It has been postulated, based upon epidemiological data, that genetic differences in the enzymes involved in the sulphation of glycosaminoglycan (GAG) side-chains of heparan sulphate (HS) proteoglycans are of crucial importance in the pathogenesis of diabetic nephropathy. An alteration in GAG metabolism is also believed to be responsible for the well-known co-occurrence of diabetic nephropathy and extrarenal micro- and macroangiopathy. In this article, recent in-vitro and in-vivo studies on the role of HS-GAG in the pathogenesis of diabetic nephropathy are discussed. Preliminary data suggest that HS-GAG treatment may be of benefit in patients with insulin-dependent diabetes mellitus, nephropathy and retinopathy. Results in patients with non-insulin-dependent diabetes mellitus are less convincing, although not completely negative.
{"title":"Heparins in diabetic microangiopathy: rationale and preliminary clinical results.","authors":"F J van Der Woude","doi":"10.1159/000054113","DOIUrl":"https://doi.org/10.1159/000054113","url":null,"abstract":"<p><p>It has been postulated, based upon epidemiological data, that genetic differences in the enzymes involved in the sulphation of glycosaminoglycan (GAG) side-chains of heparan sulphate (HS) proteoglycans are of crucial importance in the pathogenesis of diabetic nephropathy. An alteration in GAG metabolism is also believed to be responsible for the well-known co-occurrence of diabetic nephropathy and extrarenal micro- and macroangiopathy. In this article, recent in-vitro and in-vivo studies on the role of HS-GAG in the pathogenesis of diabetic nephropathy are discussed. Preliminary data suggest that HS-GAG treatment may be of benefit in patients with insulin-dependent diabetes mellitus, nephropathy and retinopathy. Results in patients with non-insulin-dependent diabetes mellitus are less convincing, although not completely negative.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 Suppl S1 ","pages":"61-7"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000054113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This paper briefly reviews the results from three recent large-scale clinical trials evaluating the benefit of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes (ACS). The available data suggest that these are promising agents for the management of ACS, particularly in improving the immediate outcome in the acute setting.
{"title":"Use of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes undergoing coronary revascularization.","authors":"J J Popma","doi":"10.1159/000054115","DOIUrl":"https://doi.org/10.1159/000054115","url":null,"abstract":"<p><p>This paper briefly reviews the results from three recent large-scale clinical trials evaluating the benefit of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes (ACS). The available data suggest that these are promising agents for the management of ACS, particularly in improving the immediate outcome in the acute setting.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 Suppl S1 ","pages":"69-71"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000054115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patients with malignant disease constitute a significant subgroup among patients with venous thromboembolism. Current results suggest that cancer patients are not only at an increased risk for thromboembolic events, particularly during chemotherapy treatment or after surgery, they also have an increased risk for bleeding complications while receiving oral anticoagulant treatment. The exact incidences of venous thromboembolic complications for the various types of cancer, however, are not well determined. Recent studies have indicated that subcutaneous low-molecular-weight heparin (LMWH) is as safe and effective as intravenous unfractionated heparin (UFH) in the initial treatment of venous thromboembolism. Moreover, a meta-analysis has provided preliminary evidence that, compared with UFH, LMWH treatment may prolong survival in cancer patients. Initiation of LMWH treatment in these patients is, therefore, recommended. Prospective randomized clinical trials to assess the optimum dose and duration of therapy are called for.
