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Anticoagulants
Kinds of Anticoagulants Terms modified by Anticoagulants Selected AbstractsRegulation of Thrombin Activity with a Bifunctional Aptamer and Hemin: Development of a New Anticoagulant and Antidote PairCHEMBIOCHEM, Issue 13 2009Jing Wang Through thick and thin: A bifunctional aptamer (BA) and hemin have been designed as an anticoagulant and antidote pair. BA, as anticoagulant, inhibits thrombin by forming a BA,thrombin complex. Because of the higher affinity between hemin and BA, once hemin is added, it replaces thrombin to form a BA,hemin complex. Thrombin is then released and reactivated to exhibit blood-clotting activity. [source] Evolution of Anticoagulant and Antiplatelet Therapy: Benefits and Risks of Contemporary Pharmacologic Agents and Their Implications for Myonecrosis and Bleeding in Percutaneous Coronary InterventionCLINICAL CARDIOLOGY, Issue S2 2007Hector M. Medina M.D., M.P.H. Abstract Periprocedural myonecrosis, as evidenced by elevated creatine kinase,myocardial bound (CK-MB) levels, occurs in up to 25% of patients undergoing percutaneous coronary intervention (PCI) and has been linked with an increased risk of adverse short- and long-term clinical outcomes. Such myonecrosis arises from three main pathophysiological mechanisms: procedure-related complications, lesion-specific characteristics (e.g., large thrombus burden, plaque volume), and patient-specific characteristics (e.g., genetic predisposition, arterial inflammation). Periprocedural myonecrosis has not been definitively identified as the cause of postprocedural ischemic events, although agents that reduce or prevent thrombosis,including aspirin, thienopyridines, heparin, low-molecular-weight heparins, glycoprotein IIb/IIIa inhibitors, and direct thrombin inhibitors,have been shown to reduce the incidence of ischemic outcomes in this population, as have agents that reduce inflammation (aspirin, statins). At the same time, antithrombotic agents are known to increase the risk of bleeding and the use of transfusions, which have likewise been associated with worse outcomes in these patients. Thus, optimal management of patients undergoing PCI represents a balance between minimizing the risk of ischemic outcomes and simultaneously minimizing the risk of major bleeding. It may be that patients who have only minor, untreated postprocedural elevations in CK-MB level (with no clinical or angiographic signs of ischemia) might have a better prognosis than patients who have normal CK-MB levels but who suffer major bleeding complications. Copyright © 2007 Wiley Periodicals, Inc. [source] CLINICAL INVESTIGATION OF UPPER GASTROINTESTINAL HEMORRHAGE AFTER PERCUTANEOUS ENDOSCOPIC GASTROSTOMYDIGESTIVE ENDOSCOPY, Issue 3 2010Shinji Nishiwaki Background:, Upper gastrointestinal (GI) hemorrhage after percutaneous endoscopic gastrostomy (PEG) is sometimes reported as one of the serious complications. Our purpose was to clarify the cause of upper GI hemorrhage after PEG. Patients and Methods:, We retrospectively investigated the causes of upper GI hemorrhage among a total of 416 patients out of 426 consecutive patients who underwent PEG in our institution, excluding 10 patients who showed upper GI tumors on PEG placement. Results:, Among 17 patients who developed upper GI hemorrhage after PEG, three and four patients showed PEG tube placement and replacement-related hemorrhage, respectively; these lesions were vascular or mucosal tears around the gastrostomy site. Ten patients experienced 12 episodes of upper GI hemorrhage during PEG tube feeding. The lesions showing bleeding were caused by reflux esophagitis (five patients), gastric ulcer (two patients), gastric erosion due to mucosal inclusion in the side hole of the internal bolster (two patients), and duodenal diverticular hemorrhage (one patient). Anticoagulants were administered in six patients, including four patients with replacement-related hemorrhage and one patient each with reflux esophagitis and gastric ulcer. Conclusions:, Reflux esophagitis was the most frequent reason for upper GI hemorrhage after PEG. The interruption of anticoagulants should be considered for the prevention of hemorrhage on the placement as well as replacement of a gastrostomy tube. [source] Rivaroxaban , an oral, direct Factor Xa inhibitor , lessons from a broad clinical study programmeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2009Sylvia Haas Abstract Anticoagulants are recommended for the prevention and treatment of venous thromboembolism (VTE), prevention of stroke in patients with atrial fibrillation (AF) and secondary prevention in patients with acute coronary syndrome (ACS). There is a clinical need for novel anticoagulants offering improvements over current standard of care, such as fixed oral dosing and no need for routine monitoring. Rivaroxaban, an oral, once-daily, direct Factor Xa inhibitor, has recently completed the RECORD phase III programme for the prevention of VTE in patients undergoing total hip or knee replacement (THR or TKR), an indication for which it is approved in Europe and Canada. It is being investigated in large-scale phase III studies for VTE treatment and prevention of stroke in patients with AF, and phase III studies will soon commence for secondary prevention in patients with ACS. Phase I studies demonstrated that no routine anticoagulation monitoring was required, while phase II studies suggested that fixed daily doses had a wide therapeutic window. The four RECORD studies consistently showed that rivaroxaban was significantly more effective than enoxaparin in the prevention of VTE after THR and TKR, with a similar safety profile. This review describes the development of this novel anticoagulant, from bench to bedside. [source] The Use of Oral Anticoagulants (Warfarin) in Older PeopleJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 8 2002American Geriatrics Society guideline abstracted from Chest 2001;S119. First