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PubMed2004

D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review.

BACKGROUND: Despite extensive literature, the diagnostic role of d-dimer for deep venous thrombosis (DVT) or pulmonary embolism (PE) remains unclear, reflecting multiple d-dimer assays and concerns about differing sensitivities and variability. PURPOSE: To systematically review trials that assessed sensitivity, specificity, likelihood ratios, and variability among d-dimer assays. DATA SOURCES: Studies in all languages were identified by searching PubMed from 1983 to January 2003 and EMBASE from 1988 to January 2003. STUDY SELECTION: The researchers selected prospective studies that compared d-dimer with a reference standard. Studies of high methodologic quality were included in the primary analyses; sensitivity analysis included additional weaker studies. DATA EXTRACTION: Two authors collected data on study-level factors: d-dimer assay used, cutoff value, and whether patients had suspected DVT or PE. DATA SYNTHESIS: For DVT, the enzyme-linked immunosorbent assay (ELISA) and quantitative rapid ELISA dominate the rank order for these values: sensitivity, 0.96 (95% confidence limit [CL], 0.91 to 1.00), and negative likelihood ratio, 0.12 (CL, 0.04 to 0.33); and sensitivity, 0.96 (CL, 0.90 to 1.00), and negative likelihood ratio, 0.09 (CL, 0.02 to 0.41), respectively. For PE, the ELISA and quantitative rapid ELISA also dominate the rank order for these values: sensitivity, 0.95 (CL, 0.85 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.03 to 0.58); and sensitivity, 0.95 (CL, 0.83 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.02 to 0.84), respectively. The ELISA and quantitative rapid ELISA have negative likelihood ratios that yield a high certainty for excluding DVT or PE. The positive likelihood values, which are in the general range of 1.5 to 2.5, do not greatly increase the certainty of diagnosis. Sensitivity analyses do not affect these findings. LIMITATIONS: Although many studies evaluated multiple d-dimer assays, findings are based largely on indirect comparisons of test performance characteristics across studies. CONCLUSION: The ELISAs in general dominate the comparative ranking among the d-dimer assays for sensitivity and negative likelihood ratio. For excluding PE or DVT, a negative result on quantitative rapid ELISA is as diagnostically useful as a normal lung scan or negative duplex ultrasonography finding.

Acute Disease↗
PubMed2001

Outpatient treatment of patients with deep-vein thrombosis or pulmonary embolism.

There have been a large number of randomized trials comparing standard unfractionated intravenous heparin with low-molecular-weight heparin for the treatment of deep-vein thrombosis, but only two of these have looked at outpatient therapy. There have been only two randomized trials including patients with symptomatic pulmonary embolism, and neither of these provided outpatient therapy. Postmortem and clinical studies have shown a strong association between pulmonary embolism and the presence of venous thrombosis in the lower limbs. Based on similar rates of venous thromboembolic recurrence and death, these studies suggest that initial treatment should be the same for deep-vein thrombosis and pulmonary embolism. The feasibility of providing outpatient care to many patients seeking treatment for deep-vein thrombosis or acute pulmonary embolism at certain tertiary care hospitals has become evident, but the data suggest that the proportion of eligible patients is institution dependent and may vary from 18% to 91%. In the author's institution, approximately 50% of patients with pulmonary embolism could be treated as outpatients, but there have been no other reports on outpatient therapy for patients with pulmonary embolism. If patients with pulmonary embolism meet criteria demonstrated to result in a higher risk of death, it is, of course, reasonable to not treat such patients on an outpatient basis. Low-molecular-weight heparin followed by oral anticoagulant therapy provides adequate therapy in most patients with deep-vein thrombosis or pulmonary embolism, and many patients can be treated as outpatients.

Administration, Oral↗
PubMed2004

Deep vein thrombosis and pulmonary embolism in two cohorts: the longitudinal investigation of thromboembolism etiology.

