Multisystem inflammatory syndrome in children (MIS‐C) and the prothrombotic state: Coagulation profiles and rotational thromboelastometry in a MIS‐C cohort

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.

Who Would Have Predicted Multisystem Inflammatory Syndrome in Children?

“…Additionally, secondary activation of auto-reactive antibodies arises in the MIS-C disease process, with some of these auto-antibodies targeted to antigens expressed in endothelial and cardiac tissues, as well as the gastrointestinal tract [23]. Along with this endothelial activation, thromboelastometry of MIS-C samples demonstrates hypercoagulability within the hyperinflammatory state [28].…”

“…MIS-C has been shown to have pro-thrombotic features with early elevations in d-dimers and fibrinogen, late elevation in platelet count, and evidence of hypercoagulability on thromboelastometry [28]. These findings and the similarity of MIS-C to KD have led to the generally uniform addition of anti-platelet agents to MIS-C treatment algorithms.…”

Clinical practice guidelines in multisystem inflammatory syndrome (MIS-C) related to COVID-19: a critical review and recommendations

“…The primary use of anticoagulants is to curtail clot formation within the arterial and venous of patients with COVID-19. A reduction in blood clots after seven to twelve weeks without prolonged fatigue or any side effects from the patient indicates that the patient’s health status is stabilized [ 23 ].…”

Intracardiac thrombosis in the three-year-old boy with normal left ventricle systolic function in MIS-C associated with COVID-19

“…A multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, a newly described condition, is a hypercoagulable state caused by hyper inflammation and cytokine storm. [1][2][3][4] Although more than half of the patients with MIS-C (76%) have biochemical evidence of coagulopathy, the prevalence of deep vein thrombosis or pulmonary emboli is low (8%). On the other hand, the most extensive published MIS-C case series have not reported thrombotic complications.…”