Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis.
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BACKGROUND AND PURPOSE: Treatment of cerebral sinus thrombosis with heparin is controversial. We conducted a double-blind, placebo-controlled multicenter trial to examine whether anticoagulant treatment improves outcome in patients with sinus thrombosis. METHODS: Patients were randomized between body weight-adjusted subcutaneous nadroparin (180 anti-factor Xa units/kg per 24 hours) and matching placebo for 3 weeks (double-blind part of trial), followed by 3 months of oral anticoagulants for patients allocated nadroparin (open part). Patients with cerebral hemorrhage caused by sinus thrombosis were also included. RESULTS: Sixty patients were enrolled, and none were lost to follow-up. In 1 patient the diagnosis proved wrong after randomization. After 3 weeks, 6 of 30 patients (20%) in the nadroparin group and 7 of 29 patients (24%) in the placebo group had a poor outcome, defined as death or Barthel Index score of <15 (risk difference, -4%; 95% CI, -25 to 17%; NS). After 12 weeks, 4 of 30 patients (13%) in the nadroparin group and 6 of 29 (21%) in the placebo group had a poor outcome, defined as death or Oxford Handicap Score of >/=3 (risk difference, -7%; 95% CI, -26% to 12%; NS). There were no new symptomatic cerebral hemorrhages. One patient in the nadroparin group had a major gastrointestinal hemorrhage, and 1 patient in the placebo group died from clinically suspected pulmonary embolism. CONCLUSIONS: Patients with cerebral sinus thrombosis treated with anticoagulants (low-molecular-weight heparin followed by oral anticoagulation) had a favorable outcome more often than controls, but the difference was not statistically significant. Anticoagulation proved to be safe, even in patients with cerebral hemorrhage. (+info)
Low-molecular-weight heparin in outpatient treatment of DVT.
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Patients with a diagnosis of acute deep venous thrombosis have traditionally been hospitalized and treated with unfractionated heparin followed by oral anticoagulation therapy. Several clinical trials have shown that low-molecular-weight heparin is at least as safe and effective as unfractionated heparin in the treatment of uncomplicated deep venous thrombosis. The use of low-molecular-weight heparin in an outpatient program for the management of deep venous thrombosis provides a treatment alternative to hospitalization in selected patients. Use of low-molecular-weight heparin on an outpatient basis requires coordination of care, laboratory monitoring, and patient education and participation in treatment. Overlapping the initiation of warfarin permits long-term anticoagulation. Advantages include a decreased incidence of heparin-induced thrombocytopenia and fewer episodes of bleeding complications. Future clinical trials evaluating the safety and efficacy of low-molecular-weight heparin in the treatment of complicated deep venous thrombosis will further define appropriate indications for use and strategies for outpatient management. (+info)
Low-molecular weight heparin restores in-vitro trophoblast invasiveness and differentiation in presence of immunoglobulin G fractions obtained from patients with antiphospholipid syndrome.
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The present study was designed to investigate the effects of immunoglobulin G obtained from patients with antiphospholipid syndrome (APS) on in-vitro models of trophoblast invasiveness and differentiation. We tested the binding of affinity-purified immunoglobulin G to human primary trophoblast cells. These antibodies affected the invasiveness and differentiation of cytotrophoblast cells after binding to the cell surface. In addition, we determined whether the drugs used to treat APS might be able to restore the trophoblast functions. Low-molecular weight heparin, in a dose-dependent manner, significantly reduced the immunoglobulin G binding to trophoblast cells and restored in-vitro placental invasiveness and differentiation. No effect was observed in the presence of acetylsalicylic acid. These observations may help in understanding the role of these treatments in women with APS. (+info)
Low-molecular-weight heparin in preventing and treating DVT.
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Low-molecular-weight heparin is a relatively recent addition to the list of therapies for prophylaxis and treatment of deep venous thrombosis (DVT). As a prophylactic, low-molecular-weight heparin is as effective as standard heparin or warfarin and does not require monitoring of the activated partial thromboplastin time or the International Normalized Ratio. Traditionally, treatment for DVT required patients to be hospitalized for administration of intravenous heparin. With subcutaneous injections of low-molecular-weight heparin, treatment of DVT can be initiated or completed in the outpatient setting with no increased risk of recurrent thromboembolism or bleeding complications. Low-molecular-weight heparin is an attractive option for use in patients with a first episode of DVT, no risk factors for bleeding and the ability to administer injections with or without the help of a visiting nurse or family member. (+info)
Reduction of myocardial damage by prolonged treatment with subcutaneous low molecular weight heparin in unstable coronary artery disease. FRISC study group. Fragmin during Instability in Coronary Artery Disease.
