D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).

Relationship between type of unprovoked venous thromboembolism and cancer location: An individual patient data meta-analysis.

BACKGROUND: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an underlying cancer. We aimed to assess the period prevalence of occult cancer detection stratified by VTE location (deep vein thrombosis [DVT], pulmonary embolism [PE] or both) and the anatomical relationship between occult cancer and VTE. METHODS: Post-hoc analysis of a systematic review and individual patient data meta-analysis of adults with unprovoked VTE with at least 12 months of follow-up. Cancer types were grouped according to thoracic, abdomino-pelvic, or other locations. RESULTS: A total of 2300 patients were eligible including 1218 with DVT only (53%), 719 with PE only (31%), and 363 with both PE and DVT (16%). The pooled 12-month period prevalence of cancer in DVT only, PE only, and DVT + PE was 5.6% (95% CI, 4.4 to 7.2), 4.3% (95% CI, 2.7 to 6.9), and 5.6% (95% CI, 1.7 to 15.5), respectively. Most occult cancers were located in the abdomen (68.4%). The proportion of patients with an abdomino-pelvic cancer was not different in patients with DVT + PE (81%; 95% CI, 54 to 96) than in those with DVT (68%; 95% CI, 57 to 78) or PE alone (65%; 95% CI, 48 to 79). CONCLUSION: The 12-month prevalence of occult cancer was similar in patients with DVT only, PE only, or both. Most cancers were located in the abdomen, and there was no relationship between VTE type and cancer location.

Treatment algorithm in cancer-associated thrombosis: Canadian expert consensus.

Management of anticoagulant therapy for the treatment of venous thromboembolism (vte) in cancer patients is complex because of an increased risk of recurrent vte and major bleeding complications in those patients relative to the general population. Subgroups of patients with cancer also show variation in their risk for recurrent vte and adverse bleeding events. Accordingly, a committee of 10 Canadian clinical experts developed the consensus risk- stratification treatment algorithm presented here to provide guidance on tailoring anticoagulant treatment choices for the acute and extended treatment of symptomatic and incidental vte, to prevent recurrent vte, and to minimize the bleeding risk in patients with cancer. During a 1-day live meeting, a systematic review of the literature was performed, and a draft treatment algorithm was developed. The treatment algorithm was refined through the use of a Web-based platform and a series of online teleconferences. Clinicians using this treatment algorithm should consider the bleeding risk, the type of cancer, and the potential for drug-drug interactions in addition to informed patient preference in determining the most appropriate treatment for patients with cancer-associated thrombosis. Anticoagulant therapy should be regularly reassessed as the patient's cancer status and management change over time.

Predicting the risk of cancer after unprovoked venous thromboembolism: external validation of the RIETE score.

Essentials Patients at high-risk of occult cancer may benefit from extensive screening. We validated the RIETE cancer score in the MVTEP study. One in three patients were classified as high-risk, 10% of whom had cancer diagnosed. The RIETE score identifies a subgroup at high risk for cancer. SUMMARY: Background Most recent trials evaluating extensive screening strategies for occult cancer in patients with unprovoked venous thromboembolism have failed, because, among other reasons, of an overall low rate of occult cancer. The RIETE investigators recently proposed a score aimed at identifying a subgroup at higher risk. Methods We retrospectively computed the RIETE score for all patients included in the MVTEP study, which evaluated the accuracy of [¹8F]fluorodeoxyglucose-positron emission tomography in the screening of occult cancer in patients with unprovoked venous thromboembolism. Performance of the RIETE score was assessed according to the proportion of patients classified in each risk group, and the corresponding rates of cancer diagnosis. Results Among the 386 patients included in the analysis, 136 patients (35.3%) were classified as high risk by the RIETE score. Cancer was diagnosed in 16 (11.8%) of them, whereas it was diagnosed in nine (3.6%) of the 250 patients with a low RIETE cancer score: odds ratio of 3.6 (95% confidence interval [CI] 1.53-8.32). The area under the receiver operating characteristic curve was 0.63 (95% CI 0.51-0.74). Conclusion The RIETE score seems to be able to identify a subgroup at high risk for cancer (10%) in our specific dataset of patients with unprovoked venous thromboembolism.

