Seminars in vascular medicine最新文献

D-dimers (DD) have shown sufficient proof of their efficiency in the last 10 years to play an important role in hemostasis laboratories for excluding thromboembolic events. Numerous reagents are available on the market but their performances differ. This overview takes stock of the methods used to evaluate the performances of DD assays, the results published in the literature, the technical parameters influencing assay performance, the difficulties caused by the lack of harmonization of DD units, and the attempts to tackle this problem. It raises the issue of the potential optimization of their use with regard to better adaptation to multidisciplinary diagnostic strategies and to target patient populations.

Venous thromboembolism (VTE) requires prolonged treatment to prevent late recurrences. However, the optimal duration of vitamin K antagonist (VKA) therapy is still controversial. More recently, D-dimer (D-d) has emerged as a predictive factor for recurrences. D-d has been evaluated both during and after VKA treatment. Some patients with DVT of the lower limbs have persistently high D-d during anticoagulation and this could reflect insufficient anticoagulation despite apparently adequate antithrombotic treatment. Altered D-d during anticoagulation is more frequent in patients with idiopathic or cancer-associated VTE than in those with secondary VTE. In subjects with an unprovoked VTE event, the time spent at near normal international normalization ratio (INR) values (< 1.5) during the first 3 months of treatment is associated with higher D-d during and after VKA treatment and with a higher risk for late recurrences. Moreover, the combination of altered D-d and inherited thrombophilia, and not residual venous obstruction, is associated with a significantly higher hazard ratio for recurrence. Preliminary results of a management study, the PROLONG study, indicate that subjects with normal D-d at 1 month after VKA withdrawal have a low risk of recurrence, and those with altered D-d have a significantly higher risk and deserve prolonged treatment.

The negative predictive value of D-dimers in the diagnosis of a recent venous thromboembolism (VTE) episode is well established. The plasma level of D-dimer is usually increased in hypercoagulable states. The measurement of D-dimer could be of clinical interest in patients with constitutional thrombophilia as there is no close relationship between the clinical expression and the genotype indicating the existence of a hypercoagulable state. Moreover, the predictive value of D-dimer testing in patients with thrombophilia has been questioned. The review of the literature and results of a recent study of our group are presented. Decreased levels of D-dimer are observed in patients receiving an oral anticoagulant treatment versus untreated patients. In contrast, no significant difference was observed between those with and those without thrombophilia among treated or untreated patients. Patients with constitutional thrombophilia are supposed to have an increased risk of postoperative VTE. The review of the existing literature could not confirm this opinion but this could be due to the fact that most patients receive a prophylactic treatment. Thus, there is an indirect evidence of its efficacy in these patients.

Normal pregnancy is associated with alterations of the hemostatic system toward a hypercoagulable state. Elevated markers of coagulation and fibrinolytic system activation, such as D-dimer, indicate increased thrombin activity and increased fibrinolysis following fibrin formation throughout pregnancy. Testing for D-dimer in pregnant women could be useful for the diagnosis and prediction of a venous thromboembolic event or pregnancy-related complications and for monitoring antithrombotic treatment. This approach, however, is hampered by the fact that even an uncomplicated pregnancy in healthy women is accompanied by a substantial increase of D-dimer. Thus, prior to clinical application reference values of D-dimer according to gestational age need to be validated. A substantial increase of D-dimer during pregnancy is seen despite thromboprophylaxis with low-molecular-weight heparin (LMWH), indicating that further studies are needed to evaluate monitoring of LMWH during pregnancy and to investigate the optimal beginning and dose of LMWH thromboprophylaxis in pregnant women.

Fibrin D-dimer, the most commonly used clinical assay for detection of coagulation activation and in vivo fibrin formation and lysis in circulating blood, has been associated with risks of cardiovascular diseases in studies published over the past 15 years. This review discusses, in turn, analytic and preanalytic considerations; associations with risk factors; and associations with coronary heart disease, atrial fibrillation, stroke and cerebrovascular disease, peripheral arterial disease, and venous thromboembolism. These associations suggest that activated coagulation and in vivo fibrin formation and lysis may play a role in arterial, intracardiac, and venous thromboembolism. The potential clinical utility of D-dimer in prediction of cardiovascular risk, in indicating patient groups for prophylactic anticoagulation and in monitoring of anticoagulation, requires further study. Harmonization of results from different assays would increase clinical utility.

Recent advances in the management of patients with suspected venous thromboembolism have both improved diagnostic accuracy as well as made management algorithms safer and more accessible. It is now clear that determination of clinical probability prior to diagnostic testing will improve patient management. D-dimer testing can be employed to decrease the need for imaging tests. Patients at low risk with a negative qualitative D-dimer can avoid imaging tests. Imaging test interpretation benefits from consideration of pretest probability also as this helps clinicians determine when a test may be falsely negative or falsely positive. Diagnostic strategies should include pretest clinical probability, D-dimer assays, and noninvasive imaging tests.

The requirement for a safe diagnostic strategy should be based on an overall posttest incidence of venous thromboembolism (VTE) of less than 1% during 3-month follow-up. The negative predictive value (NPV) during 3 months of follow-up is 98.1 to 99% after a normal venogram, 97 to 98% after a normal compression ultrasonography (CUS), and > 99% after serial CUS testing. Serial CUS testing is safe but 100 CUS must be repeated to find one or two CUS positive for deep vein thrombosis (DVT), which is not cost-effective and indicates the need to improve the diagnostic workup of DVT by the use of clinical score assessment and D-dimer testing. The NPV varies from 97.6 to 99.4% for low clinical score followed by a negative SimpiRED test, indicating the need for a first CUS. The NPV is 98.4 to 99.3% for a normal rapid enzyme-linked immunosorbent assay (ELISA) VIDAS D-dimer test result (< 500 ng/mL) irrespective of clinical score. The NPV is more than 99% for a negative CUS followed by either a negative SimpiRED test or an ELISA VIDAS test result of < 1000 ng/mL without the need to repeat a second CUS within 1 week. The sequential use of a sensitive, rapid ELISA D-dimer and clinical score assessment will safely reduce the need for CUS testing by 40 to 60%. Large prospective outcome studies demonstrate that with one negative examination with complete duplex color ultrasonography (CCUS) of the proximal and distal veins of the affected leg with suspected DVT, it is safe to withhold anticoagulant treatment, with a negative predictive value of 99.5%. This may indicates that CCUS is equal to serial CUS or the combined use of clinical score, D-dimer testing, and CUS. Pulmonary angiography is the gold standard for segmental pulmonary embolism (PE) but not for subsegmental PE. A normal perfusion lung scan and a normal rapid ELISA VIDAS D-dimer test safely excludes PE. Helical spiral computed tomography (CT) detects all clinically relevant PE and a large number of alternative diagnoses in symptomatic patients with suspected PE and can replace both the ventilation perfusion scan and pulmonary angiography to safely rule in PE and to rule out PE with an NPV of > 99%. The combination of clinical assessment, a rapid ELISA VIDAS D-dimer, followed by CUS will reduce the need for helical spiral CT by 40 to 50%.