Low-dose recombinant factor VIIa for trauma patients with coagulopathy

INTRODUCTION: Coagulopathy in injured patients is common and is generally treated with fresh frozen plasma (FFP). Response can be variable, thus complete correction may take hours and require large volumes of fluids. High-dose recombinant factor VIIa (FVIIa, Novoseven, Novo Nordisk, Bagsvaerd, Denmark) has been used off-label to treat severe coagulopathy following trauma. Expense has limited use. Recently, we began administering low dose FVIIa (1.2mg) to patients with mild to moderate coagulopathy after trauma, hypothesising that it would be effective and safe. PATIENTS AND METHODS: We retrospectively reviewed consecutive patients who received a low dose of 1.2mg of FVIIa over a 2-year period. Factor VIIa is administered after approval by a gatekeeper at the discretion of the treating physician. Demographics, injury and laboratory data were abstracted as were indications for use, source of coagulopathy, effectiveness, and complications. A two-tailed paired t-test was used to determine significant changes in coagulation parameters and blood product utilisation. RESULTS: Eighty-one patients received 84 low doses of FVIIa. The mean age of the patients was 51 (+/-22) with a mean ISS of 29 (+/-11). Seventy-three per cent were male and 67% had a traumatic brain injury (TBI) as their primary injury. The aetiology of the coagulopathy in the study population included; TBI (40%), warfarin use (22%), and cirrhosis (13%). Mean prothrombin time (PT) fell from 17.0s (+/-3.2) to 10.6s (+/-1.4) (p<0.0001). All patients had a good clinical response with no bleeding complications. Utilisation of packed red blood cells and fresh frozen plasma were significantly less in the 24h after FVIIa administration as compared to the 24h prior. Subsequent thromboembolic events were observed in 12 of the 81 patients (15%) and included; cerebrovascular accident (CVA) (6), mesenteric thrombosis (2), myocardial infarction (MI) (1), pulmonary embolism/deep venous thrombosis (PE/DVT) (2), and atrial thrombus (1). Only four of these events were thought to be related to the FVIIa administration, with two of the four contributing to a lethal outcome. CONCLUSIONS: Low dose FVIIa rapidly and effectively treats mild to moderate coagulopathy following injury. This low dose (1.2mg) FVIIa is the smallest available unit dose. It costs approximately the same as 8 units of plasma and may be cost-effective in patients who require high volume factor administration. Low dose FVIIa may be effective in coagulopathic trauma patients who are not in shock but require rapid normalisation of clotting function.     

Successful reversal of deleterious coagulopathy by recombinant factor VIIa

Effective treatment of severe or uncontrolled bleeding is a challenge for physicians in the operating room and intensive care unit. However, even aggressive conventional therapy may ultimately fail in some patients. Administration of recombinant activated factor VII (rFVIIa) may be the only remaining therapeutic option to stop life-threatening coagulopathic bleeding. We here describe the clinical course of 5 patients exhibiting severe continuous bleeding that could not be stopped by surgical intervention and appropriate hemostatic management but resolved after a mean dose of 90 microg/kg of rFVIIa (range, 90-120 microg/kg). Four of the five patients recovered completely, and one patient died after developing sepsis in multiorgan failure. In all patients, bleeding from wound surfaces stopped within minutes of the administration of rFVIIa. Coagulation measurements improved, and transfusion requirements declined considerably. No adverse effects associated with rFVIIa were observed.     

Predicting response to recombinant factor VIIa in non-haemophiliac patients with severe haemorrhage

Editor—With the exception of cases of blunt trauma, thereis no evidence from randomized controlled trials to supportthe use of recombinant factor VIIa (rFVIIa) as rescue treatmentfor severe haemorrhage in non-haemophiliacs. Uncertainty remainsregarding what dose of rFVIIa to give, when to give it, howoften, and how to optimize its efficacy. Furthermore, a crucialquestion is: who do you give rFVIIa to and who do you not give     

Predicting response to recombinant factor VIIa in non-haemophiliac patients with severe haemorrhage

Background. Despite increasing use of recombinant factor VIIa(rFVIIa) in non-haemophiliac patients, it is unclear when rFVIIamight be effective. Methods. A single centre review of consecutive non-haemophiliacpatients receiving rFVIIa for the management of severe haemorrhage.Treatments with rFVIIa were at a dose of 90 µg kg^–1repeated at three hourly intervals at the clinicians' discretion. Results. Eighteen patients received rFVIIa. Six patients survivedto discharge and 12 patients died in hospital. The median (range)Sequential Organ Failure Assessment (SOFA) score at the timeof administration of rFVIIa for the group that survived was8.0 (5–12) compared with the group that died 12.0 (7.0–14.0)(P=0.03). One of the patients who survived (17%) had organ failureat the time of rFVIIa administration compared with 11 of thosewho died (92%) (P=0.004). Fifteen patients survived long enoughto consider a second dose of rFVIIa, one patient who survivedto discharge needed more than one dose (1/6, 17%), comparedwith seven of those who later died in hospital (7/9, 78%) (P=0.04).The survivors had a significant reduction in blood product requirementsafter rFVIIa, while patients who died did not. Neither the prothrombintime nor the activated partial thromboplastin time before orafter rFVIIa predicted survival. Conclusions. High SOFA score and failure to respond to one adequatedose of rFVIIa appear to identify patients with poor prognosis.These observations may help in determining when rFVIIa treatmentis likely to be futile.     

