scholarly journals COVID-19 induces a hyperactive phenotype in circulating platelets

2020 ◽  
Author(s):  
Shane P Comer ◽  
Sarah Cullivan ◽  
Paulina B Szklanna ◽  
Luisa Weiss ◽  
Steven Cullen ◽  
...  
Keyword(s):  
Intensive Care ◽  
Platelet Function ◽  
Clinical Laboratory ◽  
Platelet Reactivity ◽  
Severe Disease ◽  
Blood Parameters ◽  
Full Blood Count ◽  
Specific Marker ◽  
Platelet Activity ◽  
Thrombotic Risk

Background Coronavirus disease 2019 (COVID-19), caused by novel coronavirus SARS-CoV-2, has to date affected over 13.3 million globally. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Objectives Here, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and non-severe COVID-19. Methods An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with non-severe disease (not requiring intensive care), general medical in-patients without COVID-19 and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. Results We show that routine clinical blood parameters including increased MPV and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit admission. Strikingly, agonist-induced ADP release was dramatically higher in COVID-19 patients compared with non-COVID-19 hospitalized patients and circulating levels of PF4, sP-selectin and TPO were also significantly elevated in COVID-19. Conclusion Distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and non-severe COVID-19. Moreover, we have determined that COVID-19 patients possess hyperactive circulating platelets. These data suggest that abnormal platelet reactivity may contribute to hypercoagulability in COVID-19. Further investigation of platelet function in COVID-19 may provide additional insights into the aetiology of thrombotic risk in this disease and may contribute to the optimisation of thrombosis prevention and treatment strategies.

scholarly journals COVID-19 induces a hyperactive phenotype in circulating platelets

PLoS Biology ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. e3001109
Author(s):  
Shane P. Comer ◽  
Sarah Cullivan ◽  
Paulina B. Szklanna ◽  
Luisa Weiss ◽  
Steven Cullen ◽  
...  
Keyword(s):  
Intensive Care ◽  
Clinical Laboratory ◽  
Platelet Reactivity ◽  
Blood Parameters ◽  
Full Blood Count ◽  
Specific Marker ◽  
Platelet Activity ◽  
Platelet Factor ◽  
Thrombotic Risk ◽  
Severity Of The Disease

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has affected over 30 million globally to date. Although high rates of venous thromboembolism and evidence of COVID-19-induced endothelial dysfunction have been reported, the precise aetiology of the increased thrombotic risk associated with COVID-19 infection remains to be fully elucidated. Therefore, we assessed clinical platelet parameters and circulating platelet activity in patients with severe and nonsevere COVID-19. An assessment of clinical blood parameters in patients with severe COVID-19 disease (requiring intensive care), patients with nonsevere disease (not requiring intensive care), general medical in-patients without COVID-19, and healthy donors was undertaken. Platelet function and activity were also assessed by secretion and specific marker analysis. We demonstrated that routine clinical blood parameters including increased mean platelet volume (MPV) and decreased platelet:neutrophil ratio are associated with disease severity in COVID-19 upon hospitalisation and intensive care unit (ICU) admission. Strikingly, agonist-induced ADP release was 30- to 90-fold higher in COVID-19 patients compared with hospitalised controls and circulating levels of platelet factor 4 (PF4), soluble P-selectin (sP-selectin), and thrombopoietin (TPO) were also significantly elevated in COVID-19. This study shows that distinct differences exist in routine full blood count and other clinical laboratory parameters between patients with severe and nonsevere COVID-19. Moreover, we have determined all COVID-19 patients possess hyperactive circulating platelets. These data suggest abnormal platelet reactivity may contribute to hypercoagulability in COVID-19 and confirms the role that platelets/clotting has in determining the severity of the disease and the complexity of the recovery path.