PURPOSE: To determine the incidence of deep vein thrombosis and pulmonary embolism in two cohorts representing regions of the United States. METHODS: The sample comprised 21,680 participants of the Atherosclerosis Risk in Communities study and the Cardiovascular Health Study. Subjects were aged >/=45 years, resided in six communities, and were followed for 7.6 years. All hospitalizations were identified and thromboses were validated by chart review. RESULTS: The age-standardized incidence of first-time venous thromboembolism was 1.92 per 1000 person-years. Rates were higher in men than women, and increased with age in both sexes. There was no antecedent trauma, surgery, immobilization, or diagnosis of cancer for 48% (175/366) of events. The 28-day case-fatality rate was 11% (29/265) after a first venous thromboembolism and 25% (17/67) for cancer-associated thrombosis. The recurrence rate 2 years after a first venous thromboembolism was 7.7% per year (95% confidence interval [CI]: 4.5% to 10.9% per year). Cancer was the only factor independently associated with 28-day fatality (relative risk [RR] = 5.2; 95% CI: 1.4 to 19.9) or recurrent thrombosis (RR = 9.2; 95% CI: 2.0 to 41.7). CONCLUSION: The incidence of venous thromboembolism in this cohort of middle- and older-aged subjects was similar to that observed in more geographically homogeneous samples. Half of cases were idiopathic. Short-term mortality and 2-year recurrence rates were appreciable, especially among subjects with cancer. Based on this study we estimate that 187,000 cases of first-time venous thromboembolism are diagnosed yearly in the United States among those aged 45 years or older.

Aged↗
PubMed1998

Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study.

BACKGROUND: The incidence of venous thromboembolism has not been well described, and there are no studies of long-term trends in the incidence of venous thromboembolism. OBJECTIVES: To estimate the incidence of deep vein thrombosis and pulmonary embolism and to describe trends in incidence. METHODS: We performed a retrospective review of the complete medical records from a population-based inception cohort of 2218 patients who resided within Olmsted County, Minnesota, and had an incident deep vein thrombosis or pulmonary embolism during the 25-year period from 1966 through 1990. RESULTS: The overall average age- and sex-adjusted annual incidence of venous thromboembolism was 117 per 100000 (deep vein thrombosis, 48 per 100000; pulmonary embolism, 69 per 100000), with higher age-adjusted rates among males than females (130 vs 110 per 100000, respectively). The incidence of venous thromboembolism rose markedly with increasing age for both sexes, with pulmonary embolism accounting for most of the increase. The incidence of pulmonary embolism was approximately 45% lower during the last 15 years of the study for both sexes and all age strata, while the incidence of deep vein thrombosis remained constant for males across all age strata, decreased for females younger than 55 years, and increased for women older than 60 years. CONCLUSIONS: Venous thromboembolism is a major national health problem, especially among the elderly. While the incidence of pulmonary embolism has decreased over time, the incidence of deep vein thrombosis remains unchanged for men and is increasing for older women. These findings emphasize the need for more accurate identification of patients at risk for venous thromboembolism, as well as a safe and effective prophylaxis.

Adolescent↗
PubMed2001

Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Pinede L, Ninet J, Duhaut P et al for the Investigators of the 'Durée Optimale du Traitement Antivitamines K' (DOTAVK) study. Circulation 2001; 103: 2453-60.

QUESTION: Is anticoagulant treatment for calf vein thrombosis for 6 weeks duration associated with acceptable recurrence and safety outcomes? Is anticoagulant therapy for 3 months duration for proximal deep vein thrombosis (DVT) or pulmonary embolism (PE) associated with acceptable recurrence and safety outcomes? POPULATION: Men and women with a first episode of symptomatic calf vein thrombosis or proximal DVT confirmed by ultrasound or venography, or PE confirmed by lung scan or angiography. Patients with pregnancy, thrombophilia, severe PE, and cancer were excluded. DESIGN AND METHODS: After treatment with heparin and oral anticoagulants targeting an INR of 2-3, patients with calf DVT were randomized to 6 weeks (n = 105) versus 3 months (n = 92) of treatment, and patients with proximal DVT and/or PE were randomized to 3 months (n = 270) versus 6 months (n = 269) of treatment. The outcome events were recurrences and major, minor, or fatal bleeding complications. The mean follow-up time was 12 months. RESULTS: A total of 736 patients were enrolled. For calf vein thrombosis the recurrence of DVT or PE after 6 weeks of therapy was 2/105 (2.0%) versus 3/92 (3.4%) with 3 months of therapy, relative risk of 0.58 (95% CI: 0.10-3.36). The rates of major bleeding were 1/105 (1.0%) and 3/92 (3.4%) respectively, relative risk of 0.29 (95% CI: 0.03-2.72). For proximal DVT or PE, the recurrence rate after 3 months of therapy was 21/270 (8.1%) versus 23/269 (8.7%) after 6 months of treatment, relative risk of 0.93 (95% CI: 0.53-1.65). The rates of major bleeding were 5/270 (1.9%) versus 7/269 (2.6%) respectively, relative risk of 0.73 (95% CI: 0.24-2.27). CONCLUSION: After isolated calf vein DVT, 6 weeks of oral anticoagulation is sufficient. For proximal DVT or PE, 3 and 6 months of anticoagulant therapy is equivalent. For patients with temporary risk factors who have a low risk of recurrence, 3 months of treatment seems to be sufficient.

