Difference In Incidence Of Venous Thromboembolism Research Articles

Thromboprophylaxis in gynecologic cancer surgery: Is extended prophylaxis with low molecular weight heparin justified?

ObjectiveEvidence on the optimal duration of thromboprophylaxis with low molecular weight heparin after gynecologic cancer surgery is scarce and the benefits of extended prophylaxis have not been validated specifically in these patients. The aim of this study is to assess the efficacy and safety of postoperative venous thromboembolism (VTE) prophylaxis with enoxaparin 40 mg for 28 days, as recommended by international guidelines, compared to 7 days in patients undergoing surgery for gynecologic cancer. Study designProspective cohort study compared to a historic cohort of women who underwent surgery for gynecologic cancer in our center between 2004 and 2014. Pre- and postoperative screening with a routine duplex scan was done in the prospective cohort. Comparative analysis of comorbidity, surgical technique and incidence of VTE, as well as prognostic factors of events and mortality. ResultsN:571 patients (28 days: 207, 7 days: 364). No significant differences were identified between groups in regard to the factors related to VTE in our series. There were no differences in VTE incidence between groups after one month (1.9% vs 1.4%; p = 0.729), 90 days (2.4% vs 2.5%; p > 0.99) or during follow-up (Breslow p = 0.156). No deaths due to VTE at 90 days were recorded. Only one case of asymptomatic DVT was identified in the screening with duplex. The incidence of postoperative bleeding was similar in both groups (0.5% vs 2.2%; p = 0.166). The presence of a history of VTE was the only independent risk factor for VTE after one month (OR 14.31 CI 95% 2.67–76.87; p = 0.002) and 90 days (OR 8.27 CI 95% 1.65–41.45; p = 0.010). No differences were identified regarding age, other comorbidities, type of tumor, stage, surgical approach, reintervention or adjuvant therapy in the multivariate analysis. ConclusionExtended prophylaxis for 28 days with enoxaparin did not improve the rates of VTE following gynecologic oncological surgery in our series compared to the 7-day therapy, although neither was this extended duration associated with adverse events or mortality.

The Influence of Race on Plasma Thrombin Generation In Healthy Subjects In Singapore.

Race is touted as an independent risk factor for venous thromboembolism (VTE), although the basis for this is varied and contentious. Comparison of plasma thrombin generation (TG) using calibrated automated thrombogram (CAT) across races offers a modality that objectively measures global hemostatic function to evaluate this influence. Direct comparative data across races are currently not available. Aim is to establish the influence of race on plasma TG. Sixty normal participants, matched for age and gender, equally representing 4 races—Caucasian, Chinese, Indian, and Malay—were recruited. Thrombin generation parameters (lag time, time to peak, peak, and endogenous thrombin potential [ETP]) in platelet-poor plasma were measured using CAT. The mean ETP (standard deviation) for the different races were Caucasians: 1338.18 (194.19) nM·min; Chinese, 1318.91 (108.90) nM·min; Indians, 1389.81 (182.61) nM·min; and Malays, 1436.21 (184.24) nM·min. Caucasians had the longest mean lag time of 2.59 ± 0.37 seconds; Indians had the highest mean peak of 284.22 ± 30.74 nM, and Malays had the longest mean time to peak of 5.47 ± 0.59 seconds. Analysis based on race did not demonstrate any significant difference for all TG parameters. The greatest mean difference of ETP between any 2 races (Malays and Chinese) was 117.30 nM·min (95% confidence interval: −45.86 to 280.46 nM·min) which was within the predefined limit of equivalence. In a cohort of healthy participants, TG mediated by plasma factors is not influenced by race and does not explain the reported racial differences in VTE incidence. For the 4 racial groups studied, the use of separate normal ranges for plasma TG might not be essential.

Relation of antifactor-Xa peak levels and venous thromboembolism after trauma.