page of article [source] Catheter Ablation of Chronic Atrial Fibrillation Targeting the Reinitiating TriggersJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2000MICHEL HAÏSSAGUERRE M.D. Trigger Ablation in Chronic AF. Introduction: We assessed the mode of reinitiation of atrial fibrillation (AF) after cardioversion and the efficacy of ablating these foci of reinitiation in patients with chronic AF. Methods and Results: Fifteen patients, 7 with structural heart disease, underwent mapping and catheter ablation of drug-resistant AF documented to he persistent for 5 ± 4 months. In all patients, cardioversion was followed by documentation of P on T atrial ectopy and early recurrence, which allowed mapping of the reinitiating trigger or the source of ectopy. Radiofrequency (RF) ablation was performed at pulmonary vein (PV) ostia using a target temperature of 50°C and a power limit of 30 to 40 W, with the endpoint being interruption of all local muscle conduction. A total of 32 arrhythmogenic PVs and 2 atrial foci (left septum and left appendage) were identified: 1, 2, and 3 or 4 PVs in 5, 3, and 6 patients. RF applications at the ostial perimeter resulted in progressively increasing delay, followed by abolition of PV potentials in 8, but potentials persisted in 6. A single ablation session was performed in 7 patients and 8 underwent two or three sessions because of recurrence of AF; ablation was directed at the same source due to recovery of local PV potential or at a different PV. No PV stenosis was noted either acutely or at repeated follow-up angiograms. Nine patients (60%) were in stable sinus rhythm without antiarrhythmic drugs at follow-up of 11 ± 8 months. Anticoagulants were interrupted in 7 patients. Conclusion: PVs are the dominant triggers reinitiating chronic AF in this patient population. Elimination of PV potentials by ostial RF applications results in stable sinus rhythm in 60%. A larger group and longer follow-up are needed to investigate further the role of trigger ablation in curative therapy for chronic AF. [source] Do anticoagulants improve survival in patients presenting with venous thromboembolism?JOURNAL OF INTERNAL MEDICINE, Issue 6 2003J. Kelly Abstract. Anticoagulants have been available since around 1940 and have become the standard of treatment for venous thromboembolism (VTE) for over four decades. However, as with other treatments which became established before the evidence-based era, there is a paucity of evidence from randomized controlled trials validating their effectiveness in preventing the most feared complication of VTE, recurrent fatal pulmonary embolism (PE). Only two such trials have been performed, the results of which conflict. The bulk of data supporting their use are derived from three sources. First, studies of thromboprophylaxis, and comparisons of shorter and longer courses of anticoagulants in high-risk patients with established VTE have clearly demonstrated their effectiveness in primary and late secondary prevention. Given that heparin has an immediate onset of action, anticoagulants should therefore also be effective in early secondary prevention, the proposed mechanism of action in the acute treatment of VTE. Secondly, studies of inadequately treated patients have consistently shown higher recurrence rates than in those adequately treated. Finally, comparisons of outcomes in untreated and treated historical series, and of untreated historical series to treated series in the modern era have shown substantially lower rates of fatal PE in anticoagulated patients. Because these differences are so marked, harmonize with our current understanding of the mechanism of action of anticoagulants and are supported by other evidence, it is much more likely that they at least partly reflect the effectiveness of anticoagulants as opposed to being explicable purely in terms of accumulated biases and a changing distribution of disease severity. [source] Management of membranous nephropathyNEPHROLOGY, Issue 4 2000Daniel Cattran SUMMARY: The Management of membranous nephropathy requires a recognition of its natural history and an ability to predict those pationts with the worst prognosis. Treatment of those at risk of progression with immunosuppressive drugs should be accompanied by additional conservative risk reduction strategies such as dietary protein restriction, blood pressure reduction, angiotensin-converting enzyme inhibitors and lipid-lowering agents. Anticoagulants should also be considered as well as medications to reduce drug toxicity. [source] Investigation of Direct Toxic and Teratogenic Effects of Anticoagulants on Rat Embryonic Development Using In Vitro Culture Method and Genotoxicity AssayANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2 2006I. I. Uysal Summary Heparin and low molecular weight heparins (LMWHs) are used to reduce the incidence of venous thromboembolism in pregnancy. Although, these agents have been shown to be safe when used during pregnancy, the studies about direct toxic and teratogenic effects of these drugs on embryonic development are limited. In this study, the effects of heparin and LMWHs on rat embryonic development were investigated by using in vitro embryo culture and micronucleus (MN) assay methods. Rat embryos were cultured in vitro in the presence of different concentrations of heparin (5,40 IU/ml), dalteparin (2.5,20 IU/ml), enoxaparin (25,100 ,g/ml) and nadroparin (1,4 IU/ml). Effects of anticoagulants on embryonic developmental parameters were compared and embryos were evaluated for the presence of any malformations. After culturing the embryos, classic MN assay was performed. Anticoagulants significantly decreased all growth and developmental parameters dose-dependently. Dalteparin and enoxaparin were found to cause more developmental toxicity than heparin and nadroparin. Along with haematoma in general, heparin and nadroparin caused maxillary deformity, situs inversus and oedema most frequently, while neural tube