Acute pulmonary embolism in times of SARS-CoV-2: Diagnostic and therapeutic management / Tromboembolismo pulmonar agudo en tiempos de SARS-CoV-2: diagnóstico y tratamiento

There is a clear association between novel coronavirus 2 infection and the diagnosis of venous thromboembolic disease, as a cosequence of the development of a systemic inflammatory response syndrome due to the activation of the coagulation cascade. It occurs in 90% of patients with severe forms of the infection, evidencing the presence of pulmonary endovascular micro and macro thrombosis. This suggests a possible clinical benefit of thromboprophylaxis according to the patient's clinical risk. The suspicion of venous thromboembolic disease in the context of this pandemic represents a diagnostic challenge due to the co-existence of similarities between both conditions in several different aspects. It should be noted that the diagnosis of acute pulmonary embolism does not exclude the possibility of simultaneous viral infection. The evaluation of patients with suspected acute pulmonary embolism in the context of the pandemic should be optimized in order to implement a rapid diagnosis and treatment to reduce the associated morbidity and mortality. This will help reducing infectious risk for health-care professionals and other patients.

Existe una clara relación entre la infección por el nuevo coronavirus 2 y el diagnóstico de enfermedad tromboembólica venosa, como consecuencia del desarrollo de un síndrome de respuesta inflamatoria sistémica debido a la activación de la cascada de la coagulación. Se presenta en el 90% de los pacientes con formas graves de la infección, lo que revela la presencia de microtrombosis y macrotrombosis intravascular pulmonar. Esto sugiere un posible beneficio clínico de la aplicación de una tromboprofilaxis adecuada al riesgo clínico de cada paciente. Asimismo, la sospecha de enfermedad tromboembólica venosa en el contexto de esta pandemia representa un reto diagnóstico debido a la existencia de similitudes entre ambas alteraciones en varios aspectos. Debe tenerse en cuenta que el diagnóstico de tromboembolismo pulmonar agudo no excluye la posibilidad de infección viral. La valoración de pacientes con sospecha de tromboembolismo pulmonar agudo en el contexto de la pandemia debe ser eficaz para establecer un diagnóstico y tratamiento con rapidez, a fin de reducir la morbilidad y mortalidad adjuntas, sin que ello eleve el riesgo de infección para los profesionales de la salud y otros pacientes.

D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

External validation of the ADA score for predicting thrombosis among acutely ill hospitalized medical patients from the APEX Trial.

The ADA (Age-D-dimer-Albumin) score was developed to identify hospitalized patients at an increased risk for thrombosis in the coronavirus infectious disease-19 (COVID-19) setting. The study aimed to validate the ADA score for predicting thrombosis in a non-COVID-19 medically ill population from the APEX trial. The APEX trial was a multinational, randomized trial that evaluated the efficacy and safety of betrixaban vs. enoxaparin among acutely ill hospitalized patients at risk for venous thromboembolism. The study endpoints included the composite of arterial or venous thrombosis and its components. Metrics of model calibration and discrimination were computed for assessing the performance of the ADA score as compared to the IMPROVE score, a well-validated VTE risk assessment model. Among 7,119 medical inpatients, 209 (2.9%) had a thrombosis event up to 77 days of follow-up. The ADA score demonstrated good calibration for both arterial and venous thrombosis, whereas the IMPROVE score had adequate calibration for venous thrombosis (p > 0.05 from the Hosmer-Lemeshow test). For discriminating arterial and venous thrombosis, there was no significant difference between the ADA vs. IMPROVE score (c statistic = 0.620 [95% CI: 0.582 to 0.657] vs. 0.590 [95% CI: 0.556 to 0.624]; ∆ c statistic = 0.030 [95% CI: -0.022 to 0.081]; p = 0.255). Similarly, for discriminating arterial thrombosis, there was no significant difference between the ADA vs. IMPROVE score (c statistic = 0.582 [95% CI: 0.534 to 0.629] vs. 0.609 [95% CI: 0.564 to 0.653]; ∆ c statistic = -0.027 [95% CI: -0.091 to 0.036]; p = 0.397). For discriminating venous thrombosis, the ADA score was modestly superior to the IMPROVE score (c statistic = 0.664 [95% CI: 0.607 to 0.722] vs. 0.573 [95% CI: 0.521 to 0.624]; ∆ c statistic = 0.091 [95% CI: 0.011 to 0.172]; p = 0.026). The ADA score had a higher sensitivity (0.579 [95% CI: 0.512 to 0.646]; vs. 0.440 [95% CI: 0.373 to 0.507]) but lower specificity (0.625 [95% CI: 0.614 to 0.637] vs. 0.747 [95% CI: 0.737 to 0.758]) than the IMPROVE score for predicting thrombosis. Among acutely ill hospitalized medical patients enrolled in the APEX trial, the ADA score demonstrated good calibration but suboptimal discrimination for predicting thrombosis. The findings support the use of either the ADA or IMPROVE score for thrombosis risk assessment. The applicability of the ADA score to non-COVID-19 populations warrants further research.Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT01583218.

