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Biomedical subjects

G Raskob

Publications and source records attributed to G Raskob.

18 recordsLinked to original sources
PubMed2003

Subcutaneous fondaparinux versus intravenous unfractionated heparin in the initial treatment of pulmonary embolism.

BACKGROUND: The standard initial treatment of hemodynamically stable patients with pulmonary embolism is intravenous unfractionated heparin, requiring laboratory monitoring and hospitalization. METHODS: We conducted a randomized, open-label trial involving 2213 patients with acute symptomatic pulmonary embolism to compare the efficacy and safety of the synthetic antithrombotic agent fondaparinux with those of unfractionated heparin and to document noninferiority in terms of efficacy. Patients received either fondaparinux (5.0, 7.5, or 10.0 mg in patients weighing less than 50, 50 to 100, or more than 100 kg, respectively) subcutaneously once daily or a continuous intravenous infusion of unfractionated heparin (ratio of the activated partial-thromboplastin time to a control value, 1.5 to 2.5), both given for at least five days and until the use of vitamin K antagonists resulted in an international normalized ratio above 2.0. The primary efficacy outcome was the three-month incidence of the composite end point of symptomatic, recurrent pulmonary embolism (nonfatal or fatal) and new or recurrent deep-vein thrombosis. RESULTS: Forty-two of the 1103 patients randomly assigned to receive fondaparinux (3.8 percent) had recurrent thromboembolic events, as compared with 56 of the 1110 patients randomly assigned to receive unfractionated heparin (5.0 percent), for an absolute difference of -1.2 percent in favor of fondaparinux (95 percent confidence interval, -3.0 to 0.5). Major bleeding occurred in 1.3 percent of the patients treated with fondaparinux and 1.1 percent of those treated with unfractionated heparin. Mortality rates at three months were similar in the two groups. Of the patients in the fondaparinux group, 14.5 percent received the drug in part on an outpatient basis. CONCLUSIONS: Once-daily, subcutaneous administration of fondaparinux without monitoring is at least as effective and is as safe as adjusted-dose, intravenous administration of unfractionated heparin in the initial treatment of hemodynamically stable patients with pulmonary embolism.

Aged↗
PubMed2001

Dose-response study of recombinant factor VIIa/tissue factor inhibitor recombinant nematode anticoagulant protein c2 in prevention of postoperative venous thromboembolism in patients undergoing total knee replacement.

BACKGROUND: With the best prophylactics now available, venous thromboembolism after total knee replacement remains substantial (25% to 27%). Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of factor VIIa/tissue factor complex that has the potential to reduce this risk. The present study was performed to determine an efficacious and safe dose of rNAPc2 for prevention of venous thromboembolism after elective, unilateral total knee replacement. METHODS AND RESULTS: This open-label, sequential dose-ranging study was conducted in 11 centers in Canada, Europe, and the United States. Five regimens were tested. Injections were administered subcutaneously on the day of surgery (day 1) and days 3, 5, and optionally, day 7. Primary efficacy outcome was a composite of overall deep vein thrombosis based on mandatory unilateral venography (day 7+/-2) and confirmed symptomatic venous thromboembolism recorded </=48 hours after the last dose of rNAPc2. Primary safety outcome was major bleeding </=72 hours after the last dose. An independent, blinded Central Adjudication Committee assessed all outcome events. Of 293 patients studied, 251 (86%) could be evaluated for primary efficacy analysis. A dosage of 3.0 microgram/kg administered within 1 hour after surgery provided the best observed results, with an overall deep vein thrombosis rate of 12.2%, a proximal deep vein thrombosis rate of 1.3%, and a major bleeding rate of 2.3%. CONCLUSIONS: A randomized, double-blind trial that compared rNAPc2 with current best prophylactics is warranted based on encouraging, first-reported clinical results for a factor VIIa/tissue factor inhibitor evaluated for thrombosis prophylaxis.

Aged↗
PubMed2001

Hemorrhagic complications of anticoagulant treatment.

