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Biomedical subjects

G E Raskob

Publications and source records attributed to G E Raskob.

At least 37 records · Page 2Linked to original sources
PubMed1998

Idiopathic thrombocytopenic purpura: A concise summary of the pathophysiology and diagnosis in children and adults.

Idiopathic thrombocytopenic purpura (ITP) is a disorder that has distinct clinical manifestations in children and adults. In children, ITP is typically abrupt in onset and self-limited in its course. Girls and boys are equally affected. In adults, ITP is typically more indolent in its onset and the course is persistent, often lasting many years or characterized by recurrent exacerbations of disease. Most patients are young women. Intracerebral hemorrhage, while rare, is the most common cause of death in children and adults with ITP. In both children and adults, the ITP is assumed to be caused by antibody-mediated platelet consumption, where Fc receptors on the macrophage bind to antibody-coated platelets resulting in an accelerated platelet destruction. However, tests for antiplatelet antibodies have not yet been established as clinically useful for management decisions. The natural history and long-term prognosis of adults with ITP remain incompletely defined.

Adult↗
PubMed1998

Different effects of heparin in males and females.

OBJECTIVE: To determine whether women have a Pharmacological predisposition to bleeding and a worse outcome than men during heparin therapy, in light of recent studies showing that women have a higher risk of bleeding complications following anticoagulant therapy for thrombotic disorders than men. DESIGN: Prospectively planned subgroup analysis of a double-blind randomized study. SETTING: Academic tertiary care hospitals in Hamilton, Ont. PATIENTS: A total of 199 consecutive patients (105 women, 93 men) presenting with proximal deep vein thrombosis. (One patient was not included due to incomplete data). OUTCOME MEASURES: Activated partial thromboplastin time (APTT) values and heparin levels were assessed every 4 to 6 hours after a standard heparin bolus and infusion. The effect of sex on heparin doses and levels was also assessed after stable therapeutic heparin infusions were achieved. RESULTS: The women had higher heparin levels than the men (0.560 [standard error of the mean, SEM 0.056] units/mL v. 0.347 [SEM 0.062] units/mL, p < 0.0001) and higher APTT values (94.9 [SEM 0.50] seconds v. 81.2 [SEM 0.53] seconds, p = 0.0002) 4 to 6 hours after being given the same heparin bolus and infusion doses. After achieving therapeutic APTT values, the women received lower heparin doses than the men (27.9 [SEM 0.24] 1000 units/24 hours v. 34.5 [SEM 0.24] 1000 units/24 hours, p < 0.0001) but had higher heparin levels (0.349 [SEM 0.035] units/mL v. 0.292 [SEM 0.036] units/mL, p = 0.034). The effect of sex was also determined after correcting for the known effects of weight and age on heparin therapy. After adjusting for patient weight, among the women, older women had higher heparin levels but, among the men, there was little effect of age. There were no sex differences with respect to bleeding complications or recurrent thromboembolic disease. CONCLUSION: Women showed alterations in the pharmacokinetics of heparin, which could explain a predisposition to bleeding complications. Under the heparin protocol used in this study, heparin doses were rapidly adjusted, which may explain why rates of bleeding complications and recurrent thromboembolism were similar in men and women. We do not recommend changes in heparin therapy based on these results, but suggest the use of protocols that assess coagulation parameters frequently and then adjust heparin doses rapidly, in order to individualize therapy. Further study is required to determine whether there are sex differences in bleeding complications associated with anticoagulant therapy, and to confirm the altered pharmacokinetics of heparin in women.

Aging↗
PubMed1998

Idiopathic thrombocytopenic purpura: diagnosis and management.

Idiopathic thrombocytopenic purpura (ITP, also known as immune thrombocytopenic purpura) in adults is principally a disease of young women. Although in some patients the onset is acute and complete resolution occurs, in most patients, the onset is insidious and the course is chronic. In spite of the relative frequency of ITP, there are important unresolved issues in its diagnosis and management. For this reason, the American Society of Hematology (ASH) chose ITP as the disease topic for its initial sponsored practice guideline in 1993. A major conclusion of the published guideline was the lack of firm evidence on which to base diagnostic procedures and management strategies. This review describes the clinical features of ITP in adults, emphasizes the principal unresolved issues in diagnosis and management, and outlines the critical areas for future research.

