Study on the Role of Recombinant Factor VIIa in the Management of Intractable Blood Loss in Patients without Inherited Bleeding Disorder in a UK District General Hospital.

Introduction: Recombinant Factor VIIa (rFVIIa) was developed in early 1990s. Since its license for use in haemophilia with inhibitors, there has been a rationale for use in the management of intractable blood loss in a wide array of clinical situations in patients without an inherited bleeding disorder such as cardiac and general surgery, acute gastrointestinal bleeding and trauma. Little data exists regarding rFVIIa use in such scenarios in the United Kingdom District General Hospitals particularly as access to rFVIIa is not universal.

Aim :We aimed to survey rFVIIa use in a UK District General Hospital with a large cardiothoracic unit to study indications for use, dosing, efficacy, safety profile, cost implications, whether adequate optimisation of coagulation profile occured prior to use in addition to the effect of rFVIIa use on blood product requirement, charting patient outcome at 24 hours and 7 days post dosing.

Methods: Retrospective review of consecutive patients receiving rFVIIa from April 2004 to April 2006 at our instituion. Data was obtained from blood bank records with information stored on an audit database. Adequate optimisation of coagulation profile was defined as achieving platelet count > 20 × 10⁹ /L, PT <1.5, APTT 30–45 secs and Fibrinogen >1 pre factorVIIa use; appropriate dose for Factor VIIa defined as 90 micrograms/kg except patients requiring warfarin reversal where 15–20 microgram/kg has been shown to be effective.

Results: 26 patients (Median age 63.5 years; 62% male) received rFVIIa during the study period. Indicaions for use were: 65% (17/26) during cardiac surgery; 23% (6/26) during general surgery; 8% (2/26) for acute GI bleed and 4% (1/26) for trauma cases. Optimisation of coagulation profile was not performed in 62% of cases due to PT>1.5; in 58% of cases APTT>45s with Fibrinogen <1 in 3% of cases prior to administration. Median dose used was 8.4 mg; 54% (14/26) received an inappropriate dosage of rFVIIa with 12 due to excessive dosage and 2 receieving sub-optimal dosage. No adverse effects were noted in 96% of cases; only 1 patient with subclavian vein thrombosis was reported 10 days post use. 65%, 31% and 4% of patients received 1, 2 and 3 doses of rFVIIa respectively. Significant differences were noted between pre and post dosing RBC (8.5u v 2.0u; 95% CI = 2.78 8.76; p = 0.001), FFP (7u v 0u; 95% CI = 2.73 7.95; p<0.001) and Platelet (2u v 0.5u; 95% CI= 0.7–2.4; p=0.001) requirement but not in cryoprecipitate use (2u v 0u; p=0.195; see table). The difference between mean blood loss pre and post Factor VIIa use was also significant (472.75 v 105.41 mls/hr; 95% CI = 187.62 547.055 ; p=0.001). The total expenditure on Factor VIIa during the study period was £124,755 of which £22,912 amounted to excess dosing. All cause mortality at 24 hours and 7 days post Factor VIIa use was 7.7% and 23.1% respectively with 11.1% discharged from hospital by 7 days.

Conclusion: This study demonstrates rFVIIa is safe and effective in promoting haemostasis and decreasing transfusion requirements in intractable bleeding post cardiac surgery and a variety of other causes. We recommend attention to optimization of coagulation prior to administration as the combination of persistent thrombocytopenia and exhaustion of coagulation factors may result in resistance to rFVIIa therapy. Appropriate dosing is of paramount importance in all cases.