{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:20:22Z","timestamp":1789017622592,"version":"build-2803163510"},"reference-count":49,"publisher":"Georg Thieme Verlag KG","issue":"08","funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["ISCIII, PI10\/02594, PI11\/00566P, PI11\/01256"],"award-info":[{"award-number":["ISCIII, PI10\/02594, PI11\/00566P, PI11\/01256"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007801","name":"Fundaci\u00f3n S\u00e9neca","doi-asserted-by":"crossref","award":["07703\/GERM\/07"],"award-info":[{"award-number":["07703\/GERM\/07"]}],"id":[{"id":"10.13039\/100007801","id-type":"DOI","asserted-by":"crossref"}]},{"name":"ISCIII","award":["FI10\/00535"],"award-info":[{"award-number":["FI10\/00535"]}]},{"name":"IMM holds a Miguel Servet-I contract from ISCIII","award":["CP13\/00126"],"award-info":[{"award-number":["CP13\/00126"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Platelet cold agglutinins (PCA) cause pseudothrombocytopenia, spurious thrombocytopenia due to ex vivo platelet clumping, complicating clinical diagnosis, but mechanisms and consequences of PCA are not well defined. Here, we characterised an atypical immunoglobulin (Ig)M PCA in a 37-year-old woman with lifelong bleeding and chronic moderate thrombocytopenia, that induces activation and aggregation of autologous or allogeneic platelets via interaction with platelet glycoprotein (GP)VI. Patient temperature-dependent pseudothrombocytopenia was EDTA-independent, but was prevented by integrin \u03b1IIb\u03b23 blockade. Unstimulated patient platelets revealed elevated levels of bound IgM, increased expression of activation markers (P-selectin and CD63), low GPVI levels and abnormally high thromboxane (TX)A2 production. Patient serum induced temperature- and \u03b1IIb\u03b23-dependent decrease of platelet count in allogeneic donorcitrated platelet-rich plasma (PRP), but not in PRP from Glanzmann\u2019s thrombasthenia or afibrinogenaemia patients. In allogeneic platelets, patient plasma induced shape change, P-selectin and CD63 expression, 14C-serotonin release, and TXA2 production. Activation was not inhibited by aspirin, cangrelor or blocking anti-Fc receptor (Fc\u03b3RIIA) antibody, but was abrogated by inhibitors of Src and Syk, and by a soluble GPVI-Fc fusion protein. GPVI-deficient platelets were not activated by patient plasma. These data provide the first evidence for an IgM PCA causing platelet activation\/aggregation via GPVI. The PCA activity persisted over a five-year follow-up period, supporting a causative role in patient chronic thrombocytopenia and bleeding.<\/jats:p>","DOI":"10.1160\/th14-11-0945","type":"journal-article","created":{"date-parts":[[2015,5,21]],"date-time":"2015-05-21T08:28:18Z","timestamp":1432196898000},"page":"313-324","source":"Crossref","is-referenced-by-count":6,"title":["An atypical IgM class platelet cold agglutinin induces GPVI-dependent aggregation of human platelets"],"prefix":"10.1160","volume":"114","author":[{"given":"Isabel","family":"S\u00e1nchez Guiu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Mart\u00ednez-Martinez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantino","family":"Mart\u00ednez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Navarro-Fernandez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faustino","family":"Garcia-Candel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca","family":"Ferrer-Mar\u00edn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicente","family":"Vicente","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Watson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Andrews","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Gardiner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Rivera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Lozano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2017,11,21]]},"reference":[{"key":"10.1160\/TH14-11-0945-1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830500206"},{"key":"10.1160\/TH14-11-0945-2","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12443"},{"key":"10.1160\/TH14-11-0945-3","first-page":"1281","volume":"50","author":"Lippi","year":"2012","journal-title":"Clin Chem Lab Med"},{"key":"10.1160\/TH14-11-0945-4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1182\/blood.V56.2.177.177","volume":"56","author":"Onder","year":"1980","journal-title":"Blood"},{"key":"10.1160\/TH14-11-0945-5","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1093\/ajcp\/97.3.359","volume":"97","author":"Cunningham","year":"1992","journal-title":"Am J Clin Pathol"},{"key":"10.1160\/TH14-11-0945-6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.1992.tb02497.x"},{"key":"10.1160\/TH14-11-0945-7","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-3886(98)00033-2"},{"key":"10.1160\/TH14-11-0945-8","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830310110"},{"key":"10.1160\/TH14-11-0945-9","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.32.598"},{"key":"10.1160\/TH14-11-0945-10","doi-asserted-by":"crossref","first-page":"e17","DOI":"10.5858\/2003-127-e17-PAWI","volume":"127","author":"Hsieh","year":"2003","journal-title":"Arch Pathol Lab Med"},{"key":"10.1160\/TH14-11-0945-11","doi-asserted-by":"publisher","DOI":"10.3109\/09537104.2010.516847"},{"key":"10.1160\/TH14-11-0945-12","first-page":"671","volume":"5","author":"Gillis","year":"2003","journal-title":"Isr Med Assoc J"},{"key":"10.1160\/TH14-11-0945-13","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)00688-4"},{"key":"10.1160\/TH14-11-0945-14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.1990.tb00412.x"},{"key":"10.1160\/TH14-11-0945-15","doi-asserted-by":"publisher","DOI":"10.3109\/09537104.2012.731545"},{"key":"10.1160\/TH14-11-0945-16","first-page":"341","volume":"37","author":"Nilsson","year":"1986","journal-title":"Scand J Haematol"},{"key":"10.1160\/TH14-11-0945-17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2004.04009.x"},{"key":"10.1160\/TH14-11-0945-18","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1983.03340180068032"},{"key":"10.1160\/TH14-11-0945-19","doi-asserted-by":"publisher","DOI":"10.1177\/1076029609347902"},{"key":"10.1160\/TH14-11-0945-20","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8652(199901)60:1<80::AID-AJH16>3.0.CO;2-Z"},{"key":"10.1160\/TH14-11-0945-21","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/84.5.640"},{"key":"10.1160\/TH14-11-0945-22","doi-asserted-by":"publisher","DOI":"10.1510\/icvts.2007.154153"},{"key":"10.1160\/TH14-11-0945-23","doi-asserted-by":"crossref","unstructured":"Kocum TH, Katircibasi TM, Sezgin AT, et al. 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