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PubMed1998

Resistance to activated protein C, highly prevalent amongst users of oral contraceptives with venous thromboembolism.

OBJECTIVE: Inherited resistance to activated protein C (APC resistance), which is caused by a single point mutation in the factor V gene, is a frequent risk factor for venous thromboembolism. The aim of this study was to determine the prevalence of APC resistance and other coagulation disorders in fertile women with venous thromboembolism and also the risk factors these women had been exposed to in connection with thromboembolic events. DESIGN: A retrospective, case-control study of 36 month duration. SETTING: The study was carried out at Blekinge Hospital, Karlskrona, Sweden. SUBJECTS: The study population comprised 27 fertile women age 16-47 years with thromboembolic complications, referred to the department of Internal Medicine at Blekinge Hospital in Karlskrona during a 36-month period. RESULTS: APC resistance was found in 10 out of 27 women. APC resistance was associated with treatment with oral contraceptives in five out of six women and with pregnancy in one of seven women. All women with resistance to APC developed venous thrombosis in association with a predisposing situation (risk situation) such as surgery, trauma, immobilization, pregnancy, inflammatory state or the use of oral contraceptives. Amongst women not resistant to APC, all but one developed thrombosis in connection with a risk situation. CONCLUSION: APC resistance was found to be highly prevalent amongst fertile women with a history of thromboembolic complication occurring during their use of oral contraceptives.

Adolescent↗
PubMed1999

Oral anticoagulant treatment in patients with mechanical heart valves: how to reduce the risk of thromboembolic and bleeding complications.

Patients with mechanical heart valves have a high risk of thrombus formation on the valve and subsequent systemic embolism. These patients therefore need to receive life-long oral anticoagulation (OAC). Despite this treatment, the overall incidence rate of major thromboembolic complications is still about 1-2 per 100 patient-years. Additionally, these patients have an increased risk of bleeding complications, ranging between 1 and 7 per 100 patient-years. To reduce both types of often very serious complications, the optimal intensity of anticoagulation needs to be established. We found a fairly wide optimal range between 2.5 and 4.9 INR (international normalized ratio) at which the incidence of both untoward events was minimal. As a target intensity, we recommend opting for the middle of this range (INR 3.0-4.0), thereby providing a safe margin at both ends. In order to further reduce thromboembolic and bleeding complications, two approaches can be considered: first of all, the management of OAC treatment needs to be optimized in order to achieve a stable therapeutic effect in as many patients as possible. Secondly, patient characteristics need to be identified that increase the thromboembolic or bleeding risk. Subsequently, the optimal intensity may need to be adjusted accordingly, at an individual level. Possible risk factors for an increased thromboembolic risk are position and type of the prosthesis. Age may increase both the risk of thromboembolism and the risk of haemorrhage.

Administration, Oral↗
PubMed2001

Increased levels of tissue plasminogen activator antigen and factor VIII activity in nonvalvular atrial fibrillation: relation to predictors of thromboembolism.

INTRODUCTION: Given that nonvalvular atrial fibrillation (AF)-associated stroke can be either cardioembolic or atherothrombotic, we investigated the relationships between nonvalvular AF and hemostatic factors reflecting intrinsic thrombogenic and atherogenic potentials (tissue plasminogen activator [t-PA] antigen, plasminogen activator inhibitor-1, and factor VIII activity). We also evaluated the clinical applicability of these hemostatic factors by examining whether AF subjects with established clinical or echocardiographic predictors of thromboembolism had higher levels of these factors. METHODS AND RESULTS: Of the 3,212 participants of a Chinese population-based study, 53 subjects (1.7%) with AF were identified. Among the hemostatic factors measured, t-PA antigen (median 12.8 vs 8.1 ng/mL; P < 0.01) and factor VIII activity (median 155% vs 133%; P < 0.05) were significantly higher in AF subjects after adjustment for age and sex. In multivariate analysis, features independently associated with t-PA antigen levels were AF, sex, body mass index, systolic blood pressure, total cholesterol, triglycerides, and left ventricular systolic dysfunction. Features independently associated with factor VIII activity levels included AF, age, and total cholesterol. Levels of both t-PA antigen and factor VIII activity were primarily elevated in AF subjects with predictors of thromboembolism (age > 75 years, hypertension, diabetes, and left ventricular systolic dysfunction), whereas in AF subjects with no thromboembolic predictors, plasma levels of hemostatic factors examined were similar to those without AF. CONCLUSION: We demonstrated that nonvalvular AF was independently associated with increased peripheral levels of t-PA antigen and factor VIII activity. Levels of both hemostatic factors were primarily elevated in AF subjects with predictors of thromboembolism. Whether these hemostatic factors are independently predictive of future thromboembolic events in AF patients requires further investigation.

