Plasma levels of activated protein C in healthy subjects and patients with previous venous thromboembolism: Relationships with plasma homocysteine levels

Marco Cattaneo, Franca Franchi, Maddalena L. Zighetti, Ida Martinelli, Daniela Asti, P. Mannuccio Mannucci

Research output: Contribution to journalArticlepeer-review

Abstract

The proteolytic enzyme activated protein C (APC) is a normal plasma component, indicating that protein C (PC) is continuously activated in vivo. High concentrations of homocysteine (Hcy) inhibit the activation of PC in vitro; this effect may account for the high risk for thrombosis in patients with hyperhomocysteinemia (HyperHcy). We measured the plasma levels of APC in 128 patients with previous venous thromboembolism (VTE) and in 98 age- and sex-matched healthy controls and correlated them with the plasma levels of total Hcy (tHcy) measured before and after an oral methionine loading (PML). Forty-eight patients had HyperHcy and 80 had normal levels of tHcy. No subject was known to have any of the congenital or acquired thrombophilic states at the time of the study. Because the plasma levels of APC and PC were correlated in healthy controls, the APC/PC ratios were also analyzed. Plasma APC levels and APC/PC ratios were significantly higher in VTE patients than in controls (P=0.03 and 0.0004, respectively). Most of the increase in APC levels and APC/PC ratios were attributable to patients with HyperHcy. Patients with normal tHcy had intermediate values, which did not differ significantly from those of healthy controls. There was no correlation between the plasma levels of tHcy or its PML increments and APC or APC/PC ratios in controls. The fasting plasma levels of APC and APC/PC ratios of 10 controls did not increase 4 hours PML, despite a 2-fold increase in tHcy. This study indicates that APC plasma levels are sensitive markers of activation of the hemostatic system in vivo and that Hcy does not interfere with the activation of PC in vivo.

Original languageEnglish
Pages (from-to)1371-1375
Number of pages5
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume18
Issue number9
Publication statusPublished - 1998

Keywords

  • Activated protein C
  • Homocysteine
  • Hypercoagulability
  • Protein C
  • Thromboembolism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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