PMID- 23731565
OWN - NLM
STAT- MEDLINE
DCOM- 20140310
LR  - 20161125
IS  - 1879-2472 (Electronic)
IS  - 0049-3848 (Linking)
VI  - 132
IP  - 1
DP  - 2013 Jul
TI  - Pharmacodynamics of recombinant activated factor VII and plasma-derived factor 
      VII in a cohort of severe FVII deficient patients.
PG  - 116-22
LID - S0049-3848(13)00153-9 [pii]
LID - 10.1016/j.thromres.2013.04.021 [doi]
AB  - Recombinant activated factor VII (rFVIIa) and plasma-derived factor VII (pdFVII) 
      are used to prevent bleedings in severe FVII deficient patients, despite their 
      short half-lifes. It is suggested that FVII levels of 15-20 IU/dL are sufficient 
      to maintain hemostasis. We analyzed the pharmacodynamic effects of FVII 
      substitution therapy in the Nijmegen Hemostasis Assay (NHA) that simultaneously 
      measures thrombin and plasmin generation. Ten severe FVII deficient patients were 
      treated with 20 mug/kg rFVIIa or 25 IU/kg pdFVII in a cross-over design. Thrombin 
      generation lag-time (TG-LT) was identified as an effect-response parameter. 
      Pharmacodynamic analysis using a maximum effect model showed 50% reduction of the 
      TG-LT effect at ~2 IU/dL FVII activity for both rFVIIa and pdFVII. The FVII 
      activity to obtain TG-LT comparable to the upper limit of normal range in healthy 
      controls (4 min) was given by the effective concentration (ECnormal), showing 
      sufficient hemostasis at 3-4 IU/dL FVII activity. No association was seen between 
      FVII activity and other thrombin or plasmin generation parameters as measured by 
      NHA. In conclusion, 3-4 IU/dL FVII activity seems sufficient to maintain 
      hemostasis in patients with severe FVII deficiency during prophylaxis. These data 
      may suggest a potential value for measurement of TG-LT in the monitoring of 
      FVII(a) therapy.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - van Geffen, Mark
AU  - van Geffen M
AD  - Department of Laboratory Medicine, Laboratory for Hematology, Radboud University 
      Nijmegen Medical Center, Nijmegen, The Netherlands.
FAU - Mathijssen, Natascha C J
AU  - Mathijssen NC
FAU - Holme, Pal A
AU  - Holme PA
FAU - Laros-van Gorkom, Britta A P
AU  - Laros-van Gorkom BA
FAU - van Kraaij, Marian G J
AU  - van Kraaij MG
FAU - Masereeuw, Roselinde
AU  - Masereeuw R
FAU - Peyvandi, Flora
AU  - Peyvandi F
FAU - van Heerde, Waander L
AU  - van Heerde WL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130531
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (Recombinant Proteins)
RN  - 9001-25-6 (Factor VII)
RN  - AC71R787OV (recombinant FVIIa)
RN  - EC 3.4.21.21 (Factor VIIa)
RN  - EC 3.4.21.5 (Thrombin)
RN  - EC 3.4.21.7 (Fibrinolysin)
SB  - IM
MH  - Adult
MH  - Cohort Studies
MH  - Factor VII/pharmacology/*therapeutic use
MH  - Factor VII Deficiency/*blood/*drug therapy/metabolism
MH  - Factor VIIa/pharmacology/*therapeutic use
MH  - Female
MH  - Fibrinolysin/metabolism
MH  - Hemostasis/drug effects
MH  - Humans
MH  - Male
MH  - Recombinant Proteins/pharmacology/therapeutic use
MH  - Thrombin/metabolism
MH  - Thrombin Time
MH  - Young Adult
OTO - NOTNLM
OT  - Factor VII
OT  - Factor VII deficiency
OT  - Factor VIIa
OT  - Plasmin generation
OT  - Rare Bleeding Disorder
OT  - Thrombin generation
EDAT- 2013/06/05 06:00
MHDA- 2014/03/13 06:00
CRDT- 2013/06/05 06:00
PHST- 2012/12/26 00:00 [received]
PHST- 2013/04/15 00:00 [revised]
PHST- 2013/04/18 00:00 [accepted]
PHST- 2013/06/05 06:00 [entrez]
PHST- 2013/06/05 06:00 [pubmed]
PHST- 2014/03/13 06:00 [medline]
AID - S0049-3848(13)00153-9 [pii]
AID - 10.1016/j.thromres.2013.04.021 [doi]
PST - ppublish
SO  - Thromb Res. 2013 Jul;132(1):116-22. doi: 10.1016/j.thromres.2013.04.021. Epub 
      2013 May 31.