Abnormalities of coagulation and fibrinolysis in homozygous sickle cell disease

Abnormalities of coagulation and fibrinolysis were studied in a group of 28 children and young adults with homozygous sickle cell disease (SCD), either in the steady state (n = 12) or during painful crisis (n = 16). Coagulation was explored by standard clotting tests and by measurement of prothrombin complex factors, factor VIII (VIII:C) and antithrombin III (ATIII), protein C (PC) and protein S (PS) activities, while fibrinolytic potential was evaluated using D-dimer, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) assays. In SCD patients, thrombin time (TT) was constantly shortened, both in the steady state (ratio to control 0.83 ± 0.08, p < 0.0001) and in crisis (0.76 ± 0.06, p < 0.0001). Mean levels of prothrombin complex were similar in asymptomatic patients to those in controls, but were significantly decreased during sickle cell crisis (p < 0.05 for factor V and p < 0.0001 for factors II,VII and X). Factor VIII:C was significantly increased, both in the steady state (207 ± 35%, p < 0.0001) and during crisis (208 ± 34 %, p < 0,0001). PS activity was reduced in the steady state (81 ± 12%, p < 0.01) and further diminished in crisis (68.5 ± 27.5%, p < 0.001), while D-dimers were significantly elevated during sickle cell crisis (1028 ± 675 ng/ml, p < 0.001). In all SCD patients, baseline levels of t-PA antigen were comparable to those in controls, whereas concentrations of PAI-1 antigen were significantly increased, either in the steady state (89.7 ± 26.3 ng/ml, p < 0.0001) or in crisis (75.0 ± 24.8 ng/ml, p < 0.0001). These results provide evidence for the presence of circulating activated clotting factors in SCD and for an imbalance of the profibrinolytic and antifibrinolytic systems most likely due to increased PAI-1 levels.