1,721,027 research outputs found
Thrombophilia in young women candidate to the pill: Reasons for and against screening
No full textScreening for thrombophilia in women candidate to the pill is still a matter of debate. Oral contraceptives may trigger venous thromboembolic events in carriers of common inherited thrombophilic defects. General screening is not cost-effective from an epidemiological point of view if the objective is to prevent death due to venous thromboembolism during oral contraception (OC). However, clinicians deal with single patients and personal and/ or family history for venous thromboembolism have limited value for identifying those women at risk of VTE complications during OC. A pharmacogenetics approach in prescribing OC on the basis of each woman's genetic make-up could increase drug safety. A proper evaluation of the cost-effectiveness, the medical, psychosocial and legal consequences is needed before general screening with genetic testing for inherited thrombophilia can be recommended before OC. Copyright © 2002 S. Karger AG. Basel
Development and use of sulodexide in vascular diseases: implications for treatment
Full text linkSergio Coccheri,1 Ferdinando Mannello2 1Cardiovascular Medicine, University of Bologna, Bologna, 2Department of Biomolecular Sciences (Section Clinical Biochemistry and Cell Biology), University 'Carlo Bo', Urbino, Italy Abstract: Sulodexide (SDX), a sulfated polysaccharide complex extracted from porcine intestinal mucosa, is a blend of two glycosaminoglycan (GAG) entities, namely a fast-moving heparin (HP) fraction and a dermatan sulfate (DS; 20%) component. The compound is unique among HP-like substances in that it is biologically active by both the parenteral and oral routes. A main feature of the agent is to undergo extensive absorption by the vascular endothelium. For this reason, in preclinical studies, SDX administered parenterally displays an antithrombotic action similar to that of HPs but associated with fewer alterations of the blood clotting mechanisms and tests, thus being much less conducive to bleeding risk than HPs. When given orally, SDX is associated with minimal changes in classic coagulation tests, but maintains a number of important effects on the structure and function of endothelial cells (EC), and the intercellular matrix. These activities include prevention or restoration of the integrity and permeability of EC, counteraction versus chemical, toxic or metabolic EC injury, regulation of EC–blood cell interactions, inhibition of microvascular inflammatory and proliferative changes, and other similar effects, thus allowing oral SDX to be considered as an endothelial-protecting agent. The best available clinical evidence of the efficacy of SDX administered orally with or without an initial parenteral phase is the following: alleviation of symptoms in chronic venous disease and especially acceleration of healing of venous leg ulcers; prevention of cardiovascular events in survivors after acute myocardial infarction; marked improvement of intermittent claudication in patients with peripheral occlusive arterial disease; and abatement of proteinuria in patients with diabetic nephropathy that may contribute to the amelioration or stabilization of kidney function. Although further clinical trials are warranted, SDX is presently widely accepted in many countries as an effective and safe long-term, endothelial-protecting drug. Keywords: sulodexide, glycosaminoglycans, chronic venous disease, cardiovascular disease, diabetic nephropath
Role of family history in identifying women with thrombophilia and higher risk of venous thromboembolism during oral contraception
No full textBackground: Unrecognized thrombophilic defects increase the risk of venous thromboembolism (VTE) in women during oral contraception (OC). We evaluated the sensitivity and specificity of a family history of VTE to identify thrombophilia in women before OC and after venous thrombotic complications during OC. Methods: Thrombophilia screening was performed after obtaining a family history by means of a standardized questionnaire in (1) thrombosis-free women before OC and (2) women after an episode of VTE during OC. Results: We evaluated 479 thrombosis-free women before OC (age range, 15-49 years); family history was positive in 49 (10.2%). Thrombophilic defects were identified in 36 participants (7.5%; 95% confidence interval [CI], 5%-10%), 3 of whom had a positive family history (8.3%). The sensitivity and positive predictive value of family history of thrombophilic defects were 8.3% (95% CI, 2%-22%) and 6.1% (95% CI, 1%-17%), respectively. We also evaluated 189 women after VTE complications during OC (age range, 15-49 years); family history was positive in 48 (25.4%; 95% CI, 19%-32%), 22 of whom had a thrombophilic defect (45.8%; 95% CI, 31%-61%). Thrombophilic defects were identified in 81 women (42.8%; 95% CI, 36%-50%). The sensitivity and positive predictive value of family history of thrombophilic defects were 27.2% (95% CI, 18%-38%) and 45.8% (95% CI 31%-61%), respectively. Conclusion: Family history of VTE has low sensitivity and positive predictive value for identifying women with thrombophilia who are more susceptible to VTE complications during OC
