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LMWH
Selected AbstractsComparison of unfractioned and low molecular weight heparin for prophylaxis of coagulopathies in 52 horses with colic: a randomised double-blind clinical trialEQUINE VETERINARY JOURNAL, Issue 5 2003K. FEIGE Summary Reasons for performing study: Unfractioned heparin (UFH) is widely used for prophylaxis of coagulation disorders, especially in colic-affected horses. However, it is accompanied by certain side effects. Objectives: To compare the efficacy and side effects of unfractioned and low molecular weight heparin (LMWH) in horses with colic. Methods: The study was carried out as a randomised, double-blind, controlled clinical trial. Fifty-two horses with colic were treated subcutaneously with either UFH (heparin calcium, 150 iu/kg bwt initially, followed by 125 iu/kg bwt q. 12 h for 3 days and then 100 iu/kg bwt q. 12 h) or LMWH (dalteparin, 50 iu/kg bwt q. 24 h). All horses underwent daily physical examination including assessment of jugular veins, local reaction to heparin injections, haematological evaluation and coagulation profiles over up to 9 days. Results: The type of heparin used did not affect the general behaviour and condition. There were significantly more jugular vein changes in horses treated with UFH. Packed cell volume decreased significantly within the first few days of UFH treatment, but did not change significantly in horses treated with LMWH. Activated partial thromboplastin time (aPTT) and thrombin time (TT) were prolonged in horses treated with UFH but not in those treated with LMWH. Conclusions: It was concluded that, in comparison to UFH, LMWH has markedly fewer side effects in horses. Potential relevance: Therefore, LMWH is recommended for prophylaxis of coagulation disorders in colic patients. [source] Current concepts for the prevention of venous thromboembolismEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2005P. Bramlage Abstract Venous thromboembolism (VTE) is a major cause of morbidity and mortality worldwide and the annual incidence of VTE is 1 per 1000. The individual risk for venous thromboembolism may be substantially higher and is determined by expositional and dispositional factors. Unfractionated heparin and warfarin have been the mainstays for the prevention of VTE until the early 1980s. Bleeding complications and side effects limited the use of these agents and subsequently low molecular weight heparins (LMWH) were introduced into clinical practice. These are most commonly used for the prophylaxis and treatment of VTE today. In the last decade, the pace of development of further anticoagulants has accelerated with the introduction of new treatment regimens and new substances. In this context, novel drugs directed against clotting factor Xa (such as fondaparinux) and direct thrombin inhibitors (such as melagatran/ximelagatran) have been developed. Fondaparinux shows a favourable efficacy/safety profile and has been documented to be cost-effective compared to enoxaparin in the US and the UK. [source] From heparins to factor Xa inhibitors and beyondEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2005S. Alban Abstract Despite some disadvantages, unfractionated heparin (UFH) and oral anticoagulants have been the only anticoagulants for prophylaxis and therapy of thromboembolic disorders for several decades. Based on the increasing knowledge of the structure and pharmacology of heparin, low molecular weight heparins (LMWH) have been developed in the 1980s. Compared to UFH, their advantages are mainly based on their reduced nonspecific binding to proteins and cells resulting in improved pharmacokinetics. In 1991, LMWH were declared as the most efficient prophylaxis in high-risk patients. Although the use of LMWH is increasing and they are today also applied for therapy and in other indications like acute coronary syndrome, they are considered not optimal concerning efficacy and safety. With the approval of fondaparinux for the prevention of venous thromboembolic disease in high-risk orthopedic patients, there might be a paradigm shift in the field of anticoagulants. Fondaparinux, a synthetic, chemically defined pentasaccharide, is the first selective inhibitor of factor Xa. By its highly specific binding to antithrombin, it selectively inhibits factor Xa and consequently prevents thrombin generation. In contrast to UFH and LMWH, it does not bind to any other cells and other proteins than antithrombin. This leads to a favourable linear pharmacokinetic profile, allowing once-daily subcutaneous application of a fixed dose without monitoring in thromboembolism prophylaxis. In addition to the evaluation of fondaparinux for further indications, chemical modifications of this pentasaccharide such as the long-acting idraparinux are currently under investigation. [source] Should patients be informed about the risk of heparin-induced thrombocytopenia before prolonged low-molecular-weight heparin thromboprophylaxis post-trauma/orthopedic surgery?EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2007Norbert Lubenow Abstract Objectives:, Heparin-induced thrombocytopenia (HIT) is an immune-mediated prothrombotic adverse drug effect that occurs less frequently with low-molecular-weight heparin (LMWH) than with unfractionated heparin (UFH) in post-trauma/orthopedic surgery patients. The life-threatening nature of HIT raises the question whether informed consent for this treatment-induced adverse effect should be obtained, particularly as LMWH is often continued during the outpatient period when clinical and platelet count monitoring become problematic. Paradoxically, refusal of thromboprophylaxis as a result of seeking informed consent could increase risk for thrombosis. Methods:, We evaluated in patients undergoing routine LMWH thromboprophylaxis post-trauma/orthopedic surgery the feasibility of obtaining informed consent, using a standardized questionnaire to determine patient preferences. We also identified the proportion of HIT patients in our laboratory comprised of trauma/orthopedic surgery patients from 1995,1997 and 2002,2004 (time periods characterized, respectively, by UFH and LMWH thromboprophylaxis for this patient population). Results:, None of 460 patients in whom informed consent was administered rejected LMWH