BACKGROUND: The platelet adenosine 5'-diphosphate (ADP) receptor P2Y(12) plays a crucial role in haemostasis. Only a few patients with haemorrhagic diathesis due to molecular defects in the P2Y(12) receptor have been described so far. We report a novel molecular defect in the gene coding for P2Y(12) in a patient with a history of epistaxis, easy bruising and excessive posttraumatic blood loss. METHODS: Platelet aggregation studies, perfusion studies, in which patient blood was perfused over collagen surfaces at arterial shear rates, and PCR and sequencing were used. RESULTS: Platelet aggregation studies showed impaired ADP and collagen-induced aggregation for patient G.S. Perfusion of patient blood over collagen surfaces showed small thrombi consisting of spread platelets overlayered with non-spread platelets. These thrombi were identical to control thrombi formed in the presence of a P2Y(12) antagonist. DNA analysis of the P2Y(12) gene revealed a novel heterozygous base pair C-->A substitution in exon 3, changing codon 258 from proline to threonine in the third extracellular loop of the P2Y(12) receptor. CONCLUSIONS: We conclude that perfusion studies with patient blood are of added value in the diagnostic process, which resulted in identification of a novel molecular defect in the P2Y(12) gene of a patient with haemorrhagic diathesis.
BACKGROUND: The platelet adenosine 5'-diphosphate (ADP) receptor P2Y(12) plays a crucial role in haemostasis. Only a few patients with haemorrhagic diathesis due to molecular defects in the P2Y(12) receptor have been described so far. We report a novel molecular defect in the gene coding for P2Y(12) in a patient with a history of epistaxis, easy bruising and excessive posttraumatic blood loss. METHODS: Platelet aggregation studies, perfusion studies, in which patient blood was perfused over collagen surfaces at arterial shear rates, and PCR and sequencing were used. RESULTS: Platelet aggregation studies showed impaired ADP and collagen-induced aggregation for patient G.S. Perfusion of patient blood over collagen surfaces showed small thrombi consisting of spread platelets overlayered with non-spread platelets. These thrombi were identical to control thrombi formed in the presence of a P2Y(12) antagonist. DNA analysis of the P2Y(12) gene revealed a novel heterozygous base pair C-->A substitution in exon 3, changing codon 258 from proline to threonine in the third extracellular loop of the P2Y(12) receptor. CONCLUSIONS: We conclude that perfusion studies with patient blood are of added value in the diagnostic process, which resulted in identification of a novel molecular defect in the P2Y(12) gene of a patient with haemorrhagic diathesis.
Authors: Anna Lecchi; Eti A Femia; Silvia Paoletta; Arnaud Dupuis; Philippe Ohlmann; Christian Gachet; Kenneth A Jacobson; Katharina Machura; Gian M Podda; Barbara Zieger; Marco Cattaneo Journal: Hamostaseologie Date: 2016-08-04 Impact factor: 1.778
Authors: Anna Lecchi; Cristina Razzari; Silvia Paoletta; Arnaud Dupuis; Lea Nakamura; Philippe Ohlmann; Christian Gachet; Kenneth A Jacobson; Barbara Zieger; Marco Cattaneo Journal: Blood Date: 2014-11-26 Impact factor: 22.113
Authors: Shaista Nisar; Martina E Daly; Augusto B Federici; Andrea Artoni; Andrew D Mumford; Stephen P Watson; Stuart J Mundell Journal: Blood Date: 2011-09-21 Impact factor: 22.113
Authors: Stefan Amisten; Oscar O Braun; Lovisa Johansson; Martin Ridderstråle; Olle Melander; David Erlinge Journal: PLoS One Date: 2008-01-23 Impact factor: 3.240