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Multisystem inflammatory syndrome in children (MIS-C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS-C cohort.
J Thromb Haemost. 2021 07; 19(7):1764-1770.JT

Abstract

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.

Authors+Show Affiliations

Division of Pediatric Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatrics, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park, NY, USA. Feinstein Institutes for Medical Research, Manhasset, NY, USA.Feinstein Institutes for Medical Research, Manhasset, NY, USA. Division of Pediatric Critical Care Medicine, Cohen Children's Medical Center, New Hyde Park, NY, USA. Division of Pediatric Cardiology, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Infectious Disease, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Hospital Medicine, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Cardiology, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Cardiology, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park, NY, USA.Division of Pediatric Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park, NY, USA. Feinstein Institutes for Medical Research, Manhasset, NY, USA.Division of Anesthesiology, North Shore University Hospital, Manhasset, NY, USA.Division of Pediatric Hematology/Oncology and Cellular Therapy, Cohen Children's Medical Center, New Hyde Park, NY, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33872443

Citation

Al-Ghafry, Maha, et al. "Multisystem Inflammatory Syndrome in Children (MIS-C) and the Prothrombotic State: Coagulation Profiles and Rotational Thromboelastometry in a MIS-C Cohort." Journal of Thrombosis and Haemostasis : JTH, vol. 19, no. 7, 2021, pp. 1764-1770.
Al-Ghafry M, Vagrecha A, Malik M, et al. Multisystem inflammatory syndrome in children (MIS-C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS-C cohort. J Thromb Haemost. 2021;19(7):1764-1770.
Al-Ghafry, M., Vagrecha, A., Malik, M., Levine, C., Uster, E., Aygun, B., Appiah-Kubi, A., Vlachos, A., Capone, C. A., Rajan, S., Palumbo, N., Misra, N., Mitchell, E. C., Wolfe, L. C., Lipton, J. M., Shore-Lesserson, L., & Acharya, S. S. (2021). Multisystem inflammatory syndrome in children (MIS-C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS-C cohort. Journal of Thrombosis and Haemostasis : JTH, 19(7), 1764-1770. https://doi.org/10.1111/jth.15340
Al-Ghafry M, et al. Multisystem Inflammatory Syndrome in Children (MIS-C) and the Prothrombotic State: Coagulation Profiles and Rotational Thromboelastometry in a MIS-C Cohort. J Thromb Haemost. 2021;19(7):1764-1770. PubMed PMID: 33872443.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multisystem inflammatory syndrome in children (MIS-C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS-C cohort. AU - Al-Ghafry,Maha, AU - Vagrecha,Anshul, AU - Malik,Marium, AU - Levine,Chana, AU - Uster,Eliza, AU - Aygun,Banu, AU - Appiah-Kubi,Abena, AU - Vlachos,Adrianna, AU - Capone,Christine A, AU - Rajan,Sujatha, AU - Palumbo,Nancy, AU - Misra,Nilanjana, AU - Mitchell,Elizabeth C, AU - Wolfe,Lawrence C, AU - Lipton,Jeffrey M, AU - Shore-Lesserson,Linda, AU - Acharya,Suchitra S, Y1 - 2021/06/04/ PY - 2021/03/31/revised PY - 2021/02/02/received PY - 2021/04/09/accepted PY - 2021/4/20/pubmed PY - 2021/7/1/medline PY - 2021/4/19/entrez KW - COVID-19 KW - MIS-C KW - ROTEM KW - SARS-CoV-2 KW - pediatric KW - thrombosis SP - 1764 EP - 1770 JF - Journal of thrombosis and haemostasis : JTH JO - J Thromb Haemost VL - 19 IS - 7 N2 - 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. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/33872443/Multisystem_inflammatory_syndrome_in_children__MIS_C__and_the_prothrombotic_state:_Coagulation_profiles_and_rotational_thromboelastometry_in_a_MIS_C_cohort_ L2 - https://doi.org/10.1111/jth.15340 DB - PRIME DP - Unbound Medicine ER -