Management of isolated anterior talofibular ligament lesion in patients suffering from chronic ankle instability: comparison of two minimally invasive surgical techniques.

OBJECTIVE: The aim of the present study was to retrospectively compare the outcomes of two minimally invasive surgical techniques in patients with isolated anterior talofibular ligament (ATFL) lesion suffering from chronic ankle instability (CAI). PATIENTS AND METHODS: Thirty-six patients with ATFL lesion suffering from CAI were treated at our department from 2010 to 2017 and retrospectively reviewed after an average time of 4 years (2 to 9 years). Eighteen patients underwent a four-step operative protocol, including: synovectomy, debridement of ATFL lesion borders, capsular shrinkage, and 21-day immobilization and non-weightbearing. Eighteen patients underwent arthroscopic Broström procedure. Patients were assessed pre-operatively and at follow-up with American Orthopedic Foot & Ankle Society Score (AOFAS) scale, Karlsson-Peterson score, Tegner activity level, and objective examination comprehending range of motion, anterior drawer test, and talar tilt test. Wilcoxon test was utilized to compare the pre-operative and follow-up status. The Mann-Whitney U test was used to make comparisons between the two surgical techniques. Statistical significance was established at p < 0.05. RESULTS: Mean overall AOFAS, Karlsson-Peterson and Tegner scores significantly increased at follow-up compared to pre-operatory status (p < 0.05). However, no statistically significant differences concerning mean AOFAS score (90.2 in the four-step group vs. 89.2 in the Broström arthroscopic group), mean Karlsson-Peterson score (88.1 and 85.9 respectively), and median Tegner activity level (6.0 vs. 5.5) were reported between the two groups (p = n.s.). The complications in the arthroscopic four-step treatment group included damage to the superficial branch of the peroneal nerve in one case. The complications in the arthroscopic Broström included nerve injury in one case and persistent local pain nearby suture knot in one case. CONCLUSIONS: Both arthroscopic Broström and a four-step operative procedure including synovectomy, debridement of ATFL lesion borders, capsular shrinkage and immobilization, improved functional outcomes in patients with ATFL lesion suffering from CAI.

Monolayer of silica nanospheres assembled onto ITO-coated glass substrates by spin-coating.

In this work, we synthesized colloidal silica nanospheres with an average size of 400 nm through the modified Stöber method and successfully fabricated an ordered close-packed silica nanosphere monolayer onto ITO-coated glass substrates using a three-step spin-coating method. ITO films showed resistivity comparable to that of commercial ITO and the silica nanosphere monolayer-coated ITO/glass substrate exhibited good optical transmittance in the visible (550 nm) and near-infrared (900 nm) regions of 62% and 82%, respectively. The results suggest that this monolayer can be used in optoelectronic devices to enhance efficiency in photovoltaic cells.

Reducing transfusion requirements following total knee arthroplasty: effectiveness of a double infusion of tranexamic acid.

OBJECTIVE: Blood loss following joint replacement surgery represents a relevant issue for orthopedic surgeons. The use of tranexamic acid (TXA) to reduce transfusion requirements has become mainstream. However, consensus about the starting time, methods, or volume of usage of TXA in joint replacement surgery has yet to be found. A retrospective study was conducted comparing pre- and post-operative infusion of TXA 15 mg/kg to a single pre-operative infusion. PATIENTS AND METHODS: 291 patients undergoing TKA were retrospectively reviewed. 109 received a single pre-operative dose of 15 mg/ kg TXA (single dose, SD group), 182 received a single pre- operative dose of 15 mg/ kg TXA followed by a second post-operative dose of 15 mg/kg TXA (double dose, DD group). The primary outcome was blood loss calculated from haematological values and perioperative transfusions. Secondary outcomes included the occurrence of major complications within the first postoperative year. RESULTS: None of the patients reported adverse events. Blood transfusions were administered to 63 patients (13.5%) in the SD and 36 in the DD group (5.7%). Significant difference between the groups was observed (p < 0.005). No significant difference between the two groups was found concerning mean blood loss in drainage after the 24th hour and postoperative hemoglobin values (p = n.s.). CONCLUSIONS: The study demonstrated that TXA possesses a good safety profile. In addition, pre- and post-operative infusion of TXA 15 mg/kg is more effective compared to single pre-operative infusion in reducing need for transfusion requirements.

Lupus anticoagulant identifies two distinct groups of patients with different antibody patterns.

