Cancer-Related Microangiopathic Hemolytic Anemia

Abstract

Cancer-related microangiopathic hemolytic anemia (CR-MAHA) is a paraneoplastic syndrome characterized by Coombs-negative hemolytic anemia with schistocytes and thrombocytopenia. We reviewed and analyzed all cases of CR-MAHA reported since 1979 (the time of the last published review on this topic) according to predefined criteria. We found 154 cases associated with solid cancer and 14 with lymphoma. Among the solid cancers, gastric, breast, prostate, lung, and cancer of unknown primary (CUP) were most common; 91.8% of cancers were metastatic, and in 19.4% of solid cancers CR-MAHA did not occur until recurrence of cancer. Lymphoma cases included Hodgkin disease, angiotropic lymphoma, diffuse large cell lymphoma, and myeloma. Evaluation of the clinical and laboratory findings revealed that only a minority of cases presented with the features of thrombotic thrombocytopenic purpura (TTP) or atypical hemolytic uremic syndrome (aHUS), with the exception of prostate cancer, where aHUS was a common presentation. Compared to hereditary or immune TTP or aHUS, disseminated intravascular coagulation and pulmonary symptoms were more common in CR-MAHA. Plasma exchange or fresh frozen plasma was rarely effective except in prostate cancer patients with aHUS. CR-MAHA responded to antitumor therapy in many patients with gastric, breast, lung, and CUP cancers. These patients had a superior survival compared to patients without chemotherapy. Compared to the prognosis of patients with metastatic cancer without CR-MAHA, the prognosis of CR-MAHA patients was greatly inferior. There is evidence that some cases of CR-MAHA in lymphoma are immune mediated.

A rare case of concurrent signet-ring carcinoma of breast and microangiopathic hemolytic anemia

“…Both of these differential diagnoses could explain the thrombocytopenia. CA-MAHA can be often confused with TTP, but the best distinguishing factor is that CA-MAHA is Coomb's negative, whereas TTP is positive [4]. …”

Paraneoplastic Syndromes

“…Around 80% of patients with solid tumors have marrow infiltrated by cancer cells, and in one study, only 4 of 154 subjects had very low or absent ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin motifs, 13) activity. 18 In contrast, patients with lymphoma and myeloma with MAHA are much more likely to have significantly decreased ADAMTS-13 activity and thrombocytopenic thrombotic purpura. Treatment consists of cancer therapy when possible.…”

“…17 In addition, a recent article identified 168 cases of microangiopathic hemolytic anemia (MAHA) in a variety of cancers, and another review identified 34 cases of autoimmune hemolytic anemia associated with Hodgkin lymphoma. 18,19 Granulocytosis A 2009 review identified 758 patients with solid tumors and white blood cell count greater than 40,000/mL. 20 Only 10% were diagnosed with paraneoplastic granulocytosis.…”

“…MAHA is mostly associated with gastric cancer, followed by breast, prostate, and lung cancers. 18 Approximately 90% of patients have metastatic cancer at the diagnosis of MAHA. Around 80% of patients with solid tumors have marrow infiltrated by cancer cells, and in one study, only 4 of 154 subjects had very low or absent ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin motifs, 13) activity.…”

Hyperbilirubinemia following lenalidomide administration

“…Thrombotic microangiopathy (TMA), which some term cancer‐related microangiopathic hemolytic anemia (CR‐MAHA) 5, can be associated with multiple myeloma but is exceedingly rare, presents with thrombocytopenia, and is usually related to treatment with bortezomib 6. Our patient did not have thrombocytopenia, so this was lower on our differential.…”