{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T04:52:44Z","timestamp":1761540764553},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,7,11]],"date-time":"2006-07-11T00:00:00Z","timestamp":1152576000000},"content-version":"vor","delay-in-days":5184,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[1992,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A new family with a bleeding diathesis and FVIII deficiency secondary to abnormal binding of von Willebrand factor (vWF) to factor VIII (FVIII) is described. Two propositi of this family, an 18\u2010year\u2010old male and a 33\u2010year\u2010old female, both with a history of epistaxis, bruising, bleeding from the gums, epistaxis, hemarthrosis, and hematoma, were analyzed. Also additional members of the same family with no bleeding history were also studied. The propositi showed normal vWF activities, low FVIII activity; one of them had been diagnosed as having hemophilia A and the other was a hemophilia A carrier. Both showed a very poor response to treatment with FVIII concentrates and desmopressin (DDAVP) but a good clinical response to cryoprecipitate. APTT was prolonged and no inhibitory activity was noticeable in their plasmas. Thirty\u2010five units per kilogram body weight of Hemofil M was infused to both propositi and FVIII reached basal level within 60 minutes of the infusion. No FVIII response at all was observed in the female after intravenous DDAVP administration. However, the male who received the infusion of 35 U\/kg body weight of Humate\u2010P achieved a normal FVIII level that was maintained for 12 hours. Multimeric analysis of vWF was normal in all the members studied. Von Willebrand factor domain for FVIII binding was assayed in the two propositi and in six other members of the same family by using a non\u2010isotopic and sensitive method, a modification of the one previously described, using the Hemofil M concentrate as exogenous FVIII. The data obtained showed that both propositi had similar binding to that observed by using plasma of a patient with severe von Willebrand disease. Furthermore, five siblings had a decreased binding of vWF to FVIII, when compared with plasma from normal individuals or patients with hemophilia A. We also observed that, for screening purpose, the ratio of bound FVIII\/immobilized vWF (at saturation of the anti\u2010vWF and offering of 1 U\/ml of exogenous FVIII) distinguished two levels of abnormality (normal range 0.70\u20131.15, propositi 0,004\u20130.007, and remaining members affected 0.25\u20130.42). The most probable explanation is that the propositi are homozygous or double heterozygous, the other five siblings affected being heterozygous for a recessive vWF defect. This more accessible assay presented here may be of help in routine analysis for diagnosing this type of von Willebrand disease, which has important implications for therapy and genetic counseling. \u00a9 1992 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.2830400105","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T13:03:24Z","timestamp":1172063004000},"page":"20-27","source":"Crossref","is-referenced-by-count":29,"title":["Further evidence for recessive inheritance of von willebrand disease with abnormal binding of von willebrand factor to factor VIII"],"prefix":"10.1002","volume":"40","author":[{"given":"M. F.","family":"Lopez\u2010Fernandez","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. J.","family":"Blanco\u2010Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. P.","family":"Casti\u00f1eira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Batlle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,11]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"895","article-title":"Review: Von Willebrand factor and von Willebrand disease","volume":"70","author":"Ruggeri ZM","year":"1987","journal-title":"Blood"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0950-3536(89)80037-X"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V74.5.1591.1591"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V75.1.20.20"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1990.tb06371.x"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830360302"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.5.1648"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830210207"},{"key":"e_1_2_1_10_2","first-page":"325","volume-title":"Coagulation and Bleeding Disorders. 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recombinant von Willebrand factor Normandy, vWF (T28M), an autosomal mutation that mimics Hemophilia A","volume":"65","author":"Sadler JE","year":"1991","journal-title":"Thromb Haemost"},{"key":"e_1_2_1_23_2","first-page":"803","article-title":"Identification of two candidate mutations in the von Willebrand factor gene of patients with von Willebrand factor defect in factor VIII binding (von Willebrand disease \u201cNormandy\u201d)","volume":"65","author":"Gaucher C","year":"1991","journal-title":"Thromb Haemost"},{"key":"e_1_2_1_24_2","first-page":"802","article-title":"Molecular characterization of a unique von Willebrand disease variant: A novel mutation affecting von Willebrand factor\/factor VIII interaction","volume":"65","author":"Nichols WC","year":"1991","journal-title":"Thromb Haemost"},{"key":"e_1_2_1_25_2","first-page":"802","article-title":"Identification and expression of a missense mutation in the factor VIII\u2010binding region of von Willebrand 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