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Subcutaneous fat accumulation and BMI associated with risk for pulmonary embolism in patients with proximal deep vein thrombosis: a population study based on 23 796 consecutive autopsies.

OBJECTIVE: Although deep vein thrombosis (DVT) and pulmonary embolism (PE) are manifestations of the same disease, far from all patients develop PE. Our objective was to investigate risk-modifying factors. SETTING, SUBJECTS AND DESIGN: Between 1970 and 1982, 23,796 autopsies, representing 84% of all in-hospital deaths in the Malmö City population, were performed, using a standardized procedure. In a case-control study nested in a population-based cohort of patients with proximal DVT, the relationship between PE and body mass index (BMI), thoracic and abdominal subcutaneous (SC) fat thickness was evaluated. RESULTS: Proximal DVT was found in 15%, of which 58% were women. Mean age in men was 4.5 years lower than in women (P<0.001). Fifty per cent of the patients had PE, half of which were fatal. Similar age- and gender distribution was found in cases and controls. Patients in the upper tertile of BMI, abdominal and thoracic SC fat thickness had, in comparison with mid-tertile, and independent of age, gender and death from cancer disease, an increased odds (95% CI) for PE of 1.24 (1.04-1.47) (P=0.014), 1.28 (1.07-1.53) (P=0.006) and 1.35 (1.13-1.61) (P=0.001), respectively, whereas in patients of the lower tertiles, a negative association was found. CONCLUSIONS: We found no differences in age- and gender distribution between PE cases and controls. BMI and SC fat thickness were markers of disease progression from proximal DVT to PE. The highly significant and independent association indicates that SC obesity may be of greater importance in venous thromboembolism as compared with cardiovascular diseases related to visceral (abdominal) obesity with lipid- and glucose metabolic disturbances.

Abdomen↗

Combined thrombophilic risk factors and essential thrombocythemia in patient with recurrent venous thromboembolic episodes-thirty-three-year follow-up.

We present the case of a 64 year-old female patient, with a clearly positive family history of venous thromboembolism (VTE), multiple VTE episodes (massive pulmonary embolism, ovarian venous plexus thrombosis, deep venous thrombosis with submassive pulmonary embolism and second deep venous thrombosis) and myocardial infarction. Laboratory tests revealed the resistance to the activated protein C, elevated FVIII and PAI-1. The patient was found to be a heterozygous carrier of FV Leiden, MTHFR C677T and PAI-1 4G/5G mutations. She was diagnosed with essential thrombocythemia at the age of 60. The thirty-three-year follow-up of our patient and detection of recurrent thrombotic episodes in the light of multiple coagulation defects with proved acquired risk factors, contributes to the risk stratification in the group of patients with very high risk. In case of our patient, we stress inadequacy of widely-accepted standard prevention measures. In our opinion, patients with very high risk require additional mechanic and specific medicament methods of VTE prevention.

Adult↗

Multidisciplinary approach to venous thromboembolism.

Venous thromboembolism shows a high incidence and a significant mortality. Even if valid methods are available, thromboembolism is underdiagnosed. There are a number of diagnostic difficulties. They concern the time of the diagnostic suspicion, the patient selection for the various procedures and their combination. These difficulties may be overcome by team work where specialists of different disciplines (surgeons, internists, experts in nuclear medicine, radiologists) integrate their competence to attain the established objectives. The integration results in "synergism", namely an added value greater than the sum of competences of the team components. Thus, an operational unit active 24 hours over 24 must be formed to diagnose and treat the largest number of cases of thromboembolism. To establish the clinical suspicion of thromboembolism is the first indispensable step for patient selection. Thromboembolism should be investigated in all patients with chest pain, dyspnea and tachypnea in the absence of preexisting cardiorespiratory disease. The team should evaluate the impact of signs and symptoms to establish a definitive clinical probability which can direct towards the suitable, least invasive imaging procedure. Perfusion scanning, when highly suggestive or normal, is conclusive. However in 70% of cases it is indeterminate. Thus it should be combined with other procedures and with the clinical assessment. In practice, many dubious cases remain unsolved. The team work represents an organizational response to this diagnostic and therapeutic inadequacy. The real change in strategy which has revolutionized the diagnosis of thromboembolism was the widespread use of color Doppler US in the diagnosis of deep vein thrombosis. Since pulmonary embolism as well as deep vein thrombosis are treated with the same therapy, it is adequate to document the thrombosis also in the absence of a definitive demonstration of embolism. The old-fashioned approach should be reversed and the investigation should be centered on the assessment of deep vein thrombosis: site, emboligenic potential, floating extremity and extension. The integration of the clinical assessment, scanning finding and color Doppler US lowers by about 20% the number of indeterminate cases and indicates the patients for whom pulmonary spiral CT or pulmonary angiography is required. In all patients with cardiorespiratory insufficiency still unsolved after the combination of noninvasive exams, pulmonary angiography or spiral CT is mandatory because of the high risk for death. The remaining ones can be followed with serial color Doppler US exams. The cost/benefit ratio shows that the noninvasive strategy is the least expensive, the least hazardous and the most effective. At present, effective therapies are available for thromboembolism. Standard heparin and low molecular weight heparin fractions, fibrinolytic agents, surgery and recently caval filters are playing a major role in secondary prophylaxis of pulmonary embolism. The therapeutic approach is conditioned by various factors: the features of thrombosis, the presence and entity of pulmonary embolism, the patient cardiorespiratory condition, possible contraindications for anticoagulant and fibrinolytic agents. The presence of such a number of variables makes the use of a therapeutic algorithm, difficult. In this phase, based on our experience we believe that the present solution lies in the activity of an operational team of experts who establish the treatment to be performed.