No previous studies have established the optimal antifactor Xa (anti-Xa) level to guide thromboprophylaxis (TPX) dosing with enoxaparin in trauma patients. We hypothesize that achieving 0.2-0.4 IU/mL anti-Xa will decrease venous thromboembolism (VTE) rates after trauma. This was a retrospective review of 194 intensive care unit patients sustaining blunt or penetrating trauma from January 2015 to March 2017. All received initial enoxaparin (30 mg BID subcutaneous) and mechanical devices for TPX. Peak anti-Xa levels were drawn after each third dose. The enoxaparin dose was adjusted up to a maximum of 60 mg BID subcutaneous until a peak level of 0.2-0.4 IU/mL was achieved. Data are expressed as mean ± SD if parametric or median (IQR) if not. The Greenfield Risk Assessment Profile score was 9 ± 4, Injury Severity Score 23 ± 14, and hospital length of stay 19 (11-38) days. The overall VTE rate was 7.2% (n = 14), with 10 deep venous thromboses (DVT) and 5 pulmonary emboli (PE). One patient had both a DVT and PE. The median time to VTE diagnosis was 14 (7-17) days. In those diagnosed with a VTE, 50.0% (n = 7) never reached 0.2-0.4 IU/mL anti-Xa and 42.8% (n = 6) were diagnosed with a VTE after achieving these levels. Prophylactic levels were achieved initially in 64 (33.0%) patients, and achieved later in 38 (19.6%) additional patients, giving an overall prophylactic rate of 52.6% (n = 102). There were no differences in VTE (6.9% vs. 7.6%, p = 0.841), DVT (3.9% vs. 6.5%, p = 0.413), or PE (3.9% vs. 1.1%, p = 0.213) rates between those who became prophylactic and those who did not. There was no difference in VTE incidence between those achieving anti-Xa peak levels of 0.2-0.4 IU/mL and those who did not. Furthermore, these levels were never achieved in some trauma patients despite repeated dosing over a >10-day period. Therapeutic study, level IV.

Efficacy of standard dose unfractionated heparin for venous thromboembolism prophylaxis in morbidly obese and non-morbidly obese critically Ill patients.

To determine the efficacy of standard dose unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis in critically ill morbidly obese patients. Retrospective single-center observational cohort study in a single tertiary teaching hospital intensive care units (ICUs) in Multiparameter Intelligent Monitoring in Intensive Care II Clinical Database. Patients 18years or older, admitted to the ICU, and received either UFH 5000 units subcutaneously twice daily or UFH 5000 units three times daily for VTE prophylaxis between 2001 and 2008 were included. Total 243 patients in the BMI ≥ 40kg/m2 group and 2813 patients in the BMI < 40kg/m2 group were identified. There was no difference in VTE incidence between the two groups. However, a strong linear association was found showing as BMI increased so did the rate of VTE incidence. Morbidly obese patients had longer hospital (17 vs. 14 days, P = 0.016) and ICU length of stay (10 vs. 8 days, P = 0.007). After controlling Padua score, logistic regression analysis revealed the odds of VTE increased by a factor of 1.026 for each one-unit increase in BMI. Additionally, having a BMI ≥ 40kg/m2 was associated with a greater likelihood of VTE incidence in males (OR 3.92) but not in females. In patients treated with standard dose UFH, morbid obesity does not increase VTE risk overall. However, BMI has a strong linear relationship with VTE incidence and morbid obesity is more likely associated with greater hospital and ICU length of stay.

Prophylactic anticoagulation to benefit younger patients under 65 years of age with metastatic lung cancer: An analysis of the 2013 Healthcare Cost and Utilization Project (HCUP) data.

6581 Background: Cancer patients have increased risk of venous thromboses. Venous thromboembolism (VTE) is reported to be a leading cause of death in cancer patients. It has been hypothesized that prophylactic anticoagulation for VTE might improve prognosis and quality of life. Based on our analysis of the 2013 HCUP data, we propose that prophylactic anticoagulation should be considered for patients younger than 65 years with metastatic lung cancer. Methods: Patients were selected using ICD-9 diagnoses codes for metastatic lung cancer and VTE. Diagnoses were stratified by site including upper extremity, lower extremity, pulmonary, abdominal and nonpulmonary thoracic VTE. Patients were stratified by age, sex, race and ethnicity. Differences in incidence of VTE among groups were calculated by the Chi-Square method using the SAS software. Results: There were a total of 16,577 VTE events amongst 182,863 cases of metastatic lung cancer. Subgroup analyses showed that patients younger than 65 years of age had 356.82 more PE events per 100,000 individuals compared to those at or older than 65 years (p &lt; 0.0001). The same age group also showed 374.83 more UE, 286.94 more nonpulmonary thoracic and 263.97 more abdominal (Abd) VTE events per 100,000 individuals (p-values, p &lt; 0.0001). There was no statistically significant difference in the incidence of LE VTE’s between the subgroups. Conclusions: Prophylactic anticoagulation should be considered in patients &lt; 65 years of age with metastatic lung cancer. Increased incidence of VTE in these patients may contribute towards greater morbidity and mortality associated with metastatic lung cancer in this subgroup. [Table: see text]

