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Published on: September 1, 2016
Thrombotic Microangiopathies and the Kidney
Anuja Java1, Richard Burwick2, Anthony Chang3
1Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
Abstract:
Thrombotic microangiopathy (TMA) is a pathological lesion that occurs due to endothelial injury. It can be seen in a heterogenous group of disorders, typically characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemia. TMA can also be renal limited with no systemic manifestations. There are multiple etiologies of a TMA with complement activation being a core underlying mechanism, although the nature and extent of complement involvement can vary. A further complicated factor is the cross talk between complement, neutrophils, and coagulation pathways in the pathophysiology of TMAs. Therefore, a thorough and systematic clinical history and laboratory evaluation are critical to establish the cause and pathophysiology of a TMA. Furthermore, TMAs are associated with significant morbidity and mortality, and timely diagnosis is key for appropriate management and to prevent end-stage kidney disease and other associated complications. In this review, we focus on the pathology, mechanisms, diagnostic work up and treatment of TMAs associated with various etiologies. We also define the complement evaluations that should be conducted in these patients and further highlight the currently approved complement therapies as well as others in the pipeline.
Insights
Thrombotic microangiopathy (TMA) involves endothelial injury, leading to anemia and low platelets. Understanding complement activation is key for diagnosing and treating this serious condition.
Area of Science:
- Nephrology
- Hematology
- Immunology
Background:
- Thrombotic microangiopathy (TMA) is characterized by endothelial injury, microangiopathic hemolytic anemia, thrombocytopenia, and end-organ ischemia.
- TMAs can present as renal-limited disease without systemic symptoms.
- Complement activation is a central mechanism in TMA, with variable involvement across etiologies.
Purpose of the Study:
- To review the pathology, mechanisms, diagnosis, and treatment of various TMA etiologies.
- To define essential complement evaluations for TMA patients.
- To highlight current and emerging complement therapies for TMAs.
Main Methods:
- Systematic review of literature on TMA pathology and mechanisms.
- Analysis of diagnostic workup strategies for TMAs.
- Evaluation of complement-mediated pathways and therapeutic interventions.
Main Results:
- TMA pathogenesis involves complex interactions between complement, neutrophils, and coagulation.
- Thorough clinical and laboratory evaluation is critical for accurate TMA diagnosis.
- Timely diagnosis and management are crucial to reduce morbidity, mortality, and prevent end-stage kidney disease.
Conclusions:
- Complement activation plays a pivotal role in diverse TMA presentations.
- Comprehensive complement assessment guides targeted therapy selection.
- Advances in complement inhibition offer promising treatment options for TMAs.
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