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Jourdi, G., Ramström, S., Sharma, R., Bakchoul, T. & Lordkipanidze, M. (2023). Consensus report on flow cytometry for platelet function testing in thrombocytopenic patients: communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis, 21(10), 2941-2952
Open this publication in new window or tab >>Consensus report on flow cytometry for platelet function testing in thrombocytopenic patients: communication from the SSC of the ISTH
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2023 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 21, no 10, p. 2941-2952Article in journal (Refereed) Published
Abstract [en]

Background: Platelet count alone does not reliably predict bleeding risk, suggesting platelet function is important to monitor in patients with thrombocytopenia. There is still an unmet need for improved platelet function diagnostics in patients with low platelet count in many clinical situations. Flow cytometry is a promising tool allowing reliable platelet function study in this setting.

Objectives: The goal of this joint project between the International Society on Thrombosis and Haemostasis (ISTH) Scientific Standardization Committee (SSC) Subcommittees on Platelet Physiology and Platelet Immunology is to provide expert consensus guidance on the use of flow cytometry for the evaluation of platelet function, particularly activation, in patients with low platelet counts.

Methods: A literature review was performed to identify relevant questions and areas of interest. An electronic expression of interest form was thereafter announced on the ISTH webpage, followed by a survey encompassing 37 issues regarding preanalytical, analytical, postanalytical, and performance aspects. Areas of disagreement or uncertainty were identified and formed the basis for 2 focus group discussions.

Results: Consensus recommendations relative to patient sample collection, preanalytical variables, sample type, platelet-count cutoff, any potential specific modification of the standard flow cytometry protocol, and results expression and reporting are proposed based on the current practices of experts in the field as well as on literature review.

Conclusion: The proposed consensus recommendations would allow standardization of protocols in upcoming clinical studies. The clinical utility of platelet function testing using flow cytometry to predict bleeding risk still needs rigorous multicenter outcome studies in patients with thrombocytopenia.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
Blood platelets, bleeding, flow cytometry, platelet activation, thrombocytopenia
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-107497 (URN)10.1016/j.jtha.2023.07.006 (DOI)001082271800001 ()37481072 (PubMedID)2-s2.0-85167832498 (Scopus ID)
Available from: 2023-08-10 Created: 2023-08-10 Last updated: 2023-10-31Bibliographically approved
Josefsson, E. C., Ramström, S., Thaler, J. & Lordkipanidzé, M. (2023). Consensus report on markers to distinguish procoagulant platelets from apoptotic platelets: communication from the Scientific and Standardization Committee of the ISTH. Journal of Thrombosis and Haemostasis, 21(8), 2291-2299
Open this publication in new window or tab >>Consensus report on markers to distinguish procoagulant platelets from apoptotic platelets: communication from the Scientific and Standardization Committee of the ISTH
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2023 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 21, no 8, p. 2291-2299Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Procoagulant platelets are a subpopulation of highly activated platelets that promote coagulation through surface-exposed, negatively charged phospholipids, especially phosphatidylserine (PS). Procoagulant platelets are important for clot stabilization during haemostasis and an increased number of these platelets is associated with thrombotic risk. There is a need for harmonisation in this area since many of the markers and methods used to assess procoagulant platelets are not specific when used in isolation but are also associated with platelet apoptosis.

OBJECTIVE: We initiated this project to identify a minimum set of markers and/or methods that can detect and distinguish procoagulant platelets from apoptotic platelets.

METHODS AND RESULTS: The study design involved a primary panel with twenty-seven international experts participating in an online survey and moderated virtual focus group meetings. Primary and secondary panel members were then invited to provide input on themes and statements generated from the focus groups. This led to a recommendation to use flow cytometry and a combination of the following three surface markers to differentiate procoagulant from apoptotic platelets: P-selectin (CD62P), PS (recognized by annexin V), and a platelet-specific receptor GPIX (CD42a) or αIIb integrin (CD41, GPIIb).