thromboprophylaxis. The patients' perception of the informed consent process and the written information provided about the risk of HIT and its risk due to clinical consequences were highly favorable. From 1995,1997 to 2002,2004, the proportion of HIT identified among trauma/orthopedic surgery patients declined from 30.3% to 1.2% (P < 0.0001). Conclusions:, Obtaining informed consent about HIT is feasible in written form and does not cause refusal of LMWH thromboprophylaxis. Despite the uncommon occurrence of HIT during LMWH thromboprophylaxis, informed consent increases patient's awareness of this potentially life-threatening adverse drug effect, an outcome that could increase outpatient recognition of the diagnosis. [source] A pilot study on systemic thrombolysis followed by low molecular weight heparin in ischemic strokeEUROPEAN JOURNAL OF NEUROLOGY, Issue 10 2006R. Mikulík Low molecular weight heparin (LMWH) administered immediately after intravenous thrombolysis (IT) may reduce the risk of arterial re-occlusion. Its benefit, however, may not outweigh the risk of intracranial hemorrhage (ICH). We sought preliminary data regarding safety of this combined therapy in an open-label, non-randomized study. The patients received either a standard anticoagulation (AC) starting 24 h after IT (the standard AC group) or AC with 2850 IU of nadroparin, given every 12 h immediately after IT (the early AC group). Sixty patients received IT treatment: 25 in the standard AC group [mean age 66, median National Institutes of Health Stroke Scale (NIHSS) 13, 64% men] and 35 in the early AC group (mean age 68, median NIHSS 13, 69% men). Symptomatic ICH occurred in one patient (4%) in the standard AC group and three patients (8.6%) in the early AC group [odds ratio (OR) 1.8; 95%CI 0.2,12.8]. At 3 months, nine patients in the standard AC group (36%) and 16 patients in the early AC group (45.7%) achieved a modified Rankin scale 0 or 1 (OR 1.2; 95%CI 0.5,3.2). Our study suggests that treatment with LMWH could be associated with higher odds of ICH, although it may not necessarily lead to a worse outcome. This justifies larger clinical trials. [source] EFNS guideline on the treatment of cerebral venous and sinus thrombosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 6 2006K. Einhäupl Cerebral venous and sinus thrombosis (CVST) is a rather rare disease which accounts for <1% of all strokes. Diagnosis is still frequently overlooked or delayed due to the wide spectrum of clinical symptoms and the often subacute or lingering onset. Current therapeutic measures which are used in clinical practice include the use of anticoagulants such as dose-adjusted intravenous heparin or body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH), the use of thrombolysis, and symptomatic therapy including control of seizures and elevated intracranial pressure. We searched MEDLINE (National Library of Medicine), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Library to review the strength of evidence to support these interventions and the preparation of recommendations on the therapy of CVST based on the best available evidence. Review articles and book chapters were also included. Recommendations were reached by consensus. Where there was a lack of evidence, but consensus was clear we stated our opinion as good practice points. Patients with CVST without contraindications for anticoagulation should be treated either with body weight-adjusted subcutaneous LMWH or dose-adjusted intravenous heparin (good practice point). Concomitant intracranial haemorrhage related to CVST is not a contraindication for heparin therapy. The optimal duration of oral anticoagulation after the acute phase is unclear. Oral anticoagulation may be given for 3 months if CVST was secondary to a transient risk factor, for 6,12 months in patients with idiopathic CVST and in those with ,mild' hereditary thrombophilia. Indefinite anticoagulation (AC) should be considered in patients with two or more episodes of CVST and in those with one episode of CVST and ,severe' hereditary thrombophilia (good practice point). There is insufficient evidence to support the use of either systemic or local thrombolysis in patients with CVST. If patients deteriorate despite adequate anticoagulation and other causes of deterioration have been ruled out, thrombolysis may be a therapeutic option in selected cases, possibly in those without intracranial haemorrhage (good practice point). There are no controlled data about the risks and benefits of certain therapeutic measures to reduce an elevated intracranial pressure (with brain displacement) in patients with severe CVST. Antioedema treatment (including hyperventilation, osmotic diuretics and craniectomy) should be used as life saving interventions (good practice point). [source] Pulmonary embolism in a patient with severe congenital deficiency for factor V during treatment with fresh frozen plasmaHAEMOPHILIA, Issue 3 2005A. García-Noblejas Summary., Thrombosis is a rare complication in patients with congenital clotting factor deficiencies. In most cases, it is related to inherited procoagulant factors, use of central venous catheters or administration of coagulation factor concentrates. There are only a few case reports about thrombotic events during treatment with fresh frozen plasma (FFP). We report the case of a patient with homozygous inherited factor V deficiency, who developed a pulmonary embolism at a time of treatment with methylene blue treated FFP (MBFFP). The patient had only two other factors predisposing to thrombosis and both were acquired: obesity and bed rest. He started anticoagulant treatment with low molecular weight heparin (LMWH) while the deficient factors were replaced with MBFFP. After 8 days of treatment the patient developed a severe respiratory insufficiency. Pulmonary haemorrhage was considered among the differential diagnosis and LMWH was stopped. An inferior vena cava filter was placed without any further thrombotic complications. To our knowledge, there are no reports about patients with clotting factor deficiencies who developed a thrombotic event during treatment with MBFFP. [source] Randomized, placebo-controlled trial of low molecular weight heparin in active ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 6 2007M.A. de