Apixaban Treatment Decreases Coagulation Activity in Patients with Acute Deep-Vein Thrombosis.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1982-1982 ◽  
Author(s):  
Yu Chen Barrett ◽  
Jessie Wang ◽  
Zhigang Yu ◽  
Andrew Shenker ◽  
Robert Knabb ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Plasma Concentration ◽  
Coagulation Activity ◽  
Mixed Effect ◽  
Vein Thrombosis ◽  
Coronary Syndrome ◽  
Accuracy And Precision ◽  
Number Of Patients ◽  
Deep Vein ◽  
D Dimer

Abstract Background: Elevated levels of coagulation markers such as D-dimer, prothrombin fragment 1+2 (F1+2), and thrombin antithrombin (TAT) have been associated with increased risk for thrombotic events. Apixaban, an oral, selective, direct inhibitor of factor Xa, was shown to be effective for the prevention and treatment of venous thromboembolism (VTE). Apixaban is also in development for stroke prevention in atrial fibrillation patients and secondary prevention in patients with acutre coronary syndrome. This study was conducted to assess changes in coagulation biomarkers after apixaban treatment. Methods: Approximately 1430 plasma samples (pre-dose, week 3 and week 12) were obtained from 520 patients who participated in a phase 2, randomized, parallel-arm, double-blind study of apixaban for the treatment of acute symptomatic deep-vein thrombosis. The study comprised 4 dose arms of approximately 130 patients each (apixaban 5 mg bid, 10 mg bid, 20 mg qd, and 1 active control arm, low molecular weight heparin [LMWH] followed by vitamin K antagonist [VKA] [target INR 2–3]). Five biomarkers, D-dimer, F1+2, TAT, modified prothrombin time (mPT), and anti-Xa activity were measured in plasma. Biomarker responses over treatment time were evaluated using an ANOVA mixed-effect model. Results: Biomarkers of thrombin generation and fibrin turnover, D-dimer, F1+2, and TAT, were significantly elevated at the time of trial randomization in all dose groups with approximately 95%, 46%, and 43% of patients showing values above the upper limit of normal range (ULN) for D-dimer, F1+2, and TAT values, respectively. The respective median biomarker values were 1662 ng/mL, 294 pmol/L, and 4.1 ng/mL. After 3 and 12 weeks of drug treatment, the biomarker values were significantly reduced in the majority of patients in all dose groups (Table). By the end of 12 weeks, the number of patients who continued to have marker values exceeding the ULN in the 4 dose groups ranged from 24% to 40%, 8% to 13%, and 7% to 12%, for D-dimer, F1+2, and TAT, respectively. Pharmacodynamic biomarkers mPT and anti-Xa activity increased with increasing apixaban exposure (R2 = 0.534 for mPT and 0.853 for anti-Xa activity). When comparing the accuracy and precision of mPT and anti-Xa assays in predicting apixaban plasma concentration, the difference between predicted and observed apixaban concentration was much lower for the anti-Xa assay compared to mPT. The median absolute error of the anti-Xa assay was 12% compared with 48% for mPT. Conclusion: 12 weeks of apixaban treatment results in pronounced reduction of coagulation activity as measured by D-dimer, F1+2, and TAT, which is consistent with the low number of thrombotic events observed in apixaban-treated patients in this study (symptomatic VTE rate of 2.5% in the combined apixaban group and the comparator group). The anti-Xa assay demonstrated very good accuracy and precision in predicting apixaban plasma concentration in this clinical trial. Table D-dimer (% Patients > ULN) F1+2 (% Patients > ULN) TAT (% Patients > ULN) Treatment Groups Predose Week 3 Week 12 Predose Week 3 Week 12 Predose Week 3 Week 12 Apixaban 5 mg bid 93% 75% 32% 43% 19% 13% 36% 13% 12% Apixaban 10 mg bid 100% 74% 31% 41% 12% 8% 44% 7% 7% Apixaban 20 mg qd 93% 74% 40% 46% 21% 16% 43% 16% 12% LMWH/VKA 98% 72% 24% 54% 10% 10% 48% 11% 9%

Diagnostic Accuracy of a New d-Dimer Assay (Sclavo Auto d-Dimer) for Exclusion of Deep Vein Thrombosis in Symptomatic Outpatients

