A hemodialysis cohort study of protocol-based anticoagulation management.

BACKGROUND: Chronic hemodialysis patients frequently require anticoagulation treatment with warfarin for a variety of co-morbidities. The optimal method for monitoring and dose adjustment of warfarin-based anticoagulation in this population, however, remains unclear. To examine this more closely, we reviewed all hemodialysis patients at a single institution on chronic warfarin therapy for a 10-month period prior to and after the institution of a standardized protocol for warfarin dose adjustment and monitoring. Anticoagulation efficacy was assessed by time within the therapeutic INR range (TTR), and resource utilization was assessed by the number of weekly INR measurements required for monitoring. RESULTS: We retrospectively analyzed 4481 patient-days of warfarin therapy data (from 25 hemodialysis patients) in the pre-protocol timeframe, and 3308 patient-days of warfarin therapy data (from 21 hemodialysis patients) in the on-protocol timeframe. Time within the therapeutic INR range (TTR) did not improve with institution of the dosing protocol-51.18% using non protocol-based management, and 51.57% using protocol-based management (p 0.73). However, overall resource utilization was reduced with institution of protocolized warfarin monitoring-from 1.71 INR measurements per patient-week pre-protocol, to 1.20 INR measurements per patient-week (p < 0.0001) post-protocol. CONCLUSIONS: In this single-center study, institution of a standardized dosing protocol in a hemodialysis population on chronic warfarin therapy did not improve the rate of on-target anticoagulation, but did result in significantly lower resource utilization. We support protocol-based warfarin management in the hemodialysis population, but future work should examine the rate of on-target anticoagulation typically achieved in this group.

Differential effects of TGFbeta and vitreous on the transformation of retinal pigment epithelial cells.

PURPOSE: In proliferative vitreoretinopathy retinal pigment epithelial (RPE) cells undergo epithelial-mesenchymal transformation (EMT). Vitreous and transforming growth factor-beta (TGFbeta) have been implicated in this EMT. The role of TGFbeta in the vitreous-mediated transformation of low-passage human RPE cells was investigated. METHODS: Cells were treated with vitreous or TGFbeta2. SB431542 was used to inhibit TGFbeta signaling. Morphology was investigated using phase-contrast or confocal microscopy. Motility was measured using a monolayer-wounding assay. Invasion was determined using basement membrane matrix-based assays. Gene expression was measured by quantitative PCR, immunohistochemistry, or immunoblotting. RESULTS: Changes in phosphorylation or cellular localization of Smad -2, -3, or -4 indicated a TGFbeta-like activity in vitreous. Cortical actin filaments in untreated cells were replaced by stress fibers after TGFbeta treatment, but peripheral actin aggregates were seen in vitreous-treated cells. SB431542 did not block the morphologic change induced by vitreous. Vitreous-treated cells exhibited increased motility and invasion, whereas TGFbeta-treated cells did not. However, SB431542 decreased vitreous-meditated changes in motility and invasion. The levels of mRNA for genes indicative of myofibroblast differentiation (alpha-SMA and CTGF) were increased by treatment with TGFbeta but suppressed by vitreous. TGFbeta or vitreous caused increased expression of Snail1. CONCLUSIONS: Vitreous or TGFbeta caused a fibroblast-like morphology and induced Snail1, a marker of EMT. TGFbeta activity in vitreous was necessary but not sufficient for the vitreous-induced motile, invasive phenotype. However, differences in the cytoskeletal organization and in the expression of CTGF and alpha-SMA suggested that TGFbeta-treatment caused differentiation along a myofibroblast pathway, whereas vitreous treatment suppressed myofibroblast formation.