key: cord-0900809-6b8dhv8b
authors: Choi, Justin J.; Wehmeyer, Graham T.; Li, Han A.; Alshak, Mark N.; Nahid, Musarrat; Rajan, Mangala; Liu, Bethina; Schatoff, Emma M.; Elahjji, Rahmi; Abdelghany, Youmna; D'Angelo, Debra; Crossman, Daniel; Evans, Arthur T.; Steel, Peter; Pinheiro, Laura C.; Goyal, Parag; Safford, Monika M.; Mints, Gregory; DeSancho, Maria T.
title: D-dimer cut-off points and risk of venous thromboembolism in adult hospitalized patients with COVID-19
date: 2020-09-17
journal: Thromb Res
DOI: 10.1016/j.thromres.2020.09.022
sha: 4d9a65086f2f6ba5a9c1d9ba0a69a6bd5fb6e21e
doc_id: 900809
cord_uid: 6b8dhv8b

nan

The novel coronavirus disease 2019 (COVID-19) pandemic has led to more than 24 million confirmed cases and over 820,000 deaths worldwide as of late August 2020.

Early observational studies reported high rates of venous thromboembolism (VTE) in critically ill patients with COVID-19. 1 A recent meta-analysis reported an incidence of 26% for VTE among 3487 patients from 30 studies based on very low-quality evidence due to heterogeneity and risk of bias. 2 Furthermore, studies have reported that elevated D-dimer values in COVID-19 are associated with a higher risk of VTE, mechanical ventilation, and mortality. [3] [4] [5] However, the clinical implications of D-dimer values are unclear. We report VTE rates and analyze the diagnostic performance and relationship of D-dimer with VTE in a large observational cohort study of hospitalized adults with COVID-19.

We conducted a retrospective observational cohort study at New York-Presbyterian Hospital/Weill Cornell Medical Center, a quaternary referral center located in the Upper East Side of Manhattan, and New York-Presbyterian/Lower Manhattan Hospital, an affiliated nonteaching hospital. We included all consecutive adult (age ≥18 years) cases of COVID-19 confirmed by a positive SARS-CoV02 reverse transcriptase-polymerase chain reaction test admitted to our two hospitals between 3 March 2020, the date of the first positive case, and 15 May 2020. For patients who remained hospitalized at the end of the study period, data collection and analysis were complete through 5 June 2020. Univariate analysis and multivariable logistic regression analysis were performed to evaluate the association between the initial D-dimer value during hospitalization, clinical characteristics, and the odds of VTE. Complete case analysis was used for the multivariable logistic regression. Clinical characteristics with P values less than 0.05 in the univariate analysis were included in the multivariable logistic regression analysis. significantly changed. We calculated 95% confidence intervals (CIs) for the likelihood ratios at each level (mutually exclusive, all-inclusive ranges for D-dimer values) to demonstrate non-overlapping CIs.

A total of 1739 hospitalized patients with COVID-19 were included in the study. The median age was 66.5 years (IQR 53.7-77.3), 59% were men, and common comorbidities included hypertension (56%), diabetes mellitus (31%) and obesity (30%). Figure 1) . Multilevel likelihood ratios significantly changed at the following D-dimer levels: <1000 ng/mL: 0.14 (95% CI, 0.07-0.30); 1000-7500 ng/mL: 1.19 (0.97-1.47); and >7500 ng/mL: 4.10 (2.94-5.71) ( Table 1) . With an overall prevalence of VTE of 16%, the posttest probabilities of VTE at each level were: 0.03 (95% CI, 0.01-0.05), 0.18 (0.14-0.23), and 0.43 (0.33-0.53), respectively.

In our study of a large cohort of hospitalized COVID-19 patients in New York City the prevalence of objectively confirmed VTE was 7%. The rate of VTE in our patients with COVID-19 was lower than what was previously reported in European and Asian studies, J o u r n a l P r e -p r o o f Journal Pre-proof but similar to a recent US study comprising 400 patients (144 critically ill) in which the overall rate VTE and the rate of VTE in critically COVID-19 patients was 4.8% and 7.6%, respectively . [1] [2] 6 Elevated D-dimer levels were associated with higher probability of VTE, consistent with reports by others. 1 Other significant predictors of VTE in our cohort included Black race, need for supplemental oxygen on presentation, higher platelet counts, and prolonged prothrombin time. Higher odds of VTE among Black patients has been reported previously. 7 A possible explanation for this is that Black patients have a greater prevalence of comorbidities such as obesity, hypertension and diabetes, and may have sickle cell trait. 8 In our analysis of the diagnostic performance of D-dimer values, we identified three levels of D-dimer that stratified patients into low-probability (<1000 ng/mL), intermediate-probability (1000-7500 ng/mL), and high-probability groups (>7500 ng/mL). With a VTE prevalence of 16% in our D-dimer analysis, the posttest probabilities of VTE at each level were 3%, 18%, and 43%, respectively. A recent study of D-dimer levels in critically ill patients with COVID-19 on intermediate-dose thromboprophylaxis reported that D-dimers <2000 ng/mL had a 100% negative predictive value for VTE and >8000 ng/mL had a significantly increased likelihood ratio, concluding that cut-off points of 2000 ng/mL and 8000 ng/mL appear useful to identify patients with low and high probability of having developed VTE, respectively. 9 We identified similar cut-off points that appear to be useful for identifying patients at varying 

Demographic, clinical characteristics and radiology reports were manually abstracted from electronic medical records using a quality-controlled protocol in a REDCap database. 1 This methodology has been previously described and to have found high interrater reliability. 2 Vital signs and laboratory values were extracted using an algorithm-based automated process from electronic medical records. The study was approved by the institutional review board, which granted a waiver of informed consent.

We evaluated age, gender, race, ethnicity, comorbidities including obesity (defined as body mass index >30 kg/m 2 ), hypertension, coronary artery disease, heart failure, diabetes mellitus, and active cancer. Presenting signs and symptoms on hospital admission included dyspnea, chest pain, initial heart rate, systolic and diastolic blood pressure, and need for supplemental oxygen at presentation (defined as within three J o u r n a l P r e -p r o o f

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

Venous thromboembolism in patients with COVID-19: Systematic review and metaanalysis

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia

Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to D-Dimer Levels

COVID and Coagulation: Bleeding and Thrombotic Manifestations of SARS-CoV2 Infection

Pulmonary Embolism in COVID-19 Patients: Awareness of an Increased Prevalence

Sickle cell trait and the potential risk of severe coronavirus disease 2019-A mini-review

Utility of D-dimers and intermediate-dose prophylaxis in critically ill patients with COVID-19

Workup Bias in Prediction Research

Prothrombin time, sec

Comorbidities Obesity (BMI 30 kg/m 2 )

Coagulation parameters b Platelet count, 10 9 per L 200

Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support

Clinical Characteristics of Covid-19 in New York City

We thank the following Weill Cornell Medicine medical students for their contributions to medical chart abstraction: Zara Adamou BA, Bryan K. Ang BA, Elena Beideck BS, Orrin S. Belden BS, Sharmi Biswas MD, Anthony F. Blackburn BS, Joshua W. Bliss PharmD,