Administration, Oral↗
PubMed1997

High antibody levels to prothrombin imply a risk of deep venous thrombosis and pulmonary embolism in middle-aged men--a nested case-control study.

Antibodies against phospholipid-binding plasma proteins, such as beta2-glycoprotein I (beta2-GPI) and prothrombin, are associated with thromboembolic events in patients with systemic lupus erythematosus and also in subjects with no evident underlying diseases. We wanted to examine whether increased levels of antibodies to negatively-charged phospholipids (cardiolipin), to phospholipid-binding plasma proteins beta2-GPI and prothrombin and to oxidised low-density lipoprotein (LDL) were associated with risk of deep venous thrombosis or pulmonary embolism in subjects with no previous thrombosis. The antibodies were measured in stored serum samples from 265 cases of deep venous thrombosis of the lower extremity or pulmonary embolism occurring during a median follow-up of about 7 years and from 265 individually matched controls. The study subjects were middle-aged men participating in a cancer prevention trial of alpha-tocopherol and beta-carotene and the cases of thromboembolic events were identified from nationwide Hospital Discharge Register. The risk for thrombotic events was significantly increased only in relation to antiprothrombin antibodies. As adjusted for body mass index, number of daily cigarettes and history of chronic bronchitis, myocardial infarction and heart failure at baseline, the odds ratio per one unit of antibody was 6.56 (95% confidence interval 1.73-25.0). The seven highest individual optical density-unit values of antiprothrombin antibodies were all confined to subjects with thromboembolic episodes. In conclusion, the present nested case-control study showed that high autoantibody levels against prothrombin implied a risk of deep venous thrombosis and pulmonary embolism and could be involved in the development of the thrombotic processes.

Aged↗
PubMed1982

Management of deep venous thrombosis and pulmonary embolism during pregnancy.

Despite venous stasis and a hypercoagulable state during pregnancy, the reported incidences of deep venous thrombosis and pulmonary embolism are remarkably low, about 1 in 2,000 and 1 in 10,000 cases, respectively. Mortality from antepartum thromboembolism has been reported in about 15 percent of untreated patients and less than 1 percent of treated patients. Adequate anticoagulant therapy significantly reduces maternal mortality and decreases postpartum morbidity. The proper anticoagulant agent for use during pregnancy has been widely debated. Coumarin compounds pass through the placenta and into the fetus. Hemorrhagic complications in the fetus are uncommon if prothrombin times are carefully controlled and if the drug is discontinued before delivery. However, coumarin during the first trimester has the teratogenic hazard of producing chondrodysplasia punctata. Heparin, in contrast, does not cross the placental barrier and is considered more effective treatment for deep venous thrombosis; however, long-term intravenous administration during pregnancy has been considered both impractical and possibly hazardous due to the risk of osteoporosis after 6 months of therapy. In our study, a combined regimen of intravenous and subcutaneous heparin was used successfully in four women with deep venous thrombosis. One patient who had recurrent embolization while on adequate intravenous heparin underwent vena caval clipping and had an uneventful Cesarian section at term with a normal infant. Another patient also underwent Caesarian section with a normal infant, while the other two women had normal vaginal deliveries at term. Miniheparin therapy was continued for 3 months postpartum, followed by long-term aspirin and Ascriptin therapy. Carefully controlled heparin therapy in a pregnant woman with deep venous thrombosis both safe and beneficial for mother and fetus.

Adolescent↗
PubMed1998

Thrombolytic therapy for venous thrombosis and pulmonary embolism.

