[Treatment of haemophilia in Austria]. / Hämophilie-Behandlung in Österreich.

This guideline is intended to provide practical guidance for the diagnosis and treatment of haemophilia in Austria. Few randomized controlled interventional trials are available addressing the treatment of haemophilia, therefore recommendations are usually based on low level of evidence and represent expert consensus.This guideline is based on the WFH guideline, published in 2020, and adapted according to the national circumstances and experience.It includes recommendations and suggestions for diagnosis and follow-up visits and pharmacological therapies for treatment and prophylaxis. Further topics comprise special aspects in children and adults with severe haemophilia, outcome measurement, and management of trauma, special bleedings and interventions, including dental procedures, inhibitors, management of haemophilia carriers, and psychosocial aspects.

The Impact of Digital Transformation on Blood Donation and Donor Characteristics.

Introduction: The management of an adequate donor pool is a constant and challenging task for blood centers in order to provide blood supply. New methods are required to streamline processes and attract (new) donors on a sustained basis. We present a digitalization method without media disruption and show the impact on our donors and their behavior. Methods: We designed and created a blood donation app that is fully compliant to all regulations and conforms to donor expectations. The presented digitalization serves the donor from preparation before the donation (health questionnaire) until completion of laboratory testing (medical report). Many other features are included and continuously attract donors to engage with the blood donation topic. Results: Eighteen months after the launch of our app, there are already 45,000 users. The digital questionnaire reduced the number of deferrals by 31.9% compared to the conventional paper questionnaire. Digital adopters show a significantly shorter donation interval (193 days compared to 316 days). In-app incentives include identification card, rapid laboratory testing results (time-to-results are two business days for 95%), and collection of badges among others. Conclusion: The presented method has changed our donor pool. Besides that, medical staff benefits from the automated process that allows focusing on the donor and their admission. On the other hand, the app has become a valid tool to manage our donor pool and attract first-time and young donors.

Bleeding phenotype in nonsevere hemophilia by International Society on Thrombosis and Haemostasis bleeding assessment tool, bleeding frequency, and the joint status.

Background: Although the phenotype of severe hemophilia has been well studied, there are still knowledge gaps in nonsevere hemophilia. Objectives: The objective of this study was to characterize the clinical bleeding phenotype in nonsevere hemophilia and its association with different factor VIII/IX assessments. Methods: This was a cross-sectional, multicenter study to investigate the bleeding phenotype in adults with nonsevere hemophilia by the number of bleeding and joint bleeding in the past 5 years, a joint score, and the International Society on Thrombosis and Haemostasis bleeding assessment tool (ISTH-BAT). Factor levels were analyzed by 1-stage (lowest in history and at study inclusion) and chromogenic assay (at study inclusion). Patients were enrolled between March 2015 and May 2019. Results: Of the 111 patients (86 with mild and 25 with moderate hemophilia), 57 patients (54.8%) reported any bleeding and 24 (23.1%) any joint bleeding in the past 5 years. A joint score ≥1 was found in 44 patients (41.9%), an ISTH-BAT ≥4 in 100 patients (90.1%), and an ISTH-BAT joint item ≥1 in 50 patients (45.0%). Within the ISTH-BAT, muscle and joint bleeds showed the largest difference between mild and moderate hemophilia. The lowest factor VIII/IX level in patients' history was best associated with bleeding outcomes. Factor was inversely associated with joint bleeds (incidence rate ratio 0.88; 95% CI, 0.79-0.98), joint score, and ISTH-BAT (odds ratios from proportional odds ordinal logistic regression 0.92; 95% CI, 0.87-0.97; and 0.89; 95% CI, 0.86-0.93, respectively). Conclusion: The occurrence of joint bleeding differentiated persons with mild and moderate hemophilia. The ISTH-BAT and lowest factor in patients' history provided valuable information of the bleeding phenotype in nonsevere hemophilia.

Nonneutralizing FVIII-specific antibody signatures in patients with hemophilia A and in healthy donors.

