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1.
Arterioscler Thromb Vasc Biol ; 42(1): 63-66, 2022 01.
Article in English | MEDLINE | ID: covidwho-1799160
2.
Platelets ; 33(2): 192-199, 2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1788407

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a pandemic syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection induces a process of inflammation and thrombosis supported by an altered platelet activation state. This platelet activation is peculiar being characterized by the formation of platelet-leukocytes rather than platelet-platelet aggregates and by an increased procoagulant potential supported by elevated levels of TF positive platelets and microvesicles.Therapeutic strategies targeting, beyond systemic inflammation (i.e. with tocilizumab, an anti interleukin-6 receptor), this state of platelet activation might therefore be beneficial. Among the antithrombotic drugs proposed as candidates to treat patients with SARS-CoV-2 infection, antiplatelet drugs, such as aspirin are showing promising results.


Subject(s)
Blood Platelets/metabolism , COVID-19/blood , Humans , SARS-CoV-2
3.
Platelets ; 33(2): 200-207, 2022 Feb 17.
Article in English | MEDLINE | ID: covidwho-1788406

ABSTRACT

Evolving evidence demonstrates that platelets have major roles in viral syndromes through previously unrecognized viral sensing and effector functions. Activated platelets and increased platelet-leukocyte aggregates are observed in clinical and experimental viral infections. The mechanisms and outcomes of platelet-leukocyte interactions depend on the interacting leukocyte as well as on the pathogen and pathological conditions. In this review, we discuss the mechanisms involved in platelet interactions with leukocytes and its functions during viral infections. We focus on the contributions of human platelet-leukocyte interactions to pathophysiological and protective responses during viral infections of major global health relevance, including acquired immunodeficiency syndrome (AIDS), dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), influenza pneumonia, and COVID-19.


Subject(s)
Blood Platelets/metabolism , Leukocytes/metabolism , Virus Diseases/blood , Humans
4.
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
5.
Front Immunol ; 13: 844701, 2022.
Article in English | MEDLINE | ID: covidwho-1775677

ABSTRACT

Background: Hemostasis and inflammation are both dysregulated in patients with moderate-to-severe coronavirus disease 2019 (COVID-19). Yet, both processes can also be disturbed in patients with other respiratory diseases, and the interactions between coagulation, inflammation, and disease severity specific to COVID-19 are still vague. Methods: Hospitalized patients with acute respiratory symptoms and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-positive (COVpos) and SARS-CoV2-negative (COVneg) status were included. We assessed adenosine diphosphate (ADP)-, thrombin receptor activator peptide 6 (TRAP)-, and arachidonic acid (AA)-induced platelet reactivity by impedance aggregometry, as well as leukocyte subtype spectrum and platelet-leukocyte aggregates by flow cytometry and inflammatory cytokines by cytometric bead array. Results: ADP-, TRAP-, and AA-induced platelet reactivity was significantly higher in COVpos than in COVneg patients. Disease severity, assessed by sequential organ failure assessment (SOFA) score, was higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. The SOFA score correlated significantly with the mean platelet volume and TRAP-induced platelet aggregability. A larger percentage of classical and intermediate monocytes, and of CD4pos T cells (TH) aggregated with platelets in COVpos than in COVneg patients. Interleukin (IL)-1 receptor antagonist (RA) and IL-6 levels were higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. IL-1RA and IL-6 levels correlated with the SOFA score in COVpos but not in COVneg patients. In both respiratory disease groups, absolute levels of B-cell-platelet aggregates and NK-cell-platelet aggregates were correlated with ex vivo platelet aggegation upon stimulation with AA and ADP, respectively, indicating a universal, but not a COVID-19-specific mechanism. Conclusion: In moderate-to-severe COVID-19, but not in other respiratory diseases, disease severity was associated with platelet hyperreactivity and a typical inflammatory signature. In addition to a severe inflammatory response, platelet hyperreactivity associated to a worse clinical outcome in patients with COVID-19, pointing to the importance of antithrombotic therapy for reducing disease severity.


