Prothrombotic Microvesicle Generation in Pediatric Cardiopulmonary Bypass: A Pilot Observational Study.

Abstract

Importance: Over 10% of children develop thrombosis after cardiac surgery for congenital heart disease. Children with a single ventricle physiology have the highest risk of thrombosis associated with increased length of the postoperative stay, neurologic complications, and mortality. To decrease these complications, research is needed to understand the mechanisms that promote cardiopulmonary bypass (CPB) surgery-induced thrombin generation and clot formation.

Objectives: The objective of this pilot observational study was to measure the generation of prothrombotic microvesicles (MVs) and thrombin generation in 21 children collected 5 minutes after initiation of CPB, at the end of CPB, upon arrival in the pediatric congenital cardiac unit (PCCU), and 20 to 24 hours after arrival in the PCCU.

Design, setting, and participants: An observational pilot study measured platelet and leukocyte MV, platelet aggregation, coagulation, and thrombin generation in 21 children undergoing CPB surgery. The study setting was a tertiary pediatric hospital. Inclusion criteria included age between birth to 5 years and weight on the day of surgery greater than three kilograms.

Main outcomes and measures: Bleeding outcomes were measured by chest tube output and thrombotic outcomes were measured by surveillance ultrasound. Laboratory outcomes of prothrombotic MVs and thrombin generation were measured by high-resolution flow cytometry and calibrated automated thrombogram, respectively.

Results: Time on CPB correlated with a significant increase in WBCs and phosphatidylserine-expressing MVs. Children with single ventricle physiology had increased levels of prothrombotic MVs (p = 0.017), platelet aggregation, peak thrombin (p = 0.019), and d-dimer (p = 0.029) upon arrival to the ICU compared with children with a dual ventricle. Only single ventricle children had a positive correlation between generation of platelet MV with peak thrombin (p = 0.010).

Conclusions and relevance: Larger prospective studies are needed to determine if prothrombotic MVs can predict children with congenital heart disease at risk for thrombotic events.