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.

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.

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

Effects of Ticlopidine of Platelet Function in Men with Stable Angina Pectoris

1985 ◽  
Vol 54 (04) ◽  
pp. 808-812 ◽  
Author(s):  
Ulf Berglund ◽  
Henning von Schenck ◽  
Lars Wallentin
Keyword(s):  
Platelet Aggregation ◽  
Angina Pectoris ◽  
Platelet Function ◽  
Plasma Levels ◽  
Platelet Reactivity ◽  
Inhibitory Effect ◽  
Controlled Study ◽  
Double Blind ◽  
Platelet Factor

SummaryThe effects of ticlopidine (T) (500 mg daily) on platelet function were investigated in a double-blind placebo-controlled study in 38 middle-aged men with stable incapacitating angina pectoris. The in vitro platelet reactivity to aggregating agents, the platelet sensitivity to prostacyclin and the plasma levels of platelet specific proteins and fibrinogen were determined before and after 4 and 8 weeks of treatment. T exerted a potent inhibitory effect on ADP- and collagen-induced platelet aggregation. The effect of T was proportional to the pretreatment reactivity to ADP and collagen. The inhibitory effect of T on the epinephrine response was less pronounced. The plasma levels of beta-thromboglobulin, platelet factor 4 and fibrinogen were not influenced by T. The platelet inhibition of prostacyclin was potentiated by T, and it was demonstrated that T and prostacyclin had synergistic inhibitory effects on platelet aggregation.

PO-38 Thrombotic risk factors in intensive care unit patients from a cancer hospital: a prospective evaluation

2010 ◽  
Vol 125 ◽  
pp. S176
Author(s):  
E. de Meis ◽  
M.M. Rosolem ◽  
S.G. Silva ◽  
L.S.G. Rabello ◽  
D.B.S. Azevedo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Prospective Evaluation ◽  
Thrombotic Risk ◽  
Cancer Hospital

Abstract 137: Thromboinflammatory Response in Patients Undergoing Transcatheter Aortic Valve Replacement Using the Sapien Xt or CoreValve

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Travis R Sexton ◽  
John Liu ◽  
Susan S Smyth
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Valve Replacement ◽  
Transcatheter Aortic Valve Replacement ◽  
Inflammatory Marker ◽  
Platelet Activity ◽  
Platelet Factor ◽  
Beneficial Effects ◽  
Transcatheter Aortic Valve ◽  
Medtronic Corevalve

Transcatheter aortic valve replacement (TAVR) has been increasingly used to treat patients with symptomatic aortic stenosis. Despite the evolution of the valves and their deployment, patients that have undergone TAVR continue to be at high risk for major adverse events following the procedure. We recently reported that TAVR elicits a thromboinflammatory state that may contribute to the observed post-procedural thrombocytopenia associated with worse clinical outcomes. With the approval of the newer generation valves and delivery systems, we have now compared thromboinflammatory responses in patients receiving the Medtronic CoreValve and Edward’s new SAPIEN XT valve. Blood cell numbers, platelet function, and biomarkers of systemic inflammation and thrombosis were analyzed in 34 sequential patients undergoing transcatheteraortic valve replacement with the Edward’s SAPIEN XT valve or the Medtronic CoreValve Following valve deployment, platelet count, platelet activity, and platelet factor 4 levels decreased, while the inflammatory marker interleukin-6 increased. There were no significant differences in any of the parameters between the two valve types. Interestingly, baseline inflammation status predicted the extent of thrombocytopenia observed in overall cohort. A comparions of the SAPIENT XT valve and the Medtronic CoreValve reveals that the new generation valves generate a lower inflammatory response than that observed in the older SAPIEN valce. Importantly, our results add to the growing body of literature that suggests the thromboinflammatory changes that occur early after TAVR may predict long-term outcomes and suggest potential beneficial effects of an anti-inflammatory strategic.

