Recombinant factorVIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A

This work was supported by funding from Biogen, including funding for the editorial and writing support in the the development of this paper

Key Issues In Inhibitor Management In Patients With Haemophilia

[No abstract available]12SUPPL.1s319s329Bray, G.L., Gomperts, E.D., Courter, S., A multicenter study of recombinant factor VIII (recombinate): Safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A. The recombinate study group (1994) Blood, 83, pp. 2428-2435Lusher, J.M., Arkin, S., Abildgaard, C.F., Schwartz, R.S., Recombinant factor VIII for the treatment of previously untreated patients with hemophilia A. Safety, efficacy, and development of inhibitors. Kogenate previously untreated patient study group (1993) N Engl J Med, 328, pp. 453-459Hay, C.R., Baglin, T.P., Collins, P.W., The diagnosis and management of factor VIII and IX inhibitors: A guideline from the UK Haemophilia Centre Doctors' Organization (UKHCDO) (2000) Br J Haematol, 111, pp. 78-90Lawrence, J.S., Johnson, J.B., The presence of a circulating anticoagulant in a male member of a hemophiliac family (1941) Trans Am Clin Climatol Assoc, 57, pp. 223-231Konkle, B.A., Ebbesen, L.S., Erhardtsen, E., Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors (2007) J Thromb Haemost, 5, pp. 1904-1913Leissinger, C., Gringeri, A., Antmen, B., Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors (2011) N Engl J Med, 365, pp. 1684-1692Gouw, S.C., Van Den Berg, H.M., Oldenburg, J., F8 gene mutation type and inhibitor development in patients with severe hemophilia A: Systematic review and meta-analysis (2012) Blood, 119, pp. 2922-2934Gouw, S.C., Van Der Bom, J.G., Auerswald, G., Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: The CANAL cohort study (2007) Blood, 109, pp. 4693-4697Iorio, A., Halimeh, S., Holzhauer, S., Rate of inhibitor development in previously untreated hemophilia A patients treated with plasma-derived or recombinant factor VIII concentrates: A systematic review (2010) J Thromb Haemost, 8, pp. 1256-1265Wight, J., Paisley, S., The epidemiology of inhibitors in haemophilia A: A systematic review (2003) Haemophilia, 9, pp. 418-435Hay, C.R., The epidemiology of factor VIII inhibitors (2006) Haemophilia, 12 (SUPPL. 6), pp. 23-28. , discussion 8-9Astermark, J., Basic aspects of inhibitors to factors VIII and IX and the influence of non-genetic risk factors (2006) Haemophilia, 12 (SUPPL. 6), pp. 8-13Hay, C.R., Palmer, B., Chalmers, E., Incidence of factor VIII inhibitors throughout life in severe hemophilia A in the United Kingdom (2011) Blood, 117, pp. 6367-6370Wacey, A.I., Kemball-Cook, G., Kazazian, H.H., The haemophilia A mutation search test and resource site, home page of the factor VIII mutation database: HAMSTeRS (1996) Nucleic Acids Res, 24, pp. 100-102Green, P.M., Montandon, A.J., Ljung, R., Haemophilia B mutations in a complete Swedish population sample: A test of new strategy for the genetic counselling of diseases with high mutational heterogeneity (1991) Br J Haematol, 78, pp. 390-397Viel, K.R., Ameri, A., Abshire, T.C., Inhibitors of factor VIII in black patients with hemophilia (2009) N Engl J Med, 360, pp. 1618-1627Viel, K.R., Machiah, D.K., Warren, D.M., A sequence variation scan of the coagulation factor VIII (FVIII) structural gene and associations with plasma FVIII activity levels (2007) Blood, 109, pp. 3713-3724Santos, A., Annichino-Bizzacchi, J.M., Ozelo, M.C., Inhibitors of factor VIII in hemophilia (2009) N Engl J Med, 361, pp. 309-310. , author reply 10Oldenburg, J., Pavlova, A., (2006) Genetic risk factors for inhibitors to factors VIII and IX.Haemophilia, 12 (SUPPL. 6), pp. 15-22Goodeve, A.C., Peake, I.R., The molecular basis of hemophilia A: Genotype-phenotype relationships and inhibitor development (2003) Semin Thromb Hemost, 29, pp. 23-30Jacquemin, M., Vantomme, V., Buhot, C., CD4+ T-cell clones specific for wild-type factor VIII: A molecular mechanism responsible for a higher incidence of inhibitor formation in mild/moderate hemophilia A (2003) Blood, 101, pp. 1351-1358Kane, W.H., Davie, E.W., Cloning of a cDNA coding for human factor V, a blood coagulation factor homologous to factor VIII and ceruloplasmin (1986) Proc Natl Acad Sci USA, 83, pp. 6800-6804Lacroix-Desmazes, S., Repesse, Y., Kaveri, S.V., Dasgupta, S., The role of VWF in the immunogenicity of FVIII (2008) Thromb Res, 122 (SUPPL. 