Reproducibility of Platelet Functional Assays under Agonist and Shear Conditions - Methods for Characterizing Platelet Reactivity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3531-3531
Author(s):  
Donald L. Yee ◽  
Angela Bergeron ◽  
Carol Sun ◽  
William May ◽  
Jennifer Wood ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Clinical Laboratory ◽  
Interindividual Variability ◽  
Platelet Reactivity ◽  
Bimodal Distribution ◽  
Variance Component Analysis ◽  
Repeated Testing ◽  
Thrombotic Risk ◽  
Functional Assays

Abstract Clinical laboratory tests that reliably measure the contribution of platelets to thrombotic risk are virtually non-existent. Optimal testing of “platelet hyperreactivity” requires assays that are able to identify reproducible differences among individuals. We have studied over 280 healthy individuals with a panel of over 100 assays of platelet function. This panel includes measurements of aggregation, activation, receptor density and other candidate markers of platelet reactivity. Platelets were studied under conditions of agonist stimulation (including arachidonic acid, ADP, epinephrine, collagen, collagen related peptide and ristocetin) and under shear (from 0 to 10,000 sec-1). We assessed the reproducibility of these assays by studying a subgroup of 27 individuals (mean age=33 years, range=24–53 years, 30% males) four times each (108 total sets of studies). The time between each phlebotomy was one week. Subjects were asked to fast overnight and to refrain from certain exposures (e.g. heavy exercise, caffeine use) immediately prior to testing. The reproducibility of assay results was assessed using variance component analysis. We observed significant interindividual variability in most assays of platelet aggregation and activation. We established agonist concentrations that yield wide interindividual variability in maximal platelet aggregation. When these data are depicted on a histogram, a bimodal distribution is observed, with one group of subjects clearly demonstrating lower inherent aggregation (< 40%) and the other group exhibiting higher levels (>60%) (see figure for epinephrine example). We determined shear rates (0 to 2000 sec-1) and identified platelet receptors (CD32, GPIa-IIa, GPIb-IX-V) and markers of platelet activation (CD62P under shear and ADP stimulation) that maximized detection of differences between individuals while minimizing variations within subjects. Individual subjects demonstrated consistent results over time on repeated testing. We have thus identified a subset of platelet assays that demonstrate striking interindividual variability (overall coefficients of variation range from 0.15 to 0.9) while maintaining good reproducibility (contribution of intraindividual to overall variance < 35%). Other functional assays we have tested demonstrated poor reproducibility, such that they should not be utilized as measures of platelet reactivity. Using assay conditions and techniques not routinely utilized in clinical practice (but that could easily be adapted for such use), we have shown that different individuals demonstrate distinct levels of platelet reactivity. Despite only minimal restrictions on environmental exposures for these healthy subjects studied repeatedly over several weeks, these assays appear to reliably characterize individuals’ platelet reactivity and are appropriate candidates for its measurement in populations of patients at risk for thrombosis or bleeding. As these assays facilitate categorization of platelet reactivity, they may also be useful for the study of genetic and environmental influences on platelet function. Figure Figure

scholarly journals A Study of Haemostatic Parameters in Patients with Philadelphia-Negative Myeloproliferative Neoplasms. Correlation with, Clinical, Laboratory, Molecular, and Treatment Characteristics

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4304-4304
Author(s):  
Nefeli Giannakopoulou ◽  
Marianna Politou ◽  
Panagiotis Theodorou Diamantopoulos ◽  
Dimitris Korakakis ◽  
Maria Efstathopoulou ◽  
...  
Keyword(s):  
Platelet Function ◽  
Clinical Laboratory ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Molecular Characteristics ◽  
Healthy Controls ◽  
Vascular Events ◽  
Thrombotic Risk ◽  
Symptomatic Carotid Stenosis ◽  
Α Angle

