Recombinant porcine factor VIII (rpFVIII) is indicated for treating bleeding episodes in acquired haemophilia A, but there are few data regarding laboratory methods to adequately monitor treatment. This study involving three Italian laboratories aimed to evaluate the analytical performance of different assays for measuring rpFVIII. Five spiked rpFVIII samples (0.5–1.5 IU/mL) were analysed on three days, in triplicate, with eleven combinations of reagents (Werfen, Boston, MA, USA: SynthasIL and SynthaFax for one-stage assay, Chromogenix Coamatic FVIII for chromogenic assay), FVIII depleted plasmas (with or without von Willebrand factor—VWF) and calibrators (HemosIL human calibrator plasma, porcine calibrator diluted in FVIII deficient plasma with or without VWF). The assays were performed on ACL TOP analysers (Werfen, Boston, MA, USA). Intra- and inter-assay and inter-laboratory Coefficient of Variation (CV%) were calculated together with percentage of recovery (% recovery) on the expected value. The results showed that the reagent combinations reaching satisfactory analytical performance are: SynthasIL/human calibrator/deficient plasma+VWF (total recovery 99.4%, inter-laboratory CV 4.04%), SynthasIL/porcine calibrator/deficient plasma+VWF (total recovery 111%, inter-laboratory CV 2.75%) and Chromogenic/ porcine calibrator/deficient plasma+VWF (total recovery 96.6%, inter-laboratory CV 8.32%). This study highlights that the use of porcine standard (when available) and FVIII deficient plasma with VWF should be recommended.

Both SARS-CoV-2 infection and vaccination have raised concern in immune-mediated diseases, including immune thrombocytopenic purpura (ITP) considering risk of de novo ITP development and ITP recurrence. Here, we report on data from a single-center retrospective–prospective collection aiming to evaluate platelet (plt) dynamics in patients (pts) with chronic ITP after COVID-19 infection (before and after vaccination) and after the first, second and third vaccine doses. Furthermore, we analyzed the serological response after the first two doses of COVID-19 vaccination. A total of 64 pts currently followed for chronic ITP who experienced COVD-19 infection and/or vaccination with an available plt count before and after such events were included in the analysis. A low incidence of ITP exacerbation following vaccine sessions (6–16%) was observed in comparison with a high frequency of exacerbation and rescue treatment necessity after COVID-19 infection in unvaccinated pts (83%). Moreover, the lower ITP exacerbation rate observed in infected pts previously vaccinated (18%) suggests further protective effects in this population. Finally, a high seroconversion rate was observed, confirming data reported in previously published studies on immune cytopenia and rheumatological diseases, but more evidence is awaited to establish the clinical impact of serological response.

Haemophilia and von Willebrand disease are the bleeding disorders most frequently encountered in the emergency department (ED), that are often the first point of contact for patients. Evidence suggests that management in the ED is currently suboptimal, mainly because the physicians have few opportunities to deal with this kind of patients. We carried out a survey to investigate the management of patients with haemophilia A in Emergency Departments (EDs), and to understand the training needs of the involved physicians. Overall, in Piedmont Region there are 32 EDs, and considering that our survey was conducted on 21 physicians working in 23 Emergency Departments (EDs), this number is representative of the Region's reality. The interviews were conducted through face-to-face meetings, including general aspects regarding the clinical characteristics and the management of patients, and self-evaluation of knowledge and interest in receiving information about the disease. In 2019, 131 patients with haemophilia A were admitted (108 adults, 23 paediatric). The best-known and most widely available and used treatments were plasma derivatives, followed by first- and second-generation recombinant FVIII. More recent recombinant and bypassing agents were less known. Half of the interviewees considered their -knowledge of bleeding disorders in general and haemophilia in particular to be "basic", and only one third defined it as "good"; however, 86% expressed great interest in receiving information about the topic. The survey confirms the needs related to the clinical management of rare inherited clotting disorders in EDs. The physicians involved are keen to overcome this lack of knowledge, and proper initiatives should be implemented.

Background: Acquired hemophilia A (AHA) is a rare bleeding disease due to autoantibodies directed against clotting factor VIII (FVIII). Treatment of AHA consists of inhibitor eradication with immunosuppressive therapy (IST) and prompt control of bleeding obtained with bypassing agents or recombinant porcine FVIII (rpFVIII). The latter has recently been licensed for management of acute bleeding in AHA. Unlike treatment with bypassing agents, rpFVIII can be monitored to provide a successful hemostatic effect and avoid overtreatment. Correlation between rpFVIII inhibitor titers and efficacy of rpFVIII treatment remains a matter of debate. Methods: We report three cases of AHA in which rpFVIII was successfully used with an unconventional schedule despite the presence of medium–high titers of the rpFVIII. The modified Nijmegen–Bethesda inhibitor assay (NBA) was used to dose porcine FVIII inhibitors. Result: The presence of rpFVIII inhibitors prior to the exposition to susoctocog-alfa, that may suggest a cross-reactivity with human FVIII inhibitors, did not affect hemostasis. Conclusion: In our experience, rpFVIII demonstrates safety and efficacy in the presence of rpFVIII inhibitors and using an unconventional schedule in both the perioperative and outpatient settings. Laboratory measurement of inhibitors against rpFVIII during treatment is described for the first time.

Background/Objectives: The approach to physical activity in people with hemophilia (PwH) is still conditioned by many difficulties. Thus, a prospective observational pilot study has been carried out aiming to evaluate how an adequate and controlled training program can slow down the onset or evolution of arthropathy and improve musculoskeletal health and quality of life. Methods: Performed from April 2022 to April 2023, this study involved nine severe hemophilic A and B patients, aged > 18 years old, on regular prophylaxis with replacement products. Participants, without changing the usual prophylaxis schedule and maintaining a trough level of at least 20% FVIII/FIX before training, were involved in physical activity twice a week. Results: After 12 months, no increase in annual bleeding ratio (ABR) was observed, and baseline joint status (as assessable by HEAD US score, HJHS, and NRS) was maintained. Even if not statistically significant, a trend toward improvement in mean HEAD US score (15.55 vs. 13.11) and HJHS (14.4 vs. 11) from baseline was observed. Some of the physical tests performed showed a significant improvement at 6 months and 12 months from baseline (5 Rep Sit to Stand, Sit and Reach, and 6-minute Walking Test), meaning an improvement in leg strength, dorsal flexibility, and aerobic resistance. Conclusions: This is the first pilot study evaluating at 360 degrees the safety and impact of a controlled physical activity in PwH. No participant experienced bleedings or a worsening in joint status, but they experienced an improvement in articular functionality. Without changing the usual prophylaxis, scheduling training sessions according to individual pharmacokinetics turned out to be a safe and a cost-effective approach.