defects were observed with dalteparin and enoxaparin. All agents also significantly induced MN formation in rat embryonic blood cells. These results indicate the possible genotoxic effects of anticoagulant agents on the developing rat embryo when applied directly. [source] Anticoagulants in pediatric cerebral sinovenous thrombosis: A safety and outcome studyANNALS OF NEUROLOGY, Issue 5 2010Mahendranath D. Moharir MBBS Objective Clinical trials are lacking in pediatric cerebral sinovenous thrombosis (CSVT). Neonates and children increasingly receive anticoagulant therapy (ACT) based on adult studies. Safety data for ACT in pediatric CSVT are scant and urgently needed. The objective was to assess the safety and outcome of ACT in pediatric CSVT. Methods In a single-center prospective study, neonates and children with CSVT received ACT (standard/low molecular weight heparin, warfarin) by standardized protocol. A study neuroradiologist (M.S.) assessed all initial and follow-up neuroimaging for intracranial hemorrhage (ICH), thrombus propagation, and recanalization. Clinical outcome was assessed with the Pediatric Stroke Outcome Measure. Results Among 162 pediatric patients, 85 received ACT at diagnosis, including 29/83 (35%) neonates and 56/79 (71%) children. Major hemorrhage occurred in 6% (6/99) of treated patients, including 14% (3/21 neonates, 2/15 children) with and 2% (0/17 neonates, 1/46 children) without pretreatment ICH. ACT-associated bleeds were all nonfatal, and clinical outcome was favorable in 50%, similar to the remaining patients (53%). Early follow-up imaging demonstrated thrombus propagation in 11/57 neonates (10/35 [28%] without and 1/22 [4%] with ACT [p = 0.037]) and 10/63 children (7/19 [37%] without and 3/44 [7%] with ACT [p = 0.006]). Propagation was associated with new venous infarcts in 10% neonates and 40% children and worse clinical outcome in children (p = 0.053). Recanalization occurred earlier and more completely in neonates (p = 0.002). Clinical outcome was unfavorable in 47%. Interpretation In pediatric CSVT, ACT appears safe. Nontreatment with ACT is associated with thrombus propagation, observed in ¼ of untreated neonates and over , of children. Anticoagulants merit strong consideration in pediatric CSVT. ANN NEUROL 2010;67:590,599 [source] Long-term Management of an Implantable Left Ventricular Assist Device Using Low Molecular Weight Heparin and Antiplatelet Therapy: A Possible Alternative to Oral AnticoagulantsARTIFICIAL ORGANS, Issue 5 2007Bart Meuris Abstract:, Between January 2004 and December 2005, out of 14 patients with decompensated heart failure who were treated with an INCOR left ventricular assist device (Berlin Heart AG, Berlin, Germany), 10 patients were kept on a long-term regime of low molecular weight heparin (LMWH) and antiplatelet therapy. The treatment objective was bridge-to-transplantation. All patients received LMWH in therapeutic doses according to body weight, in combination with daily aspirin 160 mg, clopidogrel 75 mg, and three times dipyridamole 75 mg. Effectiveness of the low molecular weight regime was monitored through measurement of antifactor Xa activity (base and peak levels). Antiplatelet therapy was monitored through weekly platelet function tests. Within this group of 10 patients, six patients successfully received transplants and four patients died, the latest death after 405 days of INCOR support. Causes of death were sepsis, intestinal hemorrhage, acute right ventricular failure, and one major stroke. Long-term management of INCOR assist devices using a combination of LMWH and antiplatelet therapy is feasible. This treatment strategy can serve as an alternative to oral anticoagulants. [source] Relationship between antithrombotic activities of fucans and their structureDRUG DEVELOPMENT RESEARCH, Issue 4 2000Catherine Boisson-Vidal Abstract A low molecular weight fucan fraction extracted from the brown seaweed Ascophyllum nodosum was previously shown to exhibit dose-related venous antithrombotic activity with an ED80 of about 20 mg/kg, 2 h after a single subcutaneous injection HCII (Colliec et al. [1991] Thromb Res 64:143,154; Mauray et al. [1995] Thromb Haemast 74:1280,1285). Its activity was comparable to that of a low molecular weight heparin (Dalteparin®). This fucan fraction is one of several, with a range of different structure parameters, prepared by degradation of the whole native fucan. These low molecular weight fractions were compared using a Wessler stasis thrombosis model in rabbits and by determination of their in vitro and ex vivo anticoagulant activities. Intravenous administrations of these fractions reduced thrombosis in a dose-dependent manner. Partial removal of sulfate groups and/or partial degradation lead to a significant decrease in their anticoagulant and antithrombotic activities. The integrity of the regular pattern of sulphation of the fucoidan is necessary for antithrombotic activity. Drug Dev. Res. 51:216,224, 2000. © 2001 Wiley-Liss, Inc. [source] Rivaroxaban , an oral, direct Factor Xa inhibitor , lessons from a broad clinical study programmeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2009Sylvia Haas Abstract Anticoagulants are recommended for the prevention and treatment of venous thromboembolism (VTE), prevention of stroke in patients with atrial fibrillation (AF) and secondary prevention in patients with acute coronary syndrome (ACS). There is a clinical need for novel anticoagulants offering improvements over current standard of care, such as fixed oral dosing and no need for routine monitoring. Rivaroxaban, an oral, once-daily, direct Factor Xa inhibitor, has recently completed the RECORD phase III programme for the prevention of VTE in patients undergoing total hip or knee replacement (THR or TKR), an indication for which it is approved in Europe and Canada. It is being investigated in large-scale phase III studies for VTE treatment and prevention of stroke in patients with AF, and phase III studies