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Biomedical subjects

A S Gallus

Publications and source records attributed to A S Gallus.

At least 19 recordsLinked to original sources
PubMed2005

Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery.

BACKGROUND: The aim of this study was to assess whether the synthetic factor Xa inhibitor fondaparinux reduced the risk of venous thromboembolism more efficiently than the low molecular weight heparin dalteparin in patients undergoing major abdominal surgery. METHODS: In a double-blind double-dummy randomized study, patients scheduled for major abdominal surgery under general anaesthesia received once-daily subcutaneous injections of fondaparinux 2.5 mg or dalteparin 5000 units for 5-9 days. Fondaparinux was started 6 h after surgery. The first two doses of dalteparin, 2500 units each, were given 2 h before surgery and 12 h after the preoperative administration. The primary outcome measure was a composite of deep vein thrombosis detected by bilateral venography and symptomatic, confirmed deep vein thrombosis or pulmonary embolism up until day 10. The main safety outcome measure was major bleeding during treatment. RESULTS: Among 2048 patients evaluable for efficacy, the rate of venous thromboembolism was 4.6 per cent (47 of 1027) with fondaparinux compared with 6.1 per cent (62 of 1021) with dalteparin, a relative risk reduction of 24.6 (95 per cent confidence interval -9.0 to 47.9) per cent (P = 0.144), which met the predetermined criterion for non-inferiority of fondaparinux. Major bleeding was observed in 49 (3.4 per cent) of 1433 patients given fondaparinux and 34 (2.4 per cent) of 1425 given dalteparin (P = 0.122). CONCLUSION: Postoperative fondaparinux was at least as effective as perioperative dalteparin in patients undergoing high-risk abdominal surgery.

Abdomen↗
PubMed2005

Deep-vein thrombosis rates after major orthopedic surgery in Asia. An epidemiological study based on postoperative screening with centrally adjudicated bilateral venography.

BACKGROUND: The incidence of postsurgical venous thromboembolism is thought to be low in Asian ethnic populations. OBJECTIVE: We studied the incidence of deep-vein thrombosis (DVT) in Asian patients undergoing major orthopedic surgery of the lower limbs. PATIENTS/METHODS: We performed a prospective epidemiological study in 19 centers across Asia (China, Indonesia, South Korea, Malaysia, Philippines, Taiwan, and Thailand) in patients undergoing elective total hip replacement (THR), total knee replacement (TKR) or hip fracture surgery (HFS) without pharmacological thromboprophylaxis. The primary endpoint was the rate of DVT of the lower limbs documented objectively with bilateral ascending venography performed 6-10 days after surgery using a standardized technique and evaluated by a central adjudication committee unaware of local interpretation. RESULTS: Overall, of 837 Asian patients screened for this survey, 407 (48.6%, aged 20-99 years) undergoing THR (n = 175), TKR (n = 136) or HFS (n = 96) were recruited in 19 centers. DVT was diagnosed in 121 of 295 evaluable patients [41.0%, (95% confidence interval (CI): 35.4-46.7)]. Proximal DVT was found in 30 patients [10.2% (7.0-14.2)]. Total DVT and proximal DVT rates were highest in TKR patients (58.1% and 17.1%, respectively), followed by HFS patients (42.0% and 7.2%, respectively), then THR patients (25.6% and 5.8%, respectively). DVT was more frequent in female patients aged at least 65 years. Pulmonary embolism was clinically suspected in 10 of 407 patients (2.5%) and objectively confirmed in two (0.5%). CONCLUSIONS: The rate of venographic thrombosis in the absence of thromboprophylaxis after major joint surgery in Asian patients is similar to that previously reported in patients in Western countries.

Adult↗
PubMed2003

The use of specific antidotes as a response to bleeding complications during anticoagulant therapy for venous thromboembolism.

