No abstract

Methods

Red blood cells (RBCs) from patients with sickle cell disease (SCD) lyse in deoxygenated isosmotic non-electrolyte solutions. Haemolysis has features which suggest that it is linked to activation of the pathway termed Psickle. This pathway is usually described as a non-specific cationic conductance activated by deoxygenation, HbS polymerisation and RBC sickling. The current work addresses the hypothesis that this haemolysis will provide a novel diagnostic and prognostic test for SCD, dependent on the altered properties of the RBC membrane resulting from HbS polymerisation. A simple test represented by this haemolysis assay would be useful especially in less affluent deprived areas of the world where SCD is most prevalent. RBCs from HbSS and most HbSC individuals showed progressive lysis in deoxygenated isosmotic sucrose solution at pH 7.4 to a level greater than that observed with RBCs from HbAS or HbAA individuals. Cytochalasin B prevented haemolysis. Haemolysis was temperature- and pH-dependent. It required near physiological temperatures to occur in deoxygenated sucrose solutions at pH 7.4. At pH 6, haemolysis occurred even in oxygenated samples. Haemolysis was reduced in patients on long-term (>5 months) hydroxyurea treatment. Several manoeuvres which stabilise soluble HbS (aromatic aldehydes o-vanillin or 5-hydroxymethyl, and urea) reduced haemolysis, an effect not due to increased oxygen affinity. Conditions designed to elicit HbS polymerisation in cells from sickle trait patients (deoxygenated hyperosmotic sucrose solutions at pH 6) supported their haemolysis. These findings are consistent with haemolysis requiring HbS polymerisation and support the hypothesis that this may be used as a test for SCD.

The aim of our review was to evaluate the evidence for and against folic acid supplementation in sickle cell disease. Folic acid has been both widely prescribed and hotly debated for the last four decades. We undertook an extensive literature based review with the aim of evaluating the clinical benefits of this supplementation and its implications on future paediatric practice. Comprehensive scientific search engines were used to locate articles published up to June 2011. A wide range of search terms were used, and article references and citations were reviewed for further leads. Studies in support of folic acid supplementation have cited low serum and erythrocyte folate levels in paediatric sickle cell patients, high incidence of megaloblastic anaemia, patient desire for folic acid and the positive effects of supplementation including; reversal of developmental delay, reduced dactylitis and reduction of homocysteine levels leading to reduced cardiovascular, stroke and venous thrombosis risk. Studies against folic acid supplementation conversely found that folate is not deficient in patients, megaloblastic change is uncommon and both these parameters are not improved with supplementation. They have shown that folic acid does not lead to improvements in haemoglobin, growth characteristics, infections, splenic sequestration and dactylitis. Possible dangerous effects of supplementation are also referred to including increased priaprism, increased twin pregnancy rates and the risk of masking cobalamin deficiency with consequent neuropsychiatric manifestations. These studies also found that homocysteine levels are not lower in sickle cell patients and cardiovascular risk is not reduced with supplementation. The conflicting results may be due to genetic polymorphisms in folic acid/homocysteine metabolism between patients, inconsistent supplementation doses and various ethnic group representations in the papers analysed. Drawing definitive conclusions is difficult due to the small number and heterogeneous nature of the studies and our review has emphasised the need for more prospective, sufficiently powered, research in this field. Till then, the safest clinical practice would be to individualise folic acid treatment for patients based on their needs and comorbidities whilst continuing to encourage compliance with more evidence based medications including Penicillin V and hydroxyurea.