Nadroparin Research Articles

0491: Nadroparine Activated Fibrinolysis and Renal Function in Patient with Stage Iib-Iiib Cervical Cancer Treated with Radiochemotherapy

0491: Nadroparine Activated Fibrinolysis and Renal Function in Patient with Stage Iib-Iiib Cervical Cancer Treated with Radiochemotherapy

Optimal Duration of Treatment in Surgical Patients With Calf Venous Thrombosis Involving One or More Veins

The aim of this study was to evaluate different durations of treatment in patients with calf venous thrombosis (CVT) involving 1 or more deep veins. The authors studied 2 groups of patients with postsurgical CVT diagnosed by echo-color Doppler. The first group consisted of 68 patients with CVT involving a single vein, and the second group consisted of 124 patients with CVT involving 2 or more veins. Immediately after diagnosis, all patients were treated with nadroparin calcium and sodium warfarin. Heparin treatment was withdrawn after 5-6 days of treatment, when the international normalized ratio (INR) was stabilized between 2 and 3. Each group was divided into 2 subgroups receiving anticoagulation treatment for 6 or 12 weeks, respectively. The endpoint was proximal extension of the thrombotic lesion, defined as the extension of the thrombus to the popliteal and/or femoral vein. In patients with single-vessel CVT there was no significant difference between the 2 subgroups, whereas in patients with CVT involving 2 or more vessels, a statistically significant difference was observed, the number of cases showing proximal extension of the thrombus being higher among patients treated for 6 weeks. Twelve weeks of anticoagulation treatment is better than 6 weeks only in patients with postsurgical CVT involving 2 or more veins.

Peripheral vascular disease endovascular management in patients scheduled for cardiac surgery: a clinical-angiographic approach

Endovascular management of peripheral vascular disease before cardiac surgery is still debated. We sought to present our preliminary experience of endovascular stent placement in patients scheduled for urgent cardiac surgery. Between November 2003 and August 2005, 20 patients scheduled for urgent coronary surgery (13 males, mean age 72.5+/-5.3 years) underwent endovascular repair of PVD on the basis of clinical and angiographic indications. Aspirin (100 mg/day) plus low molecular weight heparin (nadroparin calcium) 100 IU/kg/12 h for urgent coronary surgical revascularization was administered after the procedure. Endovascular stenting has been performed in four clinical settings: renal artery stenting prior to coronary surgery (nine patients) to decrease the impact of extracorporeal circulation on an impaired renal function, iliac artery artery angioplasty and stenting (eight patients) in order to facilitate aortic balloon pump insertion after surgery, subclavian artery angioplasty and stenting propedeutical to arterial conduits bypass surgery (one patient), carotid artery stenting before coronary surgery (two patients). All patients underwent successful endovascular repair followed by cardiac surgery. At a mean follow-up of 12+/-4.6 months all patients are alive and without evident thrombosis or restenosis of the implanted vascular stents. Endovascular treatment of PVD in patients scheduled for urgent coronary surgery may be effective, relatively safe and lasting in spite of low dose antiplatelet regimen.

Validation of the Antifactor Xa and Antifactor IIa Assays for the Potency Assessment of Nadroparin in Pharmaceutical Formulations

The low-molecular weight heparin nadroparin calcium is used clinically for the prevention and treatment of venous and arterial thrombosis. The antifactor Xa and antifactor IIa assays were validated by investigating the parameters of range, linearity (r2 = 0.9905 and r2 = 0.9914, respectively) precision, accuracy, and robustness. The 2 methods incorporated a chromogenic endpoint and detection at 405 nm, yielding good results with detection limits of 0.004 and 0.01 IU/mL and quantitation limits of 0.01 and 0.03 IU/mL, respectively, for the antifactor Xa and antifactor IIa assays. Nadroparin calcium pharmaceutical products were evaluated by the antifactor Xa assay and the antifactor IIa assay, giving potencies between 93.86 and 109.88%, with an antifactor Xa/antifactor IIa ratio between 3.2 and 3.7. The results demonstrated the validity of the assays that are useful methodologies for the routine quality control of nadroparin in pharmaceutical formulations.