2), pp. S3-6Rivard, G.E., Lillicrap, D., Poon, M.C., Can activated recombinant factor VII be used to postpone the exposure of infants to factor VIII until after 2 years of age? (2005) Haemophilia, 11, pp. 335-339Hermans, C., De Moerloose, P., Fischer, K., Management of acute haemarthrosis in haemophilia A without inhibitors: Literature review, European survey and recommendations (2011) Haemophilia, 17, pp. 383-392Kurnik, K., Bidlingmaier, C., Engl, W., New early prophylaxis regimen that avoids immunological danger signals can reduce FVIII inhibitor development (2010) Haemophilia, 16, pp. 256-262Gouw, S.C., Van Den Berg, H.M., Fischer, K., Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: The RODIN study (2013) BloodKreuz, W., Ettingshausen, C.E., Zyschka, A., Inhibitor development in previously untreated patients with hemophilia A: A prospective long-term follow-up comparing plasmaderived and recombinant products (2002) Semin Thromb Hemost, 28, pp. 285-290Santagostino, E., Mannucci, P.M., Bianchi Bonomi, A., Guidelines on replacement therapy for haemophilia and inherited coagulation disorders in Italy (2000) Haemophilia, 6, pp. 1-10Rezende, S.M., Pinheiro, K., Caram, C., Registry of inherited coagulopathies in Brazil: First report (2009) Haemophilia, 15, pp. 142-149Manco-Johnson, M.J., Abshire, T.C., Shapiro, A.D., Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia (2007) N Engl J Med, 357, pp. 535-544Kruse-Jarres, R., Inhibitors: Our greatest challenge.Can we minimize the incidence? 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(2011) Haemophilia, 17, pp. e849-e857Dimichele, D., Negrier, C., A retrospective postlicensure survey of FEIBA efficacy and safety (2006) Haemophilia, 12, pp. 352-362Valentino, L.A., Assessing the benefits of FEIBA prophylaxis in haemophilia patients with inhibitors (2010) Haemophilia, 16, pp. 263-271Brackmann, H.H., Schwaab, R., Effenberger, W., Hemophilia treatment. Side effects during immune tolerance induction (2000) Haematologica, 85, pp. 75-77Young, G., McDaniel, M., Nugent, D.J., Prophylactic recombinant factor VIIa in haemophilia patients with inhibitors (2005) Haemophilia, 11, pp. 203-207Morfini, M., Auerswald, G., Kobelt, R.A., Prophylactic treatment of haemophilia patients with inhibitors: Clinical experience with recombinant factor VIIa in European Haemophilia Centres (2007) Haemophilia, 13, pp. 502-507Jimenez-Yuste, V., Alvarez, M.T., Martin-Salces, M., Prophylaxis in 10 patients with severe haemophilia A and inhibitor: Different approaches for different clinical situations (2009) Haemophilia, 15, pp. 203-209Young, G., Auerswald, G., Jimenez-Yuste, V., PRO-PACT: Retrospective observational study on the prophylactic use of recombinant factor VIIa in hemophilia patients with inhibitors (2012) Thromb ResGupta, S., Siddiqi, A.E., Soucie, J.M., The effect of secondary prophylaxis versus episodic treatment on the range of motion of target joints in patients with haemophilia (2013) Br J Haematol, 161, pp. 424-433Carcao, M., Lambert, T., Prophylaxis in haemophilia with inhibitors: Update from international experience (2010) Haemophilia, 16 (SUPPL. 2), pp. 16-23Dimichele, D.M., Hoots, W.K., Pipe, S.W., International workshop on immune tolerance induction: Consensus recommendations (2007) Haemophilia, 13 (SUPPL. 1), pp. 1-22Lenk, H., The German Registry of immune tolerance treatment in hemophilia-1999 update (2000) Haematologica, 85, pp. 45-47Brackmann, H.H., Oldenburg, J., Schwaab, R., Immune tolerance for the treatment of factor VIII inhibitors-twenty years' 'bonn protocol' (1996) Vox Sang, 70 (SUPPL. 1), pp. 30-35Oldenburg, J., Schwaab, R., Brackmann, H.H., Induction of immune tolerance in haemophilia A inhibitor patients by the 'Bonn Protocol': Predictive parameter for therapy duration and outcome (1999) Vox Sang, 77 (SUPPL. 1), pp. 49-54Mauser-Bunschoten, E.P., Nieuwenhuis, H.K., Roosendaal, G., Van Den Berg, H.M., Low-dose immune tolerance induction in hemophilia A patients with inhibitors (1995) Blood, 86, pp. 983-988Indications and recommended doses for treating patients with factor VIII inhibitors in hemophilia A (2008) Cross-Sectional Guidelines for Therapy with Blood Components and Plasma Derivatives. Executive Committee of the German Medical Association on the Recommendation of the Scientific Advisory Board, p. 91. , German Medical AssociationCoppola, A., Margaglione, M., Santagostino, E., Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance induction of hemophilia A patients with highresponding inhibitors (2009) J Thromb Haemost, 7, pp. 1809-1815Freiburghaus, C., Berntorp, E., Ekman, M., Immunoadsorption for removal of inhibitors: Update on treatments in Malmo-Lund between 1980 and 1995 (1998) Haemophilia, 4, pp. 16-20Auerswald, G., Spranger, T., Brackmann, H.H., The role of plasmaderived factor VIII/von Willebrand factor concentrates in the treatment of hemophilia A patients (2003) Haematologica, 88, pp. EREP05Dimichele, D., The North American Immune Tolerance Registry: Contributions to the thirty-year experience with immune tolerance therapy (2009) Haemophilia, 15, pp. 320-328Mariani, G., Ghirardini, A., Bellocco, R., Immune tolerance in hemophilia-principal results from the International Registry. Report of the factor VIII and IX