Cancer effect on periprocedural thromboembolism and bleeding in anticoagulated patients.

BACKGROUND: Patients with active cancer are often on chronic anticoagulation and frequently require interruption of this treatment for invasive procedures. The impact of cancer on periprocedural thromboembolism (TE) and major bleeding is not known. PATIENTS AND METHODS: Two thousand one hundred and eighty-two consecutive patients referred for periprocedural anticoagulation (2484 procedures) using a standardized protocol were followed forward in time to estimate the 3-month incidence of TE, major bleeding and survival stratified by anticoagulation indication. For each indication, we tested active cancer and bridging heparin therapy as potential predictors of TE and major bleeding. RESULTS: Compared with patients without cancer, active cancer patients (n=493) had more venous thromboembolism (VTE) complications (1.2% versus 0.2%; P=0.001), major bleeding (3.4% versus 1.7%; P=0.02) and reduced survival (95% versus 99%; P<0.001). Among active cancer patients, only those chronically anticoagulated for VTE had higher rates of periprocedural VTE (2% versus 0.16%; P=0.002) and major bleeding (3.7% versus 0.6%; P<0.001). Bridging with heparin increased the rate of major bleeding in cancer patients (5% versus 1%; P=0.03) without impacting the VTE rate (0.7% versus 1.4%, P=0.50). CONCLUSIONS: Cancer patients anticoagulated for VTE experience higher rates of periprocedural VTE and major bleeding. Periprocedural anticoagulation for these patients requires particular attention to reduce these complications.

Fecal hemoglobin excretion in elderly patients with atrial fibrillation: combined aspirin and low-dose warfarin vs conventional warfarin therapy.

BACKGROUND: Antithrombotic prophylaxis using combined aspirin and low-dose warfarin is under evaluation in several clinical trials. However, therapy may result in increased gastrointestinal blood loss and clinical bleeding vs conventional single-agent antithrombotic therapy. METHODS: To assess differences in gastrointestinal blood loss, we measured quantitative fecal hemoglobin equivalents (HemoQuant, Mayo Medical Laboratory, Rochester, Minn) in 117 patients, mean age 71 years, 1 month after initiation of assigned therapy in the Stroke Prevention in Atrial Fibrillation III Study. Sixty-three of these patients who had characteristics for high risk of stroke were randomly assigned to conventional adjusted-dose warfarin therapy (international normalized ratio, 2.0 to 3.0) or low-dose combined therapy (warfarin [international normalization ratio,<1.5] plus 325 mg/d of enteric-coated aspirin). The remaining 54 patients with low risk of stroke received 325 mg/d of enteric-coated aspirin. RESULTS: Among the 63 at high risk of stroke, abnormal values (>2mg of hemoglobin per gram of stool) were detected in 11% and values greater than 4 mg of hemoglobin per gram of stool were found in 8%. Mean ( +/- SD) values were more for those randomly assigned to receive combined therapy (1.7 +/- 3.3 mg of hemoglobin per gram of stool vs adjusted-dose warfarin therapy, 1.0 +/- 1.9 mg/g; P=.003). The 54 nonrandomized patients with low risk of stroke receiving aspirin alone had a mean (+/- SD) HemoQuant value of 0.8 +/- 0.7mg of hemoglobin per gram of stool 1 month after entry in the study. CONCLUSIONS: Abnormal levels of fecal hemoglobin excretion were common in elderly patients with high risk of atrial fibrillation 1 month after randomization to prophylactic antithrombotic therapy. Combined warfarin and aspirin therapy was associated with greater fecal hemoglobin excretion than standard warfarin therapy, suggesting the potential for increased gastrointestinal hemorrhage.

Current concepts in anticoagulant therapy.

