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2.
EBioMedicine ; 85: 104305, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2068885

ABSTRACT

BACKGROUND: The pathogenesis of coronavirus disease 2019 (COVID-19) is characterized by enhanced platelet activation and diffuse hemostatic alterations, which may contribute to immunothrombosis/thromboinflammation and subsequent development of target-organ damage. Thrombopoietin (THPO), a growth factor essential to megakariocyte proliferation, is known to prime platelet activation and leukocyte-platelet interaction. In addition, THPO concentrations increase in several critical diseases, such as acute cardiac ischemia and sepsis, thus representing a potential diagnostic and prognostic biomarker. Furthermore, several data suggest that interleukin (IL)-6 is one of the most important inflammatory mediators involved in these phenomena, which led to explore the potential therapeutic role of IL-6 inhibitors. In this prospective cohort study, we aimed to study THPO and IL-6 concentrations in COVID-19 patients at the time of first clinical evaluation in the Emergency Department (ED), and to investigate their potential use as diagnostic and prognostic biomarkers. In addition, we sought to explore the role of THPO contained in plasma samples obtained from COVID-19 patients in priming in vitro platelet activation and leukocyte-platelet interaction. METHODS: We enrolled 66 patients presenting to the ED with symptoms suggestive of COVID-19, including 47 with confirmed COVID-19 and 19 in whom COVID-19 was excluded (Non-COVID-19 patients). As controls, we also recruited 18 healthy subjects. In vitro, we reproduced the effects of increased circulating THPO on platelet function by adding plasma from COVID-19 patients or controls to platelet-rich plasma or whole blood obtained by healthy donors, and we indirectly studied the effect of THPO on platelet activation by blocking its biological activity. FINDINGS: THPO levels were higher in COVID-19 patients than in both Non-COVID-19 patients and healthy subjects. Studying THPO as diagnostic marker for the diagnosis of COVID-19 by receiver-operating-characteristic (ROC) statistics, we found an area under the curve (AUC) of 0.73, with an optimal cut-off value of 42.60 pg/mL. IL-6 was higher in COVID-19 patients than in healthy subjects, but did not differ between COVID-19 and Non-COVID-19 patients. THPO concentrations measured at the time of diagnosis in the ED were also higher in COVID-19 patients subsequently developing a severe disease than in those with mild disease. Evaluating THPO as biomarker for severe COVID-19 using ROC analysis, we found an AUC of 0.71, with an optimal cut-off value of 57.11 pg/mL. IL-6 was also higher in severe than in mild COVID-19 patients, with an AUC for severe COVID-19 of 0.83 and an optimal cut-off value of 23 pg/ml. THPO concentrations correlated with those of IL-6 (r=0.2963; p=0.043), and decreased 24 h after the administration of tocilizumab, an IL-6 receptor blocking antibody, showing that the increase of THPO levels depends on IL-6-stimulated hepatic synthesis. In vitro, plasma obtained from COVID-19 patients, but not from healthy subjects, primed platelet aggregation and leukocyte-platelet binding, and these effects were reduced by inhibiting THPO activity. INTERPRETATION: Increased THPO may be proposed as an early biomarker for the diagnosis of COVID-19 and for the identification of patients at risk of developing critical illness. Elevated THPO may contribute to enhance platelet activation and leukocyte-platelet interaction in COVID-19 patients, thus potentially participating in immunothrombosis/thromboinflammation. FUNDING: This work was supported by Ministero dell'Università e della Ricerca Scientifica e Tecnologica (MURST) ex 60% to GM and EL.


