The use of recombinant activated factor VII for controlling life-threatening bleeding in Dengue Shock Syndrome

Abstract

To report the use of recombinant activated factor VII (rFVIIa) in controlling life-threatening bleeding episodes in patients with grades III and IV Dengue Hemorrhagic Fever (DHF), also known as Dengue Shock Syndrome. Fifteen patients (seven boys, eight girls), whose median age was 8 years, were enrolled in the study. They were divided into two groups. Group 1 included nine patients, mainly grade III, waiting for platelet concentrate, and group 2 included six patients, mainly grade IV, who had already received platelet concentrate with unresponsiveness. A single dose or repeated doses of 100 microg/kg rFVIIa was/were given at intervals of 4 h according to the bleeding symptoms. The median times from the onset of bleeding to rFVIIa initiation were 6.5 and 29.8 h in groups 1 and 2, respectively. Each patient received one to three doses. An effective response was found in eight patients (53.3%), including six patients in group 1 and two patients in group 2. They had complete cessation of bleeding without recurrence for 48 h. An ineffective response was found in seven patients (46.7%) including three patients in group 1 and four patients in group 2 for which the bleeding recurred (n = 2), temporarily slowed down (n = 3), continued (n = 1) or occurred at a new site (n = 1). These included three patients in profound shock 24-48 h before referral to comprehensive treatment centers, two patients receiving ibuprofen before hospitalization, one patient with extensive volume overloading, and one patient requiring surgical intervention to ligate the torn intercostal artery and vein. The platelet concentrate was promptly transfused to stop bleeding in patients with ineffective responses. The results revealed that the earlier initiation of rFVIIa in the mainly grade III DHF in group 1 yielded a higher effective response (66.7%) than the delayed initiation in the mainly grade IV DHF in group 2 (33.3%). Moreover, patients previously receiving ibuprofen or volume expander of low molecular weight dextran or urea-linked gelatin tended to have lower effective responses (28.6%) than patients without associated medication (75.0%). Ultimately, three of six patients with grade IV DHF died, while all nine patients with grade III DHF survived. Thus, the case-fatality rate in this study was 20%. No clinical evidence of thromboembolic complications was observed. rFVIIa seems to be effective in restoring hemostasis in a limited series of patients with Dengue Shock Syndrome exhibiting life-threatening bleeding episodes. Further study is warranted.

Cost–utility analysis of an adjunctive recombinant activated factor VIIa for on-demand treatment of bleeding episodes in dengue haemorrhagic fever

“…One of the two treatment options was assigned: a standard care or adjuvant rFVIIa in a dose of 80 mg/kg body weight [8,9]. This particular group had a representative age of patients who were most likely to be present with this condition, based on a study in Thailand [8]. The average weight of the patient was assumed to be 50 kg.…”

“…Effective response was defined as the condition in which the bleeding episode had completely stopped, and ineffective response as the condition in which the bleeding episode had worsened, remained unchanged, temporarily slowed, or had occurred at a new site [8].…”

“…If not available, data were obtained from other more or less similar clinical conditions to DHF/DSS. The data collected were clinical efficacy for each treatment option from a single RCT with DHF/DSS [8,9], incidence rate of ATE [11,12], and the assigned probability of dying after an ATE [13]. The administration dose was 80 mg/kg of rFVIIa (i.e.…”

“…Moreover, prophylactic platelet or fresh frozen plasma transfusions were not beneficial in both children [6] and adults [7]. Even if efficacy is granted, concentrated platelet transfusion for controlling massive bleeding [8] was not always readily available [9] in resource-limited settings. Thus, alternative measures should be considered to support the coagulation process and control haemorrhage and plasma leakage.…”

The Use of Recombinant Factor VIIa in Gastrointestinal Bleeding

“…Chuansumrit et al have reported an observational study of 12 patients with DSS treated with rFVIIa for life-threatening bleeding episodes comprised by hematemesis, hematochezia, and hypermenorrhea. 24 Patient ages ranged from 1-14 years. rFVIIa was administered as bolus injections varying from 100-200 µg/kg/dose.…”