Proteasome inhibitor associated thrombotic microangiopathy

Jennifer C. Yui, Jan Van Keer, Brendan M. Weiss, Adam J. Waxman, Matthew B. Palmer, Vivette D. D'Agati, Efstathios Kastritis, Meletios A. Dimopoulos, Ravi Vij, Dhruv Bansal, David M Dingli, Samih H. Nasr, Nelson Leung

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 × 109/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.

Original languageEnglish (US)
Pages (from-to)E348-E352
JournalAmerican Journal of Hematology
Volume91
Issue number9
DOIs
StatePublished - Sep 1 2016

Fingerprint

Thrombotic Microangiopathies
Proteasome Inhibitors
Hemolysis
Multiple Myeloma
Causality
Blood Platelets

ASJC Scopus subject areas

  • Medicine(all)
  • Hematology

Cite this

Yui, J. C., Van Keer, J., Weiss, B. M., Waxman, A. J., Palmer, M. B., D'Agati, V. D., ... Leung, N. (2016). Proteasome inhibitor associated thrombotic microangiopathy. American Journal of Hematology, 91(9), E348-E352. https://doi.org/10.1002/ajh.24447

Proteasome inhibitor associated thrombotic microangiopathy. / Yui, Jennifer C.; Van Keer, Jan; Weiss, Brendan M.; Waxman, Adam J.; Palmer, Matthew B.; D'Agati, Vivette D.; Kastritis, Efstathios; Dimopoulos, Meletios A.; Vij, Ravi; Bansal, Dhruv; Dingli, David M; Nasr, Samih H.; Leung, Nelson.

In: American Journal of Hematology, Vol. 91, No. 9, 01.09.2016, p. E348-E352.

Research output: Contribution to journalArticle

Yui, JC, Van Keer, J, Weiss, BM, Waxman, AJ, Palmer, MB, D'Agati, VD, Kastritis, E, Dimopoulos, MA, Vij, R, Bansal, D, Dingli, DM, Nasr, SH & Leung, N 2016, 'Proteasome inhibitor associated thrombotic microangiopathy', American Journal of Hematology, vol. 91, no. 9, pp. E348-E352. https://doi.org/10.1002/ajh.24447
Yui JC, Van Keer J, Weiss BM, Waxman AJ, Palmer MB, D'Agati VD et al. Proteasome inhibitor associated thrombotic microangiopathy. American Journal of Hematology. 2016 Sep 1;91(9):E348-E352. https://doi.org/10.1002/ajh.24447
Yui, Jennifer C. ; Van Keer, Jan ; Weiss, Brendan M. ; Waxman, Adam J. ; Palmer, Matthew B. ; D'Agati, Vivette D. ; Kastritis, Efstathios ; Dimopoulos, Meletios A. ; Vij, Ravi ; Bansal, Dhruv ; Dingli, David M ; Nasr, Samih H. ; Leung, Nelson. / Proteasome inhibitor associated thrombotic microangiopathy. In: American Journal of Hematology. 2016 ; Vol. 91, No. 9. pp. E348-E352.
@article{287a554b7ecb4736ba86bde8405373dd,
title = "Proteasome inhibitor associated thrombotic microangiopathy",
abstract = "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 × 109/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.",
author = "Yui, {Jennifer C.} and {Van Keer}, Jan and Weiss, {Brendan M.} and Waxman, {Adam J.} and Palmer, {Matthew B.} and D'Agati, {Vivette D.} and Efstathios Kastritis and Dimopoulos, {Meletios A.} and Ravi Vij and Dhruv Bansal and Dingli, {David M} and Nasr, {Samih H.} and Nelson Leung",
year = "2016",
month = "9",
day = "1",
doi = "10.1002/ajh.24447",
language = "English (US)",
volume = "91",
pages = "E348--E352",
journal = "American Journal of Hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "9",

}

TY - JOUR

T1 - Proteasome inhibitor associated thrombotic microangiopathy

AU - Yui, Jennifer C.

AU - Van Keer, Jan

AU - Weiss, Brendan M.

AU - Waxman, Adam J.

AU - Palmer, Matthew B.

AU - D'Agati, Vivette D.

AU - Kastritis, Efstathios

AU - Dimopoulos, Meletios A.

AU - Vij, Ravi

AU - Bansal, Dhruv

AU - Dingli, David M

AU - Nasr, Samih H.

AU - Leung, Nelson

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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 × 109/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.

AB - 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 × 109/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.

UR - http://www.scopus.com/inward/record.url?scp=84983060381&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84983060381&partnerID=8YFLogxK

U2 - 10.1002/ajh.24447

DO - 10.1002/ajh.24447

M3 - Article

C2 - 27286661

AN - SCOPUS:84983060381

VL - 91

SP - E348-E352

JO - American Journal of Hematology

JF - American Journal of Hematology

SN - 0361-8609

IS - 9

ER -