Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C
Hilary Whitworth, Sarah E Sartain, Riten Kumar, Katherine Armstrong, Lance Ballester, Marisol Betensky, Clay T Cohen, Rosa Diaz, Caroline Diorio, Neil A Goldenberg, Julie Jaffray, Jacquelyn Keegan, Kendra Malone, Adrienne G Randolph, Stacey Rifkin-Zenenberg, Wendy Seto Leung, Anthony Sochet, Lakshmi Srivaths, Ayesha Zia, Leslie Raffini, Hilary Whitworth, Sarah E Sartain, Riten Kumar, Katherine Armstrong, Lance Ballester, Marisol Betensky, Clay T Cohen, Rosa Diaz, Caroline Diorio, Neil A Goldenberg, Julie Jaffray, Jacquelyn Keegan, Kendra Malone, Adrienne G Randolph, Stacey Rifkin-Zenenberg, Wendy Seto Leung, Anthony Sochet, Lakshmi Srivaths, Ayesha Zia, Leslie Raffini
Abstract
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.
© 2021 by The American Society of Hematology.
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References
- Zhou F, Yu T, Du R, et al. . Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020; 395(10229):1054-1062.
- Fogarty H, Townsend L, Ni Cheallaigh C, et al. . COVID19 coagulopathy in Caucasian patients. Br J Haematol. 2020;189(6):1044-1049.
- Wang D, Hu B, Hu C, et al. . Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA. 2020; 323(11):1061-1069.
- Al-Samkari H, Karp Leaf RS, Dzik WH, et al. . COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 2020;136(4):489-500.
- Cui S, Chen S, Li X, Liu S, Wang F.. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020;18(6):1421-1424.
- Helms J, Tacquard C, Severac F, et al. ; CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis) . High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089-1098.
- Llitjos JF, Leclerc M, Chochois C, et al. . High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients. J Thromb Haemost. 2020;18(7):1743-1746.
- Middeldorp S, Coppens M, van Haaps TF, et al. . Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020;18(8):1995-2002.
- Poissy J, Goutay J, Caplan M, et al. ; Lille ICU Haemostasis COVID-19 Group . Pulmonary embolism in patients with COVID-19: awareness of an increased prevalence. Circulation. 2020;142(2):184-186.
- Malas MB, Naazie IN, Elsayed N, Mathlouthi A, Marmor R, Clary B.. Thromboembolism risk of COVID-19 is high and associated with a higher risk of mortality: a systematic review and meta-analysis. EClinicalMedicine. 2020; 29:100639.
- Lu X, Zhang L, Du H, et al. ; Chinese Pediatric Novel Coronavirus Study Team . SARS-CoV-2 infection in children. N Engl J Med. 2020; 382(17):1663-1665.
- Bixler D, Miller AD, Mattison CP, et al. ; Pediatric Mortality Investigation Team . SARS-CoV-2-associated deaths among persons aged <21 years - United States, February 12-July 31, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(37):1324-1329.
- Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P.. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet. 2020;395(10237):1607-1608.
- Verdoni L, Mazza A, Gervasoni A, et al. . An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet. 2020;395(10239):1771-1778.
- Dufort EM, Koumans EH, Chow EJ, et al. ; New York State and Centers for Disease Control and Prevention Multisystem Inflammatory Syndrome in Children Investigation Team . Multisystem inflammatory syndrome in children in New York state. N Engl J Med. 2020;383(4): 347-358.
- Feldstein LR, Rose EB, Horwitz SM, et al. ; CDC COVID-19 Response Team . Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med. 2020;383(4):334-346.
- Ramcharan T, Nolan O, Lai CY, et al. . Paediatric inflammatory multisystem syndrome: temporally associated with SARS-CoV-2 (PIMS-TS): cardiac features, management and short-term outcomes at a UK tertiary paediatric hospital. Pediatr Cardiol. 2020;41(7):1391-1401.
- Loi M, Branchford B, Kim J, Self C, Nuss R.. COVID-19 anticoagulation recommendations in children. Pediatr Blood Cancer. 2020;67(9): e28485.
