A population based, unselected, consecutive cohort of patients with acquired haemophilia A

Collins, Peter William; Macartney, Nicola J.; Davies, R. W.; Lees, Steve; Giddings, J. C.; Majer, R.V.

doi:10.1046/j.1365-2141.2003.04731.x

Cited by 146 publications

(181 citation statements)

References 15 publications

(32 reference statements)

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“…The haemostatic abnormality is due to autoantibodies inhibiting the activity of coagulation factor VIII (FVIII). In approximately 50 % of cases, acquired haemophilia is associated with other autoimmune disorders, malignancy, the peripartum, medication or multiple transfusions [1][2][3][4]. The pathogenesis of FVIII autoantibody formation in these cases as well as in idiopathic acquired haemophilia remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Acquired haemophilia caused by non-haemophilic factor VIII gene variants

Tiede¹,

Eisert²,

Czwalinna³

et al. 2010

Ann Hematol

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The aetiology of anti-factor VIII (FVIII) autoantibody formation in acquired haemophilia remains unknown. We hypothesised that encounter of antigenically different, allogeneic FVIII may challenge inhibitor formation after presentation on MHC class II. Eighteen consecutive cases with acquired haemophilia were enrolled (9 females, 9 males). A control group comprised 50 male and 50 female healthy blood donors. The coding region of the FVIII gene and the HLA-DRB1 genotype were studied. The presentation of foreign FVIII variants on the patient's MHC class II alleles was predicted using SYFPEITHI algorithm. A rare FVIII variant (E2004K) was found in 1 patient with acquired haemophilia after massive transfusion; the 2004K allele was predicted to be presented on the patient's HLA-DRB1*0101. Moreover, distribution of a polymorphism (D1241E) was significantly skewed comparing patients and controls. 3 of 3 patients with transfusion-associated disease carried 1241D in homozygous or hemizygous form and were predicted to present 1241E (foreign), but not 1241D (self), on their HLA-DRB1*0301. Therefore, encounter of 1241E may result in the presentation of a new T cell epitope in these patients. The same conditions were not found in any patient with acquired haemophilia of other causes. The expected frequency in the general Caucasoid population undergoing transfusion is 3 to 4 %. In conclusion, encounter of variant allogeneic FVIII presented on a suitable MHC background could be a risk factor for inhibitor formation.Response to Reviewers: Dear Professor Eichinger, Thank you for considering our manuscript for publication in Annals of Hematology. We would also like to thank the reviewer for valuable comments. We have addressed the comments as follows: *Only 3 cases of transfusion-associated acquired hemophilia: Indeed, acquired hemophilia associated with transfusion has rarely been reported. In our series, 3 cases among 18 consecutive patients are even more than expected from the literature. Our study suggest that immune recognition of certain FVIII variants could play a role in the pathogenesis, but formal proof would require much higher numbers of transfusion-associated cases that, in all probability, will never be collected. *Transfusion in the other cases: No, transfusion was not documented in any other case of our series. Medical histories were taken by the authors or other well-trained physicians of the department.We are sure that an association with transfusion would not have been missed in these patients. We have acknowledged this fact in the Methods section (p. 4, first para). *Frequency of 1241E in blood donations: Based on the known allelic distribution of the 1241E allele and the known sex distribution of blood donors, we determined the frequency of 1241E in singledonor blood products as 21 % (p. 4, last para). *Transfused units and interval between transfusion and acquired hemophilia: all transfusionassociated cases received multiple transfusions. Time between first transfusion and acquired hemophilia ranged...

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Section: Introductionmentioning

confidence: 99%

Acquired haemophilia caused by non-haemophilic factor VIII gene variants

Tiede¹,

Eisert²,

Czwalinna³

et al. 2010

Ann Hematol

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“…The clinical characteristics of the disease have been previously described. [1][2][3] The literature describing acquired hemophilia A is based on tertiary referral single-center cohorts, [4][5][6][7][8][9][10][11][12][13][14][15][16] larger retrospective surveys of referral center patients, 1,5,[17][18][19] and patients reported because they have been treated for bleeding. [20][21][22][23] These reports have been combined in a review and meta-analysis.…”

Section: Introductionmentioning

confidence: 99%

Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors' Organisation

Collins

Hirsch

Baglin

et al. 2006

Blood

651

1,037

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Acquired hemophilia A is a severe bleeding disorder caused by an autoantibody to factor VIII. Previous reports have focused on referral center patients and it is unclear whether these findings are generally applicable. To improve understanding of the disease, a 2-year observational study was established to identify and characterize the presenting features and outcome of all patients with acquired hemophilia A in the United Kingdom. This allowed a consecutive cohort of patients, unbiased by referral or reporting practice, to be studied. A total of 172 patients with a median age of 78 years were identified, an incidence of 1.48/million/y. The cohort was significantly older than previously reported series, but bleeding manifestations and underlying diseases were similar. Bleeding was the cause of death in 9% of the cohort and remained a risk until the inhibitor had been eradicated. There was no difference in inhibitor eradication or mortality between patients treated with steroids alone and a combination of steroids and cytotoxic agents. Relapse of the inhibitor was observed in 20% of the patients who had attained first complete remission. The data provide the most complete description of acquired hemophilia A available and are applicable to patients presenting to all

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“…No underlying disorder was found in almost one-half of the patients with the acquired inhibitor. Most patients were older than age 50 years, except those in whom the condition was related to pregnancy or the postpartum period (9).…”

Section: Discussionmentioning

confidence: 99%