{"title":"Should patients with venous thromboembolism and cancer be treated differently?","authors":"S M Smorenburg, B A Hutten, M H Prins","doi":"10.1159/000054122","DOIUrl":"https://doi.org/10.1159/000054122","url":null,"abstract":"<p><p>Patients with malignant disease constitute a significant subgroup among patients with venous thromboembolism. Current results suggest that cancer patients are not only at an increased risk for thromboembolic events, particularly during chemotherapy treatment or after surgery, they also have an increased risk for bleeding complications while receiving oral anticoagulant treatment. The exact incidences of venous thromboembolic complications for the various types of cancer, however, are not well determined. Recent studies have indicated that subcutaneous low-molecular-weight heparin (LMWH) is as safe and effective as intravenous unfractionated heparin (UFH) in the initial treatment of venous thromboembolism. Moreover, a meta-analysis has provided preliminary evidence that, compared with UFH, LMWH treatment may prolong survival in cancer patients. Initiation of LMWH treatment in these patients is, therefore, recommended. Prospective randomized clinical trials to assess the optimum dose and duration of therapy are called for.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 Suppl S1 ","pages":"91-7"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000054122","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deep vein thrombosis is a relatively common disease, amenable to therapy but with a potentially fatal outcome if untreated. The diagnosis can be made in most patients with the non-invasive imaging procedure ultrasonography, but limitations exist. As with all tests, there is a potential for false-positive and false-negative results. The latter are especially an issue for calf vein thrombi, and this in part has led to the concept of serial testing of the proximal venous system rather than imaging the calf. The premise of the repeat (serial) test is that only thrombi that extend to the proximal system are clinically relevant and such thrombi will be detected on the repeat test. However, despite the safety of the serial-testing concept, it is inconvenient and expensive. In the last few years, the diagnostic process has been improved by the validation of a clinical model that accurately categorizes patients as having low, moderate or high probability of deep vein thrombosis. Among the improvements this provides is the elimination of serial testing if the ultrasound is normal and the clinical probability low. The fibrin degradation product D-dimer has been demonstrated to have a high negative predictive value and has also proven useful in diagnostic algorithms. The combination of the D-dimer with clinical model assessment will enable diagnostic-testing strategies that are more safe, effective and convenient for patients.
{"title":"Modern approach to diagnosis in patients with suspected deep vein thrombosis.","authors":"P S Wells, D R Anderson","doi":"10.1159/000054107","DOIUrl":"https://doi.org/10.1159/000054107","url":null,"abstract":"<p><p>Deep vein thrombosis is a relatively common disease, amenable to therapy but with a potentially fatal outcome if untreated. The diagnosis can be made in most patients with the non-invasive imaging procedure ultrasonography, but limitations exist. As with all tests, there is a potential for false-positive and false-negative results. The latter are especially an issue for calf vein thrombi, and this in part has led to the concept of serial testing of the proximal venous system rather than imaging the calf. The premise of the repeat (serial) test is that only thrombi that extend to the proximal system are clinically relevant and such thrombi will be detected on the repeat test. However, despite the safety of the serial-testing concept, it is inconvenient and expensive. In the last few years, the diagnostic process has been improved by the validation of a clinical model that accurately categorizes patients as having low, moderate or high probability of deep vein thrombosis. Among the improvements this provides is the elimination of serial testing if the ultrasound is normal and the clinical probability low. The fibrin degradation product D-dimer has been demonstrated to have a high negative predictive value and has also proven useful in diagnostic algorithms. The combination of the D-dimer with clinical model assessment will enable diagnostic-testing strategies that are more safe, effective and convenient for patients.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 Suppl S1 ","pages":"10-20"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000054107","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Low-molecular-weight heparins (LMWHs) have been rigorously evaluated in the management of acute coronary ischaemia. The results of clinical trials suggest that the LMWHs (enoxaparin, dalteparin and nadroparin) are effective and safe in the treatment of unstable angina and non-Q-wave myocardial infarction. Two studies have shown enoxaparin to be more effective than unfractionated heparin in this setting. Furthermore, the pharmacologic and pharmacokinetic characteristics of LMWHs result in them having practical and economic advantages. Data on the benefits of long-term therapy with LMWHs are conflicting.
{"title":"Low-molecular-weight heparins in acute unstable coronary artery disease - an update.","authors":"A G Turpie","doi":"10.1159/000054116","DOIUrl":"https://doi.org/10.1159/000054116","url":null,"abstract":"<p><p>Low-molecular-weight heparins (LMWHs) have been rigorously evaluated in the management of acute coronary ischaemia. The results of clinical trials suggest that the LMWHs (enoxaparin, dalteparin and nadroparin) are effective and safe in the treatment of unstable angina and non-Q-wave myocardial infarction. Two studies have shown enoxaparin to be more effective than unfractionated heparin in this setting. Furthermore, the pharmacologic and pharmacokinetic characteristics of LMWHs result in them having practical and economic advantages. Data on the benefits of long-term therapy with LMWHs are conflicting.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 Suppl S1 ","pages":"72-5"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000054116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The key to understanding why certain individuals develop deep vein thrombosis at varying times, despite similar risk factors being present, is the realization of the importance of gene-gene and gene-environment interactions between risk factors. The discovery of factor V Leiden and several other coagulation abnormalities, which are now known to be common in the general population, has revolutionized the way in which the aetiology of venous thrombosis is viewed. On the basis of current knowledge, time-dependent models taking account of various forms of interaction have been developed.