Abstract Introduction Patients with Philadelphia-negative myeloproliferative neoplasms (PN-MPN) namely polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (MF) are at a higher risk for arterial and venous thrombosis that constitute a major cause of morbidity and mortality. Global coagulation assays such as thromboelastography, may be more efficient to evaluate the patient's thrombotic risk. The aim of the present study was to examine the hemostatic profile of patients with PN-MPN and correlate it with clinical, laboratory, treatment, and molecular characteristics including mutational analysis of JAK2, MPL, CALR, and polymorphisms of poly(ADP ribose) polymerase (PARP1), since a correlation of specific mutations with PARP1 polymorphisms has been reported in the literature. Materials and methods The study included adult patients with a confirmed diagnosis of PN-MPN according to the revised 2016 WHO classification. A written informed consent was obtained from all patients. The presence of splenomegaly, vascular events, PN-MPN specific therapy, and anticoagulation treatment were recorded. All the patients were assessed with complete blood count, routine coagulation tests [PT, INR, aPTT and fibrinogen, D-Dimers analyzed with the automatic coagulation analyzer Sysmex (Siemens)], platelet function performed with PFA-100 (COL, EPI, ADP), and global hemostatic potential assessed with ROTEM® Tromboelastometry (EXTEM), recording clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), lysis index at 30 (LI30) and 60 (LI60) minutes, and α angle. Mutation profiles of JAK2, MPL and CALR were defined using peripheral blood DNA. JAK2 and MPL mutations were detected using a standard PCR and CALR mutations using an HRMA-PCR assay. The rs1136410/PARP-1 (V762A) single nucleotide polymorphism (SNP), was detected with an RFLP method using the enzyme AciΙ (New England Biolabs, USA) and the digestion products were evaluated by polyacrylamide gel electrophoresis. Statistical analysis was performed using IBM SPSS statistics, version 23.0 (IBM Corporation, North Castle, NY, USA). Results Seventy-four patients were included in the study (22 PV, 47 ET, 5 MF) with a median age of 63 years (25-87) and 68 healthy controls for the SNP/PARP1 study. At the time of sample collection, 71 (95.9%) patients were under treatment [hydroxyurea (HU), 57 (77.0%); anagrelide, 19 (25.7%); ruxolitinib, 9 (12.2%); interferon alpha, 2 (2.7%); an alkylating agent, 4 (5.4%)]. In terms of anticoagulation, 47 (63.5%) patients were on aspirin, 4 (5.4%) on clopidogrel, 7 (9.5%) on a combination of the two, 3 (4.1%) on a vitamin K antagonist, and 2 (2.7%) on a Xa-inhibitor. Twenty-two (29.7%) patients had abnormally high D-Dimers (>0,5mg/l). Nineteen (25.7%) patients had developed thrombosis after diagnosis (8, ischemic stroke; 4, coronary artery disease (CAD); 3, deep vein thrombosis (DVT); 1, symptomatic carotid stenosis; 2, a combination of stroke and CAD; 1, a combination of CAD and DVT). Among 69 patients who were not receiving anticoagulation, 5 (7,2%) had an abnormal CT, 4 (5,7%) had abnormal CFT, 3 (4,3%) had an increased α angle, and 18 (26%) had an increased MCF value. Women had shorter CFT, higher α angle, and higher MCF (p<0.05 for all parameters). Patients with ET had higher MCF compared to PV and MF. Patients with mutated JAK2, CALR, or MPL had higher WBC and shorter CFT (p<0.05). Patients receiving anagrelide or alkylating agents, had statistically significant shorter CFTs, higher α angles, and higher MCFs compared to the ones receiving HU. Among 54 patients taking aspirin COL-EPI was normal in 10. Among 11 patients taking clopidogrel COL-ADP was normal in 5, implying that the antiplatelet treatment may not be sufficient in certain cases. No correlations were found between PARP1 polymorphic status and any of the studied parameters, nor between patients and healthy controls. Discussion Global assays such as thromboelastography are more useful than conventional hemostatic laboratory tests in depicting the hypercoagulable state in MPN. They may be useful in combination with other parameters such as the mutational status in identifying patients with MPN at higher risk for thrombosis and guide clinicians for the type of treatment (both cytoreductive and anticoagulants). Tests of platelet function assessment may help the clinicians adjust the type and dose of antiplatelet therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Intensive care risk estimation in COVID-19 pneumonia based on clinical and imaging parameters: experiences from the Munich cohort

2020 ◽  
Author(s):  
Egon Burian ◽  
Friederike Jungmann ◽  
Georgios A. Kaissis ◽  
Fabian K. Lohöfer ◽  
Christoph D. Spinner ◽  
...  
Keyword(s):  
Intensive Care ◽  
Clinical Laboratory ◽  
Risk Estimation ◽  
Severe Disease ◽  
Lung Parenchyma ◽  
Diagnostic Tools ◽  
Imaging Data ◽  
Forest Modelling ◽  
Imaging Parameters ◽  
Icu Treatment

