Autoimmune thrombocytopenia

Many drugs, especially quinidine and heparin, induce antibodies leading to thrombocytopenia. In most cases the antibodies are drug-dependent however, there are many examples in which the antibodies are autoimmune in nature [42], even for drugs, such as quinidine that are classically associated with drug-dependent antibodies [43], Gold therapy, in particular, is associated with autoimmune-thrombocytopenia [44],... 

Autoimmune diseases have been reported to be more frequent in human subjects treated with several recombinant cytokines [38], For instance, increased titers or the new occurrence of autoantibodies have been observed in hepatitis C patients treated with the recombinant interferons-alpha (IFNa). Quite a few clinical case reports describe the development of organ-specific as well as systemic autoimmune diseases including systemic lupus erythematosus, insulin-dependent type I diabetes mellitus, autoimmune thrombocytopenia, autoimmune hemolytic anemia, myasthenia gravis, and autoimmune thyroiditis in patients under IFNa therapy. Although the mechanism involved is not fully elucidated, the available data support the pathogenic potential of IFNa in autoimmunity [31]. In contrast, autoimmune effects associated with IFNp therapy are thought to be of lesser concern based on the current clinical evidence [38], Thyroid autoimmunity in contrast to other autoimmune diseases is frequent in patients treated with recombinant interleukin-2 (rIL-2). Thus, among 281 previously euthyroid cancer patients treated with rIL-2, up to 41%... 

Sugiyama T, Okuma M, Ushikid>i F, Sensaki s, Kanqi K, Udiino H A novd platdd aggregating factor found in a patient with defective collagen-induced platdet aggregation and autoimmune thrombocytopenia. Blood 69 1712-1720,1987. 

Selinger, S., Tsai, J., Pulini, M., Saperstein, A., Taylor, S. Autoimmune thrombocytopenia and primary biliary cirrhosis with hypoglycemia and insulin receptor autoantibodies. Ann. Intern. Med. 1987 107 686 - 688... 

In 50 patients with advanced, low-grade, non-Hodgkin s lymphoma alemtuzumab produced marked lymphopenia and neutropenia, which were the probable cause of frequent severe infections (8). Seven patients developed opportunistic infections and nine had bacterial septicemia three patients died from infectious complications. Severe resistant autoimmune thrombocytopenia has also been noted in one patient, but the evidence that alemtuzumab was involved was limited (9). 

Otton SH, Turner DL, Frewin R, Davies SV, Johnson SA. Autoimmune thrombocytopenia after treatment with Campath IH in a patient with chronic lymphocytic leukaemia. Br J Haematol 1999 106(l) 261-2. 

Pye KG, Kelsey SM, House IM, Newland AC. Severe dyserythropoiesis and autoimmune thrombocytopenia associated with ingestion of kelp supplements. Lancet 1992 339(8808) 1540. 

Autoimmune thrombocytopenia, gradually reversible on withdrawal of captopril, was reported in three patients taking captopril (11). 

Pujol M, Duran-Suarez JR, Martin Vega C, Sanchez C, Tovar JL, Valles M. Autoimmune thrombocytopenia in three patients treated with captopril. Vox Sang 1989 57(3) 218. 

A 72-year-old man with autoimmune thrombocytopenia had taken prednisone (30 mg/day) for 1 year, when he was found to have systemic lupus erythematosus (46). Prednisone was continued and he started to take chloroquine (250 mg/day) and monthly cyclophosphamide (0.75 g/m ). Three weeks after the first bolus of cyclophosphamide, he complained of fever and dyspnea, and chest X-rays showed bilateral pulmonary infiltrates. Despite prompt medical management, he died 5 days after admission with cytomegalovirus-induced interstitial pneumonia. 

Fludarabine can cause or exacerbate autoimmune thrombocytopenia in chronic lymphocytic leukemia. Two patients with chronic lymphatic leukemia who developed thrombocytopenia while taking fludarabine were treated... 

Leach M, Parsons RM, Reilly JT, Winfield DA. Autoimmune thrombocytopenia a comphcation of fludarabine therapy in lymphoproliferative disorders. Chn Lab Haematol 2000 22(3) 175-8. 

Acute exacerbation of autoimmune thrombocytopenia (30) or hemolytic anemia has been linked to macrophage activation (31), and it has been suggested that patients with previous autoimmune blood disorders are at increased risk of hematological toxicity from GM-CSF. 

Woodruff RK, Grigg AP, Firkin FC, Smith IL. Fatal thrombotic events during treatment of autoimmune thrombocytopenia with intravenous immunoglobulin in elderly patients. Lancet 1986 2(8500) 217-18. 

Sagir A, Wettstein M, Heintges T, Haussinger D. Autoimmune thrombocytopenia induced by PEG-IFN-alpha2b plus ribavirin in hepatitis C. Dig Dis Sci 2002 47(3) 562-3. 

Autoimmune diseases include autoimmune thrombocytopenia, Graves disease, hemolytic anemia, Hashimoto s thyroiditis, insulin-dependent diabetes mellitus (diabetes... 

Treatments with recombinant therapeutic cytokines occasionally induce autoimmune phenomena. In particular, IFN-a may cause or exacerbate autoimmune effects, in particular thyroiditis, but also autoimmune thrombocytopenia or autoimmune hepatitis, and systemic lupus erythematosus has been reported. Relationships between IFN-a treatment and dermatomyositis (Dietrich et al., 2000) and diabetes mellitus (Fabris et al., 2003) have been observed. In addition, increased levels of various autoantibodies have been found in patients receiving IFN-a (Vial et al., 2002). Monzani et al. 

Adverse reactions to IFNa include flu -like symptoms, a wide range of cutaneous reactions, autoimmune thrombocytopenia, and hemolytic anemia. 

Fostamatinib disodium (Tamatinib fosdium, 88), which is prodrug of Tamatinib (92) (Scheme 27), was discovered by Rigel it is currently studied in Phase II cUni-cal trials by Rigel and Astra Zeneca Pic. for treatment of B-cell lymphoma [113], Apart from that, compound 88 is also investigated as agent for neatmoit of autoimmune thrombocytopenia and rheumatoid arthritis. Because of its poor pharmaceutical properties, Tamatinib (92) is orally administered as the methylene phosphate... 

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