Association between remote major venous thromboembolism risk factors and the risk of recurrence after a first unprovoked episode.

Essentials Is remote exposure to major venous thromboembolism (VTE) risk factor related to lower recurrence? We analyzed data from the REVERSE study, a cohort of patients with no recent major risk factor. We found no association between remote risk factors and the risk of recurrence. Patients with remote VTE risk factor should be managed as having had an unprovoked VTE. SUMMARY: Background It has been shown that the risk of recurrence of venous thromboembolism (VTE) is significantly lower when provoked by a major risk factor such as surgery or trauma compared with an event that was unprovoked. Objectives In this study we aimed to assess the association between remote exposure (3-12 months prior to VTE) to major VTE risk factors and the risk of recurrent VTE. Methods This was a post-hoc analysis of the REVERSE study, a prospective cohort of 646 patients with a first VTE, not provoked by a recent (< 3 months) major risk factor. Results We found no difference in the recurrence rate in patients with or without remote exposure to major VTE risk factors, including immobilization (hazard-ratio [HR], 1.4; 95% confidence interval, 0.7-2.6), surgery (HR, 0.8; 0.3-1.9) and trauma (HR, 1.3; 0.5-3.6). Conclusion None of the tested risk factors were associated with a lower risk of recurrence during follow-up. Patients with remote exposure to major risk factors at the time of a first VTE should not be managed differently from patients with no VTE risk factors.

Thrombotic and bleeding outcomes following perioperative interruption of direct oral anticoagulants in patients with venous thromboembolic disease.

Essentials Studies evaluating the procedural interruption of direct oral anticoagulants (DOACs) are lacking. We conducted a study of the interruption of DOACs for prior venous thromboembolic disease (VTE). The post-operative risks of recurrent VTE and major bleeding are low in this patient population. A scheme based on half-life and procedure-related bleeding appears safe and efficacious. SUMMARY: Background Direct oral anticoagulants (DOACs) are increasingly being used in the setting of venous thromboembolic disease (VTE). There is little evidence to guide the peri-procedural interruption of DOACs in this patient population. A number of studies have evaluated the perioperative interruption of DOACs based on half-life of the anticoagulant and the underlying procedural bleeding risk in patient with atrial fibrillation, but it remains unclear whether these findings can be extended to patients with VTE. Objective Evaluate thrombotic and bleeding outcomes following the perioperative interruption of direct oral anticoagulation in patients with prior VTE. Methods We conducted a retrospective analysis of consecutive patients on a DOAC for prior VTE requiring temporary interruption of anticoagulation for an invasive procedure. The primary efficacy outcome was the 30-day symptomatic VTE rate, and the primary safety outcome was the 30-day major bleeding rate. Secondary outcomes included overall mortality and the rate of clinically relevant non-major bleeding. Results A total of 190 patients were included in the analysis. The 30-day VTE rate was 1.05% (95% CI, 0.29-3.8%) and the 30-day major bleeding rate was 0.53% (95% CI, 0.09-2.93%). There were no deaths during the 30-day follow-up period. The rate of clinically relevant non-major bleeding was 3.16% (95%CI , 1.46-6.72%). Conclusions The perioperative interruption of DOACs in the setting of VTE, using a strategy that considers the half-life of the DOAC and the underlying procedural bleeding risk, appears to be both safe and effective.

Performance of the age-adjusted cut-off for D-dimer in patients with cancer and suspected pulmonary embolism.

