Thrombotic microangiopathy in oncology – a review

Valério, Patrícia; Barreto, João P.; Ferreira, Hugo; Chuva, Teresa; Paiva, Ana; Maximino, José

doi:10.1016/j.tranon.2021.101081

Cited by 18 publications

(30 citation statements)

References 134 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TMA has also been associated with monoclonal gammopathy, although less so compared to C3G. In patients with frank malignancy-associated paraproteinemia (e.g., myeloma), TMA has been reported ( 43 – 46 ) and may result from therapy as well ( 47 ). Proteosome inhibitors have been shown to cause TMA ( 48 – 50 ), and hematopoietic stem-cell transplantation (HSCT) is a well-known secondary cause of TMA, even if autologous ( 51 , 52 ).…”

Section: Discussionmentioning

confidence: 99%

Thrombotic Microangiopathy, an Unusual Form of Monoclonal Gammopathy of Renal Significance: Report of 3 Cases and Literature Review

Filippone

Newman

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Monoclonal gammopathies result from neoplastic clones of the B-cell lineage and may cause kidney disease by various mechanisms. When the underlying clone does not meet criteria for a malignancy requiring treatment, the paraprotein is called a monoclonal gammopathy of renal significance (MGRS). One rarely reported kidney lesion associated with benign paraproteins is thrombotic microangiopathy (TMA), provisionally considered as a combination signifying MGRS. Such cases may lack systemic features of TMA, such as a microangiopathic hemolytic anemia, and the disease may be kidney limited. There is no direct deposition of the paraprotein in the kidney, and the presumed mechanism is disordered complement regulation. We report three cases of kidney limited TMA associated with benign paraproteins that had no other detectable cause for the TMA, representing cases of MGRS. Two of the cases are receiving clone directed therapy, and none are receiving eculizumab. We discuss in detail the pathophysiological basis for this possible association. Our approach to therapy involves first ruling out other causes of TMA as well as an underlying B-cell malignancy that would necessitate direct treatment. Otherwise, clone directed therapy should be considered. If refractory to such therapy or the disease is severe and multisystemic, C5 inhibition (eculizumab or ravulizumab) may be indicated as well.

show abstract

Section: Discussionmentioning

confidence: 99%

Thrombotic Microangiopathy, an Unusual Form of Monoclonal Gammopathy of Renal Significance: Report of 3 Cases and Literature Review

Filippone

Newman

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…In some cases, there can be overt thrombosis with luminal occlusion by fibrin thrombi. 9,10 Within the kidney, similar features can be seen in the microvasculature as well, with glomerular capillary thrombosis, severe intracapillary erythrocyte congestion (“glomerular paralysis”) and mesangiolysis. Chronic features include duplication of the glomerular basement membranes and more typical concentric intimal fibrosis of arteries and arterioles.…”

Section: Discussionmentioning

confidence: 96%

Late renal toxicity in patient with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib: A case report and literature review

Pham

Kwon

Castillo

et al. 2022

J Oncol Pharm Pract

View full text Add to dashboard Cite

Introduction Thyroid carcinoma is the most common endocrine neoplasm. Multimodal therapy including surgery, radioactive iodine (RAI) therapy, and indefinite suppression of thyroid-stimulating hormone has led to an 85% cure rate in differentiated thyroid tumors (DTT). Approximately 5–10% of patients will have recurrence or metastases that have the potential to become resistant to RAI treatment. 1 10-year overall survival rates are reported to be 10% in these patients versus 56% in patients with RAI avid disease. 2 Lenvatinib, a multi-tyrosine-kinase inhibitor (TKI), was shown to have a 65% overall response rate in addition to a significant improvement in progression-free survival (PFS), approved to treat RAI-resistant DTTs. 3 , 4 Case Report We are reporting a very rare case of late renal toxicity in a 68-year-old woman with a history of type 2 diabetes and metastatic RAI-resistant follicular thyroid carcinoma (Hurthle cell variant) who developed thrombotic microangiopathy 21 months after initiation of treatment. Management & Outcome It was determined that LEN should be held, due to worsening renal function secondary to TKI-induced kidney injury. Although the patient's renal function eventually improved and returned to her baseline after discontinuation of LEN, there was marked disease progression after drug cessation. Discussion Renal toxicity is a rare adverse event (AE) that tends to occur typically within three weeks of initiation of treatment. The utilization of TKIs can lead to glomerulosclerosis, and careful considerations and precautions should be taken by clinicians who intend to initiate TKI therapy in patients with pre-existing diabetes to prevent renal toxicity.

