The place of D-dimer testing in an integrated approach of patients suspected of pulmonary embolism

At the haemophilia centre in Malm?, Sweden, regular prophylactic treatment is begun at 1-1 1/2 years of age, before the onset of joint bleeds. The dose and dose interval are optimised by means of pharmacokinetic studies to determine the individual patient's FVIII or IX metabolism, the goal of maintaining a level > 1% of normal being taken as a guideline which experience has shown to yield satisfactory control of bleeding diathesis. An optimal model for prophylactic treatment needs to be applicable to haemophiliacs and acceptable to health authorities in a majority of the countries in the world. To fulfill these criteria, the Swedish model, which has been shown to yield most satisfactory outcome, can hopefully be further refined in the future. Were continuous infusion, using a recombinate concentrate with a prolonged half-life, technically feasible and socially acceptable to the child, we would probably have attained the optimal model of prophylactic treatment.     

The role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism

This paper describes the role of venous ultrasonography in the diagnosis of suspected deep venous thrombosis and pulmonary embolism. Inability to compress the common femoral or popliteal vein is usually diagnostic of a first episode of deep venous thrombosis in symptomatic patients (positive predictive value of about 97%). Full compressibility of both of these sites excludes proximal deep venous thrombosis in symptomatic patients (negative predictive value of about 98%). In patients with suspected deep venous thrombosis or in those who present with suspected pulmonary embolism but have a nondiagnostic lung scan, the subsequent risk for symptomatic venous thromboembolism is very low (<2% during 6 months of follow-up) provided that ultrasonography of the proximal veins remains normal in the course of 1 week (suspected deep venous thrombosis) or 2 weeks (suspected pulmonary embolism). Anticoagulation and further diagnostic testing can usually be safely withheld in these situations. Venous ultrasonography is much less reliable for the diagnosis of asymptomatic, isolated distal, and recurrent deep venous thrombosis than for the diagnosis of a first episode of proximal deep venous thrombosis in symptomatic patients. Clinical evaluation of the probability of deep venous thrombosis or pulmonary embolism, preferably by using a validated clinical model, complements venous ultrasonographic findings and helps to identify patients who would benefit from additional (often invasive) diagnostic testing. Thus, venous ultrasonography is thought to be a very valuable test for the diagnosis and management of patients with suspected deep venous thrombosis or pulmonary embolism.     

Pulmonary scintigraphy at the bedside in intensive care patients with suspected pulmonary embolism

We report the results of a longitudinal study aimed at better defining concomitant changes of both bone mineral density (BMD) and of four independent markers of bone turnover (serum osteocalcin, serum alkaline phosphatase activity, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratio) following natural menopause. The results obtained indicate that, within a relatively short period of time since cessation of gonadal function, conventional markers of bone turnover behave differently. In fact, while the mean values of hydroxyproline/creatinine ratio (felt to be a marker of bone resorption) rise immediately at the first control (19.7 +/- 11.7 months), the bone formation markers gradually increase and, as far as serum osteocalcin levels are concerned, this increment appears to be long-lasting. As a result of these changes, a negative skeletal balance follows, which is documented by the prolonged reduction of bone mineral density during the entire observation period. Mean +/- SD % measured yearly bone loss was -2.83 +/- 2.6. There was a highly significant correlation between initial and final BMD values (r = 0.908, p < 0.001; r2 = 82.5) and a weak inverse correlation (r = -0.298, p < 0.046) between initial serum alkaline phosphatase values and % yearly bone loss. In conclusion, measurement of the biological indices of bone remodelling following natural menopause indicate that the increase in osteogenesis is delayed compared to that of bone resorption; furthermore, in the immediate postmenopausal period, the actual bone mass should be considered the best predictor of future bone mass. The inverse correlation found between % yearly bone loss and serum alkaline phosphatase values seems to emphasize the importance of increased bone turnover as an independent predictor of bone loss.     

