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Thromb Haemost 2005; 93(01): 130-138
DOI: 10.1160/TH04-05-0312
Platelets and Blood Cells
Schattauer GmbH

Defective collagen-induced platelet activation in two patients with malignant haemopathies is related to a defect in the GPVI-coupled signalling pathway

Sylvia Bellucci
1   AP-HP, Hôpital Lariboisiere, Laboratory of Haematology, Paris, France
,
Marie G. Huisse
2   AP-HP, Hôpital Bichat, Laboratory of Haematology-Immunology, Paris, France
6   INSERM E348, Faculté Xavier-Bichat, Paris, France
,
Bernadette Boval
1   AP-HP, Hôpital Lariboisiere, Laboratory of Haematology, Paris, France
,
Patricia Hainaud
3   IVS, Hôpital Lariboisi#x00E8;re, Paris, France
,
Annie Robert
4   AP-HP, Hôpital Saint-Antoine, Laboratory of Haematology, Paris, France
,
Françoise Fauvel-Lafève
5   INSERM U 553, Hôpital Saint-Louis, Paris, France
,
Martine Jandrot-Perrus
6   INSERM E348, Faculté Xavier-Bichat, Paris, France
› Author Affiliations
Further Information

Publication History

Received 17 May 2004

Accepted after resubmission 10 October 2004

Publication Date:
14 December 2017 (online)

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Summary

The occurrence of a thrombocytopathy concomitantly to the development of a malignant haemopathy has been reported for some time, but little is known about the mechanism(s) involved in the platelet dysfunction. Platelet glycoprotein VI (GPVI) has now been identified as a principal platelet receptor for collagen. In this paper, we report the cases of two patients with a myelodysplasia and a B lymphopathy, respectively, who presented with thrombocytopathy in relation to a defective GPVI-mediated platelet reactivity to collagen. Thus, with regard to the different steps of adhesion, activation secretion or aggregation, patients’ platelet responses to collagen and to the GPVI specific agonists, collagen related peptide (CRP) or convulxin were null or dramatically impaired. Platelet responses to other agonists ADP, TRAP,Arachidonic acid were normal or showed only a moderate decrease. GPVI content was repeatedly normal, and binding of specific ligands, such as convulxin, satisfactory. Nevertheless, specific activating monoclonal antibodies and convulxin failed to induce platelet secretion; collagen, CRP or convulxin were unable to provoke calcium mobilisation. Furthermore, using a perfusion chamber model, we showed that ex vivo collagen-induced thrombi formation was very impaired.Taken together,these data provide evidence, for the first time, of an acquired defect in GPVI-mediated platelet reactivity to collagen, which reflects data observed in constitutional GPVI deficiencies, in two patients with malignant haemopathies.

Keywords

Collagen - glycoprotein - VI - platelet function - myelodysplasia - chronic lymphocytic leukamia
 

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