Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium

Gorog, Diana A.; Storey, Robert F.; Gurbel, Paul A.; Tantry, Udaya S.; Berger, Jeffrey S.; Chan, Mark Y; Duerschmied, Daniel; Smyth, Susan S.; Parker, William A.; Ajjan, Ramzi; Vilahur, Gemma; Badimon, Lina; Berg, Jürrien M. ten; Cate, Hugo Ten; Peyvandi, Flora; Wang, Taia T.; Becker, Richard C.

doi:10.1038/s41569-021-00665-7

Cited by 201 publications

(152 citation statements)

References 200 publications

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“…However, some variant of intravascular clotting must be occurring as evidenced by elevated D-dimer levels seen in a majority of Covid-19 patients upon admission [17], and in virtually all ICU Covid-19 patients. Elevated D-dimer levels are associated with disease severity and adverse outcomes, including mortality, in Covid-19 patients [17,18]. D-dimer elevation confirms that Factor XIII-stabilized clots (Factor XIII cross-linked protofibrils or larger) have formed, and have subsequently undergone fibrinolysis [19].…”

Section: Introductionmentioning

confidence: 92%

“…It might also clarify some of the puzzling aspects of Covid-19 pathophysiology. In Covid-19, clotting followed by lysis of those clots happens in virtually all ICU Covid-19 patients as evidenced by the markedly elevated D-dimer levels previously noted [17,18]. A determination of the SF level at which the first clots appear, as well as how long such clots persist in normal blood, would be highly informative.…”

Section: Introductionmentioning

confidence: 97%

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Fibrin Strands Will Grow from Soluble Fibrin and Hang Up In an ex vivo Microcirculatory Viscoelastic Model: Is This a Major Cause of Covid-19 Associated Coagulopathy?

Bull¹,

Hay²,

Herrmann³

2022

Preprint

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Viscoelastic testing (VET) by both TEG and ROTEM has demonstrated hypercoagulability early in Covid Associated Coagulopathy (CAC). Additional VET studies demonstrated fibrinolytic shutdown late in a majority of severely ill Covid-19 patients with associated elevation of D-dimer. Elevated d-dimer confirms that coagulation, followed by fibrinolysis, has occurred. These findings imply that, during CAC, three enzymes—thrombin, Factor XIIIa and plasmin—must have acted in sequence. However, limitations in standard VET analyses preclude exploration of the earliest phases of clot induction, as well as clot formation and clot dissolution in flowing blood. Herein we describe a novel method illuminating aspects of this unexplored area. In addition, we created an ex vivo blood flow model in which the interactions of thrombin, Factor XIII and plasmin with fibrinogen can be studied, allowing determination of Soluble Fibrin (SF), the highly unstable form of fibrin that precedes the appearance of a visible clot. This model allows determination of the SF level at which fibrin microclots begin to form and the length of time the resulting microclots persist under normal fibrinolytic attack. In addition, the flow model allows exploration of the late fibrinolytic shutdown that VET has previously demonstrated in CAC through standard methodology.

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 97%

Fibrin Strands Will Grow from Soluble Fibrin and Hang Up In an ex vivo Microcirculatory Viscoelastic Model: Is This a Major Cause of Covid-19 Associated Coagulopathy?

Bull¹,

Hay²,

Herrmann³

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…It is possible to find a prothrombotic state also in long COVID-19, due to residual persistence of the blood chemistry of inflammation and procoagulative states [49]. The most frequently reported coagulation abnormality, especially in the most severe patients, is the elevation of D-dimer, but there are also increases in fibrinogen and its degradation products, PAI-1, and von Willebrand factor, as well as low levels of antithrombin III and antiphospholipid antibodies, known for their thrombophilic effect [29,39,45,[50][51][52].…”