Treatment of bleeding in severe hemorrhagic pancreatitis with recombinant factor VIIa

Recombinant factor VIIa (rFVIIa) has been used to treat bleeding complications in patients with hemophilia. It acts at the site of vessel injury, forming a complex with tissue factor to activate the clotting cascade. Recent reports have shown rFVIIa may be a useful hemostatic agent in patients after obstetrical, urologic, trauma, or transplant procedures. We report the first documented case of bleeding from hemorrhage pancreatitis treated with rFVIIa.     

Postsurgical coagulopathy in a hemophilia A patient with inhibitors: efficacy of recombinant factor VIIa

Perioperative hemostatic management in patients with hemophilia A who develop the coagulation factor VIII (FVIII) inhibitor is challenging, because exogenous FVIII is neutralized, which boosts the inhibitor to provoke postoperative coagulopathy. Recombinant activated factor VII (rFVIIa) has become available for this type of patient, although FVIII is sometimes required. We treated a 56-year-old male patient with hemophilia A with FVIII inhibitor scheduled for total hip arthroplasty (THA) and total knee arthroplasty (TKA). We used rFVIIa for THA; however, the amount of bleeding was 2,500 ml and blood transfusion was required, which boosted FVIII inhibitor after surgery. The TKA was then scheduled for 19 months later, after the level of the inhibitor had reduced to the preoperative level. Unfortunately, rFVIIa failed to improve PT/APTT, and thus we used recombinant factor VIII (rFVIII). The amount of bleeding during TKA was 1,340 ml, while the level of the inhibitor increased to a greater level than that after THA, provoking uncontrollable bleeding. For anesthetic management in hemophilia A patients with FVIII inhibitor, anesthesiologists must pay attention to postoperative coagulopathy, and every effort should be used to minimize exposure to FVIII. Furthermore, when rFVIIa is ineffective, postponement of surgery until rFVIIa regains its efficacy may be beneficial as compared to an operation with FVIII.     

Use of recombinant factor VIIa for adjunctive hemorrhage control in trauma and surgical patients

Recombinant factor VIIa (rFVIIa) has recently been described for patients with ongoing massive bleeding in a number of different clinical scenarios. A retrospective chart review was conducted at a public level I trauma center in order to describe the use of rFVIIa in trauma and surgical patients with massive bleeding despite surgical control. Fifteen trauma and general surgical patients underwent major operative procedures and developed coagulopathy requiring massive blood product transfusion. All patients had continued life-threatening hemorrhage despite surgical control of bleeding. The mean base deficit was 6 and arterial lactate was 9.0 mmol/L. An initial dose of rFVIIa was given intravenously, followed by a second dose if there was evidence of at least a partial response. Twelve of 15 patients who had been expected to die from hemorrhage survived for greater than 48 hours, and 7 survived to hospital discharge. A partial or complete hemostatic response to rFVIIa was noted in 12 of 15 patients. The number of blood products received after administration of rFVIIa was significantly reduced and the International Normalized Ratio (INR) decreased. Our experience demonstrates that rFVIIa may reduce or completely arrest coagulopathic bleeding in trauma and surgical patients after vascular control.     

Use of activated recombinant factor VII for severe coagulopathy post ventricular assist device or orthotopic heart transplant

Background  

Ventricular assist devices(VAD) implantation/removal is a complex surgical procedure with perioperative bleeding complications occurring in nearly half of the cases. Recombinant activated factor VII (rFVIIa) has been used off-label to control severe hemorrhage in surgery and trauma. We report here our experience with rFVIIa as a rescue therapy to achieve hemostasis in patients undergoing orthotopic heart transplant (OHT) and/or VAD implantation.     

Successful treatment using recombinant factor VIIa for severe bleeding post cardiopulmonary bypass

PURPOSE: To describe a case of persistent and excessive bleeding following an aortic valve and ascending aorta replacement that was successfully managed with recombinant factor VIIa (rFVIIa). The postulated mechanisms for rFVIIa are discussed. CLINICAL FEATURES: A 75-yr-old female with no preoperative coagulopathy underwent a tissue aortic valve replacement and supracoronary ascending aorta replacement for severe aortic stenosis and an ascending aortic aneurysm. Following surgery, she bled in excess of 200 mL x hr(-1) despite a nearly normal platelet count and nearly normal coagulation parameters. The patient was surgically re-explored twice in seven hours, and despite the presence of near normal in vitro coagulation parameters, the patient continued to bleed. Multiple units of fresh frozen plasma, platelets and cryoprecipitate were administered empirically. We then administered a single 6-mg (107 microg x kg(-1)) iv dose of rFVIIa. Following the administration of rFVIIa, blood loss decreased to a total of 440 mL over the next 12 hr. CONCLUSIONS: This case describes the use of rFVIIa for intractable bleeding postcardiovascular surgery in the presence of nearly normal laboratory markers of coagulation. Further controlled laboratory and clinical studies are required to define the role of rFVIIa in patients undergoing cardiovascular surgery.