Predictive value of inflammatory and coagulation biomarkers for venous thromboembolism in COVID-19 patients.

BACKGROUND: The predictive value of coagulation markers for venous thromboembolism (VTE) in COVID-19 patients has been investigated with conflicting results. OBJECTIVE: Our aim was to investigate the correlation between biomarkers and VTE and the predictive value of D-dimer for VTE in hospitalized COVID-19 patients. METHODS: Complete blood count, inflammatory and coagulation biomarkers at admission were collected. VTE was defined as diagnosed pulmonary embolism or deep vein thrombosis. Events were defined as in-hospital death or ICU admission. Predictors of VTE were identified with Pearson prediction models. A ROC curve was constructed to assess the predictive value of D-dimer. RESULTS: 1651 participants were included, 111 VTE were identified. Events incidence was higher in the VTE group (49.5% vs 28.2%, p < 0.001). Neutrophil-lymphocyte ratio (NLR, 0.001; 95% CI 0.000-0.002; p 0.019) and D-dimer (0.00005; 95% CI 0.00002-0.00008; p < 0.001), Geneva score (0.026; 95% CI 0.012-0.040; p < 0.001) and Wells score (0.047; 95% CI 0.033-0.061; p < 0.001) were associated with VTE. D-dimer had a goor predictive value for VTE (ROC area 0.85, 95% CI 0.816-0.893), with an optimal cut-off value of 2677µg/L (Youden index of 0,602). CONCLUSIONS: Among coagulation biomarkers D-dimer had the best predictive value for VTE, but higher cut-off values should be used in COVID-19.

Point-of-Care Platform for Diagnosis of Venous Thrombosis by Simultaneous Detection of Thrombin Generation and D-Dimer in Human Plasma.

Venous thromboembolism (VTE) refers to a blood clot that starts in a vein. The risk of developing VTE is highest after major surgery or a major injury, or when someone has heart failure, cancer, or infectious disease (e.g., COVID-19). Without prompt treatment to break up clots and prevent more from forming, VTE can restrict or block blood flow and oxygen, which can damage the body tissue or organs. VTE can occur without any obvious signs, and imaging technologies are used. Alternatively rapid measurement of thrombin generation (TG) and D-dimer could be used to make a fast, portable, and easy-to-use diagnostic platform for VTE. Here, we have demonstrated a diagnostic sensing platform with the ability of simultaneous detection of TG and D-dimer in human plasma. Modifications were made to both the assay protocols to eliminate the need for sample dilution and incubation steps. Using a substantially reduced sample volume, the measurement results show comparable performance to the gold standard method. Our platform is able to deliver accurate and cost-effective results for both TG and D-dimer assays when using undiluted plasma in under 15 min. The assays presented are therefore a good candidate technology for use in a point-of-care platform to diagnose VTE.

Antiphospholipid antibodies: what is new in 2022 / Détection des anticorps antiphospholipides : actualités en 2022

Antiphospholipid syndrome (APS) is a clinicobiological entity defined by the association of thrombotic events and/or obstetric complications and the presence of persistent antiphospholipid antibodies (aPLs) detected by coagulation tests (lupus anticoagulant, LAC) and/or immunological assays (anticardiolipin and anti-glycoprotein-beta-I antibodies). The increased use of direct oral anticoagulants (DOAC) for the treatment of venous thromboembolism (VTE) is now a challenge for hematology laboratories for the diagnosis of APS. DOAC interfere with LAC screening and confirmation tests resulting in a risk of false positive results. To avoid these interferences, several solutions are suggested. Some of them rely on the use of DOAC-reversal systems (activated charcoal tablet, filter system) others on the use of reagents insensitive to DOAC presence in the sample. Detection of anti-phosphatidylserine/prothrombin antibodies may be helpful because they are strongly associated to the presence of LAC and are increasingly recognized as a useful tool in the diagnosis and prognosis of APS. Finally, positivity of LA in the setting of a viral infection is frequent and not specific to APS. During the Covid-19 pandemic, many patients developed arterial and VTE that could suggest testing for aPLs. The association between LAC and a risk of VTE or in-hospital mortality in hospitalized Covid-19 patients was not demonstrated. Moreover, aPLs do not persist after Covid-19. Currently, testing for aPLs in Covid-19 patients is not recommended.