Subject(s)
COVID-19 , Thrombosis , Humans , Thrombopoietin/metabolism , COVID-19/diagnosis , Interleukin-6 , Prospective Studies , Inflammation , Platelet Activation , Biomarkers
3.
Clin Lab ; 68(9)2022 Sep 01.
Article in English | MEDLINE | ID: covidwho-2040369

ABSTRACT

BACKGROUND: CD62P is a surface marker for platelet activation. Platelet dysfunction contributes to disproportionate intravascular microthrombosis in SARS-CoV-2. We aimed to assess the clinical significance of CD62P as a biomarker of platelet activation and its correlation to the clinical severity and outcome of COVID-19 infections. METHODS: The study included 80 COVID-19 patients and, in addition, there were 20 age and gender-matched healthy controls. Laboratory measurements included CBC, serum ferritin, LDH, CRP, D-dimer and flow cytometric assessments of the platelet markers CD42b and CD62P. The primary study outcome was patients' survival at the end of study. RESULTS: Among the studied patients, 24 patients (30.0%) died by the end of the study. Survivors had significantly lower CD62P values when compared with non-survivors [median (IQR): 75.5 (73.0 - 91.0) versus 96.0 (93.5 - 97.8), p < 0.001]. Patients with severe disease had significantly higher levels of CD62P levels [median (IQR): 95.5 (92.0 - 97.8) versus 75.0 (72.0 - 76.8), p < 0.001]. Logistic regression analysis identified D-dimer levels [OR (95% CI): 0.14 (0.03 - 0.74) and CD62P levels: OR (95% CI): 0.4 (0.17 - 0.94)] as significant predictors of mortality in multivariate analysis. CONCLUSIONS: CD62P expression on admission may be a useful prognostic maker in hospitalized Covid-19 patients. Its expression is related to other markers of inflammation and coagulopathy.


Subject(s)
COVID-19 , P-Selectin/metabolism , Biomarkers , Ferritins , Humans , Platelet Activation , Prognosis , SARS-CoV-2
5.
J Thromb Haemost ; 20(9): 2161-2163, 2022 09.
Article in English | MEDLINE | ID: covidwho-1992868
6.
Thromb Haemost ; 122(10): 1683-1692, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1947710

ABSTRACT

BACKGROUND: Activated platelets have been implicated in the proinflammatory and prothrombotic phenotype of coronavirus disease 2019 (COVID-19). While it is increasingly recognized that lipids have important structural and signaling roles in platelets, the lipidomic landscape of platelets during infection has remained unexplored. OBJECTIVE: To investigate the platelet lipidome of patients hospitalized for COVID-19. METHODS: We performed untargeted lipidomics in platelets of 25 patients hospitalized for COVID-19 and 23 noninfectious controls with similar age and sex characteristics, and with comparable comorbidities. RESULTS: Twenty-five percent of the 1,650 annotated lipids were significantly different between the groups. The significantly altered part of the platelet lipidome mostly comprised lipids that were less abundant in patients with COVID-19 (20.4% down, 4.6% up, 75% unchanged). Platelets from COVID-19 patients showed decreased levels of membrane plasmalogens, and a distinct decrease of long-chain, unsaturated triacylglycerols. Conversely, platelets from patients with COVID-19 displayed class-wide higher abundances of bis(monoacylglycero)phosphate and its biosynthetic precursor lysophosphatidylglycerol. Levels of these classes positively correlated with ex vivo platelet reactivity-as measured by P-selectin expression after PAR1 activation-irrespective of disease state. CONCLUSION: Taken together, this investigation provides the first exploration of the profound impact of infection on the human platelet lipidome, and reveals associations between the lipid composition of platelets and their reactivity. These results warrant further lipidomic research in other infections and disease states involving platelet pathophysiology.


Subject(s)
Blood Platelets , COVID-19 , Blood Platelets/metabolism , Humans , Lipidomics , P-Selectin/metabolism , Plasmalogens/metabolism , Platelet Activation , Receptor, PAR-1/metabolism , Triglycerides/metabolism
7.
Blood Adv ; 6(13): 3884-3898, 2022 07 12.
Article in English | MEDLINE | ID: covidwho-1923509

