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 post-infectious complication. We conducted a multicenter retrospective cohort study to determine the incidence of thrombosis in children hospitalized with COVID-19 or MIS-C and to evaluate associated risk factors. We classified patients into one of three groups for analysis: COVID-19, MIS-C, or asymptomatic SARS-CoV-2. Among a total of 853 admissions (426 COVID-19, 138 MIS-C, and 289 asymptomatic SARS-CoV-2) in 814 patients, there were 20 patients with thrombotic events (TE) (including 1 stroke). Patients with MIS-C had the highest incidence (6.5%, 9/138) versus COVID-19 (2.1%, 9/426) or asymptomatic SARS-CoV-2 (0.7%, 2/289). In patients with COVID-19 or MIS-C, the majority of thrombotic events (89%) occurred in patients ≥12 years. Patients > 12 years with MIS-C had the highest rate of thrombosis at 19% (9/48). Notably, 71% of TE 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% (13/564), but was 28% (5/18) in patients with thrombotic events. Our findings may help inform pediatric thromboprophylaxis strategies.

Low von Willebrand factor (VWF) in adults is associated with significant bleeding, most notably heavy menstrual bleeding (HMB) and postpartum hemorrhage, although this has not been characterized in adolescents. The objectives of this analysis of a multicenter single arm observational cohort study in adolescents with low VWF–associated HMB were to describe the bleeding phenotype, HMB severity, and related complications. Eligibility criteria included postmenarchal females <21 years of age with HMB (Pictorial Blood Assessment Chart [PBAC] score >100) and low VWF (2 values of VWF activity ≥30 and ≤50 IU/dL). Patients diagnosed with other bleeding disorders were ineligible. Clinical phenotype data, including PBAC and Bleeding Assessment Tool (BAT) scores, laboratory data, and HMB management/outcome details, were extracted. Patient demographics and clinical characteristics were summarized as medians with minimum/maximum values or frequencies with percentages. Groups were compared using a Wilcoxon rank-sum test or Fisher’s exact test. A total of 113 patients met inclusion criteria, and 2 were excluded. Ninety four percent had a significant bleeding phenotype (BAT score >2), with predominantly mucocutaneous bleeding (32%-44%), postprocedural/surgical bleeding (15%), and severe HMB (BAT HMB domain score ≥2; 90%). Bleeding complications included iron deficiency (60%), anemia (21%), transfusion (12%), and hospitalization (10%). Desmopressin challenge response in subjects tested was good and sustained. Several (48%) required combined therapy for HMB (hormonal/hemostatic), and one third did not show improvement despite therapy. Our results suggest that adolescent females with low VWF have a significant bleeding phenotype and resultant complications warranting a focus on prompt diagnosis, appropriate therapy, and prevention of complications.

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