will soon commence for secondary prevention in patients with ACS. Phase I studies demonstrated that no routine anticoagulation monitoring was required, while phase II studies suggested that fixed daily doses had a wide therapeutic window. The four RECORD studies consistently showed that rivaroxaban was significantly more effective than enoxaparin in the prevention of VTE after THR and TKR, with a similar safety profile. This review describes the development of this novel anticoagulant, from bench to bedside. [source] Appraisal of current vitamin K dosing algorithms for the reversal of over-anticoagulation with warfarin: the need for a more tailored dosing regimenEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2006Elizabeth A. Sconce Abstract:, Warfarin is the most commonly prescribed oral anticoagulant in the UK for the treatment and prevention of thromboembolic disorders. Vitamin K administration is an effective way of reversing excessive anticoagulation. Over-anticoagulated patients present with a wide range of international normalized ratio (INR) values and may respond differently to a fixed dose of vitamin K. Current dosing algorithms for vitamin K administration in the non-urgent treatment of over-anticoagulation do not take this variability in response into account. Consequently, over a third of over-anticoagulated patients still remain outside their target INR 24 h after treatment. Such patients are therefore prone to either haemorrhage (if the patient is still over-anticoagulated) or thromboembolism (if the INR reversal is over-corrected). A number of factors such as patient age, body weight, co-morbidity, frailty, warfarin daily dose and CYP2C9 and VKORC1 polymorphism could affect response to vitamin K and thus the rate and extent of INR reversal. There is a need for a more individualized approach to the reversal of over-anticoagulation in asymptomatic or mildly haemorrhagic patients in order to improve the safety of warfarin therapy. [source] Mouse recombinant protein C variants with enhanced membrane affinity and hyper-anticoagulant activity in mouse plasmaFEBS JOURNAL, Issue 22 2009Michael J. Krisinger Mouse anticoagulant protein C (461 residues) shares 69% sequence identity with its human ortholog. Interspecies experiments suggest that there is an incompatibility between mouse and human protein C, such that human protein C does not function efficiently in mouse plasma, nor does mouse protein C function efficiently in human plasma. Previously, we described a series of human activated protein C (APC) Gla domain mutants (e.g. QGNSEDY-APC), with enhanced membrane affinity that also served as superior anticoagulants. To characterize these Gla mutants further in mouse models of diseases, the analogous mutations were now made in mouse protein C. In total, seven mutants (mutated at one or more of positions P10S12D23Q32N33) and wild-type protein C were expressed and purified to homogeneity. In a surface plasmon resonance-based membrane-binding assay, several high affinity protein C mutants were identified. In Ca2+ titration experiments, the high affinity variants had a significantly reduced (four-fold) Ca2+ requirement for half-maximum binding. In a tissue factor-initiated thrombin generation assay using mouse plasma, all mouse APC variants, including wild-type, could completely inhibit thrombin generation; however, one of the variants denoted mutant III (P10Q/S12N/D23S/Q32E/N33D) was found to be a 30- to 50-fold better anticoagulant compared to the wild-type protein. This mouse APC variant will be attractive to use in mouse models aiming to elucidate the in vivo effects of APC variants with enhanced anticoagulant activity. [source] Which parameters differ in very old patients with chronic atrial fibrillation treated by anticoagulant or aspirin?FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2008Antithrombotic treatment of atrial fibrillation in the elderly Abstract The objective was to determine the main parameters taken into account for the decision of antithrombotic treatment of atrial fibrillation (AF) by vitamin K antagonist or aspirin. This was a prospective clinical study of four clinical services of geriatric medicine. Two hundred and nine inpatients, 84.7 ± 7 years (women 60.8%), with chronic AF were included. The patients were distributed into two groups (anticoagulant or aspirin) according to medical decision. All the decision criteria for treatment were recorded: cardiopathy, conditions of life, clinical examination (nutrition and autonomy, mini-mental state examination (MMSE), walking evaluation, comorbidity), subjective evaluation of risk of falls and glomerular filtration rate. The thromboembolic risk and the bleeding risk, evaluated subjectively for each patient, were compared with two scores of thrombo-embolic risk and bleeding risk. The evolution of the patients was recorded after 3 months. Student's t -test and chi-squared tests were used for statistical analysis. One hundred and two patients (48.8%) received anticoagulant and 107 patients received aspirin. Patients in the aspirin group were significantly older (86.5 ± 6.5 vs. 82.9 ± 7.1 years), with more frequent social isolation, higher systolic blood pressure, and had more important subjective bleeding risk and risk of falls. Patients in the anticoagulant group had significantly more valvulopathies and a more important subjective thromboembolic risk. Thrombo-phlebitis antecedents, dementia, denutrition and walking alterations were only slightly more frequent in patients in the aspirin group. Physicians underestimated thromboembolic risk (one-third of patients) and they overestimated bleeding risk (half of the patients). After 3 months, the two groups did not significantly differ for death, bleeding or ischaemic events. In common practice, the decision of antithrombotic treatment for AF should take into account not only cardiovascular but also geriatric criteria. [source] History of hemodialyzers' designsHEMODIALYSIS