The plasma levels of protein Z-dependent protease inhibitor increase after gynecological surgery independently of estrogen

Thromb Res. 2015 Nov;136(5):980-6. doi: 10.1016/j.thromres.2015.09.020. Epub 2015 Sep 26.


Introduction: Protein Z (PZ)-dependent protease inhibitor (ZPI) is a serine protease inhibitor that efficiently inhibits activated factor X when ZPI is in complex with PZ. We previously reported significantly higher concentrations of plasma ZPI (and PZ) in women during normal pregnancy than in non-pregnant women.

Methods: We explored the possible contribution of estrogen to the ZPI levels in patients with or without bilateral oophorectomy (OVX), which induces artificial menopause where blood estrogen levels drastically decrease. One hundred ninety-one pre-menopausal Japanese women who underwent open hysterectomy owing to neoplasms participated in this study and were divided into two groups: 98 OVX and 93 Non-OVX cases. Plasma ZPI was measured by ELISA.

Results and conclusion: Contrary to our working hypothesis, plasma ZPI levels increased significantly in the OVX group after surgery when compared with the pre-operation levels. When these patients were individually analyzed, their ZPI value also rose significantly from pre-operation to post-operation levels. In contrast, plasma PZ levels remained unchanged. The significantly increased ZPI and unchanged PZ levels were also observed in the Non-OVX group. The increased ZPI levels were not significantly related to 17β-estradiol, luteinizing hormone or follicular stimulating hormone levels, clearly indicating that estrogen did not contribute to the plasma ZPI concentrations. Typical acute phase reactants fibrinogen and C-reactive protein (CRP) were also significantly elevated after surgery in both OVX and Non-OVX groups. However, only weakly significant linear relationships were observed between ZPI and fibrinogen or CRP, indicating the presence of alternative regulatory mechanisms underlying their plasma concentrations.

Keywords: Acute phase reactant; Cancer; Coagulation inhibitors; Female hormones; Protein Z-dependent protease inhibitor; Surgery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism*
  • Adult
  • Estrogens / metabolism*
  • Gynecologic Surgical Procedures / methods*
  • Humans
  • Middle Aged
  • Protease Inhibitors / metabolism*


  • Acute-Phase Proteins
  • Estrogens
  • Protease Inhibitors