Thrombotic microangiopathies: new insights and new challenges

Zipfel, Peter F.; Heinen, Stefan; Skerka, Christine

doi:10.1097/mnh.0b013e32833aff4a

Cited by 50 publications

(37 citation statements)

References 57 publications

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“…Patients with active AAV have elevated levels of circulating C3a, C5a, soluble C5b-9, and Bb, which suggests activation of the complement system via the alternative pathway (30). As for TMA, a variety of hereditary and acquired disorders, which contribute to the loss of alternative pathway regulation on endothelial cells and on the surface of platelets, have been documented and predispose patients to TMA susceptibility (31)(32)(33)(34). Indeed, it has been suggested that most TMAs are characterized by misdirected complement activation affecting endothelial cell and platelet integrity (34).…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic Characteristics and Outcomes of Renal Thrombotic Microangiopathy in Anti-Neutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis

Chen

Wang

Huang

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Thrombotic microangiopathy (TMA) in ANCA-associated vasculitis (AAV) has been mainly reported in isolated case reports. The aim of this study was to analyze clinical and pathologic characteristics and prognosis of patients with renal TMA in ANCA-associated GN in a large cohort of Chinese patients.Design, setting, participants, & measurements Clinical and renal histopathologic data of 220 patients with biopsy-proven ANCA-associated GN from 1996 to 2013 were retrospectively analyzed. Patients were followed up for a median period of 32 (interquartile range [IQR], 12-65) months, and outcomes of patients were analyzed.Results Among the 220 patients with ANCA-associated GN, 30 were identified having concomitant renal TMA by pathologic evaluation. Compared with the non-TMA group, patients with renal TMA presented with more severe renal injury, as evidenced clinically by a higher level of serum creatinine at diagnosis (5.0 [IQR, 3.5-9.0] versus 3.2 [IQR, 1.7-6.8] mg/dl; P=0.02) and pathologically by a higher percentage of cellular crescents (15.0% [IQR, 6.9%-34.9%] versus 6.9% [IQR, 0%-21.1%]; P=0.04) and more severe interstitial infiltration (2 [IQR, 2-2] versus 2 [IQR, 1-2]; P=0.03) in renal biopsies. Furthermore, multivariate analysis showed that renal TMA was independently associated with mortality of patients with AAV after adjusting for age, sex, initial serum creatinine, tubular atrophy, and interstitial fibrosis (hazard ratio, 1.92; 95% confidence interval, 1.08 to 3.41; P=0.03) or for age, sex, the histopathologic classification scheme proposed by Berden et al. (J Am Soc Nephrol 21: 1628-1636, tubular atrophy, and interstitial fibrosis (hazard ratio, 1.95; 95% confidence interval, 1.07 to 3.55; P=0.03).Conclusions Renal TMA in ANCA-associated GN is not rare and presents with more severe renal injury. Renal TMA is independently associated with all-cause mortality in patients with AAV.

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Section: Discussionmentioning

confidence: 99%

Clinicopathologic Characteristics and Outcomes of Renal Thrombotic Microangiopathy in Anti-Neutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis

Chen

Wang

Huang

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…A specific plasma protease, the ADAMTS13 gene, is responsible for the physiologic degradation of vWF and plays a pathogenic role in a substantial proportion of familial and acute idiopathic cases of TTP. 8 A deficiency in ADAMTS13 enzyme levels, along with an inhibitory antibody, is found in most patients with idiopathic TTP. Multiple triggers, such as infection, drugs, cancer, chemotherapy, bone marrow transplantation, and pregnancy, are recognized.…”

Section: Discussionmentioning

confidence: 99%

“…Several complement genes are mutated in HUS. 8 Multifocal TMA with intimal-medial dissection by thrombi extending from foci of endothelial damage in small cerebral arteries and arterioles can be secondary to toxins. 10,11 A drug as the toxin is a rare cause of TMA.…”

Section: Discussionmentioning

confidence: 99%

Suspicious Neuroimaging Pattern of Thrombotic Microangiopathy

Ellchuk¹,

Shah²,

Hewlett³

et al. 2011

AJNR Am J Neuroradiol

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SUMMARY:The TMAs are a group of microvascular occlusive disorders characterized by thrombocytopenia and intravascular hemolysis. Literature review reveals a spectrum of neuroimaging findings, including a single case report of multifocal hemorrhagic infarctions. We present a series of 12 patients with TMA demonstrating a similar pattern of multifocal cortical and subcortical hemorrhagic infarctions.ABBREVIATIONS: ADC ϭ apparent diffusion coefficient; AML ϭ acute myelogenous leukemia; CLL ϭ chronic lymphocytic leukemia; CNS ϭ central nervous system; CTV ϭ CT venography; DIC ϭ disseminated intravascular coagulation; DWI ϭ diffusion-weighted imaging; GRE ϭ gradient recalled-echo; HIV ϭ human immunodeficiency virus; HUS ϭ hemolytic uremic syndrome; mHTN ϭ malignant hypertension; MRI ϭ MR imaging; MRV ϭ MR venography; PRES ϭ posterior reversible encephalopathy syndrome; SWI ϭ susceptibility-weighted imaging; TMA ϭ thrombotic microangiopathy; TTP ϭ thrombotic thrombocytopenic purpura; vWF ϭ von Willebrand factor T MA was defined by Symmers in 1952 1 as a lesion of arteriole and capillary wall thickening with swelling or detachment of endothelial cells from the basement membrane, accumulation of material in the subendothelial space, and lodging of fibrin-platelet thrombi at the arteriocapillary junction.2 The mechanical injury to erythrocytes results in intravascular hemolysis and schistocytosis. The intraluminal platelet thrombosis results in partial or complete obstruction of the vessel lumina.

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“…Pregnant women and women in the postpartum period accounted for a notable portion (12-31%; about 1 each 25,000 pregnancies) of the cases in some studies. For this reason TTP predominantly affects female subjects between 10 and 40 years old [5,6].…”

Section: Thrombotic Thrombocytopenic Purpura (Ttp)mentioning

confidence: 99%

“…These features are really common to various disorders, however Thrombotic Thrombocytopenic Purpura (TTP) and the Hemolytic-Uremic Syndrome (HUS), represent the major and more investigated forms whose pathogenesis has been clarified only in the last three decades [2][3][4]. Both TTP and HUS occur at a frequency of approximately 1-6 cases per one million people, may affect children and adults, and may each have several distinct subtypes with overlapping symptoms, but caused by differing pathophysiologic mechanisms [5].…”

Section: Introductionmentioning

confidence: 99%