Regular Article Glycoproteins expression on platelet membrane in inherited macrothrombocytopenias Sı ´lvia Pe ´rez-Pujol a , Miguel Lozano a, * , Gine ´s Escolar a , Maribel Dı ´az-Ricart a , Nu ´ria Pujol-Moix b , Antonio Ordinas a a Department Hemotherapy and Hemostasis, Biomedical Diagnosis Center, Hospital Clinic Provincial, Augusti ´ Pii Sunye ´ Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain b Department of Hematology, Hospital Santa Creu I Sant Pau, Authonomous University of Barcelona, Barcelona, Spain Received 20 October 2003; received in revised form 5 December 2003; accepted 9 December 2003 Abstract Introduction: Inherited giant platelet disorders (IGPD) are a heterogeneous group of rare diseases characterized by thrombocytopenia, large platelets and variable bleeding symptoms. Glycoprotein (GP) expression on platelet surface in these conditions is poorly characterized. We have investigated the expression of constitutively expressed platelet membrane GP and the response to TRAP activation in a group of patients with different forms of inherited macrothrombocytopenias. Materials and methods: Two patients diagnosed Epstein syndrome (ES), two with Bernard-Soulier syndrome (BSS) and eight with Mediterranean macrothrombocytopenia (MM) were studied using flow cytometry combined to monoclonal antibodies (MoAbs). Mean platelet volume was also measured. Results: In general, there was an increase in the binding of MoAbs directed against platelet membrane GPs in the patients studied (except, obviously, in BSS patients). The observed increase ranged between 0.9 and 3.36 times the value of the control for GPIba, between 1.36 and 7.2 times for GPIIb–IIIa and 0.94 and 8.07 times for GPIV. However, when the observed value was divided by the measured platelet volume, the estimated density was similar to controls in the case of GPIba but were increased for GPIIb – IIIa and GPIV. TRAP activation provoked significant increments in the number of copies of GPIIb –IIIa complexes present on platelet surface in controls (91%), MM patients (49%), but almost no changes in BSS platelets (6%). Conclusion: In the group of macrothrombocytopenia studied, an increase in the expression of platelet membrane GP was observed, although a wide variability exists even in patients with the same disorder. D 2004 Elsevier Ltd. All rights reserved. Keywords: Platelets; Flow cytometry; Platelet glycoproteins; Bleeding; Inherited macrothrombocytopenias 1. Introduction Inherited giant platelet disorders (IGPD) are a hetero- geneous group of rare diseases characterized by throm- bocytopenia, large platelets and variable bleeding symptoms. A proposed working classification would be to group them into three categories. The first group is based on structural defects including glycoprotein abnor- malities (Bernard-Soulier syndrome (BSS) and GPIV abnormalities), a calpain defect (Montreal platelet syn- drome) and an a-granule defect (gray platelet syn- drome). The second group is based on a distinctive morphologic finding such as neutrophil inclusions and/or systemic manifestation (May-Hegglin anomaly (MHA) and Sebastian syndrome (SS), hereditary macrothrombo- cytopenia with hearing loss, Epstein syndrome (ES) and Fechtner syndrome (FS), which also exhibits neutrophil inclusions). The third group is considered a benign anomaly, such as Mediterranean macrothrombocytopenia (MM) [1]. However, some have questioned this classi- fication suggesting adding two new groups consisting of isolated IGPD without functional abnormalities and a Wiskott-Aldrich syndrome variant-related giant platelet disorder [2]. Interestingly, recent investigations have mapped the genetic defect underlying MHA, SD, ES and FS to the same gene, i.e. the non-muscle myosin heavy chain IIA gene named MYH9 located in chro- 0049-3848/$ - see front matter D 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.thromres.2003.12.010 * Corresponding author. Tel.: +34-932-275-448; fax: +34-932-279- 369. E-mail address: mlozano@clinic.ub.es (M. Lozano). Thrombosis Research 112 (2003) 233 – 237