Search

Anemia, characterized by low blood hemoglobin level, affects about 25% of the world's population with the heaviest burden borne by women and children. Anemia leads to impaired cognitive development in children, as well as high morbidity and early mortality among sufferers. Anemia can be caused by nutritional deficiencies, oncologic treatments and diseases, and infections such as malaria, as well as inherited hemoglobin or red cell disorders. Effective treatments are available for anemia upon early detection and the treatment method is highly dependent on the cause of anemia. There is a need for point-of-care (POC) screening, early diagnosis, and monitoring of anemia, which is currently not widely accessible due to technical challenges and cost, especially in low- and middle-income countries where anemia is most prevalent. This review first introduces the evolution of anemia detection methods followed by their implementation in current commercially available POC anemia diagnostic devices. Then, emerging POC anemia detection technologies leveraging new methods are reviewed. Finally, we highlight the future trends of integrating anemia detection with the diagnosis of relevant underlying disorders to accurately identify specific root causes and to facilitate personalized treatment and care.

Many hypotheses have been proposed to explain how a glutamate to valine substitution in sickle haemoglobin (HbS) can cause sickle cell disease (SCD). We propose and document a new mechanism in which elevated tyrosine phosphorylation of Band 3 initiates sequelae that cause vaso-occlusion and the symptoms of SCD. In this mechanism, denaturation of HbS and release of heme generate intracellular oxidants which cause inhibition of erythrocyte tyrosine phosphatases, thus permitting constitutive tyrosine phosphorylation of Band 3. This phosphorylation in turn induces dissociation of the spectrin-actin cytoskeleton from the membrane, leading to membrane weakening, discharge of membrane-derived microparticles (which initiate the coagulation cascade) and release of cell-free HbS (which consumes nitric oxide) and activates the endothelium to express adhesion receptors). These processes promote vaso-occlusive events which cause SCD. We further show that inhibitors of Syk tyrosine kinase block Band 3 tyrosine phosphorylation, prevent release of cell-free Hb, inhibit discharge of membrane-derived microparticles, increase sickle cell deformability, reduce sickle cell adhesion to human endothelial cells, and enhance sickle cell flow through microcapillaries. In view of reports that imatinib (a Syk inhibitor) successfully treats symptoms of sickle cell disease, we suggest that Syk tyrosine kinase inhibitors warrant repurposing as potential treatments for SCD.

Anemia affects over 25% of the world's population with the heaviest burden borne by women and children. Genetic hemoglobin (Hb) variants, such as sickle cell disease, are among the major causes of anemia. Anemia and Hb variant are pathologically interrelated and have an overlapping geographical distribution. We present the first point-of-care (POC) platform to perform both anemia detection and Hb variant identification, using a single paper-based electrophoresis test. Feasibility of this new integrated diagnostic approach is demonstrated via testing individuals with anemia and/or sickle cell disease. Hemoglobin level determination is performed by an artificial neural network (ANN) based machine learning algorithm, which achieves a mean absolute error of 0.55 g dL−1 and a bias of −0.10 g dL−1 against the gold standard (95% limits of agreement: 1.5 g dL−1) from Bland–Altman analysis on the test set. Resultant anemia detection is achieved with 100% sensitivity and 92.3% specificity. With the same tests, subjects with sickle cell disease were identified with 100% sensitivity and specificity. Overall, the presented platform enabled, for the first time, integrated anemia detection and hemoglobin variant identification using a single point-of-care test. [ABSTRACT FROM AUTHOR]