Subject(s)
COVID-19 , Adenosine Diphosphate , Blood Platelets , Humans , Immunity, Innate , Inflammation , Interleukin 1 Receptor Antagonist Protein , Interleukin-6 , RNA, Viral , SARS-CoV-2 , Severity of Illness Index
6.
Front Immunol ; 13: 834988, 2022.
Article in English | MEDLINE | ID: covidwho-1753370

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
7.
Blood ; 139(10): 1564-1574, 2022 03 10.
Article in English | MEDLINE | ID: covidwho-1736325

ABSTRACT

Cases of de novo immune thrombocytopenia (ITP), including a fatality, following SARS-CoV-2 vaccination in previously healthy recipients led to studying its impact in preexisting ITP. In this study, 4 data sources were analyzed: the Vaccine Adverse Events Reporting System (VAERS) for cases of de novo ITP; a 10-center retrospective study of adults with preexisting ITP receiving SARS-CoV-2 vaccination; and surveys distributed by the Platelet Disorder Support Association (PDSA) and the United Kingdom (UK) ITP Support Association. Seventy-seven de novo ITP cases were identified in VAERS, presenting with median platelet count of 3 [1-9] ×109/L approximately 1 week postvaccination. Of 28 patients with available data, 26 responded to treatment with corticosteroids and/or intravenous immunoglobulin (IVIG), and/or platelet transfusions. Among 117 patients with preexisting ITP who received a SARS-CoV-2 vaccine, 19 experienced an ITP exacerbation (any of: ≥50% decline in platelet count, nadir platelet count <30 × 109/L with >20% decrease from baseline, and/or use of rescue therapy) following the first dose and 14 of 70 after a second dose. Splenectomized persons and those who received 5 or more prior lines of therapy were at highest risk of ITP exacerbation. Fifteen patients received and responded to rescue treatment. In surveys of both 57 PDSA and 43 UK patients with ITP, prior splenectomy was associated with worsened thrombocytopenia. ITP may worsen in preexisting ITP or be identified de novo post-SARS-CoV2 vaccination; both situations responded well to treatment. Proactive monitoring of patients with known ITP, especially those postsplenectomy and with more refractory disease, is indicated.


Subject(s)
COVID-19 Vaccines , COVID-19 , Purpura, Thrombocytopenic, Idiopathic , SARS-CoV-2 , Aged , Aged, 80 and over , Blood Platelets/immunology , Blood Platelets/metabolism , COVID-19/blood , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Female , Humans , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/blood , Purpura, Thrombocytopenic, Idiopathic/chemically induced , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Purpura, Thrombocytopenic, Idiopathic/immunology , Retrospective Studies , Risk Factors , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Splenectomy , United Kingdom/epidemiology
8.
J Mol Med (Berl) ; 100(4): 645-663, 2022 04.
Article in English | MEDLINE | ID: covidwho-1729277

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has significantly impacted the world and has driven many researchers into the pathophysiology of COVID-19. In the findings, there is a close association between purinergic signaling and the immune response. Then, this study aimed to evaluate alterations in the purinergic signaling in COVID-19 patients according to range severity. We divided the COVID-19 patients into moderate and severe cases following the guideless of NIH and WHO, together with clinical characteristics. The blood samples were collected to obtain PBMCs and platelets. We analyzed the ectonucleotidase activities through ATP, ADP, AMP, Ado hydrolysis, E-NTPDase1 (CD39), and 5'-NT (CD73) expression by flow cytometry in total leukocytes. The extracellular ATP was measured by bioluminescence, and cytokines were analyzed by flow cytometry. We observed a decrease in ATP hydrolysis and increased AMP hydrolysis in PBMCs for both groups. In severe cases, ATP hydrolysis was raised for the platelets, while ADP and AMP hydrolysis have risen significantly in both groups. Additionally, there was a significant increase in ADP hydrolysis in severe cases compared to moderate cases. In addition, we observed an increase in the ADA activity in platelets of moderate patients. Moderate and severe cases showed increased expression of CD39 and CD73 in total leukocytes. To finalize the purinergic signaling, extracellular ATP was increased in both groups. Furthermore, there was an increase in IL-2, IL-6, IL-10, and IL-17 in moderate and severe groups. Thus, for the first time, our findings confirm the changes in purinergic signaling and immune response in COVID-19, in addition to making it more evident that the severity range directly impacts these changes. Therefore, the therapeutic potential of the purinergic system must be highlighted and studied as a possible target for the treatment of SARS-CoV-2 disease. KEY MESSAGES: COVID-19 patients exhibit alterations in purinergic system and immune response. High levels of extracellular ATP lead to different inflammatory responses. CD39 and CD73 expression were increased in COVID-19 patients. Cytokines IL-2, IL-6, IL-10, and IL-17 also were altered in these patients. The purinergic system may be a possibility target to SARS-CoV-2 treatments.