Section: Covid-19 and Thrombosismentioning

confidence: 99%

COVID-19, Vaccines, and Thrombotic Events: A Narrative Review

Abrignani

Murrone

Luca

et al. 2022

JCM

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The coronavirus disease 2019 (COVID-19), a deadly pandemic that has affected millions of people worldwide, is associated with cardiovascular complications, including venous and arterial thromboembolic events. Viral spike proteins, in fact, may promote the release of prothrombotic and inflammatory mediators. Vaccines, coding for the spike protein, are the primary means for preventing COVID-19. However, some unexpected thrombotic events at unusual sites, most frequently located in the cerebral venous sinus but also splanchnic, with associated thrombocytopenia, have emerged in subjects who received adenovirus-based vaccines, especially in fertile women. This clinical entity was soon recognized as a new syndrome, named vaccine-induced immune thrombotic thrombocytopenia, probably caused by cross-reacting anti-platelet factor-4 antibodies activating platelets. For this reason, the regulatory agencies of various countries restricted the use of adenovirus-based vaccines to some age groups. The prevailing opinion of most experts, however, is that the risk of developing COVID-19, including thrombotic complications, clearly outweighs this potential risk. This point-of-view aims at providing a narrative review of epidemiological issues, clinical data, and pathogenetic hypotheses of thrombosis linked to both COVID-19 and its vaccines, helping medical practitioners to offer up-to-date and evidence-based counseling to their often-alarmed patients with acute or chronic cardiovascular thrombotic events.

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“…However, the underlying mechanisms of thromboembolism in patients with COVID-19 seem to be different from COVID-19-independent thromboembolism. COVID-19-associated coagulopathy seems to be mediated by excessive inflammation, endothelial activation and injury, platelet activation, impaired or dysfunctional fibrinolysis and systemic hypercoagulability 122 ; vascular endothelial cells are among the primary targets of SARS-CoV-2, and COVID-19 infection can result in endothelial damage and also in systemic vasculitis 123 . COVID-19-associated coagulopathy is probably a multifactorial combination of low-grade disseminated intravascular coagulation, thrombotic microangiopathy and released pro-inflammatory cytokines such as IL-6, which can induce tissue factor expression on mononuclear cells and subsequently initiate coagulation activation and thrombin generation 124 .…”

Section: Urological Thromboembolic Complicationsmentioning

confidence: 99%

The COVID-19 pandemic — what have urologists learned?

et al. 2022

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On 11 March 2020, the WHO declared the coronavirus disease 2019 (COVID-19) outbreak a pandemic and COVID-19 emerged as one of the biggest challenges in public health and economy in the twenty-first century. The respiratory tract has been the centre of attention, but COVID-19-associated complications affecting the genitourinary tract are reported frequently, raising concerns about possible long-term damage in these organs. The angiotensin-converting enzyme 2 (ACE2) receptor, which has a central role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion, is highly expressed in the genitourinary tract, indicating that these organs could be at a high risk of cell damage. The detection of SARS-CoV-2 in urine and semen is very rare; however, COVID-19 can manifest through urological symptoms and complications, including acute kidney injury (AKI), which is associated with poor survival, severe structural changes in testes and impairment of spermatogenesis, and hormonal imbalances (mostly secondary hypogonadism). The effect of altered total testosterone levels or androgen deprivation therapy on survival of patients with COVID-19 was intensively debated at the beginning of the pandemic; however, androgen inhibition did not show any effect in preventing or treating COVID-19 in a clinical study. Thus, urologists have a crucial role in detecting and managing damage of the genitourinary tract caused by COVID-19.

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Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium

Cited by 201 publications

References 200 publications

Fibrin Strands Will Grow from Soluble Fibrin and Hang Up In an ex vivo Microcirculatory Viscoelastic Model: Is This a Major Cause of Covid-19 Associated Coagulopathy?

Fibrin Strands Will Grow from Soluble Fibrin and Hang Up In an ex vivo Microcirculatory Viscoelastic Model: Is This a Major Cause of Covid-19 Associated Coagulopathy?

COVID-19, Vaccines, and Thrombotic Events: A Narrative Review

The COVID-19 pandemic — what have urologists learned?

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