Update to coagulopathy in COVID-19: Manifestations and management

Mucha, Simon; Dugar, Siddharth; McCrae, Keith R.; Joseph, Douglas; Bartholomew, John R.; Sacha, Gretchen L.; Militello, Michael

doi:10.3949/ccjm.87a.ccc024-up

Cited by 10 publications

(9 citation statements)

References 60 publications

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“…Microvascular thrombosis have also been reported in extrapulmonary organs, which may explain the acute onset of multiorgan failure [ 54 ]. COVID-19-associated coagulopathy (CAC) is emerged as prominent feature of severe or critically ill patients [ 55 ]. It has been reported that COVID-19 is highly thrombotic.…”

Section: Discussionmentioning

confidence: 99%

Cellular and molecular mechanisms in COVID-19 coagulopathy: role of inflammation and endotheliopathy

Cacciola

Vecchio

et al. 2021

J Thromb Thrombolysis

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Introduction Coronavirus 2 (CoV-2) infection or coronavirus disease 2019 (COVID-19) is frequently associated with microvascular thrombosis.The microthrombosis in COVID-19 is the result of the interplay between inflammation and endotheliopathy. Elevated interleukin-6 (IL-6) characterizes COVID-19 inflammation resulting in endotheliopathy and coagulopathy marked by elevated D-dimer (DD). Aim of this study is to identify and to describe the coagulation changes in 100 moderate COVID-19 patients having lung involvement and to determine the association of coagulopathy with the severity and prognosis. Methods Inflammation, endothelial and coagulation molecules were measured in moderate and mild disease. Results IL-6 and tumor necrosis factor-α (TNF-α) and tissue factor (TF), von Willebrand factor (VWF), and tissue factor pathway inhibitor (TFPI) significantly increased in moderate disease as well as D-dimer, thrombin antithrombin complex (TAT), Fibrinogen (Fib), platelet factor-4 (PF4), β-thromboglobulin (β-TG), P-selectin, and platelet adhesion. Shortened clotting time (CT) and clot formation time (CFT), high maximum clot firmness (MCF) and low LY at 30 min were present in 100% of moderate COVID-19 patients compared with mild COVID-19 patients. Conclusions These findings demonstrate that moderate COVID-19 has a profound inflammation associated with severee ndotheliopathy and intense coagulation activation uncontrolled by TFPI. Attention should be paid to coagulopathy in COVID-19. Closely monitoring of coagulation and application of appropriate anticoagulation may improve the prognosis of moderate COVID-19 and to prevent the progression to severe COVID-19 disease.

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Section: Discussionmentioning

confidence: 99%

Cellular and molecular mechanisms in COVID-19 coagulopathy: role of inflammation and endotheliopathy

Cacciola

Vecchio

et al. 2021

J Thromb Thrombolysis

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“…Markedly elevated D-dimer, out of proportion to other acute phase reactants such as CRP levels, has been associated with increased mortality in Covid-19, presumably due to underlying thrombosis. 13 For the purpose of quantifying the proportion of excess mortality attributed to a thrombophilia, we used D-dimer as a surrogate measure for a thrombotic diagnosis when a thrombotic diagnosis code was absent but the D-dimer level was markedly elevated.…”

Section: Methodsmentioning

confidence: 99%

Does the elevated (thrombosis risk of males relative to females help account for the excess male mortality observed in Covid-19? An observational study