Adult↗
PubMed2002

Venous thromboembolism epidemiology: implications for prevention and management.

Venous thromboembolism is a major health problem, with an incidence that exceeds 1 per 1000. Over 200,000 new cases occur in the United States annually. Of these, 30% of patients die within 30 days; one-fifth suffer sudden death due to pulmonary embolism. Despite improved prophylaxis, the incidence of venous thromboembolism has not changed significantly since 1980. Independent risk factors for venous thromboembolism include increasing age, male gender, surgery, trauma, hospital or nursing home confinement, malignancy, neurologic disease with extremity paresis, central venous catheter/ transvenous pacemaker, prior superficial vein thrombosis, and varicose veins; among women, the risk factors include pregnancy, oral contraceptives, and hormone replacement therapy. About 30% of surviving patients develop recurrent venous thromboembolism within 10 years. Independent predictors for recurrence include increasing age, obesity, malignant neoplasm, and extremity paresis. About 28% of patients develop venous stasis syndrome within 20 years. To reduce venous thromboembolism incidence, improve survival, and prevent recurrence and complications, patients with these characteristics should receive appropriate prophylaxis.

Age Factors↗
PubMed1983

A 5-year follow-up of the Medtronic-Hall valve: survival and thromboembolism.

Throughout the period 1977 to 1982, 436 patients underwent aortic valve replacement (AVR), 106 underwent mitral valve replacement (MVR) and 56 patients underwent double valve replacement (DVR), with the Medtronic-Hall prosthetic valve (previous equivalent: Hall-Kaster valve). Early and late mortality were 4% and 9% for AVR, 8% and 11% for the MVR and 7% and 13% in the DVR, respectively. Actuarial survival after 5 years of follow-up was 80.9% for AVR, 75.4% for MVR and 81.0% for the DVR. Thromboembolic complications included 2 cases of valve thrombosis in the AVR, in one case secondary to valve endocarditis. Eleven further thromboembolic episodes occurred in 10 patients with AVR. In MVR an aspergillus thrombus was found on the valve at autopsy in a patient dying from multiple cerebral aspergillus abscesses. Five further thromboembolic episodes occurred in 4 patients with MVR. In the DVR group there was one valve thrombosis and one further patient with a thromboembolic episode. The actuarial probability of remaining free from thromboembolism at the end of the 5 years of follow-up was 92.5% for AVR and 83.7% for MVR.

Aortic Valve↗
PubMed1999

A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group.

BACKGROUND: The efficacy and safety of thromboprophylaxis in patients with acute medical illnesses who may be at risk for venous thromboembolism have not been determined in adequately designed trials. METHODS: In a double-blind study, we randomly assigned 1102 hospitalized patients older than 40 years to receive 40 mg of enoxaparin, 20 mg of enoxaparin, or placebo subcutaneously once daily for 6 to 14 days. Most patients were not in an intensive care unit. The primary outcome was venous thromboembolism between days 1 and 14, defined as deep-vein thrombosis detected by bilateral venography (or duplex ultrasonography) between days 6 and 14 (or earlier if clinically indicated) or documented pulmonary embolism. The duration of follow-up was three months. RESULTS: The primary outcome could be assessed in 866 patients. The incidence of venous thromboembolism was significantly lower in the group that received 40 mg of enoxaparin (5.5 percent [16 of 291 patients]) than in the group that received placebo (14.9 percent [43 of 288 patients]) (relative risk, 0.37; 97.6 percent confidence interval, 0.22 to 0.63; P< 0.001). The benefit observed with 40 mg of enoxaparin was maintained at three months. There was no significant difference in the incidence of venous thromboembolism between the group that received 20 mg of enoxaparin (43 of 287 patients [15.0 percent]) and the placebo group. The incidence of adverse effects did not differ significantly between the placebo group and either enoxaparin group. By day 110, 50 patients had died in the placebo group (13.9 percent), 51 had died in the 20-mg group (14.7 percent), and 41 had died in the 40-mg group (11.4 percent); the differences were not significant. CONCLUSIONS: Prophylactic treatment with 40 mg of enoxaparin subcutaneously per day safely and effectively reduces the risk of venous thromboembolism in patients with acute medical illnesses.