BACKGROUND: Whether antibodies directed to ß2-Glycoprotein I (aß2GPI) are responsible for LA activity is not well defined. However, in the absence of such antibodies the molecule responsible for LA phenomenon is unknown. OBJECTIVE: The aim of this study was the biochemical identification of the target antigen epitope of aPL responsible of LA activity in the absence of aß2GPI antibodies together with the biological and clinical characteristics of these patients in comparison with classical triple positive patients. PATIENTS/METHODS: A comparison of patients with LA without (LA+/aß2GPI-) and those with (LA+/aß2GPI+) associated aß2GPI antibodies was performed. Size exclusion chromatography and analytical chromatography were used to identify the molecule with LA activity in patients LA+/aß2GPI-. RESULTS AND CONCLUSIONS: Analytical size-exclusion chromatography revealed a peak of 996Kd with LA activity perfectly overlapping that of IgM anti phosphatidylserine/prothrombin (aPS/PT) antibodies. Similarly, all the 25 LA+/aß2GPI- patients were positive for aPS/PT antibodies. LA+/aß2GPI- compared to 33 LA+/aß2GPI+ patients turned out to be significantly older, with a lower rate of previous thromboembolic events and a weaker LA activity. Search for aPS/PT and aß2GPI antibodies in patients with LA is useful to identify two subgroups of LA at different risk of thromboembolic events.

Low drug levels and thrombotic complications in high-risk atrial fibrillation patients treated with direct oral anticoagulants.

Essentials Direct oral anticoagulants (DOACs) do not require laboratory monitoring currently. DOAC specific measurements were performed at trough in patients with atrial fibrillation. Patients who developed thromboembolic events showed lower DOAC plasma levels. This study supports the concept of measuring DOAC levels at steady state. SUMMARY: Background Direct oral anticoagulants (DOACs) are administered at fixed doses without the need for dose adjustment according to laboratory testing. High interindividual variability in drug blood levels has been shown with all DOACs. To evaluate a possible relationship between DOAC C-trough anticoagulant levels and thromboembolic events, 565 consecutive naive patients with atrial fibrillation (AF) were enrolled in this study performed within the START Laboratory Registry. Methods DOAC-specific measurements (diluted thrombin time or anti-activated factor II calibrated for dabigatran; anti-activated FX calibrated for rivaroxaban or apixaban) at C-trough were performed locally at steady state within 15-25 days after the start of treatment. For each DOAC, the interval of C-trough levels, from the limit of quantification to the highest value, was subdivided into four equal classes, and results were attributed to these classes; the median values of results were also calculated. Thromboembolic complications occurring during 1 year of follow-up were recorded. Results Thromboembolic events (1.8%) occurred in 10 patients who had baseline C-trough levels in the lowest class of drug levels. The incidence of thromboembolic events among patients with DOAC C-trough levels in the lowest level class was 2.4%, and that in the remaining groups was 0%. The patients with thrombotic complications also had a higher mean CHA2 DS2 -VASc score than that of the total patient population: 5.3 (95% confidence interval [CI] 4.3-6.3 versus 3.0 (95% CI 2.9-3.1). Conclusion In this study cohort, thrombotic complications occurred only in DOAC-treated AF patients who had very low C-trough levels, with a relatively high CHA2 DS2 -VASc score. Larger studies are warranted to confirm these preliminary observations.

Comparison of five specific assays for determination of dabigatran plasma concentrations in patients enrolled in the START-Laboratory Register.

INTRODUCTION: Several specific assays are commercially available to determine dabigatran anticoagulant activity. Aims of this multicenter and multiplatform study were to compare five methods for dabigatran measurement and investigate their performances in the low concentration range. METHODS: Dabigatran levels were analyzed in 295 plasma samples from patients enrolled in the START-Laboratory Register by the following methods using dedicated calibrators and controls: STA-ECA II (Diagnostica Stago), standard and low range Hemoclot Thrombin Inhibitors (Hyphen BioMed), Direct Thrombin Inhibitor Assay (Instrumentation Laboratory), Direct Thrombin Inhibitor Assay (Siemens), Technoclot DTI (Technoclone). RESULTS: Methods showed variable agreement with the Hemoclot Thrombin Inhibitors assay used as reference test, with modest under- or overestimations (Bland-Altman bias from -17.3 to 4.0 ng/mL). Limits of detection and quantification varied depending on the assay (4-52 and 7-82 ng/mL, respectively). Between-run precision and accuracy were good for all methods for both quality control levels. Assay's repeatability assessed at very low dabigatran concentrations (from 10 to 60 ng/mL) was also acceptable, variability generally increased at lower drug levels. CONCLUSION: The five dabigatran-specific assays evaluated in this study provided reliable assessment of dabigatran plasma levels, although showing different performances.