Cost-Benefit Analysis↗

Pulmonary embolism: which pediatric trauma patients are at risk?

BACKGROUND/PURPOSE: Deep vein thrombosis and pulmonary embolism (DVT/PE) are rare in pediatric trauma patients, and guidelines for prophylaxis are scarce. The authors sought to identify subgroups of patients who may be at higher risk of developing DVT/PE. METHODS: Case-control study of pediatric trauma patients with DVT/PE. Odds ratios (ORs) and confidence intervals (CIs) were calculated for known risk factors of PE using matched trauma controls (chi2 analysis). RESULTS: A total of 3637 pediatric trauma patients was admitted over the last 7 years. Three patients developed DVT/PE (overall incidence, 0.08%). There were 2 girls and 1 boy, aged 15, 15, and 9 years, respectively. All 3 had an Injury Severity Score (ISS) > or =25 and an initial Glasgow Coma Score (GCS) < or =8. None of the known and potential risk factors significantly increased the OR for developing DVT/PE: age 9 years or older (OR, 3.6; CI, 0.4-26), presence of head injury (OR, 2.9; CI, 0.3-22), female sex (OR, 1.2; CI, 0.15-9.1), GCS < or =8 (OR, 9.2; CI, 0.9-230), except ISS > or =25 (OR, 82; CI, 7.6-2058). The OR for a combination of age and GCS was 106, and the OR for the 3 risk factors (age, ISS, GCS) common to all 3 patients was 114 (CI, 10-5000; P < .001). CONCLUSIONS: The overall incidence of DVT/PE in pediatric trauma patients is <0.1% and routine prophylaxis is not recommended. Children aged 9 years or older with an initial GCS < or =8 and patients with an estimated ISS > or =25 may constitute a high-risk group in which prophylaxis could be considered.

Adolescent↗

Incidence of pulmonary embolism in deep venous thrombosis.

Abnormal radionuclide phlebograms were found in 65 patients in whom simultaneous-perfusion lung scintigrams and phlebograms were performed. All these patients were on adequate treatment with heparin for deep venous thrombosis. In 28% of the cases, the diagnosis of pulmonary embolism was made because they had abnormal perfusion lung scans with normal chest radiograph and clinical symptoms of pulmonary embolism.

Adolescent↗

Can a state-of-the-art D-dimer test be used to determine the need for CT imaging in patients suspected of having pulmonary embolism?

