Platelet-mediated clumping adhesion phenotypes of P. falciparum-infected erythrocytes: A review

Abstract

Malaria is a leading cause of morbidity and mortality in the world. In general, malaria is easily treated but in a subset of cases it develops to severe disease. Severe malaria has a high rate of mortality even with the best available care. This creates the need for intensive research to fully characterise the pathogenesis of the disease in order to create future novel therapies. One of the hallmarks of malaria infections is its ability to adhere to specific sites in the body leading to severe disease syndromes such as cerebral malaria and pregnancy associated malaria. In this review, the platelet-mediated clumping adhesion phenotypes of malaria-infected erythrocytes were discussed in the context of infected erythrocyte adhesion phenotypes such as cytoadhesion and rosetting. Platelet-mediated clumping refers to a phenomenon of P. falciparum-infected erythrocytes whereby they agglutinate to form large aggregates held together by activated platelets. This unique phenotype is important because it has been associated with severe malaria in both children and adults in diverse geographical and transmission settings. The precise mechanisms by which platelet-mediated clumping occurs are yet to be precisely described. The platelet receptors implicated in this phenotype include CD36, P-Selectin and gC1qR. The parasite derived ligands that mediate this phenotype are yet to be described.