show abstract

“…Not all of these items are needed simultaneously to confirm the presence of TMA (Brocklebank et al, 2018). In fact, it is increasingly recognized that TMA may present with hypertension and/or renal function impairment with no or mild thrombocytopenia and/or no microangiopathic hemolytic anemia, ranging from subclinical laboratory abnormalities to full-blown TMA (Brocklebank et al, 2018;Estrada et al, 2019;Valério et al, 2021). In particular, also some DITMA cases have a subacute presentation with mild or only relative thrombocytopenia (>25% reduction in platelet count from Frontiers in Pharmacology frontiersin.org baseline) and gradual deterioration of renal function, and the identification of schistocytes by peripheral smear may not be documented in all cases (Eremina et al, 2008).…”

Section: Clinical Presentation Of Ditmamentioning

confidence: 99%

“…Renal-limited TMA at renal biopsy shows fibrin thrombi, glomerular mesangiolysis, subendothelial space widening with endothelial cells detaching from the glomerular basement membrane, endothelial swelling in glomeruli, arterioles and interlobular arteries with fibrinoid necrosis ( Fakhouri et al, 2017 ; Goodship et al, 2017 ). Multiple drugs have been described in association with renal-limited TMA: anti-VEGF, TK inhibitors and proteasome inhibitors ( Estrada et al, 2019 ; Valério et al, 2021 ). Renal-limited DITMA showed to benefit greatly from the withdrawal of the causative drug, with a lower relapse risk and better survival rates compared to systemic DITMA ( Izzedine and Perazella, 2015 ).…”

Section: Clinical Presentation Of Ditmamentioning

confidence: 99%

Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management

et al. 2023

View full text Add to dashboard Cite

Drug-induced thrombotic microangiopathy (DITMA) represents 10%–13% of all thrombotic microangiopathy (TMA) cases and about 20%–30% of secondary TMAs, just behind pregnancy-related and infection-related forms. Although the list of drugs potentially involved as causative for TMA are rapidly increasing, the scientific literature on DITMA is quite scarce (mostly as individual case reports or little case series), leading to poor knowledge of pathophysiological mechanisms and clinical management. In this review, we focused on these critical aspects regarding DITMA. We provided an updated list of TMA-associated drugs that we selected from a scientific literature review, including only those drugs with a definite or probable causal association with TMA. The list of drugs is heterogeneous and could help physicians from several different areas to be familiar with DITMA. We describe the clinical features of DITMA, presenting the full spectrum of clinical manifestations, from systemic to kidney-limited forms. We also analyze the association between signs/symptoms (i.e., malignant hypertension, thrombocytopenia) and specific DITMA causative drugs (i.e., interferon, ticlopidine). We highlighted their multiple different pathophysiological mechanisms, being frequently classified as immune-mediated (idiosyncratic) and dose-related/toxic. In particular, to clarify the role of the complement system and genetic deregulation of the related genes, we conducted a revision of the scientific literature searching for DITMA cases who underwent renal biopsy and/or genetic analysis for complement genes. We identified a complement deposition in renal biopsies in half of the patients (37/66; 57%), with some drugs associated with major deposits (i.e., gemcitabine and ramucirumab), particularly in capillary vessels (24/27; 88%), and other with absent deposits (tyrosine kinase inhibitors and intraocular anti-VEGF). We also found out that, differently from other secondary TMAs (such as pregnancy-related-TMA and malignant hypertension TMA), complement genetic pathological mutations are rarely involved in DITMA (2/122, 1.6%). These data suggest a variable non-genetic complement hyperactivation in DITMA, which probably depends on the causative drug involved. Finally, based on recent literature data, we proposed a treatment approach for DITMA, highlighting the importance of drug withdrawal and the role of therapeutic plasma-exchange (TPE), rituximab, and anti-complementary therapy.

show abstract

Thrombotic microangiopathy in oncology – a review

Cited by 18 publications

References 134 publications

Thrombotic Microangiopathy, an Unusual Form of Monoclonal Gammopathy of Renal Significance: Report of 3 Cases and Literature Review

Thrombotic Microangiopathy, an Unusual Form of Monoclonal Gammopathy of Renal Significance: Report of 3 Cases and Literature Review

Late renal toxicity in patient with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib: A case report and literature review

Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management

Contact Info

Product

Resources

About