Recombinant Factor VIIA in the Treatment of Bleeding

Madhu V. Midathada, MD; Paulette Mehta, MD; Milton Waner, MD; Louis M. Fink, MD

Disclosures

Am J Clin Pathol. 2004;121(1) 

In This Article

Continuous Infusion of rFVIIa

The standard modality of administration of rFVIIa is intermittent infusion every 2 to 6 hours. rFVIIa has a short half-life, only 2.5 hours, and necessitates frequent dosing intervals to maintain the levels.[121] Hence, continuous infusion seems to be more effective for maintaining rFVIIa levels. Continuous infusion of rFVIIa was first described in 1996. It has been used mostly in the treatment of hereditary or acquired hemophilia. Compared with bolus dosing, it is more convenient and less expensive; potential pitfalls are hemorrhagic complications.[122]

Baudo et al[123] reported continuous infusion of rFVIIa through a central vein catheter in 4 patients with factor VIII inhibitors; they monitored the signs for systemic activation of the hemostasis system. The parameters studied were fibrinogen, platelet count, D-dimer and, F1+2 prothrombin fragments. The F1+2 prothrombin fragments and D-dimer increased after the bolus and remained higher than the baseline values throughout the treatment period. These variations observed during the infusion period were not accompanied by clinical events. The only episode of DIC was secondary to septic shock.

Addition of heparin to reconstituted rFVIIa causes a 50% loss of activity within 4 hours of storage in the infusion system. Low-molecular-weight heparin has no such effect. Two patients treated with continuous infusion of rFVIIa on 4 occasions for surgery had no adverse effects other than repeated thrombophlebitis when the rFVIIa was not given with heparin.[124,125,126] Continuous infusion is feasible with minipumps; it eliminates 2 hourly injections and reduces the total dose of rFVIIa by 50% to 75% depending on the behavior of clearance. Continuous infusion of rFVIIa has been shown to have the advantages of maintaining a constant factor concentration, thereby reducing the risk of bleeding from excessively low trough concentrations. A reduction in factor clearance has been noted with continuous infusion, which leads to a decrease in factor consumption and thereby a requirement for smaller amounts of rFVIIa to control bleeding.

Santagostino et al[127] report their experience with use of rFVIIa as a continuous infusion in 25 patients with hemophilia and high responding inhibitors and 3 patients with nonhemophilic inhibitors. A satisfactory hemostatic response was achieved in 30 of 35 treatment courses. These findings are comparable with those in other published series using bolus administration of rFVIIa.[128,129] In contrast, the results with continuous infusion of rFVIIa in 8 patients with inhibitors to factor VIII undergoing elective surgery were disappointing. Effective hemostasis was achieved in 1 of 2 minor procedures and in 2 of 6 major operations.[130] The different outcomes observed in the 2 studies might be explained partly by the differences in the treatment intensity, but there might be other patient-specific variables that might affect the clinical responses to rFVIIa.[124]

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