COVID-19 is associated with haemostatic dysregulation, 1 with thromboembolism occurring in 25% of hospitalised COVID-19 patients and microvascular thrombi reported at autopsy. 2 Platelets are activated in COVID-19 patients requiring intensive care, 3 while limited data in mild COVID-19 shows no changes in platelet phenotype. 4 Children have low-risk of severe COVID-19 and thrombosis. 5 If haemostasis is fundamental to COVID-19 pathogenesis, then age-related haemostatic differences may protect children from COVID-19. While there is evidence of changes in leucocyte populations of non-hospitalised children and adults infected and exposed to SARS-CoV-2, 6 the effect on paediatric platelets is unknown.We investigated platelet surface-markers in adults and children who were SARS-CoV-2-positive and their household contacts. We aimed to establish whether SARS-CoV-2 induced changes in platelet phenotype in individuals with mild COVID-19.Participants were recruited from the Respiratory Infection Clinic at The Royal Children's Hospital (RCH), Melbourne, using the enrollment protocol and participant pool previously described. 6 Upon a positive SARS-CoV-2 polymerase chain reaction (PCR) test, blood collection was arranged for family members at two time points: 'acute', within two weeks of post-test and 'convalescent', 4-7 weeks posttest. Individuals were classified 'SARS-CoV-2-positive' if they tested positive, and 'SARS-CoV-2-exposed' if they tested negative on repeated tests but remained in close household contact with individuals who tested positive. All participants recovered at home. This study was approved by the RCH Human Research Ethics Committee (QA/63666/ RCHM-2020).
OBJECTIVES: To investigate platelet pathophysiology associated with pediatric extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective observational study of neonatal and pediatric ECMO patients from September 1, 2016, to December 31, 2019. SETTING: The PICU in a large tertiary referral pediatric ECMO center. PATIENTS: Eighty-seven neonates and children (< 18 yr) supported by ECMO. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Arterial blood samples were collected on days 1, 2, and 5 of ECMO and were analyzed by whole blood flow cytometry. Corresponding clinical data for each patient was also recorded. A total of 87 patients were recruited (median age, 65 d; interquartile range [IQR], 7 d to 4 yr). The median duration of ECMO was 5 days (IQR, 3–8 d) with a median length of stay in PICU and hospital of 18 days (IQR, 10–29 d) and 35 days (IQR, 19–75 d), respectively. Forty-two patients (48%) had at least one major bleed according to a priori determined definitions, and 12 patients (14%) had at least one thrombotic event during ECMO. Platelet fibrinogen receptor expression decreased (median fluorescence intensity [MFI], 29,256 vs 26,544; p = 0.0005), while von Willebrand Factor expression increased (MFI: 7,620 vs 8,829; p = 0.0459) from day 2 to day 5 of ECMO. Platelet response to agonist, Thrombin Receptor Activator Peptide 6, also decreased from day 2 to day 5 of ECMO, as measured by binding with anti-P-selectin, PAC-1 (binds activated GPIIb/IIIa), and anti-CD63 monoclonal antibodies (P-selectin area under the curve [AUC]: 63.46 vs 42.82, respectively, p = 0.0022; PAC-1 AUC: 93.75 vs 74.46, p = 0.0191; CD63 AUC: 55.69 vs 41.76, p = 0.0020). CONCLUSIONS: The loss of platelet response over time may contribute to bleeding during ECMO. These novel insights may be useful in understanding mechanisms of bleeding in pediatric ECMO and monitoring platelet markers clinically could allow for prediction or early detection of bleeding and thrombosis.
Background: Despite increasing technical improvement and extracorporeal membrane oxygenation (ECMO)-related knowledge over the past three decades, morbidity and mortality associated with bleeding and clotting complications remain high in pediatric patients undergoing ECMO. Platelets, a key element of the coagulation system, have been proposed to be the main cause of coagulopathy in the setting of ECMO. This systematic review aims to summarize and discuss the existing knowledge of platelet phenotype and function in the pediatric ECMO population.Methods: A systematic review was conducted for the Embase, Medline, and PubMed databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.Results: The detailed study selection process yielded a total of 765 studies and only 3 studies that fulfilled the selection criteria were included in this review. Techniques used to assess platelet function in the three existing studies included platelet aggregometry, flow cytometry, and thromboelastography-platelet mapping. The finding that is common to the three studies is reduced platelet function in pediatric patients during ECMO either compared to before the initiation of ECMO or in non-survivors compared to survivors. Two studies demonstrated reduced platelet aggregation that are irreversible by platelet transfusion during ECMO. Two studies reported bleeding events and mortality in children on ECMO and none of the studies investigated thrombotic events.Conclusions: This systematic review demonstrates the extremely limited information available for platelet phenotype and function in the pediatric ECMO population. Evidence from the existing literature suggests reduced platelet aggregation and increased platelet activation in children during ECMO. However, this needs to be interpreted with care due to the limitations associated with the techniques used for platelet function testing. Furthermore, the association between platelet dysfunction and clinical outcomes in the pediatric ECMO population remains elusive. Multiple research gaps have been identified when it comes to the knowledge of platelet phenotype and function of children on ECMO, highlighting the need for robust, well-designed studies in this setting.
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