Aznar J, Villa P, España F, Estellés A, Grancha S, Falcó C
Department of Clinical Pathology and the Research Center, La Fe University Hospital, Valencia, Spain.
J Lab Clin Med. 1997 Aug;130(2):202-8. doi: 10.1016/s0022-2143(97)90097-4.
The effect of antiphospholipid antibodies (aPL) on the action of activated protein C (APC) was examined in 32 patients: 19 with lupus anticoagulant (LA), 6 with anticardiolipin antibodies (aCL), and 7 with LA and aCL. Eighteen patients had a ratio of activated partial thromboplastin time (APTT) with APC to APTT without APC (APTT ratio) <2.06 (cut-off level) and no factor V Leiden mutation; these patients showed APC-resistance (APC-R) phenotype. The mean prolongation of APTT after addition of APC in a control group was 45.3 seconds, with a lower limit of 31.4 seconds. Only 3 of the 18 patients with low APTT ratio had a prolongation of <31.4 seconds; they were classified as true APC-R phenotype, whereas the other 15 patients were classified as spurious APC-R. Of the 3 patients with true APC-R, 2 had deep venous thrombosis, 1 with pulmonary embolism, and the third had recurrent abortion. Of the other 15 patients, 2 had had ischemic stroke, 1 had recurrent abortion, and 12 were asymptomatic. Circulating APC level was measured in 14 of the 18 aPL patients with a low APTT ratio; it was lower than the normal lower limit in 4 patients and within the lower limit in 2. Three of the 4 patients with reduced APC levels had a history of thrombosis. We conclude that patients with aPL who show APC-R phenotype due to a low APTT ratio without the factor V Leiden mutation can be classified into two groups: true and spurious APC-R phenotype. Since those with true APC-R phenotype could have greater thrombotic risk, adequate classification of these patients is important. Moreover, aPL can sometimes interfere with the activation of protein C, thus reducing the circulating levels of APC, and this could constitute another thrombotic risk factor.
在32例患者中检测了抗磷脂抗体（aPL）对活化蛋白C（APC）作用的影响，其中19例患有狼疮抗凝物（LA），6例患有抗心磷脂抗体（aCL），7例同时患有LA和aCL。18例患者活化部分凝血活酶时间（APTT）与加入APC后的APTT之比（APTT比值）<2.06（临界值）且无因子V Leiden突变，这些患者表现出APC抵抗（APC-R）表型。对照组加入APC后APTT的平均延长时间为45.3秒，下限为31.4秒。18例APTT比值低的患者中只有3例延长时间<31.4秒，他们被归类为真正的APC-R表型，而其他15例患者被归类为假性APC-R。在3例真正的APC-R患者中，2例有深静脉血栓形成，1例有肺栓塞，第3例有反复流产。在其他15例患者中，2例有缺血性中风，1例有反复流产，12例无症状。在18例APTT比值低的aPL患者中的14例检测了循环APC水平，4例患者低于正常下限，2例在正常下限范围内。4例APC水平降低的患者中有3例有血栓形成史。我们得出结论，aPL患者若因APTT比值低且无因子V Leiden突变而表现出APC-R表型，可分为两组：真正的和假性的APC-R表型。由于真正的APC-R表型患者可能有更高的血栓形成风险，对这些患者进行充分分类很重要。此外，aPL有时会干扰蛋白C的激活，从而降低APC的循环水平，这可能构成另一个血栓形成风险因素。
