Activation and complexation of protein C and cleavage and decrease of
protein S in plasma of patients with intravascular coagulation
MJ Heeb, D Mosher and JH Griffin
Department of Immunology, Research Institute of Scripps Clinic, La Jolla,
CA 92037.
Activated protein C (APC) is inhibited by two major plasma inhibitors
(PCIs). To find evidence for in vivo complexation of APC, immunoblotting
studies were performed on plasmas of 85 patients with suspected
disseminated intravascular coagulation (DIC). Samples from 62 of these
patients contained 5% to 35% of protein C antigen in APC:inhibitor
complexes, indicating that protein C activation and inhibition had
occurred. In 24 normal plasmas, no detectable APC:PCI complexes were
observed (less than 5%). Patients with higher levels of complexes had more
abnormal coagulation test data for DIC. The major band of APC complexes
detected by anti-protein C antibodies did not react with antibodies to the
heparin-dependent protein C inhibitor (PCI- 1) previously described.
Rather, APC was complexed with another recently described plasma protein C
inhibitor, PCI-2. Immunoblotting studies for protein S, the cofactor for
APC, revealed that the majority of the DIC patient plasmas contained a
higher than normal proportion of protein S in cleaved form, suggesting that
protein S may have been proteolytically inactivated. Protein S total
antigen levels were also found to be low in DIC patients, excluding those
with malignancy. These studies support the hypothesis that the protein C
pathway is activated during DIC.
Volume 73,
Issue 2,
pp. 455-461,
02/01/1989
Copyright © 1989 by The American Society of Hematology
