Although the disease is the product of one mutant gene inbeta globin chain, the disease phenotype is multigenic andgene polymorphism in associated genes dictate the interindividualvariations seen in SCDIn patients with SCD increasedactivation of the coagulation system and thrombosis has beenevidenced. Patients with SCD have low circulating levels ofprotein C and S and are resistance to activated protein Ccompared to healthy individuals. As mutations withprothrombotic activity influence the disease phenotype,Understanding of their influence on modulating thepathophysiology of SCD may allow prediction of the phenotypeand aid in management decisions.