Comparison of low-molecular-weight-heparin and unfractionated heparin for acute PTE

Acute pulmonary thromboembolism (PTE) is a serious high mortality pulmonary vascular disease whose effective treatment decreases morbidity and mortality. To determine if low-molecular-weight-heparin (LMWH) is clinically as efficient and safe as unfractionated heparin (UH) in patients with diagnosis of acute non-massive PTE, our study compares the efficacy, adverse effects and costs of LMWH and UH. One hundred and fourteen patients with non-massive acute PTE were randomly divided into LMWH (nadroparin calcium) and UH groups. Oxygenation index, D-dimer, fibrinogen (FG), lung ventilation/perfusion (V/Q) scan and computed tomography pulmonary angiography (CTPA) were observed before anticoagulation and on day 14 after anticoagulation. In both groups, the ABG (arterial blood gas) analysis showed PaO(2) and PaCO(2) were elevated, P(A-a)O(2) was decreased and oxygenation index (PaO(2)/FIO(2)) was elevated, D-dimer and fibrinogen were decreased, lung V/Q and CTPA showed embolized segments reduced (P<0.05). Hemorrhage and thrombocytopenia occurred in 3.5% of the LMWH group. Hemorrhage occurred in 5.3% and thrombocytopenia occurred in 7.0% of the UH group. The average cost in the LMWH group was RMB 1218.60 Yuan and RMB 1541.40 Yuan in the UH group. LMWH and UH are equally effective for treatment of non-massive acute PTE, but LMWH may have a lower prevalence of complications and is less expensive.

Clinical Diagnosis and Management of Children with Large Splenic Hemangiomas Accompanied with Consumptional Coagulopathy.

Objective To improve the diagnosis and treatment of children with large splenic hemangiomas accompanied with consumptional coagulopathy.Methods From Dec 2003 to May 2004, 2 children with large splenic hemangiomas and coagulational abnormality were admitted consecutively. Both of them were boys, aged 2.8 and 3.5 years old, respectively. Both of them had splenomegaly, and Patient 2 also had multiple bone hemangiommas(confirmed by biopsy before splenectomy) on addmission. Imaging studies failed to confirm the diagnosis of splenic hemangiomas. Both of them received 24 hours continuous subcutaneous injection of Nadroparin Calcium therapy and the coagulopathies were improved. Then, Patient 1 had splenectomy, and Patient 2 received Nadroparin Calcium therapy plus steroid and interferon therapy for 6 months, then also went to splenectomy.Results Both of the two patients had normal platelet counts and normal coagulation parameters just after their splenectomies. Histology studies confirmed the diagnoses of splenic cavernous hemangiomas. Before splenectomy, Patient 2 had a stable status for 6 months after he received Nadroparin Calcium therapy plus interferon and steroid therapy. Till March 31th, 2005, Patient 1 had disease free for 13 months, and Patient 2 had normal platlet counts and normal coagulation parameters for 5 month besides his stable multiple bone lessions.Conclusion Childhood large splenic hemangioma accompanied with consumptional coagulopathy is a rare disease, which can be cured by splenectomy. Before operation, it is necessary to improve the coagulation abnormality, and 24 hours continuous subcutaneous Nadroparin Calcium injection plus coagulation factors transfusion is effective.

Filter Run Time in CVVH: Pre- versus Post-Dilution and Nadroparin versus Regional Heparin-Protamine Anticoagulation

Background/Aims: To study the effect of different modes of continuous veno-venous haemofiltration (CVVH) on filter run time (FRT). Methods: We studied, in two consecutive prospective, randomised and crossover studies, 16 and 15 patients with acute renal failure during critical illness. Study A compared pre- versus post-dilution, and study B compared regional anticoagulation with heparin (pre-filter) and protamine (post-filter) (HP) versus nadroparin (NP) pre-filter. All CVVH sessions were standardised. Analyses were by Wilcoxon rank sum tests. Results: Study A: During pre-dilution the median FRT was 45.7 vs. 16.1 h in post-dilution CVVH (p = 0.005). The median creatinine clearance during pre-dilution was 33 vs. 45 ml/min in post-dilution (p = 0.001). Study B: During NP, median FRT was 39.5 vs. 12.3 h during HP CVVH (p = 0.045). Conclusions: Pre-dilution CVVH results in the greatest FRT but a lower plasma creatinine clearance compared to post-dilution. Regional anticoagulation with heparin-protamine resulted in a significantly shorter FRT compared to systemic NP anticoagulation.