Risk Stratification for the Development of Venous Thromboembolism in Hospitalized Patients with Cancer

Introduction: No method of venous thromboembolism (VTE) risk stratification exists for hospitalized cancer patients. The Khorana score is a validated tool in outpatients with cancer. The objective of this study was to assess the Khorana score for predicting development of VTE in cancer patients during admission to hospital.Methods: We conducted a retrospective analysis of data collected from healthcare records of consecutive, medically-ill cancer patients hospitalized between January and June 2010 in 3 academic medical centers in Canada. Objectively diagnosed symptomatic VTE during hospitalization, anticoagulant thromboprophylaxis (TP), and Khorana score variables were collected for every patient. Patients receiving therapeutic anticoagulation at admission, and those with incomplete data were excluded. The risk of VTE based on Khorana score category was evaluated using logistic regression. Continuous data were compared using a Student's t-test and expressed using the means and standard deviations. Categorical data were compared using the Pearson Chi-square test and were expressed as percentages. Statistical significance was defined as alpha less than 0.05.Results: 1398 patients were included. Mean age was 61.6 years, 51.2% were male, and mean BMI was 25.9 kg/m2. The most frequent tumor types were non-small cell lung carcinoma (12.7%) followed by lymphoma (10.9%). The median length of stay was 6 days (range 0-114 days). The most frequent reasons for hospitalization were chemotherapy (22.3%) followed by pain and palliation (21.4%). 34.5% received anticoagulant TP (n = 483/1398). The incidence of VTE was 2.9% (41/1398) overall, 5.4% (9/166) in high, 3.2% (26/817) in moderate, and 1.4% (6/415) in low Khorana score risk groups. High risk patients were significantly more likely than low risk patients to have VTE (p=0.016; OR 3.9, 95% CI 1.4-11.2). There was no difference in VTE incidence between patients who received anticoagulant TP and those who did not (3.5% vs 2.6%, p = 0.345). Patients with high risk Khorana score were more likely to receive anticoagulant TP than those with low risk Khorana score (46.4% vs. 23.9%, p <0.001, OR 2.8, 95% CI 1.9-4.0). Total incidence of major bleeding was 1.8% (25/1398). There was no difference in major bleeding between patients who received anticoagulant TP and those who did not (1.7% vs. 1.9%, p = 0.787).Conclusion: The Khorana score is predictive of VTE development in cancer patients who are hospitalized for medical illness and may be a useful tool for tailoring inpatient anticoagulant prophylaxis. DisclosuresLee:LEO: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; Bristol Myers-Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria. Carrier:BMS: Research Funding; Leo Pharma: Research Funding. Wu:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Leo Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Thromboelastography to Detect Hypercoagulability in Patients with Newly Diagnosed Acute Lymphoblastic Leukemia

