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Introduction: P-selectin is a key adhesion molecule in the pathogenesis of sickle cell disease, including acute painful event(s). Many of the mediators activated in prototypical pain crisis are also involved in other complications seen in this population. Crizanlizumab is a monoclonal antibody approved in the US in 2019 for patients of all genotypes of sickle cell disease. By blocking P-selectin, it effectively prevents acute painful event(s) and has a manageable safety profile., Areas Covered: In this review, we provide an overview of the (i) biology of P-selectin in sickle cell disease, (ii) various agents inhibiting P-selectin, (iii) pharmacology of crizanlizumab, (iv) preclinical and clinical data on crizanlizumab, and (v) its potential for other indications, ongoing studies, regulatory status, and cost issues. Further, we describe its position among other approved agents in sickle cell disease and project future directions as well., Expert Opinion: Crizanlizumab holds great promise in modulating the natural history of sickle cell disease and may have pleotropic effects. Studies are ongoing to define its role in preventing other sickle cell-related complications, non-sickle cell inflammatory states, and thrombotic disorders.

Introduction: In sickle cell disease (SCD), hemoglobin S (HbS) red blood cells (RBCs) are characteristically deformed and inflexible. Often breaking down in the circulation, they exhibit increased adhesive properties with the endothelium and activated neutrophils and platelets, increasing the risk of occlusion of the microcirculation. SCD is categorized into two sub-phenotypes: hyperhemolytic, associated with priapism, leg ulcers, pulmonary hypertension, and stroke, and high hemoglobin/viscosity, which may promote vaso-occlusion-associated pain, acute chest syndrome, and osteonecrosis., Areas Covered: The sub-phenotypes are not completely distinct. Hemolysis may trigger vaso-occlusion, contributing to vascular complications. Targeting P-selectin, a key mediator of cross-talk between hyperhemolysis and vaso-occlusion, may be beneficial for vascular and vaso-occlusion-associated complications. English-language articles from PubMed on the topic of SCD and vaso-occlusive crises (VOCs) were reviewed from 1 January 2000 to 1 January 2019 using the search terms 'sickle cell disease,' 'vaso-occlusive crises,' and 'selectin.', Expert Opinion: Besides targeting P-selectin, other strategies to counter VOCs and RBC sickling are being pursued. These include platelet inhibition to counter aggregation, intercellular adhesion, and thrombosis during VOCs; gene therapy to correct the homozygous missense mutation in the β-globin gene, causing polymerization of HbS; L-glutamine, possibly reducing oxidative stress in sickled RBCs; and fetal hemoglobin inducers.