When a bleeding complication occurs during therapy with heparin or vitamin K antagonists, there is an option to give a specific antidote. Several new anticoagulants have been developed that are likely to have some risk of bleeding complications, for which no specific antidotes are available. Interestingly, it is unknown how often the use of an antidote is necessary in clinical practice. We investigated 1877 patients treated for venous thromboembolism included in three large clinical trials, of which 181 (9.6%) had a total of 225 adjudicated bleeding episodes; 46 hemorrhages being designated as major. Some form of antidote was given to 26 (14.4%) patients with a hemorrhage. Of the patients with at least one major hemorrhage, 19 (41.3%) received an antidote. Vitamin K was given to 23 (1.2%) patients, one (0.05%) patient received protamin sulfate and seven (0.4%) patients received fresh frozen plasma. The use of antidotes was comparable for initial and long-term treatment. Antidotes were statistically significantly more frequently given in Canada as compared to other participating countries. Vitamin K was more frequently given in case of a higher international normalized ratio value. Although antidotes against anticoagulant treatment are widely available, our analysis shows that in only a very small number of patients a direct, or slow-acting antidote to reverse the anticoagulant effect was used.

Aged↗
PubMed2002

New aspects of the blood coagulation cascade, anticoagulants and vein thrombosis in Asia.

PURPOSE: This review describes recent views on blood coagulation and abnormalities of its physiological control that predispose to thrombosis, suggests that venous thrombosis and pulmonary embolism are more prevalent in Asia than was previously thought, and examines recent trials of novel anticoagulants for thrombosis prevention. SOURCES: 'Medline' was used to search for publications in English or with English language abstracts. CONTENT AND CONCLUSIONS: The study of blood coagulation is basic to understanding clotting and bleeding disorders, their prevention and treatment. Tissue factor, factor Xa, and thrombin are pivotal; together with physiological controls (positive and negative feedback loops, and natural anticoagulants) that first enhance thrombin generation but then preserve vessel patency by limiting haemostatic plug formation to areas of injury. Abnormalities in these mechanisms can increase thrombosis risk (thrombophilia). The traditional impression that venous thromboembolism is rare in Asia has been reinforced by the rarity of thrombophilic genetic polymorphisms outside of European populations. Nevertheless, there is increasing evidence for an increasing prevalence of symptomatic vein thrombosis and pulmonary embolism in Asia, and that thrombosis rates in 'high risk' clinical settings among elderly patients (as after major joint surgery or a stroke) now approach levels reported from the West. This indicates the need for greater clinical awareness of these conditions. Drugs now used routinely for thrombosis prevention in the West (especially low molecular weight heparins) are effective and relatively safe. New anticoagulants were even more effective in recent trials. There is urgent need for studies in Asia that define the locally relevant benefits and hazards of the increasing range of agents now available.

Adult↗
PubMed2001

Anticoagulation in pregnancy and the puerperium.

For the management of acute thrombotic events in pregnancy therapeutic doses of low molecular weight heparins (LMWH) may be used, unless the shorter half-life of intravenous unfractionated heparin (UH) and predictable reversibility by protamine are important. Treatment should be continued up until delivery and into the puerperium. Pregnant women who have had an acute thrombotic event should be delivered by a specialist team. In the case of recent thrombosis, delivery should be planned and the time during which anticoagulation therapy is ceased around the time of delivery should be minimised. Therapeutic doses of LMWH contraindicate the use of regional anaesthesia, and a switch to intravenous UH before delivery may allow greater flexibility in this regard. Prophylactic doses of LMWH can be used to reduce the risk of recurrent thromboembolic events in pregnancy. The regimen used will depend on the previous history, the family history and the presence of risk factors, including the genetic and acquired causes of thrombophilia. Women with mechanical heart valves are at high risk during pregnancy and require therapeutic anticoagulation throughout pregnancy under the direction of experienced specialists. Low-dose aspirin can reduce the risk of recurrent pre-eclampsia by about 15%, but the role of UH and LMWH in the prevention of recurrent miscarriage or obstetric complications associated with uteroplacental insufficiency is still uncertain.

