Proteasome inhibitor associated thrombotic microangiopathy.
A variety of medications have been implicated in the causation of thrombotic microangiopathy (TMA). Recently, a few case reports have emerged of TMA attributed to the proteasome inhibitors (PI) bortezomib and carfilzomib in patients with multiple myeloma. The aim of this case series was to better characterize the role of PI in the etiology of drug-induced TMA. We describe eleven patients from six medical centers from around the world who developed TMA while being treated with PI. The median time between medication initiation and diagnosis of TMA was 21 days (range 5 days to 17 months). Median laboratory values at diagnosis included hemoglobin-7.5 g dL(-1) , platelet count-20 × 10(9) /L, LDH-698 U L(-1) , creatinine-3.12 mg dL(-1) . No patient had any other cause of TMA, including ADAMTS13 inhibition, other malignancy or use of any other medication previously associated with TMA. Nine patients had resolution of TMA without evidence of hemolysis after withdrawal of PI. Two patients had stabilization of laboratory values but persistent evidence of hemolysis despite medication withdrawal. One patient had recurrence of TMA with rechallenge of PI. There is a strong level of evidence that PI can cause DITMA. In evaluating patients with suspected TMA, PI use should be recognized as a potential etiology, and these medications should be discontinued promptly if thought to be the cause of TMA. Am. J. Hematol. 91:E348-E352, 2016. © 2016 Wiley Periodicals, Inc.
Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Jennifer C
JC
Yui
Department of Cardiology, University Hospitals Leuven, Leuven, Belgium.
Jan
J
Van Keer
Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
Brendan M
BM
Weiss
Division of Hematology and Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
Adam J
AJ
Waxman
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Matthew B
MB
Palmer
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.
Vivette D
VD
D'Agati
Department of Clinical Therapeutics, National and Kapodistrian, University of Athens, School of Medicine, Athens, Greece.
Efstathios
E
Kastritis
Department of Clinical Therapeutics, National and Kapodistrian, University of Athens, School of Medicine, Athens, Greece.
Meletios A
MA
Dimopoulos
Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, Missouri.
Ravi
R
Vij
Division of Hematology and Oncology, Washington University School of Medicine, St. Louis, Missouri.
Dhruv
D
Bansal
Division of Hematology, Mayo Clinic, Rochester, Minnesota.
David
D
Dingli
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Samih H
SH
Nasr
Division of Hematology, Mayo Clinic, Rochester, Minnesota.|Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
Nelson
N
Leung
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069286:Bortezomib / Q000009:adverse effects; D005260:Female; D006461:Hemolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects; D061988:Proteasome Inhibitors / Q000009:adverse effects*; D012189:Retrospective Studies; D057049:Thrombotic Microangiopathies / Q000139:chemically induced* / Q000175:diagnosis
D009842:Oligopeptides; D061988:Proteasome Inhibitors; D000069286:Bortezomib; C524865:carfilzomib