Citrate anticoagulant hemodialysate in renal failure patients at high risk of bleeding

Objective: The aim of this study was to observe the anticoagulant effect of the new type of citrate anticoagulant hemodialysate in renal failure patients at high risk of bleeding. Methods: 57 patients at high risk of bleeding were given hemodialysis for 4 hours 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 hemodialysate and with no anticoagulant. Group 3 was hemodialysed with bicarbonate hemodialysate and with nadroparin calcium (a low molecular weight heparin, LMWH) as anticoagulant. Bleeding complication, coagulation of extracorporeal circuit, venous blood pressure, heart rate, QTC, activated coagulation time (ACT), ionized‐calcium (iCa++), total calcium and pH, , Na+, K+, Cl−, BUN, Cr, GPT, GST, TBIL, DBIL, as well as the blood cell counts were monitored during hemodialysis, and a scanning electron microscopic (SEM) analysis was used to investigate the morphology of thrombus formation and cellular aggregation on the interior surface of hemodialysis membranes. Results: During the hemodialysis in Group 1, venous blood pressure increased continuously, resulting in the failure of hemodialysis for 4 out of 19 patients. Hemodialysis for 4 hours in Group 2 were all successfully fulfilled. No bleeding episodes occurred. No severe clotting of dialyzers and blood accesses was observed. ACT was extended and iCa++ decreased obviously in the venous line, but ACT and iCa++ in vivo were normal. pH, tended to increase but not to metabolic alkalosis levels. Na+, K+, Cl−, GPT, GST, TBIL, DBIL, as well as the counts of blood cells were all within the normal range. There was no severe thrombus observed by SEM in the hollow fibers. In Group 3, severe bleeding complication happened to 3 out of 19 patients, and one of them died. ACT was extended obviously at the arterial end. Conclusions: The citrate anticoagulant hemodialysate was proved to be practical, safe and effective. So it is indicated for patients with an active or recently active bleeding focus.

Influence of low molecular weight heparin preparations on human internal thoracic artery contraction

Low molecular weight heparins (LMWHs) offer practical and potential pharmacological advantages over unfractionated heparin in multiple applications but have not been studied as vasoactive agents. The purpose of this study was to investigate the effects of two commercial preparations of LMWHs, enoxaparin sodium and nadroparin calcium, on vasoconstriction in the human internal thoracic artery (ITA) in vitro. Samples of redundant ITA segments obtained from 36 patients who underwent coronary artery bypass surgery were cut into 3mm wide rings and suspended in 20 ml organ bath. Activity of ITA rings precontracted with 80 mM KCl, 0.1 microM endothelin-1 (ET-1) and 1 microM norepinephrine (NE) after administration of enoxaparin and nadroparin in accumulative concentration ranging from 0.1 to 13.2 UI AXa/ml were recorded under isometric conditions by means of force transducers with digital output. The contraction after 80 mmol KCl, 0.1 microM ET-1 and 1 microM NE administration was treated as a control. Both studied LMWHs in concentration ranging from 0.12 to 13.2 UI AXa/ml did not change basal tonus and KCl precontracted ITA rings. When used in concentrations higher than 13.2 UI AXa/ml nadroparin but not enoxaparin significantly increased the tension in KCl precontracted arterial rings. In NE and ET-1 precontracted rings enoxaparin and nadroparin caused dose dependent relaxation without significant differences between both preparations. Incubation with nitric oxide blocker-Nomega-NITRO-L-ARGININE (L-NNA) in concentration 0.2 mM caused a significant attenuation of relaxant responses to both studied LMWHs in NE and ET-1 precontracted rings. LMWHs can have vasorelaxant effects on the receptor-mediated ITA vasoconstriction. The results suggest that LMWHs-induced relaxation in the human ITA is at least partially caused by nitric oxide release. Although the vasoactive effects are not the primary advantage of these drugs used as antithrombotics, such effects might have some clinical importance in the treatment and prophylaxis of graft spasm.