Value of family history in identifying women at risk of venous thromboembolism during oral contraception: Observational study
No full textCommon inherited thrombophilic defects such as factor V Leiden and G20120A mutation of the prothrombin gene inter act synergistically with oral contraceptives to increase the risk of venous thromboembolism.(1 2) The best approach to identify women at higher risk of venous thromboembolism before taking oral contraceptives is controversial. Universal screening is not cost effective because 8000 women need to be screened for factor V Leiden to detect 400 mutations and prevent one episode of venous thromboembolism.(1) Many authors recommend selective screening in women with a personal or family history of venous thromboembolism.(1) However; the effectiveness of this approach has not been proved, The aim of our study was to evaluate the sensitivity and positive predictive value of a family history of venous thromboembolism for identifying common thrombophilic defects in women without thrombosis before taking oral contraceptives
Clinical, functional and quality of life changes after balneokinesis with sulphurous water in patients with varicose veins
No full textBackground: Purpose of this study was to assess the effects of thermal hydrotherapy (balneokinesis) with a sulphurous water on clinical symptoms, quality of life and some functional parameters in patients with varicose veins. Patients and methods: 70 patients with primary or secondary symptomatic varicosis were enrolled and submitted to elastic compression therapy.Patients were then randomized to receive (50 pts, group A) or not receive (20 pts, group B) balneokinetic treatment for 12 days "on top" of elastic compression. Clinical symptoms, quality of life and functional parameters obtained with light reflex plethysmography (PPG) and laser Doppler fluxmetry (LDF) were assessed after 3 and 6 months.Results: Scores for subjective symptoms as pain, edema, and venous claudication were decreased after 6 months in both groups, but more evidently in group A submitted to balneokinesis. Some parameters related to quality of life evaluation as "bodily pain" and "emotional role" were improved only in patients undergoing balneokinesis. Regarding functional parameters, with PPG venous refilling time after foot exercise moderately increased in both groups. With LDF a significant improvement in the veno-arteriolar reflex was seen in the group treated with balneokinesis.Conclusions: These results show additional benefits of balneokinetic treatment in patients with symptomatic varices submitted to elastic compression. In fact, clinical and quality of life improvements were observed. The associated amelioration in the veno-arteriolar reflex may, support these subjective benefits
A Placebo-controlled, Double-blind Study of Mesoglycan in the Treatment of Chronic Venous Ulcers
No full textAbstractObjectives to assess the effect of treatment with mesoglycan, a sulphated polysaccharide compound, on the healing of venous ulcers. Design randomised, placebo-controlled, double-blind, multicentre trial. Methods non-diabetic outpatients with chronic venous insufficiency confirmed by duplex ultrasound, normal ankle/arm pressure index and presence of a leg ulcer were eligible. Patients were randomised to mesoglycan, 30 mg/day intramuscularly for 3 weeks followed by 100 mg/day orally, or matching placebo, as an adjunct to compression therapy and topical wound care. Treatment and observation were continued until complete ulcer healing or for 24±1 weeks. Time to ulcer healing and healing rates were estimated with the Kaplan–Meier method. Results One hundred and eighty-three patients were randomised and included in the analysis (92 mesoglycan, 91 placebo). Median ulcer area upon inclusion was 3.6 cm2in the mesoglycan group and 3.9 cm2in the placebo group. The estimated time to heal 75% of the patients was 90 days on mesoglycan versus 136 days on placebo, while the cumulative rate of healing by the end of observation was 97% versus 82%, respectively. The difference in favour of mesoglycan was statistically significant (p<0.05, centre-stratified Cox's model). The relative risk of ulcer healing with mesoglycan was 1.48. The rate of adverse events was 7/92 on mesoglycan and 6/91 on placebo. Conclusions treatment with mesoglycan in addition to established venous ulcer therapy resulted in a significantly faster and more frequent ulcer healing, and did not raise any safety concerns
