Von Willebrand factor with increased binding capacity is associated with reduced platelet aggregation but enhanced agglutination in COVID-19 patients: another COVID-19 paradox?

Biondi‐Zoccai, Giuseppe; Albante, Alida; Alessandri, Francesco; Alvaro, Domenico; Antonelli, Guido; Araimo‐Morselli, Fabio; Auricchio, Daniela; Barone, F.; Bilotta, Federico; Brisciani, Giuseppe Biondi-Zoccai Matteo; Bruno, Katia; Cappannoli, Alessandro; Cardinale, Vincenzo; Ceccarelli, Giancarlo; Celli, Paola; Chistolini, Antonio; Consolo, Stella; Croce, Claudia; Crocitti, Beatrice; Curreli, Mariaignazia; d’Ettorre, Gabriella; Daniela, Lauri De; Lazzaro, Francesco De; Fedele, Francesco; Frati, Giacomo; Galardo, Gioacchino; Giannetti, Lorena; Ianni, S.; Imperiale, Carmela; Maestrini, Viviana; Magnanimi, Eugenia; Maldarelli, Federica; Mancone, Massimo; Martelli, S.; Marullo, Antonino G. M.; Mastroianni, Claudio Maria; Messina, Teresa; Miraldi, Fabio; Pattelli, Elisa; Pecorari, Filippo; Perrella, Serena; Piazzolla, Mario; Portieri, Monica; Pugliese, Francesco; Pulcinelli, Fabio M.; Ratini, Fabiola; Ricci, Claudia; Ruberto, Franco; Santopietro, Pietro; Tellan, Guglielmo; Titi, Luca; Tordiglione, Paolo; Tosi, Antonella; Trigilia, Fausto; Santoro, Cristina; Sciarretta, Sebastiano

doi:10.1007/s11239-020-02339-6

Cited by 18 publications

(22 citation statements)

References 13 publications

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“…40 It is speculated that platelet exhaustion due to increased platelet activity in the early course of COVID-19 is a possible mechanism behind this consistent finding of reduced platelet aggregation later in the course of disease. 40 Whether the risk of thrombosis or severity of the disease can be modulated by acetylsalicylic acid (ASA) has been investigated in two ways, but only in non-ICU populations. First, a meta-analysis by Srivastava and Kumar investigated if the continuation of ASA upon hospitalization due to COVID-19 was beneficial.…”

Section: Discussionmentioning

confidence: 90%

“…Others have described increased levels of platelet-associated cytokines as well as release of αand dense-granule contents in both ICU and non-ICU COVID-19 patients, 38,39 but these findings were not related to the development of thrombosis. 38 The level of von Willebrand factor was also found to be increased 39,40 and with increased binding capacity, 40 but still platelet aggregation was reduced upon stimulation. 40 It is speculated that platelet exhaustion due to increased platelet activity in the early course of COVID-19 is a possible mechanism behind this consistent finding of reduced platelet aggregation later in the course of disease.…”

Section: Discussionmentioning

confidence: 94%

“…38 The level of von Willebrand factor was also found to be increased 39,40 and with increased binding capacity, 40 but still platelet aggregation was reduced upon stimulation. 40 It is speculated that platelet exhaustion due to increased platelet activity in the early course of COVID-19 is a possible mechanism behind this consistent finding of reduced platelet aggregation later in the course of disease. 40 Whether the risk of thrombosis or severity of the disease can be modulated by acetylsalicylic acid (ASA) has been investigated in two ways, but only in non-ICU populations.…”

Section: Discussionmentioning

confidence: 94%

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Dynamic Hemostasis and Fibrinolysis Assays in Intensive Care COVID-19 Patients and Association with Thrombosis and Bleeding—A Systematic Review and a Cohort Study

Hvas

Larsen

Adelborg

et al. 2021

Semin Thromb Hemost

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Patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19), the infectious pathology caused by severe acute respiratory syndrome coronavirus 2, have a high risk of thrombosis, though the precise mechanisms behind this remain unclarified. A systematic literature search in PubMed and EMBASE identified 18 prospective studies applying dynamic coagulation assays in ICU COVID-19 patients. Overall, these studies revealed normal or slightly reduced primary hemostasis, prolonged clot initiation, but increased clot firmness. Thrombin generation assay parameters generally were equivalent to the control groups or within reference range. Fibrinolysis assays showed increased clot resistance. Only six studies related their findings to clinical outcome. We also prospectively included 51 COVID-19 patients admitted to the ICU. Blood samples were examined on day 1, 3–4, and 7–8 with platelet function tests, rotational thromboelastometry (ROTEM), in vivo and ex vivo thrombin generation, and clot lysis assay. Data on thrombosis, bleeding, and mortality were recorded during 30 days. Primary hemostasis was comparable to healthy controls, but COVID-19 patients had longer ROTEM-clotting times and higher maximum clot firmness than healthy controls. Ex vivo thrombin generation was similar to that of healthy controls while in vivo thrombin generation markers, thrombin–antithrombin (TAT) complex, and prothrombin fragment 1 + 2 (F1 + 2) were higher in ICU COVID-19 patients than in healthy controls. Impaired fibrinolysis was present at all time points. TAT complex and F1 + 2 levels were significantly higher in patients developing thrombosis (n = 16) than in those without. In conclusion, only few previous studies employed dynamic hemostasis assays in COVID-19 ICU-patients and failed to reveal a clear association with development of thrombosis. In ICU COVID-19 patients, we confirmed normal platelet aggregation, while in vivo thrombin generation was increased and fibrinolysis decreased. Thrombosis may be driven by increased thrombin formation in vivo.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 94%