An understanding of the international normalized ratio (INR)--which was developed to standardize reporting of the prothrombin time (PT) and provide consistent regulation of anticoagulation--is important. The recommended therapeutic range for the INR (which is calculated from the patient's PT, a mean control PT, and the international sensitivity index) for oral anticoagulant treatment of most conditions is 2.0 to 3.0. In patients with mechanical cardiac valves, the INR should be at least 2.5 to 3.5. A common cause for progression of venous thromboembolic disease and treatment failure is inadequate heparinization during the first day of treatment. Therefore, an intravenous bolus of 5,000 to 10,000 U of heparin should be administered before a maintenance infusion is initiated. Also during the first day of treatment, warfarin therapy can be implemented. Overlap treatment with heparin and warfarin for 4 or 5 days is recommended. Low-molecular-weight heparins, a new class of anticoagulants, have been shown to be more effective than standard heparin in preventing venous thrombosis in orthopedic surgical patients, but at a higher cost. Patients with mechanical cardiac valves who are receiving anticoagulant therapy and are scheduled for noncardiac operations must have a risk-to-benefit assessment of the need for continuous anticoagulation performed preoperatively. Many of these patients can safely discontinue warfarin therapy for several days as outpatients before the surgical procedure. Preoperative heparin therapy and warfarin withdrawal in the hospital are recommended only for those patients with cardiac valves at high risk for systemic embolization (with a mitral valve prosthesis, cardiomyopathy, or previous thromboembolism). The concurrent use of certain drugs or presence of comorbid conditions can predispose to hemorrhagic complications of anticoagulant therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Insufficiency fractures of the pelvis that simulate metastatic disease.

Insufficiency fractures of the pelvis, which almost always occur in elderly women with osteoporosis, are often misinterpreted as metastatic disease. The initial symptom of such fractures is severe pain unassociated with an obvious history of trauma. The typical sites of involvement are the sacrum, the iliac bones, and the pubis. The plain film appearance of the sacral and iliac fractures is usually subtle and easily overlooked, and bone scans will show the abnormal areas more readily. The existence of multiple fractures not only in the pelvis but also in the vertebrae and ribs should suggest the diagnosis of insufficiency-type stress fractures. Computed tomography can exclude the presence of a destructive process and an associated soft tissue mass, as would be seen in metastatic disease. If insufficiency fractures are identified in the typical anatomic locations, bone biopsy is unnecessary.

The macroenzymes: a clinical review.

Macroenzymes are serum enzymes that have a higher molecular mass than the corresponding enzyme normally found in serum under physiologic or pathophysiologic conditions. Although no evidence convincingly indicates that macroenzymes cause disease or necessitate treatment, some patients with immunoglobulin-complexed enzyme disorders have previously been reported to have associated autoimmune diseases or malignant lesions. To address this issue, we reviewed the medical records of 42 patients in whom a macroenzyme had been detected during assessment at the Mayo Clinic between 1986 and 1990. Of these 42 patients, 21 had macro-creatine kinase, 10 had macro-lactate dehydrogenase, 6 had macro-aspartate aminotransferase, and 5 had macroamylase in the serum. Although the study group did not include all Mayo patients with this phenomenon, it represented a sufficient sample size to determine retrospectively whether specific dismissal diagnoses were present concurrently. The most common findings in this group of patients with macroenzymes were (1) advanced age (except for those with macro-aspartate aminotransferase), (2) cardiovascular disease (probably due to sampling bias), (3) malignant lesions (particularly in those with macro-creatine kinase), and (4) rheumatologic disease (in those with macro-lactate dehydrogenase). The immunoglobulin-complexed enzyme disorders are characterized by increased total serum enzyme levels that are often isolated and persistent. Physicians should be aware of the presence of macroenzymes so that invasive or costly procedures are not undertaken unnecessarily to determine the cause of increased serum enzyme levels.

Use of low-molecular-weight heparin in the treatment of venous thromboembolic disease: answers to frequently asked questions. The Thrombophilia Center Investigators.