INTERNATIONAL, Issue 2 2008Zbylut J. TWARDOWSKI Abstract Accumulation of knowledge requisite for development of hemodialysis started in antiquity and continued through Middle Ages until the 20th century. Firstly, it was determined that the kidneys produce urine containing toxic substances that accumulate in the body if the kidneys fail to function properly; secondly, it was necessary to discover the process of diffusion and dialysis; thirdly, it was necessary to develop a safe method to prevent clotting in the extracorporeal circulation; and fourthly, it was necessary to develop biocompatible dialyzing membranes. Most of the essential knowledge was acquired by the end of the 19th century. Hemodialysis as a practical means of replacing kidney function started and developed in the 20th century. The original hemodialyzers, using celloidin as a dialyzing membrane and hirudin as an anticoagulant, were used in animal experiments at the beginning of the 20th century, and then there were a few attempts in humans in the 1920s. Rapid progress started with the application of cellophane membranes and heparin as an anticoagulant in the late 1930s and 1940s. The explosion of new dialyzer designs continued in the 1950s and 1960s and ended with the development of capillary dialyzers. Cellophane was replaced by other dialyzing membranes in the 1960s, 1970s, and 1980s. Dialysis solution was originally prepared in the tank from water, electrolytes, and glucose. This solution was recirculated through the dialyzer and back to the tank. In the 1960s, a method of single-pass dialysis solution preparation and delivery system was designed. A large quantity of dialysis solution was used for a single dialysis. Sorbent systems, using a small volume of regenerated dialysis solution, were developed in the mid 1960s, and continue to be used for home hemodialysis and acute renal failure. At the end of the 20th century, a new closed system, which prepared and delivered ultrapure dialysis solution preparation, was developed. This system also had automatic reuse of lines and dialyzers and prepared the machine for the next dialysis. This was specifically designed for quotidian home hemodialysis. Another system for frequent home hemodialysis or acute renal failure was developed at the turn of the 21st century. This system used premanufactured dialysis solution, delivered to the home or dialysis unit, as is done for peritoneal dialysis. [source] Experimental study on a new type citrate anticoagulant hemodialysate in dogsHEMODIALYSIS INTERNATIONAL, Issue 1 2005G. Baosong Objective:,In this study, we initiated a new hemodialysate with citrate buffer, observed the factors that influence the citrate concentration of solution in hollow fibers when using citrate hemodialysate, and observed the anticoagulant effect and safety of the citrate hemodialysate in the experiment in dogs. Methods:,Ten dogs were given intermittent hemodialysis and were divided into 3 groups according to hemodialysis procedures. Group 1 was saline-flush hemodialysed with bicarbonate hemodialysate; Group 2 was hemodialysed with citrate hemodialysis without any anticoagulant; Group 3 was hemodialysed with bicarbonate hemodialysate and heparin. ACT, Ca++, BUN, Cr, ALT, AST, TBIL, DBIL, Na+, Cl,, , and venous pressure were monitored in the animals of each group during hemodialysis. Results:,During the hemodialysis in Group 1, venous pressure increased lastingly, resulting in the failure of hemodialysis for 2 hours. Hemodialysis for 2 hours in Group 2 were all finished successfully. ACT was extended and Ca++ decreased obviously in the venous end during hemodialysis. And ALT, AST, Ca++, K+, Na+, Cl,, after the hemodialysis in Group 2 were not changed (P > 0.05). Moreover, the clearance rate of the dialyzers with citrate dialysate increased significantly compared with those of saline-flush and heparin anticoagulation. Conclusions:,The anticoagulant and dialytic effects of the new type citrate hemodialysis are satisfactory and better than that of saline-flush. [source] Anticoagulation Options for Pediatric HemodialysisHEMODIALYSIS INTERNATIONAL, Issue 2 2003Andrew Davenport Blood coagulation in the extracorporeal hemodialysis circuit is one of the manifestations of bio-incompatibility that is related to the activation of monocytes, platelets, and the coagulation cascades. Compared to adults, in pediatric patients, the surface area of the extracorporeal circuit is increased relative to blood volume. This is due to the patient's smaller blood volume and the combination of the higher relative surface area of the dialyzer, smaller lumen lines, and small-bore vascular catheters, potentially increasing contact activation of coagulation proteins, platelets, and inflammatory cells. Although unfractionated heparin remains the most commonly used anticoagulant, low molecular weight heparin offers the advantages of a single bolus, less fibrin and platelet deposition in the dialyzer, and perhaps more importantly, less osteoporosis, hyperkalemia, and abnormal lipoprotein profile. Although regional anticoagulants are available, these are often prohibitively expensive or require increased complexity of the dialysis procedure (e.g., citrate), but have the advantage of reducing the risk of bleeding when compared to heparin. Thrombin inhibitors are now available, and with the advent of argatroban, which is metabolized in the liver, have become the anticoagulants of choice for the few patients who develop heparin-induced thrombocytopenia type II. [source] Evaluation of a new venom-based clotting assay of protein CINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 5 2008P. C. COOPER Summary Congenital protein C deficiency significantly increases the risk of venous thromboembolism, a serious and potentially lethal condition. Protein C levels can be determined by chromogenic, clotting and antigenic assays, each type of assay has differences in specificity and sensitivity to protein C deficiency. In