Análisis crítico de un artículo

Few reports have addressed the value of unfractionated heparin (UFH) or low-molecular-weight heparin in treating the fill spectrum of patients with venous thromboembolism (VTE), including recurrent VTE and pulmonary embolism. In an open, multicenter clinical trial, 720 consecutive patients with acute symptomatic VTE, including 119 noncritically ill patients (16.5%) with pulmonary embolism and 102 (14.2%) with recurrent VTE, were randomly assigned to treatment with subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm (preceded by an intravenous loading dose), or fixed-dose (adjusted only to body weight) subcutaneous nadroparin calcium. Oral anticoagulant therapy was started concomitantly and continued for at least 3 months. We recorded the incidence of major bleeding during the initial heparin treatment and that of recurrent VTE and death during 3 months of follow-up. Fifteen (4.2%) of the 360 patients assigned to UFH had recurrent thromboembolic events, as compared with 14 (3.9%) of the 360 patients assigned to nadroparin (absolute difference between rates, 0.3%; 95% confidence interval, -2.5% to 3.1%). Four patients assigned to UFH (1.1%) and 3 patients assigned to nadroparin (0.8%) had episodes of major bleeding (absolute difference between rates, 0.3%; 95% confidence interval, -1.2% to 1.7%). Overall mortality was 3.3% in each group. Subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm is as effective and safe as fixed-dose nadroparin for the initial treatment of patients with VTE, including those with pulmonary embolism and recurrent VTE.

Comparative effectiveness of several agents for preventing postoperative adhesions.

Postoperative adhesions (PAs) are usually clinically asymptomatic. Symptomatic cases, however, may present with chronic abdominal and pelvic pain, infertility, and intestinal obstruction; and they may require intensive, costly therapeutic modalities. Various agents have been used to prevent PAs, but the results indicate general suboptimal effectiveness. Our objective was to evaluate the comparative effectiveness of two pharmacologic agents for preventing PA: nadroparine calcium (low-molecular-weight heparin, or LMWH) and aprotinin, as well as a barrier agent, sodium hyaluronate/carboxymethycellulose (SCMC). Our subjects were 40 male Wistar-Albino rats divided into four groups, each consisting of 10 rats, which underwent standard cecal abrasion preceding midline laparotomy. In the control group (group 1) 1 ml of 0.9% NaCl was administered intraperitoneally before abdominal closure. In the three preventive groups, 100 U AXa (anti factor X activity) LMWH, 1800 IU aprotinin, and SCMC were administered intraperitoneally to groups 2, 3, and 4, respectively. Relaparotomy was performed on the 14th postoperative day. Visceral and abdominal wall adhesions were scored in a blinded fashion. The adhesion scores (mean +/- SD) for groups 1, 2, 3, and 4 were 2.00 +/- 0.67, 0.6.00 +/- 0.84, 1.10 +/- 0.74, and 0.20 +/- 0.42, respectively. The differences in the adhesion scores among all three preventive groups (groups 2, 3, 4) were statistically significant when compared with the control group ( p < 0.001, p = 0.017, p < 0.001, respectively). Intraperitoneal SCMC and administration of LMWH were more effective than giving aprotinin.

