Anti–factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study

Tiede, Andreas; Hofbauer, Christoph J.; Werwitzke, Sonja; Knöbl, Paul; Gottstein, S.; Scharf, Rüdiger E.; Heinz, Jürgen; Groß, Jürgen; Holstein, Katharina; Dobbelstein, Christiane; Scheiflinger, F.; Koch, Armin; Reipert, Birgit M.

doi:10.1182/blood-2015-09-672774

Cited by 54 publications

(70 citation statements)

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“…22 Tiede et al demonstrated that the presence of anti-FVIII IgA was a strong negative predictor of recurrence-free survival after achieving partial remission. 18 In our study, no bleeding occurred between the decrease in the FVIII/W ratio and the subsequent clinical relapse, indicating that close monitoring of this parameter should be very useful for pre-emptive therapy. We propose that complete remission could be considered confirmed, there may be therapeutic consequences, such as more prolonged IST in case of non-normalization of the FVIII/W ratio or early re-treatment without waiting when the ratio falls.…”

Section: Discussionsupporting

confidence: 54%

“…For detection of relapses, they also suggested that anti‐FVIII IgG could be a predictor of prognosis . Tiede et al demonstrated that the presence of anti‐FVIII IgA was a strong negative predictor of recurrence‐free survival after achieving partial remission …”

Section: Discussionmentioning

confidence: 99%

“…Concerning clinical risk factors for relapse, Collins et al found that relapse is more frequent in patients treated with steroids alone . Using specific biological markers, Tiede et al suggested that patients with anti‐FVIII IgA are at high risk of relapse.…”

Section: Introductionmentioning

confidence: 99%

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The factor VIII:C/VWF:Ag ratio as a useful tool to predict relapse in patients with acquired haemophilia A: A retrospective cohort study

et al. 2019

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Introduction Acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by the presence of autoantibodies against coagulation factor VIII (FVIII). The mortality rate remains high. International recommendations define complete remission as undetectable inhibitor (<0.6 Bethesda Units [BU]) and normal FVIII activity (FVIII:C) that persists after immunosuppressive therapy stopped. For patients achieving remission, the risk of relapse reaches 20%. The risk factors for this relapse are not well known. Aim In this study, we examined the accuracy of the FVIII/W ratio (FVIII:C/von Willebrand Factor Antigen (VWF:Ag) ratio) to predict relapse in 64 consecutive patients with AHA. Results In this cohort, all patients had a very low FVIII/W ratio at the time of diagnosis, and this value progressively increased in the first weeks of immunosuppressive treatment. In our study, 9/55 (14%) did not achieve complete remission. Twenty‐seven patients were followed long enough (more than a year) to show that in the 22 patients who did not relapse, the FVIII/W ratio remained durably normalized. By contrast, in the five patients who relapsed during follow‐up, we noted either no normalization of the FVIII/W ratio, or a secondary decrease to an abnormal value of <0.7 after initial normalization. In all patients who relapsed, the ratio was the first abnormal biological result to be observed, always preceding changes in the activated partial thromboplastin time (aPTT), FVIII:C and anti‐FVIII reappearance. Conclusion These data suggest that the FVIII/W ratio could be considered a sensitive biological marker to predict recovery and/or relapse in AHA.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

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The factor VIII:C/VWF:Ag ratio as a useful tool to predict relapse in patients with acquired haemophilia A: A retrospective cohort study

et al. 2019

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“…Therefore, it is a useful screening test for screening for circulation anticoagulants. A previous study reported IgA subclass antibody as a poor prognostic marker in AHA (Tiede et al , ). However, details regarding antibody type was not included in our study.…”

