Failure of rituximab to induce immune tolerance in a boy with severe haemophilia A and an alloimmune factor VIII antibody: a case report and review of the literature

Haemophilia ◽  
2006 ◽  
Vol 12 (3) ◽  
pp. 280-284 ◽  
Author(s):  
T. T. BISS ◽  
M. R. VELANGI ◽  
J. P. HANLEY
2021 ◽  
Vol 8 (1) ◽  
pp. 11-14
Author(s):  
Prakas Kumar Mandal ◽  
Malini Garg ◽  
Debasis Gantait ◽  
Utpal Jana

AbstractHaemophilia patients with inhibitors suffer from increased morbidity and mortality due to the ineffectiveness of factor VIII replacement. Pseudotumors are rare but dangerous complications in these patients, and nasal pseudotumors are even rarer. Here, we present the case of a young child with severe haemophilia A with high titre inhibitors who developed a nasal pseudotumor. When immune tolerance therapy was not possible due to financial constraints, he was treated with FEIBA prophylaxis and rituximab. The pseudotumor was managed with surgical excision. We conclude that epistaxis in haemophiliacs can be due to an underlying nasal pseudotumor, and highlight the use of rituximab for the eradication of inhibitors.


2004 ◽  
Vol 15 (7) ◽  
pp. 569-572 ◽  
Author(s):  
Liliana C Rossetti ◽  
Miguel Candela ◽  
Raúl Pérez Bianco ◽  
Miguel de Tezanos Pinto ◽  
Andrea Western ◽  
...  

2020 ◽  
Vol 33 (04) ◽  
pp. 302-308
Author(s):  
Hiral Shah ◽  
Tapas Kumar Kundu ◽  
Afroz Farooque Shaikh

AbstractHaemophilia is an X-linked inherited immunogenetic bleeding disorder resulting from deficiency of clotting Factor VIII (haemophilia A) or Factor IX (haemophilia B). Haemophilia patients suffer from complication of developing autoantibodies/inhibitor against clotting factors used for the treatment; most commonly patients are treated with Factor VIII replacement therapy. In modern medicine, haemophiliacs with inhibitor positive status are treated with bypassing agents such as Factor VIII inhibitor bypassing agent and immune tolerance induction therapy (ITI) because such patients do not respond to traditional factor replacement therapy during an event of active bleeding. Treatment with ITI is very expensive and it requires medical expertise. Moreover, high cost of such treatment is one part of the problem, while its availability is another problem especially in developing countries. The inhibitor status among haemophilia patients is identified by conducting a blood test which measures the Bethesda units (BU) levels in the blood. In this case report, the homoeopathic management of a patient with haemophilia A severe type (Factor VIII <1%), inhibitor positive (4 BU/mL), is presented. The patient underwent treatment for a span of 4 years. After closely assessing the patient's condition and applying the principles of homeopathy medicine selection, his frequent bleeding episodes were treated with homoeopathic medicines such as Hamamelis Virginica Q, Phosphorus, Arnica montana, Rhus toxicodendron, Calendula officinalis, and Pulsatilla nigricans. Intercurrent medicine—Tuberculinum bovinum—was given when the most indicated medicine failed to relieve the symptoms of the case and was given during non-bleeding phase. The medicines not only helped in reducing haemophilia-related bleeding episodes but also improved complaints of pain, relieved skin complaints, and showed improvement in overall psychological status of patient. It can be concluded that homeopathy medicines were able to successfully reduce the frequency of bleeding and intensity of pain in this patient. Owing to reduced bleeding, he required relatively a smaller number of factor replacement treatment compared with earlier when he was not taking homeopathy. Homoeopathy proved to be effective in managing severe haemophilia patient as a supportive therapy and was able to contribute toward reduced inhibitor levels in severe haemophilia patient.


2004 ◽  
Vol 15 (7) ◽  
pp. 569-572 ◽  
Author(s):  
Liliana C Rossetti ◽  
Miguel Candela ◽  
Ra??l P??rez Bianco ◽  
Miguel de Tezanos Pinto ◽  
Andrea Western ◽  
...  

2013 ◽  
Vol 1 (1) ◽  
pp. 5-7
Author(s):  
Bert Leenders

Abstract Haemophilia A is an X-linked congenital bleeding disorder resulting from a deficiency of factor VIII (FVIII). Therapy to prevent or treat bleeding is by replacement of the missing FVIII. However, as a consequence of treatment, patients with HA may develop inhibitory IgG antibodies to FVIII, termed “inhibitors”. When this occurs, treatment becomes more complex and costly and morbidity increases. Inhibitor formation, occurring in up to 36% of patients with severe HA, is currently one of the most significant complications affecting patients with HA [1,2]. In these two case studies, the management of bleeds in patients with inhibitors, and the long-term inhibitor eradication will be discussed.


2009 ◽  
Vol 29 (02) ◽  
pp. 151-154 ◽  
Author(s):  
Escuriola Ettingshausen ◽  
R. Linde ◽  
G. Kropshofer ◽  
L.-B. Zimmerhackl ◽  
W. Kreuz ◽  
...  

SummaryThe development of neutralizing alloanti-bodies (inhibitors) to factor VIII (FVIII) is one of the most serious complications in the treatment of haemophiliacs. Inhibitors occur in approximately 20 to 30% of previously untreated patients (PUPs), predominantly children, with severe haemophilia A within the first 50 exposure days (ED). Immune tolerance induction (ITI) leads to complete elimination of the inhibitor in up to 80% of the patients and offers the possibility to restore regular FVIII prophylaxis. However, patients with high titre inhibitors, in whom standard ITI fails, usually impose with high morbidity and mortality and therefore prompting physicians to alternate therapy regimens. Rituximab, an anti-CD 20 monoclonal antibody has been successfully used in children and adults for the management of B-cell mediated disorders. We report on the use of a new protocol including rituximab in two adolescents with severe haemophilia A and high titre inhibitors, severe bleeding tendency and high clotting factor consumption after failing standard ITI. Both patients received a concomitant treatment with FVIII according to the Bonn protocol, cyclosporine A and immunoglobulin. Treatment with rituximab resulted in a temporary B-cell depletion leading to the disappearance of the inhibitor. FVIII recovery and half-life turned towards normal ranges. In patient 1 the inhibitor reappeared 14 months after the last rituximab administration. In patient 2 complete immune tolerance could be achieved for 60 months. Bleeding frequency diminished significantly and clinical joint status improved in both patients. In patient 1 the treatment course was complicated by aspergillosis and hepatitis B infection. Conclusion: Rituximab may be favourable for patients with congenital haemophilia, high-titre inhibitors and a severe clinical course in whom standard ITI has failed. Prospective studies are required to determine safety, efficacy and predictors of success.


1976 ◽  
Vol 35 (03) ◽  
pp. 510-521 ◽  
Author(s):  
Inga Marie Nilsson

SummaryThe incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophilia B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40 % have severe, 18 % moderate, and 42 % mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B.There are 2 main Haemophilia Centres (Stockholm, Malmo) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction 1-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Sufficient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 million units of factor IX are given per year. Treatment is free of charge.Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4–18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40–50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.


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