Anti-inhibitor Coagulant Complex (Autoplex) for treatment of factor VIII inhibitors in hemophilia.
Abildgaard CF, Penner JA, Watson-Williams EJ.
Fourteen individuals with severe hemophilia complicated by factor VIII inhibitors (1 to 132 Bethesda Units) were treated for 33 bleeding episodes with a new activated prothrombin complex concentrate, Anti-Inhibitor Coagulant Complex (Autoplex, Hyland, Glendale, Calif.). Excellent or good results were observed in 21 of 25 minor bleeding episodes treated, which included joint, soft tissue, and mucous membrane hemorrhages. Eight major bleeding problems (an epidural bleed, a puncture wound, 2 serious soft tissue hemorrhages, 2 lacerations, and 2 major surgical procedures) were treated with excellent (6) or good (2) results. No serious complications were encountered, but two children developed transient hypofibrinogenemia following Autoplex infusion. Although some shortening of the prothrombin time and activated partial thromboplastin time was noted after infusion of Autoplex, there is no useful laboratory test for monitoring therapy. Despite the unknown mechanism of action for bypassing factor VIII, Autoplex appears to be a useful and needed interim product and is safe and effective. In view of the possible potentiation of thrombosis concurrent use of fibrinolytic inhibitors should be avoided.
Treatment of a high titer anti-factor-VIII antibody by continuous factor VIII administration: report of a case.
White GC 2nd, Taylor RE, Blatt PM, Roberts HR.
Daily administration of large doses of factor VIII concentrate in a hemophiliac with a high titer factor VIII inhibitor resulted in marked reduction in the titer and response of the inhibitor to factor VIII administration and made possible elbow and bilateral knee replacements under conventional factor VIII coverage. Studies performed during the course of treatment indicated that the reduction in the inhibitor was the result of specific tolerance to factor VIII.
Use of activated prothrombin complex concentrate over multiple surgical episodes in a hemophilic child with an inhibitor.
Heisel MA, Gomperts ED, McComb JG, Hilgartner M.
Optimal care of inhibitor patients during surgery.
Vermylen J, Peerlinck K.
Centre for Molecular, Katholieke Universiteit Leuven, Belgium.
The care of haemophilia patients with high titre inhibitors during surgery has always been a formidable challenge. The introduction of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) appears to be a major breakthrough for the management of such patients. Administration of rFVIIa as a continuous infusion is a very attractive option and precludes the need for very frequent (2-h) injections due to the very short half-life of the product. Successful major surgery has been performed in patients with high titre inhibitors using continuous infusion of rFVIIa. Several questions remain, however, such as optimal therapeutic level, optimal monitoring, optimal prevention of thrombophlebitis at the injection site and the necessity for antifibrinolytic agents.
Recombinant factor VIIa for patients with inhibitors to factor VIII or IX or factor VII deficiency.
Scharrer I.
Klinikum der Johann Wolfgang Goethe-Universitat, Zentrum der Inneren Medizin, Frankfurt am Main, Germany.
Inhibitors to factor VIII (FVIII) or IX (FIX) in patients with haemophilia A or B create a challenging problem for the treatment of these patients. Recombinant FVIIa (rFVIIa; NovoSeven, Novo Nordisk A/S, Bagsvaerd, Denmark) is a realistic treatment option, owing to its specific mode of action and lack of immunogenicity. This was a multicentre, open-label, compassionate-use trial in patients with severe haemophilia A (FVIII:C < 1%) or B (FIX:C < 1%) with inhibitors, acquired antibodies to FVIII or FIX, or FVII deficiency (FVII:C < 5%), for whom alternative therapies had failed or were contraindicated. Patients received rFVIIa treatment for life- or limb-threatening bleeding episodes or for coverage during essential surgery. The mean rFVIIa dose was approximately 90 microg kg-1 for haemophilia A/B and acquired inhibitor patients, and 25 microg kg-1 for FVII-deficient patients. Efficacy data for 67 treatment episodes (45 bleeding episodes, 22 surgical procedures) are presented; seven patients were treated for a concurrent serious bleeding episode and surgical procedure. At the end of treatment, rFVIIa was effective or partially effective in 85% of serious bleeding episodes. During surgery, bleeding was assessed as none or less than or equivalent to normal in 91% of surgical procedures; postoperatively, 91% of procedures were associated with no or minimal oozing. During 60 separate treatment episodes, 26 adverse events (22 nonserious, four serious) were reported in 15 patients, during 17 bleeding episodes or surgical procedures. Only 10 were considered as having a possible, probable, or unknown relationship with rFVIIa; of these, fever (n=2) and thrombophlebitis (n=3) were the most common. There was no evidence of disseminated intravascular coagulation. In conclusion, rFVIIa is an effective, well-tolerated treatment for serious bleeding episodes and bleeding associated with surgical procedures in patients with severe haemophilia A/B with inhibitors, acquired inhibitors, or FVII deficiency.