title: Coagulation activation is associated with interleukin-6 plasma levels in patients with mechanical prosthetic heart valves.
abstract: BACKGROUND
  The intensity of oral anticoagulant therapy in patients with mechanical heart valves is evaluated and controlled by the International Normalized Ratio (INR). However, intravascular coagulation activation can occur despite normal INR values and is related to clinical events. Here, anticoagulation efficiency was assessed by sensitive techniques and potential determinants of coagulation activation were identified.
  
  
  METHODS
  Forty patients were enrolled after they had undergone mechanical aortic valve replacement. As markers of coagulation activation, plasma concentrations of the D-dimer antigen were prospectively measured. The patients were classified into quartiles according to the D-dimer plasma antigen level. Serum concentrations of the inflammatory markers C-reactive protein (CRP) and Interleukin (IL)-6 were also assessed.
  
  
  RESULTS
  The D-dimer levels varied significantly despite therapeutic INR values. In patients with high D-dimer levels, the serum concentrations of IL-6 were significantly increased (top vs. bottom quartile, median, 1.35 versus 0.80 pg/ml; p<0.05), suggestive of subclinical inflammation. There was no association between the D-dimer levels and age, sex, cardiovascular risk factors or time since valve replacement.
  
  
  CONCLUSIONS
  Coagulation activation and inflammation are associated with mechanical heart valves. The D-dimer antigen and IL-6 may be more sensitive than INR and CRP to detect these states and, therefore, could prove valuable additional markers, e.g., in determining the efficacy of new anticoagulant drugs.
authors.affiliation: First Department of Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Liebe
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Kaden
authors.forename: Sanjay
authors.initials: S
authors.lastname: Isaaci
authors.forename: Martina
authors.initials: M
authors.lastname: Brueckmanni
authors.forename: Ursula
authors.initials: U
authors.lastname: Hoffmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Bertsch
authors.forename: Martin
authors.initials: M
authors.lastname: Borggrefe
authors.forename: Carl-Erik
authors.initials: CE
authors.lastname: Dempfle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001705:Bioprosthesis / Q000009:adverse effects*; D001777:Blood Coagulation; D002097:C-Reactive Protein / Q000032:analysis; D019281:Dimerization; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006350:Heart Valve Prosthesis / Q000009:adverse effects*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012680:Sensitivity and Specificity
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; C036309:fibrin fragment D; D002097:C-Reactive Protein