Thromboprophylaxis for children hospitalized with COVID‐19 and MIS‐C

Abstract

Background Limited data exist about effective regimens for pharmacological thromboprophylaxis in children with acute coronavirus disease 2019 (COVID‐19) and multisystem inflammatory syndrome in children (MIS‐C). Objectives Study the outcomes of institutional thromboprophylaxis protocol for primary venous thromboembolism (VTE) prevention in children hospitalized with acute COVID‐19/MIS‐C. Methods This single‐center retrospective cohort study included consecutive children (aged less than 21 years) with COVID‐19/MIS‐C who received tailored intensity thromboprophylaxis, primarily with low‐molecular‐weight heparin, from April 2020 through October 2021. Thromboprophylaxis was given to those with moderate to severe disease based on the World Health Organization scale and exposure to two or more VTE risk factors. Therapeutic intensity was considered for severe illness. Clinical recovery along with D‐dimer improvement determined thromboprophylaxis duration. Outcomes were incident VTEs, bleeding, and mortality. Results Among 211 hospitalizations, 45 (21.3%) received thromboprophylaxis (COVID‐19, 16; MIS‐C, 29). Median age was 14.8 years (interquartile range [IQR], 8.9–16.1). Among 35 (77.8%) with severe illness, 27 (60.0%) required respiratory support, and 19 (42.2%) required an intensive care unit stay. Median hospitalization was 6 days (IQR, 5.0–10.5). Median thromboprophylaxis duration was 19 days (IQR, 6.0–31.0) with therapeutic intensity in 24 (53.3%) and prophylactic in 21 (46.7%). Outcomes were as follows: VTE, 1 (2.2%); death, 1 (2.2%, unrelated to bleeding/thrombosis); major/clinically relevant nonmajor bleeding, 0; and minor bleeding, 7 (15.5%). D‐dimer was elevated in a majority at diagnosis (median, 2.3; IQR, 1.2–3.3 mg/ml fibrinogen‐equivalent units) and was noninformative in assessing disease severity. D‐dimer normalized at thromboprophylaxis discontinuation. Conclusions Our experience of using clinically directed thromboprophylaxis with tailored intensity approach for children hospitalized with COVID‐19 and MIS‐C favors its inclusion in current standard of care. The role of D‐dimer in directing thromboprophylaxis management deserves further evaluation.

Thromboprophylaxis for Coagulopathy Related to COVID-19 in Pediatrics: A Narrative Review

“…One patient developed DVT during anticoagulation. The rate of death is not significantly different between two groups but the rate of death is higher in patients who have not received anticoagulant [ 29 ] Schmitz et al 2022 [ 30 ] Retrospective cohort study 211 patients, of these 45 patients received thromboprophylaxis COVID-19 and MIS-C Under 21 years of age D-dimer levels elevated at least 2 times the ULN at diagnosis LMWH Based on the criteria, patients received therapeutic intensity (LMWH 1 mg/kg/dose BID or UFH 20 U/kg/h) or prophylactic intensity (LMWH 0.5 mg/kg/dose BID or UFH 10–15 U/kg/h) Tailored-intensity thromboprophylaxis is recommended in moderate to severe pediatric patients infected with COVID-19. PE or fatal VTE were not experienced with any patients and none of the patients experienced major bleeding.…”

“…PE or fatal VTE were not experienced with any patients and none of the patients experienced major bleeding. Therefore, thromboprophylaxis seems safe and effective in pediatric patients [ 30 ] COVID-19 coronavirus disease 2019, DVT deep vein thrombosis, LMWH low molecular weight heparin, MIS-C multisystem inflammatory syndrome, PE pulmonary embolism, UFH unfractionated heparin, ULN upper limit of normal, VTE venous thromboembolism …”

“…The investigators suggested that, despite the results of the study, thromboprophylaxis could be helpful in pediatric patients with moderate to severe COVID-19 classified based on the World Health Organization (WHO) progression scale; further randomized clinical trials with larger sample sizes are needed to prove this conclusion. In a recent cohort study that evaluated thromboprophylaxis in patients with MIS-C, it was demonstrated that thromboprophylaxis is useful in these patients after first considering multiple factors including rising laboratory parameters such as D-dimer levels [ 30 ]. It is imperative to consider clinical parameters such as illness severity and VTE risk factors prior to thromboprophylaxis administration and determining the dose of the agent.…”

“…Using the tailored-intensity thromboprophylaxis, which adjusts the dose of enoxaparin to a specific level of anti-Xa based on the patient's condition, is another crucial factor. The studies have shown that the median dose of LMWH for prophylaxis was 0.5 mg/kg/dose twice daily and for therapeutic intensity was 1.0 mg/kg/dose twice daily [ 30 ].…”

“…This study also showed that the enoxaparin dosing which was used in MIS-C patients is higher than that for other pediatric COVID-19-infected patients to achieve the target of anti-Xa [ 24 ]. The initial prophylactic dose of enoxaparin in this clinical trial and others was 0.5 mg/kg twice daily for patients over 2 months of age [ 24 , 30 , 32 ], which was in correlation with the recommendations from the Chest guideline regarding the general preventive dose of enoxaparin for thromboprophylaxis in pediatric patients (age-dependent dosing: < 2 months: 0.75 mg/kg per dose twice daily and ≥ 2 months: 0.5 mg/kg per dose twice daily) [ 34 ].…”