200 U/kg recommended in the Summary of Product Characteristics. Among the evaluable subjects for whom enough data has been collected, 14 bleeding episodes were resolved in 11 patients (11 initial bleeds, 2 subsequent bleeds and one (1) concurrent bleed), and five (5) bleeding episodes were not resolved in three (3) patients (3 initial bleeds and 2 subsequent bleeds). A mean of three (3) infusions (range: 1-46; median of 8.5) were required to resolved the bleeds for patients evaluable for efficacy at the time of this analysis, with an overall population mean of 6 infusions (range: 1-85; median of 13.3). Among the evaluable patients evaluable for treatment modality, six (6) were treated with rpFVIII as first line therapy for their initial bleeding event, and four (4) as first line for the subsequent bleeds. The remaining six (6) patients were treated with rpFVIII after other treatments as 2nd, 3rd or even 5th line therapy. To date, no thromboembolic events have been reported and one patient experienced a hypersensitivity reaction (rush). One therapy related serious adverse event was reported, a moderate vascular disorder (hemorrhage) considered “possibly related” to rpFVIII, which occurred more than 24 hours after the last treatment of rpFVIII.Conclusions: From this preliminary data read out of the patients currently enrolled in the Post Marketing Surveillance study ongoing in the US, rpFVIII appears to be safe and effective in patients with AHA, a disease that is confirmed to occur in a very heterogeneous way. This study, along with a similar one in Europe, will provide a relevant amount of real world clinical data and may help with further assessment of the dosing regimen as well as guidance regarding appropriate dosing in order to personalize the treatment for each individual. [Display omitted] DisclosuresCrea:Shire: Employment, Equity Ownership. Huang:Shire: Employment, Equity Ownership. Bajwa:Shire: Employment. Gringeri:Shire: Employment.

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.

Clinical characteristics and prognostic factors of acquired haemophilia A in Korea.

Acquired haemophilia A (AHA) treatment involves the haemostatic treatment for acute haemorrhage and immunosuppressive therapy (IST) to eradicate FVIII inhibitory antibodies. We assessed the clinical features of AHA and analysed treatment outcomes in Korea. We further identified prognostic factors affecting treatment outcomes. Medical records of 55 patients with AHA from 18 institutions were reviewed retrospectively. Logistic and Cox regression analyses were performed to elucidate clinical factors affecting the achievement of complete remission (CR). The primary endpoint was time to CR after IST, and secondary endpoints were time to haemostasis, the achievement of CR, and overall survival (OS). Among the 55 patients, 50 (91%) had bleeding symptoms. Bleeding was severe in 74% of patients. Thirty-six (72%) patients received haemostatic therapy. Of the 42 patients who received IST, 23 (52%) received steroid alone, with a 52% response rate, and 10 (25%) received a combination of steroid and cyclophosphamide, with an 83% response rate. Five (16%) patients relapsed after a median duration of 220 days. There were eight deaths. In the Cox regression analysis, the FVIII inhibitor titre ≥ 20 BU/mL was the only significant prognostic factor affecting time to CR and haemostasis. No significant difference was observed in OS based on the inhibitor titre. The present study demonstrated the demographic data of AHA in Korea and showed that FVIII inhibitory antibody titre was a predictor of time to achieve CR after IST.

Principles of care for acquired hemophilia.

ObjectiveTo establish clear priorities for the care of patients with acquired hemophilia A (AHA) by proposing 10 key principles of practical, holistic AHA management.MethodThese principles were developed by the Zürich Haemophilia Forum, an expert panel of European hemophilia specialists comprising physicians and nursing and laboratory specialists.ResultsThe 10 proposed principles for AHA care are as follows: (a) Improving initial diagnosis of AHA; (b) Differential diagnosis of AHA: laboratory assessment of patients with unusual bleeding; (c) Effective communication between laboratories, physicians, and specialists; (d) Improving clinical care: networking between healthcare professionals in the treating hospital and specialist hemophilia centers; (e) Comprehensive assessment of bleeding; (f) Appropriate use of bypassing agents; (g) Long‐term follow‐up and monitoring for efficacy and safety of immunosuppressive treatment; (h) Inpatient/outpatient settings; (i) Access to innovative and disruptive treatments; (j) Promotion of international collaborative research.ConclusionThe proposed principles for holistic AHA care aim to ensure swift diagnosis and optimal patient management. Key to achieving this goal is training for healthcare personnel in non‐specialist hospitals and collaboration between different specialists. We hope these principles will increase awareness of AHA in the wider medical community and catalyze efforts toward improving its practical, multidisciplinary management.

