What alternative is the for treating patients with dengue and dengue haemorrhagic fever who have a low platelet count?

Trends in Immunology
Volume 25, Issue 9, September 2004, Pages 461-464

Copyright © 2004 Elsevier Ltd All rights reserved.

Emerging roles of tissue factor in viral hemorrhagic fever

Wolfram Ruf
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

Abstract
Activation of coagulation by tissue factor (TF) is frequently observed in sepsis syndrome and is documented in certain viral hemorrhagic fevers. Coagulation protease complexes signal by activating the G-protein coupled, protease-activated receptors that regulate inflammation. Blockade of TF attenuates lethality in experimental models of Ebola virus infection but – similar to findings in bacterial sepsis – reduction of inflammation, rather than attenuation of coagulation, predicts survival of treated animals. Thus, targeting TF appears to aid the antiviral immune response in hemorrhagic fevers, and further studies are encouraged to define how TF-dependent signaling regulates immunity.



Blood Coagul Fibrinolysis. 2000 Apr;11 Suppl 1:S101-5

Recombinant activated factor VII in children with acute bleeding resulting from liver failure and disseminated intravascular coagulation

Chuansumrit A, Chantarojanasiri T, Isarangkura P, Teeraratkul S, Hongeng S, Hathirat P. Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. raajs@mahidol.ac.th

Recombinant activated factor VII (rFVIIa) was given to three children with acute bleeding resulting from liver failure and disseminated intravascular coagulation. Cases I and II (girls aged 3 years and 6 years, respectively) were diagnosed with Dengue hemorrhagic fever and prolonged shock. Case III, a boy aged 9 months, underwent left lobe hepatectomy for a hepatoblastoma, during which 60% of his liver was removed. This case was complicated by myoglobinuria, liver and renal impairment and early disseminated intravascular coagulation. All three patients exhibited active bleeding. Cases I and II received rFVIIa combined with other blood component replacement, while Case III received rFVIIa as the only hemostatic agent. A bolus of 40-180 microg/kg b.w. was administered followed by 16.5-33 microg/kg b.w. per h continuous infusion. As a result, bleeding was controlled, the prothrombin time was shortened and FVII clotting activity was significantly increased. In conclusion, rFVIIa has shown some efficacy in controlling acute bleeding in children with liver failure and disseminated intravascular coagulation.

PMID: 10850573 [PubMed - indexed for MEDLINE]



http://www.bloodcoagulation.com/pt/re/bcf/abstract.00001721-200511000-00003.htm;jsessionid=L21Np6JpdYCBXhdLcpPf3NvvMpQTB QyTKpRy5VY6yg1nrkJ2gRPD!1270838445!181195628!8091!-1

Blood Coagulation & Fibrinolysis. 16(8):549-555, November 2005.

ORIGINAL ARTICLES

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

Chuansumrit, Ampaiwan a; Wangruangsatid, Somporn b; Lektrakul, Yujinda c; Chua, Mary Ng d; Capeding, Maria Rosario Zeta e; Bech, Ole Molskov f; the Dengue Study Group

Abstract:
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 [mu]g/kg body weight) was given by intravenous bolus injection. When bleeding was not effectively controlled, a second dose of rFVIIa or placebo (100 [mu]g/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 [mu]g/kg) and placebo (145.4 +/- 53.7 [mu]g/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.

(C) 2005 Lippincott Williams & Wilkins, Inc.