Bleeding is the major complication of anticoagulant therapy. The criteria for defining the severity of bleeding varied considerably between studies, accounting in part for the variation in the rates of bleeding reported. Since the last review, there have been several meta-analyses published on the rates of major bleeding in trials of anticoagulants for atrial fibrillation and ischemic heart disease. The major determinants of oral anticoagulant-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that low-intensity oral anticoagulant therapy (targeted INR of 2.5; range, 2.0 to 3.0) is associated with a lower risk of bleeding than therapy targeted at a higher intensity. Lower-intensity regimens (INR < 2.0) are associated with an even smaller increase in major bleeding. In terms of treatment decision making for anticoagulant therapy, bleeding risk cannot be considered alone, ie, the potential decrease in thromboembolism must be balanced against the potential increased bleeding risk. The risk of bleeding associated with IV heparin in patients with acute venous thromboembolism is < 3% in recent trials. There is some evidence to suggest that this bleeding risk increases with the heparin dosage and age (> 70 years). LMW heparin is not associated with increased major bleeding compared with standard heparin in acute venous thromboembolism. Standard heparin and LMW heparin are not associated with an increase in major bleeding in ischemic coronary syndromes, but are associated with an increase in major bleeding in ischemic stroke.

Anticoagulants↗
PubMed1994

Risks for major bleeding from thrombolytic therapy in patients with acute pulmonary embolism. Consideration of noninvasive management.

OBJECTIVE: To assess the relative risks for bleeding with thrombolytic therapy in patients who are managed using pulmonary angiograms compared with those managed using noninvasive tests, primarily the ventilation-perfusion lung scan. DESIGN: A decision analysis based on data from other studies. METHODS: The risk for major bleeding in patients with pulmonary embolism who receive thrombolytic therapy after a noninvasive diagnosis was assessed from complications of thrombolytic therapy in patients with myocardial infarction, assuming that the same risk ratio for major bleeding when comparing an invasive with a noninvasive approach applied to patients with pulmonary embolism. The risk ratio was 3.3 (95% CI, 1.5 to 9.8) for major bleeding in patients with myocardial infarction. One or more major complications of pulmonary angiography occurred in 1.3% of patients (CI, 0.6% to 1.9%). RESULTS: The average reported risk was 14% (18 of 129 patients) (CI, 7.9% to 20.1%) for major bleeding in patients who had pulmonary angiography before receiving tissue plasminogen activator (tPA). The estimated risk was 4.2% (estimated CI, 1.4% to 9.3%) for major bleeding with tPA after a noninvasive diagnosis of pulmonary embolism. Assuming a risk of 1.3% for major complications from pulmonary angiography, a risk for major hemorrhage of 14.0% for an invasive diagnosis, and a risk of 4.2% for a noninvasive diagnosis, fewer complications would occur with noninvasive management if the prevalence of pulmonary embolism exceeded 21%. CONCLUSION: Among patients with suspected pulmonary embolism who are candidates for thrombolytic therapy, it is safer to use noninvasive diagnostic tests in many patients.

Acute Disease↗
PubMed1993

A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation.

BACKGROUND: Deep-vein thrombosis is a potentially life-threatening complication of total hip or knee replacement. There are few data on the effectiveness and safety of warfarin as compared with low-molecular-weight heparin as prophylaxis against this problem. METHODS: We therefore performed a randomized, double-blind trial in 1436 patients to evaluate the effectiveness and safety of low-molecular-weight heparin (given subcutaneously once daily) as compared with adjusted-dose warfarin to prevent venous thrombosis after hip or knee replacement. Treatment with the drugs was started postoperatively. The primary end point was deep-vein thrombosis as detected by contrast venography (performed a mean of 9.4 days after surgery in each group). RESULTS: Among the 1207 patients with interpretable venograms, 231 of 617 patients (37.4 percent) in the warfarin group and 185 of 590 patients (31.4 percent) in the low-molecular-weight-heparin group had deep-vein thrombosis (P = 0.03). The reduction in risk with low-molecular-weight heparin as compared with warfarin was 16 percent, and the absolute difference in the incidence of venous thrombosis was 6 percent in favor of low-molecular-weight heparin (95 percent confidence interval, 0.8 to 11.4 percent). The incidence of major bleeding was 1.2 percent (9 of 721 patients) in the warfarin group and 2.8 percent (20 of 715 patients) in the low-molecular-weight-heparin group (P = 0.04), and the absolute difference was 1.5 percent in favor of warfarin (95 percent confidence interval, 0.1 to 3.0 percent). CONCLUSIONS: Our data demonstrate that the small reduction in the incidence of venous thrombosis with low-molecular-weight heparin, as compared with warfarin, was offset by an increase in bleeding complications. Although the use of low-molecular-weight heparin is simpler, because it is administered subcutaneously without the need for monitoring, it may be more costly than warfarin. Warfarin is inexpensive, but the overall cost of its use is increased by the need to monitor the intensity of anticoagulation. At this time it is unclear which of these approaches is the most cost effective.

