Thrombin generation reveals high procoagulant potential in the plasma of sickle cell disease children

Changes in several components of the clotting system are well documented in sickle cell disease (SCD) patients. However, whether the global hemostatic potential of these patients is altered is still unclear. Calibrated automated thrombogram (R) method of thrombin generation (TG) was used to characterize the hemostatic potential of 83 SCD children (75 SS, 6 SC, and 2 S beta thal) at steady-state as compared with 50 controls of the same range of age. TG was triggered using 1 pM tissue factor and 4 mu M phospholipids with and without thrombomodulin. Thirteen SCD children were also evaluated during vaso-occlusive crisis. Protein C activity, free protein S and D-dimers levels were measured in parallel. SCD patients showed higher rates of thrombin formation, higher thrombin peak height (with and without thrombomodulin), and higher endogenous thrombin potential (ETP) than controls in the presence of thrombomodulin. Reduction of ETP (RETP) in the presence of thrombomodulin was lower in SCD group compared with controls and correlated both with protein C and protein S levels. ETP, RETP, peak height, and velocity index of TG correlated with D-dimers. Compound heterozygous patients showed an intermediate hemostatic phenotype at steady-state. No significant difference was observed when comparing TG parameters during vaso-occlusive crisis to those obtained at steady-state in the same patients. The global hemostatic potential is increased and reflects the hypercoagulable state of SCD patients even at steady-state. The relevance of this finding with respect to the risk of thrombotic complications of the disease needs further investigation. Am. J. Hematol. 2011. (C) 2011 Wiley-Liss, Inc.