Evaluation of a new rapid D-dimer assay for clinically suspected deep venous thrombosis (Liatest D-dimer).

Plasma D-Dimer analysis, using ELISA assays, has demonstrated in previous studies a high sensitivity, suggesting its utility in excluding deep venous thrombosis (DVT). To assess the performance of a new rapid plasma D-Dimer ELISA measurement in suspected DVT patients with recent clinical signs, not exceeding one week. A prospective study of patients admitted for a suspected recent DVT. Contrast venography or compression ultrasonography were performed within 24 h of admission. A new membrane based ELISA technique, which uses an immunofiltration and two complementary monoclonal antibodies was tested. Results were expressed as positive or negative. A standard plasma D-Dimer ELISA measurement was also performed. D-Dimer performances were assessed at the end of the study. 265/448 patients had a proven DVT (72 distal, 193 proximal). The sensitivity of the instantaneous method in the diagnosis of overall DVT is 92 +/- 3.4% (95% CI), and specificity is 36.6 +/- 6.9%. Positive predictive value is 67.7 +/- 4.8% and negative predictive value is 76.1 +/- 8.9%. Sensitivity and negative predictive values reach 97.9 and 94.3% in the diagnosis of proximal DVT, but only 76.3 and 79.7% in the diagnosis of distal DVT. Similar results are observed with the standard ELISA method. This new rapid plasma D-Dimer measurement appears highly sensitive, and could substitute the older ELISA methods. Both methods provide lower sensitivity in the case of a distal DVT location.

To review noninvasive methods for diagnosis of first and recurrent deep venous thrombosis and provide evidence-based recommendations for the diagnosis of deep venous thrombosis in symptomatic, asymptomatic, and pregnant patients. Accuracy (comparison with contrast venography) and management (safety of withholding anticoagulants when results were normal) studies that evaluated tests for diagnosis of deep venous thrombosis were identified from a MEDLINE search, personal files, and bibliographies of reviews and original studies. Prospective cohort studies (accuracy and management studies) and randomized comparisons (management studies) that satisfied predefined methodologic criteria were included. Sensitivity, specificity, and positive and negative predictive values were determined for accuracy studies. Rates of venous thromboembolism during long-term follow-up of patients with normal results were determined for management studies. Data from individual studies were combined under a random-effects model. The accuracy of noninvasive tests was compared, with emphasis on within-study comparisons. Recommendations for diagnosis of deep venous thrombosis were developed by a multidisciplinary group and graded according to the strength of the supporting evidence. Venous ultrasonography is the most accurate noninvasive test for the diagnosis of a first symptomatic proximal deep venous thrombosis. However, neither ultrasonography nor impedance plethysmography is accurate in asymptomatic postoperative patients. Venous ultrasonography is less accurate for symptomatic isolated distal (calf) deep venous thrombosis than for proximal deep venous thrombosis, and the clinical utility of venous ultrasonography of the distal veins is uncertain. Withholding anticoagulant therapy in symptomatic patients with suspected deep venous thrombosis who have normal results on serial venous ultrasonography or impedance plethysmography is safe. Diagnosis of recurrent deep venous thrombosis requires evidence of new thrombus formation, such as a new noncompressible venous segment detected by venous ultrasonography, conversion of a normal result on impedance plethysmography to abnormal, or presence of an intraluminal filling defect on venography. Suspected deep venous thrombosis in pregnant patients can usually be managed with serial venous ultrasonography or impedance plethysmography. In symptomatic patients with a suspected first episode of deep venous thrombosis, clinical assessment and D-dimer testing are complementary to testing with venous ultrasonography and impedance plethysmography. Patients with suspected deep venous thrombosis can usually be managed with noninvasive testing. However, if the results of this testing are nondiagnostic or are discordant with the clinical assessment, venography should be considered.

