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Response by Nechipurenko et al to Letter Regarding Article, “Clot Contraction Drives the Translocation of Procoagulant Platelets to Thrombus Surface”

2019; Lippincott Williams & Wilkins; Volume: 39; Issue: 12 Linguagem: Inglês

10.1161/atvbaha.119.313479

1524-4636

D. Yu. Nechipurenko, P Mangin, Mikhail A. Panteleev,

Blood properties and coagulation

HomeArteriosclerosis, Thrombosis, and Vascular BiologyVol. 39, No. 12Response by Nechipurenko et al to Letter Regarding Article, "Clot Contraction Drives the Translocation of Procoagulant Platelets to Thrombus Surface" Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse by Nechipurenko et al to Letter Regarding Article, "Clot Contraction Drives the Translocation of Procoagulant Platelets to Thrombus Surface" Dmitry Y. Nechipurenko, Pierre H. Mangin and Mikhail A. Panteleev Dmitry Y. NechipurenkoDmitry Y. Nechipurenko From the Department of Physics, Lomonosov Moscow State University, Russia (D.Y.N., M.A.P.) Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia (D.Y.N., M.A.P.) Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia (D.Y.N., M.A.P.) , Pierre H. ManginPierre H. Mangin Université de Strasbourg, INSERM, Etablissement Français du Sang-Grand Est, UMR_S1255, FMTS, France (P.H.M.) and Mikhail A. PanteleevMikhail A. Panteleev From the Department of Physics, Lomonosov Moscow State University, Russia (D.Y.N., M.A.P.) Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia (D.Y.N., M.A.P.) Center for Theoretical Problems of Physicochemical Pharmacology, Moscow, Russia (D.Y.N., M.A.P.) Faculty of Biological and Medical Physics, Moscow Institute of Physics and Technology, Dolgoprudny, Russia (M.A.P.). Originally published26 Nov 2019https://doi.org/10.1161/ATVBAHA.119.313479Arteriosclerosis, Thrombosis, and Vascular Biology. 2019;39:e290–e291In Response:It was reported that procoagulant platelet generation in aggregates formed in platelet-rich plasma without shear flow occurred in a synchronized manner.1 In a recent commentary on our article, these authors speculate that "thrombin from the thrombus core may diffuse outwards from the growing thrombus to potently activate peripheral platelets and induce the formation of procoagulant platelets at the thrombus surface,"2 arguing against the mechanism of contraction-driven outward displacement of procoagulant platelets we recently had reported.3While there is a general consensus on the peripheral localization of procoagulant platelets around thrombi formed on collagen,4 the underlying mechanism has remained elusive for over a decade. Using real-time confocal microscopy, we showed that a subset of procoagulant platelets first detected in the inner part of thrombi formed on fibrillar collagen under controlled shear in vitro translocated to the thrombus surface. We proposed that the contraction-driven extrusion explains why ballooned platelets are ultimately located at the thrombus periphery, leaving trails of microvesicles behind. This hypothesis was supported by the marked reduction in the peripheral localization of procoagulant platelets in MYH9 (nonmuscle myosin IIA) knockout platelet thrombi, which have defective contraction properties.3 We believe that likely the same phenomenon can be observed in Movie I in the online-only Data Supplement in the recent article by Agbani et al,1 where ballooned platelets are visualized translocating to the periphery of the thrombus. The authors probably overlooked this phenomenon because these platelets were annexin V negative (indeed, late annexin V binding was shown to conceal the early stages of procoagulant platelet translocations in our study3).While we agree with the procoagulant effect of thrombin, glycoprotein VI stimulation by collagen or collagen-related peptide alone is sufficient for inducing procoagulant activity.5,6 Importantly, our data show that the peripheral distribution of procoagulant platelets similarly occurred in the presence of hirudin and recalcified blood, arguing against a central