Subject(s)
COVID-19 , Adenosine Triphosphate/metabolism , Blood Platelets , Humans , Pandemics , SARS-CoV-2
9.
Int J Mol Sci ; 23(4)2022 Feb 19.
Article in English | MEDLINE | ID: covidwho-1715402

ABSTRACT

Platelets, which are small anuclear cell fragments, play important roles in thrombosis and hemostasis, but also actively release factors that can both suppress and induce viral infections. Platelet-released factors include sCD40L, microvesicles (MVs), and alpha granules that have the capacity to exert either pro-inflammatory or anti-inflammatory effects depending on the virus. These factors are prime targets for use in extracellular vesicle (EV)-based therapy due to their ability to reduce viral infections and exert anti-inflammatory effects. While there are some studies regarding platelet microvesicle-based (PMV-based) therapy, there is still much to learn about PMVs before such therapy can be used. This review provides the background necessary to understand the roles of platelet-released factors, how these factors might be useful in PMV-based therapy, and a critical discussion of current knowledge of platelets and their role in viral diseases.


Subject(s)
Blood Coagulation Factors/metabolism , Blood Platelets/metabolism , Extracellular Vesicles/metabolism , Virus Diseases/metabolism , Animals , Cell-Derived Microparticles/metabolism , Humans , Platelet Activation/physiology
10.
Front Immunol ; 13: 776861, 2022.
Article in English | MEDLINE | ID: covidwho-1701723

ABSTRACT

Cardiovascular dysfunction and disease are common and frequently fatal complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Indeed, from early on during the SARS-CoV-2 virus pandemic it was recognized that cardiac complications may occur, even in patients with no underlying cardiac disorders, as part of the acute infection, and that these were associated with more severe disease and increased morbidity and mortality. The most common cardiac complication is acute cardiac injury, defined by significant elevation of cardiac troponins. The potential mechanisms of cardiovascular complications include direct viral myocardial injury, systemic inflammation induced by the virus, sepsis, arrhythmia, myocardial oxygen supply-demand mismatch, electrolyte abnormalities, and hypercoagulability. This review is focused on the prevalence, risk factors and clinical course of COVID-19-related myocardial injury, as well as on current data with regard to disease pathogenesis, specifically the interaction of platelets with the vascular endothelium. The latter section includes consideration of the role of SARS-CoV-2 proteins in triggering development of a generalized endotheliitis that, in turn, drives intense activation of platelets. Most prominently, SARS-CoV-2-induced endotheliitis involves interaction of the viral spike protein with endothelial angiotensin-converting enzyme 2 (ACE2) together with alternative mechanisms that involve the nucleocapsid and viroporin. In addition, the mechanisms by which activated platelets intensify endothelial activation and dysfunction, seemingly driven by release of the platelet-derived calcium-binding proteins, SA100A8 and SA100A9, are described. These events create a SARS-CoV-2-driven cycle of intravascular inflammation and coagulation, which contributes significantly to a poor clinical outcome in patients with severe disease.


Subject(s)
Blood Platelets/metabolism , COVID-19/pathology , Cardiovascular Diseases/pathology , Endothelium, Vascular/metabolism , Platelet Activation/immunology , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/mortality , Cardiovascular Diseases/virology , Coronavirus Nucleocapsid Proteins/immunology , Endothelial Cells/metabolism , Humans , Myocardium/pathology , Phosphoproteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/metabolism
11.
Vox Sang ; 117(2): 251-258, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1685461

