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.