Le syndrome des antiphospholipides (SAPL) est une entité clinico-biologique définie par l'association de manifestations thrombotiques et/ou de complications obstétricales et la présence persistante d'anticorps antiphospholipides (aPLs) détectés par des tests de coagulation (lupus anticoagulant, LA) et/ou par des tests immunologiques (anticorps anti-cardiolipine et anticorps anti-ß2-glycoprotéine-I). L'essor des anticoagulants oraux directs (AOD) dans la prise en charge des évènements thrombotiques veineux (ETV) constitue aujourd'hui un défi pour les laboratoires d'hémostase dans le cadre du diagnostic du SAPL. Les AOD interfèrent avec les tests de dépistage et de confirmation du LA occasionnant des faux positifs. Afin de se soustraire à ces interférences plusieurs solutions sont proposées. Certaines reposent sur l'utilisation de système neutralisant l'AOD (pastille de charbon activé, système de filtre) d'autres sur l'utilisation de réactifs insensibles à la présence d'AOD. On peut également faire appel aux anticorps anti-phosphatidylsérine/prothrombine très corrélés à la présence de LA et constituant un outil de plus en plus reconnu dans le diagnostic biologique du SAPL et son pronostic. Enfin, la positivité des aPLs dans un contexte infectieux est fréquente et non spécifique du SAPL. Au cours de la pandémie Covid-19, de nombreux patients ont présentés des ETV et artériels qui ont pu motiver la recherche d'aPLs. L'association entre LA et le risque d'ETV ou la mortalité hospitalière chez les patients Covid-19 hospitalisés n'a pas été démontrée. De plus, il ne semble pas qu'il y ait de persistance de ces aPLs après la Covid-19. A ce jour, la recherche d'aPLs chez les patients atteint de Covid-19 n'est pas recommandée.

Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID-19.

Background Venous thromboembolism (VTE) contributes significantly to COVID-19 morbidity and mortality. The urokinase receptor system is involved in the regulation of coagulation. Levels of soluble urokinase plasminogen activator receptor (suPAR) reflect hyperinflammation and are strongly predictive of outcomes in COVID-19. Whether suPAR levels identify patients with COVID-19 at risk for VTE is unclear. Methods and Results We leveraged a multinational observational study of patients hospitalized for COVID-19 with suPAR and D-dimer levels measured on admission. In 1960 patients (mean age, 58 years; 57% men; 20% Black race), we assessed the association between suPAR and incident VTE (defined as pulmonary embolism or deep vein thrombosis) using logistic regression and Fine-Gray modeling, accounting for the competing risk of death. VTE occurred in 163 (8%) patients and was associated with higher suPAR and D-dimer levels. There was a positive association between suPAR and D-dimer (ß=7.34; P=0.002). Adjusted for clinical covariables, including D-dimer, the odds of VTE were 168% higher comparing the third with first suPAR tertiles (adjusted odds ratio, 2.68 [95% CI, 1.51-4.75]; P<0.001). Findings were consistent when stratified by D-dimer levels and in survival analysis accounting for death as a competing risk. On the basis of predicted probabilities from random forest, a decision tree found the combined D-dimer <1 mg/L and suPAR <11 ng/mL cutoffs, identifying 41% of patients with only 3.6% VTE probability. Conclusions Higher suPAR was associated with incident VTE independently of D-dimer in patients hospitalized for COVID-19. Combining suPAR and D-dimer identified patients at low VTE risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04818866.

Elucidating the Role of Cardiac Biomarkers in COVID-19: A Narrative Evaluation with Clinical Standpoints and a Pragmatic Approach for Therapeutics.