CONCLUSION: Procoagulant platelets are expected to be positive for all three markers, while apoptotic platelets will be positive for annexin V and the platelet specific surface receptor(s) but negative for P-selectin.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
Annexin V, Apoptosis, Flow cytometry, P-selectin, Platelet activation
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-105953 (URN)10.1016/j.jtha.2023.05.001 (DOI)001046842200001 ()37172731 (PubMedID)2-s2.0-85160852036 (Scopus ID)
Available from: 2023-05-15 Created: 2023-05-15 Last updated: 2023-09-01Bibliographically approved
Tynngård, N., Alshamari, A., Sandgren, P., Kenny, D., Vasilache, A. M., Abedi, M. R. & Ramström, S. (2023). High fragmentation in platelet concentrates impacts the activation, procoagulant, and aggregatory capacity of platelets. Platelets, 34(1), Article ID 2159018.
Open this publication in new window or tab >>High fragmentation in platelet concentrates impacts the activation, procoagulant, and aggregatory capacity of platelets
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2023 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 34, no 1, article id 2159018Article in journal (Refereed) Published
Abstract [en]

Platelets are transfused to patients to prevent bleeding. Since both preparation and storage can impact the hemostatic functions of platelets, we studied platelet concentrates (PCs) with different initial composition in regard to platelet fragmentation and its impact on storage-induced changes in activation potential. Ten whole blood derived PCs were assessed over 7 storage days. Using flow cytometry, platelet (CD41+) subpopulations were characterized for activation potential using activation markers (PAC-1, P-selectin, and LAMP-1), phosphatidylserine (Annexin V), and mitochondrial integrity (DiIC1(5)). Aggregation response, coagulation, and soluble activation markers (cytokines and sGPVI) were also measured. Of the CD41+ events, the PCs contained a median of 82% normal-sized platelets, 10% small platelets, and 8% fragments. The small platelets exhibited procoagulant hallmarks (increased P-selectin and Annexin V and reduced DiIC1(5)). Normal-sized platelets responded to activation, whereas activation potential was decreased for small and abolished for fragments. Five PCs contained a high proportion of small platelets and fragments (median of 28% of CD41+ events), which was significantly higher than the other five PCs (median of 9%). A high proportion of small platelets and fragments was associated with procoagulant hallmarks and decreased activation potential, but, although diminished, they still retained some activation potential throughout 7 days storage.

Place, publisher, year, edition, pages
Taylor & Francis, 2023
Keywords
Flow cytometry, microparticles, platelet concentrate, platelet storage, subpopulations
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-103145 (URN)10.1080/09537104.2022.2159018 (DOI)000911388400001 ()36632714 (PubMedID)2-s2.0-85146140869 (Scopus ID)
Available from: 2023-01-19 Created: 2023-01-19 Last updated: 2023-02-02Bibliographically approved
Törnudd, M., Ramström, S., Kvitting, J.-P. E., Alfredsson, J., Nyberg, L., Björkman, E. & Berg, S. (2023). Platelet Function is Preserved After Moderate Cardiopulmonary Bypass Times But Transiently Impaired After Protamine. Journal of Cardiothoracic and Vascular Anesthesia, 37(7), 1110-1120
Open this publication in new window or tab >>Platelet Function is Preserved After Moderate Cardiopulmonary Bypass Times But Transiently Impaired After Protamine
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2023 (English)In: Journal of Cardiothoracic and Vascular Anesthesia, ISSN 1053-0770, E-ISSN 1532-8422, Vol. 37, no 7, p. 1110-1120Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Previous studies have described impaired platelet function after cardiopulmonary bypass (CPB). Whether this is still valid in contemporary cardiac surgery is unclear. This study aimed to quantify changes in function and number of platelets during CPB in a present-day cardiac surgery cohort.

DESIGN: Prospective, controlled clinical study.

SETTING: A single-center university hospital.

PARTICIPANTS: Thirty-nine patients scheduled for coronary artery bypass graft surgery with CPB.