Acute Disease↗
PubMed2001

Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery.

BACKGROUND: Surgery for hip fracture carries a high risk of venous thromboembolism, despite the use of current thromboprophylactic treatments. Fondaparinux, a synthetic pentasaccharide, is a new antithrombotic agent that may reduce this risk. METHODS: In a double-blind study, were randomly assigned 1711 consecutive patients undergoing surgery for fracture of the upper third of the femur to receive subcutaneous doses of either 2.5 mg of fondaparinux once daily, initiated postoperatively, or 40 mg of enoxaparin once daily, initiated preoperatively, for at least five days. The primary efficacy outcome was venous thromboembolism up to postoperative day 11. Venous thromboembolism was defined as deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or documented symptomatic pulmonary embolism. The main safety outcomes were major bleeding and mortality from all causes. The duration of follow-up was six weeks. RESULTS: The incidence of venous thromboembolism by day 11 was 8.3 percent (52 of 626 patients) in the fondaparinux group and 19.1 percent (119 of 624 patients) in the enoxaparin group (P<0.001). The reduction in risk with fondaparinux was 56.4 percent (95 percent confidence interval, 39.0 to 70.3 percent). There were no significant differences between the two groups in the incidence of death or clinically relevant bleeding. CONCLUSIONS: In patients undergoing surgery for hip fracture, fondaparinux was more effective than enoxaparin in preventing venous thromboembolism and equally safe.

Aged↗
PubMed2004

The risk of recurrent venous thromboembolism in men and women.

BACKGROUND: Whether a patient's sex is associated with the risk of recurrent venous thromboembolism is unknown. METHODS: We studied 826 patients for an average of 36 months after a first episode of spontaneous venous thromboembolism and the withdrawal of oral anticoagulants. We excluded pregnant patients and patients with a deficiency of antithrombin, protein C, or protein S; the lupus anticoagulant; cancer; or a requirement for potentially long-term antithrombotic treatment. The end point was objective evidence of a recurrence of symptomatic venous thromboembolism. RESULTS: Venous thromboembolism recurred in 74 of the 373 men, as compared with 28 of the 453 women (20 percent vs. 6 percent; relative risk of recurrence, 3.6; 95 percent confidence interval, 2.3 to 5.5; P<0.001). The risk remained unchanged after adjustment for age, the duration of anticoagulation, and the presence or absence of a first symptomatic pulmonary embolism, factor V Leiden, factor II G20210A, or an elevated level of factor VIII or IX. At five years, the likelihood of recurrence was 30.7 percent among men, as compared with 8.5 percent among women (P<0.001). The relative risk of recurrence was similar among women who had had their first thrombosis during oral-contraceptive use or hormone-replacement therapy and women in the same age group in whom the first event was idiopathic. CONCLUSIONS: The risk of recurrent venous thromboembolism is higher among men than women.

Adult↗
PubMed2000

Venous thromboembolism and oral contraceptive use: a methodological study of diagnostic suspicion and referral bias.

BACKGROUND: In studies of oral contraceptive oral contraceptive use and risk of venous thromboembolism, bias related to heightened diagnostic suspicion and preferential referral of oral contraceptive users has been an issue. The aim of our study was to determine the presence and potential impact of diagnostic suspicion and referral bias. METHODS: We conducted a case/non-case study in 21 regional study centers in Germany and, in parallel, a conventional case-control study using the same cases but randomly selected population controls from the same areas. Women with symptoms compatible with venous thromboembolism were included in the study between 1994 and 1999, and classified as cases or non-cases (first reference group) according to the diagnostic work-up (case/non-case study). A second reference group consisted ofpopulation controls (conventional case-control study as an internal comparison for the case/non-case study): 606 cases, 462 non-cases and 2942 population controls aged 15-49 years. Adjusted unconditional regression analyses were performed. RESULTS: Adjusted odds ratios for venous thromboembolism in oral contraceptive users were systematically higher in the classical case-control study compared to the case/non-case approach (using the same cases) across all subgroup analyses (e.g. for idiopathic cases, the odds ratio was 67% higher in the case-control study: 4.33 (95% confidence interval (CI) 3.27-5.74) versus 2.60 (95% CI 1.75-3.88)). We found a significantly increasing trend of oral contraceptive use in four categories of increasingly sophisticated diagnostic tests that were applied to 1067 women with a suspicion of venous thromboembolism, irrespective of the outcome. Stratified analysis showed the diagnostic level to be a confounder. CONCLUSION: In our population-based study with the possibility of internal comparison, we found clear evidence that diagnostic suspicion and referral bias does play an important role in case-control studies of venous thromboembolism risk among oral contraceptive users. This underlines the importance of making an effort to avoid this bias when designing a new study.

