Activation of Endothelial and Coagulation Systems in Left Ventricular Assist Device Recipients

Ranjit John, Sandhya Panch, Jennifer Hrabe, Peng Wei, Anna Solovey, Lyle Joyce, Robert Hebbel

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1171-1179
Number of pages9
JournalAnnals of Thoracic Surgery
Volume88
Issue number4
DOIs
StatePublished - Oct 2009

Bibliographical note

Funding Information:
Ranjit John received funding for the study from the W. Gerald Austen Young Investigator Award, Society of Thoracic Surgeons.

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