ABSTRACT

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic raised concerns about the vulnerability of platelet supply and the uncertain impact of the resumption of elective surgery on utilization. We report the impact of COVID-19 on platelet supply and utilization across a large, integrated healthcare system in the Canadian province of British Columbia (BC). MATERIALS AND METHODS: Historical platelet use in BC by indication was compiled for fiscal year 2010/2011-2019/2020. Platelet collections, initial daily inventory and disposition data were assessed pre-COVID-19 (1 April 2018-15 March 2020) and for two COVID-19 time periods in BC: a shutdown phase with elective surgeries halted (16 March-17 May, 2020) and a renewal phase when elective surgeries resumed (18 May-27 September 2020); comparisons were made provincially and for individual health authorities. RESULTS: Historically, elective surgeries accounted for 10% of platelets transfused in BC. Initial daily supplier inventory increased from baseline during both COVID-19 periods (93/90 units vs. 75 units pre-COVID-19). During the shutdown phase, platelet utilization decreased 10.4% (41 units/week; p < 0.0001), and remained significantly decreased during the ensuing renewal period. Decreased platelet utilization was attributed to fewer transfusions during the shutdown phase followed by a decreased discard/expiry rate during the renewal phase compared to pre-COVID-19 (15.2% vs. 18.9% pre-COVID-19; p < 0.0001). Differences in COVID-19 platelet utilization patterns were noted between health authorities. CONCLUSION: Decreased platelet utilization was observed in BC compared to pre-COVID-19, likely due to a transient reduction in elective surgery as well as practice and policy changes triggered by pandemic concerns.


Subject(s)
COVID-19 , Blood Platelets , British Columbia , Elective Surgical Procedures , Humans , SARS-CoV-2
13.
J Clin Invest ; 132(4)2022 02 15.
Article in English | MEDLINE | ID: covidwho-1685790

ABSTRACT

Infection with SARS-CoV-2, the causative agent of COVID-19, causes mild to moderate disease in most patients but carries a risk of morbidity and mortality. Seriously affected individuals manifest disorders of hemostasis and a cytokine storm, but it is not understood how these manifestations of severe COVID-19 are linked. Here, we showed that the SARS-CoV-2 spike protein engaged the CD42b receptor to activate platelets via 2 distinct signaling pathways and promoted platelet-monocyte communication through the engagement of P selectin/PGSL-1 and CD40L/CD40, which led to proinflammatory cytokine production by monocytes. These results explain why hypercoagulation, monocyte activation, and a cytokine storm are correlated in patients severely affected by COVID-19 and suggest a potential target for therapeutic intervention.


Subject(s)
Blood Platelets/physiology , COVID-19/blood , Inflammation/blood , Monocytes/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/physiology , Blood Platelets/metabolism , CD40 Antigens/blood , CD40 Ligand/blood , Cell Communication , Cytokine Release Syndrome , Cytokines , HEK293 Cells , Humans , P-Selectin/blood
14.
Blood Cells Mol Dis ; 94: 102653, 2022 05.
Article in English | MEDLINE | ID: covidwho-1676413

ABSTRACT

Abnormal coagulation dynamics, including disseminated intravascular coagulopathy, pulmonary embolism, venous thromboembolism and risk of thrombosis are often associated with the severity of COVID-19. However, very little is known about the contribution of platelets in above pathogenesis. In order to decipher the pathophysiology of thrombophilia in COVID-19, we recruited severely ill patients from ICU, based on the above symptoms and higher D-dimer levels, and compared these parameters with their asymptomatic counterparts. Elevated levels of platelet-derived microparticles and platelet-leukocyte aggregates suggested the hyperactivation of platelets in ICU patients. Strikingly, platelet transcriptome analysis showed a greater association of IL-6 and TNF signalling pathways in ICU patients along with higher plasma levels of IL-6 and TNFα. In addition, upregulation of pathways like blood coagulation and hemostasis, as well as inflammation coexisted in platelets of these patients. Further, the increment of necrotic pathway and ROS-metabolic processes in platelets was suggestive of its procoagulant phenotype in ICU patients. This study suggests that higher plasma IL-6 and TNFα may trigger platelet activation and coagulation, and in turn aggravate thrombosis and hypercoagulation in severe COVID-19 patients. Therefore, the elevated IL-6 and TNFα, may serve as potential risk factors for platelet activation and thrombophilia in these patients.


