A rare case of acute kidney injury associated with autoimmune hemolytic anemia and thrombocytopenia after long-term usage of oxaliplatin

Abstract

Oxaliplatin is effective in advanced colorectal cancer and is known to have relatively few side effects, such as hemolysis and renal toxicity. We report a case of acute kidney injury (AKI) after treatment with a combination of oxaliplatin, folinic acid and 5-fluorouracil or capecitabine. The patient developed acute renal failure, hemolytic anemia and thrombocytopenia after the 34th course of chemotherapy including oxaliplatin. A positive direct antiglobulin test and detection of immunoglobulin G and complement C3b and C3d on erythrocytes suggested the diagnosis of immune-related severe intravascular hemolytic anemia. She was successfully treated and recovered using plasma exchange, corticosteroids and hemodialysis therapy. Only seven other cases of AKI associated with oxaliplatin use have been reported to date. As in this case, acute hemolysis due to autoimmune mechanisms and subsequent AKI occurred suddenly after frequent use of oxaliplatin in four of those cases. We should be aware that oxaliplatin may cause sudden life-threatening hemolysis by drug-induced antibodies and subsequent AKI, even though oxaliplatin is frequently administered without side effects. This represents the first case report of AKI-related hemolysis due to oxaliplatin in Japan.

Oxaliplatin-induced Acute Thrombocytopenia: A Case Report and Review of the Literature

“…The frequency of oxaliplatin-induced acute thrombocytopenia is unknown; however, the occurrence rate is probably underestimated because complete blood counts are not routinely performed in patients without severe allergic symptoms or bleeding tendencies. The characteristics of patients diagnosed with oxaliplatin-induced acute thrombocytopenia, including our patient, are summarized in Table. Similar to our case, previous reports (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) have shown that the onset of oxaliplatininduced acute thrombocytopenia is relatively rapid and most affected patients are women (75%) with an average age of 59.8 years (range: 38-83 years). The average number of cycles of onset of thrombocytopenia is 17.3 (range: 9-24 cycles), and all but one case (96%) occurred after 10 cycles of chemotherapy, which suggests that female sex and prolonged exposure to oxaliplatin are risk factors for the development of this reaction.…”

“…Because oxaliplatin-induced acute thrombocytopenia occurs abruptly and is sometimes life-threatening, appropriate therapy should be provided. To the best of our knowledge, 23 cases of oxaliplatin-induced acute thrombocytopenia have been reported (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). The frequency of oxaliplatin-induced acute thrombocytopenia is unknown; however, the occurrence rate is probably underestimated because complete blood counts are not routinely performed in patients without severe allergic symptoms or bleeding tendencies.…”

“…The average number of cycles of onset of thrombocytopenia is 17.3 (range: 9-24 cycles), and all but one case (96%) occurred after 10 cycles of chemotherapy, which suggests that female sex and prolonged exposure to oxaliplatin are risk factors for the development of this reaction. The average platelet count at onset is 17,000 / μL, and various symptoms such as chills (6, 7, 12, 18), fever (7), skin rashes (6, 18), abdominal or back pain (5,9,11,12), nausea (13,21), dizziness (21), mental status changes (13) and bronchospasm (18) are experienced, with the exception of bleeding tendencies. Because oxaliplatin-induced acute thrombocytopenia does not always accompany a bleeding tendency at the time of initial presentation, physicians need to pay careful attention and initiate blood testing for thrombocytopenia to manage patients with unexplained symptoms who receive oxaliplatin.…”

“…Thrombocytopenia leading to clinical bleeding typically occurs within several hours, although it sometimes occurs up to a few days (9,21). The symptoms sometimes mimic DIC related to severe infection or TTP in the acute phase, and conducting microscopic examinations of peripheral blood smears, coagulation tests and adequate culture studies for possible sepsis is necessary, especially in patients that develop im-mune hemolytic anemia (4,5,7,8,11,12,17,21). Regarding treatment, the platelet counts gradually increase with discontinuation of oxaliplatin; however, the majority of cases (83%) require platelet transfusions during the acute phase.…”

Methyl 6‐Amino‐6‐deoxy‐d‐pyranoside‐Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)‐Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism

“…However, similar to other platinum‐based anticancer drugs, oxaliplatin also induces a series of serious side effects, including neurotoxicity as a major dose‐limiting side effect, due to its strong bone marrow suppression activity . In addition, oxaliplatin‐treated patients experience severe nephrotoxicity, due to low water‐solubility‐related metal accumulation and slow excretion . A recent clinical study has indicated that toxicity to the hematopoietic system from oxaliplatin can cause the life‐threatening side effect of thrombocytopenia, which is more severe when administered in combination with 5‐fluorouracil (5‐FU) .…”