Adult↗
PubMed1997

The importance of initial heparin treatment on long-term clinical outcomes of antithrombotic therapy. The emerging theme of delayed recurrence.

BACKGROUND: Recent clinical trials of venous thromboembolism treatment suggest inadequate initial heparin therapy predisposes patients to late recurrence of thromboembolism. However, a recent review article was unable to demonstrate a relationship between initial heparin therapy and late recurrence. OBJECTIVE: To evaluate the relationship between initial heparin treatment and long-term clinical outcome in 3 consecutive, randomized, double-blind trials that used similar study designs and patient populations and objective documentation of recurrent venous thromboembolism. METHODS: The trials were performed sequentially and compared the use of continuous intravenous with subcutaneous heparin, continuous intravenous heparin for 10 or 5 days, and continuous intravenous heparin with once-daily subcutaneous low-molecular-weight heparin. All patients were followed up for 3 months to assess the a priori hypothesis that inadequate initial heparin therapy could lead to recurrent venous thromboembolism during long-term therapy with warfarin sodium. RESULTS: The following were the observed rates of recurrent venous thromboembolism: continuous intravenous heparin, 3 (5.2%) of 58 patients vs subcutaneous heparin, 11 (19.3%) of 57 patients; continuous intravenous heparin for 10 days, 7 (7.0%) of 100 patients or for 5 days, 7 (7.1%) of 99 patients; and continuous intravenous heparin, 15 (6.9%) of 219 patients vs low-molecular-weight heparin, 6 (2.8%) of 213 patients. Pooled analysis of the patients treated with continuous intravenous heparin showed that of the total 32 patients with recurrent venous thromboembolism, in 6 patients thromboembolism occurred early (< 10 days) and 26 patients thromboembolism occurred late. Of these patients, the majority (20/32 [62.5%]) had therapeutic prothrombin time or international normalized ratio values before or at the time of the recurrent thromboembolic event. CONCLUSION: Our findings demonstrate that the initial heparin treatment affects the long-term outcome. This conclusion applies when these data are analyzed for each individual study by treatment group, observed difference in outcome, and pooled analysis.

Anticoagulants↗
PubMed1997

Clinical decisions in idiopathic thrombocytopenic purpura.

The appropriate management of ITP is still a matter of debate. The incidence and course of the disease are different in children and adults, and within these groups, new-borns and pregnant women have specific needs. Yet there is little unanimity regarding how and when to treat even the most severe cases. The problem is compounded by the difficulty of differentiating ITP from other causes of thrombocytopenia.

Adolescent↗
PubMed1997

Treatment of proximal vein thrombosis with subcutaneous low-molecular-weight heparin vs intravenous heparin. An economic perspective.

BACKGROUND: Subcutaneous low-molecular-weight heparin is at least as effective and safe as classic intravenous heparin therapy for the treatment of proximal vein thrombosis. Anticoagulant monitoring is not required with low-molecular-weight heparin. OBJECTIVE: To perform an economic evaluation of these therapeutic approaches by comparing cost and effectiveness. PATIENTS AND METHODS: A randomized trial in 432 patients with proximal vein thrombosis that compared intravenous heparin and low-molecular-weight heparin with objective documentation of clinical outcomes provided the opportunity to perform an analysis of cost-effectiveness to rank these alternative therapies in terms of both their cost and effectiveness. The economic viewpoint of this analysis was that of a third-party payer (ie, a ministry of health in Canada or an insurance company in the United States). RESULTS: In the intravenous heparin-treated group, the cost incurred for 100 patients was $414,655 (Canadian dollars) or $375,836 (US dollars), with a frequency of objectively documented venous thromboembolism of 6.9%. In the low-molecular-weight heparin-treated group, the cost incurred for 100 patients was $399,403 (Canadian dollars) or $335,687 (US dollars), with a frequency of objectively documented venous thromboembolism of 2.8%, thus providing a cost saving of $15,252 (Canadian dollars) or $40,149 (US dollars). Multiple sensitivity analyses were performed, and these procedures did not alter the findings of the study. CONCLUSIONS: The findings indicate that low-molecular-weight heparin therapy is at least as effective and safe but less costly than intravenous heparin treatment. The potential for outpatient therapy in up to 37% of patients who are receiving low-molecular-weight heparin would substantially augment the cost saving.