Subcommittee (1994) Thromb Haemost, 72, pp. 155-158Mariani, G., Kroner, B., Immune tolerance in hemophilia with factor VIII inhibitors: Predictors of success (2001) Haematologica, 86, pp. 1186-1193Franchini, M., Mannucci, P.M., Inhibitors of propagation of coagulation (factors VIII, IX and XI): A review of current therapeutic practice (2011) Br J Clin Pharmacol, 72, pp. 553-562Greninger, D.A., Saint-Remy, J.M., Jacquemin, M., The use of factor VIII/von Willebrand factor concentrate for immune tolerance induction in haemophilia A patients with high-titre inhibitors: Association of clinical outcome with inhibitor epitope profile (2008) Haemophilia, 14, pp. 295-302Gringeri, A., Musso, R., Mazzucconi, M.G., Immune tolerance induction with a high purity von Willebrand factor/VIII complex concentrate in haemophilia A patients with inhibitors at high risk of a poor response (2007) Haemophilia, 13, pp. 373-379Kurth, M.A., Dimichele, D., Sexauer, C., Immune tolerance therapy utilizing factor VIII/von Willebrand factor concentrate in haemophilia A patients with high titre factor VIII inhibitors (2008) Haemophilia, 14, pp. 50-55Astermark, J., Morado, M., Rocino, A., Current European practice in immune tolerance induction therapy in patients with haemophilia and inhibitors (2006) Haemophilia, 12, pp. 363-371Garvey, B., Rituximab in the treatment of autoimmune haematological disorders (2008) Br J Haematol, 141, pp. 149-169Franchini, M., Mengoli, C., Lippi, G., Immune tolerance with rituximab in congenital haemophilia with inhibitors: A systematic literature review based on individual patients' analysis (2008) Haemophilia, 14, pp. 903-912Sorensen, B., Johansen, P., Christiansen, K., Whole blood coagulation thrombelastographic profiles employing minimal tissue factor activation (2003) J Thromb Haemost, 1, pp. 551-558De Paula, E.V., Kavakli, K., Mahlangu, J., Recombinant factor VIIa analog (vatreptacog alfa [activated]) for treatment of joint bleeds in hemophilia patients with inhibitors: A randomized controlled trial (2012) J Thromb Haemost, 10, pp. 81-89Holmberg, H.L., Lauritzen, B., Tranholm, M., Ezban, M., Faster onset of effect and greater efficacy of NN1731 compared with rFVIIa, aPCC and FVIII in tail bleeding in hemophilic mice (2009) J Thromb Haemost, 7, pp. 1517-1522Moss, J., Scharling, B., Ezban, M., Moller Sorensen, T., Evaluation of the safety and pharmacokinetics of a fast-acting recombinant FVIIa analogue, NN1731, in healthy male subjects (2009) J Thromb Haemost, 7, pp. 299-305Sorensen, B., Persson, E., Ingerslev, J., Factor VIIa analogue (V158D/E296V/M298Q-FVIIa) normalises clot formation in whole blood from patients with severe haemophilia A (2007) Br J Haematol, 137, pp. 158-165Allen, G.A., Persson, E., Campbell, R.A., A variant of recombinant factor VIIa with enhanced procoagulant and antifibrinolytic activities in an in vitro model of hemophilia (2007) Arterioscler Thromb Vasc Biol, 27, pp. 683-689Mahlangu, J.N., Coetzee, M.J., Laffan, M., Phase I, randomized, double-blind, placebo-controlled, single-dose escalation study of the rFVIIa variant BAY 86-6150 in hemophilia (2012) J Thromb Haemost, 10, pp. 773-780Karpf, D.M., Sorensen, B.B., Hermit, M.B., Prolonged halflife of glycoPEGylated rFVIIa variants compared to native rFVIIa (2011) Thromb Res, 128, pp. 191-195Sen, P., Ghosh, S., Ezban, M., Effect of glycoPEGylation on factor VIIa binding and internalization (2010) Haemophilia, 16, pp. 339-348Toschi, V., OBI-1, porcine recombinant factor VIII for the potential treatment of patients with congenital hemophilia A and alloantibodies against human Factor VIII (2010) Curr Opin Mol Ther, 12, pp. 617-625Parker, E.T., Craddock, H.N., Barrow, R.T., Lollar, P., Comparative immunogenicity of recombinant B domain-deleted porcine factor VIII and Hyate: C in hemophilia A mice presensitized to human factor VIII (2004) J Thromb Haemost, 2, pp. 605-611Kempton, C.L., Abshire, T.C., Deveras, R.A., Pharmacokinetics and safety of OBI-1, a recombinant B domain-deleted porcine factor VIII, in subjects with haemophilia A (2012) Haemophilia, 18, pp. 798-804Abshire, T.C., Brackmann, H.H., Scharrer, I., Sucrose formulated recombinant human antihemophilic factor VIII is safe and efficacious for treatment of hemophilia A in home therapy-International Kogenate-FS Study Group (2000) Thromb Haemost, 83, pp. 811-816Tarantino, M.D., Collins, P.W., Hay, C.R., Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin-free method: Pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A (2004) Haemophilia, 10, pp. 428-437Young, G., Cooper, D.L., Gut, R.Z., Dosing and effectiveness of recombinant activated factor VII (rFVIIA) in congenital haemophilia with inhibitors by bleed type and location: The experience of the Haemophilia and Thrombosis Research Society (HTRS) Registry (2004-2008) (2012) Haemophilia, 18, pp. 990-99

