Influence Of High Molecular Weight Factor VIII On The Expression Of Factor VIII Procoagulant Activity
Influence Of High Molecular Weight Factor VIII On The Expression Of Factor VIII Procoagulant Activity
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高分子量因子VIII对因子VIII促凝血活性表达的影响
DOI：
10.1055/s-0038-1652746
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发表时间：
1981
影响因子：
6.7
通讯作者：
Martin Semar
中科院分区：
文献类型：
--
作者：
Alan Johnson;M. Soberano;Steven Kowalski;Anne Fulton;V. Macdonald;Martin Semar
研究了凝血因子VIII的高分子量（HMW）和低分子量（LMW）部分在表达促凝血活性（VIIIC）中的关系。LMW VIII C通过免疫吸附色谱法制备; HMW VIII通过在4%琼脂糖中对血友病性冷冻沉淀进行色谱法制备。通过免疫吸附色谱法获得的LMW VIII C在使用von Willebrand病血浆作为底物的一个阶段部分凝血活酶时间（PTT）系统中进行测试时，得到了比使用血友病血浆作为底物更高的VIII C值。这一发现是由于基质血浆中的VIII相关抗原（VIIIR：Ag）所致。当VIIIR：Ag通过免疫吸附从血友病底物血浆中除去时，获得的低分子量VIII C的VIII C值较高。此外，将纯化的HMW VIII添加到血管性血友病底物血浆中导致PTT系统中LMW VIII C的VIII C值较低。当在两阶段试验中检测LMW VIII C时，所有VIII C均吸附至Al（OH）3。通过将LMW VIII C与血友病血浆混合来防止其吸附。从正常的未稀释的血浆中，只有5 - 21%的VIII C和没有VIII相关抗原被吸附到Al（OH）3，但在通过少量凝血酶活化正常血浆的因子VIII后，大部分VIII C被吸附。活化后无VIII相关抗原吸附。然而，当使用和不使用HMW VIII或VIIIR：Ag通过两阶段方法测定未吸附的LMW VIII C时，结果相同。我们的研究表明VIIIR：Ag在一定程度上阻止了LMW VIII C的活化。未被VIIIRiAg结合或保护的LMW VIII C通过Al（OH）3从血浆中吸附。这些发现可能有助于解释在某些患者和某些临床情况下使用一阶段和两阶段测定法发现的VIII C差异。
The relationship of the high molecular weight (HMW) moiety and low molecular weight (LMW) moiety of factor VIII in expressing procoagulant activity (VIII C) was studied. LMW VIII C was prepared by immunoadsorbent chromatography; HMW VIII was prepared by chromatographing hemophilic cryo- precipitate in 4% agarose. The LMW VIII C obtained by immunoadsorbent chromatography gave higher VIII C values when tested in the one stage partial thromboplastin time (PTT) system using von Willebrand’s disease plasma as substrate than using hemophilic plasma as substrate. This finding was shown to be due to the VIII related antigen (VIIIR:Ag) in the substrate plasmas. When the VIIIR:Ag was removed from the hemophilic substrate plasma by immuno-adsorption, the VIII C values obtained for the LMW VIII C were higher. Also, adding purified HMW VIII to the von Willebrand’s disease substrate plasma resulted in lower VIII C values for the LMW VIII C in the PTT system. When the LMW VIII C was tested in the two stage assay, all VIII C was adsorbed to A1(0H)3. The adsorption of the LMW VIII C was prevented by mixing it with hemophilic plasma. From normal undiluted plasma only 5-21% of VIII C and no VIII related antigen were adsorbed to A1(OH)3, but after activation of the factor VIII of normal plasma by small amounts of thrombin, most of the VIII C was adsorbed. No VIII related antigen was adsorbed after activation. Nevertheless, when unadsorbed LMW VIII C was assayed by the two stage method both with and without HMW VIII or VIIIR:Ag, the results were the same. Our studies suggest that VIIIR:Ag prevents to some extent the activation of LMW VIII C. LMW VIII C that is not bound or protected by VIIIRiAg is adsorbed from plasma by A1(0H)3. These findings may help explain the differences for VIII C found in some patients and certain clinical circumstances with the one and two stage assays.