Zöller B, Berntsdotter A, García de Frutos P, Dahlbäck B
Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Sweden.
Blood. 1995 Jun 15;85(12):3518-23.
Inherited resistance to activated protein C (APC), which is caused by a single point mutation in the gene for factor V, is a common risk factor for thrombosis. In this study, the prevalence of APC resistance in 18 unrelated thrombosis-prone families with inherited protein S deficiency was investigated to determine its role as additional genetic risk factor for thrombosis. In addition, a detailed evaluation of the clinical manifestations in these families was performed. Venous thrombotic events had occurred in 47% of the protein S-deficient patients (64/136) and in 7% of relatives without protein S deficiency (14/191). As estimated from Kaplan-Meier analysis, 50% of protein S-deficient family members and 12% of those without protein S deficiency had had manifestation of venous thromboembolism at the age of 45 years. The age at the first thrombotic event ranged from 10 to 81 years (mean, 32.5 years) and a large intrafamilial and interfamilial variability in expression of thrombotic symptoms was seen. The factor V gene mutation related to APC resistance was present in 6 (38%) of 16 probands available for testing; in total, the mutation was found in 7 (39%) of the 18 families. In family members with combined defects, 72% (13/18) had had thrombosis as compared with 19% (4/21) of those with only protein S deficiency and 19% (4/21) of those with only the factor V mutation. In conclusion, APC resistance was found to be highly prevalent in thrombosis-prone families with protein S deficiency and was an additional genetic risk factor for thrombosis in these families. The results suggest thrombosis-prone families with protein S deficiency often to be affected by yet another genetic defect.
由因子V基因单点突变引起的对活化蛋白C（APC）的遗传性抵抗是血栓形成的常见危险因素。在本研究中，调查了18个遗传性蛋白S缺乏的易患血栓的无关家庭中APC抵抗的患病率，以确定其作为血栓形成额外遗传危险因素的作用。此外，对这些家庭的临床表现进行了详细评估。47%的蛋白S缺乏患者（64/136）和7%的无蛋白S缺乏的亲属（14/191）发生了静脉血栓事件。根据Kaplan-Meier分析估计，50%的蛋白S缺乏家庭成员和12%的无蛋白S缺乏家庭成员在45岁时出现静脉血栓栓塞表现。首次血栓事件的年龄范围为10至81岁（平均32.5岁），血栓症状表达存在较大的家族内和家族间变异性。在16名可供检测的先证者中，6名（38%）存在与APC抵抗相关的因子V基因突变；在18个家庭中，共有7个（39%）发现了该突变。在合并缺陷的家庭成员中，72%（13/18）发生过血栓形成，而仅蛋白S缺乏的患者中这一比例为19%（4/21），仅因子V基因突变的患者中这一比例为19%（4/21）。总之，在遗传性蛋白S缺乏的易患血栓家庭中，APC抵抗非常普遍，是这些家庭中血栓形成的额外遗传危险因素。结果表明，遗传性蛋白S缺乏的易患血栓家庭往往还受到另一种遗传缺陷的影响。