Subcutaneous Adjusted-Dose Unfractionated Heparin vs Fixed-Dose Low-Molecular-Weight Heparin in the Initial Treatment of Venous Thromboembolism

Few reports have addressed the value of unfractionated heparin (UFH) or low-molecular-weight heparin in treating the full spectrum of patients with venous thromboembolism (VTE), including recurrent VTE and pulmonary embolism. In an open, multicenter clinical trial, 720 consecutive patients with acute symptomatic VTE, including 119 noncritically ill patients (16.5%) with pulmonary embolism and 102 (14.2%) with recurrent VTE, were randomly assigned to treatment with subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm (preceded by an intravenous loading dose), or fixed-dose (adjusted only to body weight) subcutaneous nadroparin calcium. Oral anticoagulant therapy was started concomitantly and continued for at least 3 months. We recorded the incidence of major bleeding during the initial heparin treatment and that of recurrent VTE and death during 3 months of follow-up. Fifteen (4.2%) of the 360 patients assigned to UFH had recurrent thromboembolic events, as compared with 14 (3.9%) of the 360 patients assigned to nadroparin (absolute difference between rates, 0.3%; 95% confidence interval, -2.5% to 3.1%). Four patients assigned to UFH (1.1%) and 3 patients assigned to nadroparin (0.8%) had episodes of major bleeding (absolute difference between rates, 0.3%; 95% confidence interval, -1.2% to 1.7%). Overall mortality was 3.3% in each group. Subcutaneous UFH with dose adjusted by activated partial thromboplastin time by means of a weight-based algorithm is as effective and safe as fixed-dose nadroparin for the initial treatment of patients with VTE, including those with pulmonary embolism and recurrent VTE.

Hypersensitivity to Nadroparin Calcium

The use of heparin to prevent or treat venous and ethyl abuse, which was stopped 20 years before pulmonary thrombosis, unstable angina and admission. In order to perform right and left side non-ST-elevation myocardial infarction is widely cardiac catheterisation, oral anticoagulants were accepted. Nowadays, for many of these indications switched to nadroparin calcium (Fraxiparine®, Sathe unfractionated heparins (UFH; molecular weight nofi-Synthelabo, Brussels, Belgium)1 7.500U AXa [MW] 3–30 kDa) are largely being replaced by IC (Institut Choay) twice daily. Ten days after startlow-molecular-weight heparins (LMWHs; MW ≤5 ing this preservative-free LMWH he developed a kDa) because of the improved pharmacokinetic and large eczematous plaque (5 × 15cm) at the injection pharmacodynamic properties as well as a better site. There was neither thrombocytopenia nor eosisafety profile of the latter.[1-3] Adverse reactions to nophilia. The lesion subsided within 1 week after heparins include haemorrhages, osteopenia and imstopping the drug and application of a topical cortimune-mediated hypersensitivity reactions, e.g. costeroid. heparin-induced thrombocytopenia without and Investigations were performed in the patient and with (fatal) thrombosis,[4-10] immediate hypersensiin a healthy control who was free of any medication. tivity reactions such as rhinoconjunctivitis,[11] asthA lymphocyte transformation test (LTT) with ma,[12] urticaria, angio-oedema and anaphylaxnadroparin calcium assessed by the incorporation is,[12-25] and delayed cutaneous reactions generally of [methyl-3H] thymidine[36] was strongly positive manifesting as infiltrated, eczematous plaques or with a stimulation index, i.e. counts per minute leukocytoclastic vasculitis (type III Arthus reaction) (cpm) of the nadroparin calcium-stimulated lymat injection sites.[26-35] phocytes divided by the cpm cultured with serumfree medium, of 135 (normal <2). Flow cytometric 1. Case Report analysis of in vitro nadroparin calcium-activated A 47-year-old man with severe heart failure due basophils (BAT)[37] showed a CD63 upregulation to a dilated cardiomyopathy was admitted for carabove spontaneous expression of 63% (normal diac transplantation screening. His medical history <15%). Meanwhile, the patient was re-administered included pacemaker implantation because of a sick nadroparin calcium accidentally, which resulted in sinus syndrome with syncope, depression, osteoan immediate local erythematous eruption of several penia, gastritis, antral ulcers, a small biliary cyst and centimetres and a generalised pruritus and urticaria.

Postoperative nadroparin administration for prophylaxis of thromboembolic events is not associated with an increased risk of hemorrhage after spinal surgery.

