{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T22:37:17Z","timestamp":1782254237339,"version":"3.54.5"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"05","funder":[{"DOI":"10.13039\/501100001030","name":"National Heart Foundation of Australia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001030","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2005]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>We have identified a patient with IgD \u03bb-type multiple myeloma who was characterized by a severe bleeding tendency, especially after puncture of arterial vessels. Both the bleeding time (&gt;25 min) and activated partial thromboplastin time (APTT) were prolonged. To clarify the underlying pathogenesis, we purified the APTT-prolonging activity from the patient\u2019s serum. The purified protein was a highly negatively-charged homodimer of the \u03bb light chain. The \u03bb dimer protein (M-protein) inhibited ristocetin-and high shear-induced platelet aggregation, dependent on platelet glycoprotein Ib\u03b1 (GPIb\u03b1), but not epinephrine-, collagen-, ADP-, thrombin-, or botrocetin-induced platelet aggregation. The \u03bb dimer protein inhibited the binding of platelets to immobilized or ristocetin-treated von Willebrand factor (VWF). Furthermore, a 39\/34 kD fragment of VWF encompassing the A1 domain specifically bound to the immobilized \u03bb dimer protein in the presence of ristocetin, suggesting that the \u03bb dimer protein directly binds to the A1 domain of VWF. To help elucidate the binding site within the A1 domain, binding of ristocetin-treated VWF to the immobilized \u03bb dimer protein was assayed in the presence of various anti-A1 domain monoclonal antibodies. Based on these data, we conclude that the \u03bb dimer protein binds to the region of the A1 domain composed of helices \u03b13 and \u03b14 and thus interferes with VWF-GPIb\u03b1 interaction. The existence of a protein that inhibits high shear-induced platelet aggregation in acquired von Willebrand disease (VWD) has only rarely been reported. The results suggest that the hemostatic function in arteries with high shear force is profoundly disrupted if the binding of GPIb\u03b1 to VWF is abrogated, supporting the relevance of shear-induced VWF interaction with GPIb\u03b1 in the initiation of the hemostatic process.<\/jats:p>","DOI":"10.1160\/th04-03-0193","type":"journal-article","created":{"date-parts":[[2005,4,13]],"date-time":"2005-04-13T13:10:02Z","timestamp":1113397802000},"page":"889-896","source":"Crossref","is-referenced-by-count":20,"title":["Characterization of a myeloma patient with a life-threatening hemorrhagic diathesis: presence of a lambda dimer protein inhibiting shear-induced platelet aggregation by binding to the A1 domain of vonWillebrand factor"],"prefix":"10.1160","volume":"93","author":[{"given":"Atsushi","family":"Shinagawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Berndt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Kaneko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumi","family":"Suzukawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Hasegawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Shigeta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiro","family":"Nagasawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2017,12,11]]},"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1160\/TH04-03-0193.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T16:31:12Z","timestamp":1540398672000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1160\/TH04-03-0193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005]]},"references-count":0,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2017,12,11]]},"published-print":{"date-parts":[[2005]]}},"URL":"https:\/\/doi.org\/10.1160\/th04-03-0193","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005]]}}}