Factor VIII antibody in a patient with mild haemophilia

Bovill, Edwin G.; Burns, SO; Golden, Elizabeth A.

doi:10.1111/j.1365-2141.1985.tb02832.x

Cited by 19 publications

(19 citation statements)

References 12 publications

(7 reference statements)

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“…Both type I and II reaction‐kinetic inhibitors have been reported in patients with mild HA, [102,103], although type II seem more frequent. This is in contrast to inhibitors in patients with severe HA, where type I are more frequently described [95].…”

Section: Inhibitor Developmentmentioning

confidence: 99%

Mild hemophilia A

Franchini

Favaloro

Lippi

2010

Journal of Thrombosis and Haemostasis

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Summary. Mild hemophilia A (HA), defined by clinical features and factor VIII coagulant activity (FVIII:C) between 0.05 and 0.40 IU mL−1, is characteristically distinct from severe HA. Indeed, although the molecular characterization of mild HA has permitted the identification of specific underlying mutations, its clinical phenotype is strikingly different from that of patients with a severe FVIII defect, where spontaneous hemorrhages or recurrent joint bleeding are usual manifestations. With aging, mild HA patients may develop complications (i.e. cancers and cardiovascular disorders), the management of which may prove challenging due to the concomitant bleeding tendency. Furthermore, the development of inhibitors provides an additional major complication in these patients, because it increases the severity of the bleeding phenotype and complicates their management. Standard management of mild HA includes the use of desmopressin and antifibrinolytic agents for minor bleeding episodes or surgical procedures, whilst major bleeding or surgery requires replacement therapy with FVIII concentrates. As regards treatment of patients with inhibitors, bypassing agents (i.e. activated prothrombin complex concentrates and recombinant activated FVII) have proven effective in the treatment of bleeding episodes, but as there are insufficient data to determine the optimal approach to immune tolerance induction in this group of patients, their optimal management remains controversial. Rituximab is a newer, promising therapeutic option for inhibitor eradication in such patients. Many aspects concerning mild HA remain to be clarified, including the molecular basis, the natural history and the optimal diagnostic and therapeutic strategies. Only large prospective studies will shed light on this condition.

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Section: Inhibitor Developmentmentioning

confidence: 99%

Mild hemophilia A

Franchini

Favaloro

Lippi

2010

Journal of Thrombosis and Haemostasis

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“…Analysis of the immune response to factor VIII in mild/moderate haemophilia Both type I and type II reaction kinetics have been described for inhibitors in patients with mild/moderate haemophilia [13,18,19]. Type I antibodies completely inhibit FVIII activity following secondorder kinetics, while type II antibodies follow more complex kinetics and cannot inhibit FVIII completely [20].…”

Section: Genetic Predisposition To Inhibitor Development In Patients mentioning

confidence: 99%

Characteristics of inhibitors in mild/moderate haemophilia A

Peerlinck¹,

Jacquemin²

2006

Haemophilia

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Patients with mild or moderate haemophilia A usually have a mild bleeding disorder requiring only occasional treatment with factor VIII (FVIII) concentrates. The frequency of inhibitor development in such patients has been the subject of several recent surveys, which significantly modified our appreciation of this complication. Studies of the anti-FVIII antibodies provided an explanation for the different bleeding phenotypes observed in mild/moderate haemophilia A patients with inhibitors. Antibodies distinguishing between the patient's mutant FVIII and the normal wild-type FVIII were characterized, in addition to antibodies inhibiting completely or only partially FVIII activity. T lymphocytes recognizing FVIII and likely involved in the development of the immune response to FVIII were successfully identified. The FVIII peptides recognized by those FVIII-specific cells bind to many major histocompatibility complex (MHC) class II molecules, which may provide an explanation for the lack of strong association between MHC haplotypes and inhibitor development. Although these studies have advanced our understanding of the conditions leading to inhibitor development, further work is required to determine whether the mode of FVIII administration significantly influences inhibitor development. Further studies of the genetic factors are also required to fully understand the mechanisms leading to inhibitor development in patients with mild/moderate haemophilia A.

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“…Inhibitor development occurs mainly in patients who themselves produce no clotting factor at all, i.e. patients with severe hemophilia, although antibodies to factor VIII in mild hemophilia have been reported [20,35]. Antibodies to the missing clotting factor are far more often seen in hemophilia A than in hemophilia B [11,26].…”

Section: Antibodies To Factor VIII or Ixmentioning

confidence: 99%