Multicenter evaluation of a new quantitative highly sensitive D-dimer assay, the Hemosil® D-dimer HS 500, in patients with clinically suspected venous thromboembolism

Introduction

D-dimer testing is widely used in conjunction with clinical pretest probability (PTP) for venous thromboembolism (VTE) exclusion. We report on a multicenter evaluation of a new, automated, latex enhanced turbidimetric immunoassay [HemosIL® D-Dimer HS 500, Instrumentation Laboratory (IL)].

Materials and Methods

747 consecutive outpatients with suspected proximal deep vein thrombosis (DVT, n = 401) or pulmonary embolism (PE, n = 346) were evaluated at four university hospitals in a management study with a 3 month follow-up. Samples were tested at each center using the new D-dimer assay on an automated coagulation analyzer [ACL TOP (IL)], with clinical cut-off for VTE at 500 ng/mL (FEU).

Results

The sensitivity and negative predictive value (NPV) were 100% for all PTP subgroups (no false negative results); for both sensitivity and NPV the lower limit of the 95% CI in patients with moderate/low PTP was higher than 95%. The overall specificity was 45.1% (95%CI: 41.1-49.3%). Higher specificity value was recorded in the low PTP subgroup [49.2% (95%CI: 41.7-56.7)]. No significant differences were found between patients suspected of having DVT or PE; sensitivity and NPV were 100%. The reproducibility of the assay was good, being the total CVs% less than 10% for D-dimer concentration near the clinical cut-off.

Conclusions

The new, highly sensitive D-dimer assay proved to be accurate when used for VTE diagnostic work-up in outpatients. Based on 100% sensitivity and NPV and lower limit of the 95% CI higher than 95%, the assay can be used as a stand-alone test in patients with non high PTP.     

Clinical probability assessment and D-dimer determination in patients with suspected deep vein thrombosis, a prospective multicenter management study

Objectives

To investigate the reliability of a combined strategy of clinical assessment score followed by a local D-dimer test to exclude deep vein thrombosis. For comparison D-dimer was analysed post hoc and batchwise at a coagulation laboratory.

Design

Prospective multicenter management study.

Setting

Seven hospitals in southern Sweden.

Subjects

357 patients with a suspected first episode of deep vein thrombosis (DVT) were prospectively recruited and pre-test probability score (Wells score) was estimated by the emergency physician. If categorized as low pre-test probability, D-dimer was analysed and if negative, DVT was considered to be ruled out. The primary outcome was recurrent venous thromboembolism (VTE) during 3 months of follow up.

Results

Prevalence of DVT was 23.5% (84/357). A low pre-test probability and a negative D-dimer result at inclusion was found in 31% (110/357) of the patients of whom one (0.9%, [95% CI 0.02-4.96]) had a VTE at follow up. Sensitivity, specificity, negative predictive value and negative likelihood ratio for our local D-dimer test in the low probability group were 85.7%, 74.5%, 98.2%, and 0,19 respectively compared to 85.6%, 67,6%, 97.9% and 0,23 using batchwise analysis at a coagulation laboratory.

Conclusion

Pre-test probability score and D-dimer safely rule out DVT in about 30% of outpatients with a suspected first episode of DVT. One out of 110 patients was diagnosed with DVT during follow up. No significant difference in diagnostic performance was seen between local D-dimer test and the post hoc batch analysis with the same reagent in the low probability group.     

Incidence and predictive factors of symptomatic thrombosis related to peripherally inserted central catheters in chemotherapy patients

Introduction

The incidence of symptomatic catheter-related deep vein thrombosis (DVT) in cancer patients remains unclear and there is a lack of reliable data on the risk factors of PICC-related DVT.

Materials and Methods

We performed a retrospective cohort study of consecutive cancer patients who received an ultrasound guided PICC line for the administration of chemotherapy. Univariable and multivariable logistic regression analyses were performed to identify risk factors for symptomatic PICC-related DVT.