principle, clotting-based assays of protein C are preferred over chromogenic assays, as they can detect some rare mutations that are missed by the chromogenic assay, however, clotting-based assays may be prone to inaccuracy because of poor specificity. We have evaluated a new venom-based clotting assay of protein C, and optimized it for use on Sysmex CA-1500 analyser. The assay was linear from 0 to 130 U/dl, a normal plasma demonstrated good inter-assay precision, with a coefficient of variation of 4.8%. The assay compared well with antigenic- and venom-based chromogenic protein C assay in normal individuals, subjects with lupus anticoagulant, and subjects with FV Leiden. Median protein C levels by clotting, chromogenic and antigen for the three subject groups were 108 U/dl, 108 IU/dl and 109 IU/dl for normal subjects, 94 U/dl, 106 IU/dl and 103 IU/dl for subjects with lupus anticoagulant, and 102 U/dl, 104 IU/dl and 100 IU/dl for subjects heterozygous for FV Leiden. Comparing levels of clotting protein C with protein C antigen by ratio (clotting/antigen), the three groups showed small differences that did not quite reach statistical significance, (mean ratios ranged from 0.95 to 1.01, anovaP = 0.0561), the lowest ratio was with the lupus anticoagulant group. Comparing clotting assay with chromogenic assay by ratio (clotting/chromogenic), the three groups did show a statistically significant difference (P = 0.0033) which was due to a difference in mean ratios between normal and lupus anticoagulant groups (ratios 1.00 and 0.91, respectively, P < 0.01). There was no statistical difference in any of the groups when comparing chromogenic protein C with protein C antigen (mean ratios ranged from 1.02 to 1.05, P = 0.3925). In a normal sample, the clotting-based protein C level was unaffected by increasing FVIII level by up to 1000 IU/dl, using intermediate purity FVIII concentrate. The new assay is considered to be a suitable assay for the routine diagnosis of protein C deficiency. [source] Antiphospholipid antibodies and hepatitis C virus infection in Iranian thalassemia major patientsINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2008S. KASHEF Summary Although the precise nature of Antiphospholipid antibodies is still not clearly defined, they are known to have association with thromboembolic events and have been found in hepatitis C virus (HCV) infection. Moreover, high prevalence of HCV infection and thrombotic risk is described in thalassemia. We aimed at investigating the prevalence of anticardiolipin antibodies (aCLAbs), lupus anticoagulant (LA), and their relation with HCV infection in Iranian thalassemic patients. Presence of anti-HCV antibody, serum HCV-RNA, aCLAbs, and LA activity was determined in 131 patients with thalassemia major (male/female: 63/68 aged 3,29 years) registered at thalassemia unit, Dastgheib Hospital, Shiraz, Iran. Sixty-one healthy controls were also included. Anti-HCV antibody was positive in 24 (18.3%), IgG aCLAbs in 56 (42.7%), and LA activity in 9 (6.9%) patients. 87.5% of patients positive for aCLAbs had a low titer of aCLAbs. Although none of the participants had a previous history of thrombosis, higher prevalence of aCLAbs was detected in thalassemic patients compared with controls. No significant difference in the prevalence of aCLAbs was found between HCV-infected and noninfected patients. A high prevalence of aCLAbs, the majority in low titers, was detected in Iranian thalassemic patients irrespective of previous history of thrombosis and presence of HCV infection. [source] Assessment of endothelial function as a marker of cardiovascular risk in patients with rheumatoid arthritisINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2010Faisel KHAN Abstract The endothelium is a major regulator of cardiovascular function and maintains an atheroprotective role through several mechanisms, including vasodilatation, inhibition of platelet aggregation, having anticoagulant and profibrinolytic effects, and having an anti-inflammatory effect. Early changes in the normal functioning of the endothelium are key initiating factors in the development and progression of atherosclerosis. These changes are present well before the presentation of clinical symptoms. Thus, researchers have focused much attention on developing methods for reliable non-invasive testing of endothelial function to allow early detection and monitoring and progression of subclinical atherosclerosis. To date, there is a wide range of methods in use to assess endothelial function, each with its own advantages and limitations. Ideally, the tests should be non-invasive to allow repeated measurements and be applicable in normal healthy subjects and also in children. Given the wide range of regulatory functions of the endothelium, it is not surprising that there is no single measure of endothelial function that provides all the necessary information regarding vascular integrity in different vascular beds. Therefore, a combination of tests examining different components of the vascular system is more appropriate. Since patients with rheumatoid arthritis have increased mortality due to cardiovascular disease, assessment of endothelial function could prove to be useful tools in the identification and monitoring of cardiovascular risk. The purpose of this review is to give a brief overview of some of the commonly used techniques for assessment of endothelial function, and in particular on those that have been used in studies of patients with rheumatoid arthritis. [source] Heterogeneity of the coumarin anticoagulant targeted vitamin K epoxide reduction system.JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 5 2006Study of kinetic parameters in susceptible, resistant mice (Mus musculus domesticus) Abstract Vitamin K epoxide reductase (VKOR) activity in liver microsomes from a susceptible and a genetically warfarin-resistant strain of mice (Mus Musculus domesticus) was analyzed to determine the mechanism of resistance to this 