VENOUS THROMBOSIS DUE TO POOR ANTICOAGULANT RESPONSE TO ACTIVATED PROTEIN-C - LEIDEN THROMBOPHILIA STUDY
VENOUS THROMBOSIS DUE TO POOR ANTICOAGULANT RESPONSE TO ACTIVATED PROTEIN-C - LEIDEN THROMBOPHILIA STUDY
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DOI：
10.1016/s0140-6736(05)80081-9
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发表时间：
1993-12-18
期刊：
影响因子：
168.9
通讯作者：
BERTINA, RM
中科院分区：
文献类型：
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作者：
KOSTER, T;ROSENDAAL, FR;BERTINA, RM
我们进行了一项基于人群的病例对照研究，以检测一种遗传性凝血系统异常的临床重要性，该异常的特征是对活化蛋白C的抗凝反应差，这与家族性血栓形成有关。在301名年龄在70岁以下的未选定的连续患者中，(21%)检测到了这种异常，首次客观地确认了深静脉血栓形成，并且没有潜在的恶性疾病。在301名年龄和性别匹配的健康对照组中，这一频率为5%(14例)。因此，对APC反应差的受试者发生深静脉血栓形成的风险增加7倍(匹配优势比6.6[95%可信区间3.6-12.0])。此外，对APC的反应程度和血栓形成风险之间存在明显的负相关关系。在患者家属中，确认了该异常的常染色体显性遗传传播方式。对APC反应差的10例血栓形成患者中，有9例父母中有1人有类似的不良反应，而在10例试验正常的患者中，有9例的父母试验同样正常。在1例对APC反应极差的患者的父母中都发现了这种异常，该患者可能是该异常的纯合子。我们得出结论，对APC的反应不良是静脉血栓形成最重要的遗传原因。它在一系列未经选择的患者中的高患病率将使所有血栓形成患者的这种异常检测都是值得的。
We undertook a population-based case-control study to test the clinical importance of a hereditary abnormality in the coagulation system, characterised by poor anticoagulant response to activated protein C (APC), which is associated with familial thrombophilia.The abnormality was detected in 64 (21%) of 301 unselected consecutive patients younger than 70 years,with a first, objectively confirmed episode of deep-vein thrombosis and without underlying malignant disease. Among 301 healthy control subjects matched for age and sex, the frequency was 5% (14 subjects). Thus, there is a seven-fold increase in risk of deep-vein thrombosis in subjects with a poor response to APC (matched odds ratio 6.6 [95% CI 3.6-12.0]). In addition, there was a clear inverse relation between the degree of response to APC and thrombosis risk. In the families of the patients an autosomal dominant mode of transmission of the abnormality was confirmed. 9 of 10 thrombosis patients with a poor response to APC had 1 parent with a similar poor response, whereas 9 of 10 patients with normal tests had parents with equally normal tests. The abnormality was found in both parents of 1 patient with an extremely poor response to APC; this patient is probably homozygous for the abnormality.We conclude that the poor response to APC is the most important hereditary cause of venous thrombosis. Its high prevalence in a series of unselected patients will make testing of all thrombosis patients for this abnormality worth while.