Vasse M, Leduc O, Borg J Y, Chrétien M H, Monconduit M
Hôpital Charles Nicolle, Rouen, France.
Thromb Res. 1994 Oct 1;76(1):47-59. doi: 10.1016/0049-3848(94)90206-2.
Resistance to Activated Protein C (APC) was evaluated using 3 different methods: two of them were based on the prolongation of the Activated Partial Thromboplastin Time (APTT) using 2 different APTT reagents in the presence of APC, whereas the third method was based on the prolongation of prothrombin time when APC is added. The three methods were significantly correlated. APTT-based assays were sensitive to factor XII deficiency, whereas thromboplastin-based assay was sensitive to factor VII deficiency (< 0.5 UI/ml), which surestimates the response to APC. In contrast, an increase in factor VIII (F. VIII) level is associated with a decreased response to APC, when APTT-based assays are used, whereas thromboplastin-based assay is unmodified. During pregnancy, a decreased response to APC is observed, which is not only due to the increase in F. VIII, since thromboplastin-based assay is also modified. In Protein S (PS) immuno-depleted plasma, the low response to APC is corrected by addition of free PS: the thromboplastin-based assay was the most sensitive one to PS deficiency. However, in patients with congenital PS deficiency, there was no correlation between APC-resistance and free PS level. In patients with lupus anticoagulant, discrepancies were observed between the 3 methods, but with a high frequency of low response to APC. For the 3 assays, there was a good differentiation and correlation between normal and pathological results, the thromboplastin-based assay being perhaps the most discriminating. However, 3 unrelated thrombophilic patients showed normal results using thromboplastin-based assay, although they were APC-resistant using APTT-based assays. For 2 patients, this discrepancy can be explained by high levels of F. VIII. For the last patient, an abnormal F. VIII, resistant to APC can be suspected.
采用3种不同方法评估对活化蛋白C（APC）的抵抗性：其中两种方法基于在APC存在的情况下使用2种不同的活化部分凝血活酶时间（APTT）试剂延长APTT，而第三种方法基于添加APC时凝血酶原时间的延长。这三种方法显著相关。基于APTT的检测对因子Ⅻ缺乏敏感，而基于组织凝血活酶的检测对因子Ⅶ缺乏（<0.5 UI/ml）敏感，这最能准确反映对APC的反应。相比之下，当使用基于APTT的检测时，因子Ⅷ（F. VIII）水平升高与对APC的反应降低相关，而基于组织凝血活酶的检测则无变化。在怀孕期间，观察到对APC的反应降低，这不仅是由于F. VIII增加，因为基于组织凝血活酶的检测也有变化。在蛋白S（PS）免疫耗尽的血浆中，通过添加游离PS可纠正对APC的低反应：基于组织凝血活酶的检测对PS缺乏最敏感。然而，在先天性PS缺乏的患者中，APC抵抗与游离PS水平之间无相关性。在狼疮抗凝物患者中，3种方法之间存在差异，但对APC低反应的频率较高。对于这3种检测，正常和病理结果之间有良好的区分和相关性，基于组织凝血活酶的检测可能最具鉴别力。然而，3名无关的血栓形成倾向患者使用基于组织凝血活酶的检测结果正常，尽管他们使用基于APTT的检测显示APC抵抗。对于2名患者，这种差异可由F. VIII水平升高来解释。对于最后一名患者，可怀疑存在对APC抵抗的异常F. VIII。