Subject(s)
COVID-19 , Cell-Derived Microparticles , Thrombophilia , Blood Platelets/metabolism , COVID-19/complications , Cell-Derived Microparticles/metabolism , Cytokines/metabolism , Humans , SARS-CoV-2 , Thrombophilia/complications , Up-Regulation
15.
Clin Lab ; 68(3)2022 Mar 01.
Article in English | MEDLINE | ID: covidwho-1675214

ABSTRACT

BACKGROUND: Covid-19 is a pandemic viral infection with high pathogenicity and contagiousness. Our aim is to evaluate the preliminary hematological findings analyzed during admission in order to determine the diagnostic value of hematological parameters in Covid-19 patients and to reveal their relationship with the severity of the disease. METHODS: Our study includes a total of 169 patients, whose diagnosis was confirmed and 93 of whom were treated in the ward, 76 of whom were treated in the Intensive Care Unit (ICU), and 67 control patients. Neutrophil-to-lymphocyte ratio (NLR), monocyte-lymphocyte (MLR) ratio, platelet-lymphocyte ratio (PLR), mean platelet volume/platelet count ratio (MPV/PLT) data on admission were analyzed retrospectively and compared. RESULTS: ICU patients had significantly higher values of NLR, MLR, PLR, and MPV/PLT (p < 0.001 for each) but had lower values of lymphocyte count and hemoglobin (p < 0.001 for each) compared to that of ward patients. According to the results of ROC analysis, the diagnostic values of NLR, MLR, PLR, and MPV/PLT parameters were statistically significant (p < 0.05). CONCLUSIONS: According to the results of our study, abnormal routine peripheral blood examination results were detected in Covid-19 patients. NLR, MLR, and PLR can be considered as independent, reliable biomarkers for assessing disease severity, hospitalization, and clinical classification in Covid-19. Therefore, it was concluded that fast, cost-effective, easily accessible admission hemogram parameters are reasonably important to predict the prognosis of Covid-19 patients.


Subject(s)
COVID-19 , Neutrophils , Blood Platelets , COVID-19/diagnosis , Humans , Lymphocytes , Monocytes , Retrospective Studies , SARS-CoV-2
16.
Int J Mol Sci ; 23(3)2022 Feb 05.
Article in English | MEDLINE | ID: covidwho-1674671

ABSTRACT

Inflammation and thrombosis are closely intertwined in numerous disorders, including ischemic events and sepsis, as well as coronavirus disease 2019 (COVID-19). Thrombotic complications are markers of disease severity in both sepsis and COVID-19 and are associated with multiorgan failure and increased mortality. Immunothrombosis is driven by the complement/tissue factor/neutrophil axis, as well as by activated platelets, which can trigger the release of neutrophil extracellular traps (NETs) and release further effectors of immunothrombosis, including platelet factor 4 (PF4/CXCL4) and high-mobility box 1 protein (HMGB1). Many of the central effectors of deregulated immunothrombosis, including activated platelets and platelet-derived extracellular vesicles (pEVs) expressing PF4, soluble PF4, HMGB1, histones, as well as histone-decorated NETs, are positively charged and thus bind to heparin. Here, we provide evidence that adsorbents functionalized with endpoint-attached heparin efficiently deplete activated platelets, pEVs, PF4, HMGB1 and histones/nucleosomes. We propose that this elimination of central effectors of immunothrombosis, rather than direct binding of pathogens, could be of clinical relevance for mitigating thrombotic complications in sepsis or COVID-19 using heparin-functionalized adsorbents.


Subject(s)
Blood Proteins/isolation & purification , Heparin/pharmacology , /drug therapy , Blood Coagulation/physiology , Blood Platelets/metabolism , Blood Proteins/metabolism , COVID-19/metabolism , Extracellular Traps/immunology , Extracellular Traps/metabolism , HMGB Proteins/isolation & purification , HMGB Proteins/metabolism , HMGB1 Protein/isolation & purification , HMGB1 Protein/metabolism , Heparin/metabolism , Histones/isolation & purification , Histones/metabolism , Humans , Neutrophils/metabolism , Platelet Activation/immunology , Platelet Factor 4/isolation & purification , Platelet Factor 4/metabolism , SARS-CoV-2/pathogenicity , Sepsis/blood , Sepsis/metabolism , Thromboplastin/metabolism , Thrombosis/drug therapy
17.
Int J Mol Sci ; 22(16)2021 Aug 10.
Article in English | MEDLINE | ID: covidwho-1662672

