Value of soluble adhesion molecules and plasma coagulation markers in assessing transplant coronary artery disease in pediatric heart transplant recipients

:  Background:  With an increasing number of heart transplantations (HTx) performed in children and an extended long-term survival of these patients, the importance of transplant coronary artery disease (TCAD) rises in this group of transplant recipients. Reliable serum markers for diagnosis or non-invasive monitoring of this disease in pediatric transplant recipients are still missing. We studied the systemic expression of adhesion molecules as well as plasma coagulation markers and the occurrence of TCAD and/or rejection in pediatric heart transplant recipients. Methods and Results:  The systemic plasma levels of soluble forms of sVCAM-1 and sICAM-1, d-dimer, tissue factor (TF), prothombin fragments F1+2, and tissue factor pathway inhibitor (TFPI) were assessed in serial venous blood samples (2–4 per patient) in 50 pediatric transplant recipients children and 63 age- and sex-matched non-transplanted controls. TCAD and rejection were diagnosed angiographically or by combined histological, echocardiographic, or clinical signs, respectively. Plasma levels of sICAM-1 and sVCAM-1, d-dimers and prothrombin fragment F1+2 but not TF and TFPI were significantly increased in children following HTx compared with non-transplanted controls (p<0.001). Among the transplanted patients, sICAM-1 levels were significantly higher in patients with angiographically detectable TCAD than in patients without evidence of TCAD (p<0.005). Plasma sICAM-1 levels above a cutoff value of 1500 ng/mL (95.5 percentile of control values) were indicative of the presence of TCAD (odds ratio 2.7; 95% confidence interval, 1.34–5.56, p = 0.022; Fisher's exact test). Only d-dimers were found to be significantly elevated in children with signs of myocardial rejection compared with those without rejection. Conclusions:  Our results suggest that plasma sICAM-1 and d-dimer levels may be potentially useful to non-invasively assess TCAD and rejection, respectively, in pediatric heart transplant recipients.