Elevated d-Dimer Levels Are Associated With Increased Risk of Mortality in Coronavirus Disease 2019

Shah, Siddharth; Shah, Kuldeep; Patel, Siddharth; Patel, Foram S; Osman, Mohammed; Velagapudi, Poonam; Turagam, Mohit K.; Lakkireddy, Dhanunjaya; Garg, Jalaj

doi:10.1097/crd.0000000000000330

Cited by 113 publications

(87 citation statements)

References 45 publications

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“…This data shows that prompt admission and clearance of SARS-CoV-2 virus may alleviate the severity and reduce fatal events by preventing the hyperfibrinolysis and inflammation. D-dimer, as a prognostic marker, is supported by other reviews [93][94][95][96] and clinical studies 1,47 . However, given the dynamic feature of plasma D-dimer, the peak D-dimer value improves the prognostic relevance [97][98][99][100][101] .…”

Section: Prognostic Relevancementioning

confidence: 81%

Insufficient fibrinolysis in COVID-19: a systematic review of thrombolysis based on meta-analysis and meta-regression

Zhao

et al. 2020

Preprint

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Background How aberrant fibrinolysis influences the clinical progression of COVID-19 presents a clinicopathological dilemma challenging intensivists. To investigate whether abnormal fibrinolysis is a culprit or protector or both, we associated elevated plasma D-dimer with clinical variables to identify a panoramic view of the derangements of fibrinolysis that contribute to the pathogenesis of COVID-19 based on studies available in the literature. Methods We performed this systematic review based on both meta-analysis and meta-regression to compute the correlation of D-dimer at admission with clinical features of COVID-19 patients in retrospective studies or case series. We searched the databases until Aug 18, 2020, with no limitations by language. The first hits were screened, data extracted, and analyzed in duplicate. We did the random-effects meta-analyses and meta-regressions (both univariate and multivariate). D-dimer associated clinical variables and potential mechanisms were schematically reasoned and graphed. Findings Our search identified 42 observational, or retrospective, or case series from six countries (n=14,862 patients) with all races and ages from 1 to 98-year-old. The weighted mean difference of D-dimer was 0.97 μg/mL (95% CI 0.65, 1.29) between relatively mild (or healthy control) and severely affected groups with significant publication bias. Univariate meta-regression identified 58 of 106 clinical variables were associated with plasma D-dimer levels, including 3 demographics, 5 comorbidies, 22 laboratory tests, 18 organ injury biomarkers, 8 severe complications, and 2 outcomes (discharge and death). Of these, 11 readouts were negatively associated with the level of plasma D-dimer. Further, age and gender were confounding factors for the identified D-dimer associated variables. There were 22 variables independently correlated with the D-dimer level, including respiratory rate, dyspnea plasma K+, glucose, SpO2, BUN, bilirubin, ALT, AST, systolic blood pressure, and CK. We thus propose that "insufficient hyperfibrinolysis (fibrinolysis is accelerated but unable to prevent adverse clinical impact for clinical deterioration COVID-19)" as a peculiar mechanism. Interpretation The findings of this meta-analysis- and meta-regression-based systematic review supports elevated D-dimer as an independent predictor for mortality and severe complications. D-dimer-associated clinical variables draw a landscape integrating the aggregate effects of systemically suppressive and locally (i.e., in the lung) hyperactive derangements of fibrinolysis. D-dimer and associated clinical biomarkers and conceptually parameters could be combined for risk stratification, potentially for tracking thrombolytic therapy or alternative interventions.

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Section: Prognostic Relevancementioning

confidence: 81%

Insufficient fibrinolysis in COVID-19: a systematic review of thrombolysis based on meta-analysis and meta-regression

Zhao

et al. 2020

Preprint

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“…Elevated D-dimer is among the most consistent markers of poor outcomes in COVID-19 patients. Several retrospective studies of hospitalized patients in Wuhan, China have demonstrated elevated D-dimer levels on admission with differing optimal cutoffs (starting at >0.5 ug/ml) to be predictive of in-hospital mortality 3,6,14,5 . However, while D-dimer at the time of admission may help stratify all COVID-19 patients according to mortality risk, it was not a significant predictor of mortality in our hospitalized cohort of COVID-19 patients with severe illness and receiving therapeutic anticoagulation for thromboprophylaxis.…”

