Inherited bleeding disorders

Abnormal bleeding is a common clinical presentation in general practice, and a rational approach to this problem is therefore required. Investigation of a suspected bleeding disorder necessitates a comprehensive history, thorough physical examination and systematic laboratory work-up. Inherited bleeding disorders (IBDs) typically manifest in childhood, but may present later in life after a haemostatic challenge (such as trauma, surgery, tooth extraction). This two-part CME series is intended to provide insight to the medical practitioner on the clinical spectrum, diagnosis and management of bleeding disorders. Bleeding due to inherited disorders is the subject of discussion in part 1 (current issue), and in part 2 (forthcoming issue) the focus is on bleeding from acquired causes. Patients diagnosed with an IBD should ideally be referred to a dedicated tertiary healthcare facility, e.g. haemophilia centre, for management and follow-up

Gene and cell therapy in South Africa: Current status and future prospects

South Africa has a high disease burden resulting from communicable and non-communicable diseases. Current therapeutic interventions rarely result in a cure and the associated lifelong treatment places a considerable strain on an overburdened health sector. Gene and cell therapies present novel alternatives to disease management, offering the promise of a single treatment and a lifelong cure. Although challenges remain, investment in the field has started to bear fruit, with a number of gene and cell therapeutics reaching the market in the past decade. To take full advantage of these developments, it is important that a proactive approach to nurturing appropriate human and material resources is adopted in the country

Home therapy for inherited bleeding disorders in South Africa: Results of a modified Delphi consensus process

Background. Optimal care of patients with inherited bleeding disorders requires that bleeding episodes are treated early, or still better prevented, through extension of patient care beyond hospital-based treatment to home-based therapy. In South Africa (SA), adoption of home therapy is variable, in part owing to lack of consensus among healthcare providers on what constitutes home therapy, which patients should be candidates for it, how it should be monitored, and what the barriers to home therapy are.Objectives. To conduct a modified Delphi process in order to establish consensus on home therapy among haemophilia healthcare providers in SA.Methods. Treaters experienced in haemophilia care were invited to participate in a consensus-seeking process conducted in three rounds. In round 1, provisional statements around home therapy were formulated as questions and collated in a structured list. In rounds 2 and 3, evolving versions of the questionnaire were administered to participants. Consensus was defined as ≥70% agreement among the participants.Results. The panel composition included an equal number of physicians and non-physicians. The participation rate was 100% through all three consensus rounds. The group reached consensus for 92% of the statements. Consensus of 100% was reached on starting home therapy in paediatric patients, requiring all patients on home therapy to sign informed consent and indemnity, and providing round-the-clock support for patients on home therapy.Conclusions. The home therapy consensus statements in this report have the potential to translate to policy on home therapy and to guide the initiation, practice and evaluation of home therapy programmes in SA.

Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa

Approximately 1 million South Africans are infected with Hepatitis C virus (HCV). The standard of care (SOC) in South Africa is combination therapy (pegylated interferon and ribavirin). HCV genotypes and/or mutations in the core/ non-structural regions have been associated with response to therapy and/or disease progression. This study examines mutations in the core (29-280 amino acids, including ~90 E1 amino acids) and NS5B (241-306 amino acids) regions on pre-treatment isolates from patients attending Johannesburg hospitals or asymptomatic South African blood donors. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Samples grouped into subtypes 1a (N=10) 1b (N=12), 3a(N=5), 4a (N=3) and 5a(N=61). Two mutations, associated with interferon resistance–R70Q and T110N–were present in 29 genotype 5a core sequences. No resistance mutation to NS5B nucleotide inhibitors, sofosbuvir was found. Six putative CD8+ and one CD4+ T-cell epitope sequence in the core region showed binding scores of <300 IC50nM to HLA alleles frequently observed in the South African population. No known CD8+ and CD4+ T-cell epitopes were mapped in the NS5B region. The analysis begs the question whether those infected with genotype 5a will benefit better on interferon-free combination therapies. This study provides new insight into one of the lesser studied HCV genotypes and compares the diversity seen in a large pre-treatment cohort with other subtypes.Poliomyelitis Research Foundation, grant 95097.http://www.elsevier.com/locate/antiviral2017-03-31hb2016Medical Virolog

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

Guideline for the treatment of myelodysplastic syndromes (MDS) in South Africa

The original publication is available at http://www.samj.org.zaIntroduction. Myelodysplastic syndromes (MDS) encompass a heterogeneous group of clonal haematopoietic disorders characterised by chronic and progressive cytopenias resulting from ineffective haematopoiesis. Treatment is complicated by differences in disease mechanisms in different subgroups, variable clinical phenotypes and risk of progression to acute myeloid leukaemia. Rationale. Changes in disease classification, prognostic scoring systems, the availability of novel treatment options and the absence of South African guidelines for the diagnosis and management of these complex disorders underpinned the need for the development of these recommendations. Methods. These recommendations are based on the opinion of a number of experts in the field from the laboratory as well as clinical settings and came from both the private and institutional academic environments. The most recent literature as well as available guidelines from other countries were discussed and debated at a number of different meetings held over a 2-year period. Results. A comprehensive set of recommendations was developed focusing on risk stratification, supportive management and specific treatment. Novel agents and their indications are discussed and recommendations are made based on best available evidence and taking into account the availability of treatments in South Africa. Conclusion. Correct diagnosis, risk stratification and appropriate therapeutic choices are the cornerstones of success in the management of patients with MDS.Publishers' Versio

Patient blood management: A solution for South Africa

For more than 70 years the default therapy for anaemia and blood loss was mostly transfusion. Accumulating evidence demonstrates a significant dose-dependent relationship between transfusion and adverse outcomes. This and other transfusion-related challenges led the way to a new paradigm. Patient blood management (PBM) is the application of evidence-based practices to optimise patient outcomes by managing and preserving the patient’s own blood. ‘Real-world’ studies have shown that PBM improves patient outcomes and saves money. The prevalence of anaemia in adult South Africans is 31% in females and 17% in males. Improving the management of anaemia will firstly improve public health, secondly relieve the pressure on the blood supply, and thirdly improve the productivity of the nation’s workforce. While high-income countries are increasingly implementing PBM, many middle- and low-income countries are still trying to upscale their transfusion services. The implementation of PBM will improve South Africa’s health status while saving costs