An 8-year-old boy was referred with anaemia and splenomegaly. Physical examination revealed short stature, thalassaemic facies, pallor and splenomegaly. The full blood count showed a hypochromic, microcytic anaemia. The serum ferritin level was normal. Haemoglobin electrophoresis revealed 56% HbF, 2.3% HbA2 and 41.7% HbA. The boy’s younger sister was subsequently found to have a mild hypochromic, microcytic anaemia with a marked increase in HbF level. Using the polymerase chain reaction (PCR) and deoxyribonucleic acid (DNA) sequencing, two different s-thalassaemia mutations were identified in the parents. Both parents therefore had a s-thalassaemia trait, while both children were compound heterozygotes. The propositus had become transfusion dependent while his sister had managed to maintain her Hb above 8.5 g/dl. The family was studied for s+-thalassaemia and hereditary persistence of fetal haemoglobin (HPFH) deletions. This showed that the daughter had inherited a single s-gene deletion from her mother while the son had not. Studies for HPFH mutations revealed that all four family members had one s-point mutation. The presence of HPFH in this family cannot be considered to have any effect on the thalassaemia major phenotype as neither of these s-mutations are known to be associated with any HbF induction. It is also possible that the daughter inherited a nondeletional HPFH gene which her brother did not.
Table I:Revised international consensus diagnostic criteria for definitive anti-phospholipid syndrome 8 At least one laboratory and one clinical criterion must be met before a diagnosis of antiphospholipid syndrome (APS) can be made.Clinical and laboratory criteria cannot be more than five years apart. Laboratory criteria *Clinical criteria * Patients should be classified according to the number of laboratory criteria met.** Lupus anticoagulant should be detected according to international guidelines. 9,10† Measured by a standardised enzyme linked immunosorbent assay (ELISA).‡ Superficial thrombosis is excluded.MPL -IgM antiphospholipid units; GPL -IgG antiphospholipid units.
In this article, the argument is made that homosexual relationships of love and commitment was known by the writers of the Bible. Though definitions like “gay” or “homosexuality” was not known, sexual identity was known. According to the anthropology of the Mediterranean people, somebody’s identity was found in the way he or she lived: “If I have a homosexual relationship, then my identity was homosexual”. This article shows that permanent homosexual relationships of love and commitment were known among the Greek philosophers. People like Plato, Aristotle and Pausanius had permanent homosexual partners. Even Paul knew about permanent homosexual relationships of love and commitment. Sufficient evidence has been found in cities like Rome, Corinth and Ephesus on the existence of such relationships.
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.
The association between intake of fruits, vegetables, and legumes with cardiovascular disease and deaths has been investigated extensively in Europe, the USA, Japan, and China, but little or no data are available from the Middle East, South America, Africa, or south Asia.We did a prospective cohort study (Prospective Urban Rural Epidemiology [PURE] in 135 335 individuals aged 35 to 70 years without cardiovascular disease from 613 communities in 18 low-income, middle-income, and high-income countries in seven geographical regions: North America and Europe, South America, the Middle East, south Asia, China, southeast Asia, and Africa. We documented their diet using country-specific food frequency questionnaires at baseline. Standardised questionnaires were used to collect information about demographic factors, socioeconomic status (education, income, and employment), lifestyle (smoking, physical activity, and alcohol intake), health history and medication use, and family history of cardiovascular disease. The follow-up period varied based on the date when recruitment began at each site or country. The main clinical outcomes were major cardiovascular disease (defined as death from cardiovascular causes and non-fatal myocardial infarction, stroke, and heart failure), fatal and non-fatal myocardial infarction, fatal and non-fatal strokes, cardiovascular mortality, non-cardiovascular mortality, and total mortality. Cox frailty models with random effects were used to assess associations