Interlaboratory variability in the measurement of direct oral anticoagulants: results from the external quality assessment scheme.

Essentials Tests for direct oral anticoagulants (DOACs) are not widely applied. These tests are perceived to be difficult to run and subjected to large between-lab variation. We carried out proficiency testing surveys for DOAC testing in Italy. Interlab variability was small and similar to that of the international normalised ratio. SUMMARY: Background Tests for direct oral anticoagulants (DOACs) are not widely available. The perception that they are difficult to perform and are subject to large between-laboratory variation makes their implementation difficult. Aims We carried out proficiency-testing surveys for DOACs within the activity of the external quality-assessment scheme of the Italian Federation of Thrombosis Centers. Design Participants were provided with coded freeze-dried plasmas without or with graded concentrations of the three main DOACs, and asked to measure prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time and DOAC concentrations with dedicated tests. The results were centralized for statistical analysis. Results and conclusions All participants (n = 235) reported results for PT and APTT, and approximately one-third reported results for DOAC concentration. PT and APTT showed variable responsiveness to DOACs: PT was more responsive to rivaroxaban than to dabigatran or apixaban. APTT was more responsive to dabigatran than to rivaroxaban or apixaban. The thrombin time ratio (test/normal) was close to unity for plasmas without dabigatran, and was high (i.e. 7.6-fold or 15.4-fold longer than the plasma free from the drug) for plasmas containing dabigatran at low (i.e. 42 ng mL-1 ) or high (i.e. 182 ng mL-1 ) concentration. Dedicated tests were responsive to the respective drugs, and their interlaboratory variability was relatively small (overall coefficients of variation of 8.7%, 8.4% or 10.3% for dabigatran, rivaroxaban and apixaban, respectively) and was comparable to that observed within the same survey for the International Normalized Ratio (i.e. 11.4%). In conclusion, tests for DOAC measurement performed reasonably well in a national quality-control scheme. Regulatory authorities should urgently issue recommendations on their use, and clinical laboratories should make them available.

International collaborative study for the calibration of proposed International Standards for thromboplastin, rabbit, plain, and for thromboplastin, recombinant, human, plain.

Essentials Two candidate International Standards for thromboplastin (coded RBT/16 and rTF/16) are proposed. International Sensitivity Index (ISI) of proposed standards was assessed in a 20-centre study. The mean ISI for RBT/16 was 1.21 with a between-centre coefficient of variation of 4.6%. The mean ISI for rTF/16 was 1.11 with a between-centre coefficient of variation of 5.7%. SUMMARY: Background The availability of International Standards for thromboplastin is essential for the calibration of routine reagents and hence the calculation of the International Normalized Ratio (INR). Stocks of the current Fourth International Standards are running low. Candidate replacement materials have been prepared. This article describes the calibration of the proposed Fifth International Standards for thromboplastin, rabbit, plain (coded RBT/16) and for thromboplastin, recombinant, human, plain (coded rTF/16). Methods An international collaborative study was carried out for the assignment of International Sensitivity Indexes (ISIs) to the candidate materials, according to the World Health Organization (WHO) guidelines for thromboplastins and plasma used to control oral anticoagulant therapy with vitamin K antagonists. Results Results were obtained from 20 laboratories. In several cases, deviations from the ISI calibration model were observed, but the average INR deviation attributabled to the model was not greater than 10%. Only valid ISI assessments were used to calculate the mean ISI for each candidate. The mean ISI for RBT/16 was 1.21 (between-laboratory coefficient of variation [CV]: 4.6%), and the mean ISI for rTF/16 was 1.11 (between-laboratory CV: 5.7%). Conclusions The between-laboratory variation of the ISI for candidate material RBT/16 was similar to that of the Fourth International Standard (RBT/05), and the between-laboratory variation of the ISI for candidate material rTF/16 was slightly higher than that of the Fourth International Standard (rTF/09). The candidate materials have been accepted by WHO as the Fifth International Standards for thromboplastin, rabbit plain, and thromboplastin, recombinant, human, plain.

External validation of the DASH prediction rule: a retrospective cohort study.

