Enoxaparin Thromboprophylaxis in Children Hospitalized for COVID-19: A Phase 2 Trial.

BACKGROUND: Evidence regarding the safety and efficacy of anticoagulant thromboprophylaxis among pediatric patients hospitalized for coronavirus disease 2019 (COVID-19) is limited. We sought to evaluate safety, dose-finding, and preliminary efficacy of twice-daily enoxaparin as primary thromboprophylaxis among children hospitalized for symptomatic COVID-19, including primary respiratory infection and multisystem inflammatory syndrome in children (MISC). METHODS: We performed a phase 2, multicenter, prospective, open-label, single-arm clinical trial of twice-daily enoxaparin (initial dose: 0.5mg/kg per dose; max: 60mg; target anti-Xa activity: 0.20-0.49IU/mL) as primary thromboprophylaxis for children <18 years of age hospitalized for symptomatic COVID-19. Study endpoints included: cumulative incidence of International Society of Thrombosis and Haemostasis-defined clinically relevant bleeding; enoxaparin dose-requirements; and cumulative incidence of venous thromboembolism within 30-days of hospital discharge. Descriptive statistics summarized endpoint estimates that were further evaluated by participant age (±12 years) and clinical presentation. RESULTS: Forty children were enrolled and 38 met analyses criteria. None experienced clinically relevant bleeding. Median (interquartile range) dose to achieve target anti-Xa levels was 0.5 mg/kg (0.48-0.54). Dose-requirement did not differ by age (0.5 [0.46-0.52] mg/kg for age ≥12 years versus 0.52 [0.49-0.55] mg/kg for age <12 years, P = .51) but was greater for participants with MISC (0.52 [0.5-0.61] mg/kg) as compared with primary COVID-19 (0.48 [0.39-0.51] mg/kg, P = .010). Two children (5.3%) developed central-venous catheter-related venous thromboembolism. No serious adverse events were related to trial intervention. CONCLUSIONS: Among children hospitalized for COVID-19, thromboprophylaxis with twice-daily enoxaparin appears safe and warrants further investigation to assess efficacy.

TWICE-DAILY ENOXAPARIN AS PRIMARY THROMBOPROPHYLAXIS IN PEDIATRIC PATIENTS HOSPITALIZED FOR COVID-19

B Conclusions: b In children hospitalized for COVID-19 related illness, primary TP with subcutaneous enoxaparin twice-daily at a starting dose of 0.5 mg/kg is safe and achieves target anti-Xa levels during hospitalization in >90% of patients. Future phase 3 trials of primary TP are warranted in hospitalized children with proinflammatory conditions such as COVID-19, for which HA-VTE risk is increased. B Introduction: b Evidence is limited on the safety or efficacy of anticoagulant thromboprophylaxis (TP) against hospital-associated venous thromboembolism (HA-VTE) in children hospitalized with COVID-19 and multisystem inflammatory syndrome in children (MIS-C). [Extracted from the article] Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombotic complications in adults, but the incidence of COVID-19-related thrombosis in children and adolescents is unclear. Most children with acute COVID-19 have mild disease, but coagulopathy has been associated with multisystem inflammatory syndrome in children (MIS-C), a postinfectious complication. We conducted a multicenter retrospective cohort study to determine the incidence of thrombosis in children hospitalized with COVID-19 or MIS-C and evaluate associated risk factors. We classified patients into 1 of 3 groups for analysis: COVID-19, MIS-C, or asymptomatic SARS-CoV-2. Among a total of 853 admissions (COVID-19, n = 426; MIS-C, n = 138; and asymptomatic SARS-CoV-2, n = 289) in 814 patients, there were 20 patients with thrombotic events (TEs; including 1 stroke). Patients with MIS-C had the highest incidence (9 [6.5%] of 138) vs COVID-19 (9 [2.1%] of 426) or asymptomatic SARS-CoV-2 (2 [0.7%] of 289). In patients with COVID-19 or MIS-C, a majority of TEs (89%) occurred in patients age ≥12 years. Patients age ≥12 years with MIS-C had the highest rate of thrombosis at 19% (9 of 48). Notably, 71% of TEs that were not present on admission occurred despite thromboprophylaxis. Multivariable analysis identified the following as significantly associated with thrombosis: age ≥12 years, cancer, presence of a central venous catheter, and MIS-C. In patients with COVID-19 or MIS-C, hospital mortality was 2.3% (13 of 564), but it was 28% (5 of 18) in patients with TEs. Our findings may help inform pediatric thromboprophylaxis strategies.

Consensus-based clinical recommendations and research priorities for anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illness.

BACKGROUND: Observational studies indicate that children hospitalized with COVID-19-related illness, like adults, are at increased risk for venous thromboembolism (VTE). A multicenter phase 2 clinical trial of anticoagulant thromboprophylaxis in children hospitalized with COVID-19-related illness has recently been initiated in the United States. To date, there remains a paucity of high-quality evidence to inform clinical practice world-wide. Therefore, the objective of this scientific statement is to provide consensus-based recommendations on the use of anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illnesses, and to identify priorities for future research. METHODS: We surveyed 20 pediatric hematologists and pediatric critical care physicians from several continents who were identified by Pediatric/Neonatal Hemostasis and Thrombosis Subcommittee leadership as having experience and expertise in the use of anticoagulant thromboprophylaxis and/or the management of COVID-19-related illness in children. A comprehensive review of the literature on COVID-19 in children was also performed. RESULTS: Response rate was 90%. Based on consensus of expert opinions, we suggest the administration of low-dose low molecular weight heparin subcutaneously twice-daily as anticoagulant thromboprophylaxis (in the absence of contraindications, and in combination with mechanical thromboprophylaxis with sequential compression devices, where feasible) in children hospitalized for COVID-19-related illness (including the multisystem inflammatory syndrome in children [MIS-C]) who have markedly elevated D-dimer levels or superimposed clinical risk factors for hospitalassociated VTE. For children who are clinically unstable or have severe renal impairment, we suggest the use of unfractionated heparin by continuous intravenous infusion as anticoagulant thromboprophylaxis. In addition, continued efforts to characterize VTE risk and risk factors in children with COVID-19, as well as to evaluate the safety and efficacy of anticoagulant thromboprophylaxis strategies in children hospitalized with COVID-19-related illness (including MIS-C) via cooperative multicenter trials, were identified among several key priorities for future research. CONCLUSION: These consensus-based recommendations on the use of anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illnesses and priorities for future research will be updated as high-quality evidence emerges.