Administration, Oral↗
PubMed1993

Duplex ultrasonography for the detection of deep vein thrombi after total hip or knee arthroplasty.

The usefulness of real-time duplex ultrasonography (DU) as a screening test for deep vein thrombosis (DVT) in high-risk patients remains uncertain. To determine the sensitivity and specificity of DU for the detection of DVT, the authors prospectively studied 178 consecutive patients after total hip (n = 113) or total knee (n = 66) arthroplasty. The deep veins from the inguinal ligament to the ankle were examined first by continuous wave and then by pulsed Doppler signals as needed with real-time gray-scale ultrasound imaging using the criteria of vein noncompressibility to define DVT. Ascending contrast venography was performed within twelve hours after DU studies. Venograms and DU were interpreted independently. DU was attempted on 177 lower extremities (2 patients refused) but was judged adequate for interpretation for only 145 (82%). Venography could not be performed for 28 lower extremities and was technically inadequate for 8 studies. The primary analysis included 119 examinations for which adequate DU and ascending venograms were interpreted. DU was positive in 17 of 27 lower extremities with DVT (23 calf, 4 proximal) diagnosed by venography (sensitivity = .63; 95% confidence interval [CI] = .42 to .81), and DU was negative in 85 of 92 lower extremities with normal venograms (specificity = .92; 95% CI = .85 to .97). A secondary analysis of 81 prospectively collected anatomically complete DU studies demonstrated a sensitivity of .80 (95% CI = .56 to .94) and a specificity of .90 (95% CI = .80 to .96).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Predicting the daily prothrombin time response to warfarin.

Our objective was to evaluate the effectiveness of a computer program to predict daily prothrombin time (PT) response to warfarin therapy using prospectively collected data. The program's predictive performance (precision) and accuracy (bias) were evaluated using fraction mean absolute error and fraction mean error, respectively. We analyzed data from 40 patients using from zero to nine PT feedbacks. The fraction mean absolute error varied from 0.058 to 0.13. The program utilized a pharmacokinetic/pharmacodynamic Bayesian forecasting system to predict prothrombin response.

Aged↗
PubMed1989

The current status and future directions of impedance cardiography in ICU.

Impedance cardiography has not achieved popularity in the Intensive Care Unit (ICU) to date probably because of the limitations in technique and interpretation associated with the altered physiology of critically ill patients, and also because of interference from other machinery in the ICU. The current climate of questioning the existing technology for bedside cardiovascular assessment however spurs the need to evaluate impedance cardiography as a noninvasive alternative. Validation in noncritically ill patients is good when compared to other technologies (e.g., thermodilution, Fick, dye dilution (r greater than 0.9)). Reliability is good with a coefficient of variation in an ICU population of 8.9%, (compared to 18.6% for thermodilution). It has also shown promise in detecting the clinically significant changes of central intravascular volume. Impedance cardiography appears to be useful for measurement of stroke volume (SV) and ejection fraction (EF). From these, left ventricular end-diastolic volume (VED) can be calculated, probably a more reliable estimate of left ventricular filling than pulmonary capillary wedge pressure (PW), measured by pulmonary artery (PA) catheter. In addition, VES can be calculated and with the knowledge of left ventricular end-systolic pressure (PES) (from invasive arterial monitoring), an end-systolic pressure-volume (ES-PV) relationship can be derived. This is thought to be a measure of contractility that is independent of preload and afterload. The ultimate test in the ICU for impedance cardiography is whether clinical outcome of critically ill patients is altered by the use of this technology. Such outcome testing is essential before the true value of impedance cardiography in the management of critically ill patients can be determined.

Cardiography, Impedance↗
PubMed1985

Risk of haemorrhage associated with long term anticoagulant therapy.