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 haemophilia and haemostatic control with recombinant porcine factor VIII: case series.

Acquired haemophilia A (AHA) is a rare acquired bleeding disorder that can present with life-threatening bleeding. To describe recent Australian use of recombinant porcine factor VIII (rpFVIII) replacement therapy as a haemostatic agent in patients with acquired haemophilia. Four patients with acquired haemophilia treated in three different institutions around Australia in the past 12 months were included in the study. Haemostatic efficacy of Obizur (Takeda) was assigned by the treating haematologist according to previously published criteria. Six bleeds were treated with rpFVIII, three of which were initially refractory to treatment with recombinant VIIa. rpFVIII was rated efficacious in 100% of bleeds by 24 h. rpFVIII loading dose was 100 U/kg (100-120 U kg-1 ) and this increased the factor VIII level (via one-stage FVIII assay) from <1-1.2% to 54-306% taken 0.5-1.5 h post-infusion. Subsequent doses ranged from 40 to 60 U/kg twice daily or daily for 3 to 13 days. No rpFVIII related adverse events occurred. Three of the four patients achieved complete remission and were weaned from immunosuppression. One patient died prior to achieving partial remission, secondary to an arterial ischaemic event. This case series demonstrates that recombinant porcine FVIII is efficacious to treat acute bleeds in acquired haemophilia, including in those who are refractory to bypassing agents. Doses of rpFVIII were able to be titrated based on FVIII level and clinical response.

Assessment of Lebanese healthcare professionals’ awareness on acquired haemophilia: a cross-sectional study

ABSTRACT Background Acquired haemophilia A (AHA) is a rare immune-mediated disorder characterised by the development of autoantibodies against factor VIII. Morbidity and mortality are in general high due to multiple factors including the age of the patient, underlying diseases, toxic effects of available treatments and bleeding itself. Objective To assess the awareness about AHA among healthcare professionals (HCPs) in Lebanon where patients can present to non-haematologists with life-threatening bleeding disorders. Methods A cross-sectional survey was conducted in September and October 2017 all over Lebanon among HCPs. The survey covered: (i) the geographic area of practice and specialty; (ii) bleeding disorders encountered within the last 2 years; (iii) assessment of knowledge on AHA; and (iv) importance of increasing awareness on AHA among HCPs. Results A total of 362 participants completed and returned the questionnaire (response rate 100%). The majority of the HCPs were practicing in Beirut (n=164; 45.3%) and were internists (n=106; 29.3%). 332 (93%) HCPs have encountered patients with bleeding problems within the last 2 years all over Lebanon. 327 (92.1%) HCPs agreed that increasing awareness on AHA among health care professionals is important. HCPs gave an average of 75.9% of correct answers on the survey. Conclusions Appropriate treatment and diagnosis are essential when dealing with AHA. Knowledge gaps exist in the clinical practice when dealing with patients who have AHA. This study shows the need for increasing awareness about AHA among HCPs in Lebanon regarding the diagnosis and treatment of this disorder.

Adaptation of recombinant activated factor VII in the treatment of acquired haemophilia A: Results from a prospective study (ACQUI-7) in France

BackgroundThe efficacy and safety of recombinant activated factor VII (rFVIIa; NovoSeven®) in patients with acquired haemophilia A (AHA) are established; however, data on daily use in clinical practice for bleeding episodes are limited. The ACQUI-7 study aimed to provide additional data on managing bleeding episodes with rFVIIa in patients with AHA. MethodsACQUI-7, a prospective, observational, multicentre study in 20 sites in France, recruited patients from 2010 to 2013. Treatment was by physician’s judgement and therapeutic practice at each site. Inclusion criteria: anti-factor VIII (FVIII) auto-antibodies ​> ​1 Bethesda Unit, FVIII activity ​< ​50% and bleeding episodes treated with rFVIIa. Data collected included description of patient characteristics, bleeding episodes leading to haemostatic treatment and rFVIIa therapy. ResultsA total of 27 patients with 27 bleeding episodes (24 [88.9%] severe) were treated with first-line rFVIIa. Most (81.5%) were affected in more than 1 site (44.4% in muscle). Nineteen patients (70.4%) were treated for up to 5 days; 24 (88.9%) had their bleeding episode controlled (including 21 severe bleeds). The maximum daily dose for controlling severe bleeds decreased from 900 ​μg/kg/24 ​h on day 1–630 ​μg/kg/24 ​h on day 5, with a corresponding reduction in maximum number of daily injections from 10 to 7. The use of rFVIIa in this population did not raise any safety concerns. ConclusionsThese real-world data confirm the effectiveness and safety of rFVIIa and provide additional information on the daily use of rFVIIa to support the management of patients with AHA.