RATIONALE AND OBJECTIVES: The purpose of this study was to determine whether a simple rapid blood test can obviate computed tomography (CT) in a sizable percentage of patients suspected of having pulmonary embolism, based on the hypothesis that negative D-dimer results could eliminate any further search for pulmonary embolism. MATERIALS AND METHODS: At the authors' institution, 2,121 sequential patients underwent a whole-blood antibody agglutination test for cross-linked fibrin degradation products (D-dimer). Of these patients, 844 had positive test results and were not further considered. A retrospective review included reports of all multisection combined CT venographic and pulmonary angiographic studies obtained within 48 hours of the D-dimer assay for the 1,277 patients with negative D-dimer results; 229 (18%) of these 1,277 patients underwent combined CT venography and pulmonary angiography, usually within 24 hours. RESULTS: Retrospective review of the imaging examinations that were discrepant with the D-dimer results revealed only three false-negative D-dimer results. Of the 229 patients in whom combined CT venography and pulmonary angiography was performed for suspected pulmonary embolism, 226 (98.7%) had no evidence of acute pulmonary embolism or deep venous thrombosis. The negative predictive value of a negative D-dimer result was therefore 98.7% (confidence interval, 96.2%-99.7%). CONCLUSION: The D-dimer assay is a simple rapid blood test that is sensitive to the presence of acute thrombosis. Very few patients with negative results have acute deep venous thrombosis or pulmonary embolism, with combined CT venography and pulmonary angiography used as the reference standard.

Acute Disease↗

The incidence of deep vein thrombosis after hip and knee arthroplasties in Japanese patients: a prospective study.

PURPOSE: To document the incidence of proximal deep vein thrombosis and pulmonary embolism in 58 consecutive Japanese patients undergoing total hip arthroplasty or total knee arthroplasty. METHODS: Patients were routinely examined for proximal deep vein thrombosis by B-mode ultrasonography before and after surgery. Those patients who had ultrasonographic findings of deep vein thrombosis were also investigated for pulmonary embolism by ventilation-perfusion lung scan. RESULTS: The incidence of deep vein thrombosis after total hip arthroplasty and total knee arthroplasty were 9.1% and 4.0% respectively, and the incidence of pulmonary embolism were 3.0% and 0%, respectively. There were no cases of fatal pulmonary embolism. CONCLUSION: The incidence of deep vein thrombosis and pulmonary embolism in Japanese patients may have increased over the last few decades.

Aged↗

Factors predictive of venous thrombotic complications in patients with isolated superficial vein thrombosis.

OBJECTIVE: Superficial vein thrombosis may be complicated with venous thromboembolism. We examined factors predictive of venous thromboembolism in superficial vein thrombosis, which, to our knowledge, had not been prospectively studied before. DESIGN AND METHODS: We performed post hoc analysis of the STENOX trial, a prospective randomized controlled trial that investigated various antithrombotic therapies in 427 hospitalized patients with objectively confirmed symptomatic isolated superficial vein thrombosis. The value of various baseline characteristics as predictive factors of venous thrombotic complications at 3 months was studied with logistic regression. Venous thrombotic complications were defined as deep vein thrombosis or pulmonary embolism, or recurrence or proximal extension of superficial vein thrombosis. RESULTS: Venous thrombotic complications occurred in 78 patients. Independent predictive factors for complications were superficial vein thrombosis of recent onset (odds ratio [OR], 3.01; 95% confidence interval [CI], 1.44-6.27), severe chronic venous insufficiency (OR, 2.75; CI, 1.10-6.89), male gender (OR, 2.17; CI, 1.28-3.68), and history of venous thromboembolism (OR, 2.07; CI 1.06-4.04). Deep vein thrombosis or pulmonary embolism occurred in 19 patients. Only severe chronic venous insufficiency was an independent predictor of this complication (OR, 4.50; CI, 1.30-15.61). CONCLUSIONS: After symptomatic isolated superficial vein thrombosis, venous thrombotic complications are relatively frequent, and are more likely to occur in men, in patients with a history of venous thromboembolism or with severe chronic venous insufficiency, or in whom superficial vein thrombosis is recent. Knowledge of such predictive factors may be useful for determining appropriate treatment in patients with superficial vein thrombosis and for designing future phase III clinical trials.

Adult↗

Acute hepatotoxicity with resultant pulmonary and cerebral embolism in guinea pigs given tunicamycin.

The hepatotoxicity of tunicamycin was studied in 8 to 10-week-old guinea pigs. Acute hepatic damage was produced consistently in guinea pigs given a single dose of 400 micrograms/kg of tunicamycin and observed at intervals up to 72 h post-injection. Significant elevations occurred in serum levels of liver enzymes and ammonia, while concentrations of serum proteins were lowered. A periportal pattern of hepatocellular damage, with death of many hepatocytes, was consistently observed by 72 h. Severe vacuolation of hepatocytes resulted from lipid accumulation and dilatation of cisternae of rough endoplasmic reticulum, and bile ductule hyperplasia was also observed. Swollen hepatocyte cytoplasm protruded into many hepatic blood vessels, and detached portions of hepatocytes produced emboli in pulmonary and cerebral capillaries, thus contributing to capillary occlusion in the brains of treated guinea pigs.

