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Low-Dose Tissue Plasminogen Activator Thrombolysis in Children

Wang, Michael M.D.; Hays, Taru M.D.; Balasa, Vinod M.D.; Bagatell, Rochelle M.D.; Gruppo, Ralph M.D.; Grabowski, Eric F. M.D., Sc.D.; Valentino, Leonard A. M.D.; Tsao-Wu, George M.D.; Manco-Johnson, Marilyn J. M.D.Pediatric Coagulation Consortium

Journal of Pediatric Hematology/Oncology: May 2003 - Volume 25 - Issue 5 - p 379-386
ORIGINAL ARTICLES: Hematology

Purpose To compare results of low-dose tissue plasminogen activator (TPA) in children with arterial and venous thrombi relative to standard published dosing.

Methods Subjects consisted of all consecutive children with objectively confirmed thrombi for whom TPA thrombolysis was clinically ordered by the authors. Initial dosing used published standard dose (0.1–0.5 mg/kg per hour). With experience, a low-dose regimen (0.01–0.06 mg/kg per hour) was given in an attempt to derive a minimal effective dose.

Results Thirty-five children were treated with TPA. Either standard or low-dose infusions of TPA resulted in complete thrombolysis of 28 of 29 (97%) acute thrombi, while all 6 chronic thrombi had a partial response. In contrast to the recommended adult-derived dosages of 0.1 to 0.5 mg/kg per hour, the authors found that initial doses of less than 0.01 mg/kg per hour were effective in 12 of 17 patients with acute thrombosis. Neonates required 0.06 mg/kg per hour. Route of administration (local or systemic) did not affect efficacy. Major bleeding occurred in only one extremely preterm infant. Minor bleeding, primarily oozing at intravenous sites, occurred in 27% of children during TPA infusions. Prophylactic unfractionated or low-molecular-weight heparin was infused concomitant with TPA in 42% of the children and did not increase the risk of bleeding.

Conclusions TPA in very low doses appears to be safe and effective for thrombolysis of acute thromboses in most children, given appropriate patient selection.

From the Department of Pediatrics at the Children's Hospital and the University of Colorado Health Sciences Center, Denver, Colorado, U.S.A. (M.W., T.H., M.J.M-J.), Children's Hospital Medical Center, Cincinnati, Ohio, U.S.A. (V.B., R.G.), University of Arizona, Tucson, Arizona, U.S.A. (R.B.), Massachusetts General Hospital, Boston, Massachusetts, U.S.A. (E.F.G.), Rush Children's Hospital, Chicago, Illinois, U.S.A. (L.A.V.), and Alaska Center for Pediatrics, Anchorage, Alaska, U.S.A. (G.T-W.). The Pediatric Coagulation Consortium comprises investigators of the Hemophilia Research Society and the American Society of Pediatric Hematology/Oncology.

Submitted for publication August 6, 2002; accepted September 13, 2002.

Address correspondence and reprint requests to Marilyn J. Manco-Johnson, M.D., Mountain States Regional Hemophilia and Thrombosis Center, University of Colorado Health Sciences Center, P.O. Box 6507, MS F416, Aurora, CO 80045–0507, U.S.A. E-mail: marilyn.manco-johnson@uchsc.edu.

© 2003 Lippincott Williams & Wilkins, Inc.