IgG-associated immune thrombocytopenia in Waldenström macroglobulinemia

Abstract

Waldenström macroglobulinemia (WM) is characterized by serum IgM monoclonal gammopathy, and only occasionally complicated by immune thrombocytopenia. Rarely, coexistence of non-IgM gammopathy in WM has been reported. Herein, we describe an 81-year-old case of WM with rapidly progressive immune thrombocytopenia accompanied by concurrent IgG gammopathy and elevation of platelet-associated IgG (PA-IgG). Immunostaining of the bone marrow specimen displayed not only IgM positive but also IgG positive plasmacytoid cells. Although dexamethasone therapy had no effect on thrombocytopenia, a modified RCD regimen (rituximab 375 mg/m(2) i.v. day 1, cyclophosphamide 375 mg/m(2) i.v. day 2 and dexamethasone 12 mg/body orally days 1-7) successfully normalized PA-IgG as well as IgG and IgM paraproteinemia and significantly increased platelet count. The current case suggests that the IgG gammopathy associated with WM is likely to be an etiology of immune thrombocytopenia and that tumor reduction, rather than immunosuppression, leads to an improvement of concurrent thrombocytopenia.

Multiple cystic lung lesions and autoimmune thrombocytopaenia developing after chemotherapy for pulmonary indolent B-cell lymphoma with plasmacytic differentiation

“…It is notable that neither the new pulmonary cysts nor the thrombocytopaenia improved in our patient with rituximab but instead responded to prednisolone. This is in contrast to autoimmune diseases directly caused by lymphoid neoplasm with monoclonal protein that does not improve unless the tumour burden is reduced by cytotoxic therapy 20…”

“…Among reports of autoimmune thrombocytopaenia in the course of WM, one patient had a confirmed PA IgM, thought to be an IgM monoclonal protein 19. Another patient presented with rapidly progressive autoimmune thrombocytopaenia, IgG monoclonal gammopathy and elevated levels of PA-IgG 20. On the other hand, there is another case report of WM in which autoimmune thrombocytopaenia developed after the tumour burden was reduced with chemotherapy.…”

Autoimmune Manifestations in Patients With Waldenström Macroglobulinemia

“…[22][23][24] A case of WM with a rapidly progressive ITP accompanied by concurrent IgG gammopathy and elevation of PA-IgG has been documented. 24 Immunostaining of the bone marrow specimen displayed not only IgM þ but also IgG þ plasmacytoid cells, suggesting an association between IgG gammopathy and WM. Reduction of tumor burden, rather than immunosuppression per se, improved the concurrent thrombocytopenia.…”

“…Reduction of tumor burden, rather than immunosuppression per se, improved the concurrent thrombocytopenia. 24 Plasmapheresis can also be of value in the management of patients with severe ITP and monoclonal gammopathy refractory to corticosteroids, splenectomy, vinca alkaloids, and high-dose intravenous gamma-globulin therapy. 25 …”

Immune-Mediated Disorders Causing Bleeding or Thrombosis in Lymphoproliferative Diseases

“…This may be true in many, but not all instances. There are several well-studied cases where patients had an IgG antibody to factor VIII 22,[151][152][153] or to platelets 11,154 in the presence of IgM paraproteinemia, in particular in WM/LPL. On the contrary, platelet antibodies, which are usually IgG antibodies may be (warm or cold) IgM antibodies 11,88,89 in IgM paraproteinemias.…”