Bièvre MD Abstract Background: In several open and 1 controlled trial, unfractionated heparin was effective in the treatment of active ulcerative colitis (UC). Low molecular weight heparin (LMWH) had a similar effect in several open studies. Methods: We studied the efficacy, safety, and tolerability of LMWH in mild to moderately active UC in a randomized, double-blind, placebo-controlled trial. In all, 29 patients with a mild or moderate recurrence of UC during salicylate treatment were randomized to receive either reviparin 3,436 IU (n = 15) subcutaneously twice daily or placebo (n = 14). The study period was 8 weeks. Treatment was discontinued if there was no improvement at 4 weeks or at any disease progression. Primary outcome measure was clinical improvement at 8 weeks measured by the Colitis Activity Index (CAI) and the Clinical Symptoms Grading (CSG, based on the CAI). Endoscopic and histologic grading and quality of life as measured by the Inflammatory Bowel Disease Questionnaire (IBDQ) were secondary outcome measures. Patients were closely monitored for adverse events. Results: Twenty of 29 patients finished the 8-week treatment period (reviparin versus placebo: 11 versus 9; P = 0.70). There was no difference in CSG, CAI, endoscopic and histologic grading, or IBDQ. Treatment was well tolerated and no serious adverse events occurred. Conclusion: In this study, treatment with LMWH showed no significant clinical advantage compared to placebo in mild to moderately active UC. (Inflamm Bowel Dis 2007) [source] Iatrogenic calcinosis cutis following nadroparin injectionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2005Simonetta Giorgini MD Accumulation of calcium in the skin is usually classified as a group of disorders referred to as calcinosis cutis. We report the case of a patient who developed iatrogenic calcinosis at the site of subcutaneous administration of low-molecular-weight heparins (LMWH) as nadroparin. This is usually used for the prevention of deep venous thrombosis, especially following renal transplantation. The role of calcium content in nadroparin is discussed. [source] Evaluating the effectiveness of a deep-vein thrombosis prophylaxis protocol in orthopaedics and traumatologyJOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 4 2009Koray Unay MD Abstract Rationale, aims and objectives, To evaluate the effectiveness of the deep-vein thrombosis (DVT) prophylaxis protocol for adult patients in a general orthopaedics and traumatology clinic. Method, We followed the DVT prophylaxis protocol in 1326 (776 female, 550 male) of 2114 adult patients admitted to the Department of Orthopaedics and Traumatology in Goztepe Research and Training Hospital. They were followed for symptomatic DVT and possible complications of low-molecular-weight heparin (LMWH) therapy. A Doppler ultrasonography (US) was performed when DVT was suspected. The medical information treatment protocols of DVT patients were recorded. Results, Doppler US was performed in 58 patients with suspected DVT. Six of these patients were diagnosed with DVT. The side effects of LMWH were upper gastrointestinal bleeding (0.5%), widespread ecchymosis of the extremities (1.9%) and heparin-induced thrombocytopenia (0.16%). Conclusion, Symptomatic DVT occurrences were similar to those in medical literature; however, there were fewer side effects of LMWH than reported in literature. [source] Inhalable liposomes of low molecular weight heparin for the treatment of venous thromboembolismJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2010Shuhua Bai Abstract This study tests the feasibility of inhalable pegylated liposomal formulations of low molecular weight heparin (LMWH) for treatment of two clinical manifestations of vascular thromboembolism: deep vein thrombosis (DVT) and pulmonary embolism (PE). Conventional distearoyl- sn -glycero-3-phosphoethanolamine (DSPE) and long-circulating pegylated (DSPE,PEG-2000 and DSPE,PEG-5000) liposomes were prepared by hydration method. Formulations were evaluated for particle size, entrapment efficiency, stability, pulmonary absorption, anticoagulant, and thrombolytic effects in rats. Pulmonary absorption was monitored by measuring plasma antifactor Xa activity; anticoagulant and thrombolytic effects were studied by measuring reduction in thrombus weight and amount of dissolved radioactive clot in the blood, respectively. Pegylated liposomal were smaller and showed greater drug entrapment efficiency than conventional liposomes. All formulations produced an increase in pulmonary absorption and circulation time of LMWH upon first dosing. Three repeated dosings of conventional liposomes resulted in decreased half-life and bioavailability; no changes in these parameters were observed with pegylated liposomes. PEG-2000 liposomes were effective in reducing thrombus weight when administered every 48,h over 8 days. In terms of thrombolytic effects and dosing frequency, PEG-2000 liposomes administered via the pulmonary route at a dose of 100,U/kg were as effective as 50,U/kg LMWH administered subcutaneously. This paper suggests that inhalable pegylated liposomes of LMWH could be a potential noninvasive approach for DVT and PE treatment. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:4554,4564, 2010 [source] Nasal administration of low molecular weight heparinJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2002John Arnold Abstract The main objective of this study was to determine if the systemic absorption of therapeutic amounts of heparin was possible following nasal administration. Sprague-Dawley rats received nosedrops containing a low molecular weight heparin (LMWH) or unfractionated heparin (UFH) formulated with or without tetradecylmaltoside (TDM). TDM is a nonionic surfactant that has been previously shown to be a potent absorption enhancer in studies with peptide drugs. LMWH/UFH absorption was determined by measuring plasma anti-Factor Xa activity. The inclusion of 0.25% TDM in nasal formulations containing LMWH resulted in a significant increase in the Cmax and area under the curve (AUC) of anti-Factor Xa activity when compared to LMWH formulated in saline alone. The addition of TDM to a nasal formulation containing UFH resulted in a much smaller increase in the Cmax and the AUC of anti-Factor Xa activity. The