Impact of COVID-19 disease on platelet reactivity and association with inflammatory parameters

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. Aside from the pulmonary manifestations, COVID-19 is associated with increased risk of venous and arterial thrombotic complications. The actual impact of SARS-CoV-2 infection on platelet reactivity and whether this is mediated by a hyperinflammatory status has not been fully elucidated to date. Objective To evaluate platelet reactivity in COVID-19 patients compared to healthy subjects and to assess the association between platelet reactivity and levels of inflammatory biomarkers among COVID-19 patients. Methods This prospective observational investigation included COVID-19 patients admitted into a tertiary care hospital and adult healthy volunteers, all of them not receiving any antiplatelet therapy. Subjects were classified in three groups: 1) Healthy subjects (HS group); 2) COVID-19 patients in a pulmonary phase (viral pneumonia and bilateral infiltrates) but without meeting criteria for systemic hyperinflammation (C19-Pulm group); and 3) COVID-19 patients in a hyperinflammation phase (C19-Infl group) meeting at least 2 of the following criteria: CRP>100mg/l, D-dimer >1000mcg/l, LDH>400U/l, ferritin>1000ng/ml, IL-6>70ng/l. Blood samples for platelet function testing and quantification of inflammatory parkers were collected at a single visit. Platelet function was measured with multiple electrode aggregometry using ADP (MEA-ADP, primary endpoint), arachidonic acid (AA) and thrombin receptor activating peptide (TRAP) as stimuli. Unadjusted analyses are presented. Results A total of 60 patients were included in the present investigation (20 in each group). A significantly greater platelet reactivity, measured with MEA-ADP, was observed in both groups of COVID-patients compared to healthy subjects (HS: 634,9±53,5, C19-Pulm: 919,9±53,5 and C19-Infl: 931,6±53,5 AU*min; p for C19-Pulm vs. HS <0,001, p for C19-Infl vs. HS <0,001, p for C19-Pulm vs. C19-Infl 0,878; Figure 1). Parallel findings were found when using AA as stimulus for platelet aggregation showing greater platelet aggregation in COVID-19 patients compared to healthy subjects, but numerical differences were not statistically significant when using TRAP. Among COVID-19 patients, when stratified by IL-6 levels splitted into tertiles, greater platelet reactivity was observed in patients with higher IL-6 concentrations (mid and upper tertile together) compared to those with values in the lower tertile, as assessed with MEA-ADP (lower tertile: 829,0±75,8, mid and upper tertile: 1028,7±56,2; p=0,043); a similar trend was observed with AA and TRAP as stimuli. Conclusion Patients with severe COVID-19 disease have greater platelet reactivity than healthy subjects. Increased IL-6 levels might be associated with the observed heightened platelet reactivity among COVID-19 patients. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

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Cross validation of the Multiple Electrode Aggregometry

Thrombosis and Haemostasis ◽

10.1160/th08-10-0669 ◽

2009 ◽

Vol 102 (08) ◽

pp. 397-403 ◽

Cited By ~ 43

Author(s):

Jolanta Siller-Matula ◽

Ghazaleh Gouya ◽

Michael Wolzt ◽

Bernd Jilma

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Cross Validation ◽

Platelet Reactivity ◽

Adenosine Diphosphate ◽

Multiple Electrode Aggregometry ◽

Vasp Phosphorylation ◽

Function Analyzer ◽

Platelet Function Analyzer ◽

Multiple Electrode

SummarySeveral test systems exist for assessment of platelet function in patients under clopidogrel or aspirin therapy. The objective was to cross-validate the Multiple Electrode Aggregometry (MEA) with three other methods used for determining platelet reactivity under treatment with clopidogrel and aspirin. Platelet function was assessed by the MEA, Vasodilator Stimulated Phosphoprotein (VASP) phosphorylation assay, Platelet Function Analyzer-100 (PFA-100) and the Cone and Platelet Analyzer. Measurements were performed in blood from nine healthy volunteers at baseline, 2, 4, 6 and 72 hours after clopidogrel and aspirin loading. The apparent effect size for clopidogrel and aspirin was greatest for the MEA: treatment induced a 19-fold difference in the arachidonic acid-induced platelet aggregation and an 11-fold difference in the adenosine diphosphate-induced platelet aggregation before/after treatment. For comparison, aspirin and clopidogrel induced only 2.0– to 2.6 -fold changes in other tests (VASP assay, Cone and Platelet Analyzer and PFA-100). Maximal effects were seen 2 hours after aspirin loading and shorter than 72 hours after clopidogrel loading. In conclusion, aspirin and clopidogrel produce stronger signals in the MEA compared to several other methods.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660138 ◽

1985 ◽

Vol 54 (04) ◽

pp. 808-812 ◽

Cited By ~ 7

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.

