Evaluation of the Safety and Efficacy of Enoxaparin Once-Daily Versus Twice-Daily Dosing for Prophylaxis in Pediatric Patients.

OBJECTIVES: Enoxaparin for the prevention of venous thromboembolism (VTE) in pediatric patients is -typically dosed twice a day. The use of once-daily dosing like that used in adult patients is limited because of a lack of safety and efficacy data. The aim of this study was to evaluate the safety and efficacy of -once-daily versus twice-daily dosing of enoxaparin for pediatric VTE prophylaxis based on incidence of thrombotic and bleeding events. METHODS: This was a 3-year retrospective chart review of enoxaparin received for VTE prophylaxis at -Cohen Children's Medical Center, New Hyde Park, NY. Exclusion criteria were age 18 years or older, and renal dysfunction. RESULTS: A total of 177 enoxaparin courses (81 in the once-daily and 96 in the twice-daily group) were included. The median dose in the once-daily group was 0.68 mg/kg/dose with dose capping at 40 mg/dose in 70% of patients. One patient in the once-daily group had a VTE, whereas no patients in the twice-daily group experienced a VTE. One major bleeding event occurred in the once-daily group (p = 0.46); however, minor bleeding events were comparable between the 2 groups (p = 0.69). CONCLUSIONS: Once-daily enoxaparin prophylaxis appears to be safe and effective based on minimal -differences in incidence of thrombotic and bleeding events when compared to twice-daily dosing. Based on this study, it may be reasonable to consider once-daily enoxaparin dosing for prophylaxis, especially in older children. A larger multicenter cohort study evaluating once-daily dosing for prophylaxis is warranted to validate the safety and efficacy specifically for risk-based dosing strategies.

Hemophagocytic Lymphohistiocytosis Gene Variants in Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) affects few children previously infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In 2020, 45 children admitted to our hospital for MIS-C underwent genetic screening with a commercial 109-immune-gene panel. Thirty-nine children were diagnosed with MIS-C, and 25.4% of the 39 MIS-C patients harbored rare heterozygous missense mutations either in primary hemophagocytic lymphohistiocytosis (pHLH) genes (LYST, STXBP2, PRF1, UNC13D, AP3B1) or the HLH-associated gene DOCK8 (four variants). We demonstrate that foamy virus introduction of cDNA for the four DOCK8 variants into human NK-92 natural killer (NK) cells led to decreased CD107a expression (degranulation) and decreased NK cell lytic function in vitro for each variant. Heterozygous carriers of missense mutations in pHLH genes and DOCK8 may serve as risk factors for development of MIS-C among children previously infected with SARS-CoV-2.

Multisystem inflammatory syndrome in children (MIS-C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS-C cohort.

BACKGROUND: Adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have had high rates of thrombosis. A novel condition in children infected with SARS-CoV-2, multisystem inflammatory syndrome in children (MIS-C), has limited data on their prothrombotic state or need for thromboprophylaxis. OBJECTIVES: We aimed to analyze the prothrombotic state using coagulation profiles, rotational thromboelastometry (ROTEM) parameters and clinical outcomes, to determine if this could aid in risk stratification for thromboprophylaxis. METHODS: This analysis included patients (<21 years of age) with a diagnosis of MIS-C (n = 40) and controls (presenting with suspicion of MIS-C but later ruled out; n = 26). RESULTS: MIS-C patients had higher levels of inflammatory markers including D-dimer (p < .0001), compared with controls, along with evidence of hypercoagulability on ROTEM with elevated evaluation of fibrinogen activity (FIBTEM) maximum clot firmness (MCF) (p < .05). For MIS-C patients with D-dimers >1000 ng/ml, there was a significant correlation of FIBTEM MCF (p < .0001) with a mean value of 37.4 (standard deviation 5.1). D-dimer >2144 ng/ml was predictive of intensive care unit admission (area under the curve [AUC] 0.80; 95% confidence interval, 0.60-0.99; p < .01; sensitivity: 82%, specificity: 75%), and elevated FIBTEM MCF (AUC 1 for >2500 ng/ml). MIS-C patients (50%) received enoxaparin thromboprophylaxis (in addition to aspirin) with significant improvement in their inflammatory and ROTEM parameters upon outpatient follow-up; none developed symptomatic thrombosis. CONCLUSIONS: Despite an observed prothrombotic state, none of the MIS-C patients (on aspirin alone or in combination with enoxaparin) developed symptomatic thrombosis. ROTEM, in addition to coagulation profiles, may be helpful to tailor thromboprophylaxis in critically ill MIS-C patients.