Off Target: Case Report of Heparin Resistance in a Neurosurgical Intensive Care Unit Patient

2021 ◽  
Vol 41 (3) ◽  
pp. 33-41
Author(s):  
Lisa Fetters ◽  
Sue Sirianni
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Factor Viii ◽  
Reference Range ◽  
Fibrinogen Level ◽  
Anterior Communicating Artery ◽  
Factor Viii Activity ◽  
Platelet Factor ◽  
Antithrombin Activity ◽  
Heparin Resistance

Introduction Heparin resistance was discovered in a patient in the surgical intensive care unit who underwent emergency endovascular coiling and later an anterior communicating artery clipping procedure to treat subarachnoid hemorrhage due to rupture of an anterior communicating artery aneurysm. Clinical Findings On intensive care unit day 17/postoperative day 3, the patient experienced shortness of breath, persistent tachycardia, and hypoxia. Bilateral pulmonary emboli, a saddle embolus, and lower-extremity and upper-extremity deep vein thrombi were diagnosed. The patient received high-dose unfractionated heparin (&gt;35 000 U/24 h), and activated partial thromboplastin times remained subtherapeutic over the next 72 hours. Diagnosis Factor VIII activity, fibrinogen, antithrombin activity, antithrombin antigen, and platelet factor 4 were measured. The results demonstrated an increase in factor VIII activity to 342% (reference range, 50%-200%), elevated fibrinogen level of 441 mg/dL (reference range, 200-400 mg/dL), antithrombin antigen level of 92% (reference range, 80%-130%), elevated antithrombin activity of 108% (reference range, 80%-100%), and negative platelet factor 4 result, indicating that the patient did not have heparin-induced thrombocytopenia and confirming the diagnosis of heparin resistance. Conclusions Risk factors for heparin resistance include antithrombin deficiency, elevation of factor VIII or fibrinogen level, elevation in heparin-binding proteins, increased heparin clearance, sepsis, trauma, and burns. The astute critical care nurse may be the first to recognize this condition in a patient, preventing a potentially fatal complication.

Norepinephrine, but not epinephrine, enhances platelet reactivity and coagulation after exercise in humans

1999 ◽  
Vol 86 (1) ◽  
pp. 133-138 ◽  
Author(s):  
Hideo Ikarugi ◽  
Tomomi Taka ◽  
Shoko Nakajima ◽  
Takanori Noguchi ◽  
Sadahiro Watanabe ◽  
...  
Keyword(s):  
Aerobic Exercise ◽  
Resting State ◽  
Platelet Reactivity ◽  
Healthy Male ◽  
Thrombotic Risk ◽  
In Vitro Method ◽  
Plug Formation ◽  
Exercise In Humans ◽  
Catecholamine Levels

The effects of exercise and catecholamines on platelet reactivity or coagulation and fibrinolysis appear to be inconsistent. This may be partly due to the methods employed in previous studies. In the present study, we investigated the effects of acute aerobic exercise and catecholamines on the thrombotic status by a novel in vitro method, shear-induced hemostatic plug formation (hemostatometry), using nonanticoagulated (native) blood. Aerobic exercise (60% maximal O2consumption) was performed by healthy male volunteers for 20 min, and the effect on platelet reactivity and coagulation was assessed by performing hemostatometry before and immediately after exercise. Exercise significantly increased shear-induced platelet reactivity, coagulation, and catecholamine levels. The effect of catecholamines on platelet reactivity and coagulation was assessed in vitro by adding catecholamines to blood collected in the resting state. The main findings of the present study are that elevation of circulating norepinephrine at levels that are attained during exercise causes platelet hyperreactivity and a platelet-mediated enhanced coagulation. This may be a mechanism of an association of aerobic exercise with thrombotic risk.

scholarly journals Laboratory Diagnostics Performance in Uganda: A Survey of Test Availability and Constraints Across 100 Laboratories