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Dynamic Hemostasis and Fibrinolysis Assays in Intensive Care COVID-19 Patients and Association with Thrombosis and Bleeding—A Systematic Review and a Cohort Study

Hvas

Larsen

Adelborg

et al. 2021

Semin Thromb Hemost

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“…Tissue damage factors such as von-Willebrand factor (vWF), fibrinogen, PAI 1, soluble thrombomodulin, or angiopoietin are elevated in plasma from COVID-19 patients. 2,30,47 Especially vWF and fibrinogen together with D-dimer and Pselectin are vital for the development of coagulopathies. In addition, NETosis has also been identified as a factor in the inflammatory response to SARS-CoV-2 as well as platelet activation.…”

Section: Platelet In Covid-19 Infectionmentioning

confidence: 99%

Platelets and COVID-19

Rohlfing¹,

Rath²,

Geisler³

et al. 2021

Hamostaseologie

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In 2019 first reports about a new human coronavirus emerged, which causes common cold symptoms as well as acute respiratory distress syndrome. The virus was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severe thrombotic events including deep vein thrombosis, pulmonary embolism, and microthrombi emerged as additional symptoms. Heart failure, myocardial infarction, myocarditis, and stroke have also been observed. As main mediator of thrombus formation, platelets became one of the key aspects in SARS-CoV-2 research. Platelets may also directly interact with SARS-CoV-2 and have been shown to carry the SARS-CoV-2 virus. Platelets can also facilitate the virus uptake by secretion of the subtilisin-like proprotein convertase furin. Cleavage of the SARS-CoV-2 spike protein by furin enhances binding capabilities and virus entry into various cell types. In COVID-19 patients, platelet count differs between mild and serious infections. Patients with mild symptoms have a slightly increased platelet count, whereas thrombocytopenia is a hallmark of severe COVID-19 infections. Low platelet count can be attributed to platelet apoptosis and the incorporation of platelets into microthrombi (peripheral consumption) and severe thrombotic events. The observed excessive formation of thrombi is due to hyperactivation of platelets caused by the infection. Various factors have been suggested in the activation of platelets in COVID-19, such as hypoxia, vessel damage, inflammatory factors, NETosis, SARS-CoV-2 interaction, autoimmune reactions, and autocrine activation. COVID-19 does alter chemokine and cytokine plasma concentrations. Platelet chemokine profiles are altered in COVID-19 and contribute to the described chemokine storms observed in severely ill COVID-19 patients.

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“…The severe phenotype of SARS-CoV-2 infection is frequently associated with elevated D-dimer [ 40 ] low platelet count [ 41 ], together with elevated von Willebrand factor and higher agglutination rates induced by ristocetin [ 42 ]. These features are strongly suggestive of systemic clotting activation and enhanced agglutination, with secondary fibrinolysis and thrombocytes consumption.…”

Section: Main Textmentioning

confidence: 99%

Research on SARS-COV-2 pandemic: a narrative review focused on the Italian contribution

Cassai

Longhini

Romagnoli

et al. 2021

J Anesth Analg Crit Care

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Background Since late 2019, a severe acute respiratory syndrome, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread with overwhelming speed causing over 214 million confirmed infections and more than 4.5 million deaths worldwide. In this framework, Italy had the second highest number of SARS-CoV-2 infections worldwide, and the largest number of deaths. A global effort of both the scientific community and governments has been undertaken to stem the pandemic. The aim of this paper is to perform a narrative review of the Italian contribution to the scientific literature regarding intensive care management of patients suffering from COVID-19, being one of the first western countries to face an outbreak of SARS-CoV-2 infection. Main body We performed a narrative review of the literature, dedicating particular attention and a dedicated paragraph to ventilatory support management, chest imaging findings, biomarkers, possible pharmacological interventions, bacterial superinfections, prognosis and non-clinical key aspects such as communication and interaction with relatives. Conclusions Many colleagues, nurses and patients died leaving their families alone. To all of them, we send our thoughts and dedicate these pages.

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Von Willebrand factor with increased binding capacity is associated with reduced platelet aggregation but enhanced agglutination in COVID-19 patients: another COVID-19 paradox?

Cited by 18 publications

References 13 publications

Dynamic Hemostasis and Fibrinolysis Assays in Intensive Care COVID-19 Patients and Association with Thrombosis and Bleeding—A Systematic Review and a Cohort Study

Dynamic Hemostasis and Fibrinolysis Assays in Intensive Care COVID-19 Patients and Association with Thrombosis and Bleeding—A Systematic Review and a Cohort Study

Platelets and COVID-19

Research on SARS-COV-2 pandemic: a narrative review focused on the Italian contribution

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