What chemotherapy drugs cause thrombocytopenia (low platelet count)?

From the Guidelines

Chemotherapy drugs, particularly platinum compounds, alkylating agents, antimetabolites, and taxanes, commonly cause thrombocytopenia through bone marrow suppression, with the severity varying by drug, dose, and individual patient factors. The risk of bleeding in patients with solid tumors during chemotherapy-induced thrombocytopenia is related to the depth and duration of the platelet nadir, although other factors contribute as well 1. Thrombocytopenia typically develops 7-14 days after chemotherapy administration and may resolve within 2-4 weeks as bone marrow function recovers. Some chemotherapy regimens, such as those including gemcitabine and cisplatin, have been associated with higher rates of thrombocytopenia, with incidences ranging from 21.3% to 52.1% in clinical trials 1. Platelet counts below 50,000/μL increase bleeding risk, while counts under 10,000/μL pose serious hemorrhage risks. Management includes platelet transfusions for severe cases (typically when counts fall below 10,000-20,000/μL), dose reductions or delays in subsequent chemotherapy cycles, and possibly granulocyte colony-stimulating factors in some regimens. Patients should be monitored with regular complete blood counts and educated about bleeding precautions, including avoiding NSAIDs, using soft toothbrushes, and seeking immediate medical attention for unusual bleeding or bruising. The American Society of Clinical Oncology recommends a threshold of 10^9/L for prophylactic platelet transfusion in patients with solid tumors during chemotherapy-induced thrombocytopenia 1. In clinical practice, the choice of chemotherapy regimen may be influenced by the toxicity profiles of the component agents, with thrombocytopenia being more common with carboplatin than with cisplatin 1. Overall, the management of chemotherapy-induced thrombocytopenia requires careful consideration of the risks and benefits of different treatment strategies, as well as close monitoring of patients to minimize the risk of bleeding complications. Key points to consider in the management of chemotherapy-induced thrombocytopenia include:

• Monitoring of platelet counts and adjustment of chemotherapy doses as needed
• Use of platelet transfusions for severe thrombocytopenia
• Education of patients about bleeding precautions and the importance of seeking immediate medical attention for unusual bleeding or bruising
• Consideration of the toxicity profiles of different chemotherapy regimens in the selection of treatment for individual patients.

From the FDA Drug Label

The carboplatin, USP-containing regimen induced significantly more thrombocytopenia and, in one study, significantly more leukopenia and more need for transfusional support. ADVERSE EXPERIENCES IN PATIENTS WITH OVARIAN CANCER NCIC STUDY

• Thrombocytopenia <100,000/mm3 70
• Thrombocytopenia <50,000/mm3 41 ADVERSE EXPERIENCES IN PATIENTS WITH OVARIAN CANCER SWOG STUDY
• Thrombocytopenia <100,000/mm3 59
• Thrombocytopenia <50,000/mm3 22

Carboplatin, USP causes thrombocytopenia. The incidence of thrombocytopenia was significantly higher in patients treated with carboplatin, USP compared to those treated with cisplatin. In the NCIC study, 70% of patients experienced thrombocytopenia with a platelet count <100,000/mm3, and 41% had a platelet count <50,000/mm3. Similarly, in the SWOG study, 59% of patients had thrombocytopenia with a platelet count <100,000/mm3, and 22% had a platelet count <50,000/mm3 2.

From the Research

Chemotherapy-Induced Thrombocytopenia

• Chemotherapy-induced thrombocytopenia (CIT) is a common complication of cancer treatment, particularly in patients with non-hematologic malignancies 3.
• The incidence of CIT varies depending on the type and dose of chemotherapy, with regimens containing gemcitabine, platinum, or temozolomide producing it most commonly 3, 4.
• CIT is related to the damage caused by chemotherapy to the bone marrow microenvironment, which affects the production of platelets 5, 6.

Risk Factors and Causes

• Patient-related variables, such as age, tumor type, and number of prior chemotherapy cycles, can determine the extent of CIT 3.
• Certain chemotherapy agents, such as alkylating agents, cyclophosphamide, and bortezomib, can cause thrombocytopenia by affecting stem cells, megakaryocyte progenitors, or platelet release 4.
• The use of carboplatin, gemcitabine, and paclitaxel has been associated with a higher risk of thrombocytopenia 6.

Diagnosis and Treatment

• Thrombocytopenia is diagnosed by a low platelet count, and it is essential to exclude other causes of thrombocytopenia, such as immune thrombocytopenia, coagulopathy, or infection 3, 4.
• Treatment options for CIT include reducing chemotherapy dose intensity, switching to other agents, or using thrombopoietic growth factors, such as romiplostim or eltrombopag 3, 4, 7.
• Thrombopoietin receptor agonists, such as romiplostim, can be used to manage persistent CIT, particularly in the context of a clinical trial or off-label use 7.

Clinical Consequences

• CIT can result in bleeding, chemotherapy treatment delays, dose reductions, and discontinuation 3, 5, 7.
• The frequency and relative risk of thrombocytopenia vary depending on the chemotherapy regimen, with combination therapies containing carboplatin, gemcitabine, or paclitaxel associated with a higher risk 6.