2016 ◽  
Vol 23 (3) ◽  
pp. 221-228 ◽  
Author(s):  
Cristina Legnani ◽  
Michela Cini ◽  
Mirella Frascaro ◽  
Giuseppina Rodorigo ◽  
Michelangelo Sartori ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Imaging Techniques ◽  
False Negative ◽  
High Specificity ◽  
Predictive Values ◽  
Cutoff Value ◽  
Vein Thrombosis ◽  
Number Of Patients ◽  
Deep Vein ◽  
D Dimer

In patients presenting non-high clinical pretest probability (PTP), a negative d-dimer can exclude venous thromboembolism without imaging tests. However, each d-dimer assay should be validated in prospective studies. We evaluated an automated d-dimer immunoassay using the Sclavo Auto d-dimer (Sclavo Diagnostics Int, Sovicille, Italy) provided by Dasit Diagnostica (Cornaredo, Milan, Italy). Three hundred two consecutive outpatients suspected of leg deep vein thrombosis (DVT) with non-high PTP were included. The Sclavo Auto d-dimer assay was evaluated on 2 analyzers (Sysmex CA-7000 and Sysmex CS-2100; Sysmex Corporation, Kobe, Japan, provided by Dasit). The cutoff value (200 ng/mL) was established a priori. Prevalence of DVT was 11.9%. Since no false-negative patients were detected, the sensitivity and negative predictive values (NPVs) were 100% (sensitivity = CA-7000: 100% [95% confidence interval, CI: 93.3-100], CS-2100: 100% [95% CI: 93.3-100]; NPV = CA-7000: 100% [95% CI: 97.9-100], CS-2100: 100% [95% CI: 98.0-100]). Specificity was 65.4% (95% CI: 59.4-71.1) and 69.2% (95% CI: 63.3-74.7) for CA-7000 and CS-2100, respectively. Specificity increased when a higher cutoff value (234 ng/mL) was used for patients aged ≥60 years without compromising the safety. Assay reproducibility was satisfactory at concentrations near the cutoff value (total coefficient of variations <10%). In conclusion, the Sclavo Auto d-dimer assay was accurate when used for DVT diagnostic workup in outpatients with non-high PTP. Based on its high sensitivity and NPV, it can be used as a stand-alone test in outpatients with non-high PTP. Given its high specificity, the number of patients in whom further imaging techniques can be avoided increased, improving the yield of the test.

scholarly journals Incidence and Risk Factors of Deep Vein Thrombosis in Hospitalized COVID-19 Patients

2020 ◽  
Vol 26 ◽  
pp. 107602962095321 ◽  
Author(s):  
Yuan Yu ◽  
Jie Tu ◽  
Bingxin Lei ◽  
Huaqing Shu ◽  
Xiaojing Zou ◽  
...  
Keyword(s):  
Risk Factors ◽  
Deep Vein Thrombosis ◽  
Incidence Rate ◽  
Vein Thrombosis ◽  
Number Of Patients ◽  
Proximal Extremity ◽  
High Level ◽  
Deep Vein ◽  
D Dimer ◽  
Extremity Veins

Deep vein thrombosis (DVT) is prevalent in patients with coronavirus disease 2019 (COVID-19). However, the risk factors and incidence rate of DVT remains elusive. Here, we aimed to assess the incidence rate and risk factors of DVT. All patients diagnosed with COVID-19 and performed venous ultrasound by ultrasound deparment between December 2019 and April 2020 in Wuhan Jin Yin-tan hospital were enrolled. Demographic information and clinical features were retrospectively collected. Notably, a comparison between the DVT and the non-DVT groups was explored. The incidence rate of venous thrombosis was 35.2% (50 patients out of 142). Moreover, the location of thrombus at the proximal extremity veins was 5.6% (n = 8), while at distal extremity veins was 35.2% (n = 50) of the patients. We also noted that patients with DVT exhibited a high level of D-dimer (OR 10.9 (95% CI, 3.3-36.0), P < 0.001), were admitted to the intensive care unit (OR 6.5 (95% CI, 2.1-20.3), P = 0.001), a lower usage of the anticoagulant drugs (OR 3.0 (95% CI, 1.1-7.8), P < 0.001). Finally, this study revealed that a high number of patients with COVID-19 developed DVT. This was observed particularly in critically ill patients with high D-dimer levels who required no anticoagulant medication.

scholarly journals Coagulation disorders in the patients with deep vein thrombosis of lower extremity

