Severe SARS-CoV-2 Infection Inhibits Fibrinolysis Leading to Changes in Viscoelastic Properties of Blood Clot: A Descriptive Study of Fibrinolysis in COVID-19

Hammer, Stefanie; Häberle, Helene; Schlensak, Christian; Bitzer, Michael; Malek, Nisar P.; Handgretinger, Rupert; Lang, Peter; Hörber, Sebastian; Peter, Andreas; Martus, Peter; Mirakaj, Valbona; Gawaz, Meinrad; Geisler, Tobias; Althaus, Karina; Rosenberger, Peter; Bakchoul, Tamam

doi:10.1055/a-1400-6034

Cited by 37 publications

(53 citation statements)

References 36 publications

(43 reference statements)

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“…It is well-correlated with the significantly elevated level of Ddimer in the severe but not in moderate patients. Similar to our finding, a recent study also reported an elevated level of PAI-1 in COVID-19 patients [58]. Consistently, another study reported elevated levels of both PIA-1 and tPA in the hospitalized COVID-19 patients.…”

Section: Discussionsupporting

confidence: 92%

SARS-CoV-2 infection induces soluble platelet activation markers and PAI-1 in the early moderate stage of COVID-19

Al-Tamimi

Yusuf

Jayakumar

et al. 2021

Preprint

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Coagulation dysfunction and thromboembolism emerge as strong comorbidity factors in severe COVID-19 patients. However, the underlying pathomechanisms are largely undefined. Here, we sought to identify the potential molecular mechanisms of SARS-CoV-2 mediated coagulopathy and thromboembolism. A broader investigation was conducted including hospitalized COVID-19 patients with (severe cases that required intensive care) or without pneumonia (moderate cases). Phenotypic and molecular characterizations were performed employing basic coagulation tests, flow cytometry-based multiplex assays, and ELISA. The investigations revealed induction of plasma P-selectin and CD40 ligand (sCD40L) in moderate COVID-19 cases which were significantly abolished with the progression of COVID-19 severity. Moreover, a profound reduction in plasma tissue factor pathway inhibitor (TFPI) and FXIII were identified particularly in the severe COVID-19. Further analysis revealed a profound induction of fibrinogen in both moderate and severe patients. Interestingly, an elevated plasminogen activator inhibitor-1 more prominently in moderate, and tissue plasminogen activator (tPA) particularly in severe COVID-19 cases were observed. Particularly, the levels of fibrinogen and tPA directly correlated with the severity of COVID-19. In summary, SARS-CoV-2 infection induces the levels of platelet activation markers soluble P-selectin and sCD40L in hospitalized COVID-19 patients. Furthermore, an attenuated level of TFPI indicates TF pathway activation and, acquired FXIII deficiency likely plays a key role in thrombus instability and promotes thromboembolism in severe cases. The progression of COVID-19 severity could be limited with anti-platelet in combination with recombinantTFPI treatment. Furthermore, thromboembolic events in severe COVID-19 patients could be minimized if treated with recombinantFXIII in combination with LMW heparin.

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Section: Discussionsupporting

confidence: 92%

SARS-CoV-2 infection induces soluble platelet activation markers and PAI-1 in the early moderate stage of COVID-19

Al-Tamimi

Yusuf

Jayakumar

et al. 2021

Preprint

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“…High levels of tPA enhanced fibrinolysis and were strongly correlated with mortality. 15 In contrast, in a different cohort a decrease of fibrinolysis was shown in severely infected patients. 16 In another study, the authors showed a strong correlation of plasminogen concentrations with mortality in COVID-19 patients.…”

Section: Introductionmentioning

confidence: 89%

“…We could confirm increased levels of PAI-1 in COIVD-19 patient-samples that indicates the involvement of the plasminogen-plasmin system, however, we saw no prognostic correlation of PAI-1 concentrations with disease severity. 15 Several newly identified blood markers were increased in patients with severe disease (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) in addition to analytes, that had already been described (CRP, IL1-ra, IL-8, IL-10, IL-18, MCP-1). 8,11,24 Published multi-omics analysis and our own observations indicate the involvement of diverse factors, that determine the final outcome of COVID-19.…”