Results

In total, 340 cancer patients obtained PICC lines for the administration of chemotherapy. Of these patients, 19 (5.6%; 95% CI: 3.6-8.6) developed symptomatic PICC-related DVT. Factors previously associated with catheter-related DVT, including side of catheter placement, lumen size, tip location, need for repositioning, and number of insertion attempts, were not significant determinants in our analysis. Patients with diabetes were three times more likely to develop PICC-related DVT (OR 3.0, p = 0.039), while the presence of COPD and metastatic cancer also increased the odds (OR 3.3, p = 0.078 and OR 2.3, p = 0.083 respectively). Diabetes remained a significant risk factor after adjustment for effect of metastases and COPD (OR 3.175, p = 0.039). Further, the presence of metastases was a significant predictor (OR 3.34, p = 0.024) in our multivariable model.

Conclusions

Symptomatic PICC-related DVT are frequent in cancer patients receiving chemotherapy. Previously described factors associated with catheter-related thrombosis were not predictive of PICC-related DVT in our study. Diabetes, advanced disease and COPD appear to increase the risk of developing PICC-related DVT in chemotherapy patients.     

Prospective diagnostic accuracy assessment of the HemosIL HS D-dimer to exclude pulmonary embolism in emergency department patients

Introduction

Chest pain and shortness of breath are among the most common symptoms requiring immediate evaluation. Testing for pulmonary embolism (PE) has become easier and widespread due to D-dimer blood tests. Safe use of these tests is only possible if sensitivity is high and they are used in non-high probability patients. We evaluated diagnostic performance of the HemosIL HS D-dimer, which despite FDA approval in 2005, has been minimally reported in prospective standard clinical care.

Materials and methods

We used a prospective observational study design to follow patients in a single center with the HemosIL HS ordered for symptoms of possible PE with positive test result if > 243 ng/ml. The outcome was PE or deep venous thrombosis (DVT) at the time of presentation or subsequent 45 days determined by structured evaluation of imaging tests, phone, or medical record follow-up in all patients.

Results

529 patients received a D-dimer and 4.7% were ultimately diagnosed with PE or DVT. The sensitivity of the HemosIL HS was 96.0% (95% CI; 79.6 to 99.9%) specificity was 65.7% (95% CI; 61.4 to 69.8%) and likelihood ratio negative was 0.06 (95% CI; 0.01 to 0.42). The probability of PE in patients with a negative D-dimer was 1/332 or 0.3% (95% CI; 0.01% to 1.67%). The receiver operator curve had an area under the curve of 0.87 and supported the current cut-point as optimal.

Conclusions

The HemosIL HS D-dimer had high sensitivity, very low negative post-test probability and is useful in excluding PE in the acute care setting.     

Circulating tissue factor positive microparticles in patients with acute recurrent deep venous thrombosis

Introduction

Circulating tissue factor positive microparticles (MPTF) were reported in a wide range of diseases with thrombotic tendency. Though D-dimer assay had a high negative predictive value for deep venous thrombosis (DVT) recurrence, there are currently no reliable positive predictors for recurrent DVT. We therefore quantified MPTF in patients with acute recurrent DVT to determine whether MPTF levels could be used to predict recurrent DVT.

Materials and Methods

Microparticles (MPs) were isolated from plasma of initial DVT patients (n = 25), recurrent DVT patients (n = 25) and sex- and age-matched healthy individuals (n = 25), stained with annexin V, cell-specific monoclonal antibodies (MoAbs) and a MoAb directed against tissue factor (TF), and analyzed by flow cytometry. We also determined the plasma procoagulant activity with a Human TF Chromogenic Activity Assay Kit.

Results

We found total MPTF to be elevated in recurrent DVT patients versus normal individuals (P = 0.001). The number of monocyte-derived MPTF in both initial and recurrent DVT was higher than in normal individuals (P < 0.01, respectively). The platelet and endothelial cell derived MPTF in recurrent DVT were significantly increased relative to other MPTF (P < 0.05), although there was no difference between initial DVT patients and normal individuals. We demonstrated elevated procoagulant activity of platelet-free plasma in DVT patients relative to normal individuals, and a positive correlation with MPTF.