Background: Patients with newly diagnosed acute lymphoblastic leukemia (ALL) are known to be hypercoagulable due to their disease and from side effects of chemotherapy. Studies have shown rates of venous thromboembolism (VTE) between 5-70% in patients with ALL (depending on various definitions and modalities of investigation) (Caruso et al, 2006, Mitchell et al, 2003). Established methods to monitor hypercoagulability or predict VTE do not exist. We have previously described methods using thromboelastography (TEG) to detect hypercoagulability (Ko et al., 2013). We believe that a global assay of hemostasis such as TEG holds promise to monitor hypercoagulability in patients with newly diagnosed ALL.Methods: This was a prospective study of newly diagnosed ALL patients between 1-21 years in whom a central venous catheter (either a peripherally inserted central catheter [PICC] or a subcutaneously implanted port) was placed at diagnosis. Patients were enrolled at Children's Hospital Los Angeles from September 2012 until July 2015. None of the patients had a known past medical or family history of thrombosis or bleeding or clotting disorders and none were taking any medications (other than induction chemotherapy) that could affect coagulation (e.g. NSAIDs). Patients had complete blood counts (CBC), TEG, and markers of thrombin generation (quantitative D-dimers, thrombin:antithrombin complexes, and prothrombin fragment 1.2) performed before initiation of treatment and then once weekly during induction until they either presented with a symptomatic VTE or completed Induction therapy. All patients had a Doppler ultrasound of the extremity in which their central venous catheter was placed at the end of induction or at presentation with symptoms suggesting thrombosis.Results: Eighty patients have been enrolled (see Table 1 for demographics) with 72 being fully evaluable currently. Three (4.3%) patients developed symptomatic VTE and 7 (15%) patients had an asymptomatic VTE for an overall incidence of VTE of 21.7%. We demonstrate that R time gradually increases over time from baseline during induction therapy. Additionally, maximum amplitude (MA) is initially diminished, but then increases with time. There were no statistically significant differences in VTE incidence between males and females, different age groups (though there was a trend towards increased incidence for older children), or CVC type (none of the patients with an implanted port had a VTE). Interestingly, MA did not seem to be associated with platelet count.Conclusion: Patients in this prospective study of patients with newly diagnosed ALL during induction at a single institution show rates of thrombosis in patients with ALL similar to that in the literature. Furthermore, TEG results demonstrated a shortening of the clotting time (R) and an increase in the clot rigidity (MA) during induction. Though not statistically significant, older children and patients with HR-ALL were more likely to have a VTE. Additional analyses will be performed to investigate the ability of the TEG, as well as the CBC and markers of thrombin generation, in predicting the development of VTE in these patients.Table 1Patient DemographicsPatient DemographicsGenderFemale33 (46%)Male38 (54%)Age< 5 years28 (39%)9-12 years26 (37%)10+ years17 (24%)Patient VTE classificationSymptomatic VTE3 (4%)Asymptomatic VTE12 (17%)No VTE56 (79%)Demographics by CVC TypeType of CVCPICCPort-a-CathTotalGenderFemale35 (45%)3 (100%)38 (48%)Male42 (55%)0 (0%)42 (53%)Age< 5 years29 (38%)2 (67%)31 (39%)9-12 years30 (39%)0 (0%)30 (38%)10+ years18 (23%)1 (33%)19 (24%)Type of ALLSR-ALL54 (70%)0 (0%)54 (68%)HR-ALL23 (30%)2 (67%)25 (31%)T-ALL0 (0%)1 (33%)1 (1%)Patient VTE classificationSymptomatic VTE3 (4%)0 (0%)3 (4%)Asymptomatic VTE12 (17%)0 (0%)12 (17%)No VTE54 (78%)2 (100%)56 (79%)Patient VTE classificationDemographics by VTESymptomatic VTEAsymptomatic VTENo VTETotalGenderFemale1 (33%)7 (58%)25 (45%)33 (46%)Male2 (67%)5 (42%)31 (55%)38 (54%)Age categories< 5 years1 (33%)4 (33%)23 (41%)28 (39%)9-12 years0 (0%)3 (25%)23 (41%)26 (37%)10+ years2 (67%)5 (42%)10 (18%)17 (24%)Type of ALLSR-ALL1 (33%)7 (58%)39 (70%)47 (66%)HR-ALL2 (67%)5 (42%)16 (29%)23 (32%)T-ALL0 (0%)0 (0%)1 (2%)1 (1%) [Display omitted] [Display omitted] DisclosuresKo:Alexion: Honoraria; NovoNordisk: Consultancy. Young:Bayer: Consultancy; Kedrion: Consultancy; Novo Nordisk: Consultancy, Honoraria; Baxter: Consultancy; Biogen Idec: Consultancy, Honoraria.

Epidural placement does not result in an increased incidence of venous thromboembolism in combat-wounded patients.

