PB0263 - Whole blood microfluidics to assess direct oral anticoagulants (DOACs) activity in neonatal cardiac patients

Background: VTEs increase morbidity and mortality in neonates with complex congenital heart disease (CCHD). Current prophylaxis consists of UFH or LMWH, requiring repeated testing to ensure therapeutic dosing. DOACs (e.g. Apixaban) are attractive alternatives due to predictable pharmacokinetics, a wide therapeutic window, and limited drug–drug interactions. Although a therapeutic range is established for adults, drug concentrations needed to mitigate clot formation in neonates have not been determined.

Aims: To determine the effects of Apixaban on platelet/fibrin deposition and clot stability using a low volume, multi-channel microfluidic device on whole blood from neonatal cardiac patients.

Methods: This IRB approved study was conducted at Children’s Hospital of Pittsburgh. A microfluidic device was used to study coagulation during corn trypsin inhibitor-treated whole blood perfusion (200 s-1, 15 min) over surface-immobilized tissue factor and collagen. Blood was drawn immediately before and 24h after surgery when thrombophrophylaxis is typically started. Platelet and fibrin deposition were monitored by fluorescence microscopy (± Apixiban).

Results: 31 neonates were enrolled. Demographics: weight 3.25±0.6 kg; GA at birth 39.1±1 weeks; age at surgery 6.9±3.6 days. Most participants had double ventricle physiology (26/31), required bypass (26/31) and intraoperative blood products (26/31). There were no significant differences (P>0.05) in Hb/Hct, platelet count, or fibrinogen concentrations pre- vs post-surgery. Time to clot-induced channel occlusion and platelet/fibrin deposition were similar in post-operative vs adult participants (7.6±3.1min vs 7.9±1.5min, and Figure 1A), the former prolonged (14.2±1.9min) and the latter reduced in pre-operative neonates. Although Apixaban had a similar effect on platelet/fibrin deposition (Figure 1B), it significantly increased channel occlusion time for of blood from post-operative neonates vs adults (11.1±4.1min vs 7.9±1.5min, respectively, P< 0.001; 0.25 µM).

Conclusion(s): Majority of post-operative neonates with CCHD are hypercoaguable compared to the preoperative state and appear to be more sensitive to Apixiban inhibition than adults based on occlusion times.