Protein S deficiency in sickle cell anemia.

To investigate the status of the protein C-protein S anticoagulant pathway in sickle cell disease, we measured protein C, total and free protein S, and C4b-binding protein levels in 20 subjects with sickle cell disease (Hb SS or SC). Mean total and free protein S levels were both significantly lower in subjects with sickle cell disease than in normal individuals, but greater reductions were observed for free S. The free protein S level was below the mean -2 SD for normal subjects in 12 subjects with sickle cell disease; the total protein S level was below this level in three subjects. Mean C4b-binding protein levels were normal in subjects with sickle cell disease, both during painful crisis and in the steady state, and no correlation was observed between the levels of C4b-binding protein and free protein S, suggesting that the low free protein S level was not caused by increased levels of C4b-binding protein. Crossed immunoelectrophoresis of plasma samples from eight subjects with sickle cell disease showed marked reductions in free protein S, with normal levels of protein S bound to C4b-binding protein. In contrast to the protein S level, mean protein C activity was normal in subjects with sickle cell disease, both during painful crisis and in the steady state. However, the protein C level was below the mean -2 SD for normal subjects on at least one occasion in four subjects with sickle cell disease.(ABSTRACT TRUNCATED AT 250 WORDS)

[1]  C. Esmon,et al.  Protein S deficiency occurs in the nephrotic syndrome. , 1987, Annals of internal medicine.

[2]  F. Taylor,et al.  Protein S is a cofactor for activated protein C neutralization of an inhibitor of plasminogen activation released from platelets. , 1987, Blood.

[3]  J. Scott,et al.  Is sickle cell crisis a thrombotic event? , 1986, American journal of hematology.

[4]  M. Nardi,et al.  Prothrombin and protein C in early childhood: normal adult levels are not achieved until the fourth year of life. , 1986, The Journal of pediatrics.

[5]  K. Stocker,et al.  Fast functional protein C assay using Protac, a novel protein C activator. , 1986, Thrombosis research.

[6]  D. Devine,et al.  Fragment D-dimer levels: an objective marker of vaso-occlusive crisis and other complications of sickle cell disease. , 1986, Blood.

[7]  P. Comp,et al.  The regulation of hemostasis: the protein C system. , 1986, The New England journal of medicine.

[8]  R. Marlar,et al.  Human endothelial cells synthesize protein S. , 1986, Blood.

[9]  C. Esmon,et al.  An abnormal plasma distribution of protein S occurs in functional protein S deficiency. , 1986, Blood.

[10]  R. Marlar,et al.  Biosynthesis and secretion of factor VII, protein C, protein S, and the Protein C inhibitor from a human hepatoma cell line. , 1986, Blood.

[11]  V. V. van Hinsbergh,et al.  Activated protein C decreases plasminogen activator-inhibitor activity in endothelial cell-conditioned medium. , 1985, Blood.

[12]  C. Esmon,et al.  Recurrent venous thromboembolism in patients with a partial deficiency of protein S. , 1984, The New England journal of medicine.

[13]  C. Esmon,et al.  Familial protein S deficiency is associated with recurrent thrombosis. , 1984, The Journal of clinical investigation.

[14]  J. Griffin,et al.  Plasma protein S deficiency in familial thrombotic disease. , 1984, Blood.

[15]  J. Nishioka,et al.  Regulation of activated protein C by thrombin-modified protein S. , 1983, Journal of biochemistry.

[16]  B. Dahlbäck.  Purification of human vitamin K-dependent protein S and its limited proteolysis by thrombin. , 1983, The Biochemical journal.

[17]  F. Walker.  Regulation of activated protein C by protein S. The role of phospholipid in factor Va inactivation. , 1981, The Journal of biological chemistry.

[18]  B. Roelofsen,et al.  Abnormalities in membrane phospholipid organization in sickled erythrocytes. , 1981, The Journal of clinical investigation.

[19]  W. Kisiel,et al.  Interaction of vitamin K dependent proteins with membranes. , 1978, Biochemistry.

[20]  G. Brewer,et al.  Elevated plasma levels of fibrinopeptide a during sickle cell anemia pain crisis–evidence for intravascular coagulation , 1978, American journal of hematology.

[21]  G. Serjeant,et al.  Coagulation Changes during the Steady State in Homozygous Sickle‐Cell Disease in Jamaica , 1975, British journal of haematology.

[22]  J. Harris,et al.  Platelet function and survival in sickle cell disease. , 1973, The Journal of laboratory and clinical medicine.