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Thrombotic Microangiopathies: Thrombus Formation Due to Common or Related Mechanisms?

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Core Concepts in Parenchymal Kidney Disease

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Abstract

Thrombotic microangiopathies (TMA) represent a spectrum of related disorders that have in common thrombocytopenia and hemolytic anemia and that may affect the kidney as well as other organs including the heart, the gastrointestinal tract, lungs, and the brain. The two major forms of TMA are hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP), and there is an ongoing discussion aiming to define how strongly the two disorders are related to each other and how common the underlying pathological mechanisms are. As the pathogenetic mechanisms of each group are more and more understood, the overlap of the two diseases, as well as reasons why they manifest in different organs, is becoming clearer. TTP has primarily neurological complications but develops also in the kidney, and HUS is primarily a kidney disease that often involves other tissues and organs, including heart and brain. In HUS endothelial cell damage and platelet activation that lead to thrombus formation are caused by defective complement action due to genetic—as well as acquired—factors including autoantibodies to Factor H. In TTP the release of multimers of von Willebrand Factor (vWF) and often defective action of the ADAMTS13 lead to thrombus formation and are caused by mutation in the ADAMTS13 gene as well as by acquired autoantibodies.

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Acknowledgments

The work of the authors is supported by the Deutsche Forschungsgemeinschaft (DFG, Sk46;Zi 432), the Bundesministerium für Forschung und Technologie (BMBF), Pro Retina Foundation Germany. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 2012-305608 “European Consortium for High-Throughput Research in Rare Kidney Diseases (EURenOmics).”

The authors have no conflict of interest. We thank Sanjeev Sethi, MD, PhD, for providing images of kidney biopsies of aHUS patients.

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Authors and Affiliations

  1. Department of Infection Biology, Leibniz Institute for Natural Product Research and Infection Biology, Jena, Germany

    Peter F. Zipfel

  2. Department of Infection Biology, Leibniz Institute for Natural Produce Research and Infection Biology eV, Jena, Thuringia, Germany

    Christine Skerka

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  1. Peter F. Zipfel
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Correspondence to Peter F. Zipfel .

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Editors and Affiliations

  1. Div. Nephrology & Hypertension, Mayo Clinic Dept. Internal Medicine, Rochester, Minnesota, USA

    Fernando C. Fervenza

  2. Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Julie Lin

  3. Mayo Clinic, Rochester, Minnesota, USA

    Sanjeev Sethi

  4. Renal Division, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts, USA

    Ajay K. Singh

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Zipfel, P.F., Skerka, C. (2014). Thrombotic Microangiopathies: Thrombus Formation Due to Common or Related Mechanisms?. In: Fervenza, F., Lin, J., Sethi, S., Singh, A. (eds) Core Concepts in Parenchymal Kidney Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8166-9_15

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