AbstractThe evolving dynamics of coronavirus disease 2019 (COVID-19) and the increasing infection numbers require diagnostic tools to identify patients at high risk for a severe disease course. Here we evaluate clinical and imaging parameters for estimating the need of intensive care unit (ICU) treatment. We collected clinical, laboratory and imaging data from 65 patients with confirmed COVID-19 infection based on PCR testing. Two radiologists evaluated the severity of findings in computed tomography (CT) images on a scale from 1 (no characteristic signs of COVID-19) to 5 (confluent ground glass opacities in over 50% of the lung parenchyma). The volume of affected lung was quantified using commercially available software. Machine learning modelling was performed to estimate the risk for ICU treatment. Patients with a severe course of COVID-19 had significantly increased IL-6, CRP and leukocyte counts and significantly decreased lymphocyte counts. The radiological severity grading was significantly increased in ICU patients. Multivariate random forest modelling showed a mean ± standard deviation sensitivity, specificity and accuracy of 0.72 ± 0.1, 0.86 ± 0.16 and 0.80 ± 0.1 and a ROC-AUC of 0.79 ± 0.1.The need for ICU treatment is independently associated with affected lung volume, radiological severity score, CRP and IL-6.

Platelet Function in CKD: A Systematic Review and Meta-Analysis

2021 ◽  
pp. ASN.2020101440
Author(s):  
Constance C.F.M.J. Baaten ◽  
Marieke Sternkopf ◽  
Tobias Henning ◽  
Nikolaus Marx ◽  
Joachim Jankowski ◽  
...  
Keyword(s):  
Systematic Review ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Meta Analysis ◽  
Uremic Toxins ◽  
Extensive Literature ◽  
Direct Effects ◽  
Platelet Activity

BackgroundPatients with CKD are at high risk for thrombotic and hemorrhagic complications. Abnormalities in platelet function are central to these complications, but reports on platelet function in relation to CKD are conflicting, and vary from decreased platelet reactivity to normal or increased platelet responsiveness. The direct effects of uremic toxins on platelet function have been described, with variable findings.MethodsTo help clarify how CKD affects platelet function, we conducted a systematic review and meta-analysis of platelet activity in CKD, with a focus on nondialysis-induced effects. We also performed an extensive literature search for the effects of individual uremic toxins on platelet function.ResultsWe included 73 studies in the systematic review to assess CKD’s overall effect on platelet function in patients; 11 of them described CKD’s effect on ex vivo platelet aggregation and were included in the meta-analysis. Although findings on platelet abnormalities in CKD are inconsistent, bleeding time was mostly prolonged and platelet adhesion mainly reduced. Also, the meta-analysis revealed maximal platelet aggregation was significantly reduced in patients with CKD upon collagen stimulation. We also found that relatively few uremic toxins have been examined for direct effects on platelets ex vivo; ex vivo analyses had varying methods and results, revealing both platelet-stimulatory and inhibitory effects. However, eight of the 12 uremic toxins tested in animal models mostly induced prothrombotic effects.ConclusionsOverall, most studies report impaired function of platelets from patients with CKD. Still, a substantial number of studies find platelet function to be unchanged or even enhanced. Further investigation of platelet reactivity in CKD, especially during different CKD stages, is warranted.

Residual platelet reactivity is an independent predictor of myocardial injury in acute myocardial infarction patients on antiaggregant therapy

2007 ◽  
Vol 98 (10) ◽  
pp. 844-851 ◽  
Author(s):  
Rita Paniccia ◽  
Emilia Antonucci ◽  
Serena Poli ◽  
Anna Maria Gori ◽  
Serafina Valente ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Platelet Function ◽  
Clinical Laboratory ◽  
Independent Predictor ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Antiplatelet Agents ◽  
The Other ◽  
Group A ◽  
Group B