Adolescent↗
PubMedDate not supplied

Thromboembolic events in the cancer patient.

Thromboembolic events are a major cause of morbidity in cancer patients and may be harbingers of occult malignancy. Trousseau's syndrome (TS) is probably the best known thromboembolic syndrome in the cancer patient, encompassing a variety of paraneoplastic thromboembolic disorders. These include spontaneous recurrent or migratory venous thromboses and arterial emboli caused by nonbacterial thrombotic endocarditis in a patient with malignancy. Although linked to almost all cancers, venous thromboembolism (VTE) is a terminal event in many cancers occurring in women, such as breast, uterine, and lung cancers (Monreal et al. Thrombosis and Haemostasis 1997;78:1316). Appropriate recognition of the syndrome is paramount because TS often requires careful medical surveillance and management. Significant complications of thromboembolic events in the cancer patient include limb ischemia and deep venous thrombosis/pulmonary embolism, which can cause devastating and permanent consequences. The rehabilitation management of these complications is reviewed, with an emphasis on diagnostic and therapeutic approaches in this patient population.

Amputation, Surgical↗
PubMed2006

Thromboembolic complications in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

AIMS: Incidence and clinical presentation of thromboembolic complications in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) were analysed. In reports on ARVD/C, thromboembolism is rarely mentioned. The possible risk factors are: right ventricle (RV) dilatation, aneurysms, and wall motion abnormalities. METHODS AND RESULTS: A group of 126 patients (89 male, 37 female, aged 43.6+/-14.3) with ARVD/C was retrospectively analysed for the presence of thromboembolic complications. The mean follow-up period was 99+/-64 months. Thromboembolic complications, i.e. pulmonary embolism (n=2), RV outflow tract thrombosis with severe RV failure (n=1), and cerebrovascular accident associated with atrial fibrillation (n=2) were observed in 4% of the patients. Spontaneous echogenic contrast was observed in seven patients with severe damage to RV. In four of them supraventricular arrhythmias resulting in heart failure were reported. Annual incidence of thromboembolic complications was 0.5/100 patients. CONCLUSIONS: (i) ARVD/C may be complicated by thrombosis. Annual incidence of such complications is significantly lower than reported for left ventricle failure. (ii) Anticoagulation should be used in ARVD/C patients with large, hypokinetic RV and slow blood flow. (iii) Patients with severe forms of ARVD/C, thrombus formation in the RV and/or spontaneous echocardiographic contrast are at higher risk of a poor outcome.

Adult↗
PubMed1992

Risk factors for fatal venous thromboembolism in young women: a case-control study.

A case-control study of fatal venous thromboembolism in young women is described. Sixty women aged between 16 and 39 who died from thromboembolism in England and Wales between 1986 and 1988 were included in the study. Two living controls matched for age and marital status were sought from the records of the general practitioner with whom each case was registered. Some 115 controls were included in the study. The cases had a significantly higher prevalence of a history of major illness, particularly thrombotic episodes, than the controls. The odds ratio (OR) of a fatal thromboembolism in women who had a history of venous thrombosis was 4.0 (95% Cl: 1.4-11.5). There was also a significantly higher frequency of a recent operation or accident amongst the cases than the controls (OR = 11.1, 95% Cl: 1.3-92.5). There was no significant excess or oral contraceptive use amongst the cases. The overall OR associated with current use of oral contraceptives was 1.6 (95% Cl: 0.7-3.4), while the corresponding OR for 'idiopathic' diseases was 2.1 (95% Cl: 0.8-5.2). These risks are considerably smaller than those observed in previous studies. The observed risk may be low because the dosage of oestrogen in modern oral contraceptive preparations has been reduced, but it may also be because the cases of fatal venous thromboembolism included in this study represent only a small proportion of all cases of venous thrombeombolism; a disease which is rarely fatal in young women. These results cannot necessarily be extrapolated to nonfatal venous thromboembolism.

