Oxaliplatin-induced Evan’s syndrome

Abstract

Sir,Oxaliplatin is a third-generation platinum compound with activity in advanced colorectal cancer. It is available in several European countries, but remains investigational in North America. Its safety profile compares favourably with the other platinum-based agents, cisplatin and carboplatin, and consists mostly of peripheral neuropathy and mild thrombocytopenia. However, there has been one previous report in the literature of fatal haemolytic anaemia caused by oxaliplatin (Desrame et al, 1999). Here we report immune-mediated thrombocytopenia and concurrent haemolytic anaemia (Evan's syndrome) that developed during oxaliplatin infusion.In November of 1999, a 56-year-old man with a 2-year history of colon cancer metastatic to liver and lung, who had progressed on first-line 5-FU and leucovorin as well as second-line irinotecan, was enrolled on a Phase II study at the Dana-Farber Cancer Institute. Treatment consisted of oxaliplatin 85 mg/m 2 by bolus infusion over 2 hours, followed by 500 mg/m 2 of leucovorin also infused over 2 hours, 5-FU 400 mg/m 2 by rapid venous infusion, and then 5-FU 2400 mg/m 2 by continuous infusion with a portable pump over 46 hours. Treatment was repeated every 2 weeks. The patient had stable disease on this regimen between November 1999 and July 2000.In July, the patient came for a routine treatment with a platelet count of 99 000 µl -1 immediately prior to infusion. During the leucovorin infusion, approximately 5 hours after the baseline bloodwork was drawn and the oxaliplatin infusion initiated, he began feeling unwell and his gums began to bleed. He subsequently developed purpura on his oral mucosa and eyelids, haematuria and haematochezia. A repeat platelet count was 6000 µl -1 .He remained haemodynamically stable throughout, and initial haemoglobin and INR were normal. He was admitted to hospital for platelet transfusion and supportive care, but quickly also developed anaemia with a drop in his haemoglobin from 108 to 78 g l -1. Peripheral smear confirmed the decreased platelets, with a left shift in red cell morphology. There was anisocytosis and polychromasia, with a high RDW of 17.3 and increased reticulocytes at 4.7%. Bilirubin rose to 4.4 mg dl -1 , with only 1.4 mg dl -1 being direct, and the LDH increased to 2148 U l -1. Laboratory testing indicated a warm antibody, with a positive direct Coomb's test with polyspecific IgG. There was no anti-C3 antibody, and the eluate reacted with all cells. His INR also rose transiently to 2.4. Clotting factor levels and fibrinogen were normal, although Fibrin Split Products were elevated at 8 µg ml -1 . Screening for heparininduced thrombocytopenia and thrombosis (HITT) was negative.The patient was treated with prednisone 75 mg orally per day, with stabilization of his blood indices over the course of 3 days after receiving a total of 4 units of single donor platelets, 3 units of packed red blood cells, and 4 units of fresh frozen plasma. He made a complete clinical recovery, with a platelet count of 122 000 µl Ϫ1 and a hemoglobin of...

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

“…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.…”

Oxaliplatin-induced acute-onset thrombocytopenia and hemorrhage: Case report and review of the literature

“…Patients treated with oxaliplatin may develop allergic or idiosyncratic reactions and, rarely, hematological emergencies (3)(4)(5). Few cases of immune-mediated hemolytic anemia and/or thrombocytopenia due to repeated oxaliplatin infusions have been reported in the literature.…”

“…We investigated 20 cases including that of the present study (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). There were 7 male cases and 13 female cases (Table I).…”

“…Results of a number of studies showed that the combination of 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) increased survival rate and reduced the risk of disease progression in patients with metastatic CRC and stage III colon cancer (1,2). Thrombocytopenia has been noted in more than 70% of patients receiving FOLFOX, but is usually self-limited and related to myelosuppression from oxaliplatin (3,4). The isolated and acute decline in platelets after FOLFOX treatment is thought to be immune-mediated, and is referred to as drug-induced immune thrombocytopenia (DIIT).…”

“…Drug-induced acute thrombocytopenia is an extremely rare side effect that may occur immediately after oxaliplatin infusion (3,4). This potentially fatal reaction is immune-mediated and may be anticipated based on mild hemorrhagic signs during previous administration.…”