title: Plasma concentration of protein Z and protein Z-dependent protease inhibitor in patients with haemophilia A.
abstract: The potential role of alterations in protein Z (PZ) concentrations in the pathogenesis of coagulation has been investigated in several studies which, however, yielded conflicting results. Protein Z deficiency may induce bleeding as well as prothrombotic tendencies and it might occur as an inherited disorder. The principal aim of the present study was to explore the concentration of protein Z and protein Z-dependent protease inhibitor (ZPI) in patients with haemophilia A. In haemophilia A patients mean plasma concentrations of PZ and ZPI were significantly higher than in healthy individuals: PZ (1.87±0.68μg/mL vs 1.49±0.54μg/mL) and ZPI (5.02±1.11μg/mL vs 4.22±0.55μg/mL), with p=0.02 and p=0.03, respectively. In the subgroup with severe haemophilia A, an in-depth analysis revealed a tendency to modulating effect of the PZ (r=-0.53; p=0.072) and a statistically significant one in the case of ZPI (rho=-0.79, p=0.002) on the bleeding rate. It simultaneously disclosed a statistically significant correlation between the number of bleeds to the joints (20.18±14.1), PZ (r=-0.72; p=0.04) and ZPI (rho=-0.88, p=0.001). With reference to this particular group of patients, the study also showed some other statistically meaningful correspondences: between PZ and ZPI (rho=0.65, p=0.02), PZ and FIX (r=-0.61, p=0.04), as well as ZPI and FVIII (rho=0.78, p=0.002). In conclusion, despite the fact that FVIII deficiency is undoubtedly the main mechanism of bleeding in haemophilia A patients, the activity of PZ/ZPI complex may play some modulating role in the matter.
authors.affiliation: Department of Haematology, Medical University of Bialystok, Bialystok, Poland. lbolkun@gmail.com
authors.forename: Lukasz
authors.initials: L
authors.lastname: Bolkun
authors.forename: Marzenna
authors.initials: M
authors.lastname: Galar
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Piszcz
authors.forename: Dorota
authors.initials: D
authors.lastname: Lemancewicz
authors.forename: Janusz
authors.initials: J
authors.lastname: Kloczko
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism; D006467:Hemophilia A / Q000097:blood*; D006470:Hemorrhage; D006487:Hemostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000494:pharmacology*; D011485:Protein Binding; D015843:Serpins / Q000378:metabolism*; D013927:Thrombosis / Q000473:pathology; D055815:Young Adult
chemical_list: D001798:Blood Proteins; D011480:Protease Inhibitors; C416370:SERPINA10 protein, human; D015843:Serpins; C026080:plasma protein Z; D005169:Factor VIII