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Seroprevalence of anti-SARS-CoV-2 IgG antibodies in hospitalized patients at a tertiary referral center in North India (Preprint)

10.2196/preprints.23937 ◽

2020 ◽

Author(s):

Dr. Animesh Ray ◽

Dr. Komal Singh ◽

Souvick Chattopadhyay ◽

Farha Mehdi ◽

Dr. Gaurav Batra ◽

...

Keyword(s):

Tertiary Care ◽

Age Groups ◽

Hospitalized Patients ◽

North India ◽

P Value ◽

Care Hospital ◽

Igg Antibodies ◽

Igg Antibody ◽

Increased Risk ◽

Significant Difference

BACKGROUND Seroprevalence of IgG antibodies against SARS-CoV-2 is an important tool to estimate the true extent of infection in a population. However, seroprevalence studies have been scarce in South East Asia including India, which, as of now, carries the third largest burden of confirmed cases in the world. The present study aimed to estimate the seroprevalence of anti-SARS-CoV-2 IgG antibody among hospitalized patients at one of the largest government hospital in India OBJECTIVE The primary objective of this study is to estimate the seroprevalence of SARS-CoV-2 antibody among patients admitted to the Medicine ward and ICU METHODS This cross-sectional study, conducted at a tertiary care hospital in North India, recruited consecutive patients who were negative for SARS-CoV-2 by RT-PCR or CB-NAAT. Anti-SARS-CoV-2 IgG antibody levels targeting recombinant spike receptor-binding domain (RBD) protein of SARS CoV-2 were estimated in serum sample by the ELISA method RESULTS A total of 212 hospitalized patients were recruited in the study with mean age (±SD) of 41.2 (±15.4) years and 55% male population. Positive serology against SARS CoV-2 was detected in 19.8%patients(95% CI 14.7-25.8). Residency in Delhi conferred a higher frequency of seropositivity 26.5% (95% CI 19.3-34.7) as compared to that of other states 8% (95% CI 3.0-16.4) with p-value 0.001. No particular age groups or socio-economic strata showed a higher proportion of seropositivity CONCLUSIONS Around, one-fifth of hospitalized patients, who were not diagnosed with COVID-19 before, demonstrated seropositivity against SARS-CoV-2. While there was no significant difference in the different age groups and socio-economic classes; residence in Delhi was associated with increased risk (relative risk of 3.62, 95% CI 1.59-8.21)

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MicroRNA as Biomarkers for Platelet Function and Maturity in Patients with Cardiovascular Disease

Thrombosis and Haemostasis ◽

10.1055/s-0041-1730375 ◽

2021 ◽

Author(s):

Oliver Buchhave Pedersen ◽

Erik Lerkevang Grove ◽

Steen Dalby Kristensen ◽

Peter H. Nissen ◽

Anne-Mette Hvas

Keyword(s):

Cardiovascular Disease ◽

Platelet Function ◽

Assessment Tool ◽

Platelet Reactivity ◽

Thrombus Formation ◽

Quality Assessment Tool ◽

Treatment And Prevention ◽

Increased Risk ◽

Meta Analyses ◽

Potential Use

AbstractPatients with cardiovascular disease (CVD) are at increased risk of suffering myocardial infarction. Platelets are key players in thrombus formation and, therefore, antiplatelet therapy is crucial in the treatment and prevention of CVD. MicroRNAs (miRs) may hold the potential as biomarkers for platelet function and maturity. This systematic review was conducted using the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). To identify studies investigating the association between miRs and platelet function and maturity in patients with CVD, PubMed and Embase were searched on October 13 and December 13, 2020 without time boundaries. Risk of bias was evaluated using a standardized quality assessment tool. Of the 16 included studies, 6 studies were rated “good” and 10 studies were rated “fair.” In total, 45 miRs correlated significantly with platelet function or maturity (rho ranging from –0.68 to 0.38, all p < 0.05) or differed significantly between patients with high platelet reactivity and patients with low platelet reactivity (p-values ranging from 0.0001 to 0.05). Only four miRs were investigated in more than two studies, namely miR-223, miR-126, miR-21 and miR-150. Only one study reported on the association between miRs and platelet maturity. In conclusion, a total of 45 miRs were associated with platelet function or maturity in patients with CVD, with miR-223 and miR-126 being the most frequently investigated. However, the majority of the miRs were only investigated in one study. More data are needed on the potential use of miRs as biomarkers for platelet function and maturity in CVD patients.

