Anticoagulants in pediatric cerebral sinovenous thrombosis: a safety and outcome study

Abstract

Objective: 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.

Methods: 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.

Results: 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%.

Interpretation: 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.