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.

Iron status determination in pregnancy using the Thomas plot.

INTRODUCTION: Physiological changes during pregnancy affect routine tests for iron deficiency. The reticulocyte haemoglobin equivalent (RET-He) and serum-soluble transferrin receptor (sTfR) assay are newer diagnostic parameters for the detection of iron deficiency, combined in the Thomas diagnostic plot. We used this plot to determine the iron status of pregnant women presenting for their first visit to an antenatal clinic in Bloemfontein, South Africa. METHODS: Routine laboratory tests (serum ferritin, full blood count and C-reactive protein) and RET-He and sTfR were performed. The iron status was determined using the Thomas plot. RESULTS: For this study, 103 pregnant women were recruited. According to the Thomas plot, 72.8% of the participants had normal iron stores and erythropoiesis. Iron-deficient erythropoiesis was detected in 12.6%. A third of participants were anaemic. Serum ferritin showed excellent sensitivity but poor specificity for detecting depleted iron stores. HIV status had no influence on the iron status of the participants. CONCLUSION: Our findings reiterate that causes other than iron deficiency should be considered in anaemic individuals. When compared with the Thomas plot, a low serum ferritin is a sensitive but nonspecific indicator of iron deficiency. The Thomas plot may provide useful information to identify pregnant individuals in whom haematologic parameters indicate limited iron availability for erythropoiesis.

Recommendations for the management of sickle cell disease in South Africa.

The spectrum of sickle cell disease (SCD) encompasses a heterogeneous group of disorders that include: (I) homozygous SCD (HbSS), also referred to as sickle cell anaemia; (ii) heterozygous SCD (HbAS), also referred to as sickle cell trait; and (iii) compound heterozygous states such as HbSC disease, HbSß thalassaemia, etc. Homozygous or compound heterozygous SCD patients manifest with clinical disease of varying severity that is influenced by biological and environmental factors, whereas subject with sickle cell trait are largely asymptomatic. SCD is characterized by vaso-occlusive episodes that result in tissue ischaemia and pain in the affected region. Repeated infarctive episodes cause organ damage and may eventually lead to organ failure. For effective management, regular follow-up with support from a multidisciplinary healthcare team is necessary. The chronic nature of the disease, the steady increase in patient numbers, and relapsing acute episodes have cost implications that are likely to impact on provincial and national health budgets. Limited resources mandate local management protocols for the purposes of consistency and standardisation, which could also facilitate sharing of resources between centres for maximal utility. These recommendations have been developed for the South African setting, and it is intended to update them regularly to meet new demands and challenges.

Phase I, randomized, double-blind, placebo-controlled, single-dose escalation study of the recombinant factor VIIa variant BAY 86-6150 in hemophilia.

BACKGROUND: BAY 86-6150 is a new human recombinant factor VIIa variant developed for high procoagulant activity and longer action in people with hemophilia with inhibitors. OBJECTIVES: To investigate the safety, tolerability, pharmacodynamics, pharmacokinetics and immunogenicity of BAY 86-6150 in non-bleeding hemophilia subjects. METHODS: The study included non-bleeding men (18-65 years of age) with moderate or severe hemophilia A or B with or without inhibitors. Sixteen subjects were randomized 3 : 1 to four cohorts of escalating doses of BAY 86-6150 (6.5, 20, 50 or 90 µg kg(-1) [n = 3 per cohort]) or placebo (n = 1 per cohort); an independent data-monitoring committee reviewed previous cohort data before the next dose escalation. Blood sampling was performed predose and postdose; subjects were monitored for 50 days postdose. RESULTS: At the tested doses, BAY 86-6150 was not associated with clinically significant adverse events or dose-limiting toxicities. BAY 86-6150 pharmacokinetics exhibited a linear dose response, with a half-life of 5-7 h. Subjects demonstrated consistent, dose-dependent thrombin generation ex vivo in platelet-poor plasma (PPP) (mean peak effect, 26-237 nm thrombin from 6.5 to 90 µg kg(-1)). Peak thrombin levels over time paralleled BAY 86-6150, with thrombin kinetics appearing to be slightly shorter; thus, circulating BAY 86-6150 retained activity. There were corresponding decreases in activated partial thromboplastin and prothrombin times. No subject developed de novo anti-BAY 86-6150 neutralizing antibodies during the 50-day follow-up. CONCLUSIONS: In this first-in-human, multicenter, randomized, double-blind, placebo-controlled, single-dose escalation study, BAY 86-6150 was tolerated at the highest dose (90 µg kg(-1)), with no safety concerns. Safety and efficacy will be further evaluated in phase II/III studies.

Haematology outreach clinics in the Free State and northern Cape.

OBJECTIVE: Evaluation of haematology outreach clinics in the Northern Cape and Free State. DESIGN: Retrospective analysis of records from March 1994 to February 1996. SETTING: Central South Africa is sparsely populated. Consultants from Bloemfontein held outpatient clinics in hospitals (with laboratories) in Bethlehem, Kimberley and Kroonstad. SUBJECTS: 117 patients with suspected haematological disease. MAIN OUTCOME MEASURES: Input measures (population, number of clinics and costs), process measures (patient numbers, patients per clinic, new consultations per clinic, patients' domicile, how they were referred, types of diagnoses and number of patients with non-haematological disorders) and output measures (attrition, changes in attendance and savings). MAIN RESULTS: The 84 clinics that were held, with 636 consultations, did not cost the State anything. Only 6% of the 117 patients had no haematological problem. Sixty-eight per cent had chronic haematological neoplasms. In Kimberley most of the patients came from Kimberley Hospital, while most of the patients at the other clinics were referred via Bloemfontein. There was only a 10% attrition rate and only one-third of patients were referred to Bloemfontein. We saved paying patients an estimated R21,260 in transport costs, while saving the State R172,992 by seeing patients at secondary, instead of tertiary, hospitals. CONCLUSIONS: It is cheaper to send a doctor to an outreach clinic than to refer patients to a central facility, provided there is enough work for a doctor at the clinic. It costs the State much less for patients to be seen at a secondary than a tertiary hospital. Positive spin-offs include academic stimulation of doctors and laboratories in the periphery, with more appropriate referrals to teaching hospitals. Weaknesses include poor availability of expensive drugs at the clinics and lack of standardised records. By commuting to outreach clinics, specialists can greatly reduce health expenditure and spread it from tertiary to lower levels. At the same time more patients have access to their services.

