Division of Neurology, the Hospital for Sick Children, Toronto, Ontario, Canada.
Ann Neurol. 2010 May;67(5):590-9. doi: 10.1002/ana.21936.
Clinical trials are lacking in pediatric cerebral sinovenous thrombosis (CSVT). Neonates and children increasingly receive anticoagulant therapy (ACT) based on adult studies. Safety data for ACT in pediatric CSVT are scant and urgently needed. The objective was to assess the safety and outcome of ACT in pediatric CSVT.
In a single-center prospective study, neonates and children with CSVT received ACT (standard/low molecular weight heparin, warfarin) by standardized protocol. A study neuroradiologist (M.S.) assessed all initial and follow-up neuroimaging for intracranial hemorrhage (ICH), thrombus propagation, and recanalization. Clinical outcome was assessed with the Pediatric Stroke Outcome Measure.
Among 162 pediatric patients, 85 received ACT at diagnosis, including 29/83 (35%) neonates and 56/79 (71%) children. Major hemorrhage occurred in 6% (6/99) of treated patients, including 14% (3/21 neonates, 2/15 children) with and 2% (0/17 neonates, 1/46 children) without pretreatment ICH. ACT-associated bleeds were all nonfatal, and clinical outcome was favorable in 50%, similar to the remaining patients (53%). Early follow-up imaging demonstrated thrombus propagation in 11/57 neonates (10/35 [28%] without and 1/22 [4%] with ACT [p = 0.037]) and 10/63 children (7/19 [37%] without and 3/44 [7%] with ACT [p = 0.006]). Propagation was associated with new venous infarcts in 10% neonates and 40% children and worse clinical outcome in children (p = 0.053). Recanalization occurred earlier and more completely in neonates (p = 0.002). Clinical outcome was unfavorable in 47%.
In pediatric CSVT, ACT appears safe. Nontreatment with ACT is associated with thrombus propagation, observed in (1/4) of untreated neonates and over (1/3) of children. Anticoagulants merit strong consideration in pediatric CSVT.
儿童脑静脉窦血栓形成(CSVT)的临床试验较为匮乏。目前,越来越多的新生儿和儿童依据成人研究结果接受抗凝治疗(ACT)。有关 ACT 治疗儿童 CSVT 的安全性数据非常有限,亟待获取。本研究旨在评估 ACT 在儿童 CSVT 中的安全性和结局。
在单中心前瞻性研究中,CSVT 新生儿和儿童采用标准化方案接受 ACT(普通/低分子肝素、华法林)治疗。研究神经放射科医生(M.S.)评估所有初始和随访的神经影像学资料,以评估颅内出血(ICH)、血栓蔓延和再通情况。采用小儿中风结局量表评估临床结局。
在 162 例儿科患者中,85 例在诊断时接受 ACT 治疗,包括 29/83(35%)例新生儿和 56/79(71%)例儿童。ACT 治疗患者中发生大出血 6%(6/99),其中 14%(3/21 例新生儿、2/15 例儿童)有且 2%(0/17 例新生儿、1/46 例儿童)无治疗前 ICH。ACT 相关出血均非致命性,50%患者临床结局良好,与其余患者(53%)相似。早期随访影像学检查显示,57 例新生儿中有 11 例(无 ACT 治疗者 10/35[28%]、有 ACT 治疗者 1/22[4%],p=0.037)和 63 例儿童中有 10 例(无 ACT 治疗者 7/19[37%]、有 ACT 治疗者 3/44[7%],p=0.006)出现血栓蔓延。10%的新生儿和 40%的儿童出现新的静脉梗死,且儿童的临床结局更差(p=0.053)。ACT 治疗的新生儿更早且更完全地实现再通(p=0.002)。47%的患儿临床结局不良。
在儿童 CSVT 中,ACT 似乎是安全的。不接受 ACT 治疗与血栓蔓延有关,未接受治疗的新生儿中(1/4)和超过(1/3)的儿童中均可见这种情况。ACT 治疗应作为儿童 CSVT 的重要考虑因素。