Previous studies identified nonneutralizing FVIII-specific antibodies in the circulation of severe and nonsevere hemophilia A (sHA and nsHA) patients without FVIII inhibitors and also in some healthy individuals. To gain a better understanding of the nature of these nonneutralizing antibody responses, we analyzed and compared anti-FVIII antibody signatures in 3 study cohorts: previously treated sHA as well as nsHA patients without FVIII inhibitors, and healthy donors. FVIII-binding IgM, IgG1-4, and IgA antibodies were differentiated, FVIII-specificity was assessed, and associated apparent affinity constants were determined. Our results indicate that the nonneutralizing FVIII-specific antibody response in all study cohorts is dominated by IgG1 and IgA. Prevalences, titers, and affinities of these nonneutralizing antibodies were higher in the hemophilia A cohorts than in healthy donors. Stratification for the anti-hepatitis C virus (HCV) antibody status demonstrated the presence of FVIII-specific IgA with elevated titers in sHA patients with an active or past HCV infection when compared with HCV antibody-positive nsHA patients or HCV antibody-negative patients and healthy donors. Increased titers and affinities of FVIII-specific IgG1 antibodies were observed in a considerable number of hemophilia A patients as opposed to healthy subjects independently of the patients' anti-HCV antibody status. Overall, our findings support the hypothesis that the generation of nonneutralizing anti-FVIII antibodies in healthy individuals and in noninhibitor hemophilia A patients might be based on similar immune mechanisms. However, differences in prevalences, titers, and affinities of these antibodies indicate distinct differences in the antibody evolution between healthy individuals and patients.

Bleeding outcomes and factor utilization after switching to an extended half-life product for prophylaxis in haemophilia A in Austria.

To prevent bleeding in severe haemophilia A [SHA, defined as factor VIII (FVIII) activity < 1%] regular prophylactic FVIII replacement therapy is required, and the benefits of factor products with extended half-life (EHL) over traditional standard half-life (SHL) are still being debated. We performed a multi-centre, retrospective cohort study of persons with SHA in Austria aiming to compare clinical outcomes and factor utilization in patients with SHA, who switched from prophylaxis with SHL to an EHL. Data were collected from haemophilia-specific patient diaries and medical records. Twenty male persons with SHA (median age: 32.5 years) were included. The most common reason for switching to the EHL was a high bleeding rate with SHL. Switch to rFVIII-Fc resulted in a significantly decreased annualized bleeding rate (ABR; median difference (IQR): - 0.3 (- 4.5-0); Wilcoxon signed-rank test for matched pairs: Z = - 2.7, p = 0.008) and number of prophylactic infusions per week (- 0.75 (- 1.0-0.0); Z = - 2.7, p = 0.007). Factor utilization was comparable to prior prophylaxis with SHL (0.0 (- 15.8-24.8) IU/kg/week; Z = - 0.4, p = 0.691). In summary, switch to EHL (rFVIII-Fc) was associated with an improved clinical outcome, reflected by ABR reduction, and less frequent infusions, without significantly higher factor usage.

Influence of blood group, von Willebrand factor levels, and age on factor VIII levels in non-severe haemophilia A.

BACKGROUND: Data on the effect of ABO blood group (ABO), von Willebrand factor (VWF) levels, and age on factor VIII (FVIII) in non-severe haemophilia A (HA) is scarce. OBJECTIVE: To investigate if ABO, VWF levels, and age have an influence on the variability of FVIII levels and consequently on the assessment of severity in non-severe HA. PATIENTS/METHODS: Eighty-nine patients with non-severe HA and 82 healthy controls were included. Data on ABO was collected and FVIII clotting activity (FVIII:C) with one-stage clotting assay (FVIII:C OSA) and chromogenic substrate assay (FVIII:C CSA), FVIII antigen (FVIII:Ag) and VWF antigen (VWF:Ag) and activity (VWF:Act) were determined. RESULTS: In HA, FVIII:C OSA and CSA and FVIII:Ag were not different between non-O (n = 42, median 15.5, interquartile range 10.4-24.0; 10.0, 6.8-26.0 and 15.2, 10.7-24.9) and O (n = 47, 14.1, 9.0-23.0; 10.0, 5.0-23.0 and 15.2, 9.3-35.5), whereas in healthy controls, non-O individuals had significantly higher FVIII levels. FVIII: C showed no relevant correlation with VWF levels in HA, but we observed strong correlations in healthy controls. Age had only a minor influence in HA, but had a considerable impact on FVIII:C in healthy controls. In multivariable regression analysis ABO, VWF:Ag and age were not associated with FVIII:C in HA, whereas this model explained 61.3% of the FVIII:C variance in healthy controls. CONCLUSIONS: We conclude that in non-severe HA ABO and VWF levels do not substantially influence the variability of FVIII levels and age has only minor effects on it, which is important information for diagnostic procedures.