INTERVENTIONS: Platelet function and numbers were measured at 6 timepoints in 39 patients during and after coronary artery bypass graft surgery; at baseline before anesthesia, at the end of CPB, after protamine administration, at intensive care unit (ICU) arrival, 3 hours after ICU arrival, and on the morning after surgery. MEASUREMENTS AND

MAIN RESULTS: Platelet function was assessed with impedance aggregometry and flow cytometry. Platelet numbers are expressed as actual concentration and as numbers corrected for dilution using hemoglobin as a reference marker. There was no consistent impairment of platelet function during CPB with either impedance aggregometry or flow cytometry. After protamine administration, a decrease in platelet function was seen with impedance aggregometry and for some markers of activation with flow cytometry. Platelet function was restored 3 hours after arrival in the ICU. During CPB (85.0 ± 21 min), the number of circulating platelets corrected for dilution increased from 1.73 ± 0.42 × 109/g to 1.91 ± 0.51 × 109/g (p < 0.001).

CONCLUSIONS: During cardiac surgery with moderate CPB times, platelet function was not impaired, and no consumption of circulating platelets could be detected. Administration of protamine transiently affected platelet function.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Cardiac surgery, cardiopulmonary bypass, flow cytometry, impedance aggegometry, platelet function, protamine
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-105541 (URN)10.1053/j.jvca.2023.03.013 (DOI)2-s2.0-85152436798 ()37059638 (PubMedID)2-s2.0-85152436798 (Scopus ID)
Available from: 2023-04-17 Created: 2023-04-17 Last updated: 2023-08-03Bibliographically approved
Deb, S., Azharuddin, M., Ramström, S., Ghosh, K., Singha, S., Romu, T. & Patra, H. K. (2023). Self-Reporting Theranostic: Nano Tool for Arterial Thrombosis. Bioengineering, 10(9), Article ID 1020.
Open this publication in new window or tab >>Self-Reporting Theranostic: Nano Tool for Arterial Thrombosis
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2023 (English)In: Bioengineering, E-ISSN 2306-5354, Vol. 10, no 9, article id 1020Article in journal (Refereed) Published
Abstract [en]

Arterial thrombosis (AT) originates through platelet-mediated thrombus formation in the blood vessel and can lead to heart attack, stroke, and peripheral vascular diseases. Restricting the thrombus growth and its simultaneous monitoring by visualisation is an unmet clinical need for a better AT prognosis. As a proof-of-concept, we have engineered a nanoparticle-based theranostic (combined therapy and monitoring) platform that has the potential to monitor and restrain the growth of a thrombus concurrently. The theranostic nanotool is fabricated using biocompatible super-paramagnetic iron oxide nanoparticles (SPIONs) as a core module tethered with the anti-platelet agent Abciximab (ReoPro) on its surface. Our in vitro feasibility results indicate that ReoPro-conjugated SPIONS (Tx@ReoPro) can effectively prevent thrombus growth by inhibiting fibrinogen receptors (GPIIbIIIa) on the platelet surface, and simultaneously, it can also be visible through non-invasive magnetic resonance imaging (MRI) for potential reporting of the real-time thrombus status.

Place, publisher, year, edition, pages
MDPI, 2023
Keywords
MRI, ReoPro, arterial thrombosis, platelet aggregations, theranostics
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:oru:diva-108659 (URN)10.3390/bioengineering10091020 (DOI)001074331200001 ()37760122 (PubMedID)2-s2.0-85172810405 (Scopus ID)
Available from: 2023-10-02 Created: 2023-10-02 Last updated: 2023-10-16Bibliographically approved
Befekadu, R., Grenegård, M., Larsson, A., Christensen, K. & Ramström, S. (2022). Dynamic Changes in Pentraxin-3 and Neprilysin in ST Segment Elevation Myocardial Infarction. Biomedicines, 10(2), Article ID 275.
Open this publication in new window or tab >>Dynamic Changes in Pentraxin-3 and Neprilysin in ST Segment Elevation Myocardial Infarction
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2022 (English)In: Biomedicines, E-ISSN 2227-9059, Vol. 10, no 2, article id 275Article in journal (Refereed) Published
Abstract [en]