ABSTRACT

Mild thrombocytopenia, changes in platelet gene expression, enhanced platelet functionality, and presence of platelet-rich thrombi in the lung have been associated with thromboinflammatory complications of patients with COVID-19. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) gets internalized by platelets and directly alters their behavior and function in infected patients remains elusive. Here, we investigated platelet parameters and the presence of viral material in platelets from a prospective cohort of 29 patients with severe COVID-19 admitted to an intensive care unit. A combination of specific assays, tandem mass spectrometry, and flow cytometry indicated high levels of protein and lipid platelet activation markers in the plasma from patients with severe COVID-19 associated with an increase of proinflammatory cytokines and leukocyte-platelets interactions. Platelets were partly desensitized, as shown by a significant reduction of αIIbß3 activation and granule secretion in response to stimulation and a decrease of surface GPVI, whereas plasma from patients with severe COVID-19 potentiated washed healthy platelet aggregation response. Transmission electron microscopy indicated the presence of SARS-CoV-2 particles in a significant fraction of platelets as confirmed by immunogold labeling and immunofluorescence imaging of Spike and nucleocapsid proteins. Compared with platelets from healthy donors or patients with bacterial sepsis, platelets from patients with severe COVID-19 exhibited enlarged intracellular vesicles and autophagolysosomes. They had large LC3-positive structures and increased levels of LC3II with a co-localization of LC3 and Spike, suggesting that platelets can digest SARS-CoV-2 material by xenophagy in critically ill patients. Altogether, these data show that during severe COVID-19, platelets get activated, become partly desensitized, and develop a selective autophagy response.


Subject(s)
COVID-19 , Humans , Macroautophagy , Platelet Activation , Prospective Studies , SARS-CoV-2
8.
Thromb Res ; 216: 120-124, 2022 08.
Article in English | MEDLINE | ID: covidwho-1915030

ABSTRACT

BACKGROUND: The coronavirus disease-2019 (COVID-19) is a systemic disease with severe implications on the vascular and coagulation system. A procoagulant platelet phenotype has been reported at least in the acute disease phase. Soluble P-selectin (sP-sel) in the plasma is a surrogate biomarker of platelet activation. Increased plasma levels of sP-sel have been reported in hospitalized COVID-19 patients associated with disease severity. Here, we evaluated in a longitudinal study the sP-sel plasma concentration in blood donors who previously suffered from moderate COVID-19. METHODS: 154 COVID-19 convalescent and 111 non-infected control donors were recruited for plasma donation and for participation in the CORE research trial. First donation (T1) was performed 43-378 days after COVID-19 diagnosis. From most of the donors the second (T2) plasma donation including blood sampling was obtained after a time period of 21-74 days and the third (T3) donation after additional 22-78 days. Baseline characteristics including COVID-19 symptoms of the donors were recorded based on a questionnaire. Platelet function was measured at T1 by flow cytometry and light transmission aggregometry in a representative subgroup of 25 COVID-19 convalescent and 28 control donors. The sP-sel plasma concentration was determined in a total of 704 samples by using a commercial ELISA. RESULTS: In vitro platelet function was comparable in COVID-19 convalescent and control donors at T1. Plasma samples from COVID-19 convalescent donors revealed a significantly higher sP-sel level compared to controls at T1 (1.05 ± 0.42 ng/mL vs. 0.81 ± 0.30 ng/mL; p < 0.0001) and T2 (0.96 ± 0.39 ng/mL vs. 0.83 ± 0.38 ng/mL; p = 0.0098). At T3 the sP-sel plasma level was comparable in both study groups. Most of the COVID-19 convalescent donors showed a continuous decrease of sP-sel from T1 to T3. CONCLUSION: Increased sP-sel plasma concentration as a marker for platelet or endothelial activation could be demonstrated even weeks after moderate COVID-19, whereas, in vitro platelet function was comparable with non-infected controls. We conclude that COVID-19 and additional individual factors could lead to an increase of the sP-sel plasma level.


