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Thromb Haemost 1990; 63(01): 048-053
DOI: 10.1055/s-0038-1645685
Original Article
Schattauer GmbH Stuttgart

Effect of Protein C and Activated Protein C on Coagulation and Fibrinolysis in Normal Human Subjects

Kenji Okajima
1   The Department of Laboratory Medicine, Kumamoto University Medical School, Kumamoto, Tokyo, Japan
,
Shin Koga
2   The Department of Medicine, Kumamoto University Medical School, Kumamoto, Tokyo, Japan
,
Megumi Kaji
2   The Department of Medicine, Kumamoto University Medical School, Kumamoto, Tokyo, Japan
,
Masayasu Inoue
3   The Department of Biochemistry, Kumamoto University Medical School, Kumamoto, Japan
,
Tomohiro Nakagaki
4   The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Tokyo Medical and Dental University, Tokyo, Japan
,
Akinobu Funatsu
4   The Chemo-Sero-Therapeutic Research Institute, Kumamoto, Tokyo Medical and Dental University, Tokyo, Japan
,
Hiroaki Okabe
1   The Department of Laboratory Medicine, Kumamoto University Medical School, Kumamoto, Tokyo, Japan
,
Kiyoshi Takatsuki
2   The Department of Medicine, Kumamoto University Medical School, Kumamoto, Tokyo, Japan
,
Nobuo Aoki
5   The Department of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
› Author Affiliations
Further Information

Publication History

Received 21 June 1989

Accepted after revision 01 November 1989

Publication Date:
02 July 2018 (online)

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Summary

Although protein C (PC) and activated protein C (APC) have been postulated to be useful for treating patients with thrombosis, their critical effect remains to be studied in human subjects. To examine whether purified PC or APC are useful for treating patients with thrombosis without showing any adverse effect, wc studied effects on coagulation and fibrinolysis in normal human subjects.

When highly purified human PC was administered intravenously to healthy subjects, plasma levels of immunoreactive PC decreased with a half-life of 10.9 h. Intravenously administered APC decreased with a half-life of 23 min as measured by prolongation of activated partial thromboplastin time (APTT). However, 1.7 h was obtained for the plasma half-life of APC when it was measured immunologically. These findings suggested that a significant fraction of the administered APC was rapidly inhibited by plasma inhibitor. Upon administration of APC, APTT was prolonged and plasma levels of clotting factor VIII (FVIII) decreased transiently as measured by clotting assay. However, when determined by a chromogenic assay method in which 120-fold diluted plasma samples were used, plasma levels of FVIII remained unchanged. Plasma levels of F-V did not decrease after APC administration. These findings suggested that prolongation of APTT and apparent decrease in plasma F-VIII clotting activity might be due to the in vitro-effect of APC present in plasma samples used. Diurnal fluctuation of plasminogen activator inhibitor in normal subjects was not affected by administration of APC.

Thus, PC or APC seems to function selectively at the site of thrombin-formation without lowering plasma levels of coagulation factors.

Keywords

Protein C - Thrombosis - Factor V - Factor VIII - Plasminogen activator inhibitor
 

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