absolute bioavailability of LMWH was increased from 4.0,±,0.4% in the absence of TDM to 19,±,0.3% in the presence of TDM. The reversibility of the absorption enhancing effect of TDM was studied by applying LMWH nasally 60 or 120 min after the enhancer. The effect of TDM on the nasal epithelia appeared to be rapidly reversible. In conclusion, nasal delivery of LMWH, but not UFH, was successful when an absorption enhancer was included to increase nasal permeability. © 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1707,1714, 2002 [source] Modulation of gastrointestinal permeability of low-molecular-weight heparin by L-arginine: in-vivo and in-vitro evaluationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 5 2006Nusrat Abbas Motlekar L-Arginine is the principal physiological precursor of nitric oxide (NO, a key neurotransmitter) that plays a versatile role in the physiology of the gastrointestinal tract. In this study, the efficacy of L-arginine in enhancing intestinal absorption of ardeparin, a low-molecular-weight heparin (LMWH) was investigated in Caco-2 cell monolayers and a rat model. Regional permeability studies using rat intestine were performed using a modified Ussing chamber. Cell viability in the presence of various concentrations of enhancer was determined by MTT assay. Furthermore, the eventual mucosal epithelial damage was histologically evaluated. LMWH formulated with L-arginine was administered orally to male Sprague-Dawley rats and the absorption of LMWH was determined by measuring plasma anti-factor Xa activity. Higher ardeparin in-vitro permeability (,3 fold) compared with control was observed in the presence of 2% L-arginine. Regional permeability studies indicated predominant absorption in the colon region. Cell viability studies showed no significant cytotoxicity below 0.8% L-arginine. The oral bioavailability of ardeparin formulated with L-arginine (250 mg kg,1) was increased by ,2 fold compared with control. The formulation was well tolerated by the rats and no abnormal histopathological findings were observed in intestinal tissues of rats exposed to L-arginine. These results suggest that L-arginine may be useful in enhancing the intestinal absorption of LMWHs. [source] Description of the chemical and pharmacological characteristics of a new hemisynthetic ultra-low-molecular-weight heparin, AVE5026JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2009C. VISKOV Summary.,Background and objectives: AVE5026 is a novel, hemisynthetic, ultra-low-molecular-weight heparin (ULMWH), which is in clinical development for prevention of venous thromboembolism. Its unique structural features result from the highly selective depolymerization of heparin by the phosphazene base that protects the antithrombin (AT)-binding site from destruction. In the present paper, we describe the chemical and biological characteristics of AVE5026, as well as its effects on experimental thrombosis as compared to those of the low-molecular-weight heparin (LMWH) enoxaparin after a single subcutaneous (s.c.) administration in certain animal models. Method and results: AVE5026 has a higher anti-factor Xa (anti-FXa) activity (,160 U mg,1) along with a catalytic anti-thrombin (anti-FIIa) activity (,2 U mg,1) as a result of its structure being strongly enriched in specific AT-binding oligosaccharides. In human plasma, potent inhibition of thrombin generation by AVE5026 was closely related to its anti-FXa activity. In a rat venous thrombosis model, AVE5026 showed a dose-dependent antithrombotic activity comparable to that of enoxaparin (ED50-AVE5026 = 1.6 mg kg,1, ED50-enoxaparin = 2.8 mg kg,1). Interestingly, non-occlusive venous thrombosis in rabbits was inhibited by an ED50 of 0.1 mg kg,1 AVE5026, whereas 0.316 mg kg,1 enoxaparin was not active. In a canine model, similarly to enoxaparin (ED50 = 1.3 mg kg,1), AVE5026 dose-dependently inhibited arterial thrombosis (ED50 = 2.0 mg kg,1). At equipotent doses, AVE5026 did not affect bleeding parameters, whereas enoxaparin showed increased hemorrhage in rats, rabbits and dogs. Conclusion: These unique structural attributes distinguish AVE5026 from the LMWH class. Based on these data in well-established arterial and venous thrombosis models, AVE5026 could represent a valuable alternative in thrombosis prevention with an improved benefit-risk profile as compared to that of enoxaparin. [source] Study of bioaccumulation of dalteparin at a prophylactic dose in patients with various degrees of impaired renal functionJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2009P. SCHMID Summary.,Background: Low-molecular-weight heparins (LMWH) have been shown to be effective and safe for prophylaxis of thromboembolic diseases. However, issues regarding safety and optimal use of LMWH arise in patients with renal insufficiency (RI). Objectives: To compare pharmacokinetic data of dalteparin for up to 3 weeks in patients with various degrees of RI. Patients and methods: Patients from general medical and surgical wards were included in this prospective cohort study and divided into three groups according to renal function: A = normal (GFR , 60 mL min,11.73 m,2), B = mild RI (GFR 30,59 mL min,11.73 m,2), C = severe RI (GFR < 30 mL min,11.73 m,2). Dalteparin was injected s.c. once daily at a prophylactic dose. Peak anti-Xa activity levels (anti-Xa) were measured 4 ± 1 h after injection on day 1 and every third day up to 3 weeks. Primary objectives were peak anti-Xa levels and adjusted anti-Xa levels, adjustment being carried out for dose and body weight. Results: A total of 42 patients could be analyzed during a median of 10 days (interquartile range IQR 4,13, range 1,20). In all groups, adjusted peak anti-Xa levels were not different on day 10 compared with day 1. No bioaccumulation >30% could be found up to day 10 even in patients with severe RI. Conclusion: The use of dalteparin at a prophylactic dose was not associated with a bioaccumulation >30% even in patients with severe renal insufficiency during a median follow-up of 10 days (IQR 4,13, range 1,20). [source] Frequency of renal impairment, advanced age, obesity and cancer in venous thromboembolism patients in clinical practiceJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2007L. M. COOK Summary.,Background:,Low-molecular-weight heparin (LMWH) dosed