PSY14 Acquired Hemophilia A (AHA) - Limits of the Awareness Push in Germany

PSY14 Acquired Hemophilia A (AHA) - Limits of the Awareness Push in Germany

An Investigational Dosing Algorithm of Emicizumab for Prophylaxis in Acquired Hemophilia a

An Investigational Dosing Algorithm of Emicizumab for Prophylaxis in Acquired Hemophilia a

Experience with Continuous Infusion of Recombinant Porcine FVIII in Patients with Acquired Hemophilia a

Background: Acquired hemophilia A (AHA) is a rare disorder with high morbidity and mortality that results from the development of autoantibodies against factor VIII (FVIII). To manage acute bleeding, recombinant porcine FVIII (rpFVIII) can be administered intravenously as a bolus dose of 50IU/kg to 200IU/kg depending on bleeding severity and the level of baseline cross-reacting anti-porcine FVIII inhibitors(Kruse-Jarres et al., 2017). Here we describe the efficacy of rpFVIII used as a continuous infusion (CI) and compare total product utilization to bolus infusions (BI). Methods: Retrospective chart review was conducted on patients with AHA who met the International Society on Thrombosis and Hemostasis criteria for major bleeding and who received rpFVIII at our institution from 2015 to 2020(Kaatz, Ahmad, Spyropoulos, &amp; Schulman, 2015). Efficacy was defined as clinical bleeding control and achievement of adequate FVIII levels. Data were collected through electronic patient records and analyzed using simple descriptive (mean ± standard deviation (SD)) and inferential statistics (T-Test, alpha=0.05). Institutional Research Ethics Board approval was obtained. Results: During the study period, 13 patients received rpFVIII (CI n=3, BI n=10). The mean age of patients receiving CI and BI was 75.3 years (SD 2.5) and 72.0 years (SD 14.5) respectively. All patients who received rpFVIII as a CI received a bolus dose ranging between 102.6IU/kg-200.8IU/kg prior to initiation of the CI. CI rates between 3.4IU/kg/hr-11.5IU/kg/hr were administered. Two of the patients receiving rpFVIII as a CI had their infusion rates adjusted according to their clinical symptoms and FVIII levels. One patient had the rpFVIII CI stopped due to an increase in anti-rpFVIII antibodies which interfered with hemostatic efficacy. Thirty-three percent of CI patients and 60% of BI patients required a red blood cell (RBC) transfusion after starting rpFVIII. Sixty-six percent of CI patients and 20% of BI patients had worsening of bleeding after initiation of rpFVIII. Lastly, rpFVIII usage in the CI group (170.4 ± 25.9 IU/kg/day) was not significantly different compared to the BI group (120.9 ± 64.4 IU/kg/day) when accounting for the duration of admission and weight of the patients (P&amp;gt;0.05). No thromboembolic events occurred in either group while receiving rpFVIII. Conclusions: Our study shows that the total amount of rpFVIII administered to patients as a CI is not significantly different to those receiving BI. The CI group required less RBC transfusions but reported more exacerbation of bleeding. Thus, the efficacy of rpFVIII given as a CI requires further evaluation in future prospective studies. Disclosures Sholzberg: NovoNordisk: Honoraria, Other: Scientific Advisory Board; Novartis: Honoraria, Other: Scientific Advisory Board; Takeda: Honoraria, Other: Scientific Advisory Board, Research Funding; Octapharma: Honoraria, Other: Scientific Advisory Board, Research Funding; Amgen: Honoraria, Other: Scientific Advisory Board, Research Funding. OffLabel Disclosure: Antihemophilic Factor (Recombinant), Porcine Sequence (OBIZUR) is a purified protein produced by recombinant DNA that is a B-domain deleted recombinant factor VIII, porcine sequence, manufactured in tissue culture in baby hamster kidney (BHK) cells. OBIZUR is indicated for the treatment of bleeding episodes in patients with Acquired Hemophilia A (AHA). OBIZUR is administered as a bolus infusion.