{"title":"Venous thrombosis: prevalence and interaction of risk factors.","authors":"F R Rosendaal","doi":"10.1159/000054106","DOIUrl":"https://doi.org/10.1159/000054106","url":null,"abstract":"<p><p>The key to understanding why certain individuals develop deep vein thrombosis at varying times, despite similar risk factors being present, is the realization of the importance of gene-gene and gene-environment interactions between risk factors. The discovery of factor V Leiden and several other coagulation abnormalities, which are now known to be common in the general population, has revolutionized the way in which the aetiology of venous thrombosis is viewed. On the basis of current knowledge, time-dependent models taking account of various forms of interaction have been developed.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 Suppl S1 ","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000054106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Studies have shown that in most patients with venous thromboembolism (VTE), continuation of treatment with vitamin K antagonists for up to 27 months significantly reduces the probability of recurrence. Likewise, prolongation of oral anticoagulation beyond 6 months is believed to be of benefit in patients with certain forms of hereditary thrombophilia. Very prolonged periods of treatment with vitamin K antagonists at standard doses, although conferring benefit regarding the risk of recurrence of VTE, are associated with an increased incidence of major bleeds and require intensive monitoring. Use of a lower intensity of anticoagulation may reduce these negative aspects and enable anticoagulation to be carried out for longer.
{"title":"For how long should the treatment with vitamin K antagonists be maintained?","authors":"S Schulman","doi":"10.1159/000054121","DOIUrl":"https://doi.org/10.1159/000054121","url":null,"abstract":"<p><p>Studies have shown that in most patients with venous thromboembolism (VTE), continuation of treatment with vitamin K antagonists for up to 27 months significantly reduces the probability of recurrence. Likewise, prolongation of oral anticoagulation beyond 6 months is believed to be of benefit in patients with certain forms of hereditary thrombophilia. Very prolonged periods of treatment with vitamin K antagonists at standard doses, although conferring benefit regarding the risk of recurrence of VTE, are associated with an increased incidence of major bleeds and require intensive monitoring. Use of a lower intensity of anticoagulation may reduce these negative aspects and enable anticoagulation to be carried out for longer.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 Suppl S1 ","pages":"89-90"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000054121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Various techniques are available for the diagnosis of pulmonary embolism (PE), including pulmonary angiography, perfusion-ventilation lung scanning, D-dimer measurement, venous ultrasonography and, most recently, helical computerized tomography of the chest. The advantages and disadvantages of these techniques, used alone or in combination, are briefly discussed. Studies have indicated that treatment with low-molecular-weight heparin (LMWH), as well as being more convenient to administer, is as safe and effective as standard heparin therapy in acute PE. However, the efficacy and safety of LMWH in patients with acute PE and haemodynamic instability requires verification. Finally, the indications of inferior vena caval filters and thrombolytic therapy are outlined.
{"title":"Modern strategy for diagnosis and treatment of pulmonary embolism.","authors":"J P Laaban","doi":"10.1159/000054108","DOIUrl":"https://doi.org/10.1159/000054108","url":null,"abstract":"<p><p>Various techniques are available for the diagnosis of pulmonary embolism (PE), including pulmonary angiography, perfusion-ventilation lung scanning, D-dimer measurement, venous ultrasonography and, most recently, helical computerized tomography of the chest. The advantages and disadvantages of these techniques, used alone or in combination, are briefly discussed. Studies have indicated that treatment with low-molecular-weight heparin (LMWH), as well as being more convenient to administer, is as safe and effective as standard heparin therapy in acute PE. However, the efficacy and safety of LMWH in patients with acute PE and haemodynamic instability requires verification. Finally, the indications of inferior vena caval filters and thrombolytic therapy are outlined.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 Suppl S1 ","pages":"21-2"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000054108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The recently reported reductions in the incidence of post-operative venous thromboembolism (VTE) are related to the widespread use of prophylactic anticoagulants. Many uncertainties remain with regard to the most effective ways to use thromboprophylaxis, however. The trend towards shorter hospital stays means that patients may receive less than the recommended 7-10 days of prophylaxis. Prolonged periods of thromboprophylaxis may be beneficial for patients at high risk of post-operative VTE, such as those undergoing major orthopaedic surgery. The relative rarity of symptomatic deep vein thrombosis and pulmonary embolism means that very large patient populations are required for studies that rely on clinical endpoints, but studies using venographic endpoints have shown 28-35 days of prophylaxis with low-molecular-weight heparin to be more effective than 10-14 days. Other factors that may influence the efficacy of thromboprophylaxis include the timing of the first injection and the choice of agent.