To determine the risk of postoperative hemorrhage during a 3-year period of early postoperative administration of nadroparin (Fraxiparin) plus compression stockings in a large cohort of patients who underwent spinal surgery. A total of 1,954 spinal procedures at different levels (503 cervical, 152 thoracic and 1,299 lumbar), performed between June 1999 and 2002 at the Department of Neurosurgery, Johann-Wolfgang-Goethe University Frankfurt, were included in this study. To prevent venous thromboembolic events (VTE), all patients were routinely treated subcutaneously with 0.3 ml of early (less than 24 h) postoperative nadroparin calcium (Fraxiparin) (2850 IU anti-Xa, Sanofi Winthrop Industrie, France) plus intra- and postoperative compression stockings until discharge. The occurrence of a postoperative hematoma (defined as a hematoma requiring surgical evacuation because of space occupation and/or neurological deterioration) and a deep venous thrombosis (DVT) were recorded in a database and analyzed retrospectively. 13 (0.7%) of the 1,954 spinal operations were complicated by major postoperative hemorrhages. In 5 of the 13 patients (38.5%) the hemorrhage occurred on the day of surgery before the administration of nadroparin. Thus, the hemorrhage rate of patients receiving nadroparin was 0.4% (8/1,949). Ten (77%) of the 13 patients with major postoperative hematoma showed a progressive neurological deficit, which resolved in 6 patients and resulted in a hematoma-related morbidity of 31% (4/13). Only 1 patient (0.05%) in this series developed a clinically evident DVT, and none of the patients suffered from pulmonary embolus during the hospital stay. Although retrospective, this is to date the largest study providing information about the hemorrhage rate associated with early postoperative anticoagulation following spinal surgery. The results confirm that early postoperative pharmacological thromboembolic prophylaxis using nadroparin in patients with spinal surgery is not associated with an increased risk of postoperative hemorrhage.

Tolerability of percutaneous coronary interventions in patients receiving nadroparin calcium for unstable angina or non-Q-wave myocardial infarction: the Angiofrax study

SUMMARYBackground: Nadroparin, a low-molecular-weight heparin (LMWH), is an alternative to unfractionated heparin for the acute management of patients with non-ST elevation acute coronary syndrome (ACS): unstable angina or non-Q-wave myocardial infarction. However, unfractionated heparin can be substituted for LMWH in patients requiring percutaneous coronary interventions (PCIs) for the duration of the procedure. The tolerability of this anti-thrombotic regimen (i.e. unfractionated heparin for the duration of PCIs, preceded and followed by subcutaneous injection of nadroparin) is not yet documented.Design and methods: This open-label 6-day study was carried out in 302 patients to test the tolerability of this anti-thrombotic regimen in patients requiring PCIs. The primary end-point of the study was the incidence of major haemorrhage over the whole study duration (6 days). The secondary end-point was the need for transfusion and vascular repair after PCI.Results: The incidence of major haemorrhage in patients undergoing coronary angiography (CA) without or with PCIs was 1.4% and 1.3%, respectively, and the incidence of minor haemorrhage was 10.7% and 23.5%, respectively. These results are consistent with published data.Conclusions: These results suggest that CA and PCIs can be performed safely in patients being treated for unstable angina or non-Q-wave myocardial infarction receiving nadroparin pre-and post-coronary procedure and/or intervention, substituted by unfractionated heparin for the duration of the intervention.

Effects of heparin fractions on the prevention of skin necrosis resulting from adriamycin extravasation: an experimental study.

Extravasation of a chemotherapeutic agent is one of the most frequent complications in cancer patients. Full-thickness skin necrosis often occurs after extravasation. Alternative approaches to treatment are local wound care, elevation, and hypothermia. It was shown that heparin prevents skin necrosis. In this experimental study, the effects of heparin fractions on the prevention of skin necrosis were compared by applying an extravasation model of Adriamycin in rats. Forty Sprague-Dawley male rats weighing 250 to 300 g were used. A total of 0.3 ml doxorubicin hydrochloride was administered subcutaneously to all rats. Ten minutes later, in the control group (group I), 1 ml normal saline was administered subcutaneously. In the first experimental group (group II), 100 U per day heparin sodium was administered in a volume of 1 ml subcutaneously. In the second experimental group (group III), nadroparin calcium (5 anti-Xa U per kilogram per day) was administered. In the third and last experimental group (group IV), dalteparin sodium (5 anti-Xa U per kilogram per day) was administered. All drugs were administered for 2 weeks. Necrotic areas were measured 4 weeks later. Statistical analysis was performed using the Kruskal-Wallis analysis of variance and the Mann-Whitney test. Heparin fractions caused a decreased ulcer rate and size than controls ( < 0.05). There was no superiority among heparin fractions. The authors think that low-molecular weight heparins are preferred, considering the higher risk of bleeding with unfractionated heparin.

