Least implicated in the pathophysiology of sickle cell disease:

 # Which is least implicated in the pathophysiology of sickle cell disease? 
a. Neutrophils 
b. Nitric oxide 
c. Platelets and coagulation factors 
d. Free hemoglobin

The correct answer is C. Platelets and Coagulation factor.

The pathophysiologic processes that lead to sickle cell disease related complications result from a combination of hemolysis and vaso-occlusion. Hemolysis occurs as a result of repeated episodes of hemoglobin polymerization/depolymerization as sickle red blood cells pick up and release oxygen in the circulation. Red blood cell membranes become abnormal from this process and red blood cells have a shortened lifespan. 

Hemolysis can occur both chronically and during acute painful vaso-occlusive crises and also results in the release of substantial quantities of free hemoglobin into the vasculature. The consumption of significant quantities of nitric oxide (NO) by this resultant free ferrous hemoglobin,  in turn, leads to abnormal regulation in vascular homeostasis. Moreover, neutrophils play a key role in the tissue damage which occurs as both neutrophil numbers are increased and evidence suggests that they are abnormally activated and adherent. Likewise, as suggested by recent data sickle red cells induce adhesion of lymphocytes and monocytes to the endothelium such that these may contribute to the pathogenesis of vascular occlusion. Platelet activation also occurs in SCD but is least implicated among the given options.

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