In PracticeThrombotic Microangiopathy, Cancer, and Cancer Drugs
Section snippets
Case Presentation
A 65-year-old man with a history of metastatic pancreatic cancer is referred from the oncology clinic for weakness and fatigue, epistaxis, new skin lesions over his shins, significantly elevated blood pressure (BP), and increased serum creatinine level. His medical history is significant for osteoarthritis of the knees, mild hypertension, and pancreatic malignancy initially treated with surgery and radiation. Recurrence developed with liver and peritoneal metastases. Medications include
Chemotherapy-induced TMA: Diagnosis, Pathophysiology, and Triggering Factors
Vascular injury as a result of chemotherapy is reported with increasing frequency.8 Although a variety of clinical disorders are described, the most devastating is TMA, a term originally proposed by Symmers.9 A sudden decrease in hemoglobin level, acute kidney injury (AKI), uncontrolled hypertension, and thrombocytopenia should alert clinicians of the possibility of TMA. When TMA is suspected, evidence supporting a microangiopathic process (schizocytes and elevated lactate dehydrogenase level)
Cancer-Related TMA
In oncology patients presenting with TMA, practitioners must differentiate cancer-related TMA from medication-induced TMA. In some patients, it can be challenging to identify whether TTP/HUS is drug induced or a result of the condition for which the drug was given. However, there are some features that distinguish the 2 conditions.6, 20, 21 Up to 90% of patients with cancer-related TMA have metastatic disease,22 whereas patients with chemotherapy-induced TMA have little or no detectable
Cancer Drug–induced TMA
Chemotherapy-induced TMA is more common than cancer-related TMA. Clinically suspected drug-induced TMA has been well documented in the last few decades, although in the past, it probably accounted for <15% of cases overall.1, 45, 46 Currently, incidence has increased and antitumor therapy has become a more common cause of TMA in cancer patients. Cancer drug–induced TMA diagnosis should be considered in the presence of cytopenia. In this circumstance, anemia and thrombocytopenia can by linked to
Management of Cancer Drug–induced TMA
Effective management of drug–induced TMA first requires accurate and rapid diagnosis. As discussed, not all the drugs manifest with hematologic findings of TMA, even in the presence of severe kidney TMA on kidney biopsy. Thus, patients receiving medications associated with TMA should be monitored for new or worsened hypertension, hematuria/proteinuria, and decreased kidney function. These findings may signal isolated kidney TMA in the absence of microangiopathic hemolytic anemia (including
Conclusion
TMA is a potentially severe kidney lesion with untoward outcomes that can complicate certain malignancies and a number of cancer therapies. It is important for clinicians to differentiate TMA due to the underlying cancer from a drug-induced cause of this endothelial injury. Drugs can be classified as type I versus type II based on the clinical and pathologic presentation, severity, and response to drug discontinuation. Newer agents leading to type II cancer drug–induced TMA and pegylated
Case Review
The patient’s kidney function continued to decline despite discontinuation of gemcitabine therapy. Hemodialysis was initiated for oliguric AKI. After 3 weeks of dialysis therapy, the patient and his family decided to discontinue dialysis treatment and he went home with hospice care. The patient died 5 days later.
Acknowledgements
Support: None.
Financial Disclosure: The authors declare that they have no relevant financial interests.
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