Combination of low molecular weight heparins with antiplatelet agents in non-ST elevation acute coronary syndromes: an update.

This article reviews the use of low molecular weight heparin (LMWH) and antiplatelet agents in the treatment of unstable angina and non-ST segment elevation myocardial infarction (NSTEMI), which together account for 1 million hospitalisations annually in the US alone. Mortality and recurrent myocardial infarction (MI) in these conditions is currently approximately 8 to 16% at 1 month, and there is a need to optimise treatment further. Since their introduction, LMWHs have been shown to be successful and well tolerated in the treatment of unstable angina and NSTEMI, but differences have been seen in their efficacy compared with the parent compound, unfractionated heparin (UFH). A meta-analysis of all LMWHs, grouped, versus UFH showed equivalent efficacy and safety. The LMWHs dalteparin sodium and nadroparin calcium have independently been shown to be as effective as UFH. However, enoxaparin sodium has been shown to have greater clinical efficacy than UFH in patients with unstable angina (UA)/NSTEMI. One area of new research is patients with UA/NSTEMI who later undergo percutaneous coronary interventions (PCI), and early data suggest enoxaparin can be safely used as an anticoagulant instead of UFH in these patients. There is a wealth of data for glycoprotein (GP) IIb/IIIa receptor antagonists (abciximab, eptifibatide, lamifiban, and tirofiban), although some are conflicting. Recent meta-analyses suggest that some benefit is conferred by using these compounds, particularly in patients who undergo PCI. Recent trials have focussed on combining GP IIb/IIIa antagonists with LMWH, and although data is still scant, the ACUTE (Anti-thrombotic Combination Using Tirofiban and Enoxaparin) and ACUTE II studies indicate the safety and potential clinical benefit of combining enoxaparin with tirofiban in patients with UA/NSTEMI not undergoing PCI, compared with UFH and tirofiban. The NICE (National Investigators Collaborating on Enoxaparin) 4 study collected data on the combination of enoxaparin and abciximab in patients undergoing PCI, and both safety and efficacy data compared well with historical data collected on the use of UFH with abciximab. The more recent NICE 3 study extended this finding to the combination of enoxaparin with abciximab, tirofiban or eptifibatide. The safety of two doses of dalteparin and abciximab had also been investigated, with the higher dose the efficacious, and also with safety, in patients undergoing PCI. In addition, a GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes) IV substudy found that dalteparin had equivalent safety to UFH when co-administered with abciximab in patients not undergoing PCI. The NICE 3 and 4 trials were not randomised comparisons, and as such there results must be interpreted with caution. Recently, the CRUISE (Coronary Revascularisation Utilizing Integrelin [eptifibatide] and Single-bolus Enoxaparin) and INTERACT (Integrelin and Enoxaparin randomised assessment of Acute Coronary Syndromes Treatment) studies have provided evidence for both the safety and efficacy of enoxaparin combined with eptifibatide in non-ST elevation patients with acute coronary syndromes. A further study (SYNERGY [Superior Yield of the New strategy of Enoxaparin, Revascularization and GlYcoprotein IIb/IIIa inhibitors]) will investigate the efficacy of the combination of enoxaparin with abciximab versus that of UFH and abciximab in a large cohort of 8000 patients. The use of GP IIb/IIIa agents and LMWH in patients with UA/STEMI has led to their use in those with ST-elevation MI, and studies indicate LMWH is efficacious and can be used safely as an adjunct to thrombolysis. New studies will investigate the use of these agents in patients with STEMI not undergoing thrombolysis and we await the results of these studies.

