Protein biomarkers for incident deep venous thrombosis in critically ill adolescents: An exploratory study

There are no tests to identify critically ill children at high risk of deep venous thrombosis (DVT). In this exploratory study, we aimed to identify proteins that are associated with incident DVT in critically ill adolescents.

Plasma samples were obtained from critically ill adolescents within 24 hours after initiation of cardiopulmonary support. The adolescents were followed with ultrasound to detect the development of DVT of the lower extremity and clinically for bleeding. Thrombin-antithrombin complex and prothrombin fragment 1+2 were measured using immunosorbent assays, whereas procoagulation and anticoagulation factors were measured using multiplex assays. Plasma samples were also analyzed using SOMAscan, an aptamer-based capture assay. The associations between DVT and the log-transformed level of the proteins were assessed using logistic regression adjusting for the presence of femoral venous catheter and severity of illness. Associations were expressed as odds ratio (OR) for every log-fold increase in level of the protein with 95% confidence interval (CI).

Plasma from 59 critically ill adolescents, of whom 9 developed incident DVT, was analyzed. The median age of the adolescents was 15.1 years (interquartile range, 14.0-16.7 years). Higher levels of thrombin-antithrombin complex (OR: 31.54; 95% CI: 2.09-475.92) and lower levels of factor XIII (OR: 0.03; 95% CI: 0.002-0.44) were associated with DVT. CD36, MIC-1, and EpoR were marginally associated with DVT. Only factor XIII was associated with clinically relevant bleeding (OR: 0.27; 95% CI: 0.08-0.97).

We identified candidate protein biomarkers for incident DVT. We plan to validate our findings in adequately powered studies.