title: Time-dependent cellular population of textured-surface left ventricular assist devices contributes to the development of a biphasic systemic procoagulant response.
abstract: OBJECTIVE
  Textured-surface left ventricular assist devices (LVAD) have been shown to enhance ventricular function and survival in patients with end-stage heart failure. Furthermore, we have described a procoagulant physiology in our LVAD population with sustained thrombin generation (elevated thrombin-antithrombin III complex and prothrombin fragment 1+2) and fibrinolysis (D-dimers), even up to 335 days after LVAD placement. To explain such sustained activation of coagulation, we speculated that the LVAD surface selectively adsorbed and promoted activation of circulating blood cells.
  
  
  METHODS
  In a prospective study of 20 patients with LVADs, we examined samples of peripheral blood as well as cells harvested from the surface of the LVADs at the time of their explantation for procoagulant proinflammatory markers.
  
  
  RESULTS
  Analysis of the cells populating the LVAD surface revealed the presence of pluripotent hematopoietic CD34(+) cells, as well as cells bearing monocyte (CD14)/macrophage (CD68) markers, which also expressed procoagulant tissue factor. Reverse transcriptase-polymerase chain reaction confirmed cellular activation on the LVAD surface, revealing transcripts for interleukin 1alpha, interleukin 2, and tumor necrosis factor alpha, in addition to vascular cell adhesion molecule-1 consistent with their capacity to continually recruit and activate circulating cells, thereby propagating their response. In the periphery, elevated levels of tissue factor were found in the plasma of patients with LVADs, along with enhanced procoagulant activity.
  
  
  CONCLUSIONS
  These observations suggest that the LVAD surface selectively absorbs and activates circulating hematopoietic precursor and monocytic cells, thereby creating a sustained prothrombotic and potentially proinflammatory systemic environment.
authors.affiliation: Department of Surgery, Physiology and Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: T B
authors.initials: TB
authors.lastname: Spanier
authors.forename: J M
authors.initials: JM
authors.lastname: Chen
authors.forename: M C
authors.initials: MC
authors.lastname: Oz
authors.forename: D M
authors.initials: DM
authors.lastname: Stern
authors.forename: E A
authors.initials: EA
authors.lastname: Rose
authors.forename: A M
authors.initials: AM
authors.lastname: Schmidt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D000990:Antithrombin III / Q000378:metabolism; D001243:Assisted Circulation / Q000295:instrumentation*; D015415:Biomarkers / Q000097:blood; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000628:therapy; D006353:Heart-Assist Devices; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D015846:Monokines / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D011446:Prospective Studies; D011516:Prothrombin / Q000378:metabolism; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015214:Antigens, Differentiation, Myelomonocytic; D000990:Antithrombin III; D015415:Biomarkers; D001779:Blood Coagulation Factors; D015815:Cell Adhesion Molecules; D007376:Interleukin-2; D015846:Monokines; D010446:Peptide Fragments; D010447:Peptide Hydrolases; D011516:Prothrombin; D012313:RNA; D013925:Thromboplastin; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C046193:antithrombin III-protease complex; C045879:prothrombin fragment 1.2