Surgery-associated acquired haemophilia and response to combined rituximab and cyclosporine treatment

Kam, Grace; Lee, Y. S.; Tan, Tao; Chow, Pierce K. H.; Ng, H. J.

doi:10.1111/j.1365-2516.2010.02458.x

Cited by 8 publications

(4 citation statements)

References 5 publications

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“…42,43 These results are in agreement with a previous report 25 in which the successful eradication of an inhibitory antibody directed against the human F.IX transgene was achieved in one rhesus macaque using the same IS regimen used here; this report did not look at the effects of IS on B and T cells or the effect of this intervention on anti-AAV NAb. Rtx in combination with CsA has been used in the clinic to eradicate inhibitor in acquired hemophilia A, 44 to treat lymphoproliferative disorders, 45 and to treat autoimmune hemolytic anemia in infants. 46 …”

Section: Discussionmentioning

confidence: 99%

Pharmacological Modulation of Humoral Immunity in a Nonhuman Primate Model of AAV Gene Transfer for Hemophilia B

et al. 2012

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Liver gene transfer for hemophilia B has shown very promising results in recent clinical studies. A potential complication of gene-based treatments for hemophilia and other inherited disorders, however, is the development of neutralizing antibodies (NAb) against the therapeutic transgene. The risk of developing NAb to the coagulation factor IX (F.IX) transgene product following adeno-associated virus (AAV)-mediated hepatic gene transfer for hemophilia is small but not absent, as formation of inhibitory antibodies to F.IX is observed in experimental animals following liver gene transfer. Thus, strategies to modulate antitransgene NAb responses are needed. Here, we used the anti-B cell monoclonal antibody rituximab (rtx) in combination with cyclosporine A (CsA) to eradicate anti-human F.IX NAb in rhesus macaques previously injected intravenously with AAV8 vectors expressing human F.IX. A short course of immunosuppression (IS) resulted in eradication of anti-F.IX NAb with restoration of plasma F.IX transgene product detection. In one animal, following IS anti-AAV6 antibodies also dropped below detection, allowing for successful AAV vector readministration and resulting in high levels (60% or normal) of F.IX transgene product in plasma. Though the number of animals is small, this study supports for the safety and efficacy of B cell-targeting therapies to eradicate NAb developed following AAV-mediated gene transfer.

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Section: Discussionmentioning

confidence: 99%

Pharmacological Modulation of Humoral Immunity in a Nonhuman Primate Model of AAV Gene Transfer for Hemophilia B

et al. 2012

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“…In addition to rituximab, examples of other potential second‐line agents include immunoadsorption‐containing protocols (as noted above) or use of calcineurin inhibitors. Numerous case studies suggest that ciclosporin may be an effective agent for inhibitor eradication (Au et al , ; Petrovic et al , ; Kam et al , ). In the majority of published case reports, calcineurin inhibitors were used as a second line agent after cyclophosphamide failed to induce an adequate response.…”

Section: Inhibitor Eradication Therapymentioning

confidence: 99%

How I manage patients with acquired haemophilia A

Sborov

Rodgers

2013

Br J Haematol

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SummaryAcquired haemophilia A (AHA) is a potentially life-threatening bleeding disorder occurring in patients without a previous personal or family history of bleeding. Development of immune-mediated autoantibodies against coagulation factor VIII is associated with a wide range of clinical disorders including pregnancy, autoimmune disorders, malignancy, or with no apparent disease. There exists great potential for morbidity and mortality related to acute and recurrent bleeding episodes, making prompt diagnosis and treatment necessary. The two primary goals of treatment focus on cessation of bleeding and eradication of the acquired factor VIII inhibitor. No randomized clinical trials have been conducted regarding treatment, so expert clinical opinion guides therapeutic intervention. This current report provides a profile of patient characteristics, an algorithm for diagnosis, and outlines treatment recommendations based upon current guidelines and clinical experience. As first-line interventions for acute bleeding and inhibitor eradication are generally accepted, we will emphasize discussion of second-line therapeutic options.

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“…Anti-CD20 lymphocyte receptor inhibitor (rituximab), alone or in combination with steroids, is reserved only for resistant cases,9 10 and in particular surgery-associated AHA 11. Remission in response to inhibitor eradication therapy takes about 4–20 weeks, with clinical signs and symptoms typically clearing ahead of the decline in inhibitor titre 6.…”

Section: Discussionmentioning

confidence: 99%

Acquired haemophilia A: an unusual postoperative complication

et al. 2016

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An African-American man aged 65 years with multiple malignancies in remission was admitted for small bowel obstruction. He was treated with laparotomy following failure of conservative management. Postoperatively, he developed intra-abdominal bleed, which persisted, despite surgical haematoma evacuation. Further haematological workup revealed isolated prolongation of activated partial thromboplastin time (aPTT) with reduced factor VIII (FVIII) activity and raised FVIII inhibitor titre. Assuming acquired haemophilia A (AHA), FVIII inhibitor bypassing activity and corticosteroids were started with subsequent resolution of the bleeding from the surgical site. The patient remained free of bleeding episodes at 3-month follow-up and the aPTT normalised. This case report highlights the association of surgery with AHA and summarises the treatments with underlying mechanisms.

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Surgery-associated acquired haemophilia and response to combined rituximab and cyclosporine treatment

Cited by 8 publications

References 5 publications

Pharmacological Modulation of Humoral Immunity in a Nonhuman Primate Model of AAV Gene Transfer for Hemophilia B

Pharmacological Modulation of Humoral Immunity in a Nonhuman Primate Model of AAV Gene Transfer for Hemophilia B

How I manage patients with acquired haemophilia A

Acquired haemophilia A: an unusual postoperative complication

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