Patient-controlled epidural analgesia (PCEA) decreases the amount of systemic opioid required for adequate analgesia and decreases the rate of opioid-induced adverse effects. Given the location of catheters required to deliver analgesics and the potential for epidural hematoma, the American Society of Regional Anesthesia and Pain Medicine recommends modification of the standard trauma venous thromboembolism (VTE) prophylaxis regimen of enoxaparin 30 mg twice daily to 40 mg daily. The objective of this retrospective study was to determine if 40-mg daily dosing would increase the incidence of VTE. With institutional review board approval, records of all combat casualties admitted to our institution between November 2010 and November 2012 were reviewed for demographics, VTE prophylaxis regimen, PCEA days, and incidence of VTE. Patients who arrived without VTE were the study cohort. Rates of VTE were compared between PCEA and no-PCEA groups. Variables were analyzed with Mann-Whitney U-test, Pearson's χ test, and Fisher's exact test. A p ≤ 0.05 was considered significant. Data are expressed as median (interquartile range). A total of 565 records were reviewed; 484 met inclusion criteria; and 181 patients (37.4%) had PCEA for 13 days (6-25 days). Age and sex were similar between the groups. PCEA patients were more often injured by dismounted improvised explosive devices (75.1% vs. 39.3%, p < 0.001), had longer hospital stays (38 days vs. 17 days, p < 0.001), had higher Injury Severity Score (ISS) (14 vs. 12, p = 0.033), and were more likely to have an amputation (66.1% vs. 20.4%, p < 0.001). Twenty-three PCEA patients (12.7%) developed VTE versus 32 no-PCEA patients (10.6%) (p = 0.464). Eleven VTE events (47.8%) occurred with the catheter in place, while 12 VTE events (52.2%) occurred 6 days (2-15 days) after removal. Although PCEA catheters were more often placed in patients prone to VTE, there was no difference in incidence of VTE with their use. These data suggest that enoxaparin 40 mg daily in patients with PCEA is not inferior to 30 mg twice daily for VTE prophylaxis in combat-wounded patients. Therapeutic study, level IV.

The Incidence of Venous Thromboembolism in Breast Reconstruction and the Efficacy of Current Prediction Models

INTRODUCTION: Venous thromboembolism (VTE) is a source of significant morbidity and mortality in surgical patients. Prediction models have been developed to determine VTE risk in plastic surgery patients including the Davison risk score1 and the 2005 Caprini risk score2. This retrospective study evaluates the incidence of symptomatic VTE in breast reconstruction and the efficacy of current models in predicting VTE in different methods of breast reconstruction. METHODS: Breast reconstruction patients by a single surgeon were retrospectively evaluated. One hundred consecutive TRAM reconstructions, one hundred consecutive implant reconstructions, and fifty consecutive latissimus reconstructions were identified. These surgical reconstructions all took place over a ten year period in which VTE chemoprophylaxis was not routinely performed. Each patient’s chart was reviewed for the parameters needed to calculate the 2005 Caprini risk score and the Davison risk score. Outpatient follow up, operative notes, and other procedures were also reviewed. Fisher’s exact test was used to calculate differences in VTE incidence and risk factor incidence. ANOVA test was used to compare mean risk scores between the reconstruction groups. RESULTS: The TRAM reconstruction group had a significantly higher VTE rate (6%) than the implant (0%) or the latissimus (0%) reconstruction groups (p<0.01). There was no significant difference (p>0.05) in the 2005 Caprini risk scores or the Davison risk scores between the TRAM, implant, and latissimus reconstruction groups (Figure 1). The Davison risk score and the 2005 Caprini score stratified the majority of patients as “high risk” with a calculated risk score ≥5 (Davison score 64.8%, 2005 Caprini score 86%). Interestingly, the VTE rate among “high risk” patients in each group was not statistically different from the overall VTE rate of each reconstruction group (p>0.05).Figure 1: Mean 2005 Caprini risk score and mean Davison risk score by breast reconstruction type. (p>0.05).CONCLUSION: TRAM reconstruction is associated with a higher VTE rate than both implant reconstruction and latissimus reconstruction. Implant and latissimus reconstruction patients appear at low risk for VTE even in the presence of many “high risk” features. Overall, neither the 2005 Caprini risk score nor the Davison risk score demonstrated effective VTE risk stratification in breast reconstruction patients. Current and future VTE prediction models should take into account the specific surgical procedure to more accurately determine VTE risk.

Randomized, Double-Blind, Multi-Dose Efficacy, Safety and Biomarker Study of the Oral Factor Xa Inhibitor DU-176b Compared with Placebo for Prevention of Venous Thromboembolism in Patients after Total Knee Arthroplasty

