儿童颅内静脉窦血栓形成抗凝治疗的队列研究

Anticoagulants therapy in pediatric cerebral venous sinus thrombosis

目的评估抗凝治疗是否可以改善患儿颅内静脉窦血栓形成（cerebral venous sinus thrombosis，CVST）的临床症状和长期生存质量。方法资料选取2006年6月至2013年6月收治的符合标准的CVST患儿58例（1个月～16岁）。其中，接受抗凝治疗（低分子肝素、华法林、尿激酶）38例，为抗凝治疗组（抗凝组）；行非抗凝对症治疗20例，为非抗凝治疗组（非抗凝组）。回顾性分析评价两组血栓复发率、抗凝相关出血率及长期预后情况。长期生存质量应用改良Rankin评分进行评估。结果治疗后出现抗凝治疗相关出血2例（5．3％）。复发5例（8．6％）中，抗凝组1例，非抗凝组4例，组间比较，差异有统计学意义（P=0．023）。死亡5例（8．6％）中，抗凝组1例，非抗凝组4例，抗凝治疗同单纯对症治疗相比降低病死率25％～30％。长期随访45例（不包括死亡5例及失访8例）临床长期预后不良6例（13．3％），整体预后不良（包括死亡5例和长期预后不良6例）11例（22％）。影响长期预后因素中足月儿预后较好（风险比0．12，P=0．045）、颅内病灶广泛预后较差（风险比15．16，P=0．042）和抗凝治疗为主要减少预后不良发生率因素（风险比0．007，P=0．024）；起病初期颅高压发生的相关因素中，新生儿窒息史患儿颅高压发生率低（风险比0．35，P=0．025）、颅内病灶广泛发生率高（风险比8．73，P=0．048）和发病时间较短治疗及时的患儿发生颅高压率较低（风险比0．89，P=0．003）。同时，抗凝治疗对于亚急性期颅高压控制有一定帮助（P=0．048）。结论对于儿童CVST（包括轻度颅内出血的CVST患儿）抗凝治疗是安全有效的治疗方法，可有效降低其复发率，延长生存时间和改善长期生存质量。

Objective To explore the clinical efficacy and long-term outcomes of anticoagulants therapy in pediatric cerebral venous sinus thrombosis （CVST）. Methods 58 CVST children aged 1 month to 16 years received an standardized anticoagulant therapy of low molecular weight heparin, warfarin and urokinase. Initial and follow-up neuroimages were evaluated for associated intracranial hemorrhage, thrombus propagation rate and long-term quality-of-life. And clinical outcome was assessed by the modified Rankin scale （mRS）. Results Among them,38/58 received anticoagulants at diagnosis. Major anticoagulation-associated hemorrhage occurred in 5.3% （2/38） and clinical outcome was favorable. Early follow-up imaging demonstrated thrombus propagation in 5/58 children （1/38 with and 4/20 without anticoagulation [P = 0. 023]）. Five deaths were associated with CVST （1 with anticoagulation）. The decreasing rate of mortality in CVST with anticoagulation was 25%-30%. Clinical outcomes of death and long-term worse prognosis were unfavorable in 22% （11/50）. The clinical risk factors of long-term outcomes were full-term infant （OR [odd ratio] 0. 12, P = 0. 045）, neuroimaging of multiple lesions （OR 15.16, P = 0. 042） and anticoagulation （OR 0. 007, P = 0. 024）. Initial intracranial hypertension was associated with neonatal asphyxia （OR 0. 35, P = 0. 025）, neuroimaging of multiple lesion （OR 8.73, P = 0.048） and onset time （OR 0.89, P = 0.003）. Furthermore anticoagulation was probably helpful for CVST children in controlling subacute intracranial pressure （P = 0. 048）. Conclusions In pediatric CVST with mild intracranial hemorrhage, anticoagulation is both safe and effective. And it may reduce the rate of mortality, enhance quality-oflife and improve long-term outcomes.