Animals↗

Using dual-detector helical CT angiography to detect deep venous thrombosis in patients with suspicion of pulmonary embolism: diagnostic value and additional findings.

OBJECTIVE: The purpose of this study was to assess the value of dual-slice helical CT angiography in detecting deep venous thrombosis in patients in whom acute pulmonary embolism was suspected and to describe the additional extrathoracic findings. SUBJECTS AND METHODS: Sixty-five consecutive patients were examined for suspected pulmonary embolism using helical CT of the chest (2.7-mm collimation; table speed, 7.5 mm/sec; 100-140 mL of contrast medium injected at a rate of 3 mL/sec) followed by CT of the lower limbs (6.5-mm collimation; table speed, 10 mm/sec) without any additional contrast medium injection. Sequential scanning of the abdomen was performed using 10-mm collimation and an interval of 40 mm. Color Doppler sonography of the lower limbs was done within 24 hr of CT by two radiologists who were unaware of CT findings. Results of CT venography were compared with those of Doppler sonography and with phlebography or repeated focalized sonography in cases of discrepancy. RESULTS: Twenty-two patients had pulmonary embolism revealed on chest CT. Sixteen patients had a deep venous thrombosis. Thirteen patients with pulmonary embolism had a deep venous thrombosis. Three patients with deep venous thrombosis had no pulmonary embolism. Sensitivity and specificity for diagnosing deep venous thrombosis with CT was 93% and 97%, respectively (kappa = 0.88). Additional extrathoracic findings were observed in four patients. CONCLUSION: Combined CT venography with dual-slice scanning is an accurate method to diagnose deep venous thrombosis that may reveal additional imaging findings in some patients with possible pulmonary embolism.

Acute Disease↗

Comparison of the oral direct thrombin inhibitor ximelagatran with enoxaparin as prophylaxis against venous thromboembolism after total knee replacement: a phase 2 dose-finding study.

BACKGROUND: Up to one third of patients who undergo total knee replacement develop deep vein thrombosis after surgery despite receiving low-molecular-weight heparin prophylaxis. Ximelagatran is a novel direct inhibitor of free and clot-bound thrombin. METHODS: We performed a randomized, parallel, dose-finding study of 600 adults undergoing elective total knee replacement at 68 North American hospitals to determine the optimum dose of ximelagatran to use as prophylaxis against venous thromboembolism after total knee replacement. Patients received either ximelagatran twice daily by mouth in blinded fixed doses of 8, 12, 18, or 24 mg or open-label enoxaparin sodium, 30 mg, subcutaneously twice daily, starting 12 to 24 hours after surgery and continuing for 6 to 12 days. We measured the 6- to 12-day cumulative incidence of symptomatic or venographic deep vein thrombosis, symptomatic pulmonary embolism, and bleeding. RESULTS: A total of 594 patients received at least 1 dose of the study drug; 443 patients were evaluable for efficacy. Rates of overall venous thromboembolism (and proximal deep vein thrombosis or pulmonary embolism) for the 8-, 12-, 18-, and 24-mg doses of ximelagatran were 27% (6.6%), 19.8% (2.0%), 28.7% (5.8%), and 15.8% (3.2%), respectively. Rates of overall venous thromboembolism (22.7%) and proximal deep vein thrombosis or pulmonary embolism (3.1%) for enoxaparin did not differ significantly compared with 24-mg ximelagatran (overall difference, -6.9%; 95% confidence interval, -18.0% to 4.2%; P=.3). There was no major bleeding with administration of 24 mg of ximelagatran twice daily. CONCLUSION: Fixed-dose, unmonitored ximelagatran, 24 mg twice daily, given after surgery appears to be safe and effective oral prophylaxis against venous thromboembolism after total knee replacement.

Administration, Oral↗

[A differentiated approach to the diagnosis of pulmonary embolism and deep venous thrombosis using multi-slice CT].