Streptokinase, urokinase, tissue plasminogen activator and similar drugs can all cause lysis of venous thrombi and pulmonary emboli, but there is small evidence that accelerated lysis achieves a significantly better clinical outcome, on average, in the shorter or longer term, than heparin alone. Thrombolytic therapy for deep leg vein thrombosis aims to restore flow and to preserve venous valves, and so to prevent chronic post-phlebitic disability, but no trial has convincingly demonstrated that the last can be achieved in more than a few patients. Only a small minority of people with extensive proximal thrombosis develop disabling post-phlebitic venous insufficiency, and there are no good clinical predictors of this outcome. As a result, any widespread use of thrombolytics would bring an immediate risk of major bleeding to many people who will never be destined to develop a clinically important problem. Thrombolytic therapy after venous thrombosis should be avoided except, perhaps, in a few carefully selected patients with severe obstruction. The case for using thrombolytics after recent pulmonary embolism is strongest in the limited number of patients with ongoing hypoxia, respiratory distress, pulmonary hypertension and right heart failure, because thrombolytic therapy often achieves an impressive and almost immediate clinical benefit in this clinical setting. Whether early relief from pulmonary artery obstruction translates into longer-term advantage over heparin remains uncertain, however, because no comparative trial has ever shown these drugs to reduce mortality after pulmonary embolism. In all cases, both the physician and the patient must balance the certainty of an immediate bleeding risk against the uncertainty of a better than marginal real benefit.

Fibrinolytic Agents↗
PubMed1998

D-dimer strategy in thrombosis exclusion--a gold standard study in 100 patients suspected of deep venous thrombosis or pulmonary embolism: 8 DD methods compared.

DD are now recognized as a valuable tool to screen patients suspected of deep venous thrombosis or pulmonary embolism before carrying out a gold standard radiologic examination. The newest methods available claim to be able to ascertain the absence of thrombosis, but they have yet to prove their efficiency. We compared the performances of 3 reference ELISA methods (D-DI Asserachrom Stago, D-dimer Enzygnost Behring and Dimertest GOLD EIA Agen), 5 recent rapid methods (VIDAS D-Dimer bioMérieux, Instant IA Stago, Simplired Agen, Nycocard D-dimer Nycomed and Accuclot D-Dimer Sigma Diagnostics) and two routine latex methods (Dimertest American Diagnostica and FDP-Slidex bioMérieux) in 100 patients. One of the rapid quantitative methods was demonstrated to have a level of efficiency comparable to that of ELISA methods. Finally, the cost and efficiency of different strategies were evaluated, the association of a routine latex method with the VIDAS D-Dimer bioMérieux being proven to be the most efficient.

Adult↗
PubMed1978

Treatment of venous thrombosis and pulmonary embolism by streptokinase.

We applied the standard treatment with streptokinase to 52 cases of deep venous thrombosis and 35 cases pulmonary embolism. Angiography demonstrated total lysis of the clot 22 times, partial lysis 42 times, and no lysis 23 times. The absence of lysis was more frequent in venous clots than in pulmonary clots. Early treatment was more effective, achieving complete lysis in 21 of 22 cases. Nevertheless, in deep venous thrombosis, late treatment can result in partial lysis and set an important venous junction free. With the standard treatment, the biologic controls showed good lysis in 75% of the cases, insufficient lysis in 15%, and no lysis in 10%. The extent of the thrombosis is an important point. The clot was totally lysed in 9 of 10 cases of localized deep venous thrombosis. In patients with pulmonary embolism, about 30% of the obstructed surface is cleared. Nevertheless, in such cases we must take into consideration not only the nonperfused pulmonary area, but also the venous starting point of the clot.

Adult↗
PubMed2006

Prevalence of factor V Leiden and prothrombin G20210A mutations in Chinese patients with deep venous thrombosis and pulmonary embolism.

Venous thromboembolism (VTE) is a common vascular disease that results in two major clinical manifestations: deep venous thrombosis (DVT) and pulmonary embolism (PE). Several genetic risk factors, especially factor V Leiden and prothrombin G20210A mutations have been reported to be related to VTE in Caucasians, but the relationship remains controversial in other populations. Thus, the objective of the present study was to compare the frequency of the two mutations and also to investigate whether acquired risk factors other than genetic mutations may play a different role in Chinese VTE patients. Thirty-five patients were diagnosed with DVT concomitant PE, 178 patients with DVT, 54 patients with PE and 102 control subjects were recruited. The mutation was determined by the polymerase chain reaction-restriction fragment length polymorphism method. Of all subjects, none was a carrier of factor V Leiden or prothrombin G20210A mutations. The frequency of surgery was significantly higher in the PE group than that in other groups. There was no significant difference among the three groups in other known risk factors. The data presented here indicate that factor V Leiden and prothrombin G20210A mutations are very rare in the Chinese population, and the genetic risk profile of VTE in the Chinese population is different from that in Caucasians.

