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Clinical phenotype in heterozygote and biallelic B ernard‐ S oulier syndrome—A case control study
Author(s) -
Bragadottir Gudrun,
Birgisdottir Elisabet R.,
Gudmundsdottir Brynja R.,
Hilmarsdottir Bylgja,
Vidarsson Brynjar,
Magnusson Magnus K.,
Larsen Ole Halfdan,
Sorensen Benny,
Ingerslev Jorgen,
Onundarson Pall T.
Publication year - 2015
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23891
Subject(s) - heterozygote advantage , ristocetin , platelet , compound heterozygosity , medicine , immunology , coagulopathy , mutation , endocrinology , von willebrand factor , biology , genotype , genetics , gene
Bernard‐Soulier syndrome (BSS) is a rare severe autosomal recessive bleeding disorder. To date heterozygous carriers of BSS mutations have not been shown to have bleeding symptoms. We assessed bleeding using a semi‐quantitative questionnaire, platelet parameters, PFA‐100 closure times, ristocetin response, GP Ib/IX expression and VWF antigen in 14 BSS patients, 30 heterozygote carriers for related mutations and 29 controls. Eight mutations in GP1BA, GP1BB or GP9 were identified including four previously unknown pathogenic mutations. Subjects with BSS reported markedly more mucocutaneous bleeding than controls. Increased bleeding was also observed in heterozygotes. Compared to controls, patients with BSS had lower optical platelet counts ( P < 0.001), CD61‐platelet counts ( P < 0.001) and higher mean platelet volume (17.7 vs. 7.8 fL, P < 0.001) and ristocetin response and closure times were unmeasurable. Heterozygotes had higher MPV (9.7 fL, P < 0.001) and lower platelet counts ( P < 0.001) than controls but response to ristocetin and closure times were normal. The VWF was elevated in both BSS and in heterozygotes ( P = 0.005). We conclude that heterozygotes for BSS mutations have lower platelet counts than controls and show a bleeding phenotype albeit much milder than in BSS. Both patients with BSS and heterozygote carriers of pathogenic mutations have raised VWF. Am. J. Hematol. 90:149–155, 2015. © 2014 Wiley Periodicals, Inc.