Crohn’s Disease, Infliximab and Idiopathic Thrombocytopenic Purpura

Infliximab: An alternative treatment for refractory immune thrombocytopenic purpura related to Crohnʼs disease?

“…Monocytes and macrophages are considered to be the main producers of soluble TNF-␣ but activated T-lymphocytes are also known to highly express substantial amounts of transmembrane (26-kDa) form of TNF-␣. 7 These data indicate that both monocytes and activated T-lymphocytes can be targets for anti-TNF-␣ antibodies. 7 Apoptosis leads to the removal of the dying cell by macrophages in a way that prevents the onset of inflammatory reactions, thus explaining the strong antiinflammatory properties observed and the sustained therapeutic response (far beyond the estimated circulating half-life of the antibody) even after a single dose of infliximab.…”

“…7 These data indicate that both monocytes and activated T-lymphocytes can be targets for anti-TNF-␣ antibodies. 7 Apoptosis leads to the removal of the dying cell by macrophages in a way that prevents the onset of inflammatory reactions, thus explaining the strong antiinflammatory properties observed and the sustained therapeutic response (far beyond the estimated circulating half-life of the antibody) even after a single dose of infliximab. Maintenance of response could be due to similar effects of infliximab to TH1 CD4-activated tissue or systemic cells and the subsequent decrease of antiplatelet antibody production from B-lymphocytes.…”

“…Therefore, the therapeutic efficacy of TNF-␣-neutralizing antibodies in CD seems, according to these data, to be related to apoptosis of TNF-␣-expressing target cells rather than to neutralization of soluble TNF-␣. 6,7 However, it is conceivable that complement-dependent cytotoxic cell lysis, in addition to the observed monocyte apoptosis, is another important mechanism that explains the effects of anti TNF-␣ treatment. 7 We recently reported a case of secondary to CD ITP, refractory to steroids and immunoglobulin treatment that had a remarkable response to infliximab infusion.…”

“…6,7 However, it is conceivable that complement-dependent cytotoxic cell lysis, in addition to the observed monocyte apoptosis, is another important mechanism that explains the effects of anti TNF-␣ treatment. 7 We recently reported a case of secondary to CD ITP, refractory to steroids and immunoglobulin treatment that had a remarkable response to infliximab infusion. 8 The rapidity of platelet increase within 3-5 days after infusion suggests a mechanism of apoptosis or cytotoxicity targeting reticuloendothelial system tissue monocytes and macrophages.…”

Concomitant Immune Thrombocytopenic Purpura and Crohn’s Disease

“…Several conditions causing thrombocytopenia in CD patients have been reported: 1) ITP (autoimmune platelet destruction); 2) druginduced thrombocytopenia, believed to induce autoimmunity or bone marrow suppression, reported following the use of anti-tumor necrosis factor (TNF)-alpha antibodies (i.e., infliximab) [6,7], 5-aminosalicylic acid [8], azathioprine [9], and low-molecular-weight heparin [10]; 3) the presence of thrombotic thrombocytopenic purpura (TTP) or hemolytic-uremic syndrome (HUS) in patients with CD [11][12][13]; 4) hematological malignancies [14] or portal hypertension (hypersplenism); and 5) deficiencies in minor elements, such as copper, during nutrition therapy for CD [15].…”