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Thromb Haemost 2000; 83(06): 923-930
DOI: 10.1055/s-0037-1613944
Commentary
Schattauer GmbH

Platelets Release Thrombopoietin (Tpo) upon Activation: another Regulatory Loop in Thrombocytopoiesis?

Claudia C. Folman
1   From the Division of Internal Medicine and Dept. of Haematology, Academic Medical Centre, Amsterdam, the Netherlands
2   Dept. of Experimental Immunohaematology, CLB and the Laboratory of Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam
,
Gabor E. Linthorst
1   From the Division of Internal Medicine and Dept. of Haematology, Academic Medical Centre, Amsterdam, the Netherlands
,
Jan van Mourik
3   Dept. of Blood Coagulation, CLB and the Laboratory of Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam
,
Gijsbert van Willigen   #
4   Dept of Haematology, Thrombosis and Haemostasis Laboratory, University Medical Centre Utrecht, the Netherlands
,
Evert de Jonge
1   From the Division of Internal Medicine and Dept. of Haematology, Academic Medical Centre, Amsterdam, the Netherlands
,
Marcel Levi
1   From the Division of Internal Medicine and Dept. of Haematology, Academic Medical Centre, Amsterdam, the Netherlands
,
Masja de Haas
2   Dept. of Experimental Immunohaematology, CLB and the Laboratory of Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam
,
Albert EGKr von dem Borne
1   From the Division of Internal Medicine and Dept. of Haematology, Academic Medical Centre, Amsterdam, the Netherlands
2   Dept. of Experimental Immunohaematology, CLB and the Laboratory of Experimental and Clinical Immunology, Academic Medical Centre, University of Amsterdam, Amsterdam
› Author Affiliations
Further Information

Publication History

Received 21 October 1999

Accepted after resubmission 04 February 2000

Publication Date:
14 December 2017 (online)

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Summary

Thrombopoietin is produced at a constant rate by the liver and kidney and is removed from the circulation upon binding and subsequent uptake via the Tpo receptor, c-Mpl, expressed by platelets and megakaryocytes. Apart from uptake, this study shows that platelets can also function as a storage pool for Tpo.

Upon stimulation with various platelet agonists, full-length biologically active Tpo was released by platelets. Platelet fractionation experiments indicated that this Tpo most likely is contained in the granules. When platelets were preincubated with Tpo-peptide mimetic or truncated Tpo prior to maximal activation, a three- to fivefold increment in Tpo release was seen, whereas, the release of other granule proteins such as vWF-propeptide or serotonin remained unchanged. Therefore, the Mpl agonists might compete with Mpl-bound Tpo, thereby releasing Tpo into the platelet supernatant.

Intravascular release of Tpo by platelets might occur in patients with massive platelet activation, as occurs in patients with disseminated intravascular coagulation. The Tpo concentration in these patients is elevated (p <0.01) and correlates with markers for thrombin generation, TAT complexes and Fl+2 (rp =0.8 and 0.9; p <0.01). This suggests that the increment in Tpo concentration was attributed to Tpo release by activated platelets in vivo, which might be instrumental in subsequent stimulation of thrombocytopoiesis.

Keywords

Thrombopoietin - Tpo - platelets activation - c-Mpl

# G. v. Willigen is a research fellow of the Catharijne Foundation and supported by the Dirk-Zwager Assink Foundation.


 

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