With the incidence of the unabated spreading of the COVID-19 (coronavirus disease 2019) pandemic with an increase in heart-related complications in COVID-19 patients, laboratory investigations on general health and diseases of heart have greater importance. The production of a higher level of clots in the blood in COVID-19 individuals carries a high risk of severe lethal pneumonia, pulmonary embolism, or widespread thromboembolism. The COVID-19 pandemic has raised awareness regarding the severe consequences for the cardiac system that might cause due to severe acute respiratory distress syndrome (SARS-CoV-2). COVID-19 causes acute respiratory distress syndrome (ARDS), acute myocardial infarction, venous thromboembolism, and acute heart failure in people with preexisting cardiac illness. However, as COVID-19 is primarily a respiratory infectious disease, there is still a lot of debate on whether and how cardiac biomarkers should be used in COVID-19 patients. Considering the most practical elucidation of cardiac biomarkers in COVID-19, it is important to note that recent findings on the prognostic role of cardiac biomarkers in COVID-19 patients are similar to those found in pneumonia and ARDS studies. The use of natriuretic peptides and cardiac troponin concentrations as quantitative variables should help with COVID-19/pneumonia risk classification and ensure that these biomarkers sustain their high diagnostic precision for acute myocardial infarction and heart failure. Serial assessment of D-dimers will possibly aid clinicians in the assortment of patients for venous thromboembolism imaging in addition to the increase of anticoagulation from preventive to marginally higher or even therapeutic dosages because of the central involvement of endothelitis and thromboembolism in COVID-19. Therefore, cardiac biomarkers are produced in this phase because of some pathological processes; this review will focus on major cardiac biomarkers and their significant role in COVID-19.

Outcome Prediction in Critically-Ill Patients with Venous Thromboembolism and/or Cancer Using Machine Learning Algorithms: External Validation and Comparison with Scoring Systems.

Intensive care unit (ICU) patients with venous thromboembolism (VTE) and/or cancer suffer from high mortality rates. Mortality prediction in the ICU has been a major medical challenge for which several scoring systems exist but lack in specificity. This study focuses on two target groups, namely patients with thrombosis or cancer. The main goal is to develop and validate interpretable machine learning (ML) models to predict early and late mortality, while exploiting all available data stored in the medical record. To this end, retrospective data from two freely accessible databases, MIMIC-III and eICU, were used. Well-established ML algorithms were implemented utilizing automated and purposely built ML frameworks for addressing class imbalance. Prediction of early mortality showed excellent performance in both disease categories, in terms of the area under the receiver operating characteristic curve (AUC-ROC): VTE-MIMIC-III 0.93, eICU 0.87, cancer-MIMIC-III 0.94. On the other hand, late mortality prediction showed lower performance, i.e., AUC-ROC: VTE 0.82, cancer 0.74-0.88. The predictive model of early mortality developed from 1651 VTE patients (MIMIC-III) ended up with a signature of 35 features and was externally validated in 2659 patients from the eICU dataset. Our model outperformed traditional scoring systems in predicting early as well as late mortality. Novel biomarkers, such as red cell distribution width, were identified.

Predictors and mortality risk of venous thromboembolism in patients with COVID-19: systematic review and meta-analysis of observational studies.

INTRODUCTION: Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in COVID-19 disease is associated with widespread inflammation and a prothrombotic state, resulting in frequent venous thromboembolic (VTE) events. It is currently unknown whether anticoagulation is protective for VTE events. Therefore, we conducted a systematic review to identify predictors of VTE in COVID-19. METHODS: We searched PubMed, EMBASE, Google Scholar, and Ovid databases for relevant observational studies of VTE in COVID-19 disease. The effect size for predictors of VTE was calculated using a random-effects model and presented as forest plots. Heterogeneity among studies was expressed as Q statistics and I2. Bias was assessed using the Newcastle Ottawa Scale for all identified observational studies. Publication bias was assessed with funnel plot analysis. RESULTS: We identified 28 studies involving 6053 patients with suspected or confirmed COVID-19. The overall pooled prevalence of VTE events was 20.7%. Male sex was associated with a higher risk of VTE events, whereas prior history of VTE, smoking, and cancer were not. VTE events were significantly higher in severely ill patients, mechanically ventilated patients, those requiring intensive care admission, and those with a low PaO2/FiO2 ratio (P/F ratio). Chronic comorbidities, including cardiovascular disease, heart failure, renal disease, and pulmonary disease, did not increase the risk of VTE events. Patients with VTE had higher leukocyte counts and higher levels of D-dimer, C-reactive protein, and procalcitonin. The occurrence of VTE was associated with increased length of stay but did not impact mortality. Therapeutic and prophylactic doses of anticoagulation were not protective against VTE. CONCLUSION: VTE in COVID-19 is associated with male gender and severe disease but not with traditional risk factors for VTE. The occurrence of VTE does not appear to be mitigated by either prophylactic or therapeutic anticoagulation. The occurrence of VTE in this population is associated with an increased length of stay but does not appear to impact mortality.

