PMID- 25879247
OWN - NLM
STAT- MEDLINE
DCOM- 20160407
LR  - 20180823
IS  - 2567-689X (Electronic)
IS  - 0340-6245 (Linking)
VI  - 114
IP  - 1
DP  - 2015 Jul
TI  - Inhibitors in nonsevere haemophilia A: outcome and eradication strategies.
PG  - 46-55
LID - 10.1160/TH14-11-0940 [doi]
AB  - In nonsevere haemophilia A (HA) patients the presence of an inhibitor may 
      exacerbate the bleeding phenotype dramatically. There are very limited data on 
      the optimal therapeutic approach to eradicate inhibitors in these patients. We 
      aimed to describe inhibitor eradication treatment in a large cohort of unselected 
      nonsevere HA patients with inhibitors. We included 101 inhibitor patients from a 
      source population of 2,709 nonsevere HA patients (factor VIII 2-40 IU/dl), 
      treated in Europe and Australia (median age 37 years, interquartile range (IQR) 
      15-60; median peak titre 7 BU/ml, IQR 2-30). In the majority of the patients 
      (71 %; 72/101) the inhibitor disappeared; either spontaneously (70 %, 51/73) or 
      after eradication treatment (75 %, 21/28). Eradication treatment strategies 
      varied widely, including both immune tolerance induction and immunosuppression. 
      Sustained success (no inhibitor after rechallenge with factor VIII concentrate 
      after inhibitor disappearance) was achieved in 64 % (30/47) of those patients 
      rechallenged with FVIII concentrate. In high-titre inhibitor patients sustained 
      success was associated with eradication treatment (unadjusted relative risk 2.3, 
      95 % confidence interval 1.3-4.3), compared to no eradication treatment. In 
      conclusion, in nonsevere HA patients most inhibitors disappear spontaneously. 
      However, in 35 % (25/72) of these patients an anamnestic response still can occur 
      when rechallenged, thus disappearance in these patients does not always equal 
      sustained response. Treatment for those requiring eradication has to be decided 
      case by case, as one single approach is unlikely to be appropriate for all.
FAU - van Velzen, Alice S
AU  - van Velzen AS
FAU - Eckhardt, Corien L
AU  - Eckhardt CL
FAU - Hart, Daniel P
AU  - Hart DP
FAU - Peters, Marjolein
AU  - Peters M
FAU - Rangarajan, Savita
AU  - Rangarajan S
FAU - Mancuso, Maria Elisa
AU  - Mancuso ME
FAU - Smiers, Frans J
AU  - Smiers FJ
FAU - Khair, Kate
AU  - Khair K
FAU - Petrini, Pia
AU  - Petrini P
FAU - Jimenez-Yuste, Victor
AU  - Jimenez-Yuste V
FAU - Hay, Charles R M
AU  - Hay CR
FAU - van der Bom, Johanna G
AU  - van der Bom JG
FAU - Yee, Thynn T
AU  - Yee TT
FAU - Fijnvandraat, Karin
AU  - Fijnvandraat K
AD  - K. Fijnvandraat, MD PhD, Emma Children's Hospital, Academic Medical Center, Room 
      number H7-228, PO Box 22660, 1100 DD Amsterdam, The Netherlands, Tel.: +31 20 566 
      2727, Fax: +31 20 566 9683, E-mail: c. j.fijnvandraat@amc.uva.nl.
CN  - INSIGHT study group
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20150416
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Antibodies)
RN  - 0 (Biomarkers)
RN  - 0 (Hemostatics)
RN  - 0 (Immunosuppressive Agents)
RN  - 839MOZ74GK (F8 protein, human)
RN  - 9001-27-8 (Factor VIII)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antibodies/*blood
MH  - Biomarkers/blood
MH  - Child
MH  - Child, Preschool
MH  - Desensitization, Immunologic/*methods
MH  - Europe
MH  - Factor VIII/adverse effects/immunology/*therapeutic use
MH  - Hemophilia A/blood/diagnosis/immunology/*therapy
MH  - Hemorrhage/blood/diagnosis/immunology/*therapy
MH  - Hemostatics/adverse effects/immunology/*therapeutic use
MH  - Humans
MH  - Immune Tolerance
MH  - Immunosuppressive Agents/*therapeutic use
MH  - Middle Aged
MH  - South Australia
MH  - Time Factors
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - Haemophilia A
OT  - eradication treatment
OT  - factor VIII inhibitors
OT  - immune tolerance induction
EDAT- 2015/04/17 06:00
MHDA- 2016/04/08 06:00
CRDT- 2015/04/17 06:00
PHST- 2014/11/13 00:00 [received]
PHST- 2015/02/13 00:00 [accepted]
PHST- 2015/04/17 06:00 [entrez]
PHST- 2015/04/17 06:00 [pubmed]
PHST- 2016/04/08 06:00 [medline]
AID - 14-11-0940 [pii]
AID - 10.1160/TH14-11-0940 [doi]
PST - ppublish
SO  - Thromb Haemost. 2015 Jul;114(1):46-55. doi: 10.1160/TH14-11-0940. Epub 2015 Apr 
      16.