Objectives. M any studies have demonstrated a significant association between cardiovascular disease and neutrophil to lymphocyte ratio (NLR). To our knowledge, no study has been reported in patients with deep venous thrombosis (DVT) which affecting proximal or distal leg. In this study we analyzed proximal and distal DVT according to the NLR. Methods. This retrospective study was obtained from patients’ records of a tertiary university hospital between May 2011 to January 2014. A total of 57 patients with the diagnosis of acute primary DVT and 30 patients as control group included in the study. All of them were confirmed with lower extremity venous duplex examinations. Of these, 37 examinations with the diagnosis of proximal DVT were compared to 20 examinations with distal DVT. The groups compared regarding to complete blood counter values. Results. Mean eosinophil level was higher in the distal DVT group (0.28±0.24 vs. 0.12±0.01, p =0.001), whereas median NLR were higher in the proximal DVT group than the distal DVT group (3.5 [0.5-4.3] vs. 2.3 [1.2-9.7], respectively; p =0.002). In addition, median NLR, leukocyte and neutrophil counts were statistically lower in the control group than the others ( p =0.014, p =0.027 and p =0.004, respectively). Conclusion. NLR, an inexpensive and easily measurable laboratory variable, was independently and significantly associated with the presence and severity of DVT, especially acute proximal DVT.

Combination of a clinical risk assessment score and rapid whole blood D-dimer testing in the diagnosis of deep vein thrombosis in symptomatic patients

Objective To investigate the regularity in and risk factors for perioperative deep venous thrombosis (DVT) and the changes in plasma D-dimer in patients with tibiofibular fracture. Methods A retrospective analysis was done of the 180 patients with tibiofibular fracture who had been treated at Department of Orthopaedics and Trauma, Xi'an Honghui Hospital from September 2014 to February 2018. They were 114 males and 66 females, aged from 16 to 83 years (average, 47.6 years). The levels of plasma D-dimer were detected at admission, one day preoperation, and 1, 3, 5 days postoperation. B-ultrasound examination of both lower extremities was performed before and after surgery. According to the results of B-ultrasound, the patients were divided into a DVT group and a non-DVT group. The 2 groups were compared in the plasma D-dimer levels measured at different time points. DVT risk factors were screened by univariate analysis, and multivariate logistic regression analysis was used to determine independent risk factors. Results Of this cohort, 54 cases (30%) developed DVT and 39 cases (21.7%) did preoperation. Of the 39 cases (mixed DVT in one and distal DVT in 38 ones), DVT disappeared in 14 postoperation. Of the 40 cases (22.2%) of postoperative DVT (proximal DVT in one, mixed DVT in one and distal DVT in 38 ones), 15 developed newly postoperation. Multivariate logistic regression analysis showed that age, time from injury to operation, pre-operative and postoperative D-dimer elevation were independent risk factors for DVT in the patients. The D-dimer levels in the DVT group were significantly higher than in the non-DVT group at one day preoperation, and 1, 3, 5 days postoperation (P<0.05). The area under the receiver operating characteristic curve was 0.704. When the critical value of D-dimer was 1.4 mg/L, its sensitivity for DVT diagnosis was 0.944 and its specificity 0.246 (poor). When the concentration of D-dimer was 4.45 mg/L, its sensitivity for DVT diagnosis was 0.574 and its specificity 0.817 (the highest). Conclusions Perioperative DVT may happen in patients with tibiofibular fracture, mostly at the distal end beyond the popliteal vein. Clinically, patients who are advanced in age, have plasma D-dimer elevation at admission and after operation, and have waited long for operation should be alert to the occurrence of DVT. The plasma D-dimer level with a recommended threshold of 4.45 mg/L may have a certain diagnostic value for patients with tibiofibular fracture. Key words: Tibia; Fibula; Fractures, bone; Deep vein thrombosis; Risk factors; D-dimer