Anesthesia, Obstetrical↗
PubMed2001

A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement.

BACKGROUND: Venous thromboembolism is a frequent complication of total hip replacement. The pentasaccharide Org31540/SR90107A, a highly selective, indirect inhibitor of activated factor X, is the first of a new class of synthetic antithrombotic agents. To determine the optimal dose for phase 3 studies, we conducted a dose-ranging study in which Org31540/SR90107A was compared with a low-molecular-weight heparin, enoxaparin, in patients undergoing total hip replacement. METHODS: In a double-blind study, patients were randomly assigned to postoperative administration of one of five daily doses of Org31540/SR90107A, given once daily, or to 30 mg of enoxaparin, given every 12 hours. Treatment was continued for 10 days or until bilateral venography was performed after a minimum of 5 days. RESULTS: Of 933 patients treated, 593 were eligible for the efficacy analysis. With Org31540/SR90107A a dose effect was observed (P=0.002), with rates of venous thromboembolism of 11.8 percent, 6.7 percent, 1.7 percent, 4.4 percent, and 0 percent for the groups assigned to 0.75 mg, 1.5 mg, 3.0 mg, 6.0 mg, and 8.0 mg of the drug, respectively, as compared with a rate of 9.4 percent in the enoxaparin group. The reduction in the risk of venous thromboembolism was 82 percent for the 3.0-mg Org31540/SR90107A group (P=0.01) and 29 percent for the 1.5-mg group (P=0.51). Enrollment in the 6.0-mg and 8.0-mg Org31540/SR90107A groups was discontinued because of bleeding complications. Major bleeding occurred 3.5 percent less frequently in the 0.75-mg group (P=0.01) and 3.0 percent less frequently in the 1.5-mg group (P=0.05) than in the enoxaparin group (in which the rate was similar to that in the 3.0-mg group). CONCLUSIONS: A synthetic pentasaccharide, Org31540/SR90107A, has the potential to improve significantly the risk-benefit ratio for the prevention of venous thromboembolism, as compared with low-molecular-weight heparin.

Adolescent↗
PubMed2001

A randomised double-blind placebo controlled trial of low molecular weight heparin as prophylaxis in preventing venous thrombolic events after caesarean section: a pilot study.

OBJECTIVE: To pilot a protocol for a national multicentre randomised trial in which a low molecular weight heparin will be compared with placebo for prevention of venous thrombotic events occurring within six weeks after caesarean section. DESIGN: Double-blind randomised controlled trial. SETTING: Tertiary care centre. PARTICIPANTS: Seventy-six women having had a caesarean section, 37 in the control group and 39 in the Dalteparin group. METHODS: Consenting patients having had an emergency or elective caesarean section were commenced on study medication 6-24 hours post-operatively. The study medication, dalteparin 2,500 iu or saline, was given subcutaneously once daily for four or five days post-operatively depending on the patient's length of stay. Patients were reviewed in hospital for operative outcomes and contacted at two and six weeks post-operatively. RESULTS: Of the 141 women given information about the trial, 76 (54%) consented to participate. Follow up to six weeks was achieved in all women who were recruited. More women in the placebo arm had general anaesthesia, but otherwise the two groups had similar characteristics at randomisation. There was only one occurrence of a deep vein thrombosis during the study. This patient was in the treatment arm and the thrombosis occurred between two and six weeks post-operatively. All other outcomes were similar in the two groups. CONCLUSION: Our experience of a 26% recruitment rate, the thrombosis rate of 1.3% (95% CI 0.03-7.1%) and the contactability of all participants two and six weeks post-operatively, indicates that this study is feasible.

Adult↗
PubMed2001

Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study.

