Protein Z and Protein Z Complex in the Acute Phase of Ischemic Stroke: Potential Markers of Coagulation and Prognostic Value in Patients Treated with Thrombolysis or Conservative Therapy

Background/Objectives: Protein Z (PZ) and the protein Z-dependent protease inhibitor (ZPI) are vitamin K-dependent regulators of coagulation that inhibit activated factor Xa. Their relevance in ischemic stroke (IS) remains insufficiently characterized, with inconsistent evidence regarding their association with stroke severity and outcomes. This study aimed to evaluate the concentrations and dynamics of PZ and ZPI in the acute phase of IS in patients treated with intravenous thrombolysis or conservative therapy and to assess their potential prognostic significance. Methods: Eighty-four patients with acute IS were enrolled and divided into two groups: group I treated with intravenous thrombolysis (rt-PA) and group II managed conservatively. PZ and ZPI concentrations were measured using ELISA on admission (day 1) and on day 7. Associations with factor X activity, the modified Rankin Scale (mRS), and the National Institutes of Health Stroke Scale (NIHSS) were analyzed using nonparametric tests and Spearman correlations (p < 0.05). Results: PZ concentrations were significantly higher in thrombolysis-treated patients than in conservatively managed patients both on day 1 (median: 2810.05 vs. 2178.50 ng/mL; p = 0.024) and day 7 (2982.90 vs. 2286.50 ng/mL; p = 0.026). A slight negative correlation between PZ and mRS on day 7 was observed in the conservative group (r = −0.360; p = 0.043). In thrombolysis-treated patients with dyslipidemia, PZ increased from day 1 to day 7, whereas it decreased in those without dyslipidemia. No significant correlations were found between PZ, ZPI, or factor X and NIHSS or ASTRAL scores. Conclusions: Higher PZ concentrations in the acute phase of IS—particularly in rt-PA-treated patients—may reflect differences related to the timing of the acute ischemic process and reperfusion status, suggesting potential utility as markers of stroke severity or outcome.