Laffan M A, Manning R
Department of Haematology, Royal Postgraduate Medical School, London, UK.
Blood Coagul Fibrinolysis. 1996 Nov;7(8):761-5. doi: 10.1097/00001721-199611000-00003.
Activated protein C resistance (APCR) has proved to be a frequent finding in association with thrombosis. The majority of patients with APCR have been found to be homozygous or heterozygous for the polymorphic variant factor V Q506 (factor V Leiden; FVQ506). However a small number of patients have APCR as assessed by functional tests but do not possess the FVQ506 polymorphism. Some of these cases are due to the presence of a lupus type anticoagulant but in this report we demonstrate that the remainder are almost entirely (nine out of ten) associated with an elevated level of FVIIIc. Spiking experiments in normal patient plasma and venous occlusion tests demonstrated that elevation of the FVIIIc results in a reduced APCR ratio and shortening of the APTT. Variation in FVIIIc, in conjunction with other factors, may therefore explain the variable phenotype associated with FVQ506 and the phenomenon of thrombosis associated APCR in the absence of FVQ506. We conclude that FVIIIc as well as FVQ506 should be taken into account when assessing thrombotic risk. APCR, elevated FVIIIc and shortened APTT have all been previously identified with an increased risk of thrombosis. It follows that resistance to APC may arise from a number of factors and is in itself a risk factor for thrombosis. The net effect of these factors is assessed in the functional test for APCR and it may be premature therefore to replace functional tests for APCR with DNA analysis alone.
活化蛋白C抵抗（APCR）已被证明是与血栓形成相关的常见现象。已发现大多数APCR患者为多态性变体因子V Q506（因子V莱顿；FVQ506）的纯合子或杂合子。然而，少数患者经功能测试评估有APCR，但不具有FVQ506多态性。其中一些病例是由于存在狼疮样抗凝物，但在本报告中我们证明，其余病例几乎全部（十分之九）与FVIIIc水平升高有关。在正常患者血浆中进行的加样实验和静脉闭塞试验表明，FVIIIc升高会导致APCR比值降低和活化部分凝血活酶时间（APTT）缩短。因此，FVIIIc的变化与其他因素一起，可能解释了与FVQ506相关的可变表型以及在不存在FVQ506时与血栓形成相关的APCR现象。我们得出结论，在评估血栓形成风险时，应同时考虑FVIIIc以及FVQ506。APCR、FVIIIc升高和APTT缩短以前都被认为与血栓形成风险增加有关。由此可见，对活化蛋白C的抵抗可能由多种因素引起，其本身就是血栓形成的一个危险因素。这些因素的综合作用在APCR功能测试中进行评估，因此仅用DNA分析取代APCR功能测试可能为时过早。