by weight is recommended as first-line therapy for the initial treatment of venous thromboembolism (VTE) and as monotherapy for long-term treatment of cancer-related VTE. In ,special populations' such as those with renal impairment or the elderly, weight-based dosing may be excessive, and capping the dose in obese patients may lead to inadequate dosing. Objectives:,We determined the frequency of ,special population' characteristics (renal impairment, advanced age, obesity) and cancer among VTE patients in clinical practice, and assessed whether these characteristics appeared to influence the type and dose of anticoagulants prescribed. Methods:,During 2004,2005, among consecutive patients with VTE at two large Canadian hospitals, the proportions with the above characteristics were calculated and treatments prescribed were determined. Results:,Of 524 VTE patients, 31% were aged > 75 years. Moderate renal impairment [creatinine clearance (CrCl) 30,59 mL min,1] was present in 20% of patients, and severe renal impairment (CrCl < 30 mL min,1) in 5% of patients. LMWH was prescribed to 67% of patients with severe renal impairment and to 83% of patients with moderate renal impairment. Body weight was > 100 kg in 15% of patients. Underdosing of LMWH by > 10% was documented in 36% of such patients compared with 8% of patients < 100 kg (P < 0.001). Among 26% of patients with active cancer, only one-third were prescribed LMWH monotherapy. Conclusions:,In clinical practice, renal impairment, advanced age, obesity and cancer are frequently present in patients with VTE. A considerable proportion of these patients may not receive the optimal type or dose of medication to treat VTE. [source] Clinical outcomes with unfractionated heparin or low-molecular-weight heparin as bridging therapy in patients on long-term oral anticoagulants: the REGIMEN registry,JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2006A. C. SPYROPOULOS Summary.,Background: Patients who receive long-term oral anticoagulant (OAC) therapy often require interruption of OAC for an elective surgical or an invasive procedure. Heparin bridging therapy has been used in these situations, although the optimal method has not been established. No large prospective studies have compared unfractionated heparin (UFH) with low-molecular-weight heparin (LMWH) for the perioperative management of patients at risk of thromboembolism requiring temporary interruption of long-term OAC therapy. Patients/methods: This multicenter, observational, prospective registry conducted in North America enrolled 901 eligible patients on long-term OAC who required heparin bridging therapy for an elective surgical or invasive procedure. Practice patterns and clinical outcomes were compared between patients who received either UFH alone (n = 180) or LMWH alone (n = 721). Results: Overall, the majority of patients (74.5%) requiring heparin bridging therapy had arterial indications for OAC. LMWH, in mostly twice-daily treatment doses, represented approximately 80% of the study population. LMWH-bridged patients had significantly fewer arterial indications for OAC, a lower mean Charlson comorbidity score, and were less likely to undergo major or cardiothoracic surgery, receive intraprocedural anticoagulants or thrombolytics, or receive general anesthesia than UFH-bridged patients (all P < 0.05). The LMWH group had significantly more bridging therapy completed in an outpatient setting or with a < 24-h hospital stay vs. the UFH group (63.6% vs. 6.1%, P < 0.001). In the LMWH and UFH groups, similar rates of overall adverse events (16.2% vs. 17.1%, respectively, P = 0.81), major composite adverse events (arterial/venous thromboembolism, major bleed, and death; 4.2% vs. 7.9%, respectively, P = 0.07) and major bleeds (3.3% vs. 5.5%, respectively, P = 0.25) were observed. The thromboembolic event rates were 2.4% for UFH and 0.9% for LMWH. Logistic regression analysis revealed that for postoperative heparin use a Charlson comorbidity score > 1 was an independent predictor of a major bleed and that vascular, general, and major surgery were associated with non-significant trends towards an increased risk of major bleed. Conclusions: Treatment-dose LMWH, mostly in the outpatient setting, is used substantially more often than UFH as bridging therapy in patients with predominately arterial indications for OAC. Overall adverse events, including thromboembolism and bleeding, are similar for patients treated with LMWH or UFH. Postoperative heparin bridging should be used with caution in patients with multiple comorbidities and those undergoing vascular, general, and major surgery. These findings need to be confirmed using large randomized trials for specific patient groups undergoing specific procedures. [source] Thrombophilia and pregnancy outcomesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2005I. PABINGER Summary., Pregnancy complications are still a challenge for physicians, because knowledge of pathomechanisms and prophylactic measures is still limited. In recent years thrombophilia as a risk factor for pregnancy complications has gained much attention in the scientific community. However, data on this topic in the literature are conflicting. Besides an established association between antiphospholipid antibodies and pregnancy loss, available data suggest additional associations for antithrombin deficiency, hyperhomocysteinemia and also for factor (F)V Leiden, prothrombin G20210A variation, and protein S-deficiency. The contribution of thrombophilia to the risk of pre-eclampsia is less well established and recent studies did not confirm earlier data suggesting an association between thrombophilia and pre-eclampsia. A limited number of prospective studies have failed to reveal an increased risk of pregnancy complications in unselected women with thrombosis risk factors. Low-molecular weight heparin (LMWH) seems to have a positive effect on pregnancy outcome after single or recurrent abortions, however, data from only one controlled trial are available. Experience in the prevention of pre-eclampsia by prophylactic heparin is very limited, and in addition, data on pregnancy complications in women with known heritable thrombophilia or a history of thrombosis are inconsistent. These women will usually have a favorable pregnancy