Section: Dovepressmentioning

confidence: 95%

Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19

Herr¹,

Mang²,

Mozafari³

et al. 2021

JIR

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Background: COVID-19 comprises several severity stages ranging from oligosymptomatic disease to multi-organ failure and fatal outcomes. The mechanisms why COVID-19 is a mild disease in some patients and progresses to a severe multi-organ and often fatal disease with respiratory failure are not known. Biomarkers that predict the course of disease are urgently needed. The aim of this study was to evaluate a large spectrum of established laboratory measurements.Patients and Methods: Patients from the prospective PULMPOHOM and CORSAAR studies were recruited and comprised 35 patients with COVID-19, 23 with conventional pneumonia, and 28 control patients undergoing elective non-pulmonary surgery. Venous blood was used to measure the serum concentrations of 79 proteins by Luminex multiplex immunoassay technology. Distribution of biomarkers between groups and association with disease severity and outcomes were analyzed. Results: The biomarker profiles between the three groups differed significantly with elevation of specific proteins specific for the respective conditions. Several biomarkers correlated significantly with disease severity and death. Uniform manifold approximation and projection (UMAP) analysis revealed a significant separation of the three disease groups and separated between survivors and deceased patients. Different models were developed to predict mortality based on the baseline measurements of several protein markers. A score combining IL-1ra, IL-8, IL-10, MCP-1, SCF and CA-9 was associated with significantly higher mortality (AUC 0.929). Discussion: Several newly identified blood markers were significantly increased in patients with severe COVID-19 (AAT, EN-RAGE, myoglobin, SAP, TIMP-1, vWF, decorin) or in patients that died (IL-1ra, IL-8, IL-10, MCP-1, SCF, CA-9). The use of established assay technologies allows for rapid translation into clinical practice.

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“…The ChAdOx1 nCov-19 vector is constructed with a human tissue plasminogen activator signal sequence [173]. This might engender thoughts of some potential coagulation activity given that tissue plasminogen activator circulates in much higher quantitation in the blood of those with COVID-19 infection versus controls [15]. The latter association is much more avid for those patients with worse disease.…”

Section: Thrombotic Events and Covid-19 Vaccinationmentioning

confidence: 99%

“…It should also be conceded that outside of the potential for thrombosis-related antibodies, alterations in platelet functionality have also been observed [13]. These events must also be seen in the context of endothelial injury or altered fibrinolysis otherwise [14][15][16]. Persistence of an anomalous clotting profile in other regards has also been proposed well after acute infections [17].…”

Section: Introductionmentioning

confidence: 99%

Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19

Cimolai

2021

SN Compr. Clin. Med.

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Advanced SARS-CoV-2 infections not uncommonly associate with the occurrence of silent or manifest thrombotic events which may be found as focal or systemic disease. Given the potential complexity of COVID-19 illnesses, a multifactorial causation is likely, but several studies have focused on infection-induced coagulopathy. Procoagulant states are commonly found in association with the finding of antiphospholipid antibodies. The correlation of the latter with thrombosis and/or clinical severity remains controversial. Although measures of antiphospholipid antibodies most commonly include assessments for lupus anticoagulant, anticardiolipin, and anti-ß2-glycoprotein-I antibodies, lesser common antibodies have been detected, and there remains speculation that other yet undiscovered autoimmune thrombotic events may yet be found. The recent discovery of post-vaccination thromboses associated with platelet factor 4 antibody has created another level of concern. The pathogenesis of antiphospholipid antibodies and their role in COVID-19-related thrombosis deserves further attention. The multifactorial nature of thrombosis associated with both infection and vaccination should continue to be studied as new events unfold. Even if a cause-and-effect relationship is variable at best, such dedicated research is likely to generate other valuable insights that are applicable to medicine generally.

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Severe SARS-CoV-2 Infection Inhibits Fibrinolysis Leading to Changes in Viscoelastic Properties of Blood Clot: A Descriptive Study of Fibrinolysis in COVID-19

Cited by 37 publications

References 36 publications

SARS-CoV-2 infection induces soluble platelet activation markers and PAI-1 in the early moderate stage of COVID-19

SARS-CoV-2 infection induces soluble platelet activation markers and PAI-1 in the early moderate stage of COVID-19

Distinct Patterns of Blood Cytokines Beyond a Cytokine Storm Predict Mortality in COVID-19

Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19

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