Födinger M, Mannhalter C, Pabinger I, Koizar D, Rintelen C, Hörl W H, Sunder-Plassmann G
Abteilung für Molekularbiologie, Universität Wien, Austria.
Nephrol Dial Transplant. 1996 Apr;11(4):668-72. doi: 10.1093/oxfordjournals.ndt.a027357.
Vascular access thrombosis represents a serious problem in haemodialysis patients. Therefore identification of relevant thrombotic risk factors is clinically valuable. Resistance to activated protein C (APC) was recently identified as a new thrombophilic defect which is caused by a single point mutation in the factor V gene. Whether this mutation predisposes to vascular access thrombosis is unknown.
The presence of factor V Leiden (mutation at nucleotide position 1691 of the factor V gene) was determined by polymerase chain reaction (PCR) analysis in 152 haemodialysis patients from all three haemodialysis units of the University Hospital of Vienna. In 61 patients (54 without mutation, 7 with heterozygous mutation) resistance to APC was evaluated. One hundred-seven individuals without renal failure (57 negative for factor V Leiden, 50 heterozygous subjects) served as controls. Haemodialysis patients with heterozygous factor V Leiden mutation were carefully investigated for thrombotic complications of vascular access, other thromboembolic events and additional putative thromboembolic risk factors.
Seven of 152 (4.6%) patients were heterozygous carriers of factor V Leiden. The mean APC resistance ration in heterozygous dialysis patients was 2.31; in the 50 heterozygous controls the ratio was 2.02. The mean APC ratio in haemodialysis patients without mutation was 3.53 in contrast to 2.95 in the control group. Not one of the seven heterozygous haemodialysis patients suffered from vascular access thrombosis of inexplicable origin. Three patients remained totally free of access thrombosis from onset of haemodialysis treatment. In four of seven patients nine events of thrombosis of the vascular access occurred, but were due to anatomical stenosis in each case. In six permanent central venous catheters no episode of occlusion or reduced blood flow requiring thrombolytic therapy was observed. Family history with regard to thrombotic events was negative in all seven patients. No thromboembolic complication occurred during 13 periods of immobilization, in the course of six pregnancies and during oral contraception.
The heterozygous carrier status for factor V Leiden does not appear to represent a risk factor for vascular access thrombosis in haemodialysis patients. This is possibly due to the fact that the functional APC activity is high and in heterozygous haemodialysis patients APC resistance ratios are very close to the normal range. However, it cannot be excluded that a homozygous factor V mutation represents an increased risk for shunt thrombosis. Therefore patients suffering from repeated and/or inexplicable shunt thrombosis should be tested for the factor V mutation to evaluate the effect of a homozygous mutation.
血管通路血栓形成是血液透析患者面临的一个严重问题。因此，识别相关的血栓形成危险因素具有临床价值。活化蛋白C（APC）抵抗最近被确定为一种新的易栓缺陷，它由因子V基因中的单点突变引起。这种突变是否易导致血管通路血栓形成尚不清楚。
通过聚合酶链反应（PCR）分析，对维也纳大学医院所有三个血液透析单元的152例血液透析患者进行因子V莱顿突变（因子V基因核苷酸位置1691处的突变）检测。对61例患者（54例无突变，7例杂合突变）进行了APC抵抗评估。107例无肾衰竭个体（57例因子V莱顿阴性，50例杂合子）作为对照。对因子V莱顿杂合突变的血液透析患者仔细调查血管通路的血栓形成并发症、其他血栓栓塞事件及其他可能的血栓栓塞危险因素。
152例患者中有7例（4.6%）为因子V莱顿杂合携带者。杂合透析患者的平均APC抵抗比值为2.31；50例杂合对照者的比值为2.02。无突变的血液透析患者的平均APC比值为3.53，而对照组为2.95。7例杂合血液透析患者中无一例发生原因不明的血管通路血栓形成。3例患者自血液透析治疗开始后完全未发生通路血栓形成。7例患者中有4例发生了9次血管通路血栓形成事件，但均因解剖学狭窄所致。6根永久性中心静脉导管未观察到需要溶栓治疗的堵塞或血流减少情况。所有7例患者的血栓形成事件家族史均为阴性。在13次制动期间、6次妊娠期间及口服避孕药期间均未发生血栓栓塞并发症。
因子V莱顿杂合携带者状态似乎并非血液透析患者血管通路血栓形成的危险因素。这可能是由于功能性APC活性较高，且杂合血液透析患者的APC抵抗比值非常接近正常范围。然而，不能排除纯合因子V突变会增加分流血栓形成的风险。因此，对于反复发生和/或原因不明的分流血栓形成患者，应检测因子V突变以评估纯合突变的影响。
