Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD
Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD
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DOI：
10.1182/blood-2007-08-109231
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发表时间：
2008-04-01
期刊：
影响因子：
20.3
通讯作者：
Rodeghiero, Francesco
中科院分区：
文献类型：
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作者：
Castaman, Giancarlo;Lethagen, Stefan;Rodeghiero, Francesco
我们前瞻性评估了77例1型血管性血友病（VWD）患者对去氨加压素的生物学反应，这些患者入选了1型VWD诊断和治疗的分子和临床标志物项目。对去氨加压素的完全应答定义为输注后瑞斯托康辅助因子活性（VWF：RCo）和凝血因子VIII活性（FVIII：C）均升高至50 IU/dL或更高，部分应答定义为VWF：RCo或FVIII：C低于50 IU/dL，但至少为基础水平的3倍。在83%的患者中观察到完全缓解; 13%部分缓解; 4%无缓解。VWF多聚体模式异常的患者与多聚体模式正常的患者相比，基础FVIII：C和VWF显著降低，VWF：RCo/Ag比值降低，去氨加压素完全反应降低（P =.002）。在D '-D3结构域中密码子1130和1205处突变的患者在输注后具有最大的相对增加，但具有最短的FVIII和VWF半衰期。大多数部分和无反应的患者在A1-A3结构域有突变。这些VWD患者对去氨加压素的反应似乎与致病突变的位置有关。微妙的多聚体异常的存在并不妨碍潜在的临床有用的反应，在典型的1型VWD。
We have prospectively evaluated the biologic response to desmopressin in 77 patients with type 1 von Willebrand disease (VWD) enrolled within the Molecular and Clinical Markers for the Diagnosis and Management of type 1 VWD project. Complete response to desmopressin was defined as an increase of both ristocetin cofactor activity (VWF:RCo) and factor VIII coagulant activity (FVIII:C) to 50 IU/dL or higher and partial response as VWF: RCo or FVIII:C lower than 50 IU/dL after infusion, but at least 3-fold the basal level. Complete response was observed in 83% of patients; partial in 13%; and no response in 4%. Patients with some abnormality of VWF multimeric pattern had significantly lower basal FVIII:C and VWF, lower VWF:RCo/Ag ratio, and less complete responses to desmopressin than patients with a normal multimeric pattern (P =.002). Patients with mutations at codons 1130 and 1205 in the D'-D3 domain had the greatest relative increase, but shortest FVIII and VWF half-lives after infusion. Most partial and nonresponsive patients had mutations in the A1-A3 domains. Response to desmopressin in these VWD patients seemed to be associated with the location of the causative mutation. The presence of subtle multimeric abnormalities did not hamper potential clinically useful responses, as in typical type 1 VWD.