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Pulmonary Manifestations in Paediatric Rheumatic Diseases (PRDs): Experience in Tertiary Care Hospital

Bangladesh Journal of Child Health ◽

10.3329/bjch.v41i2.36105 ◽

2018 ◽

Vol 41 (2) ◽

pp. 96-100

Author(s):

Mohammad Imnul Islam ◽

Kalayan Benjamin Gomes ◽

Mujammel Haque ◽

Mohammed Mahbubul Islam ◽

Manik Kumar Talukder ◽

...

Keyword(s):

Pleural Effusion ◽

Rheumatic Diseases ◽

Lupus Erythematosus ◽

Pulmonary Function Tests ◽

Tertiary Care ◽

Pulmonary Involvement ◽

Care Hospital ◽

Cross Sectional ◽

Pulmonary Manifestations ◽

Paediatric Rheumatic Diseases

Background: There are several forms of pulmonary manifestations in Paediatric Rheumatic Diseases (PRDs), not only by the disease itself, but also by infections and toxicity of medications used for treatment.Objectives: To evaluate the pulmonary manifestations and to identify their pattern in PRDs including Systemic Lupus Erythematosus (SLE), Juvenile Idiopathic Arthritis (JIA), Systemic Sclerosis (SSc), Juvenile Dermatomyositis (JDM) and Polyarteritis Nodosa (PAN) patients.Methods: It was a cross-sectional analytical study. PRDs with pulmonary problems who attended the Paediatric Rheumatololgy follow up clinic of BSMMU from January 2010 to December 2014 were enrolled in this study. All patients having PRDS with pulmonary symptoms were investigated by chest x-ray. High regulation CT scan of Chest (HRCT) and pulmonary function tests (PFTs) were done in some of the feasible cases.Results: Total 20 cases were identified as paediatric rheumatic diseases with pulmonary manifestations. Out of them 8 patients were diagnosed as SLE, 6 patients as SSc, 4 patients as JIA, and 2 patients as JDM and PAN respectively. Mean age of the patients were 8.5 years. Fever (86.8%), prolonged cough (65%), dyspnoea (29%) and chest pain (3%) were the common pulmonary features. Pneumonitis (35%), pleural effusion (29.3%), consolidation (23.5%) were important radiological findings. Chest CT were done in 5 patients and features of brochiectasis (75%), thickening (25%), pleural effusion (50%) and pneumonitis (50%) were found. The higher rate of pulmonary involvement was found in Ssc (100%). Spirometric analysis were done in only 7 patients and found restrictive pattern of defect and most of them were SSc.Conclusion: Pulmonary manifestations in PRDs were not uncommon. SLE, JIA and SSc were the predominant PRDs who had pulmonary manifestations obsevered in this study. So timely intervention of this issue could minimize morbidity and mortality of these diseases in the long run.Bangladesh J Child Health 2017; VOL 41 (2) :96-100

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Predictors of Disseminated Intravascular Coagulation in Patients with Septic Shock

ISRN Critical Care ◽

10.5402/2013/219048 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Diana J. Kelm ◽

Juan Carlos Valerio-Rojas ◽

Javier Cabello-Garza ◽

Ognjen Gajic ◽

Rodrigo Cartin-Ceba

Keyword(s):

Septic Shock ◽

Antiplatelet Therapy ◽

Disseminated Intravascular Coagulation ◽

Tertiary Care ◽

Multivariate Logistic Regression Model ◽

Care Hospital ◽

Clinical Predictors ◽

Intravascular Coagulation ◽

Early Goal Directed Therapy ◽

Increased Risk

Purpose. The goal of this study was to identify potential clinical predictors for the development of disseminated intravascular coagulation (DIC) in patients with septic shock. Material and Methods. We performed a retrospective analysis of a cohort of adult (>18 years of age) patients with septic shock admitted to a medical ICU in a tertiary care hospital from July 2005 until September 2007. A multivariate logistic regression model was used to determine the association of risk factors with overt DIC. Results. In this study, a total of 390 patients with septic shock were analyzed, of whom 66 (17%) developed overt DIC. Hospital mortality was significantly greater in patients who developed overt DIC (68% versus 38%, P<0.001). A delay in the timing of antibiotics was associated with an increased risk of the development of overt DIC (P<0.001). Patients on antiplatelet therapy prior to hospital admission and who that received adequate early goal-directed therapy (EGDT) were associated with a decreased risk of overt DIC (P<0.001). Conclusions. In our cohort of patients with septic shock, there was a risk reduction for overt DIC in patients on antiplatelet therapy and adequate EGDT, while there was an increased risk of DIC with antibiotic delay.

