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thrombotic microvascular angiopathy

Nirav Dhanesha, Prakash Doddapattar, Mehul R Chorawala, Manasa K Nayak, Koichi Kokame, Janice M Staber, Steven R Lentz, Anil K Chauhan
OBJECTIVE: ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I repeats-13) prevents microvascular thrombosis by cleaving prothrombogenic ultralarge von Willebrand factor (VWF) multimers. Clinical studies have found association between reduced ADAMTS13-specific activity, ultralarge VWF multimers, and thrombotic angiopathy in patients with diabetic nephropathy. It remains unknown, however, whether ADAMTS13 deficiency or ultralarge VWF multimers have a causative effect in diabetic nephropathy...
July 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
K Kottke-Marchant
Thrombotic micro-angiopathies (TMA) are a group of related disorders that are characterized by thrombosis of the microvasculature and associated organ dysfunction, and encompass congenital, acquired, and infectious etiologies. A hall mark of TMAs is the fragmentation of erythrocytes by the microvascular thrombi, resulting in a hemolytic anemia. There are several distinct pathophysiologies leading to microangiopathic hemolysis, ranging from decreased degradation of von Willebrand factor as seen in thrombotic thrombocytopenic purpura (TTP) to endothelial damage facilitated by Escherichia coli shiga toxin or complement dysregulation, seen in shiga toxin-related hemolytic-uremic syndrome (Stx-HUS) and complement-mediated TMA (also called atypical hemolytic-uremic syndrome), respectively...
May 2017: International Journal of Laboratory Hematology
Bérangère S Joly, Paul Coppo, Agnès Veyradier
Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia linked to disseminated microvascular platelet rich-thrombi. TTP is specifically related to a severe deficiency in ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13), the specific von Willebrand factor-cleaving protease. ADAMTS13 deficiency is most frequently acquired via ADAMTS13 autoantibodies, but rarely, it is inherited via mutations of the ADAMTS13 gene...
May 25, 2017: Blood
A M Cerbone, N Macarone-Palmieri, G Saldalamacchia, A Coppola, G Di Minno, A A Rivellese
Diabetes mellitus is commonly associated with both microvascular and macrovascular complications (coronary artery disease, cerebrovascular events, severe peripheral vascular disease, nephropathy and retinopathy). There is wide evidence demonstrating that platelet degranulation and synthesis of TxA2 are increased in diabetic patients. For this reason, many studies on anti-platelet therapy have been made to reduce thrombotic complication of diabetes mellitus. Some diabetic patients, although treated with ASA, have a high prevalence of recurrent thrombotic events, which may presumably be due to an "ASA resistance"...
December 2009: Acta Diabetologica
S Giannini, B Cresci, C Manuelli, L Pala, C M Rotella
Endothelial cells (EC) play a role in many diseases including diabetes mellitus. EC share common functions, such as angiogenesis and vascular remodeling both regulated by proliferation and apoptosis, anti-thrombotic properties, regulation of vascular tone, control in the passage of nutrients and secretion of peptides and growth factors. However, EC are characterized by site-specificity so their characteristics depend on the organs and tissues where they are. The IGF system induces important growth factors that control cell growth in different microvascular EC (mEC)...
September 2006: Journal of Endocrinological Investigation
Ulf Panzer, Oliver M Steinmetz, Rüdiger R Reinking, Tobias N Meyer, Susanne Fehr, André Schneider, Gunther Zahner, Gunter Wolf, Udo Helmchen, Patrick Schaerli, Rolf A K Stahl, Friedrich Thaiss
The recruitment of inflammatory cells into renal tissue, mainly T cells and monocytes, is a typical feature of various renal diseases such as glomerulonephritis, thrombotic angiopathies, allograft rejection, and vasculitis. T cells predominantly infiltrate the tubulointerstitium, whereas monocytes are present in the tubulointerstitial and glomerular compartment. Because chemokines play a pivotal role in leukocyte trafficking under inflammatory conditions, this study investigated whether a differential expression of chemokines contributes to the precise coordination of leukocyte subtype trafficking in a rat model of renal microvascular endothelial injury...
February 2006: Journal of the American Society of Nephrology: JASN
Nikolaos P Kadoglou, Stella S Daskalopoulou, Despina Perrea, Christos D Liapis
Diabetes mellitus (DM) is associated with an increased incidence of cardiovascular events and microvascular complications. These complications contribute to the morbidity and mortality associated with DM. There is increasing evidence supporting a role for matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of matrix metalloproteinases - TIMPs) in the atherosclerotic process. However, the relationship between MMPs/TIMPs and diabetic angiopathy is less well defined. Hyperglycemia directly or indirectly (eg, via oxidative stress or advanced glycation products) increases MMP expression and activity...
March 2005: Angiology
J A Colwell
People with type II diabetes have a twofold to fourfold increased risk of dying from the complications of cardiovascular disease. Atherosclerosis and vascular thrombosis are major contributors. The increased risk is present before fasting hyperglycemia is seen. These individuals often have a sedentary life-style, poor physical conditioning, insulin resistance, centripetal obesity, hypertension, dyslipidemia, and a prothrombotic state. Chronic hyperglycemia is then added to these risk markers. Microalbuminuria may precede hyperglycemia in type II diabetes, occurs in 30% to 40% of these individuals after diabetes is established, and is a predictor of cardiovascular events...
December 1997: Metabolism: Clinical and Experimental
P E Jennings
Patients with type II diabetes commonly die from thrombotic vascular disease. Large vessel occlusion due to thrombosis or atherosclerotic stenosis is a process accelerated by diabetes and results in premature death. Diabetic small vessel disease, with its unique microangiopathic process, underlies many of the large vessel changes as well as causing retinopathy and nephropathy. The microangiopathic changes produce a prothrombotic tendency that has been widely reported in type II diabetes. There is reduced endothelial cell production of prostacyclin and the activators of fibrinolysis, together with increased platelet reactivity...
October 1994: Journal of Diabetes and its Complications
S E Richardson, M A Karmali, L E Becker, C R Smith
Verocytotoxin-producing Escherichia coli (VTEC) infection was present in three cases of hemolytic uremic syndrome (HUS), two fatal and one non-fatal, in which detailed histopathologic investigations were conducted. Two patients had a prodrome of bloody diarrhea, one of whom required a hemicolectomy for severe bleeding. The renal histopathology was characterized primarily by glomerular thrombotic microangiopathy (TMA) with greater than 95% of glomeruli showing changes of capillary wall thickening, endothelial cell swelling, and narrowing or thrombosis of the capillary lumen...
September 1988: Human Pathology
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