BACKGROUND: Cancer patients frequently present with suspected pulmonary embolism (PE). The D-dimer (DD) test is less useful in excluding PE in cancer patients due to the lower specificity. In the general population, the age-adjusted cutoff for DD combined with a clinical decision rule (CDR) improved specificity in the diagnosis of PE. OBJECTIVES: To evaluate the safety and efficacy of the age-adjusted cutoff (defined as age∗10µg/L in patients >50years) combined with a CDR for the exclusion of PE in cancer patients. METHODS: We conducted a prospective study to evaluate the age-adjusted cutoff in patients with suspected PE. Here we report a post-hoc analysis on the performance of the age-adjusted cutoff in patients with and without cancer. The primary outcome was the rate of venous thromboembolic events (VTE) during three-month follow-up. RESULTS: Of 3324 patients with suspected PE, 429 (12.9%) patients had cancer. The prevalence of PE was 25.2% in cancer patients and 18% in patients without cancer (p<0.001). Among cancer patients with an unlikely CDR, 9.9% had a DD <500µg/L as compared with 19.7% using the age-adjusted cutoff. In patients without cancer, these rates were 30.1% and 41.9%. The proportion of cancer patients in whom PE could be excluded by CDR and DD doubled from 6.3% to 12.6%. No VTE occurred during three-month follow-up (failure rate 0.0% (95% CI 0.0-6.9%)). CONCLUSION: Compared with the conventional cutoff, the age-adjusted D-dimer cutoff doubles the proportion of patients with cancer in whom PE can be safely excluded by CDR and DD without imaging.

Evaluation of quantitative PCR for early diagnosis of Pseudomonas aeruginosa infection in cystic fibrosis: a prospective cohort study.

OBJECTIVES: Early detection of Pseudomonas aeruginosa lung positivity is a key element in cystic fibrosis (CF) management. PCR has increased the accuracy of detection of many microorganisms. Clinical relevance of P. aeruginosa quantitative PCR (qPCR) in this context is unclear. Our aim was to determine P. aeruginosa qPCR sensitivity and specificity, and to assess the possible time saved by qPCR in comparison with standard practice (culture). METHODS: A multicentre cohort study was conducted over a 3-year period in 96 patients with CF without chronic P. aeruginosa colonization. Sputum samples were collected at each visit. Conventional culture and two-step qPCR (oprL qPCR and gyrB/ecfX qPCR) were performed for 707 samples. The positivity criteria were based on the qPCR results, defined in a previous study as follow: oprL qPCR positivity alone if bacterial density was <730 CFU/mL or oprL qPCR combined with gyrB/ecfX qPCR if bacterial density was ≥730 CFU/mL. RESULTS: During follow up, 36 of the 96 patients with CF were diagnosed on culture as colonized with P. aeruginosa. This two-step qPCR displayed a sensitivity of 94.3% (95% CI 79.7%-98.6%), and a specificity of 86.3% (95% CI 83.4%-88.7%). It enabled P. aeruginosa acquisition to be diagnosed earlier in 20 patients, providing a median detection time gain of 8 months (interquartile range 3.7-17.6) for them. CONCLUSIONS: Implementing oprL and gyrB/ecfX qPCR in the management of patients with CF allowed earlier detection of first P. aeruginosa lung positivity than culture alone.

PO-29 - Age-adjusted D-dimer cutoff level increases the number of cancer patients in who pulmonary embolism can be safely excluded without CT-PA imaging: The ADJUST-PE cancer substudy.

INTRODUCTION: Patients with cancer frequently present with suspected pulmonary embolism (PE). The D-dimer test is less useful to rule out PE in cancer patients due to a lower specificity, whereas the safety of the combination of a clinical decision rule (CDR) and D-dimer test to rule out PE in these patients is unclear. In the general population, use of an age-adjusted cutoff for D-dimer in combination with a CDR has been shown to improve specificity in the diagnosis of PE. AIM: We prospectively analysed the safety and efficacy of the age-adjusted D-dimer (defined as age×10 in patients >50 years) combined with CDR for the exclusion of PE in patients with cancer. MATERIALS AND METHODS: We conducted a multicenter multinational prospective management outcome study in 19 centers in Belgium, France, The Netherlands and Switzerland, the ADJUST-PE study, to validate an age-adjusted D-dimer cut-off in patients with suspected PE. The performance of the age-adjusted D-dimer cut-off and CDR was compared between patients with and without cancer. The primary outcome was the rate of adjudicated thromboembolic events during three-month follow-up. RESULTS: Of the 3,324 patients with suspected PE, 429 (12.9%) patients had cancer. Cancer patients were older and more often had surgery or immobilisation. The prevalence of PE was 108/429 (25.2%) in cancer patients and 522/2894 (18%) in patients without cancer, p<0.001. Among cancer patients with an unlikely CDR, 27/274 (9.9%) had a D-Dimer <500 µg/L as compared with 19.7% using the age-adjusted D-dimer cut-off; in patients without cancer, these rates were 30.1% and 41.9%, respectively. The percentage of cancer patients in whom PE could be excluded based on CDR and age-adjusted D-dimer doubled from 6.3% to 12.6%. None of these cancer patients had a venous thromboembolic event during three-month follow-up, thus the failure rate was 0.0% (95% CI 0.0-6.9%). CONCLUSIONS: Compared with the usual cut-off, the age-adjusted D-dimer cut-off doubles the proportion of patients with cancer in whom PE can be safely excluded by CDR and D-dimer without need for CTPA imaging.

