Heparin-binding protein levels correlate with aggravation and multiorgan damage in severe COVID-19

Xue, Mingshan; Zeng, Yutian; Qu, Hui‐Qi; Zhang, Teng; Li, Ning; Huang, Huimin; Zheng, Peiyan; Hu, Haisheng; Zhou, Luqian; Duan, Zhifeng; Zhang, Yong; Bao, Wei; Tian, Lifeng; Hákonarson, Hákon; Zhong, Nanshan; Zhang, Xiaohua Douglas; Sun, Baoqing

doi:10.1183/23120541.00741-2020

Cited by 15 publications

(22 citation statements)

References 67 publications

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“… 28 It is possible that therapeutic-dose heparin cannot influence the cascade of inflammation, thrombosis, and organ injury in patients with advanced disease. 29-31 It is also possible that differences in the patient populations, aside from illness severity, may have contributed to these findings.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

et al. 2021

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Background Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. Methods In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care–level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d -dimer level. Results The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support–free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d -dimer cohort, 92.9% in the low d -dimer cohort, and 97.3% in the unknown d -dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis. Conclusions In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589 , NCT04505774 , NCT04359277 , and NCT02735707 .)

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Section: Discussionmentioning

confidence: 99%

Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

et al. 2021

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“…[29][30][31] It is possible that therapeutic-dose heparin is unable to influence the thrombo-inflammatory cascade and organ injury in patients with advanced disease and its sequale. [32][33][34] Among moderately-ill participants in this mpRCT, those in the high D-dimer group were at increased risk for mortality and receipt of organ support compared with those in the low D-dimer group and, accordingly, adjusted absolute treatment benefits were more apparent. Participants in the high D-dimer group were generally older with a higher prevalence of comorbid diseases.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Anticoagulation in Non-Critically Ill Patients with Covid-19

Lawler

Goligher

Berger

et al. 2021

Preprint

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Background Thrombo-inflammation may contribute to morbidity and mortality in Covid-19. We hypothesized that therapeutic-dose anticoagulation may improve outcomes in non-critically ill patients hospitalized for Covid-19. Methods In an open-label adaptive multiplatform randomized controlled trial, non-critically ill patients hospitalized for Covid-19, defined by the absence of critical care-level organ support at enrollment, were randomized to a pragmatic strategy of therapeutic-dose anticoagulation with heparin or usual care pharmacological thromboprophylaxis. The primary outcome combined survival to hospital discharge and days free of organ support through 21 days, which was evaluated with Bayesian statistical models according to baseline D-dimer. Results The trial was stopped when prespecified criteria for superiority were met for therapeutic-dose anticoagulation in groups defined by high (≥2-fold elevated) and low (<2-fold elevated) D-dimer. Among 2219 participants in the final analysis, the probability that therapeutic anticoagulation increased organ support-free days compared to thromboprophylaxis was 99.0% (adjusted odds ratio 1.29, 95% credible interval 1.04 to 1.61). The adjusted absolute increase in survival to hospital discharge without organ support with therapeutic-dose anticoagulation was 4.6% (95% credible interval 0.7 to 8.1). In the primary adaptive stopping groups, the final probabilities of superiority for therapeutic anticoagulation were 97.3% in the high D-dimer group and 92.9% in the low D-dimer group. Major bleeding occurred in 1.9% and 0.9% of participants randomized to therapeutic anticoagulation and thromboprophylaxis, respectively. Conclusions In non-critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increases the probability of survival to hospital discharge with reduced use of organ support.

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“…As stated, these benefits were not confirmed in critically ill patients. It is most likely that therapeutic doses of heparin cannot influence the inflammatory cascade, thrombosis, and organ damage in patients with endstage of COVID-19 disease, however, these actions may require consideration in the initial infection stage and/or in patients with moderate courses of disease [35][36][37].…”

Section: Thromboprophylaxismentioning

confidence: 99%

Thromboprophylaxis in patients with Covid-19

Dybowska¹,

Dybowski²,

Szturmowicz³

et al. 2022

Acta Angiologica

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For two years, the entire world has been grappling with the new challenge that is the COVID-19 pandemic. In December 2019 in China's largest province, Wuhan, Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was detected in a patient with severe respiratory failure. Shortly after, infections were detected in all regions of the world. So far, 265 million infections have been confirmed around the world, and 5.2 million of those infected have died due to COVID-19. Infection with SARS-CoV-2 is associated with an increased risk of cardiovascular complications, especially thromboembolic complications. Low-molecular-weight-heparin presents a basic form of prophylaxis against thromboembolic complications in individuals who are ill with COVID-19. Controversy still exists regarding the optimal dose of LMWH depending on disease severity, this problem requires further randomized trials.

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Heparin-binding protein levels correlate with aggravation and multiorgan damage in severe COVID-19

Cited by 15 publications

References 67 publications

Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

Therapeutic Anticoagulation in Non-Critically Ill Patients with Covid-19

Thromboprophylaxis in patients with Covid-19

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