Subject(s)
COVID-19 , Biomarkers , COVID-19 Testing , Humans , Longitudinal Studies , P-Selectin , Platelet Activation
9.
Front Immunol ; 13: 837629, 2022.
Article in English | MEDLINE | ID: covidwho-1902997

ABSTRACT

Both qualitative and quantitative platelet abnormalities are common in patients with coronavirus disease 2019 (COVID-19) and they correlate with clinical severity and mortality. Activated platelets contribute to the prothrombotic state in COVID-19 patients. Several groups have shown immune-mediated activation of platelets in critically ill COVID-19 patients. Vaccine-induced immune thrombotic thrombocytopenia is an autoimmune condition characterized by thrombocytopenia and life-threatening thrombotic events in the arterial and venous circulation. Although the initial trigger has yet to be determined, activation of platelets by immune complexes through Fc gamma RIIA results in platelet consumption and thrombosis. A better understanding of platelet activation in COVID-19 as well as in vaccine-induced thrombotic complications will have therapeutic implications. In this review, we focused on the role of immune-mediated platelet activation in thrombotic complications during COVID-19 infection and vaccine-induced immune thrombotic thrombocytopenia.


Subject(s)
Blood Platelets/physiology , COVID-19/immunology , Purpura, Thrombotic Thrombocytopenic/immunology , SARS-CoV-2/physiology , Animals , Blood Coagulation , Humans , Platelet Activation , Vaccination/adverse effects
10.
Inflammopharmacology ; 30(4): 1475-1476, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1899225

ABSTRACT

In this commentary, we make a case that the mechanism of COVID pathogenesis is related to virus-induced endothelial injury resulting in platelet activation and the formation of microthrombi both systemically and in cardiac and pulmnonary circulation which result in major causes of COVID morbidity and mortality. Aspirin by virtue of its irreversible inhibition of platelet COX-1, should reverse these platelet-induced pathogenic changes associated with COVID infection for the 6-9 day lifetime of the platelet. We also cite recent findings of a retrospective analysis that supports the use of low-dose (81 mg) aspirin to treat the symptoms associated with the early stages of COVID infection.


Subject(s)
Aspirin , COVID-19 , Aspirin/pharmacology , Aspirin/therapeutic use , Blood Platelets , COVID-19/drug therapy , Humans , Platelet Activation , Retrospective Studies
11.
Int J Mol Sci ; 23(11)2022 May 27.
Article in English | MEDLINE | ID: covidwho-1888430

ABSTRACT

Platelets play a variety of roles in vascular biology and are best recognized as primary hemostasis and thrombosis mediators. Platelets have a large number of receptors and secretory molecules that are required for platelet functionality. Upon activation, platelets release multiple substances that have the ability to influence both physiological and pathophysiological processes including inflammation, tissue regeneration and repair, cancer progression, and spreading. The involvement of platelets in the progression and seriousness of a variety of disorders other than thrombosis is still being discovered, especially in the areas of inflammation and the immunological response. This review represents an integrated summary of recent advances on the function of platelets in pathophysiology that connects hemostasis, inflammation, and immunological response in health and disease and suggests that antiplatelet treatment might be used for more than only thrombosis.


Subject(s)
Hemostasis , Thrombosis , Blood Platelets/physiology , Hemostasis/physiology , Humans , Inflammation , Platelet Activation , Platelet Function Tests
12.
Br J Haematol ; 198(2): 257-266, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1846193

ABSTRACT

To slow down the coronavirus disease 2019 (COVID-19) pandemic an unequalled vaccination campaign was initiated. Despite proven efficacy and safety, a rare but potentially fatal complication of adenoviral-vector vaccines, called vaccine-induced immune thrombotic thrombocytopenia (VITT), has emerged the pathogenesis of which seems to be related to the development of platelet-activating anti-platelet factor 4 (PF4) antibodies. While a few studies have evaluated the incidence of anti-PF4 positivity in anti-severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine recipients, to date no studies have assessed whether an antiplatelet immunological response develops and if this associates with platelet and blood clotting activation. We carried out a prospective study in healthy subjects who received the first dose of ChAdOx1 or Ad26.COV2.S or BNT162b2 vaccines to evaluate platelet-specific and non-specific immune response and in vivo platelet activation and blood clotting activation. Individuals receiving ChAdOx1 and, less so, Ad26.COV2.S developed with high frequency auto- or alloantiplatelet antibodies, increased circulating platelet-derived microvesicles and soluble P-selectin associated with mild blood clotting activation. Our study shows that an immunological reaction involving platelets is not uncommon in individuals receiving anti-SARS-CoV-2 vaccination, especially after ChAdOx1 and Ad26.COV2.S, and that it associates with in vivo platelet and blood clotting activation.