outcome referring to the European Prospective Cohort on Thrombophilia Study. In conclusion, thrombophilia screening might be justified in women with pregnancy loss and treatment with LMWH might be considered in those with pregnancy loss and thrombophilia. Further prospective studies and controlled interventional trials are urgently needed. [source] Prevention of venous thromboembolism after acute ischemic strokeJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2005P. W. KAMPHUISEN Summary., Venous thromboembolism (VTE) is a common complication after acute ischemic stroke. When screened by 125I fibrinogen scanning or venography, the incidence of deep-vein thrombosis (DVT) in stroke patients is comparable with that seen in patients undergoing hip or knee replacement. Most stroke patients have multiple risk factors for VTE, like advanced age, low Barthel Index severity score or hemiplegia. As pulmonary embolism is a major cause of death after acute stroke, the prevention of this complication is of crucial importance. Prospective trials have shown that both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are effective in reducing DVT and pulmonary embolism in stroke patients. Current guidelines recommend the use of these agents in stroke patients with risk factors for VTE. Some clinicians are concerned that the rate of intracranial bleeding associated with thromboprophylaxis may outweigh the benefit of prevention of VTE. Low-dose LMWH and UFH seem, however, safe in stroke patients. Higher doses clearly increase the risk of cerebral bleeding and should be avoided for prophylactic use. Both aspirin and mechanical prophylaxis are suboptimal to prevent VTE. Graduated compression stockings should be reserved to patients with a clear contraindication to antithrombotic agents. [source] The influence of extreme body weight on clinical outcome of patients with venous thromboembolism: findings from a prospective registry (RIETE)JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2005R. BARBA Summary.,Background:,Data evaluating the safety of using weight-based dosing of low-molecular-weight heparin (LMWH) in either underweight or obese patients with venous thromboembolism (VTE) are limited. Thus, recommendations based on evidence from clinical trials might not be suitable for patients with extreme body weight. Patients and Methods:,Patients with objectively confirmed, symptomatic acute VTE are consecutively enrolled into the Registro Informatizado de la Enfermedad TromboEmbólica (RIETE) registry. For this analysis, data from patients in the following ranges of body weight were examined: <50, 50,100, and >100 kg. Patient characteristics, underlying conditions, treatment schedules and clinical outcomes during the first 15 days of treatment were compared. Results:,As of August 2004, 8845 patients with acute VTE were enrolled from 94 participating centers. Of these, 169 (1.9%) weighed <50 kg, 8382 (95%) weighed 50,100 kg and 294 (3.3%) weighed >100 kg. Patients weighing <50 kg were more commonly females, were taking non-steriodal antiinflammatory drugs (NSAIDs), and had severe underlying diseases more often than patients weighing 50,100 kg. Their incidence of overall bleeding complications was significantly higher than in patients weighing 50,100 kg (odds ratio 2.2; 95% CI: 1.2,4.0). Patients weighing >100 kg were younger, most commonly males, and had cancer less often than those weighing 50,100 kg. Incidences of recurrent VTE, fatal pulmonary embolism or major bleeding complications were similar in both groups. Conclusions:,Patients with VTE weighing <50 kg have a significantly higher rate of bleeding complications. The clinical outcome of patients weighing over 100 kg was not significantly different from that in patients weighing 50,100 kg. [source] The use of LMWH in pregnancies at risk: new evidence or perception?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2005R. B. ZOTZ No abstract is available for this article. [source] The inhibition of blood coagulation by heparins of different molecular weight is caused by a common functional motif,the C-domainJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2003R. Al Dieri Summary.,Background:,Heparins in clinical use differ considerably as to mode of preparation, molecular weight distribution and pharmacodynamic properties. Objectives:,Find a common basis for their anticoagulant action. Methods:,In 50 fractions of virtually single molecular weight (Mr), prepared from unfractionated heparin (UFH) and four low-molecular-weight heparins (LMWH), we determined: (i) the molar concentration of material (HAM) containing the antithrombin binding pentasaccharide (A-domain); (ii) the specific catalytic activity in thrombin and factor Xa inactivation; (iii) the capacity to inhibit thrombin generation (TG) and prolong the activated partial thromboplastin time (APTT). We also calculated the molar concentration of A-domain with 12 sugar units at its non-reducing end, i.e. the structure that carries antithrombin activity (C-domain). Results:,The antithrombin activity and the effects on TG and APTT are primarily determined by the concentration of C-domain and independent of the source material (UFH or LMWH) or Mr. High Mr fractions (>15 000) are less active, probably through interaction with non-antithrombin plasma proteins. Anti-factor Xa activity is proportional to the concentration of A-domain, it is Ca2+ - and Mr-dependent and does not determine the effect on TG and APTT. Conclusion:,For any type of heparin, the capacity to inhibit the coagulation process in plasma is primarily determined by the concentration of C-domain, i.e. the AT-binding pentasaccharide with 12 or more sugar units at its non-reducing end. [source] ANTICOAGULANT EFFECTS OF LOW MOLECULAR WEIGHT HEPARIN IN HEALTHY CATSJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue S1 2004AJ Alwood Objectives: 1) Validate a chromogenic assay to measure Factor Xa inhibitory activity (anti-Xa activity) in normal feline plasma and following administration of low molecular weight heparins and unfractionated heparin. 