Prothrombin G20210A mutation and lower extremity peripheral arterial disease: a systematic review and meta-analysis.

OBJECTIVE/BACKGROUND: Despite being an important risk factor for venous thromboembolism, the role of the prothrombin G20210A mutation in patients with arterial disease remains unclear. The aim of this review was to evaluate the association of prothrombin G20210A and lower extremity peripheral arterial disease (PAD). METHODS: This was a systematic review and meta-analysis of case-control studies. A systematic review of electronic databases, including MEDLINE and Embase, was conducted to assess the prevalence of prothrombin G20210A in patients with lower extremity PAD. The main outcome was the prevalence of prothrombin G20210A in patients with lower extremity PAD. The random effects model odds ratio (OR) was used as the primary outcome measure. RESULTS: The initial electronic search identified 168 relevant abstracts of which five studies evaluating 1,524 cases of PAD and 1,553 controls were included. Prothrombin G20210A was found in 70 of 1,524 patients with lower extremity PAD and 44 of 1,553 of the controls (random effects OR 1.68, 95% confidence interval [CI] 0.8-3.2). In those with critical limb ischemia (CLI), the prevalence of prothrombin G20210A was 23 of 302 compared with 31 of 1,253 of the controls (OR 3.2, 95% CI 1.6-6.1). CONCLUSION: Despite finding no significant association between lower extremity PAD and prothrombin G20210A, the meta-analysis suggests that the prevalence of prothrombin G20210A is significantly elevated in those with atherosclerotic occlusive disease of the lower extremities presenting with CLI. Well-designed prospective cohort studies evaluating the role of prothrombin G20210A as a predictor of disease progression or adverse vascular events are highly needed.

Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis.

BACKGROUND: Recommendations for management of cancer-related venous thromboembolism (VTE) in patients already receiving anticoagulant therapy are based on low-quality evidence. This international registry sought to provide more information on outcomes after a breakthrough VTE in relation to anticoagulation strategies. METHODS: Patients with cancer and VTE despite anticoagulant therapy were reported to the registry. Data on treatments, VTE events, major bleeding, residual thrombosis symptoms and death were collected for the following 3 months. Breakthrough VTE and subsequent recurrences were objectively verified. Outcomes with different treatment strategies were compared with Cox proportional hazards regression. RESULTS: We registered 212 patients with breakthrough VTE. Of those, 59% had adenocarcinoma and 73% had known metastases. At the time of the breakthrough event, 70% were on low-molecular-weight heparin (LMWH) and 27% on a vitamin K antagonist (VKA); 70% had a therapeutic or supratherapeutic dose. After breakthrough the regimen was: unchanged therapeutic dose in 33%, dose increased in 31%, switched to another drug in 24%; and other management in 11%. During the following 3 months 11% had another VTE, 8% had major bleeding and 27% died. Of the survivors, 74% had residual thrombosis symptoms. Additional VTE recurrence was less common with LMWH than with a VKA (hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.11-0.70) but similar with unchanged or increased anticoagulant intensity (HR, 1.09; 95% CI, 0.45-2.63). The bleeding rate did not increase significantly with dose escalation. CONCLUSION: Morbidity and mortality are high after recurrence of cancer-related VTE despite anticoagulation. Further treatment appears to be more effective with LMWH than with a VKA.

Is it useful to also image the asymptomatic leg in patients with suspected deep vein thrombosis?