Subject(s)
Autoimmunity , COVID-19 Vaccines , COVID-19 , Platelet Activation , Thrombocytopenia , Ad26COVS1 , Adenoviridae , BNT162 Vaccine , Blood Coagulation , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Humans , Platelet Factor 4 , Prospective Studies , SARS-CoV-2 , Thrombocytopenia/chemically induced
13.
Front Immunol ; 13: 834988, 2022.
Article in English | MEDLINE | ID: covidwho-1817941

ABSTRACT

Patients with COVID-19 present with a wide variety of clinical manifestations. Thromboembolic events constitute a significant cause of morbidity and mortality in patients infected with SARS-CoV-2. Severe COVID-19 has been associated with hyperinflammation and pre-existing cardiovascular disease. Platelets are important mediators and sensors of inflammation and are directly affected by cardiovascular stressors. In this report, we found that platelets from severely ill, hospitalized COVID-19 patients exhibited higher basal levels of activation measured by P-selectin surface expression and had poor functional reserve upon in vitro stimulation. To investigate this question in more detail, we developed an assay to assess the capacity of plasma from COVID-19 patients to activate platelets from healthy donors. Platelet activation was a common feature of plasma from COVID-19 patients and correlated with key measures of clinical outcome including kidney and liver injury, and APACHEIII scores. Further, we identified ferritin as a pivotal clinical marker associated with platelet hyperactivation. The COVID-19 plasma-mediated effect on control platelets was highest for patients that subsequently developed inpatient thrombotic events. Proteomic analysis of plasma from COVID-19 patients identified key mediators of inflammation and cardiovascular disease that positively correlated with in vitro platelet activation. Mechanistically, blocking the signaling of the FcγRIIa-Syk and C5a-C5aR pathways on platelets, using antibody-mediated neutralization, IgG depletion or the Syk inhibitor fostamatinib, reversed this hyperactivity driven by COVID-19 plasma and prevented platelet aggregation in endothelial microfluidic chamber conditions. These data identified these potentially actionable pathways as central for platelet activation and/or vascular complications and clinical outcomes in COVID-19 patients. In conclusion, we reveal a key role of platelet-mediated immunothrombosis in COVID-19 and identify distinct, clinically relevant, targetable signaling pathways that mediate this effect.


Subject(s)
Blood Platelets/immunology , COVID-19/immunology , Complement C5a/metabolism , Receptor, Anaphylatoxin C5a/metabolism , Receptors, IgG/metabolism , SARS-CoV-2/physiology , Thromboembolism/immunology , Adult , Aminopyridines/pharmacology , Cells, Cultured , Female , Hospitalization , Humans , Male , Morpholines/pharmacology , Platelet Activation , Pyrimidines/pharmacology , Severity of Illness Index , Signal Transduction , Syk Kinase/antagonists & inhibitors
14.
Sci Rep ; 12(1): 6851, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1815595

ABSTRACT

COVID-19 is associated with an increased risk of thrombotic events. However, the pathogenesis of these complications is unclear and reports on platelet infection and activation by the virus are conflicting. Here, we integrated single-cell transcriptomic data to elucidate whether platelet activation is a specific response to SARS-CoV-2 infection or a consequence of a generalized inflammatory state. Although platelets from patients infected with SARS-CoV-2 over expressed genes involved in activation and aggregation when compared to healthy controls; those differences disappeared when the comparison was made with patients with generalized inflammatory conditions of other etiology than COVID-19. The membrane receptor for the virus, ACE-2, was not expressed by infected or control platelets. Our results suggest that platelet activation in patients with severe COVID-19 is mainly a consequence of a systemic inflammatory state than direct invasion and activation.


