PMID- 15810910
OWN - NLM
STAT- MEDLINE
DCOM- 20050609
LR  - 20220330
IS  - 1351-8216 (Print)
IS  - 1351-8216 (Linking)
VI  - 11
IP  - 2
DP  - 2005 Mar
TI  - Dose effect and efficacy of rFVIIa in the treatment of haemophilia patients with 
      inhibitors: analysis from the Hemophilia and Thrombosis Research Society 
      Registry.
PG  - 100-6
AB  - Recombinant activated factor VII (rFVIIa), licensed in 1999 for treatment of 
      haemophilia patients with inhibitors (HI), represents an important advance in the 
      therapeutic armamentarium. Standard bolus dosing ranges from 90 to 120 mcg kg(-1) 
      every 2-3 h until arrest of bleeding. As licensure, clinical use of rFVIIa has 
      increased and broadened. Clinicians now use a wide dose range, 90-300 mcg kg(-1). 
      High-dose regimens may optimize thrombin generation or burst, and may allow for 
      prolonged dose interval. The Hemophilia and Thrombosis Research Society (HTRS) 
      maintains a registry database to study haemophilia treatment and related 
      disorders, particularly treatment of acute bleeding in HI, acquired haemophilia, 
      FVII deficiency and von Willebrand's disease (VWD). To assess the effect of 
      rFVIIa dose on efficacy and safety in the treatment of acute bleeding in HI, data 
      from the HTRS database from January 2000 through June 2002 were analysed. 
      Bleeding episodes were grouped by bolus rFVIIa dose range: <100, 100-150, 150-200 
      and >200 mcg kg(-1). Investigator-reported efficacy for the first 72 h of 
      treatment was evaluated. Thirty-eight congenital HI patients were treated for 555 
      bleeding episodes. Patient age range was 1-55 years (median: 14). Bleeding 
      episodes were spontaneous (45%), caused by trauma (38%), or because of surgery, 
      dental, diagnostic, or medical procedures (17%); bleeding occurred in joint, 
      muscle, and intra/extracranial sites. Treatment location included: 80% at home, 
      12% at other facilities (treatment centres, ER, inpatient and OR), and 8% at both 
      home/other facilities. Median total dose given over 72 h was 360 mcg kg(-1) 
      (range: 40-4281, mean: 537). Bleeding stopped in 87% of the episodes. Bleeding 
      cessation rate was 84% for the three lower dose groups, and 97% for the highest 
      dose group (P < 0.001). Five patients experienced nine adverse events (AEs). AE 
      rates were <1% for <100, 5% for 100-150, 0% for 150-200, <1% for >200 mcg kg(-1) 
      dose group. Decreased therapeutic response accounted for eight of the nine AEs. 
      These data, which represent the most comprehensive report of rFVIIa use since the 
      USA licensure, demonstrate that bleeding episodes in HI patients can be treated 
      safely and effectively at home and that doses up to 346 mcg kg(-1) appear to be 
      well-tolerated. Additionally, rFVIIa doses >200 mcg kg(-1) appear to 
      significantly increase efficacy (97% in the high-dose group, compared with 84% in 
      the lower dose groups). Optimal dosing remains to be determined; specifically, 
      what the lowest effective dose is and whether a single high-dose bolus eliminates 
      the need for repeated dosing. Recombinant FVIIa appears to have a wide safety 
      margin that may allow dose escalation to address these questions.
FAU - Parameswaran, R
AU  - Parameswaran R
AD  - Indiana Hemophilia and Thrombosis Center, IN, USA.
FAU - Shapiro, A D
AU  - Shapiro AD
FAU - Gill, J C
AU  - Gill JC
FAU - Kessler, C M
AU  - Kessler CM
CN  - HTRS Registry Investigators
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Haemophilia
JT  - Haemophilia : the official journal of the World Federation of Hemophilia
JID - 9442916
RN  - 0 (Blood Coagulation Factors)
RN  - 0 (Recombinant Proteins)
RN  - 9001-25-6 (Factor VII)
RN  - AC71R787OV (recombinant FVIIa)
RN  - EC 3.4.21.21 (Factor VIIa)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Age Factors
MH  - Blood Coagulation Factors/antagonists & inhibitors
MH  - Child
MH  - Child, Preschool
MH  - Costs and Cost Analysis
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Factor VII/*administration & dosage/adverse effects/economics
MH  - Factor VIIa
MH  - Hemarthrosis/prevention & control
MH  - Hemophilia A/*drug therapy
MH  - Hemophilia B/drug therapy
MH  - Hemorrhage/prevention & control
MH  - Home Nursing
MH  - Humans
MH  - Infant
MH  - Middle Aged
MH  - Recombinant Proteins/*administration & dosage/adverse effects/economics
MH  - Registries
MH  - Retrospective Studies
MH  - Societies, Medical
EDAT- 2005/04/07 09:00
MHDA- 2005/06/10 09:00
CRDT- 2005/04/07 09:00
PHST- 2005/04/07 09:00 [pubmed]
PHST- 2005/06/10 09:00 [medline]
PHST- 2005/04/07 09:00 [entrez]
AID - HAE1075 [pii]
AID - 10.1111/j.1365-2516.2005.01075.x [doi]
PST - ppublish
SO  - Haemophilia. 2005 Mar;11(2):100-6. doi: 10.1111/j.1365-2516.2005.01075.x.