Kinetics of indium-111-labelled platelets in HIV-infected patients with and without associated thrombocytopaenia.

Seven to 12% of HIV-infected patients have thrombocytopaenia. The pathophysiology of the thrombocytopaenia is not clear. It has been variously suggested that it may be caused by an increased peripheral platelet destruction, a defect in platelet production, or by a combination of these. The aim of the study was to elucidate the pathogenesis of HIV-associated thrombocytopaenia. We determined the mean platelet life span (MPLS) and calculated the turnover of autologous indium-111-labelled platelets in 17 HIV-positive patients, seven with thrombocytopaenia. The sites of sequestration of labelled platelets were quantified. The thrombocytopaenic patients had a very short MPLS (3.0+/-3.8 h) and a marked increase in platelet production (18.2+/-12.6x10(9)/l/h). The majority of these patients (5 of 7) had excessive sequestration of platelets in the spleen. Five of the patients with a normal blood platelet count had a shortened MPLS (109+/-23 h) and increased platelet turnover (3.8+/-1.2x10(9)/l/h), i.e. the increased peripheral platelet destruction was compensated for by increased platelet production. The other five patients with a normal platelet count had normal MPLS (195+/-11 h) and slightly increased platelet production (2.5+/-0.6x10(9)/l/h). We conclude that patients with HIV-associated thrombocytopaenia have increased peripheral platelet destruction. Platelet production is elevated but is insufficient to maintain a normal peripheral platelet count. In these patients platelets are predominantly sequestrated in the spleen. Patients with HIV infection and a normal blood platelet count may also have increased platelet production. This may be an early subclinical phase in the development of full-blown HIV-associated thrombocytopaenia.

Blood transfusion in South Africa.

Sixty years of development have transformed previously small collection centres into major regional transfusion services. These organisations collect and process nearly 900,000 units of blood annually from a donor base of some 500,000 individuals with a male to female ratio of 5:3. Three quarters of the donations are from a regular pool of largely white people. The latter has both a cultural and socio-economic component that needs redress to meet expanding requests. The range of products and quality of newer technologies, including those that are centered on aphereses are commensurate with first world standards. Quality control is universally monitored and registration falls under prevailing legislation. The future of these vitally important services will need to accommodate changing priorities in South Africa. Specific challenges are a greater commitment to primary health care, the rapidly rising incidence of HIV-positivity and centralisation of some facilities including plasma fractionation.

Aspects of folate metabolism in renal failure.

Plasma and urine folate fractions were evaluated after ingestion of radioactive N5-methyl-tetrahydrofolic acid by a normal control (subject I), a patient on maintenance haemodialysis for chronic glomerulonephritis (subject 2), and an anephric patient on haemodialysis (subject 3). In subjects 1 and 2 maximal plasma radiofolate peaks appeared within 1 h of isotope ingestion. In subject 3 the radiofolate peak was delayed for 6 h although the total biofolate fraction reached a maximum at 0.5 h (comparable with findings in subject 2). Sephadex DEAE A50 chromatography showed the radiofolate fraction in subject I to be compatible with N5-methyl-tetrahydrofolic acid (peak I). In subject 2 additional radiofolate peaks 2 and 3 were found. The nature of peak 2 is unknown but peak 3 may represent 10-formyl-tetrahydrofolate. Peak I was minimally present in subject 3. This limited study suggest a defect of methyl-tetrahydrofolate metabolism in the anephric state unassociated with defective renal excretion per se. In normal urine, peak 2 predominated while urine of subject 2 had a predominant peak 3 and lesser peaks I and 2. Compared with the control, uraemic subjects 2 and 3 showed greatly decreased dialysis-resistant (bound plasma radiofolate fractions; all urinary radiofolates were fully dialysable. The unexplained radiofolate 'binder' detected with haemoglobin-coated charcoal adsorption in urine (subject 2) and occasionally in plasma, probably represents an artefact. Plasma from 27 uraemic subjects showed no abnormal in vitro radiofolate binding capacity.

In vitro binding of folates by body fluids.

It is useful to differentiate between saturated folate binders in serum (carrying endogenous folate) and unsaturated binders (investigated in the present study). These two groups of binders need not necessarily be chemically identical and the unsaturated binder may even be an in vitro artifact, especially when measured with non-physiological folates. Macromolecular binding of radio-active N-5-methyl tetrahydrofolic acid (CH3H4PteGlu) and/or folic acid (PteGlu) by human serum and urine was assessed by means of exhaustive saline dialysis, haemoglobin-coated charcoal adsorption, column chromatography with DEAE-Sephadex A-50, and sucrose gradient analysis. Binding was found to be minimal or absent. Charcoal adsorption showed a mean serum binding capacity of 0 mug/1. for PteGlu and 0.58 mug/1. for CH3H4PteGlu. In pregnancy the mean serum values were 0.23 mug/1. for PteGlu, 0.66 mjg/1. for CH3H4PteGlu, and with folate deficiency 0.30 mug/1. for PteGlu, 0.49 mug/1. for CH3H4PteGlu. Mean urinary folate binding was minimal (less than 0.5 mug/1.), and red cell haemolysate similarly revealed very low binding on exhaustive dialysis. Column chromatography showed that tracer doses of [14C]PteGlu added to serum migrated distally to the protein zone; [14C]CH3H4PteGlu similarly showed no evidence of protein binding. On a sucrose gradient [14C]PteGlu also separated clear of the protein zone.