Introduction: The objectives of this study were to assess the safety, efficacy and dose-response relationship of DU-176b for the prevention of venous thromboembolism (VTE) in Japanese patients after elective total knee arthroplasty (TKA). Changes in biomarkers in relation to VTE and bleeding were also evaluated.Methods: This was a randomized, parallel-group, placebo-controlled, double-blind, doubledummy, multicenter study. DU-176b (5–60 mg QD) or placebo was administered for 11–14 days after TKA. A placebo control was used because at the time no other anticoagulants had been approved for thromboprophylaxis after TKA in Japan. The primary efficacy endpoint included the adjudicated incidence of VTE, including asymptomatic and symptomatic deep vein thrombosis, as evaluated by venograms, and symptomatic pulmonary embolism. The primary safety endpoint included major and clinically relevant bleeding. Secondary efficacy endpoints included the pharmacodynamic (PD) indices prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), anti-FXa activity and key coagulation biomarkers including prothrombin fragment F1+2, plasmin-α2-plasmin inhibitor complex (PIC), D-dimer, thrombin-antithrombin III complex and soluble fibrin. Secondary safety endpoints included incidence of adverse events (AEs).Results: There were no clinically relevant differences in baseline demographics of the 523 patients randomized. Mean age was 71.1 ± 7.6 years, mean weight was 60.3 ± 9.9 kg and ~78% of patients were female. All DU-176b doses had significantly less VTE than placebo when each DU-176b dose group was compared with placebo (Table), and there was a dose-related response (P <0.001 across DU-176b dose). Paired comparisons showed no significant differences in VTE incidence between the 5 & 15 mg groups or between the 30 & 60 mg groups but significant differences between other paired groups (χ2 test; P<0.001 to P=0.021). PD indices were dose-related (Table, P <0.001 across DU-176b dose). After surgery, coagulation biomarkers increased with a trend for DU-176b to affect these markers more than placebo (Table, P <0.001 across DU-176b dose). The incidence of major and clinically relevant bleeding was comparable across all groups without any significant differences among groups or between DU-176b doses and placebo (Table). There were no trends in other AEs, including liver enzymes, across DU-176b dose.Conclusions: DU-176b demonstrated significant, dose-dependent reductions in VTE after TKA without increases in major or clinically relevant bleeding. There were also consistent dose-dependent changes in PD indices and coagulation biomarkers. The observed dose-dependent decreases in VTE without concomitant increases in bleeding should be further evaluated.PlaceboDU-176b 5 mgDU-176b 15 mgDU-176b 30 mgDU-176b 60 mgPrimary Efficacy Endpoint: VTEn/N (%) (95% CI)43/89 (48.3) (37.9–58.7)26/88 (29.5)* (20.0–39.1)24/92 (26.1)** (17.1–35.1)11/88 (12.5)** 5.6–19.4)8/88 (9.1)** (3.1–15.1)Primary Safety Endpoint: % Major + Clinically Relevant bleedingn/N (%)4/102 (3.9)3/103 (2.9)†5/106 (4.7)‡4/103 (3.9)‡5/106 (4.7)‡PD and Coagulation Biomarkers, all data mean ± SD post-operation/pre-treatment initiation 1–3 h post-dose Day 7N87869187878686898787PT (sec)13.5±0.913.3±0.813.3±0.713.4±0.913.1±0.612.7±0.613.3±0.8**14.9±1.5**17.8±2.7**22.1±5.9**anti-FXa activity (IU/mL)0.10±0.00.10±0.00.10±0.00.13±0.230.10±0.00.10±0.00.44±0.80**1.18±0.68**2.40±1.17**4.38±2.56**Prothrombin fragment F1+2, pM479.6±229.7431.4±257.5468.7±249.0428.9±269.0417.9±223.6588.9±228.9484.6±184.9*450.8±158.2**414.0±172.8**398.8±147.4**D-dimer μg/mL12.4±10.513.6±10.514.3±11.212.2±10.311.4±10.19.4±5.77.5±3.76.7±2.7**6.5±3.3**5.8±2.4***P<0.01, **P<0.001, †P=0.445, ‡P=1.00 vs placebo.

The Importance of Clinical Probability Assessment in Interpreting a Normal d-Dimer in Patients With Suspected Pulmonary Embolism

The d-dimer test is widely applied in the diagnostic workup of patients with suspected pulmonary embolism (PE). The objective of this study was to investigate how often the d-dimer test fails when clinical probability is not taken into account. We used data collected in 1,722 consecutive patients with clinically suspected PE to analyze the 3-month venous thromboembolism (VTE) rate in all patients with a normal d-dimer concentration and separately for patients who have a normal d-dimer concentration with an unlikely or likely clinical probability for PE, as assessed by the Wells clinical decision rule. The 3-month VTE rate in all patients with a normal d-dimer concentration (n = 563) was 2.3% (95% confidence interval [CI], 1.4 to 3.9%). In the patients with an unlikely probability of PE (n = 477), VTE was confirmed in 1.1% of the patients with a normal d-dimer concentration (95% CI, 0.4 to 2.4%). In those patients with a likely clinical probability of PE (n = 86), VTE was confirmed in 9.3% of the patients with a normal d-dimer concentration (95% CI, 4.8 to 17.3%). The difference in VTE incidence between patients with unlikely and likely clinical probabilities of PE was significant (p < 0.001). Our findings indicate that it is of utmost importance to first examine the patient and assess the clinical probability, after which the d-dimer concentration can be taken into account, in order to prevent physicians from being influenced by a normal d-dimer test result when they evaluate the clinical probability of PE. Patients with a likely clinical probability should undergo further testing, regardless of the d-dimer test outcome.

