Multisystem Inflammatory Syndrome (MIS-C) Clinical Pathway — Emergency, ICU and Inpatient

Additional Laboratory, Imaging Studies for ICU Patients with High Suspicion for MIS-C

Consider sending the following labs as part of the initial evaluation for patients meeting criteria for MIS-C with Shock and in non-shock patients with high clinical suspicion. These lab findings may support a diagnosis of MIS-C, but recognize that this syndrome is largely uncharacterized and therefore no specific diagnostic laboratory criteria are established. These labs additionally allow monitoring of end-organ.

Labs
Recommended Labs	Comments
CBC with differential	Platelet count may be normal or low, anemia for age Lymphopenia (ALC < 1000) ) is a frequent finding
Hematology smear	Look for evidence of schistocytes, burr cells, which have been observed in patients with MIS-C; Call 41777 (hematology lab) to request pathologist review
CMP	Hyponatremia is a frequent finding, increased creatinine, increased ALT/AST Normal or decreased albumin
CRP	Increased, marker of systemic inflammation
Procalcitonin	Increased, marker of inflammation (note overlap with bacterial sepsis)
ESR	Increased, marker of systemic inflammation
Triglycerides	May be elevated, particularly in patients with macrophage activation
Ferritin	Increased, marker of systemic inflammation
PT/PTT/INR	Coagulopathy, with elevated INR
D-dimer	Increased, marker of activated coagulation, marker of inflammation, non-specific
Fibrinogen	Increased, marker of activated coagulation, inflammation
LDH	Increased
Urinalysis	Evaluate for pyuria, which may be inflammatory or infectious in etiology, as well as urinary tract infection
Troponin	Marker of myocardial injury if elevated
Brain type natriuretic peptide	Marker of atrial expansion and pressure overload, which may be elevated in heart failure; in reported MIS-C cases, often elevated to a greater extent than may be expected based on clinical/echo findings, however may be normal early in disease course
Super gas with lactate	Evaluate for evidence of acidosis and/or elevated lactate suggestive of impaired perfusion
Proinflammatory cytokine panel	Results may inform choice of immunomodulatory therapy and aid in diagnosis combined with other clinical/lab data in uncertain cases Order proinflammatory cytokine panel (in house test). Do NOT order cytokine panel 12 (send out test). Routine Process Performed routinely Tuesday through Thursday Samples in lab by 9 AM are run that day Can collect overnight and store in central receiving STAT Testing Can be performed same day if results needed for critically ill pt, where results may inform best immunomodulator Discuss with DIRT APP and/or rheumatology to facilitate this testing Specimen Collect 1 mL in lithium heparin MINT GREEN-top tube NOT dark green-top tube
sC5b-9	Results may suggest complement activation and microangiopathy. Abnormal values will be followed over time by rheumatology and testing should be sent in consultation with rheumatology. Hemostatis Test Requisition Form
Save-our-specimen	Hold a gold top SST in lab for subsequent serological studies
Biobank/research	Please contact Caroline Diorio, pager 26345

Evaluation for Infection
Recommended Labs	Comments
Blood culture	As clinically indicated
Urine culture	As clinically indicated
SARS-CoV-2 PCR	Anterior nares: All patients Tracheal aspirate: Patients with artificial airways
SARS-CoV-2 Serology	Specimen 1 mL in gold top SST tube; note, this should be a different tube of blood than the save our specimen SST tube above Documented positive serology is not required for initial diagnosis or initiation of therapy. A positive serology is also NOT diagnostic of MISC but is often present in patients with MIS-C, as it indicates prior COVID exposure Talking Points and provider information for COVID-19 Serology
Rocky Mountain Spotted Fever, serology	As clinically indicated
Ehrlichia chaffeensis, serology	As clinically indicated
Adenovirus PCR, serum	As clinically indicated
Enterovirus PCR, serum	As clinically indicated
Enterovirus PCR, CSF	If concern for meningitis/encephalitis
CSF studies	If concern for meningitis/encephalitis or intracranial hypertension: opening pressure, cell counts (tube 1 and 4), protein, glucose, bacterial culture, and save our specimen Enterovirus PCR, CSF if pleocytosis present

Considerations for Initial Imaging/Additional Evaluation
Study	Comments
EKG	Evaluate ST segments, evidence of myocardial strain Arrhythmias, prolonged QTc If abnormal, consult cardiology, EP on a case-by-case basis Consider real-time cardiology EKG review Consider repeating an ECG every 48 hours, particularly if the initial ECG was abnormal or if patient's cardiac status worsens, in discussion with cardiology consult service.
Echocardiogram	Evaluate function, coronary artery dilation or aneurysms AV valve regurgitation Evaluate for signs of pulmonary hypertension as in PE
Chest X-ray	Evaluate for pulmonary edema, pneumonia, cardiomegaly,
Bedside cardiac US	Evaluate function, effusions
Head CT	If significant altered mental status or focal neurologic deficits
EEG	If significant altered mental status, focal neurologic deficits, movements of unclear etiology concerning for possible seizures
Contrast-enhanced US study (kidney, heart)	Contact Misun Hwang, pager 70979

Consider Echocardiogram/ECHO

Echocardiogram/Bedside US

Consider performing echocardiogram or bedside ultrasound to assess for:

Volume responsiveness
RV and LV qualitative systolic function
Severe RV dilation
Presence of pericardial effusion

Views to obtain on bedside US:

Transverse and longitudinal IVC views
- An IVC: aorta ratio of < 1.2:1 suggests volume depletion
- IVC diameter variability of > 50% in a non-intubated patient or > 15% in an intubated patient suggests the patient would be responsive to fluid
Subcostal view
Parasternal short axis view
Parasternal long axis view
Apical 4 chamber view

If equivocal findings on bedside US, consult cardiology for formal echo.

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The clinical pathways are based upon publicly available medical evidence and/or a consensus of medical practitioners at The Children’s Hospital of Philadelphia (“CHOP”) and are current at the time of publication. These clinical pathways are intended to be a guide for practitioners and may need to be adapted for each specific patient based on the practitioner’s professional judgment, consideration of any unique circumstances, the needs of each patient and their family, and/or the availability of various resources at the health care institution where the patient is located.

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