Reflections on the process, challenges, and lessons learned conducting remote qualitative research on violence against women during COVID-19 pandemic lockdown in South Africa

This is the final version. Available on open access from BMC via the DOI in this recordData availability: The datasets analysed in the study are available from the corresponding author on reasonable request.Background Violence against women (VAW) research is a sensitive topic, which has been conducted mainly using face-to-face methods. The COVID-19 pandemic lockdown and restrictions on movement presented an opportunity to conduct VAW research using remote methods. We discuss how we adapted methods, reflect on lessons learned, and make recommendations highlighting key considerations when conducting remote research on a sensitive topic of VAW. Methods We designed and conducted an exploratory qualitative study using remote methods with 18 men and 19 women, aged 18 years and older, who lived with their partner or spouse during lockdown in South Africa. The aim of the study was to explore experiences of COVID-19 lockdown, and its link to women and children’s experiences of violence in the homes. Data presented in this paper draws from researchers’ reflections drawn from debriefing sessions during the research process, and from participants’ interview transcripts. Findings Remote recruitment of participants took longer than anticipated, and we had to re-advertise the study. We could not ensure safety and privacy during interviews. Regardless of all the safety and privacy measures we put in place during the research process, some participants had an adult person present in the room during interviews, and the researchers had no control over interruptions. Rapport was difficult to establish without an in-person connection, which limited disclosure about violence experience (amongst women) and perpetration (amongst men). Conclusions Given the methodological and ethical challenges which limited disclosure of VAW remotely, we conclude that telephone interviews used in our study impacted on the quality of study data. Therefore, we do not recommend VAW research to be conducted remotely, unless it is essential and participants are already known to the interviewer and trust has been established.South African Medical Research CouncilDST – NRF Centre of Excellence (CoE) in Human Developmen

