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A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
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Proteasome inhibitor associated thrombotic microangiopathy
Jennifer C Yui1, Jan Van Keer2, Brendan M Weiss3
1Department of Medicine, Mayo Clinic, Rochester, Minnesota.
American Journal of Hematology
|June 12, 2016
Summary
Proteasome inhibitors (PI) can cause drug-induced thrombotic microangiopathy (DITMA) in multiple myeloma patients. Promptly discontinuing PIs is crucial for managing DITMA, with most patients recovering after medication withdrawal.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- Thrombotic microangiopathy (TMA) is a serious condition.
- Medications are known causes of TMA.
- Proteasome inhibitors (PIs) like bortezomib and carfilzomib are used for multiple myeloma.
Purpose of the Study:
- To investigate the role of proteasome inhibitors (PIs) in causing drug-induced thrombotic microangiopathy (DITMA).
- To characterize the clinical presentation and outcomes of PI-induced TMA.
Main Methods:
- A case series involving eleven patients from six international medical centers.
- Patients developed TMA while on PI therapy for multiple myeloma.
- Exclusion of other known causes of TMA.
Main Results:
- The median time from PI initiation to TMA diagnosis was 21 days.
- Key laboratory findings included low hemoglobin and platelets, elevated LDH, and impaired creatinine.
- Nine out of eleven patients resolved TMA after PI withdrawal; one recurred upon rechallenge.
Conclusions:
- Proteasome inhibitors (PIs) are a likely cause of drug-induced thrombotic microangiopathy (DITMA).
- PI use should be considered in patients presenting with TMA.
- Discontinuation of PIs is recommended for suspected DITMA.
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