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Control of bleeding in children with Dengue hemorrhagic fever using recombinant activated factor VII: a randomized, double-blind, placebo-controlled study

Chuansumrit, Ampaiwana; Wangruangsatid, Sompornb; Lektrakul, Yujindac; Chua, Mary Ngd; Capeding, Maria Rosario Zetae; Bech, Ole Molskovf; the Dengue Study Group

Blood Coagulation & Fibrinolysis: November 2005 - Volume 16 - Issue 8 - p 549–555
Original Articles

Objectives: We evaluated the efficacy and safety of recombinant activated factor VII (rFVIIa) in children aged < 18 years old with grade II or grade III Dengue hemorrhagic fever (DHF) who required blood component therapy for controlling bleeding episodes.

Study design: Patients were randomized to the rFVIIa group or placebo group in a ratio of 2: 1. rFVIIa or placebo (100 μg/kg body weight) was given by intravenous bolus injection. When bleeding was not effectively controlled, a second dose of rFVIIa or placebo (100 μg/kg) was given 30 min after the first dose.

Results: Nine and 16 patients received placebo and rFVIIa, respectively. The demographics, bleeding manifestations and grade of DHF were similar for the rFVIIa and placebo groups. Apart from petechiae and ecchymosis, one to four additional bleeding sites were found in each patient, including hematemesis (n = 15), epistaxis (n = 14), gum bleeding (n = 12), melena (n = 7), hypermenorrhea (n = 4), hematochezia (n = 2) and hematuria (n = 2). The mean total dose of rFVIIa (138.4 ± 50.9 μg/kg) and placebo (145.4 ± 53.7 μg/kg) were comparable. The efficacy of bleeding control at 2 h after the first dose was completely ceased (rFVIIa 75.0% versus placebo 44.4%), decreased (rFVIIa 18.7% versus placebo 11.2%), and unchanged or worsened (rFVIIa 6.3% versus placebo 44.4%). Some patients with active bleeding received platelet concentrates 3–12 h after the first dose of rFVIIa or placebo. The subsequent efficacy of bleeding control at 6, 12 and 24 h was comparable between the two groups. The cumulative use of red blood cells (rFVIIa 31.3% versus placebo 33.3%) and plasma (rFVIIa 25% versus placebo 22%) during the 24-h period was not significantly different between the two groups. In contrast, platelet concentrate requirement in the rFVIIa group (6.3%) was lower than the placebo (33.3%). No clinical evidence of thromboembolic complications or mortality as a result of bleeding was observed.

Conclusion: rFVIIa appears to be a useful adjunctive treatment to blood component transfusion for controlling active bleeding in children with DHF especially when platelet concentrate is not readily available.

aDepartment of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok

bDepartment of Pediatrics, Buddhachinaraj Phitsanuloke Hospital, Phitsanuloke

cDepartment of Pediatrics, Supprasithprasong Hospital, Ubonrajchathani, Thailand

dDepartment of Pediatrics, Faculty of Medicine and Surgery, University of Santo Tomas, Manila

eDepartment of Microbiology, Research Institute for Tropical Medicine, Muntilupa City, Philippines

fMedical Department, Novo Nordisk Asia Pacific Pte Ltd, Singapore

Received 10 March, 2005

Revised 17 June, 2005

Accepted 17 June, 2005

Sponsorship: supported by Novo Nordisk Asia Pacific Pte Ltd, Singapore.

Correspondence and requests for reprints to Professor Ampaiwan Chuansumrit, MD, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI Road, Bangkok 10400, Thailand. Tel: +662 201 1748; fax: +662 201 1850; e-mail: raajs@mahidol.ac.th

A complete list of the persons and institutions participating in the study appears in the Appendix.

© 2005 Lippincott Williams & Wilkins, Inc.