BACKGROUND: Venous ultrasonography is the cornerstone of the diagnostic work-up in patients with suspected deep vein thrombosis (DVT). Significant variations exist in clinical practice between centers and/or countries, e.g. proximal vs. whole-leg ultrasound, serial tests vs. single test, and combination with clinical probability and D-dimer testing. Fewer data exist on the need for bilateral leg imaging. OBJECTIVES: To assess the yield of bilateral leg ultrasonography in patients with suspected DVT. PATIENTS AND METHODS: This was a retrospective cohort study of consecutive patients with clinically suspected DVT. A single whole-leg ultrasound scan was performed in all patients. We extracted information on demographics, risk factors, clinical signs, pretest probability, side of clinical suspicion, and ultrasound results. RESULTS AND CONCLUSIONS: Among the 2804 included patients, 609 (21.8%) patients had a positive ultrasound finding. A total of 20 patients (0.8%; 95% confidence interval [CI] 0.5-1.2%) had a thrombus diagnosed in both the symptomatic leg and asymptomatic leg. Moreover, five patients (0.2%; 95% CI 0.1-0.5%) did not have a thrombus in the symptomatic leg but had a thrombus in the asymptomatic leg. Two of 2540 patients with unilateral symptoms had no proximal DVT in the symptomatic leg and a proximal DVT in the asymptomatic leg (0.08%; 95% CI 0.0-0.3%). In summary, systematic imaging of both legs in patients with suspected DVT has a very low yield, and therefore does not appear to be justified.

The risk of venous thromboembolism in renal cell carcinoma patients with residual tumor thrombus.

BACKGROUND: The clinical importance of tumor thrombus in patients with renal cell carcinoma is unknown. We sought to determine the long-term risk of venous thromboembolism (VTE) in patients with residual tumor thrombus postextraction, and to evaluate the impact of residual tumor thrombus on overall survival. PATIENTS/METHODS: A cohort study of patients with stage III-IV renal cell carcinoma undergoing nephrectomy was undertaken. The primary endpoint was the risk of VTE during a 2-year follow-up period. The secondary endpoint was 2-year overall survival. RESULTS: A total of 170 surgical renal cell carcinoma patients were included, 97 (57.1%) of whom had tumor thrombus. Patients with residual tumor thrombus following surgery had a higher risk of developing VTE than those with complete tumor thrombus resection (hazard ratio [HR] 8.7, 95% confidence interval [CI] 1.7-43.4) and no tumor thrombus (HR 6.5, 95% CI 1.7-24.7). Patient with residual tumor thrombus did not have worse overall survival than those with tumor thrombus completely resected or those without tumor thrombus. CONCLUSIONS: The presence of residual tumor thrombus is an important risk factor for VTE among renal cell carcinoma patients.

Increased risk of preoperative venous thromboembolism in patients with renal cell carcinoma and tumor thrombus.

BACKGROUND: The clinical impact of a tumor thrombus in renal cell carcinoma (RCC) patients awaiting radical nephrectomy and thrombectomy is unknown. OBJECTIVE: To determine the incidence of venous thromboembolism (VTE) in RCC patients with tumor thrombus prior to nephrectomy. PATIENTS AND METHODS: We conducted a retrospective cohort study including all late-stage (stage 3-4 excluding T1-2 N0M0) RCC patients who underwent radical nephrectomy at our institution between 1 January 2005 and 1 July 2012. Tumor thrombus was defined as the presence of an intraluminal filling defect in the renal vein, hepatic vein, portal vein, or inferior vena cava, directly extending from a renal mass detected on computed tomography. RESULTS: A total of 176 patients were included in the study. Fifty-three (30.1%) patients had tumor thrombus diagnosed on imaging Three patients with tumor thrombus (5.7%; 95% confidence interval [CI] 1.4-16.8) developed a VTE while awaiting radical nephrectomy, whereas none (0%; 95% CI 0-2.9) of the patients without a tumor thrombus had an event (P = 0.026). All three events were deep vein thrombosis. Times from tumor thrombus diagnosis to VTE were 5, 15 and 21 days. CONCLUSIONS: Tumor thrombus on imaging is a frequent finding among RCC patients awaiting nephrectomy. The presence of tumor thrombus in these patients increases the incidence of preoperative VTE.