Subject(s)
Blood Platelets , COVID-19 , COVID-19/genetics , Humans , Platelet Activation/genetics , SARS-CoV-2 , Transcriptome
15.
Arterioscler Thromb Vasc Biol ; 42(1): 63-66, 2022 01.
Article in English | MEDLINE | ID: covidwho-1799160
16.
Blood Adv ; 6(12): 3593-3605, 2022 06 28.
Article in English | MEDLINE | ID: covidwho-1799124

ABSTRACT

Platelets are hyperactivated in coronavirus disease 2019 (COVID-19). However, the mechanisms promoting platelet activation by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not well understood. This may be due to inherent challenges in discriminating the contribution of viral vs host components produced by infected cells. This is particularly true for enveloped viruses and extracellular vesicles (EVs), as they are concomitantly released during infection and share biophysical properties. To study this, we evaluated whether SARS-CoV-2 itself or components derived from SARS-CoV-2-infected human lung epithelial cells could activate isolated platelets from healthy donors. Activation was measured by the surface expression of P-selectin and the activated conformation of integrin αIIbß3, degranulation, aggregation under flow conditions, and the release of EVs. We find that neither SARS-CoV-2 nor purified spike activates platelets. In contrast, tissue factor (TF) produced by infected cells was highly potent at activating platelets. This required trace amounts of plasma containing the coagulation factors FX, FII, and FVII. Robust platelet activation involved thrombin and the activation of protease-activated receptor (PAR)-1 and -4 expressed by platelets. Virions and EVs were identified by electron microscopy. Through size-exclusion chromatography, TF activity was found to be associated with a virus or EVs, which were indistinguishable. Increased TF messenger RNA (mRNA) expression and activity were also found in lungs in a murine model of COVID-19 and plasma of severe COVID-19 patients, respectively. In summary, TF activity from SARS-CoV-2-infected cells activates thrombin, which signals to PARs on platelets. Blockade of molecules in this pathway may interfere with platelet activation and the coagulation characteristic of COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Humans , Mice , Platelet Activation , Thrombin , Thromboplastin/metabolism
17.
Haematologica ; 107(10): 2445-2453, 2022 10 01.
Article in English | MEDLINE | ID: covidwho-1779916

ABSTRACT

In order to improve the safety of COVID-19 vaccines, there is an urgent need to unravel the pathogenesis of vaccineinduced immune thrombotic thrombocytopenia (VITT), a severe complication of recombinant adenoviral vector vaccines used to prevent COVID-19, and likely due to anti-platelet factor 4 (PF4) IgG antibodies. In this study, we demonstrated that 1E12, a chimeric anti-PF4 antibody with a human Fc fragment, fully mimics the effects of human VITT antibodies, as it activates platelets to a similar level in the presence of platelet factor 4 (PF4). Incubated with neutrophils, platelets and PF4, 1E12 also strongly induces NETosis, and in a microfluidic model of whole blood thrombosis, it triggers the formation of large platelet/leukocyte thrombi containing fibrin(ogen). In addition, a deglycosylated form of 1E12 (DG-1E12), which still binds PF4 but no longer interacts with Fcγ receptors, inhibits platelet, granulocyte and clotting activation induced by human anti-PF4 VITT antibodies. This strongly supports that 1E12 and VITT antibodies recognize overlapping epitopes on PF4. In conclusion, 1E12 is a potentially important tool to study the pathophysiology of VITT, and for establishing mouse models. On the other hand, DG-1E12 may help the development of a new drug that specifically neutralizes the pathogenic effect of autoimmune anti-PF4 antibodies, such as those associated with VITT.


