Assessment of coagulation factor activation during cardiopulmonary bypass with a new monoclonal antibody.
Antithrombin-III (AT) is a key inhibitor of blood coagulation that neutralizes activated serine esterases by forming covalent modified complexes (ATm). A new monoclonal antibody directed against short-lived AT-activated serine protease complexes provides a means of measuring subclinical coagulation activity during cardiopulmonary bypass (CPB). Twelve patients undergoing CPB for coronary artery bypass grafting were studied and AT, ATm, D-dimers (DD), and several other coagulation and fibrinolytic markers were measured during the surgical procedure. There were decreases in AT, factors V, II, X, IX, protein S (total and free), C4b-binding protein, thrombomodulin, and platelets counts, whereas heparin, ACT, thrombospondin, plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) increased. ATm and the percentage of ATm available (ATm/AT) showed a peak during CPB. These results demonstrate that during CPB, the use of heparin produces an equilibrium involving increased coagulation activation and consumption in association with increased fibrinolysis. The equilibrated consumption of both coagulation and fibrinolytic factors leads to low levels of all factors after cardiac surgery. The ATm assay allows assessment of the differential effects of CPB and surgical trauma on coagulation activation. It is speculated that ATm levels may be useful in monitoring the consumption of coagulation factors.
Journois
D
D
Department of Anesthesia, Faculté Necker, Université René Descartes, Hôpital Laennec Paris, France.
Mauriat
P
P
Pouard
P
P
Marchot
P
P
Amiral
J
J
Safran
D
D
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000990:Antithrombin III / Q000032:analysis* / Q000502:physiology; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D002315:Cardiopulmonary Bypass; D002352:Carrier Proteins / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000097:blood; D015935:Complement C4b / Q000032:analysis; D003169:Complement Inactivator Proteins; D005164:Factor IX / Q000032:analysis* / Q000502:physiology; D005165:Factor V / Q000032:analysis / Q000502:physiology; D005170:Factor X / Q000032:analysis* / Q000502:physiology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006023:Glycoproteins; D006493:Heparin / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017293:Protein S / Q000097:blood; D011516:Prothrombin / Q000032:analysis* / Q000502:physiology; D011951:Receptors, Complement / Q000032:analysis; D018180:Thrombomodulin / Q000032:analysis; D019699:Thrombospondins; D010959:Tissue Plasminogen Activator / Q000097:blood
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D003169:Complement Inactivator Proteins; D005338:Fibrin Fibrinogen Degradation Products; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D017395:Plasminogen Activator Inhibitor 1; D017293:Protein S; D011951:Receptors, Complement; D018180:Thrombomodulin; D019699:Thrombospondins; C036309:fibrin fragment D; D015935:Complement C4b; D000990:Antithrombin III; D005165:Factor V; D011516:Prothrombin; D005164:Factor IX; D005170:Factor X; D006493:Heparin; D010959:Tissue Plasminogen Activator