4-hydroxycoumarin derivative. Kinetic parameters for VKOR were calculated for each strain by incubating liver microsomes with vitamin K epoxide ± warfarin. In susceptible mice, an Eadie,Hofstee plot of the data was not linear and suggested the involvement of at least two different components. Apparent kinetic parameters were obtained by nonlinear regression using a Michaelis--Menten model, which takes into account two enzymatic components. Component A presents a high Km and a high Vm, and as a consequence only an enzymatic efficiency Vm/Km was obtained (0.0024 mL/min/mg). Estimated warfarin Ki was 0.17 ,M. Component B presented an apparent Km of 12.73 ,M, an apparent Vm of 0.32 nmol/min/mg, and an apparent Ki for warfarin of 6.0 ,M. In resistant mice, the enzymatic efficiency corresponding to component A was highly decreased (0.0003,0.00066 mL/min/mg) while the Ki for warfarin was not modified. The apparent Vm of component B was poorly modified between susceptible and resistant mice. The apparent Km of component B observed in resistant mice was similar to the Km observed in susceptible mice. These modifications of the catalytic properties are associated with a single nucleotide polymorphism (T175G) in the VKOR-C1 gene, which corresponds to a Trp59Gly mutation in the protein. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:221,229, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20144 [source] Successful Heparin Desensitization: A Case Report and Review of the LiteratureJOURNAL OF CARDIAC SURGERY, Issue 4 2008Shoban Dave M.D. Moreover, heparin remains the anticoagulant of choice in cardiopulmonary bypass. We describe a patient with heparin allergy who underwent successful heparin desensitization and a review of the literature. [source] Therapeutic plasma exchange: A paired comparison of Fresenius AS104 vs.JOURNAL OF CLINICAL APHERESIS, Issue 2 2001COBE Spectra Abstract For therapeutic plasma exchange (TPE), continuous flow separators are known to be efficient as exemplified by Fresenius AS104 and COBE Spectra. The AS104 uses an interface monitoring system in the centrifuge during TPE, whereas Spectra uses computer algorithms to establish the plasma-cell interface. To determine the plasma collection efficiency (PLCE), anticoagulant (AC) volumes used, and platelets (PLT) lost of the AS104 and the Spectra, we performed a prospective paired comparison of 20 TPE (each machine). The study included 17 patients, 1.3 plasma volume exchanges (without AC), equal inlet rates, and AC ratio of 13:1. Processing times did not include reinfuse mode. Platelet loss was determined by sampling the collection bags. Inlet rates were between 60,110 ml/min. Diagnosis included peripheral neuropathies, TTP and cryoglobulinemia. The AS104 had significantly (P<0.0001) lower average whole blood processed (F:6,601 vs. S:8,584 ml), AC volume (F:532 vs. S:719 ml), and processing time (F:80 vs. S:102 minutes) than Spectra. The AS104 had significantly (P<0.0001) higher average plasma flow rates (F:53 vs. S:44 ml/minute), plasma collection efficiency (F:90 vs. S:69%), and platelet loss (F:2.0 vs. S:0.14 × 1011 plt) than Spectra. Platelet loss correlated with inlet flow rate with the AS104 but not with the Spectra. The AS104 has a significantly higher collection efficiency than Spectra allowing it to remove the same amount of plasma in significantly less time, by processing significantly less blood, using significantly less AC, but removing significantly more platelets than Spectra. J. Clin. Apheresis. 16:61,66, 2001. © 2001 Wiley-Liss, Inc. [source] Prevalence of antiphospholipid antibodies in Chilean patients with rheumatoid arthritisJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2006Iván Palomo Abstract Antiphospholipid (aPL) antibodies found in patients with autoimmune diseases are also detected in those with inflammatory diseases. The purpose of this study was to examine the prevalence of these antibodies in patients with rheumatoid arthritis (RA), and to evaluate the association of these antibodies with thrombosis and/or other clinical characteristics of this inflammatory disorder. Eighty-four patients with RA and 82 normal controls were studied. Anticardiolipin (aCL), anti-,2 glycoprotein I (anti-,2GPI), and antiprothrombin (aPT) antibodies and the lupus anticoagulant (LA) activity were determined. Seven out of 84 (8.3%) patients were positive for aCL, six out of 84 (7.2%) for anti-,2GPI, and six out of 84 (7.2%) for aPT, while in controls the overall prevalence of aPL antibodies was 3.6% (3 out of 82). All patients and controls were LA negative. There was no correlation between the presence of aPL with thrombosis and/or other clinical features of the antiphospholipid syndrome. We found aPL antibodies in 19.1% (16 out of 84) of the patients with rheumatoid arthritis and this prevalence was statistically higher than in normal controls (P<0.003). In this study, the presence of aPL antibodies was not associated with the development of thrombosis and/or thrombocytopenia. Whether the presence of aPL antibodies implies an increased risk for thrombosis and atherosclerosis in these patients should be studied further. J. Clin. Lab. Anal. 20:190,194, 2006. © 2006 Wiley-Liss, Inc. [source] Use of a new silica clotting time for diagnosing lupus anticoagulant in patients who meet the clinical criteria for antiphospholipid syndromeJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2006Panagiotis Grypiotis Abstract The silica clotting time (SCT) is a phospholipid-dependent coagulation assay used for the laboratory diagnosis of lupus anticoagulant (LA) antibodies. The sensitivity and specificity of a new commercial SCT for identifying LA in patients who meet the clinical criteria for antiphospholipid syndrome (APS), and its association with thrombotic events were evaluated here. Forty-five patients who met the clinical criteria for APS according to the Sapporo International Consensus Statement were examined. Sixty-nine patients who did