Subject(s)
COVID-19 Vaccines , COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Animals , COVID-19 Vaccines/adverse effects , Epitopes , Fibrin , Humans , Immunoglobulin Fc Fragments , Immunoglobulin G , Mice , Platelet Activation , Platelet Factor 4/adverse effects , Platelet Factor 4/metabolism , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Receptors, IgG/genetics , Receptors, IgG/metabolism , Thrombocytopenia/chemically induced , Thrombosis/pathology
18.
Int J Mol Sci ; 23(7)2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1776246

ABSTRACT

There is accumulating evidence that platelets play roles beyond their traditional functions in thrombosis and hemostasis, e.g., in inflammatory processes, infection and cancer, and that they interact, stimulate and regulate cells of the innate immune system such as neutrophils, monocytes and macrophages. In this review, we will focus on platelet activation in hemostatic and inflammatory processes, as well as platelet interactions with neutrophils and monocytes/macrophages. We take a closer look at the contributions of major platelet receptors GPIb, αIIbß3, TLT-1, CLEC-2 and Toll-like receptors (TLRs) as well as secretions from platelet granules on platelet-neutrophil aggregate and neutrophil extracellular trap (NET) formation in atherosclerosis, transfusion-related acute lung injury (TRALI) and COVID-19. Further, we will address platelet-monocyte and macrophage interactions during cancer metastasis, infection, sepsis and platelet clearance.


Subject(s)
COVID-19 , Thrombosis , Blood Platelets/pathology , Hemostasis , Humans , Immunity, Innate , Inflammation/pathology , Neutrophils/pathology , Platelet Activation , Thrombosis/pathology
19.
Front Immunol ; 13: 807934, 2022.
Article in English | MEDLINE | ID: covidwho-1775663

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a highly prothrombotic viral infection that primarily manifests as an acute respiratory syndrome. However, critically ill COVID-19 patients will often develop venous thromboembolism with associated increases in morbidity and mortality. The cause for this prothrombotic state is unclear but is likely related to platelet hyperactivation. In this review, we summarize the current evidence surrounding COVID-19 thrombosis and platelet hyperactivation. We highlight the fact that several studies have identified a soluble factor in COVID-19 patient plasma that is capable of altering platelet phenotype in vitro. Furthermore, this soluble factor appears to be an immune complex, which may be composed of COVID-19 Spike protein and related antibodies. We suggest that these Spike-specific immune complexes contribute to COVID-19 platelet activation and thrombosis in a manner similar to heparin-induced thrombocytopenia. Understanding this underlying pathobiology will be critical for advancement of future research and therapeutic options.


Subject(s)
COVID-19 , Thrombosis , Antigen-Antibody Complex/adverse effects , Humans , Platelet Activation , Platelet Factor 4 , SARS-CoV-2 , Thrombosis/etiology
20.
Minerva Anestesiol ; 88(6): 472-478, 2022 06.
Article in English | MEDLINE | ID: covidwho-1754132

ABSTRACT

BACKGROUND: Platelet activation at the early stage of COVID-19 is poorly described. The need for antiplatelet therapy in patients with COVID-19 remains controversial. We characterized the platelet activation profile in hospitalized patients at the early stage of COVID-19 using the modified prothrombinase Platelet Activation State (PAS) Assay. METHODS: Sixteen patients admitted to the emergency department of the IRCCS San Raffaele Hospital (Milan, Italy) between February 8 and April 2021 were enrolled. All patients presented with respiratory symptoms and tested positive for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Platelet activation was measured via the PAS Assay within 24 hours from patients' hospital admission. Data were compared with those measured in N.=24 healthy subjects (controls). RESULTS: Platelet activation was significantly higher in COVID-19 patients with respect to controls (PAS=0.63 [0.58-0.98%] vs. 0.46 [0.40-0.65%], respectively; P=0.03). Of note, highest PAS values were measured in the two patients with the worst clinical outcome, i.e., death because of respiratory failure (PAS=2.09% and 1.20%, respectively). No differences in standard coagulation parameters were noted between these two patients and those who were later discharged home. CONCLUSIONS: This study provides evidence of significant platelet activation state at the early stage of COVID-19 and suggests that the patient-specific platelet activation profile is a reliable clinical marker to stratify COVID-19 patients at high risk of poor clinical outcome who might potentially benefit from antiplatelet therapy.


Subject(s)
COVID-19 , Hospitalization , Humans , Platelet Activation , Platelet Aggregation Inhibitors/therapeutic use , SARS-CoV-2
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