Treatment of acquired hemophilia A, a balancing act: results from a 27-year Dutch cohort study.

Acquired hemophilia A (AHA) is a severe auto‐immune bleeding disorder. Treatment of AHA is burdensome and optimal management is still unresolved. Therefore a retrospective nationwide multi‐center cohort study (1992‐2018) was performed to evaluate clinical presentation and treatment efficacy and safety of AHA in the Netherlands. Multivariate logistic and Cox regression analysis was used to study independent associations between patient characteristics and clinical outcomes. A total of 143 patients (median age 73 years; 52.4% male) were included with a median follow‐up of 16.8 months (IQR 3.6‐41.5 months). First‐line immunosuppressive treatment was mostly steroid monotherapy (67.6%), steroids/cyclophosphamide (11.9%) and steroids/rituximab (11.9%), with success rates of 35.2%, 80.0% and 66.7% respectively, P < .05. Eventually 75% of patients achieved complete remission (CR). A high anti‐FVIII antibody titer, severe bleeding and steroid monotherapy were associated with lower CR rates. Infections, the most important adverse event, occurred significantly more often with steroid combination therapy compared to steroids alone (38.7% vs 10.6%; P = .001). Overall mortality was 38.2%, mostly due to infections (19.2%) compared to 7.7% fatal bleeds. Advanced age, underlying malignancy and ICU admission were predictors for mortality. This study showed that AHA is characterized by significant disease‐related and treatment‐related morbidity and mortality. A high anti‐FVIII titer, severe bleeding and steroid monotherapy were associated with a lower CR rate. The efficacy of steroid combination therapies however, was overshadowed by higher infection rates and infections represented the most important cause of death. The challenging and delicate balance between treatment effectivity and safety requires ongoing monitoring of AHA and further identification of prognostic markers.

Cross-reacting recombinant porcine FVIII inhibitors in patients with acquired haemophilia A.

Acquired haemophilia A (AHA) is a rare bleeding disorder caused by the development of autoantibodies to endogenous human factor VIII (hFVIII). If treatment of bleeding is required, one option is recombinant porcine FVIII (rpFVIII). Cross-reactivity between factor VIII inhibitors and rpFVIII has previously been described. The aim of this study was to retrospectively assess the incidence of cross-reacting anti-porcine inhibitors in patients diagnosed with AHA in two UK centres. The plasma of fifty-one patients diagnosed with AHA via reduced FVIII:C and positive FVIII inhibitor titre as detected with a Nijmegen-Bethesda assay (NBA) was also tested by a porcine Bethesda assay (PBA). The NBA was modified by replacement of human FVIII with rpFVIII in the PBA, with determination of residual FVIII by one-stage clotting assay. The median FVIII inhibitor titre by NBA was 22.8 BU/mL (range: 0.8-1000 BU/mL). 37% of samples exhibited linear, type 1 kinetics in the NBA. Negative PBA was observed in 26 patients, and 25 were positive (median PBA: 3.5 BU/mL; range: 0.8-120 BU/mL). Type 1 kinetics were observed in 40% of PBA-positive patients. At NBA tires of greater than 100 BU/mL, the positive predictive value for the presence of porcine cross-reactivity was 100%. At NBA below 5 BU/mL, the negative predictive value for the presence of porcine cross-reactivity was 71%. Cross-reactivity between FVIII inhibitors and rpFVIII was observed in 49% of patients. The presence of inhibitors to rpFVIII may influence the treatment choice for patients with acquired haemophilia A.

Bullous pemphigoid is a common associated disorder with acquired haemophilia A.

