Lip G.Y.H.,University of Birmingham |
Durrani O.M.,Birmingham and Midlands Eye Center |
Roldan V.,Centro Regional Of Hemodonacion |
Lip P.L.,Birmingham and Midlands Eye Center |
And 3 more authors.
International Journal of Clinical Practice | Year: 2011
Increasing number of patients presenting for ophthalmic surgery are using oral anti-coagulant and anti-platelet therapy. The current practice of discontinuing these drugs preoperatively because of a presumed increased risk of bleeding may not be evidence-based and could pose a significant risk to the patient's health. To provide an evidence-based review on the peri-operative management of ophthalmic patients who are taking anti-thrombotic therapy. In addition, we briefly discuss the underlying conditions that necessitate the use of these drugs as well as management of the operative field in anti-coagulated patients. A semi-systematic review of literature was performed. The databases searched included MEDLINE, EMBASE, database of abstracts of reviews of effects (DARE), Cochrane controlled trial register and Cochrane systematic reviews. In addition, the bibliographies of the included papers were also scanned for evidence. The published data suggests that aspirin did not appear to increase the risk of serious postoperative bleeding in any type of ophthalmic surgery. Topical, sub-tenon, peri-bulbar and retrobulbar anaesthesia appear to be safe in patients on anti-thrombotic (warfarin and aspirin) therapy. Warfarin does not increase the risk of significant bleeding in most types of ophthalmic surgery when the INR was within the therapeutic range. Current evidence supports the continued use of aspirin and with some exceptions, warfarin in the peri-operative period. The risk of thrombosis-related complications on disruption of anticoagulation may be higher than the risk of significant bleeding by continuing its use for most types of ophthalmic surgery. © 2011 Blackwell Publishing Ltd. Source
Rivera J.,Centro Regional Of Hemodonacion
Hämostaseologie | Year: 2014
Hermansky-Pudlak syndrome (HPS) is a rare, autosomal recessive disorder affecting lysosome-related organelles (LRO), including dense platelet granules. HPS causes oculocutaneous hypopigmentation, bleeding diathesis and granulomatous colitis or pulmonary fibrosis. To date, there is no curative treatment and the clinical management depends on the severity of symptoms. A prompt diagnosis of HPS patients could improve their quality of life and clinical management. However, the absence of a specific platelet function test, the wide molecular heterogeneity, and the lack of phenotype-genotype correlations hamper the rapid diagnosis. Nine subtypes of HPS have been identified as a result of mutations in nine genes that codify for proteins involved in formation and shuttle of the LRO. The molecular characterization of patients and knowledge derived from animal models of HPS contribute to the understanding of biogenesis and function of the LRO. This paper describes a patient with a novel homozygous nonsense mutation causing HPS and provides a review of the literature focusing on recent advances in the molecular characterization and physiopathology of HPS. Source
Jover E.,University of Murcia |
Marin F.,University of Murcia |
Quintana M.,University of Murcia |
Perez-Andreu J.,University of Murcia |
And 6 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2015
Calumenin inhibits gamma-carboxylation of matrix-Gla-protein preventing BMP2-dependent calcification. Our aim was to explore the clinical relevance and functionality of the CALU polymorphism rs1043550, and the relationship of calumenin time-dependent expression profile with the active calcification of human vascular smooth muscle cells (hVSMC). Coronary artery calcium score and lesion severity were assessed by cardiac computed tomography in 139 consecutive low-risk patients genotyped for rs1043550. Polymorphic (G) allele carriage was associated with lower calcium (OR: 6.19, p= 0.042). Calcified arteries from CALU 'A' allele carriers undergoing cardiovascular surgery exhibited higher residual calcification, higher calumenin immunostaining and lower matrix-Gla-protein, contrary to 'G' allele carriers. In a luciferase reporter system in vascular cells, polymorphic 'G' allele reduced the mRNA stability by 30% (p<. 0.05). Osteogenic high-phosphate media induced active differentiation of hVSMC onto functional osteoblast-like cells as demonstrated by extracellular matrix mineralization and osteoblast markers expression. Calumenin was early over-expressed at day 3 (p<. 0.05), but decreased thereafter (mRNA and protein) with implications on gamma-carboxylation system. Calumenin was found released and co-localizing with extracellular matrix calcifications. The CALU polymorphism rs1043550 affects mRNA stability and tissue availability of calumenin thus supporting the protective clinical significance. Calumenin shows a time-dependent profile during induced calcification. These data demonstrate a novel association of vascular calcification with the VSMC phenotypic transition into osteoblast-like cells. Moreover, hyperphosphatemic stimuli render calumenin accumulation in the mineralized extracellular matrix. © 2015 Elsevier Ltd. Source
De La Morena Barrio P.,University of Murcia |
Conesa M.A.V.,University of Murcia |
Gonzalez-Billalabeitia E.,University of Murcia |
Urrego E.,University of Murcia |
And 6 more authors.