between fruit, vegetable, and legume consumption with risk of cardiovascular disease events and mortality.Participants were enrolled into the study between Jan 1, 2003, and March 31, 2013. For the current analysis, we included all unrefuted outcome events in the PURE study database through March 31, 2017. Overall, combined mean fruit, vegetable and legume intake was 3·91 (SD 2·77) servings per day. During a median 7·4 years (5·5-9·3) of follow-up, 4784 major cardiovascular disease events, 1649 cardiovascular deaths, and 5796 total deaths were documented. Higher total fruit, vegetable, and legume intake was inversely associated with major cardiovascular disease, myocardial infarction, cardiovascular mortality, non-cardiovascular mortality, and total mortality in the models adjusted for age, sex, and centre (random effect). The estimates were substantially attenuated in the multivariable adjusted models for major cardiovascular disease (hazard ratio [HR] 0·90, 95% CI 0·74-1·10, ptrend=0·1301), myocardial infarction (0·99, 0·74-1·31; ptrend=0·2033), stroke (0·92, 0·67-1·25; ptrend=0·7092), cardiovascular mortality (0·73, 0·53-1·02; ptrend=0·0568), non-cardiovascular mortality (0·84, 0·68-1·04; ptrend =0·0038), and total mortality (0·81, 0·68-0·96; ptrend<0·0001). The HR for total mortality was lowest for three to four servings per day (0·78, 95% CI 0·69-0·88) compared with the reference group, with no further apparent decrease in HR with higher consumption. When examined separately, fruit intake was associated with lower risk of cardiovascular, non-cardiovascular, and total mortality, while legume intake was inversely associated with non-cardiovascular death and total mortality (in fully adjusted models). For vegetables, raw vegetable intake was strongly associated with a lower risk of total mortality, whereas cooked vegetable intake showed a modest benefit against mortality.Higher fruit, vegetable, and legume consumption was associated with a lower risk of non-cardiovascular, and total mortality. Benefits appear to be maximum for both non-cardiovascular mortality and total mortality at three to four servings per day (equivalent to 375-500 g/day).Full funding sources listed at the end of the paper (see Acknowledgments).
Background Haemophilia A (HA) is a bleeding disorder, due to a deficiency in factor VIII (FVIII). These patients are unable to produce a stable fibrin clot in the propagation phase of coagulation as they do not generate sufficient thrombin. The primary treatment for HA in South Africa remains replacement therapy with standard half-life FVIII clotting factor concentrate, aimed at reducing bleeding episodes. Objectives To evaluate the effect of varying concentrations of FVIII on whole blood (WB) clot architecture and kinetics during clot formation in patients with severe HA. Design A cross-sectional study where blood from 20 patients with HA was exposed to FVIII ex vivo and compared to a control group of 20 healthy individuals. Methods Scanning electron microscopy (SEM) was used to study WB clot architecture and thromboelastography ® (TEG ® ) was used to quantify WB clot kinetics. Results Scanning electron microscopy studies revealed that patients with HA have sparse, disorganized fibrin networks with limited crosslinking and red blood cells (RBCs) stacked in rouleaux formation. Haemophilia A blood spiked to a 10 to 15 IU/dL FVIII concentration showed improvements in the organisation of the fibrin network with some altered RBCs. In addition, blood spiked to a 30 to 35 IU/dL FVIII concentration showed an increase in fibrin formation with normal RBCs. Thromboelastography ® showed that patients with HA had an increased clot initiation time and decreased clot strength. When spiked to a 10 to 15 IU/dL FVIII concentration the clot kinetic profile showed normalization. However, an increase in FVIII concentration higher than 30 IU/dL showed altered clot architecture and kinetics. Conclusion Based on the current study, FVIII levels at 10 to 15 IU/dL improved clot kinetics but did not normalize the architecture. It may be sufficient for prevention of haemorrhages. Factor VIII levels at 30 to 35 IU/dL resulted in rapid but weaker clot formation. However, at this concentration the clot architecture was normalised which is important for haemostasis. Here it was also evident that the findings of these two modalities (TEG ® and SEM) should not be separated but interpreted in conjunction with each other.
