Thrombotic thrombocytopenic purpura due to anti-ADAMTS13 antibodies in multiple myeloma

Yao, Hubert Kouamé; Monge, Matthieu; Renou, Marianne; Lecaque, Caroline; Jaureguy, Maïté; Presne, Claire; Makdassi, R; Choukroun, Gabriel

doi:10.5414/cn107579

Cited by 16 publications

(14 citation statements)

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“…While the most common alternative causes of TMA were absent in these patients, this does not exclude the presence of other potential conditions to which the TMA may be attributed. For instance, TMA has rarely been described secondary to hematologic malignancies including MM in the absence of drug effect, but TMA secondary to MM would not be consistent with resolution of TMA after PI withdrawal. Finally, there remain unanswered questions regarding the mechanism of PI‐induced TMA which must be addressed in further studies and may be elucidated by the development of assays for PI‐dependent platelet antibodies or further study of the toxic effects of PI on endothelial tissue.…”

Section: Discussionmentioning

confidence: 99%

Proteasome inhibitor associated thrombotic microangiopathy

et al. 2016

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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. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Proteasome inhibitor associated thrombotic microangiopathy

et al. 2016

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“…Many of these patients have documented evidence of renal involvement and clinical features of thrombotic thrombocytopenic purpura, including neurologic symptoms, microangiopathic hemolytic anemia, thrombocytopenia, schistocytes on peripheral blood smear, elevated serum lactate dehydrogenase levels, and indirect hyperbilirubinemia. In one patient, ADAMTS13 activity was low because of the presence of autoantibodies (112). The pathogenesis of TMA secondary to MM may involve paraprotein-induced hyperviscosity, which may cause blood stagnation and microcirculation disturbance.…”

Section: Thrombotic Microangiopathy Associated With Paraproteinemiasmentioning

confidence: 96%

“…Rare patients with thrombotic microangiopathy (TMA) associated with MM have been reported in the literature (110)(111)(112)(113)(114)(115). Many of these patients have documented evidence of renal involvement and clinical features of thrombotic thrombocytopenic purpura, including neurologic symptoms, microangiopathic hemolytic anemia, thrombocytopenia, schistocytes on peripheral blood smear, elevated serum lactate dehydrogenase levels, and indirect hyperbilirubinemia.…”

Section: Thrombotic Microangiopathy Associated With Paraproteinemiasmentioning

confidence: 99%

Paraprotein–Related Kidney Disease: Glomerular Diseases Associated with Paraproteinemias

Motwani

Herlitz

Monga

et al. 2016

CJASN

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Paraproteins are monoclonal Igs that accumulate in blood as a result of abnormal excess production. These circulating proteins cause a diversity of kidney disorders that are increasingly being comanaged by nephrologists. In this review, we discuss paraprotein-related diseases that affect the glomerulus. We provide a broad overview of diseases characterized by nonorganized deposits, such as monoclonal Ig deposition disease (MIDD), proliferative GN with monoclonal Ig deposits (PGNMID), and C3 glomerulopathy, as well as those characterized by organized deposits, such as amyloidosis, immunotactoid glomerulopathy, fibrillary GN, and cryoglobulinemic GN, and rarer disorders, such as monoclonal crystalline glomerulopathies, paraprotein-related thrombotic microangiopathies, and membranous-like glomerulopathy with masked IgGκ deposits. This review will provide the nephrologist with an up to date understanding of these entities and highlight the areas of deficit in evidence and future lines of research.

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“…Autoantibodies against the enzyme have been described in isolated cancer cases, 55,56 yet in the majority, reduced production through liver dysfunction and/or increased clearance (possibly through consumption in a prothrombotic state) has been suggested as the main cause. 11,53 However, our results suggest that low ADAMTS13 enzyme activity can lead to severe clinical consequences when exposed to anti-VEGF state.…”

Section: /2mentioning

confidence: 99%

ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic Microangiopathy

Erpenbeck

Demers

Zsengellér

et al. 2016

Journal of the American Society of Nephrology

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Thrombotic microangiopathy (TMA) is a life-threatening condition that affects some, but not all, recipients of vascular endothelial growth factor (VEGF) inhibitors given as part of chemotherapy. TMA is also a complication of preeclampsia, a disease characterized by excess production of the VEGF-scavenging soluble VEGF receptor 1 (soluble fms-like tyrosine kinase 1; sFlt-1). Risk factors for VEGF inhibitor-related TMA remain unknown. We hypothesized that deficiency of the VWF-cleaving ADAMTS13 endopeptidase contributes to the development of VEGF inhibitor-related TMA. ADAMTS13 2/2 mice overexpressing sFlt-1 presented all hallmarks of TMA, including thrombocytopenia, schistocytosis, anemia, and VWF-positive microthrombi in multiple organs. Similar to VEGF inhibitor-related TMA in humans, these mice exhibited severely impaired kidney function and hypertension. In contrast, wild-type mice overexpressing sFlt-1 developed modest hypertension but no other features of TMA. Recombinant ADAMTS13 therapy ameliorated all symptoms of TMA in ADAMTS13 2/2 mice overexpressing sFlt-1 and normalized BP in wild-type mice. ADAMTS13 activity may thus be a critical determinant for the development of TMA secondary to VEGF inhibition. Administration of recombinant ADAMTS13 may serve as a therapeutic approach to treat or prevent thrombotic complications of VEGF inhibition.

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Thrombotic thrombocytopenic purpura due to anti-ADAMTS13 antibodies in multiple myeloma

Abstract: The association of TMA, especially TTP, and multiple myeloma is exceptional. The authors report such a case that induced irreversible renal damage, but with stable clinical and laboratory parameters with a follow-up of 4 years.

Cited by 16 publications

References 0 publications

Proteasome inhibitor associated thrombotic microangiopathy

Proteasome inhibitor associated thrombotic microangiopathy

Paraprotein–Related Kidney Disease: Glomerular Diseases Associated with Paraproteinemias

ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor–Induced Thrombotic Microangiopathy

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