Case of Venous Thromboembolia Under Enoxaparin Prophylaxis After Recovering From Acute Ischemic Stroke in Consequence of COVID-19-Related MIS-C

To the Editors:

Multisystem inflammatory syndrome in children (MIS-C) guidance has been issued by the World Health Organization and by the Centers for Disease Control and Prevention.^1,2 Pediatric acute ischemic stroke and thromboembolic conditions have been reported as rare complications of COVID-19 or MIS-C.^3–5 Venous thromboembolism has not been reported in children with no underlying disease who have undergone enoxaparin prophylaxis after recovery from MIS-C.

This previously healthy 9-year-old boy without any history of head trauma arrived at the hospital obtunded, nonverbal, with a left-sided hemiparesis and left-sided central facial paralysis. He had fever, nausea, vomiting, diarrhea, and tenesmus for 5 days. His parents had been ill with SARS-CoV-2 infection about a month prior.

Body temperature was 38.1°C, oxygen saturation 94%, respiratory rate 45 breaths and heart rate 144 beats per minute, blood pressure 85/45mmHg after norepinephrine, Glasgow coma scale was 13-points, with physical examination notable for left-sided hemiparesis (1/5 muscle strengths) and central facial paralysis, increased patellar deep tendon reflexes and left positive Babinski sign, erythematous plantar areas, and nonpurulent conjunctivitis.

Blood tests revealed a systemic hyperinflammatory state. COVID-19 nucleocapid Ig M and Ig G were positive. Brain magnetic resonance imaging with diffusion-weighted showed that exhibit restricted diffusion at the level of the right temporal lobe and Sylvian cortex (Fig. 1). Transthoracic echocardiogram demonstrated a left ventricular ejection fraction of 51% with global strain and mild mitral valve regurgitation. The thrombophilia panel result was normal. Doppler ultrasonography was negative for deep venous thrombosis.

FIGURE 1.

Hypointense signals in the ADC (A) mapping and hyperintense signals in the B1000 diffusion sequence (B) were observed at the level of the right temporal lobe and Sylvian cortex (Circles), in the patient’s first magnetic resonance imaging. ADC indicates adherent diffusion coefficient.

He was diagnosed with MIS-C based on the World Health Organization and Centers for Disease Control and Prevention criteria and treated with intravenous immunoglobulin, intravenous methylprednisolone, subcutaneous enoxaparin, and oral aspirin.

Progressive resolution of the systemic hyperinflammatory state occurred within 48–72 hours. He was discharged with prophylactic enoxaparin treatment (100 IU/kg-daily) with independence in all activities of daily living end of 14 day. On day 28 outpatient follow-up, the physical examination was normal except for mild left-sided central facial paralysis. After about a week, he was readmitted to the hospital due to swollen right upper limb without pain and tenderness. The linear swelling and reddish discoloration occurred on the median antebrachial vein trace (Fig. 2A). Because of the clinical suspicion of thrombosis, venous doppler ultrasonography was performed and showed absent flow at the level of this vein (Fig. 2B). All other venous system examinations, transthoracic echocardiogram and brain magnetic resonance imaging angiography showed no abnormalities. Blood tests include hyperinflammatory and thrombosis markers were within the normal range. Enoxaparin treatment was readjusted to 100 IU/kg-twice daily.

FIGURE 2.

Linear swelling and reddish discoloration of the skin were observed on the median antebrachial vein trace (A, arrows). Venous filling was not observed in the Doppler ultrasonography of the vein and it was unresponsive to compression (B, arrowheads).

We describe the first case of MIS-C related acute ischemic stroke with venous thromboembolism while under enoxaparin prophylaxis after recovery from MIS-C in a child with no underlying disease. We suggest that aggressive therapy to halt the cytokine storm and appropriate supportive care while considering differential diagnosis is crucial for reaching positive outcomes in children. It should be kept in mind that pediatric patients treated for MIS-C should be followed closely in terms of thromboembolism risk even if they receive anticoagulant therapy.