2) Compare the effects of two commercially available low molecular weight heparins (LMWH), unfractionated heparin (UFH), and placebo on TEG, anti-Xa activity, PT/aPTT, PCV/TS and platelet count in healthy cats. Methods: Our study consisted of two phases: 1) the evaluation of a commercially available chromogenic anti-Xa assay (Rotachrom Heparin, Diagnostic Stago) for use in cats, and 2) the evaluation of hemostatic effects of LMWH in healthy cats. Phase 1: The anti-Xa assay was validated for use in cats using feline plasma and serial dilutions of the plasma spiked with UFH, enoxaparin, and dalteparin. Phase 2: Five healthy cats were included in a randomized Latin Squares model crossover-design to compare the effects of UFH and LMWH in cats. The cats then received one of the following subcutaneously: 1) 250 IU/kg UFH QID, 2) 100 IU/kg dalteparin BID, 3) 1 mg/kg enoxaparin BID, 4) 0.25 mL/kg 0.9% saline (placebo) QID. A minimum of a two-week washout period separated each treatment period. Each drug was administered for 5 days. Blood samples were obtained to measure anti-Xa, TEG, PT/aPTT, platelet count, and PCV/TS on Days 1, 3, 5, and 6 of each treatment cycle. Samples were collected at time 0 on each sample day for all parameters and on select days at hours 4, 8, and 12 for anti-Xa and TEG. Results: Preliminary results using the validated anti-Xa assay (from the first part of this study) demonstrate that LMWH treatment results in peak anti-Xa activity at the 4-hour sampling time that returned toward baseline by 8 hours (in 5/6 cats treated with LMWH thus far). Similar anticoagulant effects were noted in the TEG parameters of cats receiving LMWH (i.e., peak effects were noted at 4 hours). Analysis of current data by linear regression identifies a relationship between anti-Xa measurements and TEG parameters for cats treated with all heparin therapies (p<0.001). A similar relationship exists between anti-Xa and aPTT. Conclusions: Preliminary results suggest an anticoagulant effect of LMWH in cats that may not be uniform across individuals. Anti-Xa activity or TEG may provide useful tools for monitoring LMWH. [source] Oral, colonic-release low-molecular-weight heparin: an initial open study of Parnaparin-MMX for the treatment of mild-to-moderate left-sided ulcerative colitisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2008L. PASTORELLI Summary Background, Efficacy of heparin and low-molecular-weight heparins (LMWHs) in inflammatory bowel disease (IBD) treatment has been suggested. The multimatrix oral formulation MMX releases active drugs in the colon, avoiding systemic absorption. Parnaparin sodium is the LMWH chosen to be carried in the MMX formulation. Aim, To assess the safety of three different oral dosages (70, 140 and 210 mg once daily) of Parnaparin-MMX (CB-01-05) in left-sided ulcerative colitis (UC). Methods, Left-sided UC patients, with a mild-to-moderate relapse were enrolled. All patients received Parnaparin-MMX for 8 weeks. Clinical Activity Index (CAI), Disease Activity Index (DAI), Endoscopic Activity Index and IBD-QoL were assessed throughout the study. A strict clinical and laboratory follow-up, including assessment of anti-factor Xa activity, was performed. Clinical remission was defined as CAI <4. Results, Ten UC patients were enrolled. One patient retired for clinical deterioration. No relevant side effects, including either interference with haemostasis parameters or increased bleeding, were observed. At the end of the treatment, seven patients (70%) were in clinical remission, only one achieving endoscopic healing. Mean final CAI, DAI and IBD-QoL scores were significantly improved from baseline. Conclusions, Parnaparin-MMX appears to be a safe treatment option in mild-to-moderate UC. Controlled studies are warranted. [source] Cell-mediated Delivery and Targeted Erosion of Vascular Endothelial Growth Factor-Crosslinked HydrogelsMACROMOLECULAR RAPID COMMUNICATIONS, Issue 14 2010Sung Hye Kim Abstract We have previously reported a novel polymeric delivery vehicle that is assembled via interaction between heparin and the vascular endothelial growth factor (VEGF). Here, the cell-responsiveness of this hydrogel,including the delivery of VEGF in response to VEGFR-2 overexpressing PAE/KDR cells (porcine aortic endothelial cells (PAE) equipped with the transcript for the kinase insert domain receptor (KDR)), consequent erosion of the hydrogel matrix, and cellular response,are highlighted. The release of VEGF and hydrogel erosion reached 100% only in the presence of PAE/KDR. The [PEG-LMWH/VEGF] hydrogel (PEG,=,poly(ethylene glycol), LMWH,=,low molecular weight heparin) correspondingly prompted increases in VEGFR-2 phosphorylation and proliferation of PAE/KDR cells. This study proves that growth factor-crosslinked hydrogels can liberate VEGF in response to specific receptors, causing gel erosion and desired cell responses. The promise of these approaches in therapeutic applications, including targeted delivery, is suggested. [source] Ability of low-molecular-weight heparin to alleviate proteinuria by inhibiting respiratory syncytial virus infectionNEPHROLOGY, Issue 7 2008YANNAN GUO SUMMARY: Aim: Low-molecular-weight heparin (LMWH) is a negatively charged glycoprotein and has a very similar structure to that of cell surface heparin sulfate (HS). Thus, LMWH, an analog of HS, may inhibit positively charged respiratory syncytial virus (RSV) infection through cooperative electrostatic association. Methods: In this study, rats were respectively treated with 400 IU/kg LMWH before, during or after being inoculated with 6 × 106 plaque-forming unit (PFU) RSV. RSV and normal control groups were respectively inoculated by RSV and virus-free Dulbecco's modified Eagle's medium (DMEM). HeLa cells in vitro were pretreated with LMWH, elastase (ELA), heparinase (HpaIII) and protamine before being inoculated with 6 × 101 PFU RSV. RSV infectivity was determined by in situ hybridization and plaque assay. Results: After inoculation, the urinary protein excretion and serum parameters in LMWH-treated rats were significantly lower than those in the RSV group. No abnormalities of glomerular structure were observed in LMWH-treated groups whereas swelling and slight hypercellularity in minority glomeruli and foot process effacement were observed in the RSV group. RSV RNA of LMWH-treated rats had weaker expression than that of the RSV group. In vitro, RSV infection in RSV + LMWH, HpaIII + ELAI, protamine + ELAI, ELAI, HpaIII and protamine treatment cells were significantly