Methods
Population: This retrospective case series included patients who were diagnosed with MIS-C and admitted to Boston Children’s Hospital from February 1, 2020 through September 1, 2020. This study was approved by our institutional review board.
Data collection and definitions: The electronic medical record was reviewed to obtain patients’ demographic, clinical, and laboratory data. Patients were diagnosed with MIS-C per the Centers for Disease Control and Prevention’s case definition: age < 21 years presenting with fever, laboratory evidence of inflammation, and clinically severe illness requiring hospitalization; with multisystem (≥2) organ involvement; no alternative plausible diagnosis; and positive for current or recent SARS-CoV-2 infection by reverse transcriptase polymerase chain reaction (RT-PCR), serology or antigen test, or COVID-19 exposure within the past 4 weeks.23 All MIS-C cases were adjudicated by rheumatologists and cardiologists.
Demographic data including age and gender were collected. Clinical data were collected including baseline comorbidities, hospital course, and any bleeding or thrombosis events. Bleeding was defined per the International Society on Thrombosis and Haemostasis (ISTH): major bleeding (fatal or in critical area or organ), clinically relevant non-major bleeding (requiring intervention by a medical provider, hospitalization/increased level of care, or further evaluation) or minor bleeding (all other events).24,25 Thrombosis was described as any progressive or new thrombosis that is clinically symptomatic or diagnosed on imaging, including deep vein thrombosis, sinus venous thrombosis, stroke and pulmonary embolism. Ventricular dysfunction was defined as a left ventricular ejection fraction <55%. Coronary artery Z-scores were calculated using the Boston formula: coronary artery dilation was defined as coronary artery Z-score ≥2 but <2.5 and coronary artery aneurysms were defined as coronary artery Z-score ≥2.5.26
Basic laboratory studies related to bleeding and inflammation were collected, including initial and peak values. TEG with platelet mapping data was performed in an institutional laboratory certified by the Clinical Laboratory Improvement Amendments. TEG variables collected included: reaction time (R time, minutes), which measures latency until clot formation begins; kinetic clot time (K time, minutes) and rate of clot formation (alpha angle, degrees), which measure velocity of clot formation; maximum amplitude (MA, mm), which measures maximum clot strength; and percentage of clot lysis 30 minutes after the MA is reached (Ly30), which measures fibrinolysis. A hypercoagulable state is characterized by a lower R time, K time and Ly-30 and a higher alpha angle or maximum amplitude. Platelet mapping was also performed and collected as percent of inhibition of arachidonic acid (AA) and adenosine diphosphate (ADP). TEG data was compared to the profiles from age- and gender- matched controls, who were patients who had TEG profiles collected prior to cardiac surgery, with no anticoagulation or antiplatelet therapies, and with negative SARS-CoV-2 testing.
The use and dosage of prophylactic and therapeutic anticoagulant and antiplatelet therapies were also collected. Treatment course was based on individual clinician preference, with guidance from our institution’s Cardiac Antithrombosis Management Program.
Statistical Analyses: Descriptive statistics are presented using means with standard deviations or medians with interquartile ranges for continuous variables as appropriate, and the distribution of variables was visualized using histograms and tests for heteroscedasticity. Frequencies and proportions were presented for categorical variables. TEG with platelet mapping was compared to controls via Student’s t-test and Wilcoxon rank sum test. Pearson’s and Spearman correlation were used to assess relationships between TEG parameters and inflammatory markers. Significance was determined as P < 0.05. Statistical analyses were performed with Stata.