JNCCN Journal of the National Comprehensive Cancer Network | Year: 2015
Purpose: Although diabetes mellitus (DM) is recognized as a risk factor for chemotherapy-induced neurotoxicity, its true impact on intensity and time course of peripheral neuropathy is still unclear. The goal was to analyze the relevance of preexisting DM to weekly paclitaxel-induced peripheral neuropathy (PIPN). Methods: We performed a retrospective case-control study (1:2) including a total of 129 patients with breast cancer (43 with DM and 86 controls) treated with single-agent weekly paclitaxel (wP). Results: Compared with controls, patients with DM treated with wP experienced PIPN more frequently (74.4% vs 58.4%; P=.016) and with higher severity (grade 2-3: 51.2% vs 27.7%; P=.014). A significant delay in PIPN resolution was observed in women with DM (P=.001) and, in a multivariate analysis, DM was the only independent predictor for delayed recovery (hazard ratio [HR], 0.16; 95% CI, 0.05-0.55; P=.003). After 2 years, 68.7% of patients with DM (vs 29.2% of women without DM) still experienced PIPN, which was functionally significant (grade 2-3) in 18.2%. Conclusions: Significantly more dose delays and reductions because of PIPN occurred in patients with DM. Preexisting DM associates with long-lasting significant PIPN in patients treated with wP. Benefits and risks of long-term significant PIPN should be carefully balanced in patients with DM before starting wP chemotherapy. © JNCCN - Journal of the National Comprehensive Cancer Network. Source
Martinez-Martinez I.,Centro Regional Of Hemodonacion |
Ordonez A.,Centro Regional Of Hemodonacion |
Navarro-Fernandez J.,University of Murcia |
Perez-Lara A.,University of Murcia |
And 7 more authors.
Haematologica | Year: 2010
Background Identification of mutations in the SERPINC1 gene has revealed different mechanisms responsible for antithrombin deficiency. Deletions and nonsense mutations associate with type I deficiency. Certain missense mutations cause type II deficiency by affecting the heparin binding site or the reactive center loop, while others result in type I deficiency by intracellular retention or RNA instability. Design and Methods We studied the molecular, biochemical, proteomic and glycomic characterization of a new natural mutant (K241E) that may be classified as pleiotropic. Results The mutation caused a significant decrease in the anticoagulant activity mainly due to a reduced heparin affinity and a modification of the electrostatic potential that might explain the impaired ability of the mutant protein to form complexes with the target protease in the absence of heparin. Mass spectrometry and glycomic analyses confirmed an increased molecular weight of 800 Da in the mutant protein possibly due to core-fucosylation, provoking the loss of heparin affinity. Additionally, carriers of this mutation also have a minor mutant isoform that still followed normal glycosylation, retaining similar heparin affinity to wild-type α-antithrombin, and certain anticoagulant activity, which may explain the milder thrombotic risk of patients carrying this mutation. Similar results were observed using recombinant K241E antithrombin molecules. Conclusions Our data suggest a new mechanism involved in antithrombin type II deficiency by indirectly affecting the glycosylation of a natural variant. Additional studies are required to confirm this hypothesis. © 2010 Ferrata Storti Foundation. Source