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Trends and causes of maternal mortality in a tertiary care hospital over five years: 2013-2017

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.35.4.1091 ◽

2019 ◽

Vol 35 (4) ◽

Author(s):

Sonia Rafiq ◽

Wajeeha Syed ◽

Simi Fayaz Ghaffar

Keyword(s):

Maternal Mortality ◽

Maternal Death ◽

Tertiary Care Hospital ◽

Tertiary Care ◽

Maternal Mortality Ratio ◽

Care Hospital ◽

Creative Commons ◽

Increased Risk ◽

Mortality Ratio ◽

Public Health Challenge

Background and Objective: Maternal death measurement is essential to a country’s wellbeing and development status. In emerging countries like Pakistan, it remains an intimidating and failed public health challenge. Objectives of our audit were to estimate trends and causes of maternal demise in Lady Reading Hospital, Peshawar, Pakistan. Methods: Between January 2013 to December 2017, a retrospective study was carried out at Medical Teaching Institute, Lady Reading Hospital, Peshawar. A structured proforma was used to collect data from the medical records. To detect trends in mother demise maternal mortality ratio was calculated for each year and for all five years, Spss version 23 was used for data analysis. Results: In the five-year periods 134 deaths were recorded. The maternal mortality during the study period was 431/100,000 live births. An unstable trend in mortality with two crowning periods in 2013 and 2017 was observed. Hemorrhage persisted as the foremost cause of maternal death over the five years period, accounting for 47.76% deaths followed by hypertension, accounting for 25.37% deaths. An increased risk of 35.08% was observed among women aged 25-29 years, followed by 26.11% in 20-24 years and 23.88% in >30 years. Conclusion: There is a decreasing trend of maternal death from 2013 to 2016 but a slight increase was noted in 2017. Hemorrhage was the top cause responsible for the maternal death. doi: https://doi.org/10.12669/pjms.35.4.1091 How to cite this:Rafiq S, Syed W, Ghaffar SF. Trends and causes of maternal mortality in a tertiary care hospital over five years: 2013-2017. Pak J Med Sci. 2019;35(4):---------. doi: https://doi.org/10.12669/pjms.35.4.1091 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Study of antimicrobial use in paediatric inpatients in a tertiary care hospital in Ahmedabad, India

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20205430 ◽

2020 ◽

Vol 8 (1) ◽

pp. 35

Author(s):

Hetal N. Jeeyani ◽

Rutvik H. Parikh ◽

Sheena Sivanandan ◽

Harsh J. Muliya ◽

Shivam N. Badiyani ◽

...

Keyword(s):

Bacterial Resistance ◽

Tertiary Care ◽

Antibiotic Use ◽

Antibiotic Prescribing ◽

Care Hospital ◽

Antimicrobial Drugs ◽

Prescribing Indicators ◽

Inappropriate Use ◽

Increased Risk ◽

The Mean

Background: Inappropriate use and overuse of antibiotics are important factors leading to increased bacterial resistance apart from increased risk of adverse reactions. The aim of this study was to derive antibiotic use percentage, study its pattern and compare antibiotic prescribing indicators with standard indicators.Methods: This prospective observational study was conducted from 1st August 2018 to 31st July 2019 on paediatric inpatients from 1 month to 14 years. All the relevant data was taken from the case records of patients at the time of discharge. The data included: age, sex, hospital stay, clinical diagnosis and details of antimicrobial treatment.Results: From 989 patients, 85.9% were diagnosed with infectious illness, of which 60.1% had viral and 36.7% had bacterial infection. The use of antimicrobial drugs was 42.7% and antibiotics was 40.4%. The mean number of antibiotics received was 1.13±0.31. 90% patients received single antibiotic. 88.8% drugs were prescribed by generic name and 99% drugs were prescribed from essential drug formulary. 17 different antibiotics were used out of which ceftriaxone (62.5%) was the most commonly used. Groupwise, antibiotic use was cephalosporins (68.4%), penicillin (20.2%), aminoglycosides (4.31%), fluoroquinolones (0.9%) and macrolides (0.22%). The use of higher antibiotics like vancomycin (3.86%) and carbapenems (0.68%) was quite less.Conclusions: The antibiotic use in our hospital was higher than the WHO standard but less as compared to majority of other studies. Use of cephalosporins was more and penicillin was less as compared to other studies. This suggests that there is a need of implementing antibiotic stewardship programs to enhance rational antibiotic prescribing.