Low-molecular-weight heparins (LMWHs) represent an important therapeutic advance in the treatment of patients with venous thromboembolism. The use of LMWH has potential advantages in comparison with the use of standard unfractionated heparin (UH), including decreased binding to nonanticoagulant-related plasma proteins, greater bioavailability, longer half-life, and lower incidence of the heparin-induced thrombocytopenia syndrome. Because of the predictable anticoagulant response of LMWH when administered subcutaneously, laboratory monitoring is unnecessary, and the drug can be used to treat selected patients with venous thromboembolism in outpatient setting. Numerous studies have shown that the treatment of venous thromboembolism with LMWH is as safe and effective as that with standard UH when both are used appropriately. Allied health personnel can easily teach most patients to self-administer LMWH subcutaneously for home use. Transition of the treatment regimen to oral warfarin anticoagulation necessitates an overlap with heparin (UH or LMWH) for at least 4 to 5 days, and the international normalized ratio should ideally be 2.0 or higher for 2 consecutive days before heparin therapy is discontinued. A practical understanding of the pharmacology, risks, and benefits of LMWH in the treatment of venous thromboembolism will enhance the primary-care physician's ability to care for patients safely and cost-effectively.

Renal cell carcinoma associated with sarcoidlike tissue reaction.

A 60-year-old man was referred to our institution with the diagnosis of sarcoidosis. Because of several months' complaint of right flank pain and weight loss, the patient had consulted his local physician. After an extensive workup revealed only cholelithiasis, he underwent a cholecystectomy for presumed chronic cholecystitis. At the time of operation, biopsy of several liver nodules and peripancreatic nodes revealed noncaseating granulomas, consistent with sarcoidosis. On initial examination at our institution, the patient had microhematuria. A chest roentgenogram demonstrated multiple pulmonary nodules, an abdominal computed tomographic scan showed an indeterminate left renal mass, and magnetic resonance imaging of the spine revealed abnormal signals in the body of T-12. Open-lung biopsy showed an adenocarcinoma with clear cell features, likely of renal origin. The patient was diagnosed as having a metastatic renal carcinoma associated with a sarcoidlike tissue reaction. Although noncaseating granulomas have been reported in association with other malignant lesions, to our knowledge this is the first report of such an association with renal carcinoma. In addition, this case illustrates several points. First, sarcoidosis is a multisystem disorder with protean extrapulmonary manifestations. In fact, all our patient's findings could have been attributed to sarcoidosis. Second, noncaseating granulomas occur with many types of processes, including infections, chemical exposures, and, as in this case, neoplasms. Thus, noncaseating granulomas are not pathognomonic for sarcoidosis. Third, sarcoidosis is a clinical diagnosis that cannot be based on histologic findings alone.

Recent advances in the management of venous thromboembolism.

Deep venous thrombosis and pulmonary embolism are frequently diagnosed in patients encountered in a primary-care practice. In the past 10 years, many important advances have been made regarding the management of these disorders. Risk factors have been better defined than in the past. Several new prophylactic measures--such as external pneumatic compression of the lower extremities, dihydroergotamine in combination with heparin, adjusted-dose heparin, and two-step warfarin therapy--can be used to help prevent deep venous thrombosis in surgical patients. The use of serial impedance plethysmography has expanded options for noninvasive diagnosis of deep venous thrombosis. Correlations between pulmonary embolism and ventilation-perfusion lung scan patterns have been clarified. Although much has been learned about heparin and warfarin that affect common management decisions, the indications for thrombolytic therapy for venous thromboembolism remain controversial. Finally, studies have shown that calf vein thrombi that are not detectable by impedance plethysmography and that show no evidence of proximal propagation by serial impedance plethysmography do not require treatment.

Pancreatic pseudocyst that compressed the inferior vena cava and resulted in edema of the lower extremities.

To our knowledge, edema of the lower extremities has not previously been reported as a sign of a pancreatic pseudocyst. In this case report, we describe a 66-year-old man in whom such a lesion compressed the inferior vena cava and caused pronounced leg swelling. After drainage of the pseudocyst, the edema did not recur. Although the most well-known complications of pancreatic pseudocyst are pain, hemorrhage, rupture, infection, and obstruction of adjacent viscera, bilateral edema of the lower extremities can be the initial manifestation of this lesion.

Management of atrial fibrillation in adults: prevention of thromboembolism and symptomatic treatment.

