dengue is an arboviral disease endemic in most of the tropical countries with recurrent epidemics .
although dengue is known to cause hepatic involvement commonly , it only occasionally results in fulminant liver failure ( flf ) , which has a high mortality .
n - acetyl cysteine ( nac ) , a precursor of glutathione , is an effective antioxidant scavenging for oh radicals have shown to be effective mainly in acetaminophen and even in non - acetaminophen - induced flf .
activated recombinant factor vii ( rfviia ) was initially developed to overcome the limitations of existing treatments for patients with congenital hemophilia and inhibitors .
clinical success in this arena led to experimental use in other coagulopathies as well . to the best of our knowledge ,
this is the first reported case of dengue hemorrhagic fever complicated by fulminant liver failure and massive hemorrhage successfully managed with nac and rfviia .
a 37-year - old previously healthy man who was a teetotaler admitted with fever , repeated vomiting , body aches , and fatigue for four days .
examination revealed a temperature of 100f , tachycardia ( 106/min ) , normotension , and tachypnea ( 28/minute ) .
investigations showed leukocyte count ; 5.1  10/l ( neutrophils 53% , lymphocytes 41% ) , and platelets ; 60  10/l , hemoglobin ; 14.1 g / dl with hematocrit of 43.4% , aspartate aminotransferase ( ast ) ; 220 u
/ l , alanine aminotransferase ( alt ) ; 157 u / l on admission . presumptive diagnosis of dhf was made considering the clinical picture and prevailing outbreak in the country .
close monitoring with replacement of maintenance volume of fluids was started in both oral and intravenous means . during next 36 hours , he had clinical and hematological evidence of ongoing plasma leakage but remained hemodynamically stable .
next day , he was shifted to intensive care unit due to agitation and drowsiness .
platelet count dropped to less than 10  10/l during day 5 and 6 of the illness and subsequently started rising gradually .
u / l ) in seventh day of illness with prolongation of prothrombin time of 19.8s ( inr ; 1.7 ) activated partial thromboplastin time ( 89s ) , and elevated serum bilirubin .
chest x - ray and ultrasonography of abdomen showed bilateral pleural effusions and moderate ascites .
liver failure treatments started with intravenous vitamin k , thiamine , lactulose , and oral metronidazole .
in the same day , worsening agitation and sensorium ( grade iii hepatic encephalopathy ) necessitated elective intubation and mechanical ventilation .
blood sugar was monitored , and his serum sodium levels maintained at 145 - 150 mmol / l range .
an internal jugular central venous access was secured following transfusion of platelets and fresh frozen plasma ( ffp ) .
twenty percent manitol infusion was administered 12 hourly for 48 hours , and nac intravenous infusion was continued for 72 hours .
bleeding was difficult to control with transfusion of platelets , fresh frozen plasma , and pack red cells alone .
this prompted us to administer him with 3 doses of rfviia following transfusion of cryoprecipitate to replenish fibrinogen levels in serum .
patient 's central venous pressure started rising ( 24 - 29 cmh2o ) by ninth day with of illness necessitating a considerable dose of frusemide to achieve a safe level of cvp ( 8 - 12 cmh2o ) .
dengue igm and igg ( elisa ) were positive , while malarial smear , hepatitis panel , leptospira serology , and hiv elisa became negative .
however , the course of his illness was complicated initially by ventilator - associated pneumonia with acenetobacter and later by pseudomonas , necessitating antibiotic cover with netilmycine and ceftazidime .
he was extubated following 7 days of ventilatory support and managed to be discharged after 18 days of hospital stay .
dengue hemorrhagic fever is defined as the presence of fever , thrombocytopenia , and evidence of capillary leak with serological evidence of acute infection by dengue virus .
current management of dhf is mainly focused on meticulous fluid management during leakage phase of the illness . in dhf ,
an antibody - dependent immune mechanism is in play , by which non - neutralizing antibodies of previous dengue infection complexes with the new infecting serotype enhancing its uptake .
liver damage is due to viral replication in hepatocytes , cytokine - related damage , and partly due to ischemic hepatitis .
fulminant liver failure is defined as rapid onset of acute encephalopathy and coagulopathy ( inr 1.5 ) in the setting of liver failure less than 6 weeks duration . since the liver is capable of regenerating to a large extent as underlying cause of hepatocyte injury
is controlled with supportive medical therapy , fhf in principle sustains potential for a complete recovery .
fulminant liver failure due to dengue infection with subsequent complete recovery has been reported rarely .
flf may be associated with changes in systemic hemodynamic , i.e. , tissue hypoxia , which contributes to multiple - organ failure .
recent studies have shown that nac administered to patients with flf ( non - paracetamol - induced ) increases oxygen delivery and improves survival .
morbidity and mortality in dhf is mainly associated with either prolonged shock or fluid overload .
activated recombinant factor vii is a coagulation protein that induces hemostasis by directly activating factor x. there were some evidences on safety and efficacy of rfviia for controlling hemorrhage in patients without hemophilia .
since inadvertent administration of blood products would worsen the fluid overload in dhf , the place for rfviia seems to be invaluable to arrest life - threatening bleeding as in our patient .
so far , there was no clear information about the prophylactic or therapeutic use of rfviia in dhf .
the use of nac and rfviia despite limited evidence presumably had a greater impact on recovery of our patient .
therefore , this case highlights the potential use of rfviia and nac along with aggressive supportive measures in cases of near - fatal dhf for a successful outcome .
prevention of ischemic injury of liver by meticulous fluid resuscitation during the leakage phase of dengue fever is of paramount importance .
dengue may occasionally lead to flf , has to be treated promptly with aggressive supportive measures .
indication of rfviia to arrest uncontrolled internal bleeding and the place of nac in non - acetaminophen - induced flf in complicated dhf is a platform for discussion .
 consensus on management of complicated cases of dengue infection is evolving . dengue hemorrhagic fever ( dhf ) occasionally progress to fulminant liver failure with high fatality rate . 
 inadvertent use of blood products to control massive bleeding in dengue shock syndrome may worsen fluid overload and subsequently the multi - organ dysfunction . 
 we report a case of 37-years - old sri lankan man who developed fulminant liver failure and massive bleeding associated with dhf , subsequently recovered completely with supportive measures including administration of n - acetyl cysteine and activated recombinant factor vii 
 . in conclusion , prevention of ischemic injury to liver and adoption of early aggressive supportive measures in complicated cases of dengue hemorrhagic fever is crucial for a favorable outcome . 
 indications for rfviia to arrest uncontrolled internal bleeding and use of nac in non - acetaminophen - induced acute liver failure in complicated dhf are a platform for discussion . 
INTRODUCTION
CASE REPORT
DISCUSSION
CONCLUSION