2003 ◽  
Vol 131 (5-6) ◽  
pp. 201-207 ◽  
Author(s):  
Dragan Milic ◽  
Miljko Pejic ◽  
Danilo Stojiljkovic ◽  
Aleksandar Karanikolic ◽  
Sasa Zivic ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Factor Vii ◽  
Common Finding ◽  
Diagnostic Strategy ◽  
Coagulation Disorders ◽  
Coagulation Activity ◽  
Vein Thrombosis ◽  
Deep Vein ◽  
D Dimer

PURPOSE Venous thromboembolism is a relevant social and health care problem for its high incidence, pulmonary embolism-related mortality and long-term sequelae which may be disabling (post-thrombotic syndrome and ulceration). PROCEDURES The aim of our work was to establish the presence of coagulation disorders (hypercoagulable states) in the patients with deep vein thrombosis (DVT) of the leg. Prospectively we have analyzed a group of 30 patients with echosono-graphicaly verified DVT of the leg who were admitted to the department of vascular surgery from August 1st 2000 to July 31st 2001.The following parameters were monitored: prothrombin time (PT) partial thromboplastin time (PTT), fibrinogen (Fib), alpha 2 antiplasmin (A-2 AP), D-dimer (DD), antithrombin III (AT III) and factor VII. FINDINGS Activation of the coagulation process was registered. The values of monitored coagulation parameters are shown in table 1. Plasma levels of monitored parameters in the patients with DVT of the leg were significantly higher than in the control subjects. CONCLUSION In patients with a DVT a hypercoagulable state is common finding. Some parameters of coagulation activity such as D-dimer might be of great interest in the diagnostic strategy of DVT.

Apixaban decreases coagulation activity in patients with acute deep-vein thrombosis

2011 ◽  
Vol 105 (01) ◽  
pp. 181-189 ◽  
Author(s):  
Jessie Wang ◽  
Robert Knabb ◽  
Puneet Mohan ◽  
Yu Chen Barrett
Keyword(s):  
Deep Vein Thrombosis ◽  
Plasma Levels ◽  
Bleeding Events ◽  
Coagulation Activity ◽  
Treatment Groups ◽  
Vein Thrombosis ◽  
Acute Deep Vein Thrombosis ◽  
Deep Vein ◽  
D Dimer ◽  
All Treatment

SummaryIn patients with acute deep-vein thrombosis (DVT), apixaban, a direct oral factor Xa inhibitor, showed efficacy and safety similar to low-molecular-weight heparin followed by vitamin K antagonist (LMWH/VKA). We evaluated biomarkers of coagulation activity in relation to treatment dose, duration and clinical outcome. Patients (N = 520) with symptomatic DVT were randomised to receive apixaban (5 mg bid, 10 mg bid or 20 mg qd) or LMWH/VKA for 12 weeks. Plasma D-dimer, prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) levels were measured at baseline, and weeks 3 and 12 after treatment. Median plasma levels of D-dimer, F1+2 and TAT were elevated at baseline. At weeks 3 and 12, biomarker levels were normalised in most patients in all treatment groups, consistent with the low rate of venous thromboembolism (VTE) observed. Median reduction in D-dimer was similar in all treatment groups; percentage of patients with D-dimer above upper limit of normal decreased from 95% to 24–40% at week 12. F1+2 decline was greater with LMWH/VKA than apixaban. F1+2 in the apixaban groups changed to a similar extent (>84% of patients had F1+2 within reference range at week 12). Magnitude of TAT reduction was not quantifiable. In conclusion, levels of coagulation biomarkers decreased over 12 weeks of treatment with apixaban or LMWH/VKA in most patients with acute VTE. Baseline D-dimer and F1+2 were higher in patients with recurrent symptomatic VTE than in those without. Plasma levels of coagulation biomarkers did not appear to correlate with total bleeding events.

D-Dimers, Thrombin Antithrombin III Complexes and Prothrombin Fragments 1 + 2: Diagnostic value in Clinically Suspected Deep Vein Thrombosis

1991 ◽  
Vol 65 (01) ◽  
pp. 028-032 ◽  
Author(s):  
B Boneu ◽  
G Bes ◽  
H Pelzer ◽  
P Sié ◽  
H Boccalon
Keyword(s):  
Deep Vein Thrombosis ◽  
Antithrombin Iii ◽  
High Sensitivity ◽  
Diagnostic Value ◽  
Predictive Values ◽  
Vein Thrombosis ◽  
High Negative Predictive Value ◽  
Deep Vein ◽  
D Dimer ◽  
Mercury Strain Gauge