Anticoagulants↗
PubMed1997

Subcutaneous low-molecular-weight heparin vs warfarin for prophylaxis of deep vein thrombosis after hip or knee implantation. An economic perspective.

BACKGROUND: Postoperative venous thrombosis and pulmonary embolism present a major clinical threat to patients undergoing total hip or knee arthroplasty. We performed an economic evaluation of warfarin sodium and subcutaneous low-molecular-weight heparin sodium prophylaxis comparing cost and effectiveness. METHODS: A consecutive series of 1436 patients who underwent hip or knee arthroplasty comparing these 2 regimens in a randomized trial with objective documentation of outcomes provided the opportunity to perform economic evaluations for Canada and the United States. RESULTS: Deep vein thrombosis was documented in 231 (37.4%) of 617 patients given warfarin and in 185 (31.4%) of 590 patients given low-molecular-weight heparin (P = .03). In Canada, warfarin and low-molecular-weight heparin (tinzaparin sodium) incurred costs per 100 patients of $11,598 and $9,197, respectively, providing a cost savings of $2,401 for the low-molecular-weight heparin group. The drug cost of low-molecular-weight heparin (tinzaparin) was $6 per day and for warfarin was $0.32 per day. Sensitivity analysis showed that low-molecular-weight heparin is more costly if drug costs are increased by 1.5-fold (ie, the cost of tinzaparin is increased from $6 per day to $8.82 per day or more). In the United States, the analysis was also not definitive; low-molecular-weight heparin was more costly than warfarin at drug costs of $15 and $2.01 per day, respectively. CONCLUSIONS: Our findings indicate that the decision to use low-molecular-weight heparin or warfarin prophylaxis in patients undergoing major joint replacement surgery is a finely tuned trade-off. Prophylaxis with low-molecular-weight heparin is equally or more effective than the more complex prophylaxis with warfarin. Major bleeding is uncommon but less frequent with warfarin use. The most significant parameters that influence the comparative cost-effectiveness are the cost of the drug, the cost of international normalized ratio monitoring, and the costs associated with major bleeding. The analysis also demonstrates that the results are health care system dependent (Canada vs US). In Canada, low-molecular-weight heparin (tinzaparin) is less costly because it avoids the need for international normalized ratio monitoring. In the United States, the drug cost for low-molecular-weight heparin will likely be the principal determinant of relative cost-effectiveness.

Adult↗
PubMed1997

Duration of anticoagulant treatment for venous thrombosis.

Patients with deep-vein thrombosis require long-term anticoagulant treatment to prevent recurrent venous thromboembolism. Anticoagulant treatment should be continued for at least 3 months in patients with a first-episode of proximal deep-vein thrombosis. In patients with a second-episode of venous thromboembolism, treatment should probably be continued for at least 1 year, because stopping treatment at 3 to 6 months is associated with a high rate of recurrent venous thromboembolism. Indefinite treatment may be indicated in patients with a second-episode of venous thromboembolism, but further clinical trials are required to clarify the risk and benefit of indefinite treatment. Further clinical trials are also required to determine if a longer course of treatment is indicated for subgroups of patients based on clinical characteristics and laboratory features (such as those with idiopathic thrombosis versus postoperative thrombosis, and those with or without identifiable molecular markers of a high risk of recurrent venous thromboembolism such as the factor V Leiden gene mutation).

Anticoagulants↗
PubMed1996

Monitoring low-dose warfarin therapy by a central laboratory and implications for clinical trials and patient care. The Coumadin Aspirin Reinfarction (CARS) Pilot Study Group.

The central laboratory provides International Normalized Ratio results in close agreement with the local laboratory for monitoring the anticoagulant effect of low-dose warfarin. A central laboratory may have practical advantages for patients in rural areas that lack laboratory facilities for anticoagulant monitoring.

