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The heterogeneous clinical presentation, biochemical and genetic abnormalities in HS and HE have been well documented. The need to raise the awareness of HSt, albeit its much lower prevalence than HS, is due to the undesirable outcome of splenectomy in these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The scope of this guideline is to identify the characteristic clinical features, the red cell parameters (including red cell morphology) for these red cell disorders associated, respectively, with defective cytoskeleton (HS and HE) and abnormal cation permeability in the lipid bilayer (HSt) of the red cell. The current screening tests for HS are described, and their limitations are highlighted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An appropriate diagnosis can often be made when the screening test result(s) is reviewed together with the patient's clinical\/family history, blood count results, reticulocyte count, red cell morphology, and chemistry results. SDS\u2013polyacrylamide gel electrophoresis of erythrocyte membrane proteins, monovalent cation flux measurement, and molecular analysis of membrane protein genes are specialist tests for further investigation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Specialist tests provide additional evidence in supporting the diagnosis and that will facilitate the management of the patient. In the case of a patient's clinical phenotype being more severe than the affected members within the immediate family, molecular testing of all family members is useful for confirming the diagnosis and allows an insight into the molecular basis of the abnormality such as a recessive mode of inheritance or a <jats:italic>de novo<\/jats:italic> mutation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.12335","type":"journal-article","created":{"date-parts":[[2015,3,18]],"date-time":"2015-03-18T15:27:10Z","timestamp":1426692430000},"page":"304-325","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":154,"title":["<scp>ICSH<\/scp> guidelines for the laboratory diagnosis of nonimmune hereditary red cell membrane disorders"],"prefix":"10.1111","volume":"37","author":[{"given":"M.\u2010J.","family":"King","sequence":"first","affiliation":[{"name":"Membrane Biochemistry NHS Blood and Transplant Bristol UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Gar\u00e7on","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie Centre de Biologie Humaine, CHU d'Amiens Amiens France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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