ABSTRACT

BACKGROUND: Today there are many devices that can be used to study blood clotting disorders by identifying abnormalities in blood platelets. The Total Thrombus Formation Analysis System is an automated microchip flow chamber system that is used for the quantitative analysis of clot formation under blood flow conditions. For several years, researchers have been using a tool to analyse various clinical situations of patients to identify the properties and biochemical processes occurring within platelets and their microenvironment. METHODS: An investigation of recent published literature was conducted based on PRISMA. This review includes 52 science papers directly related to the use of the Total Clot Formation Analysis System in relation to bleeding, surgery, platelet function assessment, anticoagulation monitoring, von Willebrand factor and others. CONCLUSION: Most available studies indicate that The Total Thrombus Formation Analysis System may be useful in diagnostic issues, with devices used to monitor therapy or as a significant tool for predicting bleeding events. However, T-TAS not that has the potential for diagnostic indications, but allows the direct observation of the flow and the interactions between blood cells, including the intensity and dynamics of clot formation. The device is expected to be of significant value for basic research to observe the interactions and changes within platelets and their microenvironment.


Subject(s)
Blood Coagulation , Blood Platelets/physiology , Lab-On-A-Chip Devices/standards , Microfluidics/methods , Thrombosis/blood , Blood Platelets/metabolism , Humans , Microfluidics/instrumentation , Thrombosis/diagnosis
18.
Pathol Res Pract ; 231: 153782, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1655042

ABSTRACT

The novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 outbreak, spread rapidly and infected more than 140 million people with more than three million victims worldwide. The SARS-CoV-2 causes destructive changes in the immunological and hematological system of the host. These alterations appear to play a critical role in disease pathology and the emerging of clinical manifestations. In this review, we aimed to discuss the effect of COVID-19 on the count, function and morphology of immune and blood cells and the role of these changes in the pathophysiology of the disease. Knowledge of these changes may help with better management and treatment of COVID-19 patients.


Subject(s)
Blood Platelets/virology , Erythrocytes/virology , Granulocytes/virology , Monocytes/virology , SARS-CoV-2 , COVID-19/blood , COVID-19/virology , Cell Count , Cell Shape , Humans
19.
J Am Soc Nephrol ; 33(2): 259-278, 2022 02.
Article in English | MEDLINE | ID: covidwho-1650730

ABSTRACT

Kidney disease is a known risk factor for poor outcomes of COVID-19 and many other serious infections. Conversely, infection is the second most common cause of death in patients with kidney disease. However, little is known about the underlying secondary immunodeficiency related to kidney disease (SIDKD). In contrast to cardiovascular disease related to kidney disease, which has triggered countless epidemiologic, clinical, and experimental research activities or interventional trials, investments in tracing, understanding, and therapeutically targeting SIDKD have been sparse. As a call for more awareness of SIDKD as an imminent unmet medical need that requires rigorous research activities at all levels, we review the epidemiology of SIDKD and the numerous aspects of the abnormal immunophenotype of patients with kidney disease. We propose a definition of SIDKD and discuss the pathogenic mechanisms of SIDKD known thus far, including more recent insights into the unexpected immunoregulatory roles of elevated levels of FGF23 and hyperuricemia and shifts in the secretome of the intestinal microbiota in kidney disease. As an ultimate goal, we should aim to develop therapeutics that can reduce mortality due to infections in patients with kidney disease by normalizing host defense to pathogens and immune responses to vaccines.


Subject(s)
COVID-19/etiology , Immunologic Deficiency Syndromes/etiology , Renal Insufficiency, Chronic/complications , Adaptive Immunity , Blood Platelets/immunology , COVID-19/immunology , COVID-19 Vaccines/immunology , Gastrointestinal Microbiome/immunology , Humans , Immunity, Innate , Immunologic Deficiency Syndromes/immunology , Immunologic Deficiency Syndromes/prevention & control , Immunophenotyping , Models, Immunological , Pandemics , Renal Insufficiency, Chronic/immunology , Risk Factors , SARS-CoV-2 , Seroconversion
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