Abstract
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.
Highlights
Sickle cell disease (SCD) is one of the commonest severe inherited disorders (Steinberg et al 2001; Rees et al 2010)
Haemolysis is stimulated by factors which promote HbS polymerisation and reduced by those which stabilise soluble Hb
In parallel experiments performed in saline, red blood cells (RBCs) sickling, indicative of HbS polymerisation, was observed under conditions which supported haemolysis
Summary
Sickle cell disease (SCD) is one of the commonest severe inherited disorders (Steinberg et al 2001; Rees et al 2010). It results from the presence in patients’ red blood cells (RBCs) of the mutated haemoglobin (Hb) HbS, rather than the normal adult HbA. The polymerisation event leads to multiple clinical complications which are features of the disease. These complications fall into two main types: a chronic anaemia and acute ischaemic disorders (such as stroke, osteonecrosis and acute chest syndrome) (Steinberg et al 2001). This strategy would be valuable in more economically deprived areas of the world (such as Western Africa) where the disease is most prevalent
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