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Thromb Haemost 1998; 80(05): 735-742
DOI: 10.1055/s-0037-1615351
Review Article
Schattauer GmbH

A Glanzmann Thrombasthenia-like Phenotype Caused by a Defect in Inside-Out Signaling through the Integrin αIIbβ3

Yoshiaki Tomiyama
1   From the Second Department of Internal Medicine, Osaka University Medical School
,
Masamichi Shiraga
1   From the Second Department of Internal Medicine, Osaka University Medical School
,
Seiji Kinoshita
3   From the Department of Pediatrics, Higashi Osaka Central Hospital, Osaka
,
Hironobu Ambo
4   From the Department of Internal Medicine, Keio University, Tokyo, Japan
,
Yoshiyuki Kurata
2   From the Department of Blood Transfusion, Osaka University Hospital, Osaka
,
Yuji Matsuzawa
1   From the Second Department of Internal Medicine, Osaka University Medical School
,
Thomas J. Kunicki
5   From the Departments of Molecular and Experimental Medicine and Vascular Biology, the Scripps Research Institute, La Jolla, CA, USA
› Author Affiliations
Further Information

Publication History

Received 13 January 1998

Accepted after revision 04 August 1998

Publication Date:
07 December 2017 (online)

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Summary

Activation of the platelet integrin αIIbβ3, an essential step in platelet aggregation, is regulated by intracellular signal pathways (inside-out signaling). In this study, we characterize a 35-year-old Japanese female, HM, with a life-long history of mucocutaneous bleeding. HM showed a Glanzmann thrombasthenia-like phenotype with normal expression of αIIbβ3, and failure of platelet aggregation induced by various agonists. An activation-independent ligand mimic monoclonal antibody (mAb), OP-G2, and RGDS peptides bound normally to the patient‘s αIIbβ3„ while an activating anti-β3 mAb, AP5, induced normal aggregation of HM platelets. The nucleotide sequence of the entire coding region of the patient‘s αIIb and β3, including the cytoplasmic domains of each subunit, revealed no abnormalities. Agonist-induced phosphorylation of platelet pleckstrin and myosin light chain was not impaired. Recently, we proposed that a Na+/Ca2+ exchanger is involved in inside-out signaling, especially in the case of chymotrypsin-induced αIIbβ3 activation (Blood 88: 2594, 1996). However, chymotrypsin-induced platelet aggregation occurred normally in patient HM. Measurement of changes in cytosolic free calcium concentration ([Ca2+]i) revealed that the plateau level of [Ca2+]i after thrombin stimulation was significantly inhibited in patient HM. Our data suggest that patient HM exhibits a Glanzmann thrombasthenia-like phenotype associated with an abnormality in inside-out signaling which would otherwise activate αIIbβ3.

 

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