Abstract
Introduction: Recently, there has been an increase in using rFVIIa for uncontrolled bleeding in non hemophilic patients. While evidence-based guidelines exist for using rFVIIa in hemophilia, none are available for its off-label use. We report four cases who were treated with rFVIIa for massive uncontrolled hemorrhage.
Method: Four [3 female (F) and one male (M)] critically ill patients with a median age of 59.25 years (range 49–78) exhibiting massive, life-threatening bleeding were treated with rFVIIa after conventional therapy [transfusion of fresh frozen plasma (FFP), red blood cell (RBC), platelet (Plt) and cryopreciptate (cryo)] had failed to control the blood loss. The starting dose was 90 μg/kg. If there was no response within 20 minutes, a second dose of 90 μg/kg was given. The median rFVIIa number of treatments were 4 (range 1–8). Treatment efficacy was evaluated after each dose and was based on : the amount of hemorrhage judged visually, and the number of red blood cell units required to maintain a stable hemoglobin level of > 8g/dl. Clinical response was rated as complete (no transfusion requirement, or change from severe to minor type of bleeding), partial (decrease of hemorrhage from severe to moderate), or failure (no change of hemorrhage and/or no change in transfusion requirement). rFVIIa was given in conjunction with transfusion of packed RBC in order to avoid further loss of clotting factors. If there was no response after a total of >200 μg/kg, the indications for rFVIIa administration were re-checked.
Results: After administration of rFVIIa, three patients had a complete response with cessation of bleeding. There was a decrease in the transfusion requirements in the single non-responder case who later died of massive myocardial ischemia. Most studies have shown that use of rFVIIa yields better results when given earlier rather than later. Nevertheless, our first patient encounter showed good result despite initiation of the therapy 3 weeks after the onset of bleeding. Finally, patient number 3 showed the first successful reported use of rFVIIa for bleeding associated with multiple myeloma.
Conclusion: rFVIIa is effective in the life-threatening emergencies. However, because of the potential thrombotic complications, off-label use should probably be limited to life-threatening blood loss not otherwise controlled by other interventions. Cost/benefit ratio should also be evaluated on a case by case basis.
Age (years)/sex details of the caused of bleeding Bleeding sites Period between the bleeding and the rFVIIa infusion dose/frequency Transfusion requirement pre-/post-rFVIIa Transfusion requirement pre-/post-rFVIIa Response after rFVIIa treatment /Response after rFIIa treatement/ 78/F Coumadin toxicity (INR >10) Gross hematuria, epistaxis, hematochezia, hematemesis 3 weeks 90 μg/kg, 4 doses RBC 17/4,Plt 18/3,FFP 26/2,Cry 5/0 6.8/10.2 Complete in 24 hours/Recovered (INR 1.9) 51/F colon adenocarcinoma (Post-surgical) Surgical incision, Intra-abdominal 48 hours 0 μg/kg, 3 doses RBC 16/3, FFP 5/1 4/10 Complete in 48 hours/Recovered 59/M Multiple myeloma, (PT 44.9, INR 4.5, PTT 37) Hematemesis, hematochezia, melena 72 hours 90 μg/kg, 1 dose RBC 13/2, FFP 4/0 6.5/9.8 Complete in 3 hours/Recovered 49/F Hepatitis C cirrhosis (liver failure). Hematemesis, melena 48 hours 90 μg/kg, 8 doses RBC 12/7, FFP 7/3 6/- Partial in 24 hours/Died
Off-label use of recombinant activated coagulation factor VII for bleeding may raise the risk of arterial thrombosis