Section: Discussionmentioning

confidence: 99%

Post-Anticoagulant D-dimer as a Highly Prognostic Biomarker of COVID-19 Mortality

Song

Reva

et al. 2020

Preprint

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Importance: Clinical biomarkers that accurately predict mortality are needed for the effective management of patients with severe COVID-19 illness. Objective: To determine whether D-dimer levels after anticoagulation treatment is predictive of in-hospital mortality. Design: Retrospective study using electronic health record data. Setting: A large New York City hospital network serving a diverse, urban patient population. Participants: Adult patients hospitalized for severe COVID-19 infection who received therapeutic anticoagulation for thromboprophylaxis between February 25, 2020 and May 31, 2020. Exposures: Mean and trend of D-dimer levels in the 3 days following the first therapeutic dose of anticoagulation. Main Outcomes: In-hospital mortality versus discharge. Results: 1835 adult patients (median age, 67 years [interquartile range, 57-78]; 58% male) with PCR-confirmed COVID-19 who received therapeutic anticoagulation during hospitalization were included. 74% (1365) of patients were discharged and 26% (430) died in hospital. The study cohort was divided into four groups based on the mean D-dimer levels and its trend following anticoagulation initiation, with significantly different in-hospital mortality rates (p<0.001): 49% for the high mean-increase trend (HI) group; 27% for the high-decrease (HD) group; 21% for the low-increase (LI) group; and 9% for the low-decrease (LD) group. Using penalized logistic regression models to simultaneously analyze 67 variables (baseline demographics, comorbidities, vital signs, laboratory values, D-dimer levels), post-anticoagulant D-dimer groups had the highest adjusted odds ratios (ORadj) for predicting in-hospital mortality. The ORadj of in-hospital death among patients from the HI group was 6.58 folds (95% CI 3.81-11.16) higher compared to the LD group. The LI (ORadj: 4.06, 95% CI 2.23-7.38) and HD (ORadj: 2.37; 95% CI 1.37-4.09) groups were also associated with higher mortality compared to the LD group. Conclusions and Relevance: D-dimer levels and its trend following the initiation of anticoagulation have high and independent predictive value for in-hospital mortality. This novel prognostic biomarker should be incorporated into management protocols to guide resource allocation and prospective studies for emerging treatments in hospitalized COVID-19 patients.

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“…1,31 Increased D-dimer levels are associated with the need for hospitalisation and ICU admission, 8,32 reflect the severity of disease and predict outcomes. 8,[33][34][35][36][37][38][39] Prothrombin time (PT) was found to be modestly prolonged at admission in nonsurvivors and in patients requiring ICU admission, but not in those not requiring ICU admission. 8 Some studies have reported significantly lower platelet levels in patients with more severe disease and have demonstrated a correlation between thrombocytopenia and mortality.…”

Section: Diagnosis Of Cac Biochemical Markersmentioning

confidence: 99%

Hypercoagulopathy in Severe COVID-19: Implications for Acute Care

et al. 2020

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COVID-19 was first described in late 2019 and has since developed into a pandemic affecting more than 21 million people worldwide. Of particular relevance for acute care is the occurrence of COVID-19-associated coagulopathy (CAC), which is characterised by hypercoagulability, immunothrombosis and venous thromboembolism, and contributes to hypoxia in a significant proportion of patients. This review describes diagnosis and treatment of CAC in the emergency department and in intensive care. We summarise the pathological mechanisms and common complications of CAC such as pulmonary thrombosis and venous thromboembolic events and discuss current strategies for thromboprophylaxis and therapeutic anti-coagulation in the acute care setting.

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Elevated d-Dimer Levels Are Associated With Increased Risk of Mortality in Coronavirus Disease 2019

Abstract: Supplemental Digital Content is available in the text.

Cited by 113 publications

References 45 publications

Insufficient fibrinolysis in COVID-19: a systematic review of thrombolysis based on meta-analysis and meta-regression

Insufficient fibrinolysis in COVID-19: a systematic review of thrombolysis based on meta-analysis and meta-regression

Post-Anticoagulant D-dimer as a Highly Prognostic Biomarker of COVID-19 Mortality

Hypercoagulopathy in Severe COVID-19: Implications for Acute Care

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