Thrombin Generation in Patients with Coronavirus Disease 2019

Benati, Marco; Salvagno, Gian Luca; Nitto, Simone De; Gelati, Matteo; Lavorgna, Barbara; Fava, Cristiano; Minuz, Pietro; Lippi, Giuseppe

doi:10.1055/s-0041-1722844

Cited by 16 publications

(17 citation statements)

References 20 publications

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“…All these studies demonstrated normal TG profile in COVID-19 under thromboprophylaxis. Additionally, a recent small observation by Benati M. et al [35] on ST Genesia ® as well, confirmed the presence of prolonged lag time and time to peak in COVID-19 patients vs. controls.…”

Section: Discussionmentioning

confidence: 54%

Thrombin generation in patients with COVID-19 with and without thromboprophylaxis

Campello

Bulato

Spiezia

et al. 2021

Clinical Chemistry and Laboratory Medicine (CCLM)

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Objectives Thrombin generation (TG) with and without thrombomodulin (TM) was evaluated in COVID-19 patients with different disease severity and thromboprophylaxis regimen, in order to understand the prothrombotic profile. Methods We enrolled consecutive patients with confirmed diagnosis of COVID-19 admitted to Medical Departments (MD) or Intensive Care Units (ICU), and 54 healthy controls. Results Eighty-nine patients were included (mean age 60.4±16.1 years, 68.5% male); 33.7% admitted to ICU. Twenty-four patients (26.9%) were enrolled before thromboprophylaxis administration; 45 patients (50.6%) received standard and 20 (22.5%) intermediate sub-therapeutic dose thromboprophylaxis. Overall, patients with COVID-19 showed a TG profile comparable to that of healthy subjects (i.e. comparable peak height, endogenous thrombin potential [ETP] with and without TM). The only exception was lag time and time to peak, prolonged in COVID-19 patients vs. controls. MD patients showed a similar TG profile to healthy controls, and ICU patients showed significantly decrease ETP (p=0.030) compared to MD. As for thromboprophylaxis, TG profile was significantly increased in COVID-19 patients without thromboprophylaxis vs. controls and vs. those with thromboprophylaxis. In this latter group, ETP inhibition was significantly decreased (p=0.0003) and positively correlated with anti-Xa activity (r=0.49, p=0.0017). However, patients with thromboprophylaxis had similar TG profile vs. controls. Intermediate dose thromboprophylaxis more effectively inhibited TG in severe COVID-19 patients by increasing ETP inhibition via ETP with TM reduction vs. standard dose. Conclusions COVID-19 patients showed increased TG at diagnosis. Standard thromboprophylaxis reduced TG to levels of healthy controls. Intermediate sub-therapeutic thromboprophylaxis more effectively inhibited TG by decreasing ETP with TM.

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Section: Discussionmentioning

confidence: 54%

Thrombin generation in patients with COVID-19 with and without thromboprophylaxis

Campello

Bulato

Spiezia

et al. 2021

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…4 Platelet activation may also occur as a consequence of thrombin generation occurring after concomitant activation of blood coagulation. 26 Moreover, direct SARS-CoV-2 and spike protein binding to platelet angiotensin-converting enzyme 2 (ACE2) has been shown to activate platelets in vitro, while spike has been shown to potentiate thrombus formation in vivo. Such SARS-CoV-2/spike to platelet ACE2 binding results in platelet stimulation, causing release of coagulation factors and inflammatory cytokines, with promotion of leukocyte-platelet aggregates formation.…”

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confidence: 99%

Mean Platelet Volume Predicts Severe COVID-19 Illness

Lippi

Henry

Favaloro

2021

Semin Thromb Hemost

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“…As inflammation results in further TF expression, thrombin generation represents initiation of a vicious cycle, which promotes the procoagulant state. 23,45 Neutrophil extracellular traps and damage-associated molecular patterns may also be involved in the procoagulant profile in patients with COVID-19. 46 Inflammation Therapeutic Target in the Management of VTE Anticoagulation therapy represents an effective option in preventing VTE and the propagation of VTE events.…”

Section: Covid-19 Vte and Inflammationmentioning

confidence: 99%

Involvement of Inflammation in Venous Thromboembolic Disease: An Update in the Age of COVID-19

Poredoš

2021

Semin Thromb Hemost

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The inflammatory process is strongly involved in the pathophysiology of venous thromboembolism (VTE) and has a significant role in disease prediction. Inflammation most probably represents a common denominator through which classical and nonclassical risk factors stimulate thrombotic process. Inflammation of the venous wall promotes the release of tissue factor, inhibits the release of anticoagulant factors, and hampers endogenous fibrinolysis. Systemic inflammatory response also inhibits restoration of blood flow in the occluded vessel. Recent studies indicate that increased inflammatory response (“cytokine storm”) is related to prothrombotic state and thromboembolic events in patients with coronavirus disease 2019 (COVID-19). The growing evidence of involvement of inflammation in the pathogenesis of VTE indicates the importance of anti-inflammatory treatment and prevention of VTE. While aspirin was shown to be effective in prevention of recurrent venous thrombosis after treatment with anticoagulant drugs, some other anti-inflammatory drugs like nonsteroidal anti-inflammatory agents may have prothrombotic effect, thus potentially increasing the risk of VTE. Recently, new specific anti-inflammatory drug inhibitors of inflammatory markers that have been shown to be involved in the pathogenesis of VTE are being searched. As thrombogenesis is based on activation of coagulation provoked by inflammation, then prevention and treatment of VTE should include both anticoagulant and anti-inflammatory agents. Combined treatment is related to increased risk of bleeding complications, therefore subtherapeutic doses of both drugs should be used to improve the efficacy of management of VTE without increasing the risk of bleeding.

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Thrombin Generation in Patients with Coronavirus Disease 2019

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Cited by 16 publications

References 20 publications

Thrombin generation in patients with COVID-19 with and without thromboprophylaxis

Thrombin generation in patients with COVID-19 with and without thromboprophylaxis

Mean Platelet Volume Predicts Severe COVID-19 Illness

Involvement of Inflammation in Venous Thromboembolic Disease: An Update in the Age of COVID-19

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