Asymmetry of the calves in the assessment of patients with suspected acute pulmonary embolism

PURPOSE: The purpose of this investigation was to evaluate measured asymmetry of the calves in the assessment of patients with suspected pulmonary embolism (PE). METHODS: Patients randomized for pulmonary angiography in the collaborative study of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) were evaluated. Only patients in whom the circumference of the calves was measured were included in this evaluation of PIOPED data. Among these, 232 had angiographically diagnosed PE and 446 had no PE by angiography. For purposes of comparison, measurements of the calves also were made in a nonrandomized current cohort of 101 healthy subjects. All calf measurements were made 10 cm below the tibial tuberosity. RESULTS: Asymmetry in the circumference of the calves of 1 cm or more was measured in 101 of 232 or 44% (95% confidence interval [CI], 37 to 51%) with PE, 176 of 446 or 39% (95% CI, 34 to 44%) without PE, and in 6 of 101 or 6% (95% CI, 1 to 11%) control subjects (PE vs control subjects, p < 0.001; subjects without PE vs control subjects, p < 0.001; PE vs no PE, p = NS). Among patients with PE, the addition of calf asymmetry of 1 cm or more to qualitative signs of deep venous thrombosis increased the prevalence of a detectable abnormality of the lower extremities from 62 of 232 or 27% (95% CI, 21 to 33%) to 129 of 232 or 56% (95% CI, 49 to 63% [p < 0.001]). CONCLUSION: Asymmetry of the calves of 1 cm or more is abnormal. Such asymmetry of the calves did not distinguish between patients with PE and those with no PE. When considered in proper perspective with other nonspecific signs and symptoms in patients with suspected acute PE, however, subtle calf asymmetry may call attention to the possibility of thromboembolic disease. The observation of subtle asymmetry may indicate a need for noninvasive diagnostic tests of the lower extremities to determine whether deep venous thrombosis is present.     

Prophylaxis of venous thrombosis and pulmonary embolism in patients with acute traumatic spinal cord lesions

Twenty-one patients with acute traumatic spinal cord lesions who were admitted to our Spinal Unit during 1974 have been treated with Calcium Heparin, using a dosage of 5000-7500 i.u. at 12-hourly intervals from the first days after the lesion until the use of a wheelchair, as a prophylactic measure in order to prevent venous thromboembolism. Of these 21 patients 18 received this treatment continuously, with a resulting 0 per cent of venous thrombosis and 0 per cent of pulmonary embolisms. In the three remaining cases, treatment had to be temporarily interrupted and in one case clinical thrombo-phlebitis was clearly evident. No case of pulmonary embolism was registered. We consider this technique to be very useful in the prophylaxis of thrombo-embolic complications in this type of patient. The use of this type of prophylactic therapy, results and conclusions are discussed.     

Diagnosis of deep venous thrombosis and pulmonary embolism

Diagnostic evaluation in the patient with suspected deep vein thrombosis (DVT) and pulmonary embolism (PE) includes a clear correlation between clinical probability, test selection and test interpretation. Real-time B-mode ultrasound with color Doppler remains the imaging technique of choice in suspected DVT. The ventilation/perfusion (V/Q) lung scan is the preferred diagnostic modality in suspected PE. The D-dimer assay may be useful in excluding PA. New diagnostic techniques, including spiral computerized tomography may further modify the diagnostic algorithm.     

Clinical and echocardiographic findings in patients with suspected acute aortic dissection