Because of its prevalence in the population and its associated underlying diseases and morbidity, atrial fibrillation (AF) is an important and costly health problem. Advancing age, diabetes, heart failure, valvular disease, hypertension, and myocardial infarction predict the occurrence of AF within a population. The management of AF is complex and involves prevention of thromboembolic complications and treatment of arrhythmia-related symptoms. Stroke occurs in 4.5% of untreated patients with AF per year. Independent risk factors for stroke in nonrheumatic patients with AF are advanced age; a history of prior embolism, hypertension, or diabetes; and echocardiographic findings of left atrial enlargement and left ventricular dysfunction. Warfarin decreases stroke by two-thirds and death by one-third; aspirin is only about half as effective overall and is insufficient therapy for those with risk factors for stroke. Options for thromboembolic prophylaxis are use of warfarin for all in whom it is safe or, alternatively, warfarin for those with risk factors and aspirin for those without risk factors. One-half of the patients with AF are 75 years of age or older. The uniform applicability and relative safety of warfarin therapy in this age-group are controversial. Specific therapy for the arrhythmia should be dictated by the need to control symptoms. Symptomatic treatments include rate-control medications and strategies designed to terminate and prevent arrhythmia recurrence. Digoxin, beta-adrenergic blockers, verapamil, and diltiazem slow excessive ventricular rates in patients with AF and may favorably manage comorbid conditions. The efficacy of anti-arrhythmic medications is only 40 to 70% per year in preventing recurrences of AF, and these agents, except amiodarone, may increase the risk of sudden death in patients with certain types of organic heart disease and AF. The use of nonpharmacologic symptomatic therapies such as atrioventricular node modification or ablation with a rate-response pacemaker or surgical intervention is increasing.

Macroenzyme as a cause of unexplained elevation of aspartate aminotransferase.

Aspartate aminotransferase (AST) can exist as a macroenzyme by forming a complex with an immunoglobulin. This immunoglobulin-complexed macromolecule can cause an elevation in serum AST activity, which may be detected on routine blood chemistry analysis and erroneously considered to indicate the presence of liver disease. Clinicians should be aware of this phenomenon so patients are not subjected to unnecessary procedures. In patients with unexplained AST elevation, liver and muscle disease can be biochemically excluded by the finding of normal serum levels of alanine aminotransferase and creatine kinase. The presence of macro-AST can be determined by exclusion chromatography, electrophoresis, and activation assays with pyridoxal 5-phosphate. The elevated AST values can persist for many years.

Lack of effect of Lactobacillus GG on antibiotic-associated diarrhea: a randomized, placebo-controlled trial.

OBJECTIVES: To assess the efficacy of Lactobacillus GG in preventing antibiotic-associated diarrhea (AAD) in adults and, secondarily, to assess the effect of coadministered Lactobacillus GG on the number of tests performed to determine the cause of diarrhea. PATIENTS AND METHODS: In this prospective, randomized, double-blind, placebo-controlled trial conducted from July 1998 to October 1999, 302 hospitalized patients receiving antibiotics were randomized to receive Lactobacillus GG, 20 x 10(9) CFU/d, or placebo for 14 days. Subjects recorded the number of stools and their consistency daily for 21 days. The primary outcome was the proportion of patients who developed diarrhea in the first 21 days after enrollment. Weekly telephone follow-up was also performed. Results were analyzed in an intention-to-treat fashion. RESULTS: Diarrhea developed in 39 (29.3%) of 133 patients randomized to receive Lactobacillus GG and in 40 (29.9%) of 134 patients randomized to receive placebo (P=.93). No additional difference in the rate of occurrence of diarrhea was found between treatment and placebo patients in a subgroup analysis of those treated with beta-lactam vs non-beta-lactam antibiotics. Too few patients had stool cultures, additional laboratory tests for diarrhea, or a positive diagnosis of Clostridium difficile infection to assess between-group differences. CONCLUSION: Lactobacillus GG in a dose of 20 x 10(9) CFU/d did not reduce the rate of occurrence of diarrhea in this sample of 267 adult patients taking antibiotics initially administered in the hospital setting.