AIM: To compare clinical outcomes in a randomised comparison of treatment with danaparoid sodium (a heparinoid), or dextran 70, for heparin-induced thrombocytopaenia (HIT) plus thrombosis. METHODS: Forty-two patients with recent thrombosis and a clinical diagnosis of probable HIT who presented at ten Australian hospitals during a study period of six and one half years were randomly assigned to open-label treatment with intravenous danaparoid or dextran 70, each combined with oral warfarin. Thirty-four patients (83%) had a positive platelet aggregation or 14C-serotonin release test for HIT antibody. Twenty-five received danaparoid as a bolus injection of 2400 anti-Xa units followed by 400 units per hour for 2 h, 300 units per hour for 2 h, and then 200 units per hour for five days. Seventeen received 1000 mL dextran 70 on day one and then 500 mL on days 2-5. Patients were reviewed daily for clinical evidence of thrombus progression or resolution, fresh thrombosis or embolism, bleeding or other complications. The primary trial endpoint was the proportion of thromboembolic events with complete clinical resolution by the time of discharge from hospital. RESULTS: With danaparoid, there was complete clinical recovery from 56% of thromboembolic events compared to 14% after dextran 70 (Odds Ratio 10.53, 95% Confidence Interval 1.6-71.4; p = 0.02). Clinical recovery with danaparoid was complete or partial in 86% of thromboembolic events compared with 53% after dextran 70 (Odds Ratio 4.55, 95% Confidence Interval 1.2-16.7; p = 0.03). Overall clinical effectiveness of danaparoid was rated as high or moderate in 88% of patients compared with 47% for dextran 70 (p = 0.01). One patient given danaparoid died of thrombosis compared with three patients given dextran 70. The platelet count returned to normal after a mean of 6.7 days with danaparoid and 7.3 days with dextran 70. There was no major bleeding with either treatment. CONCLUSION: danaparoid plus warfarin treatment for HIT with thrombosis is effective, safe, and superior to dextran 70 plus warfarin.

Aged↗
PubMed2000

Consensus guidelines for warfarin therapy. Recommendations from the Australasian Society of Thrombosis and Haemostasis.

The anticoagulant effect of warfarin should be kept at an international normalised ratio (INR) of about 2.5 (desirable range, 2.0-3.0), although a higher level may be better in a few clinical conditions. The risk of bleeding increases exponentially with INR and becomes clinically unacceptable once the INR exceeds 5.0. Warfarin therapy should be continued for around six weeks for symptomatic calf vein thrombosis, and for 3-6 months after proximal deep vein thrombosis (DVT) that occurs after surgery or limited medical illness. Therapy for six months or longer could be considered for DVT occurring without an obvious precipitating factor, proven recurrent venous thromboembolism (VTE), or if there are continuing risk factors. Oral anticoagulants prevent ischaemic stroke in atrial fibrillation (AF). Maximum efficacy requires an INR > 2.0, but some benefit remains at an INR of 1.5-1.9. Patients aged over 75 years are at greatest risk of intracranial bleeding during warfarin therapy for AF, and the target INR may be reduced to 2.0-2.5, or perhaps as low as 1.5-2.0, in such patients. Warfarin should be withheld if it is more likely to cause major bleeding than to protect from stroke (e.g., in young people with isolated AF where the annual baseline risk of stroke is < 1%). In patients with AF, aspirin is less effective than warfarin (much less effective after such patients have had a stroke or transient cerebral ischaemia). In people with prosthetic heart valves, an INR of 2.5-3.5 is probably sufficient for bileaflet or tilting disc valves, but a higher target INR is necessary for caged ball or caged disc valves. The addition of aspirin (100 mg/day) further decreases the risk of embolism but increases the risk of gastrointestinal bleeding.

Aged↗
PubMed2000

Preventing venous thromboembolism in general medical inpatients and after an ischaemic stroke.

