Abstract
Introduction: Protein Z (PZ) is a vitamin K-dependent factor, involved as a cofactor of PZ-dependent protease inhibitor (ZPI) that inhibits the activated factor X on phospholipid surface. A severe PZ deficiency could be associated with ischemic arterial diseases. The aim of this study was to evaluate the influence of PZ plasma levels on thrombin generation (TG) and to detect a hypercoagulable state in patients with PZ deficiency.
Patients and Methods: Young patients with personal history of arterial thrombosis and PZ deficiency were included. PZ concentrations were assessed using ELISA method. TG assay was performed using PPP containing 5 pM or 1 pM tissue factor and 4 μM phospholipids with and without thrombomodulin. Then, we focussed on the influence of successive overloads with purified PZ in two patients with PZ deficiency (Pat1PZdef and Pat2PZdef) and industrial PZ deficiency (IndPZdef).
Results: First, in 13 patients with PZ deficiency, none influence of PZ level was reported on TG assay parameters. Second, TG profiles performed on Pat1PZdef, Pat2PZdef and IndPZdef were close to the reference TG profile. In presence of TM, there was no difference in TG parameters according to PZ plasma levels. After each overload, real PZ plasma levels were underestimated; differences in standards of purified PZ between the two manufacturers might explain such results.
Conclusion: The absence of influence of PZ concentration on TG assay is reliable to the absence of well-demonstrated clinical consequences of PZ deficiency in arterial thrombosis. Clinical consequences of protein Z deficiency warranted further studies.