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AIMS: Several studies have proved heparin useful in treating patients with unstable coronary artery disease. The present study investigates whether Selvester QRS scoring for estimation of myocardial infarct size increases the incidence of detection of acute myocardial infarction during follow-up in a trial of patients with unstable angina/non-Q wave myocardial infarction treated with low molecular weight heparin or placebo. Finally it will be discussed how the QRS score, used for end-point identification, impacts on the power calculation in clinical trials. METHODS AND RESULTS: Electrocardiographic data on 1276 patients (644 in the placebo group, 632 in the low molecular weight heparin treatment group) were available. All ECGs were scored according to the Selvester QRS scoring method. At 40 days, more patients in the placebo than in the heparin group had achieved a threshold level of QRS score (25.9% vs 21.1%, P=0.05). Myocardial infarction, diagnosed as per the classic Q wave criteria, occurred in 3.7% of patients in the placebo group and in 0.9% in the low molecular weight heparin group at 6 days (P=0.002). At 40 days, the rates were 8.2% (placebo) and 5.7% (low molecular weight heparin, P=0.2). By combining the classic criteria with the Selvester method the myocardial infarction end-point rate in both groups was almost doubled (8.2% to 14.4% in the placebo group and 5.7% to 11.1% in the low molecular weight heparin group, P=0.07). The 216 patients with non-evaluable electrocardiograms did not differ from the 1276 patients as regards baseline characteristics; however, they had a significantly poorer prognosis, with a death/myocardial infarction rate of 20% at 40 days, compared with 8% among the patients with evaluable electrocardiograms (P<0.00001). CONCLUSION: Long-term subcutaneous treatment with low molecular weight heparin decreases the number of subsequent myocardial infarctions - determined both conventionally and by an increase in QRS score - in patients with unstable coronary artery disease. Silent myocardial infarctions detected by QRS score, as well as clinical myocardial infarctions, could be used as end-points in clinical trials of ischaemic heart disease and thus lower the population needed for obtaining statistical power. (+info)
Superselective intraarterial fibrinolysis in central retinal artery occlusion.
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Intraarterial fibrinolysis was performed in three patients with acute central retinal artery occlusion using recombinant tissue plasminogen activator as a fibrinolytic agent. In two cases the ophthalmic artery was selectively catheterized, and in the other a thrombolytic drug was infused into the ophthalmic artery by way of the meningeal collaterals. All patients experienced visual improvement. Fibrinolysis can produce better results than obtained from conservative treatment. A good prognosis can be achieved if the treatment starts within the first 4 to 5 hours after occlusion. (+info)
Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin : clinical implications for heparin-induced thrombocytopenia.
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BACKGROUND: Cardiopulmonary bypass (CPB) induces platelet activation with release of platelet factor 4 (PF4), and patients are exposed to high doses of heparin (H). We investigated whether this contributes to the development of antibodies to H-PF4 and heparin-induced thrombocytopenia (HIT). METHODS AND RESULTS: CPB was performed with unfractionated heparin (UFH) in 328 patients. After surgery, patients received UFH (calcium heparin, 200 IU. kg-1. d-1) (group 1, n=157) or low-molecular-weight heparin (LMWH, Dalteparin, 5000 IU once daily) (group 2, n=171). Eight days after surgery, antibodies to H-PF4 were present in 83 patients (25.3%), 46 in group 1 and 37 in group 2 (P=0.12). Most patients (61%) had IgG1 to H-PF4, but only 8 samples with antibodies induced platelet activation with positive results on serotonin release assay. HIT occurred in 6 patients in group 1, but no thrombocytopenia was observed in subjects receiving LMWH, although 2 had high levels of antibodies with positive serotonin release assay results. When antibodies to H-PF4 were present, mean platelet counts were lower only in patients with FcgammaRIIA R/R131 platelets. CONCLUSIONS: These results provide evidence that the development of antibodies to H-PF4 after CPB performed with UFH is not influenced by the postoperative heparin treatment. The antibodies associated with high risk of HIT are mainly IgG1, which is present at high titers in the plasma of patients continuously treated with UFH. (+info)
Characterization of [3H]-heparin binding in human vascular smooth muscle cells and its relationship to the inhibition of DNA synthesis.
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1. The glycosaminoglycan heparin inhibits vascular smooth muscle cell (VSMC) proliferation and migration, but the mechanism of its antiproliferative action remains unclear. Heparin has been reported to bind to high affinity cell surface sites on animal VSMC before undergoing receptor mediated endocytosis resulting in signal transduction into the cytoplasm and modulation of genes involved in proliferation. In this study, we have characterized the binding of [3H]-heparin to human saphenous vein-derived VSMC and examined whether there is any relationship between the affinity of [3H]-heparin binding and the inhibitory effect of heparin and its structural analogues on DNA synthesis. 2. At 4 degrees C [3H]-heparin binding to human VSMC occurred in a specific, time and concentration-dependent manner and was not influenced by the removal of calcium ions. Binding of the ligand appeared to occur to the cell surface and was both saturable and reversible. Kinetic and steady state data indicated a single class of binding sites. 3. The pharmacology of [3H]-heparin binding was examined in displacement studies using unlabelled heparin and structural analogues. A comparison of the rank potencies of heparin, heparan sulphate fraction II, low molecular weight heparin and trehalose octasulphate showed that there was a marked discrepancy between their estimated affinities in the binding assays and their effect on DNA synthesis. 4. In summary, we have characterized the heparin binding site on human saphenous vein-derived VSMC. Our findings suggest that the action of heparin and its analogues on DNA synthesis does not simply reflect an interaction with the cell-associated heparin binding site defined in these studies, but may also be determined by the internalization and metabolism of the glycosaminoglycan(s). (+info)