[EGFR activating mutation in lung adenocarcinoma: risk factor of thromboembolic event?]. / Mutation EGFR dans les adénocarcinomes broncho-pulmonaires: facteur de risque de MVTE ?

Cancer is a known risk factor for the development of venous thromboembolism (VTE) and in particular, adenocarcinoma of the lung is known to be associated with a higher risk of thromboembolic event. EGFR activating mutations are more frequently found in this histological subtype than in other lung cancers. We report three cases of VTE in patients with adenocarcinoma of the lung and EGFR activating mutation. Our reported case series is atypical because the VTE event occurred early in the adenocarcinoma history: either leading to the diagnosis of cancer, or appearing very early in the management of the neoplasm.

[Septic pulmonary embolism after removal of a venous access device for septic thrombophlebitis]. / Emboles pulmonaires septiques après ablation d'une chambre implantable pour thrombophlébite septique.

Septic thrombophlebitis on a central venous access device (CVAD) is a rare and serious complication. According to current guidelines, the device should be removed and antibiotics be given. The risk of septic thrombophlebitis is related to the migration of septic emboli to the lung, a potentially fatal event, particularly in frail patients with lung cancer. We report a case observed in a 66-year-old man with multiple metastatic lung cancer who had a CVAD and who developed septic thrombophlebitis leading to coagulase-negative staphylococcal bacteriemia. After removal of the CVAD, the thrombophlebitis was complicated by pulmonary embolism affecting the entire network of the right lung.

[Epidemiology and risk factors of venous thromboembolism]. / Épidémiologie et facteurs de risque de la maladie veineuse thromboembolique.

INTRODUCTION: Venous thromboembolism (VTE) is a common disease. The incidence rises markedly with increasing age; over the age of 75, the annual incidence reaches 1 per 100. BACKGROUND: Besides major risk factors (surgery, trauma and acute medical illness), four risk factors have to be taken into account in the management of VTE: increasing age, cancer, previous history of VTE and pregnancy. To date, with the exception of the antiphospholipid syndrome and antithrombin deficiency, "thrombophilias" do not appear to change the management of VTE. VIEWPOINTS: "Thrombophilias" are useful tools for understanding the pathophysiology of VTE. Therefore, further studies are needed to identify new biological anomalies and their impact on the risk of VTE. Recently, links between VTE and atherosclerosis have been demonstrated, leading to new concept of pan-vascular disease and prevention. CONCLUSIONS: VTE is a major public health problem. The knowledge of VTE risk factors is of major importance in identifying high-risk patients and in reducing the incidence and mortality of VTE.

[Validation of a clinical prediction rule for the diagnosis of deep vein thrombosis of the lower limbs in primary care]. / Validation d'un score de prédiction clinique de la thrombose veineuse profonde des membres inférieurs spécifique à la médecine générale.

PURPOSE: Patients with suspected deep vein thrombosis (DVT) are often managed on an outpatient basis. The aim of the study was to validate a clinical prediction rule specifically for use in primary care to help physicians in their decision to start anticoagulant therapy while awaiting ultrasound examination. PATIENTS AND METHODS: Between September 2007 and October 2008, 194 general practitioners prospectively included patients with clinically suspected DVT without clinically suspected pulmonary embolism. All patients underwent a standardized clinical assessment in order to collect items included in the clinical prediction rule (personal history of venous thromboembolism +1, immobilization in previous month+1, estrogen contraceptive+2, active malignancy+3, swelling of the calf+1, the presence of an alternative diagnosis more likely than that of DVT-3. DVT unlikely if score<2, likely if score≥2). RESULTS: Among the 164 included patients, 56 (34%) had DVT of them 28 (17%) had a proximal DVT. Proportions of confirmed DVT were 29% in the unlikely group and 43% in the likely group against 26% and 63% respectively in the derivation study. CONCLUSIONS: This clinical prediction rule might not fulfill the required conditions to be considered as a usable help in the ambulatory management of DVT. Variations of the cut-off value could enhance its performance.