The coagulation and fibrinolytic responses of baboons after in vivo thrombin generation--effect of interleukin 6.
Disseminated intravascular coagulation (DIC) may lead to severe thrombotic or hemorrhagic complications. The present work was undertaken to study the effect of interleukin 6 (IL-6) on variations of key coagulation and fibrinolytic parameters in plasma in a baboon model of experimental DIC induced by injection of factor Xa and phospholipids at dosages leading to partial (48%) or complete fibrinogen depletion. Transient increases of D-dimer, fibrinopeptide A, thrombin-antithrombin and the activated partial thromboplastin time were observed. Each parameter had a particular (time and Xa/phospholipid dose dependent) pattern of changes. The principal effect of IL-6 was a more rapid restoration of fibrinogen concentrations and of overall coagulation tests. Injection of factor Xa/phospholipids led also to a rapid increase of tissue-type plasminogen activator (t-PA) the extent of which was dependent on Xa/phospholipid dose. Pretreatment with IL-6 induced a threefold increase of basal t-PA and a corresponding increase of the t-PA response. Plasminogen activator inhibitor type 1 (PAI-1) concentrations did not change after low dose Xa/phospholipids, but increased eightfold after high dose Xa/phospholipids, IL-6 pretreatment induced within 8 h a twentyfold increase of PAI-1 but no further increase was observed after injection of factor Xa/phospholipids. Thus, in vivo thrombin generation leads to dynamic modifications of the coagulation and fibrinolytic systems. The principal effect of IL-6 is a more rapid normalization of overall coagulation tests, due to normalization of fibrinogen, and an increased t-PA release response which is partially counteracted by increased PAI-1 concentrations.
Kruithof
E K
EK
Division of Angiology and Hemostasis, University Hospital, Geneva, Switzerland.
Mestries
J C
JC
Gascon
M P
MP
Ythier
A
A
D000818:Animals; D000990:Antithrombin III / Q000032:analysis; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000276:immunology; D015951:Factor Xa; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D005344:Fibrinopeptide A / Q000032:analysis; D015850:Interleukin-6 / Q000494:pharmacology*; D010215:Papio; D010314:Partial Thromboplastin Time; D010447:Peptide Hydrolases / Q000032:analysis; D010743:Phospholipids; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000096:biosynthesis*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000097:blood
D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D010743:Phospholipids; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D005344:Fibrinopeptide A; D000990:Antithrombin III; D010447:Peptide Hydrolases; D013917:Thrombin; D015951:Factor Xa; D010959:Tissue Plasminogen Activator