lower than that of the RSV control, and that in RSV + LMWH was the least. There were no significant differences in RSV infection between ELAI + LMWH and RSV control. Conclusion: Our study confirmed that there is a correlation between RSV and proteinuria in rats. LMWH can alleviate proteinuria in rats through inhibiting RSV from binding with HS which plays an important role in the onset of RSV infection. [source] Warfarin or Low-Molecular-Weight Heparin Therapy does not Prolong Pig-To-Primate Cardiac Xenograft FunctionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2005Guerard W. Byrne Microvascular thrombosis is a prominent feature in cardiac delayed xenograft rejection (DXR). We investigated the impact of warfarin or low-molecular-weight heparin (LMWH) anti-coagulation on xenograft function using a heterotopic pig-to-primate model. Donor hearts were from CD46 transgenic pigs and baboon immunosuppression included tacrolimus, sirolimus, anti-CD20 and TPC, an ,-galactosyl-polyethylene glycol conjugate. Three groups of animals were studied. Group 1 (n = 9) was treated with warfarin, Group 2 (n = 13) with LMWH and Group 3, received no anti-coagulant drugs. The median duration of xenograft function was 20 days (range 3,62 days), 18 days (range 5,109 days) and 15 days (range 4,53 days) in Groups 1 to 3 respectively. Anti-coagulation achieved the targeted international normalized prothrombin ratio (INR) and anti-factor Xa levels consistent with effective in vivo therapy yet, no significant impact on median xenograft function was observed. At rejection, a similar histology of thrombosis and ischemia was apparent in each group and the levels of fibrin deposition and platelet thrombi in rejected tissue was the same. Anti-coagulation with warfarin or LMWH did not have a significant impact on the onset of DXR and microvascular thrombosis. However, a role for specific anti-coagulant strategies to achieve long-term xenograft function cannot be excluded. [source] Low-molecular-weight heparins and angiogenesis,APMIS, Issue 2 2006KLAS NORRBY The involvement of the vascular system in malignancy encompasses not only angiogenesis, but also systemic hypercoagulability and a pro-thrombotic state, and there is increasing evidence that pathways of blood coagulation and angiogenesis are reciprocally linked. In fact, cancer atients often display hypercoagulability resulting in markedly increased thromboembolism, which requires anti-coagulant treatment using heparins, for example. Clinical trials reveal that treatment with various low-molecular-weight heparins (LMWHs) improves the survival time in cancer patients receiving chemotherapy compared with those receiving unfractionated standard heparin (UFH) or no heparin treatment, as well as in cancer patients receiving LMWH as thrombosis prophylaxis during primary surgery. This anti-tumor effect of the heparins appears to be unrelated to their anti-coagulant activity, but the mechanisms involved are not fully understood. Tumor growth and spread are dependent on angiogenesis and it is noteworthy that the most potent endogenous pro- and anti-angiogenic factors are heparin-binding proteins that may be affected by systemic treatment with heparins. Heparin and other glycosaminoglycans play a role in vascular endothelial cell function, as they are able to modulate the activities of angiogenic growth factors by facilitating the interaction with their receptor and promoting receptor activation. To date, preclinical studies have demonstrated that only LMWH fragments produced by the heparinase digestion of UFH, i.e. tinzaparin, exert anti-angiogenic effects in any type of tissue in vivo. These effects are fragment-mass-specific and angiogenesis-type-specific. Data on the effect of various LMWHs and UFH on endothelial cell capillary tube formation and proliferation in vitro are also presented. We hope that this paper will stimulate and facilitate future research designed to elucidate whether the anti-angiogenic or anti-tumor effects of commercial LMWHs in their own right are agent specific and whether anti-angiogenic properties increase the anti-tumor properties of the LMWHs in the clinic. [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] Antenatal pulmonary embolism: risk factors, management and outcomesBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 4 2008M Knight Objectives, To estimate the incidence of antenatal pulmonary embolism and describe the risk factors, management and outcomes. Design, A national matched case,control study using the UK Obstetric Surveillance System (UKOSS). Setting, All hospitals with consultant-led maternity units in the UK. Participants, A total of 143 women who had an antenatal pulmonary embolism between February 2005 and August 2006. Two hundred and fifty nine matched control women. Methods, Prospective case and control identification through the UKOSS monthly mailing. Main outcome measures, Incidence and case fatality rates with 95% CIs. Adjusted odds ratio estimates. Results, One hundred per cent of UK consultant-led obstetric units contributed data to UKOSS. A total of 143 antenatal pulmonary embolisms were reported, representing an estimated incidence of 1.3 per 10 000 maternities (95% CI 1.1,1.5). Seventy per cent of women had identifiable classical risk factors for thromboembolic disease. The main risk factors for pulmonary embolism were multiparity (adjusted odds ratio [aOR] 4.03, 95% CI 1.60,9.84) and body mass index , 30 kg/m2 (aOR 2.65, 95% CI 1.09,6.45). Nine women who had a pulmonary embolism should have received antenatal thromboprophylaxis with low-molecular-weight heparin (LMWH) according to national guidelines; only three (33%) of them did. Six women (4%) had a pulmonary embolism following antenatal prophylaxis with LMWH; three of these women (50%) were receiving lower than recommended doses. Two women had recurrent pulmonary emboli (1.4%, 95% CI 0.2,5.1%). Five women died (case fatality 3.5%, 95% CI 1.1,8.0%). Conclusions, Significant severe morbidity from thromboembolic disease underlies the maternal deaths from pulmonary embolism in the UK. This study has shown some cases where thromboprophylaxis was not provided according to national guidelines, and there may be scope for further work on guideline implementation. [source] | ||||||||||||||||||||||||||||