Although the estimated incidence of acquired haemophilia A (AHA) in Singapore is similar to those reported in the literature, we have observed differences in the frequency of their associated diseases, particularly bullous pemphigoid (BP). We investigated the actual incidence of BP among our AHA cohort, their clinical characteristics and treatment outcomes. 6 out of 37 (16%) patients with AHA had BP, making it the most common underlying disorder in our cohort. The median age at diagnosis of AHA was 76years old with a female preponderance. Most patients had their AHA diagnosed after BP with the median time between BP to AHA diagnosis being 107.5days. Initial haemostasis was achieved, and factor VIII inhibitor was eliminated in all patients with a median time of disappearance being 52days. Two patients had recurrence of their factor VIII inhibitor during the tapering of their immunosuppression. There was no relationship between the relapse of BP and AHA. This study suggests that BP is a common association with AHA. These patients respond well to bypassing agent and immunosuppression. However, they have a higher recurrence of factor VIII inhibitor and should be monitored closely for relapse during the tapering period of their immunosuppression.

Clinical utility of sample preheat treatment in a modified Nijmegen-Bethesda assay (mNBA) for inhibitor monitoring in congenital and acquired haemophilia A: A single-centre four-year experience.

Laboratory monitoring for factor VIII inhibitors ideally requires samples with the lowest possible factor VIII (FVIII) level, potentially challenging in patients with congenital haemophilia A (CHA) receiving regular prophylaxis and acquired haemophilia A (AHA) patients with endogenous FVIII. Inactivation of FVIII by preheating (preheat treatment, PHT) of patient plasma has been suggested to facilitate monitoring. To evaluate the clinical utility of PHT prior to inhibitor analysis by modified Nijmegen-Bethesda assay (mNBA) in patients with CHA and AHA. Inhibitor screening by mNBA under standard conditions and with PHT at 56°C for 30, 60 and 90 minutes was evaluated. FVIII inhibitor results between 2007 and 2010 without PHT (720 results from 222 CHA and AHA patients), and between 2011 and 2014 post-PHT (1102 results from 302 patients) were available for analysis. Of total 1822 results available, 61% were from severe HA patients, 22% from mild and moderate HA and 16% from AHA. Pre-PHT, 74% of samples were analysed by the mNBA, and the remaining 26% were not tested as FVIII levels were>20 IU/dL as per local protocol. Postintroduction of PHT (90 and 60 minutes), 96% of samples received were analysed for an inhibitor. Post-PHT in patients with AHA (n = 26), 69% of samples tested with factor VIII levels >20 IU/dL were found to have detectable inhibitor. FVIII inhibitor testing using PHT at 56°C for 60 minutes facilitates inhibitor surveillance of CHA on prophylaxis. Potentially, 30 minutes at 56°C might be equally efficacious. In AHA receiving immunosuppression, monitoring of inhibitor titre after initial factor VIII response might enable personalized immunosuppression.

Reduced-intensity, risk factor\u2013stratified immunosuppression for acquired hemophilia A: single-center observational study

Immunosuppressive therapy (IST) is administered to patients with acquired hemophilia A (AHA) to eradicate autoantibodies against coagulation factor VIII (FVIII). Data from registries previously demonstrated that IST is often complicated by adverse events, in particular infections. This pilot study was set out to assess the feasibility of reduced-intensity, risk factor–stratified IST. We followed a single-center consecutive cohort of twenty-five patients with AHA receiving IST according to a new institutional treatment standard. Based on results from a previous study, GTH-AH 01/2020, patients were stratified into “poor risk” (FVIII < 1 IU/dl or inhibitor ≥ 20 Bethesda units (BU)/ml) or “good risk” (FVIII ≥ 1 IU/dl and inhibitor < 20 BU/ml). Outcomes were compared between the current cohort and the GTH registry as a historic control (n = 102). Baseline characteristics of the cohort were not different from the historic control. Partial remission, defined as FVIII recovered to > 50 IU/dl, was achieved by 68% of patients after a median time of 112 days, which was lower and significantly later than in the historic control (hazard ratio: 1.8, 95% confidence interval 1.2–2.8). Complete remission, overall survival, and frequency of fatal infections were not different. Grade 3 and 4 infections were more frequent. The impact of risk factors that was observed in the historic cohort was no longer apparent, as partial and complete remission and overall survival were similar in “good risk” and “poor risk” patients. In conclusion, reduced-intensity, risk factor–stratified IST is feasible in AHA but did not decrease the risk of infections and mortality in this cohort.

Identifying risk factors and optimizing standard of care for patients with acquired haemophilia A: Results from a Czech patient cohort.

