Bernadette Garvey

Rituximab in the treatment of autoimmune haematological disorders

Current treatment regimens for haematological autoimmune diseases are relatively non‐selective and are often associated with considerable toxicity. Recently, it has become clear that B cells play a key role in both the development and perpetuation of autoimmunity, suggesting that B‐cell depletion could be a valuable treatment approach for patients with autoimmune diseases. This article reviews data supporting the use of rituximab – an anti‐CD20 monoclonal antibody that specifically depletes B cells – in four key autoimmune haematological disorders: idiopathic thrombocytopenic purpura (ITP); autoimmune haemolytic anaemia (AIHA); acquired haemophilia; and thrombotic thrombocytopenic purpura (TTP). Although treatment of ITP, AIHA, acquired haemophilia and TTP with rituximab is still relatively uncommon, results from case series and small phase II trials indicate that patients of all ages can respond to rituximab, irrespective of the number or type of prior treatments that they have received. Moreover, patients with these diseases receiving rituximab experienced predominantly mild adverse events, with only a few serious adverse events reported. These data suggest that rituximab provides an effective and well‐tolerated alternative treatment option for patients with ITP, AIHA, acquired haemophilia and TTP, many of whom have limited treatment choices.

Role of platelet surface glycoprotein Ibα and P‐selectin in the clearance of transfused platelet concentrates

BACKGROUND:  Role of P‐selectin (CD62) and glycoprotein (GP) Ibα in posttransfusion clearance of platelet concentrates (PCs) is unclear.

A rabbit model for monitoring in vivo viability of human platelet concentrates using flow cytometry

BACKGROUND : Viability in vivo of novel platelet components cannot be readily determined in human transfusions. Elaboration of valid animal models may be useful for this purpose.

Management of Chronic Autoimmune Thrombocytpenic Purpura (ITP) in Adults

The management of thrombocytopenia in adults is a therapeutic challenge requiring not only the science but the art of medicine. The disease is usually chronic and a third of those affected will have significant thrombocytopenia despite attempts at presently accepted forms of management. Adults tolerate moderate degrees of thrombocytopenia and treatment of asymptomatic patients with platelet counts greater than 30 x 10(9)/L is usually not required. Steroids, splenectomy, and the use of steroid-sparing immunosuppressive drugs remain the mainstay of treatment, although short-term responses to intravenous immunoglobulin (IVIg) and anti-D may be beneficial. The multitude of therapies with anecdotal reports of responses attests to the frustration felt by hematologists in the management of this disease when conventional treatments fail.

Combined use of orgaran and reopro during coronary angioplasty in patients unable to receive heparin

Orgaran, a heparinoid, has been used successfully in patients with heparin‐induced thrombocytopenia. We report three cases in which Orgaran was combined with the glycoprotein IIb/IIa receptor antagonist Reopro during coronary angioplasty. Orgaran was given as a single intravenous bolus of 1500 anti‐factor Xa units. No ischemic or hemorrhagic complications occurred during or following the procedure. Cathet. Cardiovasc. Intervent. 46:352–355, 1999.

Clinical and immunologic effects of Staphylococcal protein A immunoadsorption therapy for inhibitor to factor VIII

Abstract A 74-year mild hemophiliac with an inhibitor to factor VIII underwent five 2-L plasma immunoadsorption procedures with a Staphylococcal protein A (Prosorba) column over 7 days. Initially, the inhibitor level increased from 56 to 154 BU/mL. Serum immunoglobulins, immune complexes, C3 and C4 fell progressively with each procedure: C3a was increased. Before therapy, the patient had increased cytotoxic T and activated T cells which decreased to the normal range with treatment. The proportion of T inducer cell and CD4:CD3 ratios increased progressively with each treatment. Natural killer cell activity remained unchanged. Unstimulated patient lymphocytes showed high proliferative activity, but after therapy there was markedly reduced response to mitogens. Both patient and normal lymphocytes showed marked increase in thymidine incorporation when incubated with adsorbed plasma (from column outlet), compared to incubation with unadsorbed plasma (column inlet). The patients serum showed a progressive rise in this “mitogenicity” effect, maximal after the third procedure, then declining to pre-treatment levels after the fifth procedure. After the third immunoadsorption, inhibitor level was 70 BU/mL and he was given prednisone and cyclophosphamide; after the fifth procedure it was 32 BU/mL and 6 months later was undetectable. Although subsequent decrease in the inhibitor may have been due to the plasma immunoadsorption, it is important to note that this treatment may be paradoxically associated with a rise in antibody levels. In addition to antibody changes, Staph. protein A perfusion affected cellular immunity.

Rituximab in the treatment of autoimmune haematological disorders – response to Provan et al

We thank Dr Provan and colleagues for drawing to our attention their publication (Provan et al, 2007), which reported patients with auto-immune haematological diseases treated with a lower dose of Rituximab than that used in the treatment of non-Hodgkin lymphoma. We appreciate this information because the most appropriate dose for patients with auto-immune haematological disorders is, as yet, unknown. Any information indicating effectiveness with a reduced dose is of value. As stated by Dr Provan et al in their letter, the utilization of Rituximab in auto-immune haematological disease is an off-label use and therefore information such as that reported by Provan et al (2007) will be of value in determining the most appropriate dose in these disorders.