key: cord-0839244-m0t816zu
authors: Al‐Ghafry, Maha; Aygun, Banu; Appiah‐Kubi, Abena; Vlachos, Adrianna; Ostovar, Gholamabbas; Capone, Christine; Sweberg, Tod; Palumbo, Nancy; Goenka, Pratichi; Wolfe, Lawrence C.; Lipton, Jeffrey M.; Acharya, Suchitra S.
title: Are children with SARS‐CoV‐2 infection at high risk for thrombosis? Viscoelastic testing and coagulation profiles in a case series of pediatric patients
date: 2020-10-24
journal: Pediatr Blood Cancer
DOI: 10.1002/pbc.28737
sha: e20b3e4d21d7de6f0148dfe602d2ae552be325cd
doc_id: 839244
cord_uid: m0t816zu

The coagulopathy of the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is well documented in adults, with increases in D‐dimer and prothrombin time found to be strong predictors of mortality, and anticoagulation shown to decrease this mortality. Viscoelastic parameters such as elevations in maximum clot firmness (MCF) on rotational thromboelastometry (ROTEM) have correlated with a hypercoagulable state in adults with SARS‐CoV‐2. We report our experience in children infected with SARS‐CoV‐2, with noted elevations in D‐dimer and MCF on ROTEM (indicating hypercoagulability). Exploration of viscoelastic testing to provide additional laboratory‐based evidence for pediatric‐specific risk assessment for thromboprophylaxis in SARS‐CoV‐2 is warranted.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was found to induce an increased incidence of thrombosis 1, 2 and strokes 3 in adults. They developed a recognizable coagulopathy, characterized by increased thrombin generation, 4 decreased fibrinolysis, elevated D-dimers, and a prolonged prothrombin time (PT), which was found to be a strong predictor of mortality, with pulmonary microthrombi contributing significantly. 5 Anticoagulation has been shown to decrease this mortality. 6 Rannucci et al 7 In an effort to explore the utility of viscoelastic testing, we added ROTEM to routine coagulation testing in children admitted with SARS-CoV-2. The objective was to determine if standard coagulation tests and ROTEM testing could be obtained in these children to assess its feasibility in determining thrombosis risk; if so, were changes in clot strength in children during an acute SARS-CoV-2 infection comparable to that seen in adults. We report our experience in this retrospective case series of eight children with SARS-CoV-2 infection. 

The demographics and laboratory values of eight hospitalized children diagnosed with SARS-CoV-2 infection are shown in Table 1 Abnormal laboratory data included lymphopenia (37.5%), mild thrombocytopenia (13%), prolonged PT (50%), elevated ferritin (37%) and C-reactive protein (88%). Elevations in D-dimer levels (75%) and fibrinogen (88%) were observed on the day ROTEM was drawn for analyses. Figure S1 for a temogram of patient #8).

In addition to increased hypercoagulability, Nougier et al 4 demonstrated significantly increased thrombin generation in SARS-CoV-2 patients admitted to the ICU versus non-ICU patients, along with higher tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), and thrombin activatable fibrinolysis inhibitor levels. It is hypothesized that local tPA is overwhelmed by high PAI-1 levels, tipping the balance toward hypercoagulability. There is limited availability of measuring thrombin generation at institutions, but the study team used a modified ROTEM parameter that correlated with thrombin generation, and could be more accessible to clinicians and researchers.

We further noted that in the early stages of infection, children under age 21 had elevated fibrinogen, D-dimer and CRP (all suggestive of a highly inflammatory state), in addition to lymphopenia and prolonged PT (similar to those observed in adults). However, our pediatric cohort did not develop symptomatic thromboembolic events or increased mortality, despite demonstration of a comparable hypercoagulable state.

Although our patient population was heterogeneous with respect to clinical course and level of coagulopathy, our small sample size precludes a demonstrable correlation between fibrinogen, D-dimers or viscoelastic testing or its predictive value in assigning risk for thrombosis on prophylactic anticoagulation in children. However, we demonstrated that ROTEM testing is feasible and recommend that its utility in determining the hypercoagulable state merits further study in children, who we and others, have shown can exhibit clinical severity and laboratory evidence of a coagulopathy identical to that seen in adults with SARS-CoV-2.

Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Large-vessel stroke as a presenting feature of Covid-19 in the young

Hypofibrinolytic state and high thrombin generation may play a major role in SARS-COV2 associated thrombosis

D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19

Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy

The procoagulant pattern of patients with COVID 19 acute respiratory distress syndrome

COVID-19-related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure

COVID-19 and its implications for thrombosis and anticoagulation

Scientific and standardization committee communication: clinical guidance on the diagnosis, prevention and treatment of venous thromboembolism in hospitalized patients with COVID-19

COVID-19 anticoagulation recommendations in children

ROTEM) in children: age-related reference ranges and correlations with standard coagulation tests

Thromboelastographic results and hypercoagulability syndrome in patients with coronavirus disease 2019 who are critically ill

Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis

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