Weiss H J, Pietu G, Rabinowitz R, Girma J P, Rogers J, Meyer D
J Lab Clin Med. 1983 Mar;101(3):411-25.
FVIII/VWF in plasma and platelets was studied by various methods in 16 patients with von Willebrand's disease. These methods included measurements of both VIIIR:Ag and VIIIR:RCo levels, radio-crossed immunoelectrophoresis, analysis of the dose-response curves with both fluid-phase and two-site immunoradiometric assays, and SDS-agarose-acrylamide gel electrophoresis. Studies of normal plasma and platelets by the last-named method disclosed the presence of nine to 10 clearly resolvable bands with molecular weights of approximately 1 to 10 X 10(6) and unresolved higher-molecular-weight material, consistent with the previously described multimeric structure of FVIII/VWF. The multimeric structure and antigenic reactivity of FVIII/VWF were normal in 11 patients with type I von Willebrand's disease. However, measurements of the VIIIR:Ag content in plasma and platelets disclosed the presence of three subgroups. In one (type I-1), the VIIIR:Ag content of both plasma and platelets was decreased; in type I-2, VIIIR:Ag was decreased in plasma but normal in platelets, whereas the reverse was found in two patients with type I-3. In five patients with type IIA von Willebrand's disease we observed various abnormalities in the multimeric structure and antigenic reactivity of FVIII/VWF. The distinguishing features in two patients, designated type IIA-1 and IIA-2, were a decreased amount of high-molecular-weight FVIII/VWF and an impaired antigenic reactivity in both plasma and platelets; the defects in type IIA-2 were qualitatively different and more strikingly abnormal than those in type IIA-1. In three other patients, designated type IIIA-3, a less severe deficit of high-molecular-weight FVIII/VWF in plasma was observed and, in addition, the multimeric structure of FVIII/VWF in platelets was normal. The findings in this study demonstrate that a variety of defects in the synthesis, release, antigenic reactivity, and multimerization of FVIII/VWF are probably responsible for the heterogeneous findings in patients with von Willebrand's disease.
采用多种方法对16例血管性血友病患者血浆和血小板中的FVIII/VWF进行了研究。这些方法包括VIIIR:Ag和VIIIR:RCo水平的测定、放射交叉免疫电泳、液相和双位点免疫放射分析剂量反应曲线以及SDS-琼脂糖-丙烯酰胺凝胶电泳。用最后一种方法对正常血浆和血小板进行研究发现，存在9至10条清晰可辨的条带，分子量约为1至10×10⁶，还有未分辨的高分子量物质，这与先前描述的FVIII/VWF多聚体结构一致。11例I型血管性血友病患者的FVIII/VWF多聚体结构和抗原反应性正常。然而，血浆和血小板中VIIIR:Ag含量的测定显示存在三个亚组。在一个亚组（I-1型）中，血浆和血小板中的VIIIR:Ag含量均降低；在I-2型中，血浆中VIIIR:Ag降低，但血小板中正常，而在两名I-3型患者中情况相反。在5例IIA型血管性血友病患者中，我们观察到FVIII/VWF的多聚体结构和抗原反应性存在各种异常。在两名分别命名为IIA-1和IIA-2的患者中，其特征是高分子量FVIII/VWF数量减少，血浆和血小板中的抗原反应性受损；IIA-2型的缺陷在性质上有所不同，且比IIA-1型更明显异常。在另外三名分别命名为IIIA-3型的患者中，观察到血浆中高分子量FVIII/VWF的缺乏程度较轻，此外，血小板中FVIII/VWF的多聚体结构正常。本研究结果表明，FVIII/VWF在合成、释放、抗原反应性和多聚化方面的各种缺陷可能是血管性血友病患者出现异质性表现的原因。