2021 ◽  
Author(s):  
Noel Namuhani ◽  
Suzanne N Kiwanuka ◽  
Martha Akulume ◽  
Simeon Kalyesubula ◽  
William Bazeyo ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Disease Diagnosis ◽  
Sub Saharan Africa ◽  
Essential Medicines ◽  
Full Blood Count ◽  
Laboratory Diagnostics ◽  
Cross Sectional ◽  
Laboratory Services ◽  
Control And Prevention ◽  
Sub Saharan

Abstract Background Clinical laboratory services are a critical component of the health system for effective disease diagnosis, treatment, control and prevention. However, many laboratories in Sub Saharan Africa remain dysfunctional. The high costs of tests in the private sector also remain a hindrance to accessing testing services. This study aimed at assessing the functionality of laboratories based on test menus and the associated constraints in Uganda. Methods This cross sectional quantitative study involved an assessment of 100 laboratories randomly selected in 20 districts from four regions of the country. Sixteen percent of the studied laboratories were regional hub laboratories. Laboratory in charges and managers in each of the selected laboratories were interviewed. A checklist for laboratory supplies adapted from the Essential Medicines and Health supplies list for Uganda, (2012) was used to assess availability of testing supplies. Data was analyzed using excel and STATA 14. Results At the point of assessment, generally, all laboratories were able to perform malaria tests and HIV tests. All the hub laboratories conducted malaria tests and TB screening. Less than half had electrolytes tests due to lack of equipment, nonfunctioning equipment and lack of reagents. Full blood count tests were missing in 25% of the hub laboratories mainly due to lack of equipment. The lack of reagents (66.7%) and the lack of equipment (58.3%) caused the majority 10/16 of the hubs to routinely referred specimens for tests that are supposed to be carried out in these laboratories due to lack of reagents (66.7%) and non-functional equipment (58.3%). Although officially recognized as an operational structure, Hub laboratories lacked a list of essential and vital supplies. Conclusions Most laboratories performed well for the common tests. However, many laboratories did not meet testing requirements especially for the advanced tests according to standard testing menus for Uganda due to non-functioning equipment, lack of equipment and reagents. Hubs lack list of essential supplies. Therefore, there is need to provide equipment to laboratories, repair the non-functional ones and develop an essential list of supplies for the hub laboratories.

scholarly journals Clopidogrel Resistance: Current Issues

2016 ◽  
Vol 6 (1) ◽  
pp. 38-46
Author(s):  
NS Neki
Keyword(s):  
Antiplatelet Therapy ◽  
Dual Antiplatelet Therapy ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Antiplatelet Agents ◽  
Clinical Problem ◽  
Coronary Intervention ◽  
Platelet Activity ◽  
Clopidogrel Resistance ◽  
Underlying Mechanisms

Antiplatelet agents are mainly used in the prevention and management of atherothrombotic complications. Dual antiplatelet therapy, combining aspirin and clopidogrel, is the standard care for patients having acute coronary syndromes or undergoing percutaneous coronary intervention according to the current ACC/AHA and ESC guidelines. But in spite of administration of dual antiplatelet therapy, some patients develop recurrent cardiovascular ischemic events especially stent thrombosis which is a serious clinical problem. Antiplatelet response to clopidogrel varies widely among patients based on ex vivo platelet function measurements. Clopidogrel is an effective inhibitor of platelet activation and aggregation due to its selective and irreversible blockade of the P2Y12 receptor. Patients who display little attenuation of platelet reactivity with clopidogrel therapy are labeled as low or nonresponders or clopidogrel resistant. The mechanism of clopidogrel resistance remains incompletely defined but there are certain clinical, cellular and genetic factors including polymorphisms responsible for therapeutic failure. Currently there is no standardized or widely accepted definition of clopidogrel resistance. The future may soon be realised in the routine measurement of platelet activity in the same way that blood pressure, cholesterol and blood sugar are followed to help guide the therapy, thus improving the care for millions of people. This review focuses on the methods used to identify patients with clopidogrel resistance, the underlying mechanisms, metabolism, clinical significance and current therapeutic strategies to overcome clopidogrel resistance.J Enam Med Col 2016; 6(1): 38-46

Sign in / Sign up

Export Citation Format

Share Document