Clinical trials and meta-analyses have shown that low-molecular-weight heparin and unfractionated heparin are effective in preventing deep vein thrombosis (DVT) in acutely ill medical inpatients who are at risk as they are likely to be bedridden for 6 days or more. It is not known, however, if such prophylaxis can also reduce the likelihood of fatal pulmonary embolism or decrease all-causes mortality in this patient population. No recommendations can be made regarding thromboprophylaxis in those at a lower risk of venous thromboembolism or in short-stay inpatients, as these have not yet undergone clinical trial. Current evidence suggests that high doses of heparin should be avoided after an acute ischaemic stroke, as the results of recent large trials suggest any potential treatment benefit in preventing DVT is cancelled by the increased intracranial bleeding risk caused from the underlying disease.

Acute Disease↗
PubMed1999

Towards the safer use of warfarin I: an overview.

There has been an exponential increase of warfarin usage in the community since several large and well-designed clinical trials have consistently found that warfarin can safely prevent embolic stroke in people with atrial fibrillation. Safe and effective warfarin treatment requires a case-by-case evaluation of each patient's clinical condition and risk factors for bleeding. It also demands a therapeutic partnership where patients can accept an educated responsibility for managing their own condition. This requires mutually understood plans for ongoing management, including dose adjustment and responses to under- or overdose and to bleeding complications.

Adult↗
PubMed1999

Towards the safer use of warfarin II: results of a workshop.

The use of oral anticoagulation therapy (ACT) is expanding. Due to the combination of the narrow therapeutic range and relatively unpredictable pharmacokinetics and pharmacodynamics, there are relatively high risks involved in using this treatment. The purpose of this paper is to present the results of a focus group's canvassing of ways to improve the management of the use of oral anticoagulants. Recommendations proposed include: (i) better patient selection; (ii) more patient involvement and research into the appropriateness of the current use of ACT in Australia; (iii) increased production, dissemination and implementation of ACT guidelines; (iv) assessment of home and practice ACT monitoring; and (v) research into the effectiveness of academic detailing and the use of management plans by dedicated ACT educators.

Anticoagulants↗
PubMed1999

Comparison of an age adjusted warfarin loading protocol with empirical dosing and Fennerty's protocol.

AIM: A warfarin loading protocol adjusting doses for age was compared to both Fennerty's protocol (Fenn) and empirical dosing (Emp). METHODS: Patients beginning warfarin were randomised to receive doses according to either the age adjusted (Age) protocol or Fenn. Data were retrospectively collected for patients who had begun warfarin in the previous six months to represent empirical dosing. The study was performed on inpatients being commenced on warfarin for the first time at two teaching hospitals. MAIN OUTCOME MEASURES: Endpoints were time to reach a stable, therapeutic International Normalised Ratio (INR) between 2-3, the number of patients experiencing an INR > or =4 in the first week and the number of patients who had a dose held in the first week. RESULTS: Thirty-five patients were assessed in the Age group, 28 in the Fenn group, and 123 patients for the Emp group. Patients using the Age protocol achieved a stable, therapeutic INR more rapidly than either the Fenn (p=0.003, log rank test) or Emp (p<0.001) group. The Age group had a lower proportion of patients experiencing an INR > or =4 in the first week (p<0.05) as well as a lower proportion having doses held in the first week (p<0.01). There were no differences between Emp and Fenn for any of the endpoints. CONCLUSION: Adjustment of warfarin loading doses for age exhibits clear superiority over the use of Fenn or Emp. This becomes increasingly important as the average age of patients being warfarinised increases, with the recognition that atrial fibrillation requires anticoagulation. Fenn consistently overdosed elderly patients, especially those aged 80 years and older.

Age Factors↗
PubMed1999

Applying risk assessment models in orthopaedic surgery: overview of our clinical experience.

