Sampram E S, Lindblad B, Dahlbäck B
Department of Vascular and Renal Diseases, Malmö University Hospital, Lund University, Sweden.
J Vasc Surg. 1998 Oct;28(4):624-9. doi: 10.1016/s0741-5214(98)70086-2.
The frequency of activated protein C (APC) resistance, caused by factor V R506Q gene mutation and abnormal APC ratio, in patients with peripheral vascular diseases was analyzed.
All patients electively admitted to the vascular ward unit of our tertiary care academic medical center from January 1995 through October 1996 (n = 679) were prospectively analyzed using an APC-resistance screening test to determine the frequency of abnormal APC ratio (< or =2.6). Baseline activated partial thromboplastin time (APTT) and its prolongation after the addition of a standard amount of APC were determined. The factor V R506Q gene mutation (Leiden) was analyzed in patients with an APC ratio less than 3.0. Statistical comparisons were made to an age-matched control population (n = 278).
The factor V Leiden gene mutation or abnormal APC ratio was detected in 154 of the patients (22.7%), compared with 34 of 278 the control subjects (12.2%; t = 13.65; P < .001). The factor V Leiden gene mutation was found in 102 patients (15.2%), compared with 29 control subjects (10.4%; t = 4.64; P < .05); an abnormal APC ratio was found in 132 patients (19.8%), compared with 26 (9.8%) of controls (t = 14.56; P < .001). The frequency of the factor V Leiden gene mutation was significantly increased in patients with femoro-popliteal occlusive disease (n = 126), to 21.6% (t = 16.94; P< .001), and venous disease (n = 50), to 36.0% (t = 20.93; P< .001). Overall, 63% of the patients with abnormal APC ratios tested positive for the factor V Leiden gene mutation. A significantly increased frequency of APC resistance was demonstrated in patients undergoing aorto-iliac (n = 37) or femoro-crural graft reconstructions (n = 72); it was found in 41% and 35%, respectively (P < .001). In addition, a significantly increased frequency of APC resistance was found in patients who suffered from occlusion after reconstruction; 13 of 41 (32%) had the factor V Leiden gene mutation (P < .001), and 19 of 39 (49%) had an abnormal APC ratio (P < .001).
The factor V Leiden gene mutation and abnormal APC ratios are significantly increased in patients with lower extremity peripheral vascular disease and failed reconstructions. An abnormal APC ratio was seen without factor V Leiden gene mutation in 37% of patients with peripheral vascular diseases, suggesting additional causes of an abnormal APC ratio, exclusive of gene mutation.
分析外周血管疾病患者中由因子V R506Q基因突变和异常活化蛋白C（APC）比值导致的APC抵抗的发生率。
对1995年1月至1996年10月期间我院三级医疗学术中心血管病房择期收治的所有患者（n = 679）进行前瞻性分析，采用APC抵抗筛查试验确定异常APC比值（≤2.6）的发生率。测定基础活化部分凝血活酶时间（APTT）及其在加入标准量APC后的延长情况。对APC比值小于3.0的患者进行因子V R506Q基因突变（莱顿突变）分析。与年龄匹配的对照组人群（n = 278）进行统计学比较。
154例患者（22.7%）检测到因子V莱顿基因突变或异常APC比值，而278例对照者中有34例（12.2%）检测到（t = 13.65；P <.001）。102例患者（15.2%）发现因子V莱顿基因突变，对照者中有29例（10.4%）（t = 4.64；P <.05）；132例患者（19.8%）发现异常APC比值，对照组中有26例（9.8%）（t = 14.56；P <.001）。股腘动脉闭塞性疾病患者（n = 126）中因子V莱顿基因突变的发生率显著增加，达21.6%（t = 16.94；P<.001），静脉疾病患者（n = 50）中达36.0%（t = 20.93；P<.001）。总体而言，APC比值异常的患者中有63%因子V莱顿基因突变检测呈阳性。在接受主-髂动脉（n = 37）或股-小腿移植血管重建的患者中，APC抵抗的发生率显著增加；分别为41%和35%（P <.001）。此外，重建后发生闭塞的患者中APC抵抗的发生率显著增加；41例中有13例（32%）有因子V莱顿基因突变（P <.001），39例中有19例（49%）有异常APC比值（P <.001）。
下肢外周血管疾病患者和重建失败患者中因子V莱顿基因突变和异常APC比值显著增加。37%的外周血管疾病患者在无因子V莱顿基因突变的情况下出现异常APC比值，提示除基因突变外，异常APC比值还有其他原因。