Epidemiology and Treatment of Patients with Haemophilia in Austria-Update from the Austrian Haemophilia Registry.

The Austrian Haemophilia Registry collects epidemiological data on patients with haemophilia, on treatment modalities and potential side effects. The Registry covers more than 85% of the assumed total number of haemophilia patients in Austria. This report summarizes data on 753 patients: 84.3% (635) have haemophilia A and 15.7% (118) have haemophilia B. Patients' median age is 34 years (range: 1-93 years). Of the total cohort, 39.0% (294) patients have severe haemophilia, 11.3% (85) moderate haemophilia, and 49.4% (372) mild haemophilia. Of the patients with severe haemophilia, 38.4% (113) have been infected with hepatitis C virus (HCV) and 12.6% (37) are human immunodeficiency virus (HIV) positive. Overall, 10.6% (67) of patients with haemophilia A and 1.7% (2) of those with haemophilia B have had an inhibitor in their history. Among patients with severe haemophilia, 68.4% (201) receive prophylaxis and 28.6% (84) receive on-demand therapy. There are 65.0% (191) patients with severe haemophilia who are treated with recombinant products. In conclusion, most patients with severe haemophilia receive prophylactic treatment. HCV and HIV infections are still important issues in the Austrian haemophilia population.

[Treatment of haemophilia in Austria]. / Hämophiliebehandlung in Österreich.

This guideline which is endorsed by the Austrian Society of Haemophilia, the Austrian Society of Paediatrics, and the Austrian Society of Haematology & Medical Oncology is intended to give a clear and practical guidance for diagnosing and treating haemophilia in Austria. In the treatment of haemophilia there are few controlled interventional trials, and recommendations usually have a rather low level of evidence.The main basis for this paper are the new international guidelines by the World Federation of Hemophilia, published in 2013. These were adapted according to the local situation and experience.Covered topics are diagnostics, control visits, pharmacological treatment options, prophylaxis and treatment in children and adults, possible problems arising in haemophilia carriers and special aspects like home therapy, options for venous catheters, management of various traumas, bleedings and interventions, including dental procedures, and last not least inhibitors and their treatment.

Effects of peripheral blood stem cell mobilization with granulocyte-colony stimulating factor and their transcoronary transplantation after primary stent implantation for acute myocardial infarction.

BACKGROUND: There is increasing evidence that transplantation of autologous stem cells improves cardiac function after acute myocardial infarction (AMI). For propagation of peripheral blood stem cells (PBSCs), application of granulocyte-colony stimulating factor (G-CSF) has been shown to be feasible, effective, and safe. We sought to evaluate a clinical and angiographic long-term safety profile of G-CSF application combined with transcoronary PBSC transplantation after recent stent implantation for AMI. METHODS: In patients with AMI and successful primary stenting of the infarct-related coronary artery, pharmacological bone marrow stimulation with G-CSF was initiated on the second postinterventional day. At least after 4 days of G-CSF therapy, apheresis as well as transcoronary transplantation of PBSCs was performed. The PBSCs were infused via a balloon catheter which was inflated inside the stent. Ventriculography and quantitative coronary angiography were performed at baseline and after 6 months. RESULTS: In the 20 patients who received PBSCs, mean left ventricular ejection fraction improved from 46.4% +/- 8.1% at baseline to 54.3% +/- 11% after 6 months (P < .001) because of an increase in systolic function in the infarct region. Control coronary angiography revealed a significant in-stent restenosis of the infarct-related coronary artery, defined as >50% stenosis, in 8 patients (40%), which was complicated by reinfarction in 2 patients (10%). CONCLUSIONS: Transcoronary transplantation of G-CSF-mobilized PBSCs favorably influences cardiac function and can be performed without adverse periprocedural events. However, significant in-stent restenosis and reinfarction seem to occur frequently during the following 6 months.