Haemostatic profile of the San (Bushmen) relocated to Schmidtsdrif.

OBJECTIVE: To document the routine haemostatic variables of a group of San relocated from Namibia to South Africa. DESIGN: Cross-sectional study done in two stages. SETTING: Schmidtsdrif military camp in late 1990 and early 1991. SUBJECTS: Healthy adult San volunteers: 31 males and 54 females from the Vasakela and Barakwena groups in 1990; 135 males from the Vasakela group in 1991. The subjects were all soldiers or their dependants. MAIN OUTCOME MEASURES: The following tests were performed: activated partial thromboplastin time, prothrombin time, thrombin time, fibrinogen and coagulation factors V, VII, VIII, IX, X, XI and XII. The results were compared with a Western population reference group (N = 50). MAIN RESULTS: Almost all the haemostatic variables were statistically significantly lower than those of the reference group. The mean derived fibrinogen concentration in the plasma in the first stage of the study (1990) was significantly higher, but this reverted to normal during the second stage (1991), perhaps reflecting a general improvement in health. CONCLUSIONS: Even though the San are one of the best studied groups of indigenous people, this is the first published report on their haemostatic condition. The generally lower levels of haemostatic variables may reflect the lower prevalence of cardiovascular disease in the San. The population needs to be followed up as they westernise.

A phenylalanine 402 to leucine mutation is responsible for a stable inactive conformation of antithrombin.

In a South African family with antithrombin deficiency and unexplained thrombosis, genomic DNA analysis revealed a substitution of Phe 402 by Leu. This mutation involves an amino acid located in the carboxyterminal side of the antithrombin reactive loop and has already been observed in a French family (antithrombin Maisons-Laffitte). In both cases, the expression of the mutation is pleiotropic, i.e. results in a reduction in the circulating concentration of antithrombin and impairs both its anti-thrombin activity and its ability to bind heparin. The effect of a denaturing agent (sodium dodecyl sulfate) on the recognition of the plasma antithrombin by a polyclonal antibody was studied in an immuno-enzymatic assay. The Phe to Leu mutation decreased the sensitivity to denaturation, suggesting that the mutation increases the stability of the protein. Whether this stable conformation is due to a partial insertion of the amino-terminal side of the reactive loop, which would explain how both protease binding and heparin binding are affected, remains to be determined.

Haematological condition of the San (Bushmen) relocated from Namibia to South Africa.

A cross-sectional study was undertaken to assess the haematological condition of the San (Bushmen) relocated from Namibia to South Africa. We studied 238 subjects--145 men and 93 women; none of the women was pregnant. We performed full blood counts and estimations of serum vitamin B12, folate, ferritin and erythrocyte folate concentrations. The mean haemoglobin concentration among the men was 14.7 g/dl and 19 (13%) were anaemic; among the women it was 13.8 g/dl and 18 (19%) were anaemic. Thirteen (9%) of the men and 22 (24%) of the women had low concentrations of serum ferritin, and 38 (26%) of the men and 22 (24%) of the women had erythrocyte folate concentrations of less than 270 nmol/l. Three (2%) men and 4 (4%) women had serum vitamin B12 concentrations of less than 120 pmol/l. Eighty-one (56%) of the men and 76 (82%) of the women had eosinophilia, probably because of parasitic infections. It would appear from this and previous studies that prolonged exposure of these hunter-gatherers to a Western lifestyle has resulted in a high prevalence of anaemia, caused by low iron and folate intakes, complicated by alcohol consumption.

Glucose-6-phosphate dehydrogenase (G6PD) electrophoretic variants and the PvuII polymorphism in southern African populations.

Southern African Bantu-speaking negroid and San populations were examined with regard to the glucose-6-phosphate dehydrogenase (G6PD) PvuII restriction fragment length polymorphism (RFLP) showing alleles of 4 kb and 1.6 kb, called Type 1 and Type 2, respectively. The standardized disequilibrium coefficient for the electrophoretic G6PD types and PvuII alleles in the Southern African population was 0.28. The molecular lesion causing the GdA mutation is the same in the San and Southern African negroid populations. GdA chromosomes are found in association with both the Type 1 and Type 2 alleles, whereas none of the 62 GdB chromosomes from the Southern African populations had the Type 2 allele. Five of the 44 GdB chromosomes studied in the American Black population had the Type 2 allele, indicating that the GdB allele in the two populations may have different origins. The presence of all 3 A- deficiency mutations in the G6PD A gene, in a region where the ancestral population was thought to have predominantly G6PD B, may be explained by their origin in Africa after the divergence of the races.

Premature closure of the ductus arteriosus causing intra-uterine death. A case report.

A case of hydrops fetalis with intra-uterine death after premature closure of the ductus arteriosus because of inhibition of premature labour by the administration of indomethacin is presented. The physiology of acute and chronic intra-uterine constriction of the ductus arteriosus and the effects of indomethacin on the fetal circulation are discussed. Mention is also made of the moral conflict confronting the doctor in the management of an affected fetus during the third trimester.