Essentials Predicting recurrences may guide therapy after unprovoked venous thromboembolism (VTE). We evaluated the DASH score in 827 patients with unprovoked VTE to verify prediction accuracy. A DASH score ≤ 1 had a cumulative recurrence risk at 1 year of 3.6%, as predicted by the model. The DASH score performed better in younger (< 65 years old) subjects. SUMMARY: Background The DASH prediction model has been proposed as a guide to identify patients at low risk of recurrence of venous thromboembolism (VTE), but has never been validated in an independent cohort. Aims To validate the calibration and discrimination of the DASH prediction model, and to evaluate the DASH score in a predefined patient subgroup aged > 65 years. Methods Patients with a proximal unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) who received a full course of vitamin K antagonist or direct oral anticoagulant (> 3 months) and had D-dimer measured after treatment withdrawal were eligible. The DASH score was computed on the basis of the D-dimer level after therapy withdrawal and personal characteristics at the time of the event. Recurrent VTE events were symptomatic proximal or distal DVT/PE, and were analyzed with a time-dependent analysis. Observed 12-month and 24-month recurrence rates were compared with recurrence rates predicted by the DASH model. Results We analyzed a total of 827 patients, of whom 100 (12.1%) had an objectively documented recurrence. As compared with the original DASH cohort, there was a greater proportion of subjects with a 'low-risk' (≤ 1) DASH score (66.3% versus 51.6%, P < 0.001). The slope of the observed versus expected cumulative incidence at 2 years was 0.71 (95% confidence interval 0.51-1.45). The c-statistic was lower for subjects aged > 65 years (0.54) than for younger subjects (0.72). Conclusions These results confirm the validity of DASH prediction model, particularly in young subjects. The recurrence risk in elderly patients (> 65 years) was, however, > 5% even in those with the lowest DASH scores.

Variability of cut-off values for the detection of lupus anticoagulants: results of an international multicenter multiplatform study.

Essentials Between-lab variations of cut-off values in lupus anticoagulant detection are unknown. Cut-off values were calculated in 11 labs each testing plasma from 120 donors with 3 platforms. Major variation was observed even within the same platform. Cut-off values determined in different labs are not interchangeable. SUMMARY: Background Cut-off values for interpretation of lupus anticoagulant (LA) detection are poorly investigated. Aims (i) To assess whether results from healthy donors were normally distributed and (ii) the between-laboratories differences in cut-off values for screening, mixing and LA confirmation when calculated as 99th or 95th centiles, and (iii) to assess their impact on the detection rate for LA. Methods Each of 11 laboratories using one of the three widely used commercial platforms for LA detection was asked to collect plasmas from 120 healthy donors and to perform screening, mixing and LA confirmation with two methods (activated partial thromboplastin time [APTT] and dilute Russell viper venom [dRVV]). A common set of LA-positive or LA-negative freeze-dried plasmas was used to assess the LA detection rate. Results were centralized (Milano) for statistical analysis. Results and conclusions (i) Clotting times or ratios for healthy subjects were not normally distributed in the majority of cases. The take-home message is that cut-off values should be determined preferably by the non-parametric method based on centiles. (ii) There were relatively large inter-laboratory cut-off variations even within the same platform and the variability was marginally attenuated when results were expressed as ratios (test-to-normal pooled plasma). The take-home message is that cut-off values should be determined locally. (iii) There were differences between cut-off values calculated as 99th or 95th centiles that translate into a different LA detection rate (the lower the centile the greater the detection rate). The take-home message is that cut-off values determined as the 95th centile allow a better LA detection rate.

Poor comparability of coagulation screening test with specific measurement in patients receiving direct oral anticoagulants: results from a multicenter/multiplatform study.

