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Alexander S Gallus

Publications and source records attributed to Alexander S Gallus.

7 recordsLinked to original sources
PubMed2006

Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial.

OBJECTIVE: To determine the efficacy and safety of the anticoagulant fondaparinux in older acute medical inpatients at moderate to high risk of venous thromboembolism. DESIGN: Double blind randomised placebo controlled trial. SETTING: 35 centres in eight countries. PARTICIPANTS: 849 medical patients aged 60 or more admitted to hospital for congestive heart failure, acute respiratory illness in the presence of chronic lung disease, or acute infectious or inflammatory disease and expected to remain in bed for at least four days. INTERVENTIONS: 2.5 mg fondaparinux or placebo subcutaneously once daily for six to 14 days. OUTCOME MEASURE: The primary efficacy outcome was venous thromboembolism detected by routine bilateral venography along with symptomatic venous thromboembolism up to day 15. Secondary outcomes were bleeding and death. Patients were followed up at one month. RESULTS: 425 patients in the fondaparinux group and 414 patients in the placebo group were evaluable for safety analysis (10 were not treated). 644 patients (75.9%) were available for the primary efficacy analysis. Venous thrombembolism was detected in 5.6% (18/321) of patients treated with fondaparinux and 10.5% (34/323) of patients given placebo, a relative risk reduction of 46.7% (95% confidence interval 7.7% to 69.3%). Symptomatic venous thromboembolism occurred in five patients in the placebo group and none in the fondaparinux group (P = 0.029). Major bleeding occurred in one patient (0.2%) in each group. At the end of follow-up, 14 patients in the fondaparinux group (3.3%) and 25 in the placebo group (6.0%) had died. CONCLUSION: Fondaparinux is effective in the prevention of asymptomatic and symptomatic venous thromboembolic events in older acute medical patients. The frequency of major bleeding was similar for both fondaparinux and placebo treated patients.

Acute Disease↗
PubMed2005

Travel, venous thromboembolism, and thrombophilia.

Current evidence indicates that prolonged air travel predisposes to venous thrombosis and pulmonary embolism. An effect is seen once travel duration exceeds 6 to 9 hours and becomes obvious in long-haul passengers traveling for 12 or more hours. A recent records linkage study found that increase in thrombosis rate among arriving passengers peaked during the first week and was no longer apparent after 2 weeks. Medium- to long-distance travelers have a 2- to 4-fold increase in relative thrombosis risk compared with nontravelers, but the averaged absolute risk is small (approximately one symptomatic event per 2 million arrivals, with a case-fatality rate of approximately 2%) and there is no evidence that thrombosis is more likely in economy class than in business- or first-class passengers. It remains uncertain whether and to what extent thrombosis risk is increased by short-distance air travel or prolonged travel by motorcar, train, or other means. Most travelers who develop venous thrombosis or pulmonary embolism also have one or more other predisposing risk factors that may include older age, obesity, recent injury or surgery, previous thrombosis, venous insufficiency, malignancy, hormonal therapies, or pregnancy. Limited (though theoretically plausible) evidence suggests that factor V Leiden and the prothrombin gene mutation predispose to thrombosis in otherwise healthy travelers. Given that very many passengers with such predispositions do not develop thrombosis, and a lack of prospective studies to link predisposition with disease, it is not now possible to allocate absolute thrombosis risk among intending passengers or to estimate benefit-to-risk ratios or benefit-to-cost ratios for prophylaxis. Randomized comparisons using ultrasound imaging indicate a measurable incidence of subclinical leg vein thrombosis after prolonged air travel, which appears to increase with travel duration and is reduced by graded pressure elastic support stockings. Whether this surrogate outcome measure translates into clinical benefit remains unknown, but support stockings are likely to be more effective and have less adverse effects than the use of aspirin.

Aerospace Medicine↗
PubMed2005

Management options for thrombophilias.

Thrombophilias may be inherited or acquired, continuing or transient, and may contribute strongly or weakly to thrombosis. They may predispose to venous thromboembolism alone or also to artery occlusion. Advice on management must recognize these variations. The presence of an inherited thrombophilia should not alter the intensity of anticoagulant therapy, given that antithrombin, protein C, or protein S deficiency, factor V Leiden, and the prothrombin G20210A mutation are not unusually anticoagulant resistant. However, they can increase the optimal treatment duration after a first thromboembolic event. Optimal duration depends on the balance between thrombosis risk off treatment and bleeding risk during extended anticoagulant therapy, and needs to be separately estimated for each individual with thrombosis and thrombophilia. The higher the thrombosis risk and the lower the bleeding risk, the longer the optimal treatment duration. This balance favors continued (but perhaps not indefinite) therapy in antithrombin, protein C, and protein S deficiency, and perhaps also in patients with the factor V Leiden or prothrombin mutations if their bleeding risk is low. Thrombosis that complicates active malignancy, the antiphospholipid syndrome, or heparin-induced thrombocytopenia needs special consideration: recent clinical trials suggest that low molecular weight heparins are more effective than warfarin in thrombosis with cancer, and that a more intense warfarin effect is not needed for patients with antiphospholipid syndrome and thrombosis. Debate continues about the place of screening for presymptomatic but affected relatives of patients with thrombosis and an inherited predisposition. It is essential that any family testing be done only with the informed consent of all concerned. Given consent, there is general support for family testing in antithrombin, protein C, or protein S deficiency and where the factor V Leiden or prothrombin mutation is strongly penetrant and expressed. There is, however, a strong argument that any testing in families in which clotting factor polymorphisms are weakly expressed should be restricted to young women when they consider hormonal contraception or pregnancy, given that these acquired factors multiply the risk.