The requirement for a safe diagnostic strategy should be based on an overall post-test incidence of venous thromboembolism (VTE) of less than 1% during 3 month follow-up. Compression ultrasonography (CUS) has a negative predictive value (NPV) of 97 to 98% indicating a post-CUS incidence of deep vein thrombosis (DVT) of 2 to 3%. A post-CUS DVT incidence of 3% implicates that 90 to 120 DVTs per 1 million inhabitants will be overlooked each year indicating the need to improve the diagnostic work-up of DVT as much as possible. The qualitative D-dimer test (SimpliRed) has a sensitivity of 82 to 89% and a negative predictive value of 94 to 95% indicating a 5 to 6% post-test incidence of DVT, which is not sensitive enough for venous thrombosis exclusion. The post-test DVT incidence could be reduced from 3.2% to 0.6% in one study and from 11% to 2% in another study by the combination of a normal CUS and low clinical score and from 4,5% to 1.6% by the combination of low clinical score and a negative SimpliRed test in one study. The combination of a negative CUS and a negative SimpliRed test reduced the post-test incidence of DVT from 2.6% to < 1% or even < 1%o in two management studies without the need of a repeated CUS on the basis of which anticoagulant therapy can safely be withheld. The rapid quantitative turbidimetric D-dimer assay (Tinaquant) has a sensitivity and a negative predictive value (NPV) of 97.7% with a 2.3% post-test incidence of DVT. The combination of a normal Tinaquant D-Dimer test result plus a low to moderate clinical score reduces the post-test incidence of DVT from 2.3 to 0,6% without the need of CUS testing in 29% of patients with suspected DVT. The rapid ELISA VIDAS D-dimer assay has a sensitivity and NPV of 98,6 and 99.5% in two management studies for the exclusion of DVT irrespective of clinical score. The combination of a normal ELISA VIDAS D-Dimer test with clinical score assessment will reduce the post-test DVT incidence of less than 0.5% and the need for CUS testing by 40 to 50%. It is concluded that the sequential use of a rapid quantitative D-dimer test, clinical score and CUS appears to be safe and the most cost-effective diagnostic work-up of DVT.

Practicability and quality of outpatient management of acute deep venous thrombosis

Evidence for Safe Exclusion of Deep Vein Thrombosis (DVT) by a Rapid ELISA D-Dimeer Test at Cut-Off Levels of 500 and 1000 Ng/Ml in 1046 Consecutive Outpatients with Suspected DVT.

Association between inflammation biomarkers, anatomic extent of deep venous thrombosis, and venous symptoms after deep venous thrombosis.

Duplex and color Doppler sonography (DUS) is currently the technique of choice for the diagnosis of deep venous thrombosis (DVT) in symptomatic patients, because it has proven safe and cost-effective, with a very high sensitivity and specificity (96% and 98%, respectively) for the diagnosis of proximal DVT. Several issues regarding its method and clinical indications remain controversial, however. Although isolated calf vein thrombosis does not seem to have a significant adverse outcome in the short term, scanning the calf only in patients with localized symptoms or signs is cost-effective. Bilateral examination is indicated in high-risk patients or when screening asymptomatic patients. When negative, a complete DUS examination of the proximal and distal veins, at least down to the level of the popliteal trifurcation, allows withholding anticoagulant therapy without the risk of major complications. This examination may be repeated if signs or symptoms worsen. Some populations of asymptomatic patients at high risk of DVT may benefit from DUS screening. Bilateral DUS examination of lower limb veins should be performed as the initial examination in the workflow of pulmonary embolism only in patients with risk factors for DVT. Recurrent thrombosis is a challenging diagnosis for all imaging modalities. A diagnostic strategy combining clinical probability score and D-dimer test may refine the selection of patients. The pitfalls and limitations of venous DUS are related to vein anatomy, flow changes, technical issues, and operator expertise.

The diagnosis of deep vein thrombosis (DVT) in outpatients is difficult to establish. The classical clinical signs of DVT are unspecific and found in several other conditions besides DVT. Therefore, these patients are subjected to elaborate, expensive invasive or noninvasive procedures that actually confirm DVT in only 20-30% of patients in this setting. A prospective management decision study, based on a pretest clinical probability (PCP) estimation, compression ultrasonography (CUS), and a rapid enzyme-linked immunoadsorbent assay (ELISA) D-dimer test, is proposed. The PCP model of Wells allows for reasonably accurate classification of patients into low, moderate and high probability for suffering DVT. Combined with CUS, high predictability is achieved. The D-dimer assays presently available can be rapidly performed and are accurate to a high degree, especially in ruling out DVT. It is proposed to establish a "Rational Diagnosis of Deep Vein Thrombosis (RADIA DVT)" model to be tested in a large number of patients with suspected DVT. This model would be less expensive to perform and likely yield a highly accurate diagnosis on the basis of which anticoagulant therapy could be initiated or withheld.

