Anti-ADAMTS13 Autoantibodies: From Pathophysiology to Prognostic Impact-A Review for Clinicians.

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease in which platelet-rich microthrombi cause end-organ ischemia and damage. TTP is caused by markedly reduced ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. ADAMTS13 autoantibodies (autoAbs) are the major cause of immune TTP (iTTP), determining ADAMTS13 deficiency. The pathophysiology of such autoAbs as well as their prognostic role are continuous objects of scientific studies in iTTP fields. This review aims to provide clinicians with the basic information and updates on autoAbs' structure and function, how they are typically detected in the laboratory and their prognostic implications. This information could be useful in clinical practice and contribute to future research implementations on this specific topic.

Surgery and Prophylaxis with Susoctocog-Alfa in Acquired Hemophilia: Case Series and Literature Review.

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.

Impact of COVID-19 Infection, Vaccination, and Serological Response in Immune Thrombocytopenic Purpura Patients: A Single-Center Global Analysis.

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.

Management of patients with bleeding disorders and educational needs regarding hemophilia a in 23 italian emergency departments - Results from a survey conducted in Piedmont.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

ADAMTS13 Autoantibodies and Burden of Care in Immune Thrombotic Thrombocytopenic purpura: New Evidence and Future Implications.

The introduction Caplacizumab in the management of Immune thrombotic thrombocytopenic purpura (iTTP) has raised different questions, considering its cost-efficacy and the optimal immunosuppressive treatment (IST) to associate. A retrospective multicenter collection of 42 first iTTP cases was conducted to identify variables associated with a higher burden of care and necessity of an implemented IST with early Rituximab (RTX) rescue. A significant correlation resulted between ADAMTS13 inhibitors (ADAMTS13inh) at diagnosis with total plasma exchange (PEXtot) and PEX needed to achieve clinical response (PEXtoCR, r = 0.46; r = 0.48), along with age (r = - 0.31; r = -0.35), platelet count (r = -0.30; r = -0.30), LDH (r = 0.44; r = 0.41) and total bilirubin (r = 0.54; r = 0.35). ADAMTS13inh also correlated with number of days of hospitalization (DoH, r = 0.44). A significant difference was observed in terms of median ADAMTS13inh titer at diagnosis in patient treated with RTX rescue and those responding to only steroid treatment. Thus, ADAMTS13inh titer resulted a marker of iTTP burden of care, associated with higher number of PEXtot, PEXtoCR, DoH and higher probability of needing RTX rescue to achieve clinical response and could be a useful tool for management of new iTTP cases and an interesting variable to optimize iTTP cases stratification in future Caplacizumab cost-efficacy analysis.

Extended half-life rFIX in major surgery-How to improve clinical practice: An intraindividual comparison.

Practical, safe, and effective hemostatic approach to orthopedic surgery using Extended Half-Life factor IX in hemophilia B. By intraindividual comparison, we found a lower FIX consumption, number of infusions, and cost compared to plasma-derived FIX.