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Predictors of mortality in adult patients with dengue: a study from South India

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20181495 ◽

2018 ◽

Vol 6 (5) ◽

pp. 1605 ◽

Cited By ~ 1

Author(s):

Vasudeva Acharya ◽

Mohammed Fahad Khan ◽

Srinivas Kosuru ◽

Sneha Mallya

Keyword(s):

Renal Failure ◽

Prothrombin Time ◽

Tertiary Care ◽

P Value ◽

Bleeding Tendency ◽

Care Hospital ◽

Laboratory Parameters ◽

Prolonged Prothrombin Time ◽

Risk Of Death ◽

Increased Risk

Background: Dengue is one of the important causes of acute febrile illnesses in India. Dengue can be a fatal disease, however there are no reliable markers which can predict mortality among these patients.Methods: A prospective cross sectional study was done in patients who were admitted to a tertiary care hospital with features of dengue fever. A total of 364 patients with IgM dengue serology positive were included in the study. Relevant clinical and laboratory parameters were collected from all patients. Association between clinico-laboratory parameters with mortality was studied using appropriate statistical methods.Results: Among the 364 patients recruited in this study, 14 (3.85%) patients died. Mortality among patients with age group 18-40 years was 2.04%, in patients aged above 40 years was 7.56%. Mortality among patients with hypotension was 42.42% (14 out of 33), bleeding manifestations was 15.38% (8/52), platelets <20,000/mm3 was 10.41% (10/96), ALT >200 was 13.04% (6/46), AST>200 was 12.34% (10/81), prolonged prothrombin time was 60%(12/20), renal failure was 28%(14/50), encephalopathy was 31.57% (6/19), multi organ dysfunction syndrome(MODS) was 43.33% (13/30), acute respiratory distress syndrome (ARDS) was 45.45% (5/11), pleural effusion was 7.5% (6/80).Conclusions: The overall mortality in the present study was 3.85%. Following variables were associated with increased risk of death among the dengue patients: Age >40 years, presence of hypotension, platelets <20000 cells/mm3, ALT>200U/L, AST>200U/L, prolonged prothrombin time, presence of renal failure, encephalopathy, MODS, ARDS and bleeding tendency (p value <0.05). Early identification of factors associated with mortality can help to make appropriate decision on care required.

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Platelet Function Disturbance During Veno-Venous ECMO in ARDS Patients Assessed by Multiple Electrode Aggregometry—A Prospective, Observational Cohort Study

Journal of Clinical Medicine ◽

10.3390/jcm8071056 ◽

2019 ◽

Vol 8 (7) ◽

pp. 1056 ◽

Cited By ~ 4

Author(s):

Saskia Wand ◽

Jan Felix Huber-Petersen ◽

Joern Schaeper ◽

Claudia Binder ◽

Onnen Moerer

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Extracorporeal Circulation ◽

Inverse Correlation ◽

Negative Effects ◽

Multiple Electrode Aggregometry ◽

Observational Cohort ◽

And Function ◽

The Impact ◽

Multiple Electrode

Extracorporeal (veno-venous) membrane oxygenation (vvECMO) has been shown to have negative effects on platelet number and function. This study aimed to gain more information about the impact of vvECMO on platelet function assessed by multiple electrode aggregometry (MEA). Twenty patients with the indication for vvECMO were included. Platelet function was analyzed using MEA (Multiplate®) before (T-1), 6 h (T0), one (T1), two (T2), three (T3), and seven (T4) days after the beginning of vvECMO. Median aggregational measurements were already below the normal reference range before vvECMO initiation. Platelet aggregation was significantly reduced 6 h after vvECMO initiation compared to T-1 and spontaneously recovered with a significant increase at T2. Platelet count dropped significantly between T-1 and T0 and continuously decreased between T0 and T4. At T4, ADP-induced platelet aggregation showed an inverse correlation with the paO2 in the oxygenator. Platelet function should be assessed by MEA before the initiation of extracorporeal circulation. Although ECMO therapy led to a further decrease in platelet aggregation after 6 h, all measurements had recovered to baseline on day two. This implies that MEA as a whole blood method might not adequately reflect the changes in platelet function in the later stages of extracorporeal circulation.

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