Once-weekly prophylaxis with 40 IU/kg nonacog beta pegol (N9-GP) achieves trough levels of >15% in patients with haemophilia B: Pooled data from the paradigm™ trials.

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Core data set on safety, efficacy, and durability of hemophilia gene therapy for a global registry: Communication from the SSC of the ISTH

BackgroundGene therapy for people with hemophilia (PWH) will soon become available outside current clinical trials. The World Federation of Hemophilia (WFH), in collaboration with International Society of Thrombosis and Hemostasis Scientific and Standardization Committee (ISTH SSC), the European Haemophilia Consortium (EHC), the US National Hemophilia Foundation (NHF), the American Thrombosis and Hemostasis Network (ATHN), industry gene therapy development partners and Regulatory liaisons have developed the Gene Therapy Registry (GTR), designed to collect long- term data on all PWH who receive hemophilia gene therapy.ObjectiveThe objectives of the GTR are to record the long- term safety and efficacy data post gene therapy infusion and to assess the changes in quality of life and burden of disease post- gene- therapy infusion.MethodsThe GTR is a prospective, observational, and longitudinal registry developed under the guidance of a multi- stakeholder GTR Steering Committee (GTR SC), composed of health care professionals, patient advocates, industry representatives, and regulatory agency liaisons. All PWH who receive gene therapy by clinical trial or commercial product will be invited to enrol in the registry through their hemophilia treatment centers (HTCs). The registry aims to recruit 100% of eligible post gene therapy PWH globally. Through an iterative process, and following the guidance of the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), the GTR SC has developed a core set of data to be collected on all patients post gene therapy.ResultsThe core data set includes demographic information, vector infusion details, safety, efficacy, quality of life and burden of disease.ConclusionsThe GTR is a global effort to ensure that long term safety and efficacy outcomes are recorded and analysed and rare adverse events, in a small patient population, are identified. Many unknowns on the long- term safety and efficacy of gene therapy for hemophilia may also be addressed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163440/2/jth15023.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163440/1/jth15023_am.pd

Safety and pharmacokinetics of anti-TFPI antibody (concizumab) in healthy volunteers and patients with hemophilia: a randomized first human dose trial

BACKGROUND: Prophylaxis with either intravenous (i.v.) factor VIII (FVIII) or FIX is the gold standard of care for patients with severe hemophilia. A monoclonal antibody (concizumab) targeting tissue factor pathway inhibitor (TFPI) that can be administered subcutaneously (s.c.) has the potential to alter current concepts of prophylaxis in hemophilia. OBJECTIVES: To evaluate the safety and describe the pharmacokinetics and pharmacodynamics of single-dose concizumab in healthy volunteers and patients with hemophilia A or B. METHODS: In this first human dose, phase 1, multicenter, randomized, double-blind, placebo-controlled trial escalating single i.v. (0.5-9000 μg kg(-1) ) or s.c. (50-3000 μg kg(-1) ) doses of concizumab were administered to healthy volunteers (n = 28) and hemophilia patients (n = 24). RESULTS: Concizumab had a favorable safety profile after single i.v. or s.c. administration. There were no serious adverse events and no anti-concizumab antibodies. No clinically relevant changes in platelets, prothrombin time, activated partial thromboplastin time, fibrinogen, or antithrombin were found. A dose-dependent procoagulant effect of concizumab was seen as increased levels of D-dimers and prothrombin fragment 1 + 2. Nonlinear pharmacokinetics of concizumab was observed due to target-mediated clearance. A maximum mean AUC0-∞ of 33 960 h μg mL(-1) and a maximum mean concentration of 247 μg mL(-1) was measured at the highest dose. CONCLUSIONS: Concizumab showed a favorable safety profile after i.v. or s.c. administration and nonlinear pharmacokinetics was observed due to target-mediated clearance. A concentration-dependent procoagulant effect of concizumab was observed, supporting further study into the potential use of s.c. concizumab for hemophilia treatment

