Impact of Abnormal Leukocyte Count in the Pathophysiology of Sickle Cell Anemia

BACKGROUND: Sickle cell disease (SCD) is a hereditary disease that causes deoxygenated erythrocytes to stiffen, resulting in vaso-occlusive crises, endothelial damage, organ failure and systemic consequences. An abnormal leukocyte count is associated with a worse clinical picture in SCD. METHODS: I studied the link between an abnormal leukocyte count and sickle cell disease. I used the PRISMA guidelines to conduct a systematic review of 5 different clinical literatures that discussed the link. Use of databases including Web of Science, Scopus, Cochrane Library, MEDLINE, ScienceDirect, EMBASE, and JSTOR to make our findings. FINDINGS: SCD is a red cell disorder, but an elevated leukocyte count plays a significant role in its pathophysiology. Sickled red cells adhere better to leukocytes when compared to normal red cells, which explains the worse clinical picture seen in sickle cell patients. Hydroxyurea therapy inhibits the recruitment and invasion of neutrophils, which lowers vaso-occlusion. INTERPRETATIONS: An elevated leukocyte count is responsible for worse clinical manifestations in SCD, eg, clinical stroke, acute chest syndrome, end organ damage, and infarction pain. Leukocytes attach to erythrocytes and vascular endothelium to cause vaso-occlusion, responsible for these effects. They also elaborate inflammatory mediators to aid the process. The higher the leukocyte count, the worse the effects. Hydroxyurea is very helpful in disrupting several pathways of leukocyte contribution to SCD pathophysiology. Therefore, more research on other pharmacologic agents that interfere with this disease process is necessary. Lastly, there is a need for further research into the effects of a reduced leukocyte count in SCD pathophysiology.