A systematic review and meta-analysis of racial disparities in deep vein thrombosis and pulmonary embolism events in patients hospitalized with coronavirus disease 2019.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with an increased risk of venous thromboembolism (VTE). Recent studies have characterized racial disparities in the incidence of VTE. The aim of our study was to present a systematic review and meta-analysis to assess the association between race and VTE in patients hospitalized with COVID-19. METHODS: We performed a systematic literature review to evaluate the number of deep vein thrombosis (DVT) and pulmonary embolism (PE) events reported by racial groups in patients hospitalized with COVID-19. For the qualitative analysis, independent reviewers extracted the data from eligible studies, and we used the Newcastle-Ottawa scale to assess the quality of design and content for accurate interpretation. For the quantitative analysis, we pooled the odds ratios with Der Simonian and Laird random effects models. RESULTS: The qualitative analysis included 11 studies, with 6 included in the meta-analysis. All studies were observational, retrospective cohort studies, except for one retrospective case-control study. Six studies were eligible for the meta-analysis owing to the high interstudy heterogeneity; thus, the variable reports of racial groups reduced the cohort to Black/African American and White patients (n = 9723) in the analysis. The estimated proportion for DVT and PE events for Black/African American and White patients was 0.07 (95% confidence interval, 0.00-0.10) and 0.04 (95% confidence interval, 0.00-0.07), respectively. The P value of .13 suggested nonsignificant differences in the VTE rates between Black/African American and White patients. CONCLUSIONS: In our study, the proportion of DVT and PE events between Black/African American and White patients with COVID-19 were comparable. Future COVID-19 studies should include systematic racial group reporting to identify any disparities in the setting of VTE events.

Major hemorrhage and mortality in COVID-19 patients on therapeutic anticoagulation for venous thromboembolism.

We observed multiple fatal intracranial hemorrhages shortly after initiating therapeutic anticoagulation for treatment of venous thromboembolism (VTE) in COVID-19 patients suggesting increased anticoagulation risk associated with COVID-19. The objective of this study is to quantify risk of major hemorrhage in hospitalized COVID-19 patients on therapeutic anticoagulation for deep venous thrombosis (DVT) or pulmonary embolism (PE). Hospitalized patients with COVID-19 receiving therapeutic anticoagulation for DVT, PE or both at four New York City hospitals were evaluated for hemorrhagic complications. These were categorized as major (including fatal) or clinically relevant non-major according to the criteria of the International Society of Thrombosis and Haemostasis. Hemorrhagic complications were correlated with clinical and laboratory data, ICD-10 code diagnoses and type of anticoagulation treatment. Minor hemorrhages were excluded. Major/clinically relevant hemorrhages occurred in 36 of 170 (21%) hospitalized COVID-19 patients being treated with therapeutic anticoagulation for VTE including 4 (2.4%) fatal hemorrhages. Hemorrhage was 3.4 times more likely with unfractionated heparin 27/76 (36%) compared to 8/81 (10%) with low molecular weight heparin (p = 0.002). Multivariate analysis showed that major hemorrhage was associated with intubation (p = 0.04) and elevated serum LDH (p < 0.001) and low fibrinogen (p = 0.05). Increased risk of hemorrhagic complications in treating VTE in hospitalized COVID-19 patients should be considered especially when using unfractionated heparin, in intubated patients, with low fibrinogen and/or elevated LDH. Checking serum fibrinogen and LDH before initiating therapeutic anticoagulation and monitoring coagulation parameters frequently may reduce bleeding complications.

[Coronavirus infection and risk of postoperative venous thromboembolic events]. / Koronavirusnaya infektsiya i risk posleoperatsionnykh venoznykh tromboembolicheskikh sobytii u khirurgicheskikh bol'nykh.