{"title":"Extended prophylaxis against venous thromboembolism following total hip and knee replacement.","authors":"R D Hull, G F Pineo","doi":"10.1159/000054109","DOIUrl":"https://doi.org/10.1159/000054109","url":null,"abstract":"<p><p>The recently reported reductions in the incidence of post-operative venous thromboembolism (VTE) are related to the widespread use of prophylactic anticoagulants. Many uncertainties remain with regard to the most effective ways to use thromboprophylaxis, however. The trend towards shorter hospital stays means that patients may receive less than the recommended 7-10 days of prophylaxis. Prolonged periods of thromboprophylaxis may be beneficial for patients at high risk of post-operative VTE, such as those undergoing major orthopaedic surgery. The relative rarity of symptomatic deep vein thrombosis and pulmonary embolism means that very large patient populations are required for studies that rely on clinical endpoints, but studies using venographic endpoints have shown 28-35 days of prophylaxis with low-molecular-weight heparin to be more effective than 10-14 days. Other factors that may influence the efficacy of thromboprophylaxis include the timing of the first injection and the choice of agent.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 Suppl S1 ","pages":"23-31"},"PeriodicalIF":0.0,"publicationDate":"1999-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000054109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21485668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Monocyte tissue factor may play a role in the physiological or pathological triggering of blood coagulation. It is well known that unfractionated heparin and low molecular weight heparins inhibit extrinsic thrombin generation. However, this notion has never been confirmed in a physiological model using tissue factor obtained from stimulated human monocytes. This is the purpose of this study. It was important to obtain a pure preparation of monocytes with no platelet contamination. This was possible by leukapheresis and elutriation. Under sterile and endotoxin-free conditions, the process does not activate tissue factor expression by monocytes. We adapted the technique of thrombin generation on an automatic analyzer and used human monocyte tissue factor to trigger thrombin generation. Our results show that unfractionated and low molecular weight heparins potently inhibit monocytic tissue factor induced thrombin generation. The comparison of low molecular weight heparins suggests that molecules with higher anti-IIa/anti-Xa ratios exert a stronger inhibitory effect. These data may be relevant to explain the therapeutic effects of unfractionated and low molecular weight heparins in cardiovascular disorders such as unstable angina.
{"title":"Comparative inhibition of LPS-activated human monocyte-induced thrombin generation by unfractionated heparin and low molecular weight heparins.","authors":"P Nguyên, M G Rémy, G Potron","doi":"10.1159/000022517","DOIUrl":"https://doi.org/10.1159/000022517","url":null,"abstract":"<p><p>Monocyte tissue factor may play a role in the physiological or pathological triggering of blood coagulation. It is well known that unfractionated heparin and low molecular weight heparins inhibit extrinsic thrombin generation. However, this notion has never been confirmed in a physiological model using tissue factor obtained from stimulated human monocytes. This is the purpose of this study. It was important to obtain a pure preparation of monocytes with no platelet contamination. This was possible by leukapheresis and elutriation. Under sterile and endotoxin-free conditions, the process does not activate tissue factor expression by monocytes. We adapted the technique of thrombin generation on an automatic analyzer and used human monocyte tissue factor to trigger thrombin generation. Our results show that unfractionated and low molecular weight heparins potently inhibit monocytic tissue factor induced thrombin generation. The comparison of low molecular weight heparins suggests that molecules with higher anti-IIa/anti-Xa ratios exert a stronger inhibitory effect. These data may be relevant to explain the therapeutic effects of unfractionated and low molecular weight heparins in cardiovascular disorders such as unstable angina.</p>","PeriodicalId":12910,"journal":{"name":"Haemostasis","volume":"29 6","pages":"301-9"},"PeriodicalIF":0.0,"publicationDate":"1999-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000022517","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21688850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}