Adult↗
PubMed1998

Management of venous thrombosis and pulmonary embolism after gynecological surgery.

We experienced 23 cases of venous thrombosis after gynecological surgery for the past 12 years at Tokyo Women's Medical University Hospital, representing 0.345 % of all patients. Eighteen of the 23 cases had deep venous thrombosis (DVT) including five cases followed by pulmonary embolism (PE), and five cases had PE without any symptoms of DVT. The main risk factors for thrombosis in these 23 patients were (1) obesity, DM, hyperlipidemia; (2) huge abdominal tumor, severe adhesion; and (3) hemoconcentration, post-treatment of severe anemia. The onset of PE varied from 1 to 3 postoperative days, when the patients started to walk. Five cases had dyspnea, chest pain, and decreased PaO2 levels without leg pain, while five cases showed only calf pain and tenderness with decreased PaO2 levels. PE was confirmed by immediate diagnostic images such as RI venography with ventilation and perfusion lung scan, pulmonary arterial CT, or pulmonary arteriography. Two patients died and eight patients recovered. The best way of managing venous thrombosis might be as follows: (1) identify the risk factors of thrombosis before surgery; (2) perform prophylactic leg exercises in bed and/or active anticoagulant therapy depending on the degree of risk factors; (3) rapid diagnosis with the images; and (4) proper treatment.

Adult↗
PubMedDate not supplied

Low-molecular-weight heparins versus unfractionated heparin in the treatment of deep vein thrombosis and pulmonary embolism.

In the United States, there are approximately 217,000 patients with deep-vein thrombosis hospitalized each year. The cause for these thrombotic events include surgery, trauma, malignancy, hereditary thrombotic disorders, stroke, spinal cord injury, and idiopathic. Frequently, a number of these patients are cared for in rehabilitation units or centers to improve their functional status. This rehabilitation process is often interrupted with the development of deep vein thrombosis and or pulmonary embolism. These patients are placed on bedrest and, often, are transferred to an acute care hospital to receive continuous infusion unfractionated heparin with a targeted activated partial thromboplastin time of 1.5-2.5 times the baseline value and warfarin to achieve an international normalized ratio of 2-3. Recently, the low-molecular-weight heparins have been shown to be as or more effective than unfractionated heparin, have less major bleeding complications, and do not require laboratory monitoring of coagulation tests to adjust medications. The purpose of this article is to review the efficacy and safety of low-molecular-weight heparins and provide physiatrists with a rationale approach for managing patients with deep vein thrombosis and or pulmonary embolism on their respective units.

Activities of Daily Living↗
PubMed1994

[Prevention and treatment of deep venous thrombosis: prevention of pulmonary embolism].

Deep vein thrombosis (DVT), if not properly treated, may be complicated by pulmonary embolism in about 50% of the cases within 3 months. Therefore, effective prevention of pulmonary embolism relies on three cornerstones: correct prophylaxis, early diagnosis, and correct treatment of DVT. In prophylaxis of DVT, low-dose heparin is effective in preventing postoperatory DVT and pulmonary embolism in medium risk operations, and also in "medical" DVT. In high risk operations and patients, personalized low-dose heparin, oral anticoagulants and especially low-molecular weight heparins have been used. The available controlled trials demonstrate that the low-molecular weight heparins are especially efficacious and also cost-effective in high risk situations as elective hip surgery. Validated techniques for early diagnosis of DVT are phlebography and, in symptomatic proximal DVT, also venous echotomography. Therapy of overt DVT is usually performed with infusional or subcutaneous heparin at therapeutic doses, followed by moderate range oral anticoagulants. In the initial treatment, low-molecular weight heparins at single subcutaneous daily dosing can substitute for standard heparin. Indication to thrombolytic therapy should be restricted to selected cases; thrombectomy has limited application. Caval filters may be useful in strictly selected indications, especially in presence of contraindications or resistance to anticoagulant treatments.

Anticoagulants↗