OBJECTIVES: The objective of this study was to define the range of clinical presentations, echocardiographic findings, and underlying final diagnoses in patients with clinically suspected acute aortic dissection. METHODS AND RESULTS: This study was designed as a retrospective review of clinical and echocardiographic data in consecutive patients evaluated for clinically suspected acute aortic dissection. The study population consisted of 75 studies in 74 consecutive patients referred for urgent or emergency evaluation because of signs and symptoms suggesting acute aortic dissection. A history and physical examination designed to elicit the cause of chest pain, evidence of congestive heart failure, and other cardiovascular abnormalities was performed in each patient. All patients underwent transesophageal echocardiography by experienced operators. Routine 12-lead electrocardiograms and chest radiographs were available for review in the majority of patients. Magnetic resonance imaging or computed tomography was performed in only 5 (6%) and 34 (44%) patients, respectively. Contrast aortography was performed in 21 (27%) patients. For the entire patient cohort, the most prevalent symptom was chest pain alone (n = 31; 41%) or chest pain in conjunction with back pain (n = 23; 31%). Classic "tearing" pain was an infrequent symptom. Syncope or other neurologic findings were present in 15 (20%) patients. Acute aortic dissection was responsible for 34 (45%) of the 75 presentations, with 31 (41% of total evaluations, 92% of dissections) involving the ascending aorta (Stanford type A, DeBakey type 1 or 2). Alternate major cardiovascular diagnoses, including acute myocardial infarction, primary valvular disease, or pericardial disease, were established in 12 (16%) cases. Aortic pathology, other than dissection, was found in 15 (20%) cases. Transesophageal echocardiography established the diagnosis responsible for the symptoms in 61 (81%) cases. CONCLUSIONS: Symptoms in patients with acute aortic dissection are more variable than commonly recognized. Transesophageal echocardiography is an accurate primary diagnostic tool in patients with clinically suspected acute aortic dissection. It allows rapid diagnosis of dissection and can identify alternate cardiovascular pathology responsible for the symptoms in a significant number of patients without acute dissection.     

The clinical features of acute pulmonary embolism in ambulatory patients

OBJECTIVE: To identify clinical findings and predisposing conditions associated with acute pulmonary embolism (PE) in ambulatory patients being evaluated for PE. METHODS: A prospective observational study was conducted. A standardized multicomponent data collection form was administered to ambulatory subjects being evaluated for PE. The diagnosis of PE was confirmed or excluded using a combination of scintillation lung scanning, lower-extremity venous Doppler ultrasonography, and selective use of pulmonary angiography. RESULTS: Data collection was completed for 170 subjects, with 26 (15%) cases of PE. Subjects with PE were significantly older (56 vs 41 years, 99% CI for difference of 15 years [6 to 25 years]), were more likely to report unexplained dyspnea (92% vs 69%, 99% CI for difference of 23% [7% to 40%]), and waited longer after symptom onset to seek medical evaluation (73 vs 36 hours, 99% CI for difference of 37 hours [11 to 63 hours]). No difference was found for multiple variables commonly associated with PE. Assignment to risk categories was of limited diagnostic utility. For example, low-risk assignment yielded 85% sensitivity, 20% specificity; high-risk assignment: 31% sensitivity, 85% specificity, with diagnostic accuracy below 80% in both categories. CONCLUSIONS: Among outpatients selected for evaluation for PE, further risk stratification demonstrated poor diagnostic utility. Clinical features alone cannot be used to differentiate presence or absence of PE in at-risk ambulatory patients.     

Clinical diagnosis and management of the patient with deep venous thromboembolism and acute pulmonary embolism

Pulmonary embolism is the third most common acute cause of death in the United States. There are approximately 500,000 cases annually in this country, leading to death in 50,000. Subjective symptoms and objective findings can oftentimes be confusing and nonspecific. A pulmonary embolism is defined as an occlusion of one or more pulmonary vessels by material that has traveled there from outside of the lung and is usually caused by a dislodged thrombus that originated in the deep veins of the legs or pelvis. Risk factors include older age, prior thromboembolism, immobility, cancer, chronic disease, congestive heart failure, pelvic and lower extremity surgery, varicosities, obesity, and oral contraception. This article will discuss current modalities that are used in the evaluation of deep venous thromboembolism and pulmonary embolism and include ventilation/perfusion scan, ultrasonography, impedance plethysmography, pulmonary angiography, and newer tests including D-dimer assays and spiral computed tomography. Medical management including simple and complex decision making, anticoagulation, and thrombolytic therapy will also be discussed. An ounce of prevention is worth a pound of gold--identification of risk factors and the use of appropriate therapeutic measures can reduce an individual's risk for deep venous thromboembolism and pulmonary embolism.     

