Alpha-2-macroglobulin inhibits the anticoagulant action of activated protein C in cord and adult plasma.
Healthy newborns have a very low risk of thrombosis. It has been suggested that this is partly due to the anticoagulant effect of alpha-2-macroglobulin (a2-M). This broad-spectrum protease binding glycoprotein is physiologically elevated in newborns over adult values and has been shown to complex generated alpha-thrombin. In our present study, we point out that a2-M also acts as a procoagulant by inhibiting activated protein C (APC). In all experiments performed in cord and adult plasma the anticoagulant action of APC was diminished in a dose-dependent manner when a2-M levels were successively elevated, reflected in increased thrombin potential (TP), and enhanced at low a2-M levels, reflected in decreased TP.
Cvirn
G
G
Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, and Department of Pediatrics, University of Graz, Austria. gerhard.cvirn@klinikum-graz.at
Gallistl
S
S
Muntean
W
W
D000328:Adult; D000925:Anticoagulants / Q000037:antagonists & inhibitors* / Q000097:blood; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D005312:Fetal Blood / Q000737:chemistry* / Q000378:metabolism; D006490:Hemostatics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D011486:Protein C / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011516:Prothrombin / Q000187:drug effects / Q000378:metabolism; D013917:Thrombin / Q000187:drug effects / Q000378:metabolism; D019851:Thrombophilia / Q000097:blood; D000511:alpha-Macroglobulins / Q000494:pharmacology*
D000925:Anticoagulants; D006490:Hemostatics; D010446:Peptide Fragments; D011486:Protein C; D000511:alpha-Macroglobulins; C045879:prothrombin fragment 1.2; D011516:Prothrombin; D013917:Thrombin