Adolescent↗
PubMed1996

Validated questionnaire for the identification of previous personal or familial venous thromboembolism.

The recognition of previous episodes of venous thromboembolism is of primary importance for the diagnosis of familial thrombophilia. Since there is no validated method to diagnose past venous thromboembolism for epidemiologic purposes, the authors administered a questionnaire to a group of subjects who had had venous thromboembolism in the past and to a group of normal controls. Both cases and controls were less than age 65 years and were identified by the discharge diagnosis International Classification of Diseases codes of records of the Vicenza general hospital, Italy, from 1975 to 1992. Cases were further validated by critical review of pertinent medical records. For each key question, the sensitivity and specificity were computed; questions were then aggregated into sets of maximal sensitivity and specificity. The best diagnostic efficiency (98.2%) was obtained by a set of questions about past symptoms and anticoagulant treatment; this set showed a very high specificity (99.4%), but a low sensitivity (37.1%). A higher sensitivity (71.3%) was obtained without loss of specificity (98.9%) by retaining as positive those subjects who gave a history of venous thromboembolism and anticoagulant treatment or those who had a history of venous thromboembolism and venous reflux at Doppler ultrasound scanning but had no treatment. The combined use of the questionnaire and Doppler scan is suggested for epidemiologic surveys in population.

Female↗
PubMed2001

Risk of venous thromboembolism in carriers of factor V Leiden with a concomitant inherited thrombophilic defect: a retrospective analysis.

Factor V Leiden is the most common genetic defect associated with venous thromboembolism. Its clinical expression is limited and shows a wide intrafamilial and interfamilial variation, which might be explained by the influence of other genetic risk factors. We retrospectively studied 226 patients with factor V Leiden and documented venous thromboembolism (probands) and 400 first-degree carrier relatives to assess the contribution of concomitant genetic risk factors to the occurrence of venous thromboembolism. The prothrombin G20210A mutation was found in 8.3%, homozygosity of factor V Leiden in 7.2%, and inherited deficiencies of antithrombin, protein C or protein S in 4.7% of symptomatic carriers (probands and relatives), as compared with 6.0, 3.4 and 0.9% of asymptomatic carriers, respectively. The total follow-up time in relatives was 11 049 years. Prevalences of venous thromboembolism were 10.8% in single heterozygous factor V Leiden carrier relatives, 16.0% in double-heterozygotes for factor V Leiden and the prothrombin mutation, 36.8% in homozygotes for factor V Leiden, and 40.0% in double-heterozygotes for factor V Leiden and an inherited deficiency of protein C or protein S. Annual incidences in these groups were 0.39, 0.57, 1.41, and 4.76%, respectively. Multivariate analysis showed a small, non-significant additional effect of the prothrombin mutation on the risk of venous thromboembolism in heterozygotes for factor V Leiden [adjusted hazard ratio, 1.3; 95% confidence interval (CI), 0.5-3.8]. This effect was more pronounced for homozygosity of factor V Leiden (adjusted hazard ratio, 3.9; 95% CI, 1.7-9.0) and inherited protein C or protein S deficiencies (adjusted hazard ratio, 17.5; 95% CI, 3.8-81.2). Our data provide evidence of clustering of the evaluated genetic thrombophilic defects in symptomatic factor V Leiden carriers and support the assumption that the clinical expression of factor V Leiden depends on clustering in a part of carriers.

Adult↗
PubMed1995

Effectiveness of pneumatic leg compression devices for the prevention of thromboembolic disease in orthopaedic trauma patients: a prospective, randomized study of compression alone versus no prophylaxis.

A prospective, randomized clinical trial in 304 orthopaedic trauma patients with hip and pelvic fractures was conducted to investigated the effectiveness of pneumatic sequential leg compression devices (PSLCDs) for the prevention of thromboembolic disease. The control group received no specific form of prophylaxis. Patients were followed by venous Doppler, duplex can, and ventilation perfusion lung scans. The study end-point was documented pulmonary embolism and/or deep vein thrombosis. The incidence of a venous thromboembolic event in the control group was 11% and in the experimental group 4%. This difference was statistically significant (p = 0.02). These patients were also stratified into hip and pelvic fracture groups. In the hip fracture patients, the control group had a thromboembolic event incidence of 12% and the experimental group 4%. This difference was also statistically significant (p = 0.03). In the pelvic fracture group there was a thromboembolic incidence of 11% in the controls, demonstrating this patient population to be at significant risk. In this group, the PSLCDs were not statistically shown to be effective. Pneumatic leg compression devices are effective in reducing the incidence of thromboembolic events in patients with hip fractures.

