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.