Batlle J, Lopez Fernandez M F, Campos M, Justica B, Berges C, Navarro J L, Diaz Cremades J M, Kasper C K, Dent J A, Ruggeri Z M
Blood. 1986 Dec;68(6):1207-12.
The absence of large von Willebrand factor (vWF) multimers from plasma is a characteristic of Type IIA von Willebrand's disease (vWD) and is thought to contribute to the clinical expression of this disorder. Recently, three IIA patients have been reported in whom intermediate and large multimers could be restored if blood were collected in 5 mm EDTA, 6 mmol/L N-ethylmaleimide, and 1 mmol/L leupeptin. This suggested that absence of large multimers resulted from in vitro proteolysis. We have now collected blood from ten Type IIA vWD patients in these inhibitors but were not able to detect large multimers in the plasma of any of them. In addition, intermediate-sized multimers were reduced or completely absent in all. The inclusion of inhibitors in the citrate anticoagulant, as compared to citrate alone, was found to increase the relative proportion of intermediate multimers in some patients but had no effect in others, and in none did it restore large multimers to plasma. The results with platelet vWF were more varied. Four patients showed an absence or decrease of large multimers, whereas in seven patients large multimers were present. When compared with citrate anticoagulant alone, the inclusion of inhibitors in the anticoagulant had little or no effect on the platelet multimeric pattern. 1-Deamino-8-D-Arginine Vasopressin (DDAVP) was administered to six patients from five families. Two patients from one family showed complete correction and a third patient showed almost complete correction of her bleeding time. Two patients showed minimal correction and one showed no detectable correction. An increase in multimer size after DDAVP tended to be associated with correction of the bleeding time. However, in no case did the largest multimers appear in plasma even in patients with complete bleeding time correction. The presence or absence of inhibitors in the anticoagulant had little or no effect on the multimeric pattern after DDAVP. These results indicate that Type IIA vWD is a heterogeneous disorder in which absence of largest and intermediate multimers is an in vivo phenomenon.
血浆中缺乏大分子量血管性血友病因子（vWF）多聚体是IIA型血管性血友病（vWD）的一个特征，并且被认为与该疾病的临床表现有关。最近，有报道称3例IIA型患者，如果血液采集于含有5 mmol/L乙二胺四乙酸（EDTA）、6 mmol/L N - 乙基马来酰胺和1 mmol/L亮抑酶肽的溶液中，其中等大小和大分子量的多聚体能够得以恢复。这表明大分子量多聚体的缺失是由体外蛋白水解所致。我们现在从10例IIA型vWD患者中采集了加入这些抑制剂的血液，但在他们任何一人的血浆中均未能检测到大分子量多聚体。此外，所有患者中等大小的多聚体均减少或完全缺失。与单独使用枸橼酸盐抗凝剂相比，在枸橼酸盐抗凝剂中加入抑制剂，发现在一些患者中可增加中等多聚体的相对比例，但在其他患者中则无作用，且在任何患者中均未使大分子量多聚体恢复至血浆中。血小板vWF的结果则更为多样。4例患者显示大分子量多聚体缺失或减少，而7例患者存在大分子量多聚体。与单独使用枸橼酸盐抗凝剂相比，在抗凝剂中加入抑制剂对血小板多聚体模式几乎没有影响。对来自5个家系的6例患者给予1 - 去氨基 - 8 - D - 精氨酸血管加压素（DDAVP）。来自一个家系的2例患者出血时间完全纠正，第3例患者出血时间几乎完全纠正。2例患者出血时间轻度纠正，1例患者未检测到出血时间纠正。DDAVP给药后多聚体大小增加往往与出血时间的纠正相关。然而，即使在出血时间完全纠正的患者中，血浆中也从未出现最大分子量的多聚体。抗凝剂中抑制剂的存在与否对DDAVP给药后的多聚体模式几乎没有影响。这些结果表明，IIA型vWD是一种异质性疾病，其中最大分子量和中等大小多聚体的缺失是一种体内现象。