Section: Discussionmentioning

confidence: 92%

Outcome of CARE: a 6‐year national registry of acquired haemophilia A in China

et al. 2019

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Summary Acquired haemophilia A (AHA) is a rare haemorrhagic disorder caused by autoantibodies directed against the functional epitopes of coagulation factor VIII (FVIII). Its management relies on prompt diagnosis, control of bleeding and eradication of the inhibitor by immunosuppression. China Acquired Hemophilia Registry (CARE), a nationwide multicentre registry, was intended to survey the status of AHA and standardize its diagnosis and therapy in China. One hundred and eighty‐seven registered patients had an average age of 52 years. Diagnosis was delayed in 46·5% patients. There was a significant delay from diagnosis to immunosuppressive therapy in 68·3% patients. Bleeding control was significantly higher in patients treated with prothrombin complex concentrate (PCC) versus FVIII replacement therapy (84·6% vs. 34·4%; P < 0·001). Inhibitor eradication with a combination of steroids and cyclophosphamide showed a higher partial remission (PR) rate (92·2% vs. 70·3%) and stable complete remission (CR) rate (82·8% vs. 48·6%) than with steroids alone. Logistic regression model showed age and malignancy were significantly related to survival at final follow‐up. The mean age for the survivors [51 years (IQR, 35–65 years)] was significantly lower than that of the non‐survivors [79 years (IQR, 67–86 years)] (P < 0·001). Overall survival was higher in non‐malignancy group than malignancy group (94·9% vs. 70%) (OR = 1·313; 95% CI, 0·913–1·889, P = 0·015).

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“…2,4,14 Relapses have been reported in up to 23% of cases. 2,9,15,16 Although some factors have been associated with a better survival (age <60 years, non-malignant underlying conditions), 3,17 or the probability of obtaining a remission, 17,18 the long-term natural history of patients who relapse after initial complete response to IST and factors predisposing to relapse remain only partially addressed and not well understood. [2][3][4]7,[9][10][11] This retrospective study describes the relapse pattern and long-term outcome of a large cohort of patients affected by AHA.…”

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confidence: 99%

Relapse pattern and long‐term outcomes in subjects with acquired haemophilia A

et al. 2019

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Introduction Acquired haemophilia A (AHA) is a rare autoimmune bleeding disorder caused by neutralizing antibodies against factor VIII (FVIII). Despite significant initial morbidity and mortality, most patients achieve remission with immunosuppressive therapy. Aim Long‐term follow‐up data from the Quebec Reference Centre for Inhibitors (QRCI) were analysed to identify factors predictive of AHA relapse and the influence of relapse on survival. Methods Criteria used to define AHA were levels of FVIII <0.3 IU/mL and FVIII inhibitor titres ≥0.6 Bethesda Units (BU). Complete remission was defined as FVIII >0.5 IU/mL and/or FVIII inhibitor titres <0.6 BU while not on immunosuppression. Results Between 2000 and 2012, 111 subjects met the inclusion criteria and were followed for a median of 25.6 months. Ninety per cent of them reached remission on immunosuppression in a median time of 45 days. Fourteen patients presented one or more relapses in a median time of 13.4 months. Most relapse episodes were successfully treated. Associated lymphoproliferative syndromes (LPS) were predictive of relapse, whereas FVIII activity and inhibitor titres at initial diagnosis or immunosuppressive regimens were not. The overall survival (OS) was the same, with or without relapse. Conclusion Among the recognized potential risk factors for relapse, only LPS was statistically significant. The long‐term follow‐up of our patients also showed that late or multiple relapses may occur, but that relapse is not associated with a worse OS. Thus, long‐term follow‐up is important for optimal management of AHA.

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Anti–factor VIII IgA as a potential marker of poor prognosis in acquired hemophilia A: results from the GTH-AH 01/2010 study

Abstract: Key Points This study is the first to assess the prognostic value of FVIII-specific antibody data in patients with AHA. Anti-FVIII IgA, but not immunoglobulin G, autoantibodies at baseline are potential predictors of recurrence and poor outcome of AHA.

Cited by 54 publications

References 26 publications

The factor VIII:C/VWF:Ag ratio as a useful tool to predict relapse in patients with acquired haemophilia A: A retrospective cohort study

The factor VIII:C/VWF:Ag ratio as a useful tool to predict relapse in patients with acquired haemophilia A: A retrospective cohort study

Outcome of CARE: a 6‐year national registry of acquired haemophilia A in China

Relapse pattern and long‐term outcomes in subjects with acquired haemophilia A

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