Nadroparin calcium: Calcinosis cutis at injection sites following subcutaneous administration: 2 case reports

Nadroparin calcium: Calcinosis cutis at injection sites following subcutaneous administration: 2 case reports

Low Molecular Weight Heparin Treatment in Steroid Refractory Ulcerative Colitis: Clinical Outcome and Influence on Mucosal Capillary Thrombi

Background : In ulcerative colitis, a state of hypercoagulation has frequently been observed. Unfractionated heparin has shown beneficial effects as an adjuvant treatment of steroid refractory ulcerative colitis in open trials and in one placebo-controlled trial. Low molecular weight heparin (LMWH) offers advantages in the method of administration, but it has not been evaluated in severe ulcerative colitis. We therefore assessed the tolerability, safety and potential therapeutical effects of LMWH in hospitalized patients with steroid refractory ulcerative colitis. Methods : Twenty-five patients with severely active ulcerative colitis were included in an open-labelled trial. All patients had a flare-up of disease under glucocorticosteroid treatment. Nadroparine calcium 5.700 IE anti-Xa/0.6 mL s.c. was self-administered twice daily for 8 weeks. Patients were monitored for possible adverse events, and changes in clinical symptoms and in laboratory, endoscopical and histological results were analysed. Results : Tolerability and compliance were excellent and no serious adverse events occurred. In 20 of 25 patients, a good clinical and laboratory response was observed. Also, the endoscopic and histological signs of inflammation were found to be significantly improved. However, this was not accompanied by a significant reduction in the number of mucosal microvascular thrombi after 8 weeks of LMWH treatment. Conclusion : LMWH may be a safe adjuvant therapy for patients with active, glucocorticosteroid refractory ulcerative colitis.

Low molecular weight heparin versus oral anticoagulants in the long-term treatment of deep venous thrombosis

Purpose: The purpose of this study was to evaluate whether low molecular weight heparin (LMWH) could be equal or more effective than conventional oral anticoagulants (OAs) in the long-term treatment of deep venous thrombosis (DVT). Methods: One hundred fifty-eight patients with symptomatic DVT of the lower limbs confirmed by means of duplex ultrasound scan were randomized to receive 3 to 6 months' treatment with nadroparine calcium or acenocoumarol. Quantitative and qualitative duplex scan scoring systems were used to study the evolution of thrombosis in both groups at 1, 3, 6, and 12 months. Results: During the 12-month surveillance period, two (2.5%) of the 81 patients who received LMWH and seven (9%) of the 77 patients who received OAs had recurrence of venous thrombosis (not significant). In the LMWH group no cases of major bleeding were found, and four cases (5.2%) occurred in the OA group (not significant). The mortality rate was nine (11.1%) in the LMWH group and 7.8% in the OA group (not significant). The quantitative mean duplex scan score decreased in both groups during the follow-up and had statistical significance after long-term LMWH treatment on iliofemoral DVT (1, 3, 6, and 12 months), femoropopliteal DVT (1-3 months), and infrapopliteal DVT (first month). Duplex scan evaluation showed that the rate of venous recanalization significantly increased in the common femoral vein at 6 and at 12 months and during each point of follow-up in the superficial and popliteal veins in the LMWH group. Reflux was significantly less frequent in communicating veins after LMWH treatment (17.9% vs 32.2% in the OA group). The reflux rates in the superficial (22.4% in the LMWH group, 30.6% in OA group) and deep (13.4% vs 17.7%) venous system showed no significant differences between groups. Conclusions: The unmonitored subcutaneous administration of nadroparine in fixed daily doses was more effective than oral acenocoumarol with laboratory control adjustment in achieving recanalization of leg thrombi. With nadroparine, there was less late valvular communicating vein insufficiency, and it was at least as efficacious and safe as oral anticoagulants after long-term administration. These results suggest that LMWHs may therefore represent a real therapeutic advance in the long-term management of DVT. (J Vasc Surg 2001;33:77-90.)