Rituximab‐associated acute thrombocytopenia: An under‐diagnosed phenomenon

Abstract

Acute infusion reactions are the most common documented adverse reactions reported with rituximab, with overt cytokine release syndrome, and hematological adverse events being much rarer. The clinical course of a patient with mantle cell lymphoma, who developed acute thrombocytopenia and leukopenia following rituximab administration, is described and the literature reviewed. Serum complement and the levels of three cytokines-TNF-a, IL-6, and IL-1, were measured 2 days after the infusion of rituximab by using ELISA assay. Drug-dependent antibodies against platelets were evaluated by two procedures as follows: an immunofluorescence test applying flow cytometry and Monoclonal Antibody Immobilization of Platelet Antigen (MAIPA). Serum levels of TNF-a were significantly increased compared with normal, whereas those of IL-6 and IL-1 were not increased significantly. Flow cytometry assay and the MAIPA assay failed to detect rituximab-dependent antibodies against platelets. Complement levels were decreased compared with normal. Literature search yielded 10 publications reporting on another 15 patients. The most common type of lymphoma was mantle cell lymphoma, six patients had bone marrow involvement, and 10 patients had splenomegaly. In 10 patients, acute cytopenia was preceded by cytokine release syndrome or infusion-related symptoms. Usually, thrombocytopenia was not associated with bleeding manifestations. Thrombocytopenia was the most commonly acute cytopenia reported. The postulated pathogenesis is associated with cytokine release syndrome and complement activation. Patients with potential risk factors like splenomegaly and bone marrow involvement, who develop clinical manifestations compatible with cytokine release syndrome, should be closely monitored for rituximab-associated cytopenia. Am. J. Hematol. 84:247-250, 2009. V

Approach to the Diagnosis and Management of Drug-Induced Immune Thrombocytopenia

“…Possible mechanisms include the formation of circulating immune complexes causing platelet lysis by complement activation [30][31][32] or direct binding to the CD20 antigen on the surface of platelets [30,32,33]. Thrombocytopenia is often preceded by infusion-related symptoms and cytokine secretion and may present with features of disseminated intravascular coagulation.…”

Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia

“…The thrombocytopenias may be related to ITP or may be related to treatment with RTX as this has previously been reported. 13 One patient in the RTX1DXM group and 2 patients in the DXM group were withdrawn from the study because of adverse events. For …”

Rituximab-induced Acute Thrombocytopenia in High Tumor Burden Follicular Lymphoma

“…A total of 15 such cases have been reported; 13 cases had MCL (6)(7)(8)(9)(10)(11)(12)(13)(14), one small lymphocytic lymphoma (15) and one lymphoplasmacytic lymphoma (16). Therefore, the mechanism of RIAT remains unclear.…”

“…Rituximab-induced acute thrombocytopenia (RIAT) that occurs within a few days of rituximab administration has been rarely reported in patients with NHL (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). A total of 15 such cases have been reported in the literature.…”

“…A total of 15 such cases have been reported in the literature. Interestingly, RIAT has been described almost exclusively in patients with mantle cell lymphoma (MCL) (6)(7)(8)(9)(10)(11)(12)(13)(14). MCL is a rare subtype of NHL, accounting for only 5% of NHL cases.…”