Adult↗
PubMed1996

Effect of critical injury on plasma antithrombin activity: low antithrombin levels are associated with thromboembolic complications.

OBJECTIVE: Determine whether severe injury results in decreased plasma antithrombin (AT) activity and whether this decreased AT activity is associated with thromboembolic complications. DESIGN: Prospective observational. SUBJECTS: A total of 157 critically injured trauma patients. METHODS: Each patient underwent laboratory analysis on arrival to the emergency room at hours 8, 16, 24, and 48, and days 3, 4, 5, and 6. Laboratory analyses included AT, tissue factor pathway inhibitor, protein C, prothrombin fragment 1.2, thrombin-antithrombin complex, and D-dimer. Patients were followed for thromboembolic complications including: deep venous thrombosis (DVT), pulmonary embolus, disseminated intravascular coagulation (DIC) and adult respiratory distress syndrome (ARDS). RESULTS: Mean Injury Severity Score was 23 (+/-11). AT activity fell below normal in 95 (61%) patients; AT activity rose to greater than normal in 51 (32%) patients. Nine (6%) patients developed DVT, two (1%) pulmonary embolus, 13 (8%) DIC and 26 (17%) ARDS. Using logistic regression analysis, low AT levels were a significant predictor of DVT, DIC, and ARDS (p < 0.05). Supranormal At levels were associated with closed head injury (p < 0.05). D-dimer levels were inversely correlated with AT (p < 0.05). CONCLUSIONS: AT activity was depressed in critically injured patients. Patients with head injury developed supranormal AT activity. The risk factors for AT deficiency mimicked those for thromboembolism. Patients with decreased AT activity were at increased risk for thromboembolic complications. Given heparin's dependence on AT, these data call into question the use of unmonitored heparin thromboembolism prophylaxis.

Adult↗
PubMed1987

Thromboembolic complications in renal allograft recipients. A report from the prospective randomized study of cyclosporine versus azathioprine-antilymphocyte globulin.

The incidence of arterial and venous thromboembolic complications was compared in 224 renal allograft recipients who were prospectively randomized and stratified by risk to treatment with either cyclosporine-prednisone (CsA-P) (n = 117) or azathioprine-prednisone-antilymphocyte globulin (AZA-P-ALG) (n = 107). Thirteen CsA patients (11%) had 22 thromboembolic events, while 19 AZA patients (18%) had 24 events (P = 0.22). There was no significant difference between the 2 regimens in the number of patients with each type of venous or arterial event or in the number of patients with multiple or lethal events. The incidence of "minor" complications (all except myocardial infarction and stroke) in the related donor subgroup (n = 85) and the overall incidence of thromboembolism in the diabetic subgroup (n = 125) were both significantly higher in AZA-treated patients (P = 0.008 and 0.045, respectively). Thus, CsA immunosuppression does not appear to be a risk factor for thromboembolic disease, and it may in fact lower the incidence of thromboembolism in diabetic renal allograft recipients.

Adolescent↗
PubMed2000

D-dimer for the diagnosis of venous thromboembolism.

D-dimer, a breakdown product of cross-linked fibrin has been extensively evaluated as a diagnostic test for acute venous thromboembolism. Rapid, highly sensitive D-dimer assays are now available that are suitable for testing in the emergency setting. Preliminary studies suggest that when using a highly sensitive D-dimer assay, a negative test result may,be sufficient to exclude the diagnosis of venous thromboembolism without need for further testing. Less sensitive, but more specific D-dimer assays are also available. The negative predictive value of these latter assays is insufficient to exclude venous thromboembolism on the basis of a negative test result alone. However, their utility is increased by identifying patient populations at low risk for venous thromboembolism using consideration of clinical probability or radiographic testing. Further, large multicenter management studies are required to confirm the safety of relying on a negative D-dimer result to exclude the diagnosis of venous thromboembolism.

Antifibrinolytic Agents↗