Venous thromboembolism, oral contraceptives and high prothrombin levels
No full textTheG20210A prothrombin mutation, associated with elevated prothrombin levels, is a risk factor for venous thromboembolism (VTE) and displays a strong interaction with oral contraceptives (OC). Nodata are available onVTE risk ofOCuse in women with high prothrombin levels, either associated or not with themutation. The aim of this study was to evaluate the risk of VTE in OC users with high prothrombin levels, either including or excluding carriers of the prothrombin mutation. Prothrombin levels were measured by a chromogenic assay in 152 women who suffered from VTE in reproductive age and in 296 healthy women. Subjects carrying thrombophilic alterations other than the G20210A prothrombin mutation were excluded. Prothrombin levels were stratified into quartiles. The OR of subjects in the upper quartile were 3.10[95%confidence interval (CI)1.73-5.55] and2.07(95%CI1.11-3.85)in all women and in those not carrying the prothrombin mutation, respectively. Among the 152 patients, 88 had experienced VTE during OC; in the control group we considered as OC users the women who had used OC for at least 6 months in the 2 years before presentation but had stopped the treatment at least 3 months before the time of blood sampling (n=127).For the interaction betweenOCand prothrombin levels only the two extreme strata of prothrombin were considered. Women with the lowest prothrombin levels and who did not use OC were used as reference category. The VTE risk of using OC in subjects with prothrombin levels in the upper quartile was increased5.4-fold (95%CI2.38-12.3) and3.5-fold (95%CI1.48-8.22) in all women and in those not carrying the prothrombin mutation, respectively. We conclude that elevated prothrombin levels, even in women without the G20210A prothrombin mutation, are associated with an increased risk for venous thromboembolism and that oral contraceptive use potentiates such association. © 2003 International Society on Thrombosis and Haemostasis
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Additive thrombin inhibition by fast moving heparin and dermatan sulfate explains the anticoagulant effect of sulodexide, a natural mixture of glycosaminoglycans
No full textIntroduction: The aim of the study was to evaluate the mechanism of the anticoagulant action of sulodexide, a mixture of glycosaminoglycans (GAGs) composed of dermatan sulfate (DS) and fast moving heparin (FMH), in vitro. Materials and methods: Thrombin clotting time (TCT) was measured in human platelet poor plasma (PPP). A chromogenic substrate assay was used to determine the pseudo-first order constant kinetic of thrombin inhibition (k′=kobs/min) either in defibrinated PPP or antithrombin (AT) or heparin cofactor II (HCII) depleted defibrinated PPP in the absence and presence of sulodexide or its components, alone and in combination. The interaction between DS and FMH was analysed by both the algebraic fractional and isobole graphical methods. Results: Sulodexide, DS and FMH produced a dose-dependent prolongation of TCT with unclottable TCT at sulodexide above 4 μg/ml and at DS or FMH above 5 μg/ml. Sulodexide and its components alone and in combination produced a dose-dependent linear increase in the rate of thrombin inhibition in defibrinated PPP. The algebraic fractional and the isobole graphical methods indicated an additive effect between DS and FMH. In AT depleted PPP, the dose-dependent increase in k′ produced by sulodexide was significantly lower than in PPP, while the dose-dependent increase in k′ produced by DS was similar to the increase produced in PPP. In HCII depleted PPP, the dose-dependent increase in k′ produced by sulodexide was significantly lower than in PPP, while the dose-dependent increase in k′ produced by FMH was similar to the increase produced in PPP. Conclusions: Thrombin inhibition produced by sulodexide is due to the additive effect of its components, namely, HCII catalysis by DS and AT catalysis by FMH. © 2003 Elsevier Science Ltd. All rights reserved
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