Low protein Z levels and the risk of thrombophilia

Abstract

Protein Z (PZ) is a vitamin K-dependent plasma glycoprotein whose physiological function is still not clearly defined. Studies suggest that protein Z inhibits the procoagulant activity of activated factor X (Xa), in the presence of Ca2+, phospholipids and another plasma protein, protein Z-dependent protease inhibitor (ZPI). This will result in down-regulation of coagulation. Low PZ levels were found to enhance the risk of arterial thrombosis, but not venous thrombosis which, could possibly lead to stroke and acute coronary syndromes. Controversial results were obtained regarding PZ levels and ischaemic stroke. A high frequency PZ deficiency was also found among women with one early primary foetal loss, predominantly between the 10th and 19th week of pregnancy. In this study 153 healthy individuals were tested for PZ antigen levels, using Asserachrom PZ ELISA kit from Diagnostica Stago, in order to determine a reference range for the Maltese population and the frequency of PZ deficiency in these individuals. PZ levels were also investigated in a group of 52 patients that were divided as follows: Group I: 32 patients who suffered recurrent foetal loss; Group 2: 13 patients who suffered a thromboembolic event; Group 3: 7 patients who suffered an ischaemic stroke. We compared the mean PZ level in each patient group with the mean PZ level obtained in the normal group. We also compared the frequency of PZ deficiency occuring in each patient group with that of the normal group. Results showed compliance with those obtained by other studies. We found that PZ levels have a wide total range in the Maltese population. Statistical analysis showed that there is no relationship between PZ levels and age or gender. Results of patients also concorded with those of other research groups. Statistical comparisons of the mean PZ level in each patient group with that of the normal group indicated that there is no significance difference among the means. Moreover, the frequency of PZ deficiency found in the patients was similar to that found in normal individuals. Thus we concluded that there is no relationship between PZ levels and the risk of recurrent foetal loss, thromboembolic event or ischaemic stroke. We are aware of our limitations and thus further studies are definitely required to clarify the role of PZ in such thrombophilic states.