Protein Z levels and anti-protein Z antibodies in patients with arterial and venous thrombosis☆

Abstract 

Introduction

The thrombotic risk associated with protein Z (PZ) deficiency is unclear. Anti-protein Z (anti-PZ) has been described as a risk factor in unexplained embryo demise. The aim of our study was to evaluate a possible PZ deficiency and presence of anti-PZ antibodies on thrombotic diseases.

Material and methods

We performed a case-control study on 114 patients with preexisting arterial or venous thrombosis (50 and 64, respectively). Thrombosis was studied based on etiology (creating factor risk subgroups) and on specific thrombotic disease.

Results

PZ levels of patients were significantly lower compared to controls (1709+−761.3 ng/mL vs. 2437+−964.7 ng/mL P=0.001). The high arterial risk factor subgroup showed the lowest PZ level (1267.5+−609 ng/mL) whereas the rest of arterial and venous etiological subgroups presented similar PZ levels. Patients with peripheral artery disease had the lowest PZ level (1022+−966 ng/mL). The rest of arterial and venous thrombotic diseases presented similar PZ levels. A significant increased risk for arterial and venous thrombosis for the lowest (<1685 ng/mL) quartile of PZ has been founded (OR:52, P=0.001 and OR:18, P=0.007, respectively). Anti-PZ antibodies were negative in the majority of patients, although mean anti-PZ IgG antibody levels in the arterial thrombosis group were significantly higher compared to venous thrombosis and control groups (P=0.05 and P=0.005, respectively).

Conclusions

The results suggest that both arterial and venous thrombotic events are related to low PZ levels and that low PZ concentrations are associated with thrombosis in our study. In arterial thrombosis our findings strengthen previous studies that related low PZ levels to atherosclerotic disease. Anti-PZ antibodies do not seem to play a potent role in thrombosis.

Abbreviations:: PZ, protein Z, anti-PZ, anti-protein Z, ZPI, protein Z-dependent protease inhibitor, Xa, activated factor X, OD, optical density, AU, arbitrary unit, PBS, phosphate buffered saline, NCEP-III, National Cholesterol Education Program, ANOVA, analysis of variance, SD, standard deviation, OR, Odds ratios.

Keywords: Anti-Protein Z, Arterial thrombosis, Protein Z, Venous thrombosis, Protein Z deficiency, Thrombophilia