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Thromb Haemost 2007; 97(06): 965-973
DOI: 10.1160/TH06-12-0680
Platelets and Blood Cells
Schattauer GmbH

Parnaparin, a low-molecular-weight heparin, prevents P-selectindependent formation of platelet-leukocyte aggregates in human whole blood

Norma Maugeri
1   Laboratory of Cell Biology and Pharmacology of Thrombosis, Research Laboratories, “John Paul II” Centre for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
,
Giovannina Di Fabio
1   Laboratory of Cell Biology and Pharmacology of Thrombosis, Research Laboratories, “John Paul II” Centre for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
,
Miriam Barbanti
2   Alfa Wassermann, Bologna, Italy
,
Giovanni de Gaetano
1   Laboratory of Cell Biology and Pharmacology of Thrombosis, Research Laboratories, “John Paul II” Centre for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
,
Maria Benedetta Donati
1   Laboratory of Cell Biology and Pharmacology of Thrombosis, Research Laboratories, “John Paul II” Centre for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
,
Chiara Cerletti
1   Laboratory of Cell Biology and Pharmacology of Thrombosis, Research Laboratories, “John Paul II” Centre for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
› Author AffiliationsFinancial support: This work was partially supported by Alfa-Wasserman, Bologna, Italy and by the Italian Ministry of University and Research (MIUR, Programma Triennale di Ricerca, decreto 1588).
Further Information

Publication History

Received 01 December 2006

Accepted after resubmission 21 March 2007

Publication Date:
27 November 2017 (online)

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Summary

Parnaparin, a low-molecular-weight heparin (LMWH), prevents platelet activation and interaction with polymorphonuclear leukocyte (PMN) in a washed cell system. The in-vitro effect of parnaparin was studied here on platelet-PMN aggregates formed with more physiologic approaches in whole blood, in parallel with unfractionated heparin and enoxaparin, another LMWH. Citrated blood from healthy subjects was stimulated: i) from passage through the “Platelet Function Analyzer” (PFA-100), a device that exposes blood to standardized high shear flow through collagen/ADP cartridges; ii) by collagen and ADP (2 and 50 µg/ml, respectively) added in combination under stirring in an aggregometer cuvette; iii) with recombinant Tissue Factor, to generate thrombin concentrations able to activate platelets without inducing blood clotting, or iv) the Thrombin Receptor Activating Peptide-6 (TRAP-6). Platelet P-selectin and platelet-PMN aggregates were measured by flow cytometry upon stimulation of blood. Fibrinogen binding to platelets and markers of PMN activation were also detected. Platelet P-selectin expression and platelet-PMN aggregate formation were induced in all four activation conditions tested. Parnaparin prevented in a concentration-dependent manner (0.3–0.8 IUaXa/ml) the expression of P-selectin and the formation of mixed aggregates, while the two reference heparin preparations had a much weaker effect. Platelet fibrinogen binding and PMN activation markers (fibrinogen binding, CD11b and CD40) were also prevented by parnaparin. These data extend in more physiological systems of platelet activation, the anti-inflammatory profile of parnaparin, previously reported in washed cells. The greater effect of parnaparin, as compared to the reference heparins, could be due to chemico-physical differences possibly unrelated to their anticoagulant effect.

Keywords

LMWH - inflammation - platelet-PMN aggregates - P-selectin
 

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