role of thrombin diffusion (Figure 5A and Figure 3 in the online-only Data Supplement in the study by Nechipurenko et al). Moreover, the study by Agbani et al1 did not provide a direct evidence of any role of thrombin and its diffusion in the peripheral distribution of procoagulant platelets, indicating that their model is rather speculative. There is in fact evidence to the contrary, demonstrating that thrombin inhibitors did not abrogate formation of balloons around aggregates in their experiments (Figure 4A in the study by Agbani et al), although they affected its synchrony.Finally, we believe that the hypothetical mechanism explaining the predominant peripheral distribution of ballooned platelets by thrombin diffusion from the core of thrombus is self-contradictory because the basic reaction-diffusion-convection mechanisms imply that thrombin concentration at the outer sites of thrombus should be diminished comparing to the inner sites.7,8 Thus, it is not clear how the significant increase in the number of procoagulant platelets at thrombus periphery can be explained by diffusing thrombin activity.Thus, in our article, we provide a direct evidence for the contraction-driven redistribution of procoagulant platelets being the major cause of their peripheral localization in thrombi formed under flow conditions in vitro. The surface distribution of procoagulant platelets does not depend on thrombin activity and hence cannot be generally explained by the alternative mechanism based on thrombin diffusion, as suggested by Agbani et al.DisclosuresNone.FootnotesFor Disclosures, see page e291.References1. Agbani EO, Williams CM, Hers I, Poole AW. Membrane ballooning in aggregated platelets is synchronised and mediates a surge in microvesiculation.Sci Rep. 2017; 7:2770. doi: 10.1038/s41598-017-02933-4CrossrefMedlineGoogle Scholar2. Agbani EO, Hers I, Poole AW. Temporal contribution of the platelet body and balloon to thrombin generation.Haematologica. 2017; 102:e379–e381. doi: 10.3324/haematol.2017.166819CrossrefMedlineGoogle Scholar3. Nechipurenko DY, Receveur N, Yakimenko AO, Shepelyuk TO, Yakusheva AA, Kerimov RR, Obydennyy SI, Eckly A, Léon C, Gachet C, et al. Clot contraction drives the translocation of procoagulant platelets to thrombus surface.Arterioscler Thromb Vasc Biol. 2019; 39:37–47. doi: 10.1161/ATVBAHA.118.311390LinkGoogle Scholar4. de Witt SM, Verdoold R, Cosemans JM, Heemskerk JW. Insights into platelet-based control of coagulation.Thromb Res. 2014; 133(suppl 2):S139–S148. doi: 10.1016/S0049-3848(14)50024-2CrossrefMedlineGoogle Scholar5. Alberio L, Safa O, Clemetson KJ, Esmon CT, Dale GL. Surface expression and functional characterization of alpha-granule factor V in human platelets: effects of ionophore A23187, thrombin, collagen, and convulxin.Blood. 2000; 95:1694–1702.CrossrefMedlineGoogle Scholar6. Abaeva AA, Canault M, Kotova YN, Obydennyy SI, Yakimenko AO, Podoplelova NA, Kolyadko VN, Chambost H, Mazurov AV, Ataullakhanov FI, et al. Procoagulant platelets form an α-granule protein-covered "cap" on their surface that promotes their attachment to aggregates.J Biol Chem. 2013; 288:29621–29632. doi: 10.1074/jbc.M113.474163CrossrefMedlineGoogle Scholar7. Kuprash AD, Shibeko AM, Vijay R, Nair SC, Srivastava A, Ataullakhanov FI, Panteleev MA, Balandina AN. Sensitivity and robustness of spatially dependent thrombin generation and fibrin clot propagation.Biophys J. 2018; 115:2461–2473. doi: 10.1016/j.bpj.2018.11.009CrossrefMedlineGoogle Scholar8. Tomaiuolo M, Stalker TJ, Welsh JD, Diamond SL, Sinno T, Brass LF. A systems approach to hemostasis: 2. Computational analysis of molecular transport in the thrombus microenvironment.Blood. 2014; 124:1816–1823. doi: 10.1182/blood-2014-01-550343CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails December 2019Vol 39, Issue 12 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/ATVBAHA.119.313479PMID: 31770029 Originally publishedNovember 26, 2019 PDF download Advertisement SubjectsBasic Science ResearchMechanismsPhysiologyPlatelets