Thromb Haemost 2019; 119(03): 407-420
DOI: 10.1055/s-0039-1677875
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

Role of Platelet Size Revisited—Function and Protein Composition of Large and Small Platelets

Stefan Handtke
1  Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
,
Leif Steil
2  Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Abteilung Funktionelle Genomforschung, Universitätsmedizin Greifswald, Greifswald, Germany
,
Raghavendra Palankar
1  Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
,
Jane Conrad
2  Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Abteilung Funktionelle Genomforschung, Universitätsmedizin Greifswald, Greifswald, Germany
,
Simran Cauhan
1  Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
,
Luise Kraus
1  Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
,
Myriam Ferrara
1  Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
,
Vishnu Dhople
2  Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Abteilung Funktionelle Genomforschung, Universitätsmedizin Greifswald, Greifswald, Germany
,
Jan Wesche
1  Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
,
Uwe Völker
2  Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Abteilung Funktionelle Genomforschung, Universitätsmedizin Greifswald, Greifswald, Germany
,
Andreas Greinacher
1  Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
,
Thomas Thiele
1  Institut für Immunologie und Transfusionsmedizin, Universitätsmedizin Greifswald, Greifswald, Germany
› Author Affiliations
Funding This work was supported by the Deutsche Forschungsgesellschaft (DFG-SFB TRR 240, A06 to RP and A11 to AG) and Forschungsverbund für Molekulare Medizin, Universitätsmedizin Greifswald.
Further Information

Publication History

07 June 2018

10 December 2018

Publication Date:
06 February 2019 (eFirst)

Abstract

Epidemiological studies found an association between increased platelet size and the risk for thrombotic complications, but functional differences of large and small platelets remain poorly understood due to a lack of standardized protocols separating platelets with different size. We designed a protocol to separate large and small platelets from 15 mL whole blood. Separated large and small platelet fractions differed in mean platelet volume: 12.1 fl (10.3–13.8 fl) versus 7.7 fl (6.8–9.5 fl, p < 0.01), and forward scatter mean fluorescence intensity: 24.75 (19.9–30.9) versus 16.85 (11.3–20.6; p < 0.01). Similar fold differences were observed in cell diameter and plateletcrit. Large platelets express 30 to 50% more glycoprotein (GP) Ia, GPIb, GPIIIa, GPVI and P2Y12 on their membranes compared with small ones. Single large platelets covered a 50% larger area on a collagen surface. Adhesion to collagen was faster in large platelets compared with small ones indicating enhanced outside-in signal transduction in large platelets via collagen receptors. In contrast, integrin activation was more pronounced in small platelets after ADP stimulation. Proteome analysis revealed that 80 of the 894 proteins quantified differed in abundance: ADP-ribosylation factor 1/3, guanosine triphosphate-binding protein SAR1a, Voltage-dependent anion-selective channel protein 3 and guanylate cyclase soluble sub-unit α-3 were higher abundant in large, whereas immunoglobulins, haptoglobin, hemopexin, α-1-antitrypsin, serotransferrin and vitronectin were more abundant in small platelets. We conclude that some functions and the protein composition of large and small platelets differ, which cannot only be explained by the size difference. Our data suggest different functional roles of large and small platelets.

Authors' Contributions

S.H., L.S., T.T. and A.G. designed the experiments; S.H., L.S., R.P., J.C., S.C., L.K., M.F., V.D. and J.W. performed the experiments; S.H., L.S., R.P. and T.T. analysed the data; and S.H., L.S., U.V., A.G. and T.T. wrote the manuscript.


Supplementary Material