Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort

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Abstract

Gemcitabine has been associated with thrombotic microangiopathy (TMA). We conducted a national retrospective study of gemcitabine-associated TMA (G-TMA).

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Guidelines on the use of therapeutic apheresis in clinical practice--evidence-based approach from the Apheresis Applications Committee of the American Society for Apheresis.

Joseph Schwartz, Marisa Marques, … (2009)

The American Society for Apheresis (ASFA) Apheresis Applications Committee is charged with a review and categorization of indications for therapeutic apheresis. Beginning with the 2007 ASFA Special Issue (fourth edition), the subcommittee has incorporated systematic review and evidence-based approach in the grading and categorization of indications. This Fifth ASFA Special Issue has further improved the process of using evidence-based medicine in the recommendations by refining the category definitions and by adding a grade of recommendation based on widely accepted GRADE system. The concept of a fact sheet was introduced in the Fourth edition and is only slightly modified in this current edition. The fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis. The article consists of 59 fact sheets devoted to each disease entity currently categorized by the ASFA as category I through III. Category IV indications are also listed. Copyright 2010 American Society for Apheresis.

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Kidney Diseases Associated With Anti-Vascular Endothelial Growth Factor (VEGF)

Hassan Izzedine, Bernard Escudier, Catherine Lhommé … (2014)

Abstract Expanded clinical experience with patients taking antiangiogenic compounds has come with increasing recognition of the renal adverse effects. Because renal histology is rarely sought in those patients, the renal consequences are underestimated. Antiangiogenic-treated-cancer patients, who had a renal biopsy for renal adverse effects from 2006 to 2013, were included in the current study. Clinical features and renal histologic findings were reviewed. Our cohort was 100 patients (58 women) with biopsy-proven kidney disease using anti-vascular endothelial growth factor (VEGF) therapy with a mean age of 59.8 years (range, 20–85 yr). Patients were referred for proteinuria, hypertension, and/or renal insufficiency. Kidney biopsy was performed 6.87 ± 7.18 months after the beginning of treatment. Seventy-three patients experienced renal thrombotic microangiopathy (TMA) and 27 patients had variable glomerulopathies, mainly minimal change disease and/or collapsing-like focal segmental glomerulosclerosis (MCN/cFSGS). MCN/cFSGS-like lesions developed mainly with tyrosine-kinase inhibitors, whereas TMA complicated anti-VEGF ligand. Thirty-one percent of TMA patients had proteinuria up to 1 g/24 h. Half of TMA cases are exclusively renal localized. Pathologic TMA features are intraglomerular exclusively. MCN/cFSGS glomeruli displayed a high abundance of KI-67, but synaptopodin was not detected. Conversely, TMA glomeruli exhibited a normal abundance of synaptopodin-like control, whereas KI-67 was absent. Median follow-up was 12 months (range, 1–80 mo). Fifty-four patients died due to cancer progression. Hypertension and proteinuria resolved following drug discontinuation and antihypertensive agents. No patient developed severe renal failure requiring dialysis. Drug continuation or reintroduction resulted in a more severe recurrence of TMA in 3 out of 4 patients requiring maintenance of anti-VEGF agents despite renal TMA. In conclusion, TMA and MCN/cFSGS are the most frequent forms of renal involvement under anti-VEGF therapy. Careful risk-benefit assessment for individual patients should take into account risk factors related to the host and the tumor.

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ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes.

Catherine S. McFadden, W Erber, N Yutaka … (2012)

Schistocytes are fragments of red blood cells (RBCs) produced by extrinsic mechanical damage within the circulation. The detection of schistocytes is an important morphological clue to the diagnosis of thrombotic microangiopathic anemia (TMA). Reporting criteria between different laboratories, however, are not uniform, owing to variability of shape and nature of fragments, as well as subjectivity and heterogeneity in their morphological assessment. Lack of standardization may lead to inconsistency or misdiagnosis, thereby affecting treatment and clinical outcome. The Schistocyte Working Group of the International Council for Standardization in Haematology (ICSH) has prepared specific recommendations to standardize schistocyte identification, enumeration, and reporting. They deal with the type of smear, method of counting, morphological description based on positive criteria (helmet cells, small, irregular triangular, or crescent-shaped cells, pointed projections, and lack of central pallor). A schistocyte count has a definite clinical value for the diagnosis of TMA in the absence of additional severe red cell shape abnormalities, with a confident threshold value of 1%. Automated counting of RBC fragments is also recommended by the ICSH Working Group as a useful complement to the microscope, according to the high predictive value of negative results, but worthy of further research and with limits in quantitation. © 2011 Blackwell Publishing Ltd.

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Author and article information

Journal

Title: British Journal of Clinical Pharmacology

Abbreviated Title: Br J Clin Pharmacol

Publisher: Wiley

ISSN (Print): 0306-5251

ISSN (Electronic): 1365-2125

Publication date Created: December 18 2018

Publication date Created: February 2019

Publication date (Electronic): December 18 2018

Publication date (Print): February 2019

Volume: 85

Issue: 2

Pages: 403-412

Affiliations

[1 ]Department of NephrologyAix‐Marseille University AP‐HM Hôpital de la Conception Marseille France

[2 ]Department of Clinical Pharmacology and Pharmacovigilance, Regional Centre of PharmacovigilanceAix‐Marseille University AP‐HM Hôpital de la Timone Marseille France

[3 ]Department of Clinical Pharmacology and PharmacovigilanceAix‐Marseille University AP‐HM Hôpital de la Timone Marseille France

[4 ]INSERM UMR_S 1106, INS, Inst Neurosciences SystemsAix Marseille University Marseille France

[5 ]Department of Apheresis, Regional Reference Center for Thrombotic MicroangiopathyAix‐Marseille University AP‐HM Hôpital de la Conception Marseille France

[6 ]Aix‐Marseille University C2VN, INSERM 1263, INRA 1260 Marseille France

[7 ]Department of Public HealthAix‐Marseille University AP‐HM Hôpital de la Timone Marseille France

[8 ]Department of Clinical OncologyAix‐Marseille University AP‐HM Hôpital de la Timone Marseille France

[9 ]Department of Clinical Oncology, Institut Paoli Calmettes, Laboratory of Molecular OncologyAix‐Marseille University CRCM INSERM UMR 1068 Marseille France

[10 ]Department of Parmacy, OncoPharma UnitAix‐Marseille University AP‐HM Hôpital de la Timone Marseille France

[11 ]Regional Center of PharmacovigilanceDijon University Hospital Dijon France

[12 ]Medical intensive care unit, Regional Center for Thrombotic Microangiopathy, Hôpital Charles NicolleRouen University Hospital Rouen France

[13 ]Laboratory of ImmunologyAP‐HP Hôpital Européen Georges Pompidou Paris France

[14 ]Department of Hematology, French Reference Center for Thrombotic Microangiopathy (www.cnr‐mat.fr)Paris 6 University Paris France

Article

DOI: 10.1111/bcp.13808

PMC ID: 6339967

PubMed ID: 30394581

SO-VID: e4034f41-d881-4610-8874-1d164beaab15

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Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort

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Most cited references 32

Guidelines on the use of therapeutic apheresis in clinical practice--evidence-based approach from the Apheresis Applications Committee of the American Society for Apheresis.

Kidney Diseases Associated With Anti-Vascular Endothelial Growth Factor (VEGF)

ICSH recommendations for identification, diagnostic value, and quantitation of schistocytes.

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