Brief observation
A Rare Hematological Adverse Event Induced by Bevacizumab: Severe Thrombocytopenia

https://doi.org/10.1016/j.amjmed.2012.04.026Get rights and content

Abstract

Background

Bevacizumab, a monoclonal antibody to vascular endothelial growth factor-A, is approved for the treatment of various malignancies, and its hematological toxicities are considered infrequent.

Methods

A colorectal cancer patient receiving chemotherapy (5-fluorouracil and oxaliplatin) plus bevacizumab developed acute, severe thrombocytopenia. We postulated that this thrombocytopenia could be directly triggered by bevacizumab.

Results

A man with stage IV colorectal cancer and synchronous liver metastasis had received 10 cycles of FOLFOX plus bevacizumab (5 mg/kg) without significant hematological toxicity. Due to thrombocytopenia, oxaliplatin was withdrawn after cycle 11. On cycle 12, shortly after bevacizumab infusion and before 5-fluorouracil infusion, the patient developed fever, lower limbs purpura, grade 1 proctorrhagia, and epistaxis. Platelets had decreased from 105,000/mm3 to 3000/mm3 within 1 hour after bevacizumab infusion. Flow cytometry identified platelet-associated immunoglobulins. Despite 2 apheresis-derived platelet transfusions, oral corticotherapy, and gamma globulin infusions, thrombocytopenia persisted, but was finally successfully treated with a peptibody thrombopoietin mimetic, which was introduced 28 days after the last bevacizumab infusion.

Conclusions

Clinicians should keep in mind that bevacizumab can induce acute and potentially severe immune-mediated thrombocytopenia.

Section snippets

Case Report

A 73-year-old man with a past history of diabetes, hypertension, and genitourinary tuberculosis, was diagnosed with stage IV colon carcinoma with synchronous liver metastasis. He received neo-adjuvant FOLFOX regimen (5-fluorouracil, leucovorin, and oxaliplatin) for 6 cycles, and subsequently underwent primary tumor resection and left liver lobectomy. Adjuvant FOLFOX was given for 6 cycles. At first evaluation, liver metastases were diagnosed, and the patient was started on irinotecan plus

Discussion

We describe a case of acute immune-mediated thrombocytopenia triggered by bevacizumab. Bevacizumab has mild hematological toxicities per se but has been shown to slightly increase hematological adverse events when combined with chemotherapy.1 Of note, thrombocytopenia did not seem to be dose-dependent during bevacizumab dose escalation from 3 mg/kg to 20 mg/kg in breast cancer patients.6 Recently, it has been suggested that bevacizumab could induce nonsevere and reversible thrombocytopenia.7 In

References (20)

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    Citation Excerpt :

    Thrombocytopenia defined as a platelet count below the lower limit of 150,000 platelets/μL blood can be caused by a variety of reasons, one of the foremost being immune thrombocytopenia, formerly known as idiopathic thrombocytopenic purpura (ITP) [1]. Thrombocytopenia can be an isolated disorder or develop secondary to or in association with drug treatments [1–5] or conditions such as viral or bacterial infections [1,6–8]. Whatever the etiology of thrombocytopenia, thrombocytopenic patients have an increased risk of bleeding, which can be fatal in rare cases [1,9,10].

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Funding: None.

Conflict of Interest: Dr Mir and Dr Coriat have acted as paid consultants for Roche; Prof Goldwasser has acted as a paid consultant for Amgen. Other authors have no conflict of interest to declare.

Authorship: All authors had access to the data and a role in writing the manuscript.

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