Protein Z in Patients with Newly Diagnosed Multiple Myeloma

Background Patients with multiple myeloma (MM) are relatively high risk of developing thromboembolic events. The pathogenesis of prothrombotic coagulation abnormalities in MM is not clear and probably of multifactorial origin. The deficiency of natural anticoagulant mechanisms, acquired resistance to protein C and reduced protein S function, has been described as one of the possible reason of hypercoagulable state in MM patients. Protein Z/Z-dependent protease inhibitor (PZ/ZPI) is a new anticoagulant system has been recently describe. PZ is a vitamin K-dependent protein which serves as cofactor for the ZPI that inactivates activated factor X, XI and IX by different mechanisms. Some reports suggest that protein Z deficiency might imbalance the haemostatic system with thrombotic consequences. However, to the best of our knowledge, no data are available regarding the potential role of protein Z in prothrombotic coagulation abnormalities in MM.

Aim: The aim of our study was to evaluate the plasma concentration of protein Z in relation to disease stage, type and levels monoclonal protein in patients with newly diagnosed untreated multiple myeloma.

Methods: The study population consisted of 41 patients (25 male, 16 female; median age: 63 years) with newly diagnosed untreated multiple myeloma. The presence of monoclonal serum immunoglobulin was found in 33 patients (25 and 8 with IgG and IgA paraprotein, respectively). The disease stage was evaluated according to Durie and Salmon criteria: 4 patients-stage I, 28 patients-stage II and 19 patients-stage III; in 8 of them abnormal renal function (serum creatinine value ≥2.0 mg/dl) was observed. The control group was formed by 19 healhty individuals with age and sex comparable with the patients. Protein Z plasma levels were measured using a commercial enzyme-linked immunosorbent assay (Asserachrom Protein Z; Diagnostica Stago, Asnieres) following the manufacturer’s instruction.

Results: The median protein Z plasma levels in patients with multiple myeloma and control subjects were similar. Median PZ levels were 1.45 ug/ml (range 0.27–3.17 ug/ml) in patients and 1.37ug/ml (range 0.34–1.96 ug/ml) in controls (p≥0.05). No significant correlation was found between protein Z plasma levels and disease stage, monoclonal serum immunoglobulin concentration, and renal function as well.

Conclusions: Our results suggest that protein Z is not an independent risk factor for thrombosis and does not play a significant role in the mechanism of thrombotic complication in patients with multiple myeloma.