Anticoagulants↗
PubMed2003

Warfarin and acetaminophen interaction.

A 74-year-old man who was receiving warfarin for atrial fibrillation experienced an abrupt increase in his international normalized ratio (INR) after taking acetaminophen. To investigate this effect, the patient's anticoagulation therapy was stabilized, and he was given acetaminophen 1 g 4 times/day for 3 days. His INR rose from 2.3 before receiving acetaminophen to 6.4 on the day after acetaminophen was discontinued. Warfarin was stopped for 2 days, and the patient's INR returned to 2.0. Warfarin was restarted at the same dosage, and his INR remained within 2.0-3.0 for 6 months. Factor VII activity decreased from 29.4% before acetaminophen therapy to 15.5% when his INR was 6.4, and factor X activity fell from 27.0% to 20.2%. His warfarin plasma concentration was 1.54 microg/ml before acetaminophen compared with 1.34 microg/ml when his INR was 6.4. No significant changes in drug intake, clinical status, diet, or lifestyle were noted. Changes in INR of this magnitude with the addition of another drug during stable anticoagulation therapy suggest a drug interaction. The lack of an increase in warfarin plasma concentration associated with the increased INR suggests a possible pharmacodynamic mechanism for this interaction. Acetaminophen or a metabolite may enhance the effect of oral coumarin anticoagulants by augmenting vitamin K antagonism. Thus, the anticoagulant effect of warfarin may be significantly elevated after only a few days of acetaminophen therapy. Patients receiving warfarin should be counseled to have their INR monitored more frequently when starting acetaminophen at dosages exceeding 2 g/day.

Acetaminophen↗
PubMed2002

Heparin pentasaccharide.

Fondaparinux (a synthetic heparin analogue) (Sanofi-Synthelabo; Paris, France and Organon Research; Oss, The Netherlands) is the subject of intense recent clinical evaluation for the prevention and treatment of venous and arterial thromboembolism. The drug replicates the sulphated antithrombin-binding pentasaccharide sequence in heparin and induces potent and specific antithrombin-mediated anti-Xa activity with excellent bioavailability and a long circulating half-life of 18 hours that makes it ideal for once-daily subcutaneous dosing. Its very short chain length ensures this heparin pentasaccharide (PS) is devoid of anti-factor IIa activity. No need for laboratory monitoring is anticipated. Fondaparinux does not cross-react ex vivo with the anti-platelet antibodies responsible for heparin-induced thrombocytopenia. Fondaparinux was evaluated in four large, randomized, placebo-controlled, double-blind phase III trials of deep vein thrombosis prevention after major joint surgery where the PS given after surgery was compared with a low molecular weight heparin (LMWH). LMWH was started before surgery in two comparisons and soon after surgery in the others. The trials shared the same blindly adjudicated efficacy and safety endpoints: efficacy was measured by recording subclinical deep vein thrombosis detected by screening with bilateral venography, plus clinically suspected and confirmed symptomatic thrombosis and embolism; safety was indicated by the rate of major bleeding. Bleeding was considered major if it caused death or reoperation, affected an internal organ, or was overt and associated with a bleeding index of 2 or more. By comparison with LMWH, 2.5 mg/d of the PS beginning 4 to 8 hours after wound closure reduced venous thromboembolism rates by 56% and 26% after elective hip replacement, 63% after knee replacement, and 62% after hip fracture surgery. In three studies and overall, the effect was statistically very significant and included similarly reduced rates of proximal deep vein thrombosis. In absolute terms, the DVT rates with PS are the lowest yet seen after major joint surgery. Trends toward more major bleeding with PS in three studies were statistically significant in one trial. PS did not increase risks from reoperation, internal bleeding, or death because of bleeding, because between-group differences were caused entirely by an excess of patients with a raised bleeding index. Post hoc analysis suggests this excess can be explained by too-early postoperative drug administration and may be avoided without loss of efficacy by giving the first PS injection 6 to 8 hours after surgery. Results of phase III treatment trials for DVT/PE will soon be available, but studies in coronary artery disease are less advanced.

Animals↗
PubMed2002

Travel and venous thrombosis.

Debate continues about whether and to what extent travel predisposes to venous thrombosis and pulmonary embolism (PE). Almost certainly, the strength of any association was greatly exaggerated in recent press reports. Conclusions from case-control studies vary, with some finding no excess of recent travel among patients with venous thromboembolism and others reporting a two-four fold excess. The strongest evidence that prolonged air travel predisposes to thrombosis comes from the travel history of people who present with PE immediately after landing. Two independent analyses suggest that the risk of early embolism increases exponentially with travel times beyond 6 hours and may reach 1:200,000 passengers traveling for more than 12 hours. The most likely explanation is venous stasis in the legs from prolonged sitting, and there is evidence (preliminary and controversial) that elastic support stockings may prevent deep vein thrombosis in people who travel long-distances. There is an urgent need for more and better studies to define the absolute hazard from travel-related thrombosis and the personal risk factors that may contribute. Without these, it is difficult to give a balanced account to people who intend to travel or to consider definitive prevention trials. Case reports suggest that in most cases, travel-related thrombosis has affected people who were also at risk because of previous thrombosis, recent injury, or other predispositions. This makes it sensible to target such "at risk" people with advice about hazards and precautions, at least until formal study validates some other approach.

Aerospace Medicine↗