Utility of nocturnal home oximetry for case finding in patients with suspected sleep apnea hypopnea syndrome

OBJECTIVE: To evaluate prospectively the validity of home oximetry for case finding in patients clinically suspected of having the sleep apnea hypopnea syndrome (SAHS). DESIGN: Blinded comparison of home oximetry and polysomnographic nocturnal recordings. SETTING: Sleep clinic of a tertiary referral center. PATIENTS: A total of 240 outpatients referred because of reported sleep disturbances or daytime hypersomnia compatible with the diagnosis of SAHS. MEASUREMENTS: All participants had nocturnal home oximetry followed by a conventional polysomnographic study. The two recordings were interpreted blindly. Home oximetry test results were classified as abnormal (suspicion of sleep-related breathing abnormalities) in the presence of repetitive, short-duration arterial oxyhemoglobin saturation. (SaO2) fluctuations without any absolute or relative decrease in the SaO2 threshold. The diagnosis of SAHS was confirmed when the apnea-plus-hypopnea index was greater than 10. RESULTS: Based on the results of the polysomnographic sleep study, 110 patients had SAHS (apnea-plus-hypopnea index, 38.1 +/- 2.5/h; mean +/- SE). Home oximetry test results were interpreted as abnormal in 176 patients (this included 108 patients with SAHS and 68 without SAHS) and were read as normal in 62 patients without SAHS and in 2 with SAHS. Home oximetry testing had a sensitivity of 108/110 or 98.2% (95% Cl, 93.6% to 99.8%); a specificity of 62/130 or 47.7% (Cl, 38.8% to 56.6%); a positive predictive value of 108/176 or 61.4%; and a negative predictive value of 62/64 or 96.9%. CONCLUSIONS: A negative home oximetry test result is helpful in ruling out the diagnosis of SAHS in patients clinically suspected of having this syndrome, because a negative test result reduced the probability from 54.1% to 3.1% in our patients. However, a positive oximetry test increased the probability from 46% to 61.4% in our group of patients.     

A simplified, practical echocardiographic approach for 3-dimensional surfacing and quantitation of the left ventricle: clinical application in patients with abnormally shaped hearts

The goal of this study was to validate the quantitative accuracy of a system for 3-dimensional (3D) echocardiographic reconstruction of the left ventricle to assess its volume and function in human beings by using 3 apical views as a simplified technique to promote practical clinical application. End-diastolic and end-systolic volumes (EDV, ESV) and ejection fraction (EF) were obtained by 3D echocardiography in 50 patients with dilated or geometrically distorted left ventricles and compared with values from magnetic resonance imaging (20 consecutive patients), angiography (22 consecutive patients), and radionuclide imaging (8 consecutive patients). Three-dimensional results were also compared with 2-dimensional (2D) echocardiographic estimates. Three-dimensional left ventricular reconstruction provided values that correlated and agreed well with pooled data from the other techniques for EDV (y = 0.93x + 9.1, r = 0.95, standard error of the estimate [SEE] = 15.2 mL, mean difference = -0.5 +/- 15.4 mL), ESV (y = 0.94x + 4.3, r = 0. 96, SEE = 11.4 mL, mean difference = 0.4 +/- 11.5 mL), and EF (y = 0. 90x + 4.1, r = 0.92, SEE = 6.2%, mean difference = -0.9 +/- 6.4%) (all mean differences not significant versus 0), with greater errors by 2D echocardiography. Intraobserver and interobserver variabilities of 3D echocardiography were less than 6% for EDV, ESV, and EF. The overall time for image acquisition and 3D reconstruction was 5 to 8 minutes. Although this 3D method uses only a small number of apical views, it accurately calculates EDV, ESV, and EF in patients with dilated and asymmetric left ventricles and is more accurate than 2D echocardiography. The flexible surface fit used to combine the 3 views provides a convenient visual output as well as quantitation. This simple and rapid 3D method has the potential to facilitate routine clinical applications that assess left ventricular function and changes that occur with remodeling.     