Although venous thromboembolism has occasionally been reported after hospital discharge in patients who have undergone total hip replacement (THR), this risk has not been fully quantified and the usefulness of a prophylactic treatment has not been evaluated. We conducted a single-centre prospective randomised double-blind clinical trial in 2 parallel groups of patients who had undergone THR and were free of deep venous thrombosis (DVT) at discharge, as assessed by bilateral ascending venography. During hospitalisation, all patients received a low molecular weight heparin, enoxaparin (enoxaparin sodium), as a prophylactic treatment for venous thromboembolism. Just before hospital discharge (15 +/- 1 days from surgery) 179 consecutive patients were randomly assigned to receive subcutaneous enoxaparin 40mg (n = 90) or placebo (n = 89) once daily for 21 +/- 2 days. The primary efficacy outcome was defined as the occurrence of DVT and/or documented pulmonary embolism (PE). DVT was assessed by ascending bilateral venography performed 21 +/- 2 days after randomisation or earlier if necessary. Secondary efficacy outcomes were the occurrence of proximal and distal DVT. Safety outcomes were defined as the occurrence of major and minor haemorrhage, other adverse events and changes in laboratory parameters. All patients underwent a 3-month follow-up. There were no deaths or cases of clinical PE during the study and the follow-up periods. In 173 patients with evaluable venograms, analysis of efficacy on an intention-to-treat basis showed that the incidence of DVT at day 21 was significantly lower in the enoxaparin group (6 of 85; 7.1%) than in the placebo group (17 of 88; 19.3%; p = 0.018), a risk reduction of 63%. Distal DVT was less frequent in the enoxaparin group than in the placebo group (1.2 vs 11.4%; p = 0.006) but there was no significant difference between groups in the incidence of proximal DVT. A 'per-protocol' analysis of efficacy in 155 patients confirmed the results for total and distal DVT, but also showed a trend in efficacy in favour of enoxaparin with regard to the incidence of proximal DVT (p = 0.064). Enoxaparin was safe in comparison with placebo: only 2 minor bleedings occurred in the enoxaparin group and there was no difference in the incidence of other adverse events between the 2 groups. In patients undergoing THR, the risk of late-occurring DVT remained high during the 21 days after hospital discharge in the placebo group. Prophylactic treatment with enoxaparin reduced the risk and was well tolerated in this context.

Influence of Preceding Length of Anticoagulant Treatment and Initial Presentation of Venous Thromboembolism on Risk of Recurrence After Stopping Treatment: Analysis of Individual Participants' Data From Seven Trials

The objective was to investigate the delay between the onset of DVT symptoms and start of anticoagulation in common practice, assess whether this has any impact on the recanalization of venous thrombosis over one year follow up. A prospective observational study on 76 consecutive patients (39 men, 51.3%) with DVT diagnosed using compression ultrasound (CUS). Timing was classified as very early treatment ≤72 hours, early treatment ˂7 days and late treatment ≥7 days from onset of symptoms. Further development of the disease was monitored by CUS in scheduled visits 1, 3, 6 and 12 months after the start of treatment. Mean delay from symptom onset to the start of anticoagulation was 11.1 days (median 7 days, range 1-42 days) with significant difference (p˂0.05) between proximal (12.9 days, median 30 days) and distal DVT (6.5 days, median 2 days). In less than 25% of all patients, with both proximal and distal DVT, treatment was started very early (≤72 hours), 40 patients (52.6%) received late treatment ≥7 days. There was a positive correlation between delay, average time of complete recanalization (≤72 hours 4.2 months, ≥7 days 5.3 months, p˂0.05) and rate of incomplete recanalization (≤72 hours 7.3%, ≥7 days 30.9%, p˂0.01) in proximal DVT, not in distal DVT. There was a delay of ≥7 days in treating in more than half of our patients. The mean interval between clinical onset and start of treatment was significantly shorter and a delay ≥7 days significantly less frequent in patients with distal DVT compared to patients with proximal DVT. A very significant positive correlation between delay in treatment and rate of incomplete recanalization of proximal and distal thrombosis indicates that delayed anticoagulation could be a signal risk factor for the incomplete recanalization and development of PTS.

Deep Venous Thrombosis and Pulmonary Embolism