Conclusions

The elevated MPTF could be a potentially predictor for DVT recurrence. Further studies are needed to validate its sensitivity and specificity.     

Has the incidence of deep vein thrombosis in patients undergoing total hip/knee arthroplasty changed over time? A systematic review of randomized controlled trials

Background

There is a perception in the orthopaedic and thromboembolism community that the incidence of deep vein thrombosis (DVT) has decreased in patients undergoing total knee arthroplasty (TKA) or total hip arthroplasty (THA).

Objectives

To assess the incidence of DVT with warfarin thromboprophylaxis over time in patients undergoing elective TKA or THA.

Methods

The MEDLINE, EMBASE, and Cochrane Library databases were searched to October 2006, supplemented by a manual search of reference lists. Two reviewers independently extracted data on study characteristics, quality and the frequency of total, symptomatic and proximal DVT.

Results

Fourteen studies (4,423 patients) were included. Total and proximal DVT after TKA declined over time (r = − 0.75, p = 0.031; r = − 0.86, p = 0.007 respectively). Total and proximal DVT after THA did not change. The risk of developing DVT after TKA was significantly higher than after THA (OR 1.85, 95% CI 1.6 - 2.14; p < 0.0001). The risk of developing symptomatic DVT after THA was significantly higher than after TKA (OR 2.18, 95% CI 1.11 - 4.27; p = 0.012).

Conclusions

The incidence of DVT in patients undergoing elective TKA appears to have declined in patients receiving warfarin thromboprophylaxis.     

Unprovoked proximal venous thrombosis is associated with an increased risk of asymptomatic pulmonary embolism

Introduction

Pulmonary embolism (PE) is common in patients with deep venous thrombosis (DVT). The outcome of DVT with concomitant symptomatic PE is worse than the outcome of isolated DVT. The risk factors for DVT and simultaneous asymptomatic PE have not been systematically studied yet.

Aim

To evaluate the frequency and risk factors for asymptomatic PE in patients with DVT.

Patients/methods

In 155 consecutive patients with a first episode of DVT and no PE symptoms, a ventilation-perfusion lung scan was performed. Body mass index (BMI) and waist-to-hip ratio (WHR) were calculated and concentrations of D-dimer, high-sensitivity CRP (hsCRP), tissue plasminogen activator (t-PA) and troponin were measured. Laboratory tests for thrombophilia were performed.

Results

Asymptomatic PE was present in 36% of patients. No differences in gender, age, BMI and WHR were found between the patients with and without PE. PE was more common in patients with proximal DVT than in those with distal DVT (42% vs. 17%, p < 0.01), and in patients with unprovoked DVT compared to patients with provoked DVT (51% vs. 28%, p < 0.01). The risk of silent PE was the highest in patients with unprovoked proximal DVT (OR, 6.9; 95% CI, 2.3–21.0). Patients with asymptomatic PE had significantly higher values of D-dimer, hsCRP, t-PA and troponin than patients with isolated DVT.

Conclusions

Asymptomatic PE affected more than one third of patients with a first DVT. Unprovoked proximal DVT is the most important risk factor for the occurrence of silent PE.     

Safety of excluding acute pulmonary embolism based on an unlikely clinical probability by the Wells rule and normal D-dimer concentration: A meta-analysis

Introduction

The Wells clinical decision rule (CDR) and D-dimer tests can be used to exclude pulmonary embolism (PE). We performed a meta-analysis to determine the negative predictive value (NPV) of an “unlikely” CDR (≤ 4 points) combined with a normal D-dimer test and the safety of withholding anti-coagulants based on these criteria.

Methods

Prospective studies that withheld anti-coagulant treatment from patients with clinically suspected PE and an “unlikely” CDR in combination with a normal D-dimer concentration without performing further tests were searched for in Medline, Cochrane and Embase. Primary endpoints were the recurrence rate of venous thromboembolism (VTE) and PE-related mortality during 3-months follow-up.