Essentials Prothrombin and partial thromboplastin time (PT/PTT) measure direct oral anticoagulants (DOACs). PT, PTT and specific tests for DOACs were performed on patients treated for atrial fibrillation. Normal PT/PTT don't exclude DOAC activity and their prolongation doesn't confirm DOAC action. The use of PT or PTT to evaluate DOAC activity could cause dangerous misinterpretations. SUMMARY: Background Prothrombin time (PT) and activated partial thromboplastin time (APTT) have been proposed to measure the effect of oral anti-activated factor X (FXa) or anti-activated FII drugs, respectively. Aims To evaluate the relationships and responsiveness of PT and APTT versus direct oral anticoagulant (DOAC) concentrations measured with specific coagulation tests performed with different platforms in four Italian anticoagulation clinics. Methods Six hundred and thirty-five patients with atrial fibrillation participated in the study: 240 were receiving dabigatran, 264 were receiving rivaroxaban, and 131 were receiving apixaban. Blood was taken at trough and peak within the first month (15-25 days) of treatment. PT, APTT, diluted thrombin time (dTT) calibrated for dabigatran and anti-FXa calibrated for rivaroxaban or apixaban were determined. Results For dabigatran, the correlation between APTT and dTT ranged from r = 0.80 to r = 0.62. For rivaroxaban, the correlation between the anti-FXa assay and PT ranged from r = 0.91 to r = 0.73. For apixaban, the correlation between the anti-FXa assay and PT was lower than for the two other drugs (r = 0.81 to r = 0.54). Despite the above significant correlations, the responsiveness of PT or APTT was relatively poor. A discrepancy between global testing and DOAC plasma concentrations was shown in a considerable proportion of patients, depending on the platform and drug, with values ranging from 6% to 62%. Conclusions Overall, poor responsiveness of the screening tests to DOAC concentrations was observed. PT and APTT normal values cannot exclude DOAC anticoagulant activity, and PT or APTT prolongation is not always associated with DOAC anticoagulant effect as determined with specific tests.

OC-15 - Risk factors for cancer development after idiopathic venous thromboembolism.

INTRODUCTION: Idiopathic venous thromboembolism (VTE) is associated with the risk of cancer but the risk factors for cancer development in such patients are still uncertain. AIM: To assess risk factors for the development of cancer after a standard course of anticoagulation in patients with first episode of idiopathic VTE. MATERIALS AND METHODS: Subjects were enrolled in the three large prospective multicentre studies: PROLONG (NEJM 2006) PROLONG II (Blood 2010) and DULCIS (Blood 2014). Women whose index event was hormone related were excluded from the analysis. The development of cancer was recorded during a 2-year follow-up. RESULTS: 1,805 patients were enrolled (M/F: 510/453), mean age: 62, median: 67; range:18-87 years). Cancer developed in 55 patients (3% ; 1.7% pt-years) of whom 15 (2.0%; 1.1% pt-years) had PE with or without DVT and 40 (3.8%; 2.1% pt-years) had DVT without PE (p=0.03). The development of cancer was associated with DVT without PE (HR:1.8; 95% CI: 1.1-3.3) and age >65 (HR: 2.5; 95%: 1.3-4.9). Among patients with DVT, with or without PE, the development of cancer was associated with the presence of residual vein obstruction>4mm (RVO) at compression ultrasound (HR: 1.8, 95% CI: 1.1-3.3) and age>65 (HR: 2.8; 95% CI: 1.3-6.2). CONCLUSIONS: Age>65 years, DVT without PE and the presence of RVO are significantly associated with the risk of developing cancer after a first episode of idiopathic VTE over a two-year follow-up.

Comparison between different D-Dimer cutoff values to assess the individual risk of recurrent venous thromboembolism: analysis of results obtained in the DULCIS study.

INTRODUCTION: D-dimer assay, generally evaluated according to cutoff points calibrated for VTE exclusion, is used to estimate the individual risk of recurrence after a first idiopathic event of venous thromboembolism (VTE). METHODS: Commercial D-dimer assays, evaluated according to predetermined cutoff levels for each assay, specific for age (lower in subjects <70 years) and gender (lower in males), were used in the recent DULCIS study. The present analysis compared the results obtained in the DULCIS with those that might have been had using the following different cutoff criteria: traditional cutoff for VTE exclusion, higher levels in subjects aged ≥60 years, or age multiplied by 10. RESULTS: In young subjects, the DULCIS low cutoff levels resulted in half the recurrent events that would have occurred using the other criteria. In elderly patients, the DULCIS results were similar to those calculated for the two age-adjusted criteria. The adoption of traditional VTE exclusion criteria would have led to positive results in the large majority of elderly subjects, without a significant reduction in the rate of recurrent event. CONCLUSION: The results confirm the usefulness of the cutoff levels used in DULCIS.

D-dimer use for deep venous thrombosis exclusion in elderly patients: a comparative analysis of three different approaches to establish cut-off values for an assay with results expressed in D-dimer units.

