Von Willebrand disease R1374C:: Type 2A or 2M?: A challenge to the revised classification.: High frequency in the northwest of Spain (Galicia)
Von Willebrand disease R1374C:: Type 2A or 2M?: A challenge to the revised classification.: High frequency in the northwest of Spain (Galicia)
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DOI：
10.1002/ajh.20470
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发表时间：
2005-11-01
影响因子：
12.8
通讯作者：
Batlle, J
中科院分区：
文献类型：
--
作者：
Penas, N;Pérez-Rodríguez, A;Batlle, J
最初诊断为1型血管性血友病（VWD）的患者在几项研究中进行了更详尽的分析后被重新分类为2型。本研究的目的是（1）重新分析先前诊断为I型的患者，以获得更准确的诊断;（2）比较血管性血友病因子（VWF）ristocytokine辅因子测定（VWF：RCo）和VWF胶原结合测定（VWF：CB），以评估后者在VWD诊断中取代前者测定的可能性。来自两个无血缘关系的大家庭的21例患者和104名正常对照进行了研究。检测VWF：Ag、VWF：RCo、FVIII凝血活性（FVIII：C）、出血时间（BT）、PFA（100）和VWF的多聚体分析。还通过测序VWF基因上的外显子28进行遗传分析。患者表现出较低水平的VWF：Ag和VWF：RCo，VWF：RCo/VWF-Ag之间的分离，以及血浆VWF中所有大小的多聚体的存在。VWF：CB的结果取决于所用胶原的类型。遗传学分析表明R1374 C突变是2 M型VWD的致病基因。在西班牙西北部（加利西亚）观察到高频率的R1374 C突变。有些类型的2 M VWD被误诊为I型VWD。VWF：CB（含I型胶原）试验无法区分R1374 C VWF的检测血小板结合。这证实了VWF：CB不能替代VWF：RCo，诊断VWD时应同时进行检测。
Patients initially diagnosed with type 1 von Willebrand disease (VWD) have been reclassified as type 2 after a more exhaustive analysis in several studies. Our study's objectives were (1) to reanalyze patients that were previously diagnosed as type I to achieve a more accurate diagnosis and (2) to compare the von Willebrand factor (VWF) ristocetin cofactor assay (VWF:RCo) and the VWF collagen binding assay (VWF:CB) in order to evaluate the possibility of replacing the former assay with the latter in the diagnosis of VWD. Twenty-one patients from two large unrelated families and 104 normal controls were studied. VWF:Ag, VWF:RCo, FVIII coagulant activity (FVIII:C), bleeding time (BT), PFA(100), and multimeric analysis of VWF were tested. Genetic analysis by sequencing exon 28 on the VWF gene was also carried out. Patients presented lower levels of VWF:Ag and VWF:RCo, a dissociation between VWF:RCo/VWF-Ag, and the presence of all sizes of multimers in plasma VWF. The results for VWF:CB varied depending on the type of collagen used. The genetic analysis showed that the mutation R1374C Is responsible for type 2M VWD. A high frequency of the R1374C mutation Is observed In northwestern Spain (Galicia). Some types of 2M VWD are misdiagnosed as type I VWD. The VWF:CB (with type I collagen) assay was unable to discriminate detective platelet binding of the R1374C VWF. This confirms that VWF:CB cannot substitute for VWF:RCo, and both should be tested when diagnosing VWD.