Abstract P2085: Whole Blood Microfluidics To Assess Direct Oral Anticoagulant (doac) Activity And Reversal In Neonatal Cardiac Patients

Circulation Research(2022)

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摘要
Introduction: VTEs increase morbidity in neonates with congenital heart disease. Although heparin is the main therapy for prevention / treatment, DOACs are attractive alternatives due to ease of administration, no dependence on antithrombin and wider therapeutic window. Preclinical studies to evaluate their effects on clot formation and antidote reversal are hampered by a lack of low volume assays that permit multiple analyses. Hypothesis: A low volume microfluidic system can reproducibly measure activity and reversibility of DOAC-induced alterations in coagulation. Methods: A microfluidic device was used to study whole blood (WB) coagulation in response to co-immobilized tissue factor and collagen. Blood was drawn before and 24h after surgery. Platelet and fibrin deposition were monitored by fluorescence microscopy (Apixaban ± andexanet). Results: 34 neonates were enrolled. Most participants had double ventricle physiology, required bypass and blood products. There was no difference (P>0.05) in Hb / Hct, platelet count, or fibrinogen levels pre- vs post-surgery. Time to clot-induced channel occlusion and platelet / fibrin deposition were similar in post-operative vs adult participants (7.6±3.1 min vs 7.9±1.5 min; Figure 1A), the former prolonged (14.2±1.9 min) and the latter reduced in pre-operative patients. Although Apixaban reduced clot formation (Figure 1B), it prevented channel occlusion in most post-operative neonates vs adults (60% vs 20%). Andexanet reversed its effects, restoring coagulation to non-treatment levels. Conclusions: WB microfluidics demonstrated that post-operative neonates are hypercoagulable compared to the pre-operative state and are responsive to apixaban, the effects of which can be reversed with Andexanet.
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关键词
Pediatric cardiology, Venous thrombosis, Anticoagulants
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