Results

Four studies including 1660 consecutive patients were identified. The pooled incidence of VTE after initial exclusion of acute PE based on an “unlikely” CDR and normal D-dimer was 0.34% (95%CI 0.036-0.96%), resulting in a NPV of 99.7% (95%CI: 99.0-99.9%, random effects-model). The risk for PE related mortality was very low: 1/1660 patients had fatal PE (0.06%, 95%CI 0.0017-0.46%).

Conclusion

Acute PE can be safely excluded in patients with clinically suspected acute PE who have an “unlikely” probability and a negative D-dimer test and anticoagulant treatment can be withheld. There is no need for additional radiological tests in these patients to rule out PE.     

Risk of deep venous thrombosis (DVT) in bedridden or wheelchair-bound multiple sclerosis patients: A prospective study

Background

Multiple sclerosis (MS) often causes progressive loss of mobility, leading to limb paralysis. Venous and lymphatic stasis is a risk condition for venous thromboembolism (VTE). There is, however, no data on the frequency of VTE complicating the progression of MS. The aim of this study was to assess the frequency of deep vein thrombosis (DVT) in patients with late-stage MS attending a neurology center for rehabilitation.

Patients and Methods

A total of 132 patients with MS were enrolled, 87 women and 45 men, mean age 58 ± 11 years. The disease had started on average 18.7 years before; patients reported 9.6 hours bedridden per day or 14.3 hours wheelchair-bound. Only 25 patients reported a residual ability to walk alone or with help. Lower limb edema was present in 113 patients, bilateral in 41 cases. At admission all patients underwent extended compression ultrasonography. Their plasma D-dimer levels were measured. No antithrombotic prophylaxis was given.

Results

DVT was found in 58 patients (43.9%); 32 had a history of VTE. Forty of these patients (69%) had chronic lower limb edema, in 19 cases bilateral. D-dimer levels in the DVT patients were significantly higher than in patients without DVT (553 ± 678 vs. 261 ± 152 ng/mL, p = 0.0112, Mann-Whitney Test). Nearly half the DVT patients (26, 45%) had high D-dimer levels (701 ± 684 ng/mL). Of the 74 patients without DVT, 48 had normal D-dimer (193.37 ± 67.28 ng/mL) and 26 high (387.61 ± 187.42 ng/mL).

Conclusions

The frequency of DVT in late-stage MS may be over 40%. The long history of the disease means the onset of each episode cannot be established with certainty. A number of patients with positive CUS findings had negative D-dimer values, suggesting a VTE event in the past. However, the level of DVT risk in this series should lead physicians to consider the systematic application of long-term preventive measures.     

Low level of factor V is associated with development of deep-vein thrombosis in Japanese patients

Background

Factor V, having two functions (procoagulant and anticoagulant), is a key factor in blood coagulation, and low plasma levels of factor V may be a risk factor for thrombosis.

Objective

The levels of plasma factor V antigen (FV:Ag), and the phospholipid binding capability of Factor V (FV:PL-bound) were evaluated in patients with deep-vein thrombosis (DVT).

Methods

Levels of FV:Ag, and FV:PL-bound were expressed as a percentage of the normal level found in pooled plasma from control subjects. One hundred and twenty-three Japanese patients with deep-vein thrombosis (DVT) were included, with 100 age and sex-matched healthy control subjects.

Results

The FV:Ag, and FV:PL-bound values were significantly lower in DVT patients than in healthy subjects (p < 0.05 and p < 0.005, respectively). Among the 123 patients, 30 for FV:Ag (24.4%), and 32 for FV:PL (26%) had less than the arbitrary cutoff point (set at the 5th percentile of the value for FV:Ag and FV:PL-bound from healthy subjects), and the odds ratios (ORs) were 6.1 (95% confidence interval [CI], 2.3-16.5) and 6.7 (95%CI, 2.5-17.9), respectively. When patients with a deficiency of natural anticoagulants (antithrombin, protein C, and protein S) were excluded from the analysis, the ORs increased for all patients (6.6 for FV:Ag (95%CI, 2.4-18.3) and 7.4 for FV:PL-bound (95%CI, 2.7-20.3). Moreover, twenty-one (17%) of the 123 DVT patients, and 1 (1%) of 100 control subjects had values below the cutoff points for both FV:Ag and FV:PL-bound, and the OR was 21.6 (95%CI, 2.85-163.1).