SummaryIn this study we sought to evaluate if platelet function measured after percutaneous coronary intervention (PCI) affects the severity of myocardial infarction (MI), measured by markers of cardiac necrosis. We measured platelet function by both a point-of-care assay (PFA-100) and platelet-rich plasma aggregation by two agonists (arachidonic acid –AA- and 2 and 10 μM ADP) in 367 patients with MI after PCI (200 patients on dual antiplatelet agents – group A- and 167 on dual antiplatelet agents plus GpIIb/ IIIa inhibitors – group B). One hundred twenty-one (32.9%) patients were found to have a residual platelet reactivity (RPR) by PFA (CT/EPI <203 sec): 74/200 (37%) in group A and 47/167 (28.1%) in group B (p=0.07). In 129 (35.1%) patients we found a RPR by AA-PA: 80/200 (40%) in group A and 49/167 (29.3%) in group B (p<0.05). Seventeen out of 367 (4.6%) were found to have a RPR by ADP2-PA [15/200 (7.5%) in group A and 2/167 (1.2%) in group B; p<0.005] and 88/367 (23.9%) by ADP10-PA [64/200 (32%) in group A and 24/167 (14.4%) in group B, p<0.0001]. CK-MB and cTnI mean peak values were significantly higher in the first tertile of CT/ADP and CT/EPI distribution with respect to the other tertiles and they were significantly higher in patients with RPR by CT/EPI in both groupA and group B patients. CK-MB and cTnI peak values were significantly higher in the third tertile of AA-PA,ADP 2 μM-PA and ADP 10 μM-PA distribution with respect to the other tertiles and were significantly higher in patients with RPR by AA-PA and by ADP 10-PA in both group A and group B patients. Multivariate analysis revealed platelet function as an independent predictor of CK-MB and cTnI peak values in both groups of patients independently of clinical, laboratory ad procedural parameters. In conclusion, we found that the severity of MI in patients with MI undergoing primary PCI is influenced by a persistent platelet activation on multiple antiplatelet therapy.

P2481The effect of DPP-4i, GLP-1RA, SGLT-2i and long-acting insulin on platelet function in patients with type 2 diabetes mellitus

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P K Stampouloglou ◽  
A Antonopoulos ◽  
G Siasos ◽  
E Bletsa ◽  
K Batzias ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Glycosylated Hemoglobin ◽  
Treatment Intensification ◽  
Antiplatelet Treatment ◽  
Thrombotic Risk

Abstract Background Patients with type 2 diabetes mellitus (T2DM) are at higher risk for thrombotic events. Platelet function may be used to assess prothrombotic state in patients with cardiovascular disease. Purpose We aimed to investigate whether the administration of novel antidiabetic agents influence platelet function in TDM2 patients. Patients and methods We 60 enrolled consecutive patients with T2DM, on stable antidiabetic therapy, who did not achieve therapeutic targets. Subjects were assessed to receive an additional anti-diabetic agent; dipeptidyl peptidase-4 inhibitor (DPP4i, n=14), glucagon like peptide-1 receptor agonist (GLP1RA, n=24), sodium/glucose cotransporter-2 inhibitor (SGLT2i, n=22). Platelet reactivity was measured with PFA-200 collagen/epinephrine (c-EPI) and PFA-200 collagen/ADP (c-ADP) closure time. Glycosylated hemoglobin (HbA1c), c-EPI and c-ADP were assessed at baseline and 3 months after treatment intensification. Results There was no difference between the study groups regarding gender, age, hypertension, dyslipidemia, smoking, Hba1c and CADP or CEPI (p=NS for all) at baseline. All groups achieved better glycemic control in terms of HbA1c values between baseline and follow-up (for DPP4i: 7.4±0.2% vs 6.7±0.2%, for GLP1RA: 8.3±0.2% vs 6.9±0.1%, for SGLT2i: 7.5±0.1% vs 6.7±0.1% and for insulin 9.8±0.5% vs 7.7±0.4%, p<0.001 for all). After a 3 month-period, treatment intensification with these novel agents did not influence c-EPI and c-ADP values [155.4±6.64 sec vs 152.9±8.28 sec (p=0.678) and 106.6±4.30 sec vs 106.8±3.93 sec (p=0.955) respectively] in whole population. In subgroup analysis, for patients off antiplatelet treatment (n=31), c-EPI was significantly decreased from 148.4±8.5 to 129.8±13.9 sec (p=0.036), but not c-ADP (from 105.4±5.3 to 99.3±4.9 sec, p=0.094). In patients who did receive antiplatelets (n=37), c-EPI and c-ADP were not significantly changed (c-EPI 163.1±10.9 to 179.6±13.9 sec p=0.201 and c-ADP from 106.6±8.2 sec to 114.6±7.3 sec, p=0.318) respectively. Conclusion Antiplatelet treatment prevents thrombotic risk in T2DM patients receiving novel antidiabetics. The effects of novel antidiabetics on platelet reactivity -as well as any distinct class properties- merits further investigation. Acknowledgement/Funding None

scholarly journals PLGA-PEG Nanoparticles Show Minimal Risks of Interference with Platelet Function of Human Platelet-Rich Plasma