- Goldenberg NA, Sochet A, Albisetti M, et al. ; Pediatric/Neonatal Hemostasis and Thrombosis Subcommittee of the ISTH SSC . Consensus-based clinical recommendations and research priorities for anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illness. J Thromb Haemost. 2020;18(11):3099-3105.
- Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG.. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2): 377-381.
- Harris PA, Taylor R, Minor BL, et al. ; REDCap Consortium . The REDCap Consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208.
- Cordoro KM, Reynolds SD, Wattier R, McCalmont TH.. Clustered cases of acral perniosis: clinical features, histopathology, and relationship to COVID-19. Pediatr Dermatol. 2020;37(3):419-423.
- Centers for Disease Control and Prevention. Multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19). . Accessed 30 July 2020.
- Mitchell LG, Goldenberg NA, Male C, Kenet G, Monagle P, Nowak-Göttl U; Perinatal and Paediatric Haemostasis Subcommittee of the SSC of the ISTH. Definition of clinical efficacy and safety outcomes for clinical trials in deep venous thrombosis and pulmonary embolism in children. J Thromb Haemost. 2011;9(9):1856-1858.
- Abarca-Gómez L, Abdeen ZA, Hamid ZA, et al. ; NCD Risk Factor Collaboration (NCD-RisC) . Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet. 2017;390(10113):2627-2642.
- Ippolito Bastidas H, Márquez-Pérez T, García-Salido A, et al. . Cerebral venous sinus thrombosis in a pediatric patient with COVID-19. Neurol Clin Pract. 2020;11(2): e208-e210.
- Essajee F, Solomons R, Goussard P, Van Toorn R.. Child with tuberculous meningitis and COVID-19 coinfection complicated by extensive cerebral sinus venous thrombosis. BMJ Case Rep. 2020;13(9):e238597.
- Del Borrello G, Giraudo I, Bondone C, et al. . SARS‐CoV‐2 associated coagulopathy and thromboembolism prophylaxis in children: a single centre observational study. J Thromb Haemost. 2021;19(2):522-530.
- Raffini L, Huang Y-S, Witmer C, Feudtner C.. Dramatic increase in venous thromboembolism in children’s hospitals in the United States from 2001 to 2007. Pediatrics. 2009; 124(4):1001-1008.
- Miesbach W, Makris M.. COVID-19: coagulopathy, risk of thrombosis, and the rationale for anticoagulation. Clin Appl Thromb Hemost. 2020;26:1076029620938149.
- Zhang L, Feng X, Zhang D, et al. . Deep vein thrombosis in hospitalized patients with coronavirus disease 2019 (COVID-19) in Wuhan, China: prevalence, risk factors, and outcome [published correction appears in Circulation. 2020;142(2):e33]. Circulation. 2020;142(2): 114-128.
- Mahajerin A, Branchford BR, Amankwah EK, et al. . Hospital-associated venous thromboembolism in pediatrics: a systematic review and meta-analysis of risk factors and risk-assessment models. Haematologica. 2015;100(8):1045-1050.
- Witmer CM, Takemoto CM.. Pediatric hospital acquired venous thromboembolism. Front Pediatr. 2017;5:198.
- Goyal MK, Simpson JN, Boyle MD, et al. . Racial and/or ethnic and socioeconomic disparities of SARS-CoV-2 infection among children. Pediatrics. 2020;146(4): e2020009951.
- Alcendor DJ. Racial disparities-associated COVID-19 mortality among minority populations in the US. J Clin Med. 2020; 9(8):2442.
- COVID-19 anticoagulation in children - thromboprophylaxis. .
- Diorio C, Anderson EM, McNerney KO, et al. . Convalescent plasma for pediatric patients with SARS-CoV-2-associated acute respiratory distress syndrome. Pediatr Blood Cancer. 2020;67(11):e28693.
- Chiotos K, Bassiri H, Behrens EM, et al. . Multisystem inflammatory syndrome in children during the COVID-19 pandemic: a case series. J Pediatric Infect Dis Soc. 2020; 9(3):393-398.
- Diorio C, McNerney KO, Lambert M, et al. . Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations. Blood Adv. 2020;4(23):6051-6063.
Source: PubMed