This literature review was conducted to determine: (a) the rate of bleeding (major, minor and fatal) during long term oral anticoagulant therapy (greater than 4 weeks) in various disorders (ischaemic cerebrovascular disease, prosthetic cardiac valves, chronic atrial fibrillation, ischaemic heart disease and venous thrombosis); and (b) the clinical and laboratory risk factors which predispose such patients to bleeding. Using strictly defined methodological criteria, 167 studies were evaluated and classified into 1 of 5 categories based on the strength of the study design, with level I (randomised trials) representing studies which provided the most reliable information and level V (cases series) the least reliable. The risk of bleeding was substantial, and was most marked in patients with ischaemic cerebrovascular disease (29%), ischaemic heart disease (19%) and venous thromboembolism (23%). Major bleeding in venous thrombosis and cerebrovascular disease was frequently associated with an underlying risk factor. In venous thromboembolism these coexisting conditions (cancer, recent surgery and paraplegia) were also predisposing factors for thrombosis. In cerebrovascular disease major bleeding was almost always intracerebral, possibly because of associated hypertension or the cerebrovascular disease per se. We were unable to determine whether bleeding events were concentrated soon after commencing anticoagulant therapy. Haemorrhagic episodes frequently occurred when the prothrombin time (or thrombotest) was within the targeted therapeutic range, but the relationship between bleeding and the level of anticoagulant therapy was properly evaluated in only 1 study (in venous thrombosis) which demonstrated that the risk of bleeding was reduced by using a less intense anticoagulant regimen. In conclusion, the risk of bleeding during oral anticoagulant therapy is substantial. Our analysis was limited by the lack of concise reporting of clinical and laboratory information and we would suggest that future clinical studies report these in greater detail.

Anticoagulants↗
PubMed1982

Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis.

We have previously reported that long-term therapy with warfarin is effective for preventing recurrent venous thromboembolism in patients with proximal-vein thrombosis but that there is an appreciable risk of hemorrhage. To determine whether that risk could be reduced without a loss of effectiveness, we randomly allocated 96 patients with proximal-vein thrombosis to a group receiving less intense anticoagulant therapy, with a mean prothrombin time of 26.9 seconds using the Manchester comparative reagent (corresponding Simplastin time, 15 seconds), or a group given more intense therapy, with a mean Simplastin time of 19.4 seconds (corresponding prothrombin time 41 seconds with the Manchester comparative reagent) (P less than 0.001). Two of 47 patients (4 per cent) in the less intensely treated group had hemorrhagic complications, as compared with 11 of 49 patients (22 per cent) in the more intensely anticoagulated group (P = 0.015 by the two-tailed test). This difference was due to minor bleeding episodes. The frequency of recurrent venous thromboembolism was low in both groups (2 per cent). Our findings indicate that less intense anticoagulant therapy is associated with a low frequency of recurrent venous thromboembolism (2 per cent) and a reduced risk of hemorrhage.

Administration, Oral↗
PubMedDate not supplied

Self-reported diagnostic and management strategies in childhood idiopathic thrombocytopenic purpura: results of a survey of practicing pediatric hematology/oncology specialists.

PURPOSE: To assess current physician self-reported practices regarding initial management of childhood idiopathic thrombocytopenic purpura (ITP) and to determine physician self-reported willingness to participate in randomized clinical trials comparing different initial management strategies. PATIENTS AND METHODS: A questionnaire was mailed in November 1997 to all 720 members of the American Society of Pediatric Hematology/Oncology asking how they would diagnose and manage ITP in children 18 months, 5 years, and 15 years of age who were experiencing either dry purpura (cutaneous hemorrhage only) or wet purpura (active mucous membrane hemorrhage). Specific questions dealt with bone marrow aspiration, hospital admittance, treatment strategy, and specific doses of corticosteroids and intravenous immunoglobulin. RESULTS: The response rate to the questionnaire was 57%. Most respondents indicated they usually perform a bone marrow aspirate when corticosteroids are to be prescribed and administer drug therapy to patients with newly diagnosed ITP with wet or dry purpura. Only 16% of respondents would administer no drug therapy to a child with dry purpura. Intravenous immunoglobulin (IVIG) was preferred to steroids, with anti-D immunoglobulin prescribed less frequently. Hospital admittance often was used for patients with dry purpura and usually recommended for patients with wet purpura. Most respondents expressed willingness to randomize patients with dry purpura to IVIG versus no therapy and those with wet purpura to IVIG versus prednisone as part of a randomized controlled clinical trial. CONCLUSIONS: The self-reported care of the patient with ITP was influenced by the severity of presentation (dry versus wet purpura). Most physicians reported they would administer specific drug treatment in both scenarios. This survey illustrates the diverse diagnostic and management strategies currently used in childhood ITP. Because no one therapeutic approach is predominant and a scientific basis for decision making in childhood ITP has not been developed, future randomized trials are warranted. On the basis of these survey results, such trials are desired by most pediatric hematology/oncology specialists.

Adolescent↗