Pentraxin-3 (PTX3) and neprilysin have been associated with increased morbidity and mortality in chronic inflammatory disease and heart failure, but these biomarkers have been studied less in patients with ST segment elevation myocardial infarction (STEMI). We investigated the dynamic changes in these biomarkers, as well as the well-known C-reactive protein (CRP), in STEMI patients. PTX3, neprilysin and CRP were measured in samples from 165 STEMI patients, collected at the acute stage, 1-3 days after and 3 months after percutaneous coronary intervention (PCI), and from 40 healthy donors. Patient survival was followed for approximately 8 years after the PCI. As compared with samples from healthy donors, plasma levels of CRP and PTX3 were significantly increased in the acute samples and 1-3 days after PCI, but not at 3 months. CRP levels peaked at 1-3 days, while PTX3 was similarly high in both acute and 1-3 days samples. For neprilysin, no significant differences were observed at the group level. We found no significant differences when comparing patients with patent versus occluded culprit vessels or between patients having a thrombus aspiration or not. However, we found a significant reduction in survival for individuals with PTX3 above the median, both for samples collected at the acute stage and 1-3 days after PCI (p = 0.0001 and p = 0.0008, respectively). For CRP, no significant differences were observed using this approach, but patients above the reference range for healthy donors in the acute samples showed significantly lower survival (p = 0.0476). Conclusions: Survival analysis suggests that PTX3 might be a promising marker to predict mortality in this patient population.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
C-reactive protein, PTX3 protein, ST elevation myocardial infarction, neprilysin, survival analysis, thrombectomy
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-97695 (URN)10.3390/biomedicines10020275 (DOI)000770833500001 ()35203485 (PubMedID)2-s2.0-85123618888 (Scopus ID)
Note

Funding agencies:

Örebro University Hospital Research Foundation

AFA Insurance

Region Örebro County

Available from: 2022-02-28 Created: 2022-02-28 Last updated: 2022-10-31Bibliographically approved
Befekadu, R., Grenegård, M., Larsson, A., Christensen, K. & Ramström, S. (2022). Levels of soluble tumor necrosis factor receptor 1 and 2 are associated with survival after ST segment elevation myocardial infarction. Scientific Reports, 12(1), Article ID 14762.
Open this publication in new window or tab >>Levels of soluble tumor necrosis factor receptor 1 and 2 are associated with survival after ST segment elevation myocardial infarction
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2022 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 14762Article in journal (Refereed) Published
Abstract [en]

The soluble tumor necrosis factor receptors (sTNFR1 and sTNFR2) are suggested to play dual roles on physiological and pathophysiological actions of TNF-α. The aim of this study was to investigate the dynamic changes of these biomarkers in patients with ST-segment elevation myocardial infarction (STEMI). Blood was collected from 165 STEMI patients at admission, 1-3 days and 3 months after percutaneous coronary intervention (PCI) and from 40 healthy blood donors. sTNFR1 and sTNFR2 were measured with ELISA. The plasma levels of both sTNFR1 and sTNFR2 were significantly higher than in healthy donors at all three time points. We found no significant differences in sTNFR1 or sTNFR2 when comparing patients with patent versus occluded culprit vessels, or between patients having a thrombus aspiration or not. Survival analysis was performed comparing patients with levels of biomarkers above and below the median values at that time point. We found significant differences in survival for sTNFR2 in acute samples (p = 0.0151) and for both sTNFR1 and sTNFR2 in samples 1-3 days after PCI (p = 0.0054 and p = 0.0003, respectively). Survival analyses suggest that sTNFR1 or sTNFR2 could be promising markers to predict mortality in STEMI patients after PCI.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-101044 (URN)10.1038/s41598-022-18972-5 (DOI)000847803100078 ()36042366 (PubMedID)2-s2.0-85136959494 (Scopus ID)
Funder
Region Örebro County
Note

Funding agencies:

