Glueck C J, Crawford A, Roy D, Freiberg R, Glueck H, Stroop D
Cholesterol Center, Jewish Hospital, Cincinnati, Ohio 45229, USA.
J Bone Joint Surg Am. 1996 Jan;78(1):3-13. doi: 10.2106/00004623-199601000-00002.
Thirty-three (75 per cent) of forty-four unselected children who had Legg-Perthes disease were found to have coagulation abnormalities. Twenty-three children had thrombophilia (a deficiency in antithrombotic factor C or S, with an increased tendency toward thrombosis); nineteen of the twenty-three children had protein-C deficiency and four had protein-S deficiency. Seven children had a high level (0.25 gram per liter or more) of lipoprotein(a), a thrombogenic, atherogenic lipoprotein associated with osteonecrosis in adults. Three children had hypofibrinolysis (a reduced ability to lyse clots). The mean age of the children when the Legg-Perthes disease was first diagnosed was 5.8 +/- 2.7 years, and the mean age at the time of the present study was 10.1 +/- 4.4 years. At least one of the first-degree relatives of eleven of the nineteen probands who had a low protein-C level had a low protein-C level as well; all of these low levels represented previously undiagnosed familial protein-C deficiency. The eleven probands who had familial protein-C deficiency were more likely to have early onset of Legg-Perthes disease (at or before the age of five years) than the eleven children who had normal levels of protein C, protein S, and lipoprotein(a) as well as normal fibrinolytic activity (chi-square = 6.6; p = 0.01). At least one first-degree relative of one of the four probands who had a low protein-S level had a low protein-S level and previously undiagnosed familial protein-S deficiency. At least one first-degree relative of six of the seven probands who had a high level of lipoprotein(a) had a familial high level of lipoprotein(a). Six of the seven children who had a high level of lipoprotein(a) also had a low level of stimulated tissue-plasminogen activator activity, the major initiator of fibrinolysis. At least one first-degree relative of one of the three probands who had normal levels of protein C, protein S, and lipoprotein(a) but low stimulated tissue-plasminogen activator activity also had low stimulated tissue-plasminogen activator activity (familial hypofibrinolysis). Legg-Perthes disease, thrombophlebitis, premature myocardial infarction, and stroke, which are ramifications of the familial thrombophilic-hypofibrinolytic disorders, were common in the first and second-degree relatives of the thirty-three children with Legg-Perthes disease who also had thrombophilic-hypofibrinolytic disorders.
在44例未经挑选的患有Legg-Perthes病的儿童中，有33例（75%）被发现存在凝血异常。23名儿童患有血栓形成倾向（抗血栓因子C或S缺乏，血栓形成倾向增加）；这23名儿童中有19名患有蛋白C缺乏症，4名患有蛋白S缺乏症。7名儿童的脂蛋白(a)水平较高（每升0.25克或更高），脂蛋白(a)是一种促血栓形成、促动脉粥样硬化的脂蛋白，与成人骨坏死有关。3名儿童存在纤溶功能低下（溶解血栓的能力降低）。Legg-Perthes病首次诊断时儿童的平均年龄为5.8±2.7岁，本研究时的平均年龄为10.1±4.4岁。在19名蛋白C水平低的先证者中，有11名的至少一位一级亲属蛋白C水平也低；所有这些低水平均代表先前未被诊断出的家族性蛋白C缺乏症。与11名蛋白C、蛋白S和脂蛋白(a)水平正常且纤溶活性正常的儿童相比，11名患有家族性蛋白C缺乏症的先证者更有可能在5岁及以前发病（χ²=6.6；p=0.01）。在4名蛋白S水平低的先证者中，有1名的至少一位一级亲属蛋白S水平低且患有先前未被诊断出的家族性蛋白S缺乏症。在7名脂蛋白(a)水平高的先证者中，有6名的至少一位一级亲属脂蛋白(a)水平家族性升高。7名脂蛋白(a)水平高的儿童中有6名的刺激组织纤溶酶原激活物活性水平也低，刺激组织纤溶酶原激活物是纤溶的主要启动因子。在3名蛋白C、蛋白S和脂蛋白(a)水平正常但刺激组织纤溶酶原激活物活性低的先证者中，有1名的至少一位一级亲属刺激组织纤溶酶原激活物活性也低（家族性纤溶功能低下）。Legg-Perthes病、血栓性静脉炎、过早心肌梗死和中风是家族性血栓形成倾向-纤溶功能低下疾病的后果，在33名患有Legg-Perthes病且也患有血栓形成倾向-纤溶功能低下疾病的儿童的一级和二级亲属中很常见。