not meet the clinical criteria for APS, and 20 blood donors were used as controls. Plasma samples from the patients and controls were tested for LA using a new commercial SCT with low and high synthetic phospholipid concentrations. The results were compared with those obtained by diluted Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT). SCT's sensitivity for identifying LA in patients who met the clinical criteria of APS was higher compared to APTT and dRVVT (53.3% vs. 31.1% and 31.1%), and the specificities of these assays were 96.6%, 100%, and 98.9%, respectively. When dRVVT was combined with SCT, and dRVVT was combined with APTT their sensitivities were 57.7% and 48.8%, and their specificities were 96.6% and 98.9%, respectively. A stepwise logistic regression analysis indicated that the combination of dRVVT with SCT was associated with total thrombotic events (odds ratio (OR)=11.5, 95% confidence interval (CI)=1.25,106.3, P=0.031) as well as with venous thrombosis (OR=4.09, 95% CI=1.16,14.43, P=0.028). According to our results, SCT is the most sensitive assay for identifying LA in patients who meet the clinical criteria for APS. Moreover, the highest sensitivity was reached with a combination of SCT and dRVVT. The method's association with total thrombotic events and venous thrombosis was in fact significant. J. Clin. Lab. Anal. 20:15,18, 2006. © 2006 Wiley-Liss, Inc. [source] Intravascular histiocytosis presenting with extensive vulvar necrosisJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2009Pedram Pouryazdanparast Intravascular histiocytosis (IVH) is a rare reactive cutaneous lesion of unknown pathogenesis. Most cases are reported in association with rheumatoid arthritis, and cutaneous eruptions typically occur near swollen joints. The skin changes have included erythematous and violaceous macules, papules, plaques and indurated patches with a livedo-like pattern of erythema. We report the first case of IVH presenting with florid vulvar necrosis in an 87-year-old patient without a history of rheumatoid arthritis. Physical examination revealed an edematous, exudative and diffusely necrotic vulva with erythema surrounding the areas of necrosis, extending out to the thighs. The debrided skin revealed an extensively necrotic epidermis and multiple clusters of markedly dilated blood vessels within the dermis. These vessels contained fibrin thrombi admixed with numerous CD68+ and CD163+ histiocytes. Her skin changes improved significantly after surgical debridement and treatment with antibiotics. Interestingly, our patient was also found to have a lupus anticoagulant with elevated anticardiolipin antibodies. This is the first report of IVH possibly related to a thrombogenic diathesis associated with a hypercoagulable state. A diagnosis of IVH is important and may necessitate further clinical evaluation to exclude the possibility of co-existent systemic disease. [source] The Role of Enoxaparin in Interventional Management of Patients with Acute Coronary SyndromesJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 5 2003CINDY L. GRINES M.D., F.A.C.C. Interventional management strategies involving early angiography and percutaneous coronary intervention (PCI) are increasingly widespread in the management of patients with acute coronary syndromes (ACS). Notwithstanding the benefits of early intervention, there is a significant risk of postprocedural thrombotic complications and a need to optimize antithrombotic regimens for use before and during PCI. It is clear that the current standard therapy with unfractionated heparin (UFH) and aspirin can be improved upon, in terms of both efficacy and safety. The low-molecular-weight heparin(s) (LMWHs) offer pharmacologic and practical advantages over UFH. The LMWH enoxaparin has recently emerged as the anticoagulant of choice for the acute management of ACS. Enoxaparin has also demonstrated sustained benefits over UFH in patients proceeding to PCI, and as a procedural anticoagulant. Combination therapy with enoxaparin and a glycoprotein IIb/IIIa inhibitor may further improve the efficacy and safety of antithrombotic treatment during coronary interventions, as a result of the drugs' complementary mechanisms of action. Early clinical evidence supports the use of enoxaparin in combination with glycoprotein IIb/IIIa inhibitors in high-risk patients with ACS. Ongoing, large-scale, randomized controlled studies will help to clarify the role of enoxaparin in interventional cardiology, either as the primary anticoagulant or as part of a combination regimen, and to define optimal regimens for treatment. (J Interven Cardiol 2003;16:357,366) [source] Antiphosphatidylethanolamine antibodies in recurrent early pregnancy loss and mid-to-late pregnancy loss,JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4 2004Toshitaka Sugi Abstract Aim:, Associations have been reported between antiphospholipid antibodies (aPL), mainly anticardiolipin antibodies (aCL) and/or the lupus anticoagulant, and recurrent pregnancy losses (RPL). However, relatively few studies describing antiphosphatidylethanolamine antibodies (aPE) have been reported. We describe the prevalence of aPL to both cardiolipin and phosphatidylethanolamine in patients with RPL. Methods:, Patients with recurrent early pregnancy losses (n = 145) and mid-to-late pregnancy loss(es) (n = 26) were screened for aPE and aCL. Results:, In patients with recurrent early pregnancy losses, prevalence of immunoglobulin G (IgG) aPE (17.9%, P = 0.001) and immunoglobulin M (IgM) aPE (12.4%, P = 0.01) was significantly higher than in the control group. In patients with mid-to-late pregnancy loss(es), prevalence of IgM aPE (19.2%, P = 0.008) and IgG aCL (23.1%, P = 0.02) was significantly higher than in the control group. Conclusion:, Our data suggest that aPE may be a risk factor in patients with mid-to-late pregnancy loss(es) as well as recurrent early pregnancy losses. [source] | ||||||||||||||||||||||||||||||||||||||||||||||