Conclusions

These results suggest that low levels of factor V are associated with development of DVT, and may be a predictor for DVT.     

Efficacy and safety of enoxaparin in Japanese patients undergoing curative abdominal or pelvic cancer surgery: Results from a multicenter, randomized, open-label study

Background

Enoxaparin sodium (enoxaparin) is used worldwide for the prevention of venous thromboembolism (VTE). Registration trials of enoxaparin have been conducted primarily in Caucasian populations, and its preventive use in Japanese patients has yet to be established. To address this, we evaluated the efficacy and safety of postoperative enoxaparin in Japanese patients undergoing surgery for abdominal cancer.

Methods

This multicenter, open-label study randomized 151 Japanese patients undergoing curative surgery for abdominal cancer to enoxaparin 20 mg twice daily for 14 days, started 24-36 hours after surgery (n = 113) or intermittent pneumatic compression (IPC) as a reference (n = 38). IPC was performed at least once in both groups between randomization and surgery. The primary efficacy endpoint was the incidence of VTE in the modified intention-to-treat (mITT) population. The primary safety outcome was the incidence of any bleeding during treatment and follow-up.

Results

Incidence of VTE was 1.2% (95% CI, 0.03-6.53%) (1/83 patients) in the enoxaparin group and 19.4% (95% CI, 7.45-37.47%) (6/31 patients) in the IPC group. In the safety population, 10/109 patients in the enoxaparin group (9.2%; 95% CI, 4.49-16.23%) and 3/38 patients in the IPC group (7.9%; 95% CI, 1.66-21.38%) experienced a bleeding event. There were no cases of fatal bleeding or bleeding into any critical organ.

Conclusions

These favorable efficacy and safety data support the use of enoxaparin (20 mg twice daily for 14 days started 24-36 hours after surgery) in Japanese patients undergoing abdominal or pelvic cancer surgery.     

The impact of co-morbid conditions on family history of venous thromboembolism in Whites and Blacks

Introduction

Our objectives were to compare the magnitude of family history as a risk factor for venous thromboembolism (VTE) risk between Blacks and Whites, and to assess the impact of co-morbid conditions on familial risk for VTE.

Materials and methods

We used data from the Genetic Attributes Thrombosis Epidemiology (GATE) study, a matched case-control study which enrolled Blacks and Whites aged 18-70 years in Atlanta, Georgia. A total of 1,094 case patients with a deep vein thrombosis (DVT) or pulmonary embolism (PE) and 1,264 control patients were interviewed about their family history.

Results

Family history of VTE was a statistically significant risk factor for VTE among Blacks (odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.0-4.1; P value < 0.0001) and among Whites (OR = 2.7, 95% CI 1.9-3.7; P value < 0.0001); among Blacks and Whites who were obese or had hypertension; among Blacks who had diabetes mellitus or cancer; as well as among males and females, and across all age categories. Family history of VTE increased the risk of VTE among Blacks with cancer by about 6-fold, whereas among Blacks without cancer the increased risk due to a positive family history was about 3-fold; a 2-fold relative difference. In addition, family history was a risk factor for VTE among case patients with DVT only or with PE only. The effect of family history generally was stronger among those with recurrent episodes of VTE compared with a first episode of VTE. For example, family history of any VTE was a strong risk factor among Black females with recurrent VTE compared with Black females with first VTE (OR = 3.9, 95% CI 2.0-7.5; P value < 0.0001).

