Protein S deficiency in men with long-term human immunodeficiency virus infection.

Decreases in protein S levels have recently been reported in some human immunodeficiency virus (HIV)-infected patients. To examine predisposing factors, 25 men randomly selected from a long-term study of HIV-infected patients were studied. The minimum mean duration of HIV seropositivity in this group was 106.6 months (range 15 to 143 months). No patients were anticoagulated at the time of the study. Three of the 25 randomly selected patients gave a history of thrombosis, in each instance occurring after the onset of HIV positivity. Two of the 3 patients with thrombosis had more than one episode. Coagulation studies showed that 3 of 3 (100%) of the patients with thrombosis and 16 of 22 (72.7%) of those without previous thrombosis had decreased free protein S. Mean-free and total protein S levels were statistically lower for HIV-infected patients with and without previous thrombosis compared with healthy male controls. C4b-binding protein was not increased in study patients with decreased protein S levels. Decreases in protein S levels did not correlate with CD4+ cell levels, CDC class, p24 antigen positivity, zidovudine (AZT) use, or Pneumocystis carinii prophylaxis. The duration of disease statistically correlated with decreases in protein S levels (r = .37, P < .05). A linear correlation existed between increasing IgG anticardiolipin antibody levels and decreasing free protein S antigen (r = .67, P < .005). This study shows that protein S deficiency is common in long-term HIV-infected patients and is caused by a decrease in the free protein, rather than by changes in the bound complex. The data suggest that protein S deficiency is not correlated with HIV disease severity but may predispose patients to thromboembolic complications.

Protein S and C antigen levels in proteinuric patients: dependence on type of glomerular pathology.

The cause of the thrombotic tendency in nephrotic patients is unknown. Recent reports of thrombotic complications in patients with deficiencies of protein C or protein S (natural inhibitors of coagulation) have raised the possibility that decreased levels of these proteins may play a role in the hypercoagulable state of nephrotic patients. We measured the levels of protein C, total protein S, and free protein S antigens in 42 patients (21 nephrotic and 21 non-nephrotic) with one of four types of glomerular pathology: diabetic nephropathy (DM), focal glomerular sclerosis (FGS), membranous glomerulonephritis (MGN), and chronic renal failure due to hypertension (CRF). Protein C and total protein S antigen levels were significantly higher in FGS and MGN than they were in DM or CRF. Free protein S levels were lower in DM than they were in MGN. Protein C, total protein S, and free protein S levels did not significantly correlate with either serum albumin or degree of proteinuria. The mean levels of the three proteins did not differ between nephrotic and non-nephrotic patients. Free protein S and protein C were, however, significantly correlated (P less than .005 and P less than .002, respectively) with the type of glomerular pathology, independent of differences in age, sex, serum albumin, or degree of proteinuria. These data suggest that abnormalities of free protein S and protein C are related to the nature of the underlying renal disease, rather than to the degree of proteinuria.