PROTEIN-C AND PROTEIN-S IN HOMOZYGOUS SICKLE-CELL DISEASE - DOES HEPATIC-DYSFUNCTION CONTRIBUTE TO LOW-LEVELS

The aim of this study was to confirm reports of low protein C (PC) and S (PS) concentrations in steady-state patients with homozygous sickle cell (SS) disease when compared to a racially matched normal haemoglo bin (AA) control group and to examine the mechanisms of this reduction with respect to hepatic function, coagulation activation and haematol ogical indices. In 36 SS patients and 35 AA race-matched controls PC ( functional and immunoreactive), PS (free and total) were measured. C4B binding protein (C4B) was assessed by immunoelectrophoresis and D-dim er by ELISA. Hepatic function was assessed by prothrombin (PT) time (4 9 SS, 64 AA), factor V (34 SS, 36 AA) and factor VII concentrations (2 8 SS, 29 AA), Proteins induced in vitamin IC absence or antagonism (PI VKA) were sought in 12 SS's. The relationship between PC, PS and total bilirubin, haemoglobin (Kb) F and reticulocyte count was also assesse d.PC, PS and C4B were lower in SS disease. SS patients had longer PT t imes, and lower factor V and VII concentrations in comparison to AA co ntrols. PC (functional and immunoreactive) and free PS correlated with PT. Within SS genotype PT correlated negatively with factor V and fac tor VII. Factor V and VII were positively correlated. PIVKAs were not detected. There was no correlation between PC, PS and D-dimer, haemoly tic rate or Hb F concentration. Prolongation of PT time, low factor V and VII suggest that hepatic dysfunction, rather than coagulation acti vation or haemolytic rate, accounts for the reduced concentrations of PC and PS in steady-state SS disease. The absence of PIVKAs suggests a hepatocellular problem.