Recombinant factor VIIa: review of efficacy, dosing regimens and safety in patients with congenital and acquired factor VIII or IX inhibitors

Emory University, Atlanta, Georgia, United States
Journal of Thrombosis and Haemostasis (Impact Factor: 5.55). 07/2004; 2(6):899-909. DOI: 10.1111/j.1538-7836.2004.00759.x
Source: PubMed

ABSTRACT Recombinant factor (rF)VIIa has been available to clinicians since 1996 and has an excellent safety record after almost three-quarters of a million doses have been administered. This paper will review the current clinical experience with rFVIIa dosing in acquired and congenital hemophilia with inhibitors and chronicle all spontaneous and clinical trial reports of thrombotic adverse events as of April 2003. Standard dosing of rFVIIa (90 micro g kg(-1)) allows binding of FVIIa to the surface of an activated platelet and can directly activate factor X in the absence of tissue factor. Experience with bolus dosing suggests that higher dosing (>200 micro g kg(-1)) may be more efficacious in treating hemophilia patients. Clinical trials are ongoing to validate this observation. Continuous infusion dosing may be efficacious for major surgery but high infusion rates (50 micro g kg(-1) h(-1)) might be needed. The relationship between dose of rFVIIa, amount of thrombin generated and measurable FVIIa level is still not known and perhaps newer testing which measures thrombin generation might be more advantageous. Relatively few thrombotic events have been associated with rFVIIa. Known factors predisposing to thrombosis were present in 20 of the 25 (80%) hemophilia patients who were reported spontaneously or who developed a thrombosis during a clinical trial. Additionally, thrombotic events have not increased despite a growing experience with higher dosing of rFVIIa.

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Available from: Gili Kenet, Jul 30, 2015
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    • "Identified published reports on parallel use of aPCC ( FEIBA ) and r - FVIIa ( NovoSeven ) . Diagnosis Case ( s ) Age ( years ) , sex aPCC / r - FVIIa infusions Doses administered Complication Reference HA + inhibitor haematomas 1 2 2# Sequential 90 lg / kg r - FVIIa / 2 h 75 iu / kg aPCC / 12 h PE Rosenfeld et al ( 2002 ) HA + inhibitor 1 26 # Sequential 84 lg / kg r - FVIIa aPCC dose unknown AMI Abshire and Kenet ( 2004 ) Acquired HA 1 57 $ Sequential 20 – 48 lg / kg r - FVIIa aPCC dose unknown DVT + PE Abshire and Kenet ( 2004 ) Acquired HB 1 70 # Sequential r - FVIIa dose unknown aPCC dose unknown DIC Abshire and Kenet ( 2004 ) Acquired HA 1 55 # Sequential 80 lg / kg r - FVIIa aPCC dose unknown Cerebral thrombosis Abshire and Kenet ( 2004 ) Acquired HA 1 56 $ Sequential r - FVIIa dose unknown aPCC dose unknown DIC Abshire and Kenet ( 2004 ) "
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    • "The treatment of bleeding in ageing haemophilia patients with inhibitors include the use of APCC and rFVIIa and , if residual FVIII is still present , of desmopressin ( Mannucci , 1997 ; Abshire & Kenet , 2004 ; Dimichele & Negrier , 2006 ) . There are concerns regarding the use of bypassing agents in these elderly patients considered at risk of thrombotic complica - tions . "
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