Conclusion

Our study indicated that the adjusted attributable fraction for VTE was 16.9% among Blacks vs. 18.3% among Whites, and certain co-morbid conditions could further increase the risk of VTE associated with a positive family history of VTE.     

Outpatient management of acute deep vein thrombosis: results from the OTIS-DVT registry

Objectives

We aimed to investigate clinical practice patterns for the outpatient management of acute deep vein thrombosis (DVT).

Methods

In the prospective Outpatient Treatment of Deep Vein Thrombosis in Switzerland (OTIS-DVT) registry, 534 consecutive outpatients with acute DVT (49% proximal, 24% recurrent, and 12% cancer-associated) were enrolled: 41% patients were managed in private angiology practice, 34% in an outpatient hospital department, and 25% in private general or internal medicine practice.

Results

For diagnosis, ultrasound was used in 95% and D-dimer testing in 53%. Low-molecular-weight heparin (LMWH) was prescribed for a median (IQR) duration of 7 (5-12) days in 83% of patients, and vitamin K-antagonists for 163 (92-183) days in 81%. Mechanical measures to prevent post-thrombotic syndrome were prescribed in 83%; compression stockings or bandages for a median (IQR) duration of 364 (101-730) days from hospital physicians, and 92 (45-183) days from private practice physicians (p < 0.001). Among patients with symptomatic proximal DVT, mechanical measures were prescribed for at least 2 years in 24% patients; 55% in hospital, and 6% in private practice (p < 0.001). Among patients with cancer-associated DVT, the median (IQR) duration of LMWH therapy was 16 (8-45) days, and 35% received LMWH for less than 90 days.

Conclusions

The OTIS-DVT registry provides representative information on clinical practice patterns for outpatients with acute DVT managed by hospital or private practice physicians. The use of mechanical measures in patients with symptomatic proximal DVT and the administration of LMWH for a long-term therapy of cancer-associated DVT require improvement to comply with current guidelines.     

Accuracy and safety of (99m)Tc-labeled anti-D-dimer (DI-80B3) Fab' fragments (ThromboView®) in the diagnosis of deep vein thrombosis: A phase II study

Background

The assessment of patients with suspected deep vein thrombosis (DVT) remains challenging despite current diagnostic algorithms. ^99mTc-labelled DI-DD3B6/22-80B3 Fab´ fragments (^99mTc-DI-80B3, ThromboView®) is a novel diagnostic test that uses a radiolabelled humanized monoclonal antibody fragment specific for the D-dimer region of cross-linked fibrin to detect DVT. This test has an anatomic component to locate DVT and a functional component to differentiate acute (newly formed) thrombus from inactive (old) thrombus.

Methods

In a multi-centre prospective cohort trial we investigated the diagnostic accuracy and safety of ^99mTc-DI-80B3 in consecutive patients with suspected DVT who had the diagnosis confirmed or excluded by venography.

Results

We enrolled 94 patients with suspected DVT of whom 12 did not have ^99mTc-DI-80B3 imaging, leaving 82 patients for the safety analysis. Of these patients, there were 16 with non-evaluable imaging (11 venography, 7 ^99mTc-DI-80B3, both in two patients) leaving 66 patients for the accuracy analysis. ^99mTc-DI-80B3 imaging was well-tolerated: 2 patients developed urticaria; none developed serious adverse events. For proximal DVT, the sensitivity (84.2%; 95% confidence interval [CI]: 62.4-94.5) and specificity (97.6%; CI: 83.3-99.4) were highest when the combined 0.25-hour and 3-hour ^99mTc-DI-80B3 images were used. The accuracy was lower for distal DVT, irrespective of the images used. There were insufficient patients to comment on the accuracy of ^99mTc-DI-80B3 imaging for suspected recurrent DVT.

Conclusions

^99mTc-DI-80B3 (ThromboView®) is a novel diagnostic modality for patients with suspected DVT with a promising accuracy and safety profile that justifies additional clinical development in diagnostic accuracy and clinical management studies.     