OBJECTIVE: To determine whether patients with perioperative or previous coronavirus infection (CVI) have a greater risk of venous thromboembolic events (VTE). MATERIAL AND METHODS: A multiple-center regional prospective retrospective cohort study included elective and emergency patients who underwent surgery in November 2020. The primary endpoint was VTE (PE/DVT) within 30 days after surgery. CVI was stratified as perioperative (7 days before surgery - 30 days after surgery), recent (1-6 weeks before surgery) and remote (≥7 weeks before surgery) infection. There was no information about prevention or preoperative anticoagulation at baseline data collection. RESULTS: Incidence of postoperative VTE was 1.5% (10/650) in patients without CVI, 33.3% (3/9) in patients with perioperative CVI, 18.1% (2/11) in patients with recent CVI and 8.3% (1/12) in patients with remote CVI. After adjusting the confounders, patients with perioperative and recent CVI remained at a higher risk of VTE. In general, VTEs were independently associated with 30-day mortality. In patients with CVI, mortality rate among ones without VTE was 21.7% (5/23), with VTE - 44.4% (4/9). CONCLUSION: Patients with perioperative CVI have a higher risk of postoperative VTE compared to those without CVI and patients with previous CVI and no residual symptoms. Mortality in this group is also higher than in other cohorts.

[Annual review of venous thromboembolism in 2021].

In the past year, significant progress has been made in the field of venous thromboembolism (VTE) including risk assessment and anticoagulation prevention, diagnostic strategies and model exploration, new drug development and disease management. Particularly, major breakthroughs have been made in the prevention of VTE with FXI inhibitors and the prevention of novel coronavirus pneumonia with coagulation alterations and anticoagulation interventions. Here, we reviewed the progress and achievements in the field of VTE in the past year, aiming to provide evidence and ideas for the diagnosis, treatment and future studies of VTE.

Thrombotic events in critically ill children with coronavirus disease 2019 or multisystem inflammatory syndrome in children.

PURPOSE OF REVIEW: To provide an update regarding what is known about thrombotic events and thromboprophylaxis in critically ill children with SARS-CoV-2 infection. RECENT FINDINGS: Pediatric patients with SARS-CoV-2 generally have mild illness; however, intensive care is required in about 20-30% of hospitalized children with COVID-19 and an even higher proportion in those with MIS-C. Increased rates of thrombosis have been observed in adults hospitalized with COVID-19, and clinical trials have attempted to optimize thromboprophylaxis. There is significant variability in the estimated incidence of thrombosis in pediatric patients (0-27%) because of variation in patient populations and study design. Multiple studies demonstrate an increased rate of thrombosis compared with baseline in hospitalized pediatric patients. Few studies have evaluated risk factors for thrombosis, but critical illness, older age, and other known thrombosis risk factors appear to increase the risk. Thromboprophylaxis strategies are inconsistent, with little evidence of efficacy but few reports of major bleeding. SUMMARY: Critically ill children with SARS-CoV-2-related illnesses are at increased risk of thrombosis. Thromboprophylaxis should be considered in select patients with COVID-19 or MIS-C, though the optimal strategy is not yet known. More data is required to guide practice to prevent thrombosis in this population.

Evaluation of D-dimer levels measured by different analytical methods in COVID-19 patients.

Clinicians experience some challenges due to the lack of standardization of test, although D-dimer is a prognostic marker for COVID-19. We compared the clinical and analytical performances of D-dimer results obtained from different devices, kits and methods in patients with a diagnosis of COVID-19. Thirty-nine patients with a diagnosis of COVID-19 and 24 healthy individuals were included in the study. D-dimer levels were measured with Innovance D-DIMER kit (immunoturbidimetric method) on Sysmex CS-2500 and BCS XP and VIDAS D-Dimer Exclusion II kit (enzyme-linked fluorescence method) on mini VIDAS. The studies of precision, method comparison and clinic performance were performed. The variation coefficients in all systems were within the acceptable imprecision (7.8%). Bias%(12.5%) between BCS XP and Sysmex CS-2500 was lower than the acceptable Bias%(15.5%). Bias% values (19.2% and 33.3%, respectively) between Mini VIDAS with BCS XP and Sysmex CS-2500 were higher than the acceptable Bias%. The correlation coefficients among all systems were 0.89-0.98. For 500 ng/ml FEU, there was almost perfect agreement between BCS XP and Sysmex CS-2500, a moderate agreement between Mini VIDAS and BCS XP and Sysmex CS-2500. The cut-off values for distinguishing between individuals with and withoutCOVID-19 were Mini VIDAS, Sysmex CS-2500 and BCS XP 529, 380 and 390 ng/ml FEU, respectively. The immunoturbidimetric method can be used as an alternative to the enzyme-linked fluorescent method because of satisfactory agreement at the different thresholds proposed for venous thromboembolism. However, it is recommended to follow up COVID-19 with the D-dimer results obtained by the same assay system.