Treatment of factor XI inhibitor using recombinant activated factor VIIa

Abstract

A 30-year-old female with severe factor XI deficiency of 0-2% acquired factor XI inhibitor following many infusions for fresh frozen plasma (FFP) for surgical procedures starting at 4 years of age. Seven months before this inhibitor was diagnosed, surgery was complicated by prolonged bleeding resistant to FFP, requiring epsilon aminocaproic acid (EACA) and surgical packing. The inhibitor was measured at 2.2 Bethesda units, 7 months since the last FFP. The inhibitor was confirmed as specific anti-XI and anti-XIa binding by patient's IgG to immobilized factor XI and factor XIa from whole plasma and purified IgG. For repair of a painful anterior cruciate ligament (ACL) defect she was given recombinant factor VIIa (rVIIa) at 90 mug kg(-1), starting one-half hour preoperatively and continued every 2 h for 8 h when haemostasis was complete. Thereafter the rVIIa was given every 3 h for two doses, and then every 4 h for four doses at which time she was discharged on EACA which was continued for 6 days. There was excellent haemostasis during and following the surgery. There was no evidence of consumptive coagulopathy, with no change in the fibrinogen, platelet count, or D-D dimer; and no increase of platelet factor 4, beta-thromboglobulin, or prothrombin fragment F 1.2. The thrombin-antithrombin complex increased over baseline after 24 h. There was no postoperative deep vein thrombosis or pulmonary embolus. In this patient with a factor XI inhibitor, the recombinant factor VIIa was effective and safe, ensuring adequate haemostasis with no thrombotic complications. This product which was designed for patients with inhibitors to factor VIII or factor IX, and factor VII deficiency, has now been given successfully to four patients with factor XI inhibitors.

Effects of recombinant activated factor VII on thrombin-mediated feedback activation of coagulation

“…The management of FXI(À) patients remains controversial; however, rFVIIa [22,23] and antifibrinolytic agents [24,25] have been used instead of plasma exchange/transfusion.…”

Factor XI deficiency—resolving the enigma?

“…[33][34][35] Experimental work has shown that a lower amount of rVIIa is required for thrombin generation in FXI-deficient plasma than in severe hemophilia A or B plasmas. 36 Use of lower doses of rVIIa (15-20 μg/kg) may reduce the risk of thrombosis observed in a series of patients treated for surgery where the conventional dose of 90 μg/kg was used.…”

The obstetric and gynaecological management of women with inherited bleeding disorders – review with guidelines produced by a taskforce of UK Haemophilia Centre Doctors’ Organization

“…As for all blood products there are concerns about the risk of transfusion-transmitted infections. Recombinant factor VIIa (rFVIIa) has been used successfully in these patients [92][93][94], although it is as yet unlicensed in this setting. Its short half-life makes it unsuitable for use to cover labour, but could be used for management of elective caesarean section.…”