Clinical and Biomolecular Studies on Thrombophilia in Children.

为了解患儿人数及临床情况，我们采用问卷调查的方法，在全国范围内对儿童血栓形成进行了调查。我们向1319名医生发出了第一份问卷，得到了806份回答(61.1%)。其中先天性抗凝血酶(AT)缺陷13 7个家系15例，蛋白C(PC)缺陷14 6/182(2 7例)，蛋白S(PS)缺陷62/84(16例)，肝素辅因子缺乏症(HC-II 2/3(0)例)，血浆蛋白原异常65/65+α(7例)，纤维蛋白原异常47/57(13例)，其他16/20(4例)，总计475/6 0 1(82例)。通过第二次问卷调查，82例患者中有36例(43.9%)得到了回答。其中儿童血栓栓塞史阳性组21例(AT4、PC10、PS7)，儿童期血栓栓塞史阴性组15例(AT3、PC4、PS8)。前一组性别比为男性11：女性10。发病年龄介于新生儿期和青春期之间。血栓栓塞症的主要首发事件为深静脉血栓形成(DVT)、肺血栓栓塞症(PTE)、脑血栓等，实验室检查显示AT、PC和PS(I型，杂合子)活性和抗原水平中等偏低，仅3例PC和PS活性和抗原水平极低，8例进行了基因分析。这些病例在血栓栓塞症初期使用了多种抗血栓药物，每次确诊后多采用华法林进行预防治疗。以凝血酶原时间-INR和/或血栓试验作为监测指标，评价止血效果良好。提示对亲血栓症患儿进行仔细、持续的观察是最重要的。还进行了有关儿童血栓形成的其他临床和生物分子研究。

In order to know the patients' number and its clinical conditions, we conducted a nation-wide survey of thrombophilia in children using questionnaire. We sent the first questionnaire to 1, 319 medical doctors and got 806 answers (61.1 %). They are as follows; congenital antithrombin(AT) deficiency 137 families/190 cases (15 children), protein C (PC) deficiency 146/182(27), protein S (PS) deficiency 62/84(16), heparin cofactor-Iiciency (HC-II2/3(0), abnormal plasminogenemia 65/65+α (7), abnormal fibrinogenemia 47/57 (13), others 16/20 (4), and totally 475/601 (82). We got answers of 36 cases (43.9 %) from 82 cases by the 2nd questionnaire. It was divided into 2 groups, positive history of thromboembolic events in childhood, 21 cases (AT 4, PC10, PS7) and negative history of those in childhood, 15 cases (AT3, PC4, PS8). Sex ratio of theformergroup was M11: F10. Age at onset of the events was ranged between newborn period and adlescence. Main initial events of thromboembolism were deep vein thrombosis in lower extremity (DVT), pulmonary thromboembolism (PTE), brain embolism and etc. Laboratory examinations showed medium low levels of activity and antigen of AT, PC and PS (Type I, heterozygote) in the majority of the cases and extremely low levels of those of PC and PS in only 3 cases, gene analysis was performed in 8 cases. Several kinds of antithrombotic agents were used at the in itial events of thromboembolism in these cases and warfarin was mostly applied for prophylaxis treatment after establishment of each diagnosis. Prothrombin time-INR and/or Thrombotest were used as a monitor to evalute good hemostatic control. It is suggested that careful and continuous observation is most important in children with thrombophilia. Other clinical and biomolecular studies on thrombophilia in children were also performed.