Characterization of the hypercoagulable state in patients with sickle cell disease

The pathophysiology of sickle cell disease (SCD) is complex, with increasing evidence of a pronounced prothrombotic state. We investigated thrombin generation in SCD utilizing calibrated automated thrombography (CAT) and D-dimer, with subsequent correlation to clinical disease. The study included 51 patients homozygous for hemoglobin S, either admitted for vaso-occlusive crisis (VOC) (n = 34) or while in steady state and being seen in outpatient clinic (n = 37). Twenty patients had blood drawn during both VOC and steady state. Mean values for CAT and D-dimer were compared between groups. Mean values for patients with and without clinical complications such as avascular necrosis and stroke were also compared. Linear regression was used to evaluate correlation to number of hospitalizations and for all pediatric patients, transcranial doppler (TCD) velocities. The mean D-dimer during VOC (2743 ± 3118 ng/ml) was significantly higher than during steady state (1151 ± 802, p < 0.0001). Comparison of crisis and steady state by CAT also revealed a significant difference in all phases of thrombin generation, including mean endogenous thrombin potential (1381 ± 295 nM vs 923 ± 316, p < 0.0001) and peak thrombin generated (284 ± 9 vs 223 ± 18, p = 0.0002). There were no significant differences in mean values for the clinical outcomes examined in adults. In pediatric patients, however, increased TCD velocities correlated with steady state D-dimer (r2 = 0.32, p = 0.02) and thrombin-antithrombin complex (r2 = 0.28, p = 0.04. Hypercoagulable markers distinguish between patients with SCD during and between VOC, but do not correlate with specific clinical phenotypes.