INTRODUCTION: The use of adapted cut-off values in the elderly, combined with clinical probability (PTP), increases the proportion of patients in whom venous thromboembolism (VTE) can be safely excluded, compared with the conventional cut-off value of 500 µg/L fibrinogen equivalent units (FEU). We evaluated the clinical performance of three different approaches to establish cut-off values for a D-dimer assay whose results are expressed in D-dimer units (D-DU). METHODS: HemosIL D-dimer HS assay (Instrumentation Laboratory) was performed in 279 consecutive outpatients with suspected deep venous thrombosis (DVT) and nonhigh PTP. RESULTS: Considering patients >60 years, the number of negative D-dimer results increased using the modified (376 ng/mL if ≥60 years) and the age-adjusted cut-off (age years × 5 ng/mL if >50 years) compared to the conventional one (230 ng/mL for all patients; 54.6%, 58.2%, and 25.0%, respectively), with no false-negative results. The higher increase was observed in patients >80 years (43.9%, 56.1%, and 8.8%, respectively). CONCLUSION: For the HemosIL D-dimer HS, the use of specific cut-off values in older subjects with suspected DVT and nonhigh PTP increases the number of patients in whom DVT can be safely excluded.

Obstetric implications of fetal inherited thrombophilia in thrombophilic women.

OBJECTIVES: The relationship between fetal thrombophilic polymorphism and adverse pregnancy outcomes is still unclear. The aim of this study is to evaluate if fetal thrombophilia may affect obstetric and perinatal outcomes in thrombophilic women. STUDY DESIGN: From 2007 to 2011 all patients with a known inherited thrombophilic mutation consecutively admitted to our labor ward at ⩾25weeks of gestation with a singleton viable pregnancy were considered eligible for the purpose of the study. At the age of 1year, the infants were tested for inherited thrombophilic mutations. Patients were then divided into two groups according to the presence or absence of any neonatal mutation. MAIN OUTCOME MEASURES: The following outcome variables were then compared between the two groups: gestational age at delivery, birth weight, incidence of hypertensive disorders of pregnancy and SGA neonates. RESULTS: Overall, 67 pregnancies of 49 women were studied. Among them, the G20210A Prothrombin (32/67 or 47.7%) mutation and the Factor V Leiden mutation (31/67 or 46.3%) were the commonest findings, with a single patient presenting both. A thrombophilic mutation was found in 38 mother-infant pairs. The risk of all maternal and perinatal events including the incidence of hypertensive disorders disorders (5/29 or 17.2% vs 6/38 or 15.7% p=1.00) and of SGA neonates (3/29 or 10.3% vs 7/38 or 18.4%, p=0.49) was comparable between the two groups irrespective of the associated fetal thrombophilia. CONCLUSIONS: Our data suggest that women with inherited thrombophilia carrying a thrombophilic fetus are not at increased risk of adverse pregnancy outcomes.

The Wells rule and D-dimer for the diagnosis of isolated distal deep vein thrombosis.

BACKGROUND: Pretest clinical probability with the Wells rule and D-dimer have been widely investigated for the diagnosis of symptomatic proximal deep vein thrombosis (DVT) of the lower limbs, but they have not been formally tested for symptomatic isolated distal DVT diagnosis. OBJECTIVE: To evaluate the diagnostic accuracy of the Wells rule and D-dimer for isolated distal DVT. DESIGN, SETTING, AND PATIENTS: This was a single-center, cross-sectional study including 873 consecutive outpatients with suspected DVT, in whom pretest clinical probability determination, D-dimer determination (STA Liatest; cut-off of < 500 ng mL(-1) ) and complete compression ultrasonography of both lower limbs were performed. RESULTS: The isolated distal DVT prevalence was 12.4% (90/725). The sensitivity of the Wells rule for isolated distal DVT was 47% (95% confidence interval [CI] 36-57%), the specificity was 74% (95% CI 70-77%), and the negative and positive predictive values were 91% (95% CI 88-93%) and 20% (95% CI 15-26%), respectively. Patients with isolated distal DVT had higher D-dimer levels than patients without DVT (1759 ± 1576 vs. 862 ± 1079 ng mL(-1) , P = 0.0001). D-dimer was negative in 13 patients with isolated distal DVT. D-dimer sensitivity and specificity for isolated distal DVT were 84% (95% CI 75-91%) and 50% (95% CI 46-54%), respectively, with a negative predictive value of 96% (95% CI 93-98%). In patients with low pretest clinical probability, the D-dimer negative predictive value was 99% (95% CI 95-100%). CONCLUSION: In clinically suspected DVT with negative proximal compression ultrasonography, pretest clinical probability with the Wells rule has a low diagnostic accuracy for isolated distal DVT. D-dimer has a better negative predictive value, but alone it does not exclude isolated distal DVT. In patients with low pretest clinical probability, D-dimer had a negative predictive value of > 95% for isolated distal DVT.