Cohen

Anderson

Ren

et al. 2021

Preprint

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ObjectivesWe sought to determine whether underlying thrombophilia helps account for excess Covid-19 mortality rates in males relative to females. Specifically, we asked: What is the contribution of thrombophilia to the excess Covid-19 mortality risk among malesãDesignCross-sectional observational study.SettingData were sourced from electronic medical records (EMRs) drawn from over 200 US hospital systems.Participants16,576 patients hospitalized with Covid-19, aged 40 and above.Main outcome measuresThe primary study outcome was Covid-19 mortality. We measured: 1) the mortality rate of male patients relative to female patients, 2) the rate of thrombotic diagnoses occurring during hospitalization for Covid-19 in male and female patients, and 3) the mortality rate when evidence of thrombosis was present. We used hospital EMR data to determine the rates of a thrombotic diagnosis by sex, and D-dimer levels to help identify undiagnosed thrombosis.ResultsThe Covid-19 mortality rate of males was higher than that of females by 16.1%. Males with Covid-19 also had a 25.4% higher rate of receiving a thrombotic diagnosis compared to females with Covid-19. The mortality rate of all patients with a thrombotic diagnosis was 42.4%—a rate over twice that of Covid-19 patients without a thrombotic diagnosis (adjusted OR 2.4 (2.17 to 2.65), p-value < .001). When defining thrombosis as either a documented thrombotic diagnosis or markedly elevated D-dimer levels, over half of the excess mortality in male patients could be explained by thrombophilia.ConclusionsOur findings suggest the higher Covid-19 mortality rate in males may be significantly accounted for by the increased propensity for thrombophilia among males. This thrombotic tendency is additive to the thrombotic risk associated with Covid-19. Understanding the mechanisms that underlie male thrombophilia may allow for the advancement of effective anticoagulation strategies that reduce Covid-19 mortality.Strengths and limitations of this studyTo our knowledge, this population study is the first to provide evidence of a sex-based clinical association that may help explain the excess Covid-19 mortality in males compared to females.This was an observational study using diagnosis codes and natural language processing (NLP) extractions of detailed electronic health record (EHR) data for 16,576 hospitalized patients with Covid-19.We evaluated underlying thrombosis based on both an inpatient thrombotic diagnosis as well as a markedly elevated D-dimer level relative to CRP level.A limitation of this study was that a portion of the estimated excess male mortality was based on the analysis of a subset of 3,442 patients that had serial D-dimer and CRP levels measured in the hospital, and that a potential undercount of these patients was possible due to the use of NLP.

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“…Point-of-care ultrasound (POCUS) might reduce the need for CTPAs in these patients in already overwhelmed acute and critical health care systems worldwide, particularly in low- and middle-income [ [8] , [9] , [10] ]. Recent consensus statements recommend the use of POCUS as an initial test in critically ill COVID-19 patients [ 3 , 5 , 11 , 12 ]. However literature on POCUS in the detection of PE in these patients is still limited.…”

Section: Introductionmentioning

confidence: 99%

“…Combining different POCUS modalities (lung, deep veins, and cardiac) to detect pulmonary embolism has been advocated as well [ 3 , 5 , 11 , 12 , 25 ]. In the emergency department (ED) setting there are promising results of multi-organ POCUS in the detection of PE [ 7 , 10 , 26 ], while others found no benefit [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Multi-organ point-of-care ultrasound for detection of pulmonary embolism in critically ill COVID-19 patients – A diagnostic accuracy study

Lieveld

Heldeweg

Smit

et al. 2022

Journal of Critical Care

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Purpose Critically ill COVID-19 patients have an increased risk of developing pulmonary embolism (PE). Diagnosis of PE by point-of-care ultrasound (POCUS) might reduce the need for computed tomography pulmonary angiography (CTPA), while decreasing time-to-diagnosis. Materials & methods This prospective, observational study included adult ICU patients with COVID-19. Multi-organ (lungs, deep vein, cardiac) POCUS was performed within 24 h of CTPA, looking for subpleural consolidations, deep venous thrombosis (DVT), and right ventricular strain (RVS). We reported the scan time, and calculated diagnostic accuracy measures for these signs separately and in combination. Results 70 consecutive patients were included. 23 patients (32.8%) had a PE. Median scan time was 14 min (IQR 11–17). Subpleural consolidations' diagnostic accuracy was: 42.9% (95%CI [34.1–52.0]). DVT's and RVS' diagnostic accuracy was: 75.6% (95%CI [67.1–82.9]) and 74.4% (95%CI [65.8–81.8]). Their sensitivity was: 24.0% (95%CI [9.4–45.1]), and 40.0% (95%CI [21.3–61.3]), while their specificity was: 88.8% (95%CI [80.8–94.3]), and: 83.0% (95%CI [74.2–89.8]), respectively. Multi-organ POCUS sensitivity was: 87.5% (95%CI [67.6–97.3]), and specificity was: 25% (95%CI [16.9–34.7]). Conclusions Multi-organ rather than single-organ POCUS can be of aid in ruling out PE in critically ill COVID-19 and help select patients for CTPA. In addition, finding RVS can make PE more likely, while a DVT would preclude the need for a CTPA. Registration: www.trialregister.nl : NL8540.

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Update to coagulopathy in COVID-19: Manifestations and management

Cited by 10 publications

References 60 publications

Cellular and molecular mechanisms in COVID-19 coagulopathy: role of inflammation and endotheliopathy

Cellular and molecular mechanisms in COVID-19 coagulopathy: role of inflammation and endotheliopathy

Does the elevated (thrombosis risk of males relative to females help account for the excess male mortality observed in Covid-19? An observational study

Multi-organ point-of-care ultrasound for detection of pulmonary embolism in critically ill COVID-19 patients – A diagnostic accuracy study

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