Haemostatic and inflammatory biomarkers in advanced chronic heart failure: role of oral anticoagulants and successful heart transplantation.
Advanced chronic heart failure (CHF) is associated with abnormal haemostasis and inflammation, but it is not known how these abnormalities are related, whether they are modified by oral anticoagulants (OAT), or if they persist after successful heart transplantation. We studied 25 patients with CHF (New York Heart Association class IV, 10 of whom underwent heart transplantation) and 25 age- and sex-matched healthy controls by measuring their plasma levels of prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, factor VII (FVII), fibrinogen, von Willebrand factor (VWF), tumour necrosis factor (TNF), soluble TNF receptor II (sTNFRII), interleukin 6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelial-selectin (E-selectin) and thrombomodulin. CHF patients had higher plasma levels of TAT, D-dimer, t-PA, fibrinogen, VWF, TNF, IL-6, sTNFRII, sVCAM-1 (P = 0.0001), sICAM-1 (P = 0.003) and thrombomodulin (P = 0.007) than controls. There were significant correlations (r = 0.414-0.595) between coagulation, fibrinolysis, endothelial dysfunction and inflammation parameters, which were lower in those patients treated with OATs. Heart transplantation led to reductions in fibrinogen (P = 0.001), VWF (P = 0.05), D-dimer (P = 0.05) and IL-6 levels (P = 0.05), but all the parameters remained significantly higher (P = 0.01-0.0001) than in the controls. Advanced CHF is associated with coagulation activation, endothelial dysfunction and increased proinflammatory cytokine levels. Most of these abnormalities parallel each other, tend to normalize in patients treated with OATs and, although reduced, persist in patients undergoing successful heart transplantation, despite the absence of clinical signs of CHF.
Cugno
Massimo
M
Department of Internal Medicine, University of Milan, Milan, Italy. massimo.cugno@unimi.it
Mari
Daniela
D
Meroni
Pier Luigi
PL
Gronda
Edoardo
E
Vicari
Francesco
F
Frigerio
Maria
M
Coppola
Raffaella
R
Bottasso
Bianca
B
Borghi
Maria Orietta
MO
Gregorini
Luisa
L
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D000990:Antithrombin III / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D006333:Heart Failure / Q000097:blood* / Q000276:immunology* / Q000628:therapy; D016027:Heart Transplantation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000032:analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011184:Postoperative Period; D047992:TNF Receptor-Associated Factor 2; D018180:Thrombomodulin / Q000032:analysis; D010959:Tissue Plasminogen Activator / Q000032:analysis; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014841:von Willebrand Factor / Q000032:analysis
D000925:Anticoagulants; D015415:Biomarkers; D002352:Carrier Proteins; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; C101338:PSMD2 protein, human; D017395:Plasminogen Activator Inhibitor 1; D047992:TNF Receptor-Associated Factor 2; D018180:Thrombomodulin; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator