Children and young adults hospitalized for severe COVID-19 exhibit thrombotic coagulopathy
Corresponding Author
William B. Mitchell
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Correspondence
William B. Mitchell, Children's Hospital at Montefiore, Division of Pediatric Hematology/Oncology, 3411 Wayne Ave, 9th Floor, Bronx, NY 10467.
Email: [email protected]
Search for more papers by this authorJennifer Davila
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorJanine Keenan
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorJenai Jackson
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorAdit Tal
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorKerry A. Morrone
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorEllen J. Silver
Albert Einstein College of Medicine, Department of Pediatrics, Division of General Academic Pediatrics, Bronx, New York
Search for more papers by this authorSarah O'Brien
Nationwide Children's Hospital, Division of Hematology and Oncology, Columbus, Ohio
Search for more papers by this authorDeepa Manwani
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorCorresponding Author
William B. Mitchell
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Correspondence
William B. Mitchell, Children's Hospital at Montefiore, Division of Pediatric Hematology/Oncology, 3411 Wayne Ave, 9th Floor, Bronx, NY 10467.
Email: [email protected]
Search for more papers by this authorJennifer Davila
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorJanine Keenan
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorJenai Jackson
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorAdit Tal
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorKerry A. Morrone
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorEllen J. Silver
Albert Einstein College of Medicine, Department of Pediatrics, Division of General Academic Pediatrics, Bronx, New York
Search for more papers by this authorSarah O'Brien
Nationwide Children's Hospital, Division of Hematology and Oncology, Columbus, Ohio
Search for more papers by this authorDeepa Manwani
Albert Einstein College of Medicine, Department of Pediatrics, Division of Hematology and Oncology, Bronx, New York
Search for more papers by this authorAbstract
We report the clinical and laboratory coagulation characteristics of 27 pediatric and young adult patients (2 months to 21 years) treated for symptomatic COVID-19 at a children's hospital in the Bronx, New York, between March 1 and May 31, 2020. D-Dimer was > 0.5 μg/mL (upper limit of normal) in 25 (93%) patients at admission; 11 (41%) developed peak D-dimer > 5 μg/mL during admission. Seven (26%) patients developed venous thromboembolism: three with deep vein thrombosis and four with pulmonary embolism. Requirement of increased ventilatory support was a risk factor for thrombosis (P = 0.006). Three of eight (38%) patients on prophylactic anticoagulation developed thrombosis; however, no patients developed VTE on low-molecular-weight heparin prophylaxis titrated to anti-Xa level. Manifestation of COVID-19 disease was severe or critical in 16 (59%) patients. Four (15%) patients died of COVID-19 complications: all had comorbidities. Elevated D-dimer and increased VTE rate were observed in this young cohort, particularly in those with severe respiratory complications, suggesting thrombotic coagulopathy. More data are needed to guide thromboprophylaxis in this age group.
CONFLICTS OF INTEREST
The authors declare no competing financial conflicts.
Supporting Information
| Filename | Description |
|---|---|
| pbc28975-sup-0001-FigureS1.png1 MB | Supporting Information Material |
| pbc28975-sup-0002-TableS1.docx24.2 KB | Table S1. Characteristics of patients with sickle cell disease (n = 5) |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020; 46: 1089-1098. https://doi.org/10.1007/s00134-020-06062-x.
- 2Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of coronavirus disease. Crit Care Med. 2020; 48(9): 1358-1364. https://doi.org/10.1097/ccm.0000000000004458.
- 3Iba T, Levy JH, Levi M, Thachil J. Coagulopathy in COVID-19. J Thromb Haemost. 2020; 18(9): 2103-2109. https://doi.org/10.1111/jth.14975.
- 4Iba T, Connors JM, Levy JH. The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflamm Res. 2020; 69(12): 1181-1189. https://doi.org/10.1007/s00011-020-01401-6.
- 5Castagnoli R, Votto M, Licari A, et al. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review. JAMA Pediatrics. 2020; 174(9): 882-889. https://doi.org/10.1001/jamapediatrics.2020.1467.
- 6Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in China. Pediatrics. 2020; 145(6):e20200702. https://doi.org/10.1542/peds.2020-0702.
- 7Du H, Dong X, Zhang JJ, et al. Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status. Allergy. 2020; 76: 510-532. https://doi.org/10.1111/all.14452.
- 8Romani L, Chiurchiù S, Santilli V, et al. COVID-19 in Italian pediatric patients: the experience of a tertiary children's hospital. Acta Paediatr. 2020; 109: 2311-2312. https://doi.org/10.1111/apa.15465.
- 9Jiang L, Tang K, Levin M, et al. COVID-19 and multisystem inflammatory syndrome in children and adolescents. Lancet Infect Dis. 2020; 20(11): e276-e288. https://doi.org/10.1016/s1473-3099(20)30651-4.
- 10Shekerdemian LS, Mahmood NR, Wolfe KK, et al. Characteristics and outcomes of children with coronavirus disease 2019 (COVID-19) infection admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. 2020; 174(9): 868-873. https://doi.org/10.1001/jamapediatrics.2020.1948.
- 11A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020; 20(8): e192-e197. https://doi.org/10.1016/s1473-3099(20)30483-7
- 12Monagle P, Chan AKC, Goldenberg NA, et al. Antithrombotic Therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141(2 Suppl): e737S-e801S. https://doi.org/10.1378/chest.11-2308.
- 13Wang TF, Milligan PE, Wong CA, Deal EN, Thoelke MS, Gage BF. Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients. Thromb Haemost. 2014; 111(1): 88-93. https://doi.org/10.1160/th13-01-0042.
- 14Klok FA, Kruip M, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020. https://doi.org/10.1016/j.thromres.2020.04.013.
- 15Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020; 18(5): 1094-1099. https://doi.org/10.1111/jth.14817.
- 16Pan D, Sze S, Minhas JS, et al. The impact of ethnicity on clinical outcomes in COVID-19: a systematic review. EClinicalMedicine. 2020; 23:100404. https://doi.org/10.1016/j.eclinm.2020.100404.
- 17Rentsch CT, Kidwai-Khan F, Tate JP, et al. Covid-19 by race and ethnicity: a national cohort study of 6 million United States veterans. medRxiv. 2020. https://doi.org/10.1101/2020.05.12.20099135.
- 18Morrone KA, Strumph K, Liszewski MC, et al. Acute chest syndrome in the setting of SARS-COV-2 infections—a case series at an urban medical center in the Bronx. Pediatric Blood Cancer. 2020; 67(11):e28579. https://doi.org/10.1002/pbc.28579.
- 19Llitjos 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. https://doi.org/10.1111/jth.14869.
- 20Avruscio G, Camporese G, Campello E, et al. COVID-19 and venous thromboembolism in intensive care or medical ward. Clin Transl Sci. 2020; 13(6): 1108-1114. https://doi.org/10.1111/cts.12907.
- 21Sun Y, Dong Y, Wang L, et al. Characteristics and prognostic factors of disease severity in patients with COVID-19: the Beijing experience. J Autoimmun. 2020; 112:102473. https://doi.org/10.1016/j.jaut.2020.102473.
- 22Nutescu EA, Spinler SA, Wittkowsky A, Dager WE. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother. 2009; 43(6): 1064-1083. https://doi.org/10.1345/aph.1L194.
- 23Cuker A. ASH 2020 guidelines on the use of anticoagulation in patients with COVID-19: draft recommendations.
- 24Goldenberg NA, Sochet A, Albisetti M, et al. 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. https://doi.org/10.1111/jth.15073.