Örebro University Hospital

AFA Insurance

Available from: 2022-09-01 Created: 2022-09-01 Last updated: 2022-10-31Bibliographically approved
Szanto, T., Zetterberg, E., Ramström, S., Leinøe, E. B., Holme, P. A., Antovic, J. P., . . . Lassila, R. (2022). Platelet function testing: Current practice among clinical centres in Northern Europe. Haemophilia, 28(4), 642-648
Open this publication in new window or tab >>Platelet function testing: Current practice among clinical centres in Northern Europe
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2022 (English)In: Haemophilia, ISSN 1351-8216, E-ISSN 1365-2516, Vol. 28, no 4, p. 642-648Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Platelet function tests are used to screen and diagnose patients with possible inherited platelet function defects (IPFD). Some acquired platelet dysfunction may be caused by certain drugs or comorbidities, which need to be excluded before testing.

AIMS: To identify current practice among centres performing platelet function tests in Northern Europe.

METHODS: A total of 14 clinical centres from Sweden (six), Finland (two), Denmark (two), Norway (one), Estonia (two) and Iceland (one) completed the survey questionnaire, the population capture area of about 29.5 million.

RESULTS: Six of the 14 (42.8%) centres providing platelet function assessment represent comprehensive treatment centres (EUHANET status). A Bleeding score (BS) or ISTH bleeding assessment tool (ISTH BAT score) is evaluated in 11/14 (78.6%) centres and family history in all. Five/14 centres (35.7%) use structured preanalytical patient instructions, and 10/14 (71.4%) recorded questionnaire on the preassessment of avoidance of any drugs or natural products affecting platelet functions. Preliminary investigations of screening tests of coagulation are performed in 10/14 (71.4%), while in 4/14 (28.6%), the diagnostic work-up of IPFD and von Willebrand disease (VWD) is performed simultaneously. The work-up of IPFD includes peripheral blood smear in 10/14 (71.4%), platelet aggregometry in all, flow cytometry in 10/14 (71.4%) and Platelet Function Analysis (PFA) in 3/11 (28.6%). Molecular genetic diagnosis is available in 7/14 (50%) centres.

CONCLUSIONS: The considerable variability in the current practice illustrates the need for harmonization between the Northern European centres according to the international registers (i.e. EUHASS) and IPFD guidelines (ISTH, EHA).

Place, publisher, year, edition, pages
Blackwell Publishing, 2022
Keywords
Blood platelet disorders, data collection, platelet function testing, platelets, survey
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:oru:diva-98863 (URN)10.1111/hae.14578 (DOI)000790857600001 ()35510959 (PubMedID)2-s2.0-85131352379 (Scopus ID)
Note

Funding agency:

Helsinki University Hospital TYH2020318

Available from: 2022-05-06 Created: 2022-05-06 Last updated: 2022-08-22Bibliographically approved
Törnudd, M., Al Ghraoui, M. R., Wahlgren, S., Björkman, E., Berg, S., Kvitting, J.-P. E., . . . Ramström, S. (2022). Quantification of platelet function: a comparative study of venous and arterial blood using a novel flow cytometry protocol. Platelets, 33(6), 926-934
Open this publication in new window or tab >>Quantification of platelet function: a comparative study of venous and arterial blood using a novel flow cytometry protocol
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2022 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 33, no 6, p. 926-934Article in journal (Refereed) Published
Abstract [en]