Race and sex differences in long-term survival rates for elderly patients with pulmonary embolism

OBJECTIVES: The goal of this study was to provide estimates of race- and sex-specific survival rates over a 10-year period for a cohort of 49,752 Medicare patients admitted to the hospital in 1984 with a diagnosis of pulmonary embolism. METHODS: Data were derived from Medicare Provider Analysis and Review Record inpatient claims files and the National Death Index file. RESULTS: For a primary diagnosis of pulmonary embolism, median survival times among Black men and women were 2.5 years and 5.2 years, respectively; for White men and women, the median survival times were 4.3 years and 5.9 years, respectively. Median survival times for Black men and women and White men and women with a secondary diagnosis of pulmonary embolism were 0.4 years, 0.7 years, 0.8 years, and 1.4 years, respectively. Survival rates declined with advancing age. CONCLUSIONS: Overall, survival rates among Blacks were lower than those among Whites, and men had lower survival rates than women. These survival estimates provide new insights into outcomes following pulmonary embolism in hospitalized elderly people.     

Patent foramen ovale is an important predictor of adverse outcome in patients with major pulmonary embolism

BACKGROUND: Right-to-left shunt through a patent foramen ovale is frequently diagnosed by contrast echocardiography and can be particularly prominent in the presence of elevated pressures in the right side of the heart. Its prognostic significance in patients with pulmonary thromboembolism, however, is unknown. METHODS AND RESULTS: The present prospective study included 139 consecutive patients with major pulmonary embolism diagnosed on the basis of clinical, echocardiographic, and cardiac catheterization criteria. All patients underwent contrast echocardiography at presentation. The end points of the study were overall mortality and complicated clinical course during the hospital stay defined as death, cerebral or peripheral arterial thromboembolism, major bleeding, or need for endotracheal intubation or cardiopulmonary resuscitation. Patent foramen ovale was diagnosed in 48 patients (35%). These patients had a death rate of 33% as opposed to 14% in patients with a negative echo-contrast examination (P=.015). Logistic regression analysis demonstrated that the only independent predictors of mortality in the study population were a patent foramen ovale (odds ratio [OR], 11.4; P<.001) and arterial hypotension at presentation (OR, 26.3; P<.001). Patients with a patent foramen ovale also had a significantly higher incidence of ischemic stroke (13% versus 2.2%; P=.02) and peripheral arterial embolism (15 versus 0%; P<.001). Overall, the risk of a complicated in-hospital course was 5.2 times higher in this patient group (P<.001). CONCLUSIONS: In patients with major pulmonary embolism, echocardiographic detection of a patent foramen ovale signifies a particularly high risk of death and arterial thromboembolic complications.     

Utility of stress echocardiography in the triage of patients with atypical chest pain from the emergency department

We followed 108 patients presenting to the emergency department with atypical chest pain and triaged with stress echocardiography. One-year cardiac event-free survival was 100% with a negative stress echocardiogram and 25% with a positive study.     

Effects of heparin therapy on fibrinolysis in patients with pulmonary embolism

Previous investigations suggested that heparin administration to humans enhances the tissue type plasminogen activator (tPA) levels in blood, but it remains uncertain whether this effect induces fibrinolysis. We studied the effect of therapeutic levels of heparinization on plasma markers for fibrinolysis in patients suspected of pulmonary embolism (PE). Blood samples were taken from 49 consecutive patients; 28 had confirmed PE, 21 had PE excluded. On admission, the plasma levels of plasmin-alpha 2antiplasmin complexes and D-dimer were significantly higher in the patient group with PE compared to those in whom PE was excluded. After heparinization the tPA levels increased in both groups, showing that this effect was not dependent on the initial level of activity of fibrinolysis. In spite of this increment in tPA levels, the concentrations of plasmin-alpha 2antiplasmin complexes and D-dimer decreased. In conclusion, although heparinization in patients with or without pulmonary embolism does lead to elevated tPA:Ag levels, this is not accompanied by enhanced fibrinolysis.     