The effect of emicizumab prophylaxis on health-related outcomes in persons with haemophilia A with inhibitors: HAVEN 1 Study

Introduction: Persons with haemophilia A (PwHA) with inhibitors to factor VIII often experience decreased health-related outcomes. In HAVEN 1 (NCT02622321), there was a statistically significant reduction in bleeding with emicizumab prophylaxis versus no prophylaxis. Aim: Describe health-related outcomes in PwHA with inhibitors in HAVEN 1. Methods: PwHA with inhibitors aged 6512\ua0years previously on episodic bypassing agents (BPAs) were randomized to emicizumab prophylaxis (Arm A; n\ua0=\ua035) or no prophylaxis (Arm B; n\ua0=\ua018); participants previously on BPA prophylaxis received emicizumab prophylaxis (Arm C; n\ua0=\ua049). Health-related outcomes assessed at baseline and monthly thereafter: Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL), Haemophilia-specific Quality of Life Questionnaire for Children Short Form (Haemo-QoL SF), EuroQol 5-Dimensions 5-Levels (EQ-5D-5L) index utility score (IUS) and visual analogue scale (EQ-VAS) and work/school days. Days hospitalized also recorded. Results: At week 25, differences (ANCOVA) in adjusted mean scores (95% confidence interval) favoured Arm A versus B for Haem-A-QoL \u201cTotal\u201d score (14.0 [5.6, 22.5]; P\ua0=\ua00.002) and \u201cPhysical Health\u201d (21.6 [7.9, 35.2]; P\ua0=\ua00.003); EQ-VAS ( 129.7 [ 1217.6, 121.82]; P\ua0=\ua00.017); and IUS ( 120.16 [ 120.25, 120.07]; P\ua0=\ua00.001); mean scores are comparable in Arms A and C. Throughout the study, a greater proportion of participants on emicizumab prophylaxis than no prophylaxis exceeded questionnaire-specific responder thresholds. Mean proportion of missed work days and number of days hospitalized were lower with emicizumab prophylaxis than no prophylaxis. Conclusions: In PwHA with inhibitors, emicizumab prophylaxis was associated with substantial and meaningful improvements in health-related outcomes

Prophylaxis is the new standard of care in patients with haemophilia

Randomised controlled clinical trial evidence on prophylaxis as optimal care for patients with haemophilia was generated more than a decade ago. However, this knowledge has not translated into clinical practice in South Africa (SA) owing to many barriers to prophylaxis. These include the high treatment burden imposed by prophylaxis (frequent injections two to four times a week), the need for intravenous access to administer replacement clotting factor therapies, and the higher volume of clotting factor required compared with episodic treatment. The recently introduced non-factor therapies in haemophilia care have addressed many of these barriers. For example, emicizumab, which is currently the only globally approved non-factor therapy, can be administered subcutaneously less frequently (weekly, fortnightly or every 4 weeks) and has led to global adoption of prophylaxis as the standard of care in haemophilia by the bleeding disorders community. Haemophilia A is the most prevalent clotting factor deficiency in SA, with >2 000 people diagnosed to date. However, only a few of these patients are currently on prophylaxis. In this ‘In Practice’ article, we review the rationale for prophylaxis, outline its goals and benefits, and provide evidence-based guidance on which haemophilia patients should be prioritised for emicizumab prophylaxis. This consensus guidance facilitates the adoption of prophylaxis as a national policy and the new standard of care in haemophilia in SA.http://www.samj.org.zadm2022HaematologyPaediatrics and Child Healt