Kenet Gili, Kirkham Fenella, Niederstadt Thomas, Heinecke Achim, Saunders Dawn, Stoll Monika, Brenner Benjamin, Bidlingmaier Christoph, Heller Christine, Knöfler Ralf, Schobess Rosemarie, Zieger Barbara, Sébire Guillaume, Nowak-Göttl Ulrike
Israel National Haemophilia Centre, Sheba Medical Centre, Tel-Hashomer, Israel.
Lancet Neurol. 2007 Jul;6(7):595-603. doi: 10.1016/S1474-4422(07)70131-X.
The relative importance of previous diagnosis and hereditary prothrombotic risk factors for cerebral venous thrombosis (CVT) in children in determining risk of a second cerebral or systemic venous thrombosis (VT), compared with other clinical, neuroimaging, and treatment variables, is unknown.
We followed up the survivors of 396 consecutively enrolled patients with CVT, aged newborn to 18 years (median 5.2 years) for a median of 36 months (maximum 85 months). In accordance with international treatment guidelines, 250 children (65%) received acute anticoagulation with unfractionated heparin or low-molecular weight heparin, followed by secondary anticoagulation prophylaxis with low-molecular weight heparin or warfarin in 165 (43%).
Of 396 children enrolled, 12 died immediately and 22 (6%) had recurrent VT (13 cerebral; 3%) at a median of 6 months (range 0.1-85). Repeat venous imaging was available in 266 children. Recurrent VT only occurred in children whose first CVT was diagnosed after age 2 years; the underlying medical condition had no effect. In Cox regression analyses, non-administration of anticoagulant before relapse (hazard ratio [HR] 11.2 95% CI 3.4-37.0; p<0.0001), persistent occlusion on repeat venous imaging (4.1, 1.1-14.8; p=0.032), and heterozygosity for the G20210A mutation in factor II (4.3, 1.1-16.2; p=0.034) were independently associated with recurrent VT. Among patients who had recurrent VT, 70% (15) occurred within the 6 months after onset.
Age at CVT onset, non-administration of anticoagulation, persistent venous occlusion, and presence of G20210A mutation in factor II predict recurrent VT in children. Secondary prophylactic anticoagulation should be given on a patient-to-patient basis in children with newly identified CVT and at high risk of recurrent VT. Factors that affect recanalisation need further research.
与其他临床、神经影像学和治疗变量相比，既往诊断和遗传性血栓形成前危险因素在儿童脑静脉血栓形成（CVT）中对第二次脑或全身静脉血栓形成（VT）风险的相对重要性尚不清楚。
我们对396例年龄从新生儿到18岁（中位年龄5.2岁）连续入组的CVT患者的幸存者进行了随访，中位随访时间为36个月（最长85个月）。根据国际治疗指南，250名儿童（65%）接受了普通肝素或低分子肝素的急性抗凝治疗，随后165名儿童（43%）接受了低分子肝素或华法林的二级抗凝预防。
在入组的396名儿童中，12名立即死亡，22名（6%）出现复发性VT（13例脑部；3%），中位时间为6个月（范围0.1 - 85个月）。266名儿童可进行重复静脉成像。复发性VT仅发生在首次CVT在2岁以后诊断的儿童中；潜在的基础疾病没有影响。在Cox回归分析中，复发前未使用抗凝剂（风险比[HR] 11.2，95%置信区间3.4 - 37.0；p<0.0001）、重复静脉成像显示持续闭塞（4.1，1.1 - 14.8；p = 0.032）以及凝血因子II中G20210A突变的杂合性（4.3，1.1 - 16.2；p = 0.034）与复发性VT独立相关。在出现复发性VT的患者中，70%（15例）在发病后6个月内发生。
CVT发病年龄、未进行抗凝治疗、持续静脉闭塞以及凝血因子II中存在G20210A突变可预测儿童复发性VT。对于新确诊的CVT且有复发性VT高风险的儿童，应根据个体情况给予二级预防性抗凝治疗。影响再通的因素需要进一步研究。
