title: Activation of endothelial and coagulation systems in left ventricular assist device recipients.
abstract: BACKGROUND
  The paucity of organ donors has necessitated redirecting research toward finding alternative means to a heart transplant, such as left ventricular assist devices (LVADs) that will serve not merely as bridge-to-transplant but also as destination therapy. To better understand hemorrhagic and thromboembolic complications that currently limit the use of such devices, we studied the endothelial and coagulation system changes in LVAD recipients with time.
  
  
  METHODS
  We studied these markers of endothelial dysfunction: circulating endothelial cells and expression of E-selectin, vascular cell adhesion molecule, intercellular adhesion molecule, and tissue factor on circulating endothelial cells, thrombin generation (prothrombin fragments 1,2 and thrombin/antithrombin), and fibrinolysis (D-dimer). Our study group consisted of 21 LVAD recipients (on day 0 and on postoperative days 1, 7, 30, 90, and 180) and 7 control patients undergoing non-LVAD cardiac surgery.
  
  
  RESULTS
  Baseline values of intercellular adhesion molecule, E-selectin, tissue factor, thrombin/antithrombin, and D-dimer were significantly higher in LVAD recipients than the normal range. Markers of thrombin generation (thrombin/antithrombin and prothrombin fragments 1,2) and fibrinolysis (D-dimer) peaked postoperatively and declined to baseline levels or below by 3 months. But the expression of inducible endothelial markers (intercellular adhesion molecule, E-selectin, tissue factor) on circulating endothelial cells increased postoperatively, then decreased but remained elevated above preoperative levels for up to 6 months. In our control patients, baseline levels of intercellular adhesion molecule, E-selectin, tissue factor, D-dimer, and thrombin/antithrombin were lower and decreased significantly by day 7, as compared with LVAD recipients (p < 0.05).
  
  
  CONCLUSIONS
  Left ventricular assist device recipients experienced significant baseline activation of endothelial and coagulation systems, further accentuated in the early postoperative period. Left ventricular assist device recipients also had prolonged activation of the endothelial and coagulation systems, suggesting activation of the extrinsic (tissue factor) pathway of thrombosis mediated by sustained endothelial dysfunction in these patients. Further studies are needed to determine the clinical influence of such changes in LVAD recipients.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota 55455, USA. johnx008@umn.edu
authors.forename: Ranjit
authors.initials: R
authors.lastname: John
authors.forename: Sandhya
authors.initials: S
authors.lastname: Panch
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hrabe
authors.forename: Peng
authors.initials: P
authors.lastname: Wei
authors.forename: Anna
authors.initials: A
authors.lastname: Solovey
authors.forename: Lyle
authors.initials: L
authors.lastname: Joyce
authors.forename: Robert
authors.initials: R
authors.lastname: Hebbel
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001777:Blood Coagulation / Q000502:physiology*; D002452:Cell Count; D019040:E-Selectin / Q000097:blood / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000473:pathology / Q000601:surgery*; D006353:Heart-Assist Devices; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000276:immunology; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011184:Postoperative Period; D011379:Prognosis; D011446:Prospective Studies; D013925:Thromboplastin / Q000276:immunology / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000276:immunology
chemical_list: D015415:Biomarkers; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D013925:Thromboplastin