title: Abnormalities of coagulation and fibrinolysis in homozygous sickle cell disease.
abstract: 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 int he 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.
authors.affiliation: Laboratoire d'Hématologie, Hôpital Militaire de Tunis, Montfleury, Tunisie.
authors.forename: B
authors.initials: B
authors.lastname: Nsiri
authors.forename: N
authors.initials: N
authors.lastname: Gritli
authors.forename: F
authors.initials: F
authors.lastname: Bayoudh
authors.forename: T
authors.initials: T
authors.lastname: Messaoud
authors.forename: S
authors.initials: S
authors.lastname: Fattoum
authors.forename: S
authors.initials: S
authors.lastname: Machghoul
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000235:genetics; D001777:Blood Coagulation / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male