SummaryThis study was performed to determine the accuracy of D-Dimer fibrin derivatives, thrombin-antithrombin III (TAT) complexes and prothrombin fragments 1 + 2 (F 1 + 2) determinations for the diagnosis of deep vein thrombosis (DVT). One hundred and sixteen consecutive patients referred to the angiology unit of our hospital for a clinically suspected DVT were investigated. They were submitted to mercury strain gauge plethysmography and to ultrasonic duplex scanning examination; in cases of inconclusive results or of proximal DVT (n = 35), an ascending phlebography was performed. After these investigations were completed, the diagnosis of DVT was confirmed in 34 and excluded in 82. One half of the patients were already under anticoagulant therapy at the time of investigation. The 3 biological markers were assayed using commercially available ELISA techniques and the D-Dimer was also assayed with a fast latex method. The normal distribution of these markers was established in 40 healthy blood donors. The most accurate assay for the diagnosis of DVT was the D-Dimer ELISA which had both a high sensitivity (94%) and a high negative predictive value (95%). The D-Dirner latex, TAT complexes and F 1 + 2 were far less sensitive and provided negative predictive values which ranged between 78 and 85%. In spite of positive and significant correlations between the levels of ihe 3 markers, their association did not improve their overall accuracy for detecting D\/L Therefore, with the exception of the D-Dimer ELISA, these markers were of little value for the diagnosis of DVT in this specific population.

Evaluation of a New Rapid Quantitative D-dimer Assay in Patients with Clinically Suspected Deep Vein Thrombosis

1996 ◽  
Vol 75 (03) ◽  
pp. 412-416 ◽  
Author(s):  
Armando D’Angelo ◽  
Gabriella D’Alessandro ◽  
Loredana Tomassini ◽  
Jean Louis Pittet ◽  
G Dupuy ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Predictive Value ◽  
Cost Savings ◽  
Pretest Probability ◽  
First Episode ◽  
Consecutive Series ◽  
Vein Thrombosis ◽  
Baseline Testing ◽  
Deep Vein ◽  
D Dimer

SummaryThe sensitivity and specificity for deep vein thrombosis (DVT) of a new rapid, quantitative and precise (total imprecision < 10%) D-dimer assay suitable for individual measurements (VIDAS D-DIMER, bio-Merieux, France) were evaluated in a consecutive series of 103 in- and out-patients submitted to serial compression ultrasonography (C-US) for the clinical suspicion of DVT (n = 66) or of DVT recurrence (n = 37) and symptoms lasting from 1 to 15 days. DVT was found in 22 patients at baseline testing and no patient with an initially negative C-US developed vein incompressibility at follow up. The time elapsed from the onset of symptoms was negatively associated with D-dimer levels both in patients with and in those without DVT. In the entire series of patients, the sensitivity of a positive D-dimer test (≥1.0 Μg/ml) for the presence of DVT was 96% (21/22 patients, 95% confidence interval 75-100%) with a specificity of 75% (64-84%), a negative predictive value of 98% (90-100%), a positive predictive value of 51% (35-67%), and an overall accuracy of 80% (70-87%). A normal D-dimer value (0.22 Μg/ml) was observed in one patient with DVT and symptoms lasting from 15 days. The approach of withholding C-US testing in patients with symptoms lasting from less than 11 days and D-dimer levels below the cut-off value was compared to serial C-US testing alone in a cost-effectiveness analysis subdividing the 66 patients with a first episode according to their clinical pretest probability of DVT. Thrombosis was detected in 6.7% of the patients in the low probability group (n = 15), 16.7% of the patients in the moderate probability group (n = 24), 51.9% of the patients in the high probability group (n = 27) and 8.1% of patients with suspected DVT recurrence. Calculated cost-savings for each DVT diagnosed ranged from 5% in the high pretest probability group to 55% in the low pretest probability group and to 77% in patients with suspected DVT recurrence.The safety of avoiding C-US testing in symptomatic patients with a negative D-dimer test should be evaluated in clinical management studies.

D-Dimer Test and Diagnosis of Deep Vein Thrombosis: A Comparative Study of 7 Assays

1996 ◽  
Vol 76 (04) ◽  
pp. 518-522 ◽  
Author(s):  
A Elias ◽  
I Aptel ◽  
B Huc ◽  
J J Chale ◽  
F Nguyen ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Latex Agglutination ◽  
Lower Limbs ◽  
First Episode ◽  