Studies of platelet function in surgical patients often involve both arterial and venous sampling. Possible effects of different sampling sites could be important, but have not been thoroughly investigated. We aimed to compare platelet function in arterial and venous blood samples using a novel flow cytometry protocol and impedance aggregometry. Arterial and venous blood was collected before anesthesia in 10 patients undergoing cardiac surgery of which nine was treated with acetylsalicylic acid until the day before surgery. Flow cytometry included simultaneous analysis of phosphatidylserine exposure, active conformation of the fibrinogen receptor (PAC-1 binding), alpha-granule and lysosomal release (P-selectin and LAMP-1 exposure) and mitochondrial membrane integrity. Platelets were activated with ADP or peptides activating thrombin receptors (PAR1-AP/PAR4-AP) or collagen receptor GPVI (CRP-XL). Leukocyte-platelet conjugates and P-selectin exposure were evaluated immediately in fixated samples. For impedance aggregometry (Multiplate (R)), ADP, arachidonic acid, collagen and PAR1-AP (TRAP) were used as activators. Using impedance aggregometry and in 27 out of 37 parameters studied with flow cytometry there was no significant difference between venous and arterial blood sampling. Arterial blood showed more PAC-1 positive platelets when activated with PAR1-AP or PAR4-AP and venous blood showed more monocyte-platelet and neutrophil-platelet conjugates and higher phosphatidylserine exposure with CRP-XL alone and combined with PAR1-AP or PAR4-AP. We found no differences using impedance aggregometry. In conclusion, testing of platelet function by flow cytometry and impedance aggregometry gave comparable results for most of the studied parameters in venous and arterial samples. Flow cytometry identified differences in PAC-1 binding when activated with PAR1-AP, exposure of phosphatidyl serine and monocyte/neutrophil-platelet conjugates, which might reflect differences in blood sampling technique or in flow conditions in this patient cohort with coronary artery disease. These differences might be considered when comparing data from different sample sites, but caution should be exercised if a different protocol is used or another patient group is studied.

Place, publisher, year, edition, pages
Taylor & Francis, 2022
Keywords
Flow cytometry, impedance aggregometry, platelet function
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-97258 (URN)10.1080/09537104.2021.2019209 (DOI)000746724500001 ()35073813 (PubMedID)2-s2.0-85123823315 (Scopus ID)
Note

Funding agency:

County Council of Östergötland LIO661221 LIO-603321

Available from: 2022-02-07 Created: 2022-02-07 Last updated: 2023-12-08Bibliographically approved
Tynngård, N., Alshamari, A., Månsson, F. & Ramström, S. (2022). Variation in activation marker expression within the platelet population - a new parameter for evaluation of platelet flow cytometry data. Platelets, 33(8), 1113-1118
Open this publication in new window or tab >>Variation in activation marker expression within the platelet population - a new parameter for evaluation of platelet flow cytometry data
2022 (English)In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 33, no 8, p. 1113-1118Article in journal (Refereed) Published
Abstract [en]

In flow cytometry, individual cells are investigated. Platelet activation is normally reported in form of percentage of platelets expressing the marker (positive platelets) and/or mean/median fluorescence intensity (MFI) for the entire analyzed population. None of these take into account the variance of the marker expression between individual platelets. This can be obtained as data on coefficient of variation (CV). This study explores if CV provides additional information regarding platelet function. Samples from platelet concentrates (PCs) prepared by apheresis- (n = 13) and interim platelet unit (IPU) technique (n = 26) and stored for 6-7 days were included and compared. Spontaneous- and agonist-induced expression of activation markers (fibrinogen binding and exposure of P-selectin, LAMP-1, and CD63) was investigated as percentage positive platelets, MFI and CV. Spontaneous expression of P-selectin as percentage positive platelets and MFI was higher for IPU PCs than apheresis PCs, which in contrast had higher agonist-induced activation. CV for spontaneous fibrinogen binding and P-selectin exposure was larger for apheresis PCs, while IPU PCs generally had larger CV for P-selectin, LAMP-1, and CD63 after agonist stimulation. Our findings show that CV adds additional information when assessing platelet activation by providing data on the variation in activation responses within the platelet population.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2022
Keywords
Blood platelets, coefficient of variation, CV, flow cytometry, platelet activation
National Category
Hematology
Identifiers
urn:nbn:se:oru:diva-100312 (URN)10.1080/09537104.2022.2078490 (DOI)000827090900001 ()35848430 (PubMedID)2-s2.0-85134154962 (Scopus ID)
Funder
Region ÖstergötlandÖrebro University
Note

Funding agency:

ALF Grants

Available from: 2022-08-02 Created: 2022-08-02 Last updated: 2022-10-27Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-1920-3962

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