2020 ◽  
Vol 21 (24) ◽  
pp. 9716
Author(s):  
Rana Bakhaidar ◽  
Sarah O’Neill ◽  
Zebunnissa Ramtoola
Keyword(s):  
Drug Delivery ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
Platelet Activity ◽  
Blood Constituents ◽  
Activation Profile ◽  
The Impact

The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0–2.2 mg/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations ≥0.25 mg/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.

scholarly journals 12-lipoxygenase activity plays an important role in PAR4 and GPVI-mediated platelet reactivity

2013 ◽  
Vol 110 (09) ◽  
pp. 569-581 ◽  
Author(s):  
Jennifer Yeung ◽  
Patrick L. Apopa ◽  
Joanne Vesci ◽  
Moritz Stolla ◽  
Ganesha Rai ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Activation ◽  
Platelet Function ◽  
Platelet Reactivity ◽  
Selective Inhibition ◽  
Platelet Activity ◽  
12 Lipoxygenase ◽  
Deficient Mice ◽  
Cox 1

SummaryFollowing initial platelet activation, arachidonic acid is metabolised by cyclooxygenase-1 and 12-lipoxygenase (12-LOX). While the role of 12-LOX in the platelet is not well defined, recent evidence suggests that it may be important for regulation of platelet activity and is agonist- specific in the manner in which it regulates platelet function. Using small molecule inhibitors selective for 12-LOX and 12-LOX-deficient mice, the role of 12-LOX in regulation of human platelet activation and thrombosis was investigated. Pharmacologically inhibiting 12-LOX resulted in attenuation of platelet aggregation, selective inhibition of dense versus alpha granule secretion, and inhibition of platelet adhesion under flow for PAR4 and collagen. Additionally, 12-LOX-deficient mice showed attenuated integrin activity to PAR4-AP and convulxin compared to wild-type mice. Finally, platelet activation by PARs was shown to be differentially dependent on COX-1 and 12-LOX with PAR1 relying on COX-1 oxidation of arachidonic acid while PAR4 being more dependent on 12-LOX for normal platelet function. These studies demonstrate an important role for 12-LOX in regulating platelet activation and thrombosis. Furthermore, the data presented here provide a basis for potentially targeting 12-LOX as a means to attenuate unwanted platelet activation and clot formation.

scholarly journals Intensive Care Risk Estimation in COVID-19 Pneumonia Based on Clinical and Imaging Parameters: Experiences from the Munich Cohort

2020 ◽  
Vol 9 (5) ◽  
pp. 1514 ◽  
Author(s):  
Egon Burian ◽  
Friederike Jungmann ◽  
Georgios A. Kaissis ◽  
Fabian K. Lohöfer ◽  
Christoph D. Spinner ◽  
...  
Keyword(s):  
Intensive Care ◽  
Clinical Laboratory ◽  
Risk Estimation ◽  
Severe Disease ◽  
Lung Parenchyma ◽  
Diagnostic Tools ◽  
Imaging Data ◽  
Forest Modelling ◽  
Imaging Parameters ◽  
Icu Treatment

The evolving dynamics of coronavirus disease 2019 (COVID-19) and the increasing infection numbers require diagnostic tools to identify patients at high risk for a severe disease course. Here we evaluate clinical and imaging parameters for estimating the need of intensive care unit (ICU) treatment. We collected clinical, laboratory and imaging data from 65 patients with confirmed COVID-19 infection based on polymerase chain reaction (PCR) testing. Two radiologists evaluated the severity of findings in computed tomography (CT) images on a scale from 1 (no characteristic signs of COVID-19) to 5 (confluent ground glass opacities in over 50% of the lung parenchyma). The volume of affected lung was quantified using commercially available software. Machine learning modelling was performed to estimate the risk for ICU treatment. Patients with a severe course of COVID-19 had significantly increased interleukin (IL)-6, C-reactive protein (CRP), and leukocyte counts and significantly decreased lymphocyte counts. The radiological severity grading was significantly increased in ICU patients. Multivariate random forest modelling showed a mean ± standard deviation sensitivity, specificity and accuracy of 0.72 ± 0.1, 0.86 ± 0.16 and 0.80 ± 0.1 and a receiver operating characteristic-area under curve (ROC-AUC) of 0.79 ± 0.1. The need for ICU treatment is independently associated with affected lung volume, radiological severity score, CRP, and IL-6.

Sign in / Sign up

Export Citation Format

Share Document