Major joint surgery (elective hip or knee replacement, or hip fracture) carries a high risk of postoperative deep vein thrombosis (DVT) and pulmonary embolism. DVT prophylaxis has become an essential part of routine management, since several preventive methods, including low-molecular-weight heparins (LMWHs) and oral anticoagulants, are effective and safe in major joint surgery. Clinically important questions remain about the best way to use LMWHs for DVT prevention. The need for preoperative dosing, whether to give LMWHs once or twice daily, and the most suitable duration of prophylaxis remain issues of debate. Reports of local bleeding after spinal or epidural anaesthesia/analgesia in orthopaedic surgery patients given LMWH may make anaesthetists more reluctant to combine regional anaesthesia with LMWH prophylaxis, especially if a preoperative dose is required. The worldwide trend towards early transfer of postoperative patients from hospital to a convalescent facility or home has increased the need for formal recommendations about the optimal duration of prophylaxis. Ever shorter hospital admissions after elective surgery mean that prophylaxis given only in hospital may not be sufficient.

Anticoagulants↗
PubMed1998

Thrombolytic therapy for venous thrombosis and pulmonary embolism.

Streptokinase, urokinase, tissue plasminogen activator and similar drugs can all cause lysis of venous thrombi and pulmonary emboli, but there is small evidence that accelerated lysis achieves a significantly better clinical outcome, on average, in the shorter or longer term, than heparin alone. Thrombolytic therapy for deep leg vein thrombosis aims to restore flow and to preserve venous valves, and so to prevent chronic post-phlebitic disability, but no trial has convincingly demonstrated that the last can be achieved in more than a few patients. Only a small minority of people with extensive proximal thrombosis develop disabling post-phlebitic venous insufficiency, and there are no good clinical predictors of this outcome. As a result, any widespread use of thrombolytics would bring an immediate risk of major bleeding to many people who will never be destined to develop a clinically important problem. Thrombolytic therapy after venous thrombosis should be avoided except, perhaps, in a few carefully selected patients with severe obstruction. The case for using thrombolytics after recent pulmonary embolism is strongest in the limited number of patients with ongoing hypoxia, respiratory distress, pulmonary hypertension and right heart failure, because thrombolytic therapy often achieves an impressive and almost immediate clinical benefit in this clinical setting. Whether early relief from pulmonary artery obstruction translates into longer-term advantage over heparin remains uncertain, however, because no comparative trial has ever shown these drugs to reduce mortality after pulmonary embolism. In all cases, both the physician and the patient must balance the certainty of an immediate bleeding risk against the uncertainty of a better than marginal real benefit.

Fibrinolytic Agents↗
PubMed1998

Thromboprophylaxis in non-surgical patients: who, when and how?

Because of the serious lack of useable, relevant information, most recommendations for prevention of thrombosis in non-surgical patients are extrapolations from much larger clinical trials experienced in surgery. Directly relevant evidence comes predominantly from very small randomized trials, many of them open label and carried out more than 20 years before the introduction of more recent and important changes in clinical care that may have substantially reduced the baseline thrombosis risk. In these early studies, low-dose heparin and low-molecular-weight heparins prevented subclinical deep vein thrombosis in ischaemic stroke, myocardial infarction and among elderly medical inpatients. Although it is likely that these drugs also prevent subclinical deep vein thrombosis after spinal cord injury or other major trauma, and when patients require intensive medical care, the supporting evidence in these circumstances comes mainly from cohort studies and poorly controlled comparisons. In contrast, the heparins have not reduced mortality or demonstrably prevented pulmonary embolism after ischaemic stroke or among elderly medical inpatients in large and well-conducted clinical endpoint trials, from which no clinically important benefit could be demonstrated. From analyses it is suggested that such benefit is probably more difficult to demonstrate for medical than for surgical patients. In the absence of sufficient information that is specific to medical patients, various forms of prophylaxis known to be effective in surgery will continue to be applied in high-risk individuals. After venous thromboembolism, it now appears that the best duration of oral anticoagulant therapy to prevent a recurrence is determined to a greater extent by whether the thrombotic episode was idiopathic or triggered by a clinically recognizable cause, whether it was transient or continuing, and whether the deep vein thrombosis was extensive, limited to the calf veins or was a first or recurrent event.

Aged↗