The effects of race/ethnicity and sex on the risk of venous thromboembolism

Recently, studies on large diverse populations have described important ethnic/racial differences in venous thromboembolism incidence, and sex has been reported as an important predictor of recurrence. We review the influence of race/ethnicity and sex on venous thromboembolism, concentrating on articles from 2005 to 2007. Most studies found that women have a 40-400% lower risk of recurrent venous thromboembolism than men. Studies of ethnicity/race on risk provide strong evidence that African-American patients are the highest risk group for first-time venous thromboembolism, while Hispanic patients' risk is about half that of Caucasians. African-Americans and Hispanics have a higher risk of recurrence than Caucasians, but sex and the type of index venous thromboembolism event seem to play a role in this risk. Asian/Pacific Islanders have a markedly lower risk of first-time and cancer-associated venous thromboembolism. There is little difference in incidence in African-Americans, Hispanics, and Caucasians diagnosed with cancer. Sex does not seem to be associated with risk in cancer patients. Sex and race/ethnicity are important factors in the risk of first-time and recurrent venous thromboembolism and need to be included as risk assessment and diagnostic prediction tools are developed or updated.

A Phase II Study of the Safety and Efficacy of a Novel Oral fXa Inhibitor (LY517717) for the Prevention of Venous Thromboembolism Following TKR or THR.

Background: There is a continuing need for safe, effective and convenient therapies for prophylaxis of venous thromboembolism (VTE) after major orthopedic surgery. LY517717 (LY), an oral direct inhibitor of activated factor X (fXa), has been well tolerated in healthy subjects and is being developed to address these needs.Objective: To assess the safety and efficacy of LY and to determine whether one or more doses of LY is non-inferior to enoxaparin in preventing VTE in patients undergoing total knee replacement (TKR) or total hip replacement (THR).Methods: In a double-blind, double-dummy, dose-escalation study, patients undergoing TKR or THR were randomized to receive one of six oral doses of LY (25, 50, 75, 100, 125 or 150mg) or enoxaparin, 40 mg SC once daily. LY was administered fasting 6–8 hours after wound closure and then each morning. Enoxaparin was administered the night before surgery and then every evening. Both treatments were continued for a total of 6–10 doses. Patients underwent mandatory bilateral venography within 12 hours of the last dose of oral study drug and were assessed for symptomatic deep vein thrombosis (DVT), pulmonary embolism (PE) and bleeding events through day 30 (±7). All VTE and bleeding events were adjudicated by a blinded independent central adjudication committee. DVT detected by mandatory venography and symptomatic DVT and PE events were included in the combined VTE endpoint. Non-inferiority would be declared if the upper limit of the 90% confidence interval (CI) for the absolute difference in VTE incidence between an LY dose and enoxaparin was less than 0.14.Results: 511 subjects were randomized. 507 patients received at least one dose of LY or enoxaparin and were included in the safety analyses. 391 patients had an evaluable bilateral venogram or experienced an objectively confirmed clinical VTE and were included in the efficacy analyses. The 3 lowest doses were stopped early due to lack of efficacy, and the study was completed with the 3 highest doses. VTE and bleed event data through the treatment and follow-up periods are summarized in the table. The 100, 125 and 150 mg doses of LY were non-inferior to enoxaparin in the incidence of symptomatic or venographic DVT or PE (upper limits for the 90% CI of the absolute differences are 0.13, 0.05 and 0.01, respectively). Adjudicated bleed events were uncommon in both LY and enoxaparin patients.Conclusion: The 100, 125 and 150 mg doses of LY517717 were as efficacious as enoxaparin 40 mg for the prevention of VTE following TKR or THR in this study. LY was safe and well tolerated by study patients, with no significant difference in bleeding risk compared with enoxaparin. [Display omitted]