Correlation between echocardiographic changes and parameters of pulmonary function in patients with arterial hypertension

This study comprised 30 patients with mild or moderate arterial hypertension (according to classification of the World Health Organization) in whom some echocardiogram and parameters of the lung function were studied in order to establish correlation between them. A good correlation exists between LV (left ventricle) mass index and vital capacity (r = 0.562, p < 0.01), ejection fraction and forced mid expiratory flow (r = 0.717, p < 0.01), LV mass index and Tiffenau index (r = 0.620, p < 0.01), shortening fraction and forced mid expiratory flow (r = 0.591, p < 0.01), airways resistance and posterior wall thickness (r = 0.591), p < 0.01) and between LV mass index and total lung capacity (r = 0.821, p < 0.01). There was not a good correlation or it was not significant (p > 0.05) between other echocardiographic changes and lung function tests.     

Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolism with low-molecular-weight heparin: a comparison of patient self-injection with homecare injection

BACKGROUND: The outpatient treatment of patients with deep vein thrombosis and pulmonary embolism using low-molecular-weight heparin has the potential to reduce health care costs, but it is unclear if most patients with deep vein thrombosis and pulmonary embolism can be treated as outpatients. In the published studies, more than 50% of patients were excluded from outpatient treatment for reasons such as comorbid conditions, short life expectancy, concomitant pulmonary embolism, and previous deep vein thrombosis, and many patients were not treated entirely at home. We sought to determine if expanding patient eligibility for the outpatient treatment of deep vein thrombosis and pulmonary embolism affects the safety and effectiveness of the treatment, and to determine if patient self-injection compared with injections administered by a homecare nurse affected these outcomes. PATIENTS AND METHODS: We treated as outpatients all patients with deep vein thrombosis and pulmonary embolism, except for those with massive pulmonary embolism, high risk for major bleeding or an active bleed, phlegmasia, and patients hospitalized for reasons that prevented discharge. We compared 2 models of outpatient care to determine feasibility, safety, and efficacy. Both models involved nurse managers who provided daily patient contact and ongoing treatment; however, in one model the patients were taught to inject themselves and in the other model homecare nurses administered the injections. We expanded the population of patients eligible for outpatient treatment by including many patients not treated at home in previous studies. Most patients in our study were treated with dalteparin sodium, 200 U/kg every 24 hours, for a minimum of 5 days. Therapy with warfarin sodium was started on the day of diagnosis or the following day. Patients were followed up for 3 months to determine rates of recurrent venous thromboembolism, bleeding, and death. RESULTS: In this study, 194 (83%) of 233 consecutive patients were deemed eligible and treated as outpatients. Of the 39 patients who did not receive home therapy, 20 had concomitant medical problems responsible for their admission or were already inpatients, 6 had massive pulmonary embolism, 6 refused to pay for the dalteparin therapy, 4 had active bleeding, and 3 had phlegmasia cerulea dolens, which required treatment with intravenous narcotics for pain control. More than 184 (95%) of the 194 patients were treated entirely at home. There was no significant difference (P>.99) in the rate of recurrent venous thromboembolic events between the patients who were injected by homecare nurses (3/95 [3.2%]) and those who injected themselves (4/99 [4.0%]). Combining the 2 models, the overall recurrent event rate was 3.6% (95% confidence interval, 1.5%-7.4%). Similarly, there were no significant differences in rates of major hemorrhage (2/95 vs 2/99; P>.99), minor hemorrhage (8/95 vs 2/99; P = .06), and death (6/95 vs 8/99; P = .63). The overall rate of major hemorrhage was 2.0% (95% confidence interval, 0.6%-5.2%). CONCLUSIONS: We demonstrate that more than 80% of patients at our tertiary care hospital could be treated at home using 1 of the 2 models of care we describe. Our results demonstrate that patients can safely and effectively perform home self-injection under the supervision of a hospital-based nurse. Injections at home by a homecare nurse are similarly effective. Our overall rates of recurrent venous thromboembolism, bleeding, and death are at least as favorable as those previously reported despite using 1 dose per day of dalteparin for most patients.