Comparison of the clinical usefulness of two quantitative D-Dimer tests in patients with a low clinical probability of pulmonary embolism

Background

Quantitative D-Dimer tests are established methods in the non-invasive diagnostic management to rule out venous thromboembolism (VTE). The diagnostic performance and the clinical efficiency different D-Dimer assays in the exclusion of pulmonary embolism (PE) have not yet been compared in a clinical outcome study.

Objective

Evaluation of the efficiency and safety of excluding the diagnosis of PE with two different quantitative D-Dimer assays in consecutive patients with clinically suspected PE.

Patients and Methods

We studied the VTE-failure rate of 2206 consecutive patients with an unlikely clinical probability in whom VIDAS or Tinaquant D-Dimer tests were performed.

Results

The prevalence of PE in 1238 patients whose D-Dimer level was analyzed with Tinaquant assay was 11%. The VIDAS assay group consisted of 968 patients with a PE prevalence of 13%. The VIDAS assay had a sensitivity of 99.2% (95%CI; 96- > 99.9%), the Tinaquant assay of 97.3% (95%CI; 93 -99%). The negative predictive value (NPV) in the Tinaquant assay group was 99.4% (95%CI 98-99.8%) in comparison to 99.7% (95%CI 99-> 99.9%) in the VIDAS assay group. During 3 month of follow-up, there were no fatal cases of PE among patients with normal D-Dimer and unlikely clinical probability in both D-Dimer assay groups. In addition, the test efficiency of Tinaquant assay was significantly higher in comparison to VIDAS assay (52% vs 42%, p < 0.001).

Conclusion

Both Tinaquant and VIDAS D-Dimer tests perform equally well in combination with an unlikely clinical probability in excluding PE. The Tinaquant test was shown to be more efficient.     

Incidence and time course of asymptomatic deep vein thrombosis with fondaparinux in patients undergoing total joint arthroplasty

Introduction

There are many reports concerning fondaparinux prophylaxis of asymptomatic deep vein thrombosis (DVT) after total hip arthroplasty (THA) or total knee arthroplasty (TKA), but little is known about the time course of aymptomatic DVT development during the administration of fondaparinux. The aim of the present study was to define the incidence and time course of aymptomatic DVT development during administration of fondaparinux, and to assess the efficacy of fondaparinux in resolving DVT.

Materials and Methods

We studied consecutive71 patients who underwent THA surgery, and 30 patients who underwent TKA surgery with fondaparinux prophylaxis. Patients received once-daily subcutaneous injections of 2.5 mg of fondaparinux for 14 days after surgery. DVT was diagnosed by ultrasonography, and it was scheduled on the day of surgery on day 1, day 4, and day 14 after surgery.

Results

In patients who received fondaparinux for 14 days after THA surgery, the incidence of DVT was 0% on the day of the surgery, 13.6% at day 1, 27.1% at day 4, and 11.9% at day 14. In patients who received fondaparinux for 14 days after TKA surgery, the incidence of DVT was 4.2% on the day after surgery, 50.0% at day 1, 58.3% at day 4, and 20.8% at day 14. The incidence of DVT after THA or TKA surgery at day 14 was significantly reduced compared to that at day 4.

Conclusion

The incidence of asymptomatic DVT up to day 4 was high, but with 14 days continued treatment of fondaparinux, the incidence of asymptomatic DVT occurring at postoperative day 4 was significantly reduced at day 14.     

