title: Anti-c5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis.
abstract: Sepsis and trauma are the two most common causes of disseminated intravascular coagulation and multiple organ dysfunction syndrome. Both disseminated intravascular coagulation and the systemic inflammatory response syndrome often lead to multiple organ dysfunction syndrome. The current studies have evaluated the relationship between the anaphylatoxin, C5a, and changes in the coagulation/fibrinolytic systems during the cecal ligation and puncture (CLP) model of sepsis in rats. CLP animals treated with anti-C5a had a much improved number of survivors (63%) compared to rats treated with pre-immune IgG (31%). In CLP rats treated with pre-immune IgG there was clearly increased procoagulant activity with prolongation of the activated partial thromboplastin time and prothrombin time, reduced platelet counts, and increased levels of plasma fibrinogen. Evidence for thrombin formation was indicated by early consumption of factor VII:C, subsequent consumption of factors XI:C and IX:C and anti-thrombin and increased levels of the thrombin-anti-thrombin complex and D-dimer. Limited activation of fibrinolysis was indicated by reduced plasma levels of plasminogen and increased levels of tissue plasminogen activator and plasminogen activator inhibitor. Most of these parameters were reversed in CLP rats that had been treated with anti-C5a. Production of C5a during sepsis may directly or indirectly cause hemostatic defects that can be reduced by blockade of C5a.
authors: Departments of Pathology and Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors: Ines J
authors: IJ
authors: Laudes
authors: Jeffrey C
authors: JC
authors: Chu
authors: Sujata
authors: S
authors: Sikranth
authors: Markus
authors: M
authors: Huber-Lang
authors: Ren-Feng
authors: RF
authors: Guo
authors: Niels
authors: N
authors: Riedemann
authors: J Vidya
authors: JV
authors: Sarma
authors: Alvin H
authors: AH
authors: Schmaier
authors: Peter A
authors: PA
authors: Ward
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000991:Antithrombins / Q000187:drug effects / Q000378:metabolism; D001779:Blood Coagulation Factors / Q000187:drug effects* / Q000378:metabolism; D015936:Complement C5a / Q000737:chemistry / Q000276:immunology*; D004195:Disease Models, Animal; D005164:Factor IX / Q000187:drug effects / Q000378:metabolism; D005165:Factor V / Q000187:drug effects / Q000378:metabolism; D005167:Factor VII / Q000187:drug effects / Q000378:metabolism; D005169:Factor VIII / Q000187:drug effects / Q000378:metabolism; D005172:Factor XI / Q000187:drug effects / Q000378:metabolism; D005174:Factor XII / Q000187:drug effects / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000187:drug effects / Q000378:metabolism; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D008297:Male; D010314:Partial Thromboplastin Time; D010446:Peptide Fragments / Q000276:immunology; D010976:Platelet Count; D011517:Prothrombin Time; D051381:Rats; D020318:Rats, Long-Evans; D018805:Sepsis / Q000097:blood* / Q000401:mortality; D013047:Specific Pathogen-Free Organisms; D015996:Survival Rate; D013917:Thrombin / Q000187:drug effects / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000991:Antithrombins; D001779:Blood Coagulation Factors; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; C036309:fibrin fragment D; D015936:Complement C5a; D005165:Factor V; D005167:Factor VII; D005169:Factor VIII; D005164:Factor IX; D005174:Factor XII; D005340:Fibrinogen; D005172:Factor XI; D013917:Thrombin