Urinary 11‐dehydrothromboxane B2 aspirin efficacy testing is sensitive to perioperative inflammation in pediatric solid‐organ transplant patients

• Published in: Pediatric blood & cancer 2022-02, Vol.69 (2), p.e29413-n/a
• Main Authors: Boucher, Alexander A., Francisco, Brenton J., Pfeiffer, Amanda, Martin, Matthew, Martin, Janine, Shova, Amy, Nathan, Jaimie D., Tiao, Gregory M., Luchtman‐Jones, Lori
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; anticoagulation therapy; Aspirin; Aspirin - therapeutic use; Blood Platelets; CD3 antigen; Child; Child, Preschool; Discordance; Hematology; hematology—hemostasis and thrombosis; Humans; Infant; Infant, Newborn; Inflammation; Inflammation - drug therapy; Kidney transplantation; Liver transplantation; Morbidity; Oncology; Organ Transplantation - adverse effects; Pancreas; Pancreatic islet transplantation; pediatric hematology/oncology; Pediatrics; Platelet Aggregation; Platelet Aggregation Inhibitors - pharmacology; Platelet Aggregation Inhibitors - therapeutic use; platelets; Sensitivity analysis; Surgery; Thromboembolism; Thrombosis - drug therapy; Thrombosis - etiology; Thrombosis - prevention & control; Thromboxane B2 - analogs & derivatives; Thromboxane B2 - pharmacology; Transplants & implants; Young Adult
• ISSN: 1545-5009; 1545-5017
• DOI: 10.1002/pbc.29413

Background Evidence for aspirin efficacy testing in pediatrics is limited, especially outside of cardiology, yet thrombotic events have high morbidity in other areas such as pediatric transplant surgery. Debates about whether thromboembolic events while on aspirin represent “aspirin resistance” or “high on‐treatment platelet reactivity” persist, given the poor intertest agreement between testing platforms. Procedure This prospective observational study involved measuring aspirin efficacy using ex vivo testing of platelet aggregation (VerifyNow‐Aspirin, VN) and urine 11‐dehydrothromboxane B2 (AsprinWorks, UTxB2) contemporaneously at up to three time points after major noncardiac organ transplant surgery. The collection days (CD) were the second and seventh days after stable aspirin dosing and then a convalescent time point 2‐9 months later. Results Fifty‐five participants (age range, 0‐21 years) were enrolled, having undergone total pancreatectomy with islet autotransplantation (N = 36), orthotopic liver transplantation (N = 18), and combined liver‐kidney transplantation (N = 1). Platelet reactivity measured by VN remained unchanged, whereas UTxB2, which was elevated postoperatively, decreased significantly from CD1 to CD2 and CD3. Discordance in therapeutic efficacy was noted per manufacturer cutoffs, with therapeutic VN results in 86% of tests, whereas 12% of UTxB2 were therapeutic. Age‐based stratification of UTxB2 results using previously published pediatric median levels increased overall UTxB2 therapeutic rates (80%) and intertest concordance (67% vs 27% if using adult range). No thrombotic events were observed. Conclusions Our data suggest that urine thromboxane production may be an underappreciated reflection of postoperative inflammation. Validation of pediatric normal ranges for UTxB2 is a critical next step.