Background: Acute myeloid leukaemia (AML) is a heterogeneous group of myeloid neoplasms for which two international classification systems exist: the 2022 World Health Organization (WHO) and international consensus classification of myeloid neoplasms (ICC), with an emphasis on molecular abnormalities.Aim: To determine the molecular-genetic profile of AML in the South African public sector.Setting: The Charlotte Maxeke Johannesburg Academic Hospital, Somatic Cell Genetics Unit, National Health Laboratory Service, South Africa.Methods: All newly diagnosed AML cases analysed with next generation sequencing (NGS) between January 2019 and December 2022 were retrospectively reviewed. Clinical and laboratory data were obtained from the laboratory information system.Results: In total, 194 AML cases were tested by NGS (162 classifiable), with a median age of 42 years for adults and 7 years for the paediatric cohort. There were 21 cases of AML with mutated TP53 (ICC), 5 of which were unclassifiable with the WHO classification system. In t(8;21) (q22;q22.1), KIT and FLT3-ITD mutations were present in 43% and 20% of cases respectively; FLT3-ITD in 50% of acute promyelocytic leukaemia (APL) and ~20% of AML with NPM1 were triple mutated (NPM1, DNMT3A, FLT3-ITD).Conclusion: This study revealed a high proportion of exon 17 KIT mutations in t(8;21), FLT3-ITD mutations in APL and triple mutated AML with mutated NPM1, all of which are likely to be driving the poor outcomes seen in these AML subgroups in our setting.Contribution: This is the first nationwide description of the molecular-genetic landscape of AML in the South African public sector.
Human immunodeficiency virus (HIV) infection not only leads to a compromised immune system, but also disrupts normal haematopoiesis, resulting in the frequent manifestation of cytopenias (anaemia, thrombocytopenia and neutropenia). Although there is a definite association between the severity of cytopenia and HIV disease stage, this relationship is not always linear. For example, cytopenias such as thrombocytopenia may occur during early stages of infection. The aetiology of these haematological abnormalities is complex and multifactorial, including drug-induced impaired haematopoiesis, bone marrow suppression due to infiltration of infectious agents or malignant cells , HIV-induced impaired haematopoiesis, and several other factors. In this review, we describe the frequencies of anaemia, thrombocytopenia and neutropenia reported for HIV-infected, treatment-naïve cohorts studied in eastern and southern sub-Saharan African countries. We present a rational approach for the use of diagnostic tests during the workup of HIV-infected patients presenting with cytopenia, and discuss how HIV impacts on haematopoietic stem/progenitor cells (HSPCs) resulting in impaired haematopoiesis. Finally, we describe the direct and indirect effects of HIV on HSPCs which result in defective haematopoiesis leading to cytopenias.
Summary Over recent decades tremendous progress has been made in diagnosing and treating haemophilia and, in resource‐rich countries, life expectancy of people with haemophilia ( PWH ) is now close to that of a healthy person. However, an estimated 70% of PWH are not diagnosed or are undertreated; the majority of whom live in countries with developing health care systems. In these countries, designated registries for people with haemophilia are often limited and comprehensive information on the natural history of the disease and treatment outcomes is lacking. Taken together, this means that planning efforts for future treatment and care of affected individuals is constrained in countries where it is most needed. Establishment of standardized national registries in these countries would be a step towards obtaining reliable sociodemographic and clinical data for an entire country. A series of consensus meetings with experts from widely differing countries with different health care systems took place to discuss concerns specific to countries with developing health care systems. As a result of these discussions, recommendations are made on parameters to include when establishing and harmonizing national registries. Such recommendations should enable countries with developing health care systems to establish standardized national haemophilia registries. Although not a primary objective, the recommendations should also help standardized data collation on an international level, enabling treatment and health care trends to be monitored across groups of countries and providing data for advocacy purposes. Greater standardization of data collation should have implications for optimizing resources for haemophilia care both nationally and internationally.
'%3e%3cpath fill='%23001489' d='M0 0v6h9V0z'/%3e%3cpath fill='%23e03c31' d='M0 0v3h9V0z'/%3e%3cg stroke='%23fff' stroke-width='2'%3e%3cpath id='d' d='m0 0 4.5 3L0 6m4.5-3H9'/%3e%3cuse xlink:href='%23b' stroke='%23ffb81c' clip-path='url(%23c)'/%3e%3c/g%3e%3cuse xlink:href='%23d' fill='none' stroke='%23007749' stroke-width='1.2'/%3e%3c/g%3e%3c/svg%3e)
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