Combined use of clinical pre-test probability and D-dimer test in the diagnosis of preoperative deep venous thrombosis in colorectal cancer patients

The preoperative prevalence of deep venous thrombosis (DVT) in patients with colorectal cancer may be as high as 8%. In order to minimize the risk of pulmonary embolism, it is important to rule out preoperative DVT. A large study has confirmed that a negative D-dimer test in combination with a low clinical pre-test probability (PTP) can be safely used to rule out the tentative diagnosis of DVT in cancer patients. However, the accuracy in colorectal cancer patients is uncertain. This study assessed the diagnostic accuracy of a quantitative D-dimer assay in combination with the PTP score in ruling out preoperative DVT in colorectal cancer patients admitted for surgery. Preoperative D-dimer test and compression ultrasonography for DVT were performed in 193 consecutive patients with newly diagnosed colorectal cancer. Diagnostic accuracy indices of the D-dimer test were assessed according to the PTP score. The negative predictive value, positive predictive value, sensitivity and specificity were 99% (95% confidence interval (CI), 95-100%), 17% (95% CI, 9-26), 93% (95% CI, 68-100%) and 61% (95% CI, 53-68%), respectively. In conclusion, the combined use of pre-test probability and D-dimer test may be useful in ruling out preoperative DVT in colorectal cancer patients admitted for surgery.     

Pleural ELFA D-dimer assay: a surrogate marker for malignant pleural effusion

Background

Malignant pleural effusion is associated with enhanced fibrinolysis. However, no data are available concerning the precise role of pleural D-dimer assay in pleural effusion. We therefore assessed the role of pleural D-dimer assay in predicting malignant pleural effusion.

Patients and Methods

A prospective laboratory investigation was conducted in a tertiary care teaching hospital. The study included consecutive patients with pleural effusion who presented at the Pulmonary Department between November 2009 and May 2010. Blood and pleural D-dimer levels were measured by Enzyme Linked Fluorescent assay (ELFA). The results were correlated with the clinical, laboratory, and radiological findings, and with the final diagnosis of the pleural fluid.

Results

A total of 103 patients with pleural effusion were included in the study. The Pleural ELFA D-dimer results were found to be positively correlated with pleural etiology of malignancy (p = 0.0001). Pleural etiology was also correlated with pleural LDH, pleural protein, pleural PH, pleural glucose, pleural and blood CRP, but not with ADA. In a binary logistic regression, only the pleural ELFA D-dimer assay was a significant predictor of the malignant pleural effusion (odds ratio 1.007; 95% confidence interval 1.002-1.012; p = 0.007). The area under the receiver operating characteristics curve for malignancy was 0.79. A D-dimer level of 146 mg/ml had a sensitivity of 82% and a specificity of 74%.

Conclusions

We found high D-dimer levels among malignant pleural effusion. D-dimer might be useful as a simple, noninvasive, surrogate marker for malignant pleural effusion.     

Risk of deep vein thrombosis in patients with cellulitis and erysipelas : A systematic review and meta-analysis

Introduction

The occurrence of deep vein thrombosis (DVT) is often considered in patients with cellulitis and erysipelas because of the common presentation of unilateral limb swelling, erythema and pain. Different authors however have reached different conclusions about the prevalence of DVT in these patients and for the need for compression ultrasound (CUS). The purpose of this study is to determine the prevalence of DVT in patients with cellulitis and erysipelas, and inform the utility of CUS.

Methods

A systematic literature search was conducted of Medline and Cochrane for studies that reported groups of patients with cellulitis or erysipelas who had CUS to evaluate for DVT. Study quality assessment was based on the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies. The incidence rates from the included studies were pooled using a random-effects model to calculate an overall DVT rate. Individual and pooled DVT rates with corresponding upper and lower limits were graphed as a forest plot. Between-study heterogeneity was estimated using the I² statistic.

Results

Nine studies were included totaling 1054 patients with cellulitis or erysipelas with 18 DVTs. The overall pooled incidence rate was 2.1% (95% confidence interval, 0.5%-9.1%) for proximal DVT and 3.1% (95% confidence interval, 1.9%-4.9%) for any DVT. When analyzed separately, the pooled incidence rate for the three retrospective studies was 1.1% (95% CI, 0.6%-2.2%), while the rate for the six prospective studies was 7.8% (95% CI, 4.2%-14.2%).

Conclusion

The risk of DVT in cellulitis and erysipelas is low compared to the average risk of patients referred for CUS and comparable to low risk patients as determined by the commonly employed Wells criteria.