Constitutive hypercoagulability in pediatric sickle cell disease patients with HbSS genotype

Background Constitutive inflammation and hemostatic activation have been identified as key contributors to the pathophysiology of Sickle Cell Disease (SCD), leading to clinical consequences such as vaso-occlusive crises and stroke. Patients with HbSS and HbSC genotypes are reported to have different symptoms, as do patients in steady-state and crisis situations. Differences among these groups remain unclear in pediatric patients. Objectives To compare hemostatic activity in HbSS and HbSC pediatric patients during steady-state, in crisis, and in clinical follow-up. Compare HbSS and HbSC patients to normal healthy children. Methods The whole blood coagulation assay thromboelastography (TEG) was used to assess hemostatic activity. In parallel, flow cytometry was used to assess procoagulant surface expression of platelets and red blood cells (RBCs). Results TEG results indicated no significant differences in clotting onset (R time), clot maximum amplitude (MA) or maximum rate of thrombus generation (TGRmax) among steady-state, crisis and follow-up subgroups of HbSS and HbSC patients. TEG parameters did not differ significantly between HbSC patients and healthy children, while HbSS patients showed significantly shorter R time and greater MA and TGRmax, all indicative of a constitutive hypercoagulable state. Flow cytometry results did not detect increased platelet integrin αIIbβ3 activation or RBC procoagulant surface expression in SCD patients compared to unaffected children. Conclusions Our results indicate that pediatric SCD patients with the HbSS genotype have constitutively activated hemostasis relative to HbSC patients and healthy children. It remains to be determined how treatments which improve clinical outcomes in SCD patients affect this constitutively hypercoagulable state.