PURPOSE: To establish a differentiated protocol for multi-slice CT (MSCT) examinations in cases of clinically suspected pulmonary embolism (PE) using pulmonary CT-angiography (CTA) and indirect CT-phlebography (CTP). MATERIALS AND METHODS: 161 patients with suspected PE were examined using an MSCT (SOMATOM Volume Zoom; Siemens, Forchheim, Germany). After intravenous administration of 120 ml of contrast material, a thin collimation chest-CT scan was performed (120 kV, 100 mAs, collimation: 4 x 1 mm). If PE was present, or previous examinations and clinical signs suggested deep venous thrombosis (DVT), a CTP was subsequently completed. CTPs were performed using a 4 x 5 mm protocol (120 kV, 170 mAs). Venous phase scanning, starting from the pelvic crest, was completed in the popliteal fossa three minutes after contrast material injection. In 73 extremities, CTP were compared to the results of ultrasound, phlebography and autopsy. Scan ranges were documented in all patients. Cumulative doses were calculated for male and female subgroups. RESULTS: 62 patients in our series suffered from PE and in 47 of these patients deep venous thrombosis was seen additionally. Of the 99 patients without PE, 47 also received indirect CTP. CTP confirmed the suspicion and extent of DVT in 8 patients. Only in 2 of 39 patients (5.1 %) was previously unknown DVT found, despite the exclusion of PE. Regarding DVT, sensitivity was 94.3 % and specificity was 92.1 % for indirect CTP. Cumulative chest CT doses averaged 3.3 mSv for males and 4.2 mSv for females, the calculated CTP dosage was 9.3 mSv (according to ICRP 60). CONCLUSIONS: The examination protocol presented is suitable for clinical usage in patients with suspected PE. If PE is confirmed, indirect CTP is justified, so that detailed information of the venous system can be obtained. However, the relatively high radiation dosage of an additional CTP requires a strict indication regiment in patients with a negative CTA.

Adult↗

Hemostatic abnormalities in patients with pulmonary embolism compared with that in deep vein thrombosis.

We investigated hemostatic abnormalities in 37 patients with deep vein thrombosis (DVT) and pulmonary embolism (PE) (PE patients) and in 40 patients with DVT without PE (DVT patients). Plasma fibrinogen, thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex, fibrin-D-dimer, activated protein C (APC)-protein C inhibitor (PCI) complex, von Willebrand factor (vWf), tissue plasminogen activator (t-PA), PA inhibitor-I (PAI-1), and thrombomodulin levels in both PE and DVT patients were significantly increased compared with normal volunteers. Plasma APC-PCI complex, PAI-1, and vWf levels in PE patients were significantly higher than those in DVT patients without PE. These findings indicate that PE patients are more hypercoagulable and hypofibrinolytic than DVT patients. Plasma TAT, APC-PCI complex, PAI-1, and vWf levels were the most sensitive indicators for PE. In these patients, increases in TAT and APC-PCI complex suggest DVT and increased PAI-1 and vWf suggest the risk of onset of PE.

Aged↗

Pulmonary embolism during and after pregnancy.

BACKGROUND: Venous thromboembolic disease is among the most common causes of morbidity and mortality during pregnancy. The clinical evaluation alone is insufficient for the diagnosis of venous thromboembolic disease, and the normal pregnant state makes this evaluation even more challenging. DIAGNOSIS: Objective testing is the mainstay of diagnosis, including compression ultrasound, impedance plethysmography, ventilation-perfusion scanning, computed tomography scanning, and pulmonary angiography. All of these tests can be safety performed during pregnancy. TREATMENT: If deep vein thrombosis or pulmonary embolism is diagnosed, anticoagulation should be initiated. Either (unfractionated) heparin or low molecular weight heparin is an acceptable treatment for acute venous thromboembolic disease. Both have risks and benefits, but both can be used safely during pregnancy. Intravenous heparin is the treatment of choice surrounding delivery due to its short half life. Because of the risk of adverse effects on the fetus, warfarin is not generally used during pregnancy. Unstable pulmonary embolism is difficult to treat during pregnancy, as there are minimal data regarding the safety and efficacy of thrombolytic therapy, inferior vena cava filters, and embolectomy during pregnancy. Case reports and case series suggest that thrombolytic therapy may be associated with lower risks of fetal loss than embolectomy. CONCLUSIONS: Venous thromboembolic disease is a significant cause of morbidity and mortality during pregnancy and the puerperal period. Objective testing is critical to establish the diagnosis and can be safely performed during pregnancy. Anticoagulation with heparin is the mainstay of therapy during the pregnancy, but patients may be transitioned to warfarin after delivery.

Anticoagulants↗