Aged↗
PubMed1996

Aging and heparin-related bleeding.

BACKGROUND: Many studies have suggested that elderly patients are at increased risk of bleeding during heparin therapy. OBJECTIVE: To establish whether the risk of bleeding in the elderly results from concomitant risk factors or is associated with the aging process itself. METHODS: One hundred ninety-nine patients who presented with proximal deep vein thrombosis were treated with a standard intravenous heparin protocol in a double-blind, randomized, prospective study. Bleeding complications were monitored. Activated partial thromboplastin times and heparin levels were assessed 4 to 6 hours after a standard intravenous heparin bolus and infusion. Heparin doses and heparin levels were also assessed after stable therapeutic heparin infusion rates were established. RESULTS: There was an increase in total and major bleeding complications with aging (P < .05) that was not accounted for by standard risk factors for bleeding. Aging was associated with an increase in heparin levels (r = .239, P = .003) and a tendency for an increase in activated partial thromboplastin time (r = .134, P = .07) after standard heparin doses. Aging was also associated with lower heparin dose requirements (r = .267, P = .003) after therapeutic activated partial thromboplastin times were achieved. CONCLUSION: Aging is a risk for heparin-related bleeding that may be explicable by age-related changes in the pharmacologic characteristics of heparin.

Adult↗
PubMed1996

Oral anticoagulant therapy.

Oral anticoagulant therapy is effective antithrombotic treatment for several indications. The results of prothrombin time monitoring should be reported as the International Normalized Ratio (INR). An INR of 2 to 3 is the recommended therapeutic range for all indications except for the prevention of systemic embolism in patients with mechanical heart valves and for the long-term treatment of patients with myocardial infarction, for whom an INR range of 2.5 to 3.5 is recommended. Oral anticoagulant therapy with warfarin sodium is the preferred approach for preventing stroke in most patients with atrial fibrillation. The available data suggest that warfarin is more effective than aspirin. Aspirin, 325 mg/d, is indicated for patients in whom warfarin is contraindicated or in patients less than 75 years of age who are at low risk for stroke because risk factors are absent. In patients 75 years of age or more, close monitoring of warfarin treatment is prudent to avoid major bleeding due to poor anticoagulant control. In selected patients, patient-self-monitoring and adjustment of warfarin treatment using a portable prothrombin time monitor may be effective and safe.

Administration, Oral↗
PubMed1996

Pulmonary embolism among patients with a nearly normal ventilation/perfusion lung scan.

BACKGROUND: Among patients with nearly normal ventilation/perfusion (V/Q) lung scans in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED), pulmonary embolism (PE) was diagnosed more frequently in those who underwent pulmonary angiography than in those in whom PE was diagnosed on the basis of an adverse outcome while receiving no anticoagulant therapy. This may suggest that an adverse outcome is not apparent in patients with PE of such mild severity that the V/Q scan is nearly normal. If this were the case, patients with mild PE might not require treatment. PURPOSE: The purpose of this investigation was to evaluate patients in PIOPED with nearly normal-V/Q lung scans. The V/Q scans and clinical characteristics of those in whom PE was diagnosed or excluded by pulmonary angiography (angiography group) were compared with those in whom PE was diagnosed or excluded by the presence or absence of an adverse outcome while not receiving anticoagulant therapy (outcome group). If the characteristics were the same, it would suggest that some patients with mild PE do well without treatment. If the characteristics were different, it would indicate that there is no evidence from these data that mild PE need not be treated. METHODS: Data from PIOPED were evaluated from patients with suspected acute PE who had V/Q scans interpreted as nearly normal. There were 75 patients in the angiography group and 90 patients in the outcome group. Patients with entirely normal V/Q scans were excluded. RESULTS: PE was more frequent in the angiography group than in the outcome group, 8 of 75 (11%) vs 0 of 90 (0%) (p < 0.01). In patients with nearly normal V/Q scans who were in the outcome group in comparison to the angiography group, the V/Q scan showed fewer mismatched segmental perfusion defects, a lower percentage of low-probability V/Q interpretations by one of the two V/Q readers (compared with very low or normal probability), and a generally lower clinical assessment. CONCLUSION: The observed lower frequency of PE in the outcome group in comparison to the angiography group can be attributed to a lower likelihood of PE in this group of patients with nearly normal V/Q scans in comparison to those who underwent pulmonary angiography. There is no evidence from these data that occasional patients with nearly normal V/Q scans who have PE do not require treatment.

