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Blood, 1 July 2007, Vol. 110, No. 1, pp. 4-5.
Clot busting in kids: less PTS?CHILDREN'S HOSPITAL OF PHILADELPHIA
Goldenberg and colleagues' retrospective analysis of pediatric patients with high-risk, occlusive lower extremity deep vein thrombosis (DVT) suggests that thrombolytic therapy with tPA (with or without mechanical thrombolysis) may decrease the risk of postthrombotic syndrome (PTS).
Clear indications for thrombolytic therapy in children have been restricted to patients with life, organ, or limb-threatening thrombosis, due to concerns regarding the risk of bleeding. Prior reports of high rates of serious bleeding complications in neonates and children using relatively high doses of tissue plasminogen activator (tPA) have been followed by more recent case studies in which lower doses of tPA and more stringent patient selection have resulted in less bleeding.2 Long-term follow-up studies of children with DVT are lacking, but intermediate reports suggest that the rates of PTS are similar to those seen in adults. Since the majority of these children are anticipated to have many years of active physical life ahead of them, concerns for long-term venous insufficiency are a more pressing issue than in an elderly population. In this issue, Goldenberg and colleagues retrospectively analyze a group of pediatric patients with high-risk proximal lower extremity DVT to determine if patients who received a thrombolytic regimen had a lower risk of developing PTS compared with those who received anticoagulation alone. Importantly, they compared patients who were at highest risk of developing PTS—those with occlusive thrombus and laboratory markers predictive of poor outcome (elevated D-dimer and Factor VIII).3 Nine children who received tPA were compared with 13 who received anticoagulation alone. Not surprisingly, thrombolysis (administered for varying durations with or without mechanical thrombolysis) achieved clot resolution in 8 of 9 patients, compared with 5 of 13 in the anticoagulation-alone group. One patient in the thrombolysis group had significant bleeding, though this was judged to be unrelated to the tPA. The presence of PTS at 18 to 24 months was determined using a standardized instrument that was adapted for children and validated by the authors, scoring both physical exam abnormalities and functional limitations. There was a significant difference in the percentage of patients who had any evidence of PTS: 22% (thrombolysis) versus 77% (anticoagulation), with a P value of .01. Several of the patients in the anticoagulation group had isolated edema without functional limitations, and the clinical impact of this finding over time is not known. When patients with both physical and functional abnormalities were compared, the results still favored thrombolysis, but this difference was no longer statistically significant. Though this is a very small study, with the usual limitations of a retrospective design, it does provide preliminary data to support a multiple-center, randomized clinical trial to assess the safety and efficacy of thrombolysis in high-risk pediatric patients. Paramount to this trial will be the careful selection of patients at greatest risk of developing PTS, vigilant attention to a uniform protocol, close monitoring of coagulation parameters, and standardized outcome measurements. The growing recognition of PTS in children who have greater potential for long-term sequelae makes this an imperative clinical challenge for pediatric hematologists.
Footnotes
Conflict-of-interest disclosure: The author declares no competing financial interests.
REFERENCES
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| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
