Maintaining blood flow in the extracorporeal circuit: haemostasis and anticoagulation

Webb, Andrew R.; Mythen, Monty; Jacobson, D.; Mackie, IJ

doi:10.1007/bf02425162

Cited by 61 publications

(35 citation statements)

References 60 publications

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“…Heparin is widely used as an anticoagulant in hemodialysis (48). Although no significant difference in the prevalence of A␤2M amyloidosis was found between patients on continuous ambulatory peritoneal dialysis and those on hemodialysis carefully matched for time on dialysis and age at the onset of dialysis (49), the present study suggests that heparin could exert a subtle effect for the development of A␤2M amyloidosis under some clinical conditions.…”

Section: Molecular Environment Of A␤2m Amyloid Deposition In Vivocontrasting

confidence: 49%

Glycosaminoglycans Enhance the Trifluoroethanol-Induced Extension of β2-Microglobulin–Related Amyloid Fibrils at a Neutral pH

Yamamoto¹,

Yamaguchi²,

Hara³

et al. 2004

Journal of the American Society of Nephrology

143

140

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Abstract. ␤ 2 -Microglobulin-related (A␤2M) amyloidosis is a frequent and serious complication in patients on long-term dialysis, and ␤ 2 -microglobulin is a major structural component of A␤2M amyloid fibrils. Several biologic molecules inhibiting the depolymerization of A␤2M amyloid fibrils at a neutral pH were found recently. The effect of trifluoroethanol and glycosaminoglycans (GAG) on the extension of the fibrils at a neutral pH was investigated with the use of fluorescence spectroscopy with thioflavin T, circular dichroism spectroscopy, and electron microscopy. Trifluoroethanol at concentrations of up to 20% (vol/vol) caused fibril extension of heparin-stabilized seeds, inducing a subtle change in the tertiary structure of ␤ 2 -microglobulin and stabilizing the fibrils at a neutral pH. This extension reaction followed a first-order kinetic model. In addition, some GAG, especially heparin, dose-dependently enhanced the fibril extension. These results suggest that some GAG, especially heparin, may bind to the fibrils and enhance their deposition in vivo. Thus, the experimental system described here should be useful to search for the factors that accelerate A␤2M amyloid deposition in vivo. In addition, the interference of the binding of GAG to A␤2M amyloid fibrils may be an attractive therapeutic modality.␤ 2 -Microglobulin-related (A␤2M) amyloidosis is a frequent and serious complication in patients on long-term dialysis (1). Carpal tunnel syndrome and destructive arthropathy associated with cystic bone lesions are the major clinical manifestations of A␤2M amyloidosis (2,3). Several biochemical and cell biologic studies have revealed that intact ␤ 2 -microglobulin (␤2-m) is a major structural component of amyloid fibrils deposited in the synovial membrane of the carpal tunnel (4 -7), but the mechanism of the deposition of these amyloid fibrils is still incompletely understood. Although the retention of ␤2-m in the plasma seems to be prerequisite (8), other factors, such as the age of the patient, the duration of dialysis, and the type of dialysis membrane used, may also be involved (9 -11).We and other groups have proposed that a nucleationdependent polymerization model could explain the general mechanism of amyloid fibril formation in vitro, in various types of amyloidosis (12)(13)(14)(15)(16)(17). This model consists of two phases: a nucleation phase and an extension phase. Nucleus formation requires a series of association steps of monomers, which are thermodynamically unfavorable, representing the rate-limiting step in amyloid fibril formation in vitro. Once the nucleus (n-mer) has been formed, further addition of monomers becomes thermodynamically favorable, resulting in rapid extension of amyloid fibrils according to a first-order kinetic model (12,14,16).The extension of A␤2M amyloid fibrils, as well as the formation of the fibrils from ␤2-m, is greatly dependent on the pH of the reaction mixture, with the optimum pH at approximately 2.0 to 3.0 (16,17). However, they readily depolymerize into monomeri...

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Section: Molecular Environment Of A␤2m Amyloid Deposition In Vivocontrasting

confidence: 49%

Glycosaminoglycans Enhance the Trifluoroethanol-Induced Extension of β2-Microglobulin–Related Amyloid Fibrils at a Neutral pH

Yamamoto¹,

Yamaguchi²,

Hara³

et al. 2004

Journal of the American Society of Nephrology

143

140

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“…Even though the retrospective design of this study did not allow a direct comparison with other anti-haemostatic strategies, our experience strongly suggests that prostacyclin does not carry an unduly high risk of bleeding complications or substantial haemodynamic intolerance while keeping the extracorporeal circuit patent long enough to allow the delivery of an adequate dose of renal replacement therapy. Platelets are considered key factors in the genesis of circuit clotting during extracorporeal circulation, whatever the anticoagulation protocol used [3,5,22,31]. Extracorporeal circulation activates platelets by foreign surface contact, shear stress, air-blood interaction and mechanical damage [22].…”

Section: Discussionmentioning

confidence: 99%

“…Extracorporeal circulation activates platelets by foreign surface contact, shear stress, air-blood interaction and mechanical damage [22]. By inducing platelet dysfunction and consumption, these stimuli can paradoxically increase the risk of both circuit clotting and patient bleeding [5,10,31,32,33,34,35,36].…”

Section: Discussionmentioning

confidence: 99%

Continuous haemofiltration in acute renal failure with prostacyclin as the sole anti-haemostatic agent

et al. 2002

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“…Successful application of CRRT, however, depends on adequate extracorporeal circuit (EC) life. The duration of EC life in turn hinges on anticoagulation [5]. The need for anticoagulation has to be balanced against the increased risk of bleeding in high-risk patients.…”

Section: Introductionmentioning

confidence: 99%

Continuous veno-venous hemofiltration without anticoagulation in high-risk patients

2000

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Maintaining blood flow in the extracorporeal circuit: haemostasis and anticoagulation

Cited by 61 publications

References 60 publications

Glycosaminoglycans Enhance the Trifluoroethanol-Induced Extension of β2-Microglobulin–Related Amyloid Fibrils at a Neutral pH

Glycosaminoglycans Enhance the Trifluoroethanol-Induced Extension of β2-Microglobulin–Related Amyloid Fibrils at a Neutral pH

Continuous haemofiltration in acute renal failure with prostacyclin as the sole anti-haemostatic agent

Continuous veno-venous hemofiltration without anticoagulation in high-risk patients

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