Acute Disease↗
PubMed1996

Low molecular weight heparin for the prevention and treatment of venous thromboembolism.

Low molecular weight heparin is effective for the prevention and treatment of venous thromboembolism. Low molecular weight heparin has the practical advantage that it does not require anticoagulant monitoring and dose adjustment. The simplified therapy provided by low molecular weight heparin will allow many patients with venous thromboembolism to be cared for in an outpatient setting, with a potential for major savings in health care costs. For preventing venous thromboembolism after hip or knee replacement, and after general abdominal surgery, further cost effectiveness studies are required to determine the ultimate clinical role of low molecular weight heparin.

Abdomen↗
PubMed1995

The low-probability lung scan. A need for change in nomenclature.

BACKGROUND: The prognosis in patients with suspected pulmonary embolism who have a low-probability lung scan has been the focus of much clinical debate. This is particularly so in patients with underlying cardiac and pulmonary disease, because these disorders frequently cause low-probability lung scans in the absence of pulmonary embolism. Historically, the clinical response has been to exclude pulmonary embolism and withhold treatment on the basis of a low-probability lung scan, which has been regarded as synonymous with a good prognosis. METHODS: A prospective cohort-analytic study to evaluate prognosis, using long-term follow-up, in patients with inadequate cardiorespiratory reserve who have presented with suspected pulmonary embolism (inadequate cardiorespiratory reserve, ie, pulmonary edema, right-ventricular failure, hypotension, syncope, acute tachyarrhythmia, abnormal spirometry [forced expiratory volume in 1 second, < 1.0, or vital capacity, < 1.5 L], or abnormal arterial blood gases [PO2, < 50 mm Hg, or PCO2, > 45 mm Hg]). RESULTS: The outcomes of the 77 consecutive patients with low-probability lung scans, suspected pulmonary embolism, and inadequate cardiorespiratory reserve were compared with those in 711 consecutive patients with good cardiorespiratory reserve and nondiagnostic lung scans who were entered into the study over the same period of time. Six (7.8%) of the 77 patients died within days of entry with autopsy-proven pulmonary embolism compared with one (0.14%) of the 711 patients with nondiagnostic lung scans (P < .0001). CONCLUSIONS: Our findings indicate that the term low-probability lung scan should be abandoned in reference to patients with inadequate cardiorespiratory reserve, because it is not synonymous with a good prognosis and is, indeed, misleading.

Adult↗
PubMed1995

Effect of treatment with low-dose warfarin-aspirin on activated factor VII.

Factor VII is an independent risk factor for ischemic heart disease. We performed a prospective study to evaluate the effect of combined low-dose warfarin-aspirin on activated factor VII (factor VIIa) and to determine if abruptly stopping this treatment is associated with a rebound in the level of factor VIIa. Thirty-three patients with clinically stable coronary artery disease were treated with combined 3 mg warfarin and 80 mg aspirin daily for 8 weeks. The factor VIIa level was measured before treatment, weekly during treatment, and 2 weeks after stopping treatment. The mean percent of pretreatment levels of factor VIIa for weeks 1 through 8 of treatment were 60%, 60%, 72%, 70%, 71%, 70%, 74%, and 87%, respectively (P < .05 compared with pretreatment for weeks 1 through 7 inclusive); 2 weeks after stopping treatment, the level was 122% (95% confidence interval [CI]; 111% to 133%; P < .001 compared with pretreatment). The mean percent level of factor VIIa on-treatment was 74% (P < .001). Factor VIIa is reduced by 26% on average during treatment. This finding provides further rationale for the antithrombotic effect of low-dose warfarin. The results suggest a rebound in the factor VIIa level may occur after treatment is stopped. The potential rebound and its clinical importance should be evaluated by further studies.

Aged↗