Acquired haemophilia A (AHA) is a rare autoimmune disorder, characterized by bleeds of varying severity caused by autoantibodies against factor VIII (FVIII). Identify risk factors associated with AHA-related deaths/relapses and assess the effect of increased corticosteroid doses. AHA patients treated across two specialist centres in the Czech Republic, generally receiving first-line haemostatic therapy with rFVIIa and immunosuppression with corticosteroids/cyclophosphamide, were included. We analysed the association between early death (within 8weeks of diagnosis [considered disease-related]) and age, malignancy, FVIII levels and bleeding severity. Risk factors associated with reduced 2-year survival and relapse incidence, and the effect of increased corticosteroid doses on early death and remission were also assessed. The demographics of the described cohort (n=66) were similar to other AHA registries. Early death occurred in 20% of cases. Unlike age and malignancy, FVIII levels <1% and severe bleeding were associated significantly with early death (P=.010 and P=.046, respectively). Patients with underlying malignancy or requiring continued haemostatic therapy exhibited significantly decreased 2-year survival compared with those without these risk factors (P=.007 and P=.006, respectively). Patients with an underlying autoimmune disease relapsed significantly more than those without (P=.015). Higher corticosteroid doses were associated with a significantly increased incidence of early deaths (P<.001), but also with early remission (P<.001). Based on this rather large patient cohort, we were able to evaluate the significance of several risk factors associated with treatment outcomes in AHA and the effect of initial treatment with corticosteroids on survival and time to remission.

Susoctocog-alfa (Obizur®) in the treatment of nine elderly patients with acquired haemophilia A: an Italian multicentre real world experience.

In 2016, a new recombinant B-domain deleted porcine FVIII (rpFVIII) was licensed in Italy for the treatment of acquired haemophilia A (AHA). But only a few cases of patients receiving this have been reported in the literature. Here we report the largest registry of the use of rpFVIII for the treatment of AHA. The objective of this retrospective study was to describe the efficacy and the safety of susoctocog-alfa for AHA. We studied a population of nine patients, recruited in five Italian haemophilia centres presenting AHA, and treated with Obizur® as first- or second-line therapy. fir RESULTS: rpFVIII was used as a first-line therapy in one-third of the patients. The median delay between clinical onset and diagnosis was 16 days. Initial bolus of infused susoctocog-alfa was 100 IU/kg, lower than the recommended dose. The treatment was maintained for a median of four days. Only one patient with serious co-morbidities and recurrent infections was treated for 32 days. All patients reached a complete resolution of AHA, and no recurrences were reported. Two patients developed a low-titre inhibitor against rpFVIII, neither experienced any complications. In our real world experience, susoctocog-alfa was proven to be an effective and safe therapeutic option for patients with AHA, also at a lower than recommended dosage. In our report, the appearance of low-titre inhibitors.

Acquired Haemophilia A in Association with Influenza A and Urinary Tract Infection.

The lack of awareness of and experience with acquired haemophilia (AHA) suggests that diagnosis is frequently delayed, resulting in suboptimal treatment.AHA should be suspected in recent-onset abnormal bleeding in patients not receiving anticoagulant treatment, and in the presence of isolated prolonged activated partial thromboplastin time (aPTT).Treatment is based on eradication of the inhibitor, control of the bleeding and identification of underlying conditions.

Efficacy of therapeutic plasma exchange in a patient with coagulation inhibitors (acquired haemophilia A) – A case report

Acquired haemophilia A (AHA) is a rare disorder with mostly idiopathic aetiology that leads to factor VIII (FVIII) deficiency due to coagulation inhibitors formation. Treatment protocol includes immunosuppression and Factor VIII bypassing agents including activated Prothrombin Complex Concentrates (PCC). Nevertheless, the role of plasma exchange is not clear in the treatment of AHA. We report a case of 73 year old male who presented with haematuria, prolonged activated partial thromboplastin time (APTT) and a very high titres of Factor VIII inhibitors of 98 Bethesda units (BU) and was diagnosed with acquired haemophilia A. He failed to respond to multiple immunosuppressive therapies including rituximab. Therefore, therapeutic plasma exchange (TPE) therapy was planned due to persistence of haematuria despite immunosuppressive therapies. After five cycles of plasma exchange, APTT became normal, haematuria subsided and Factor VIII inhibitors became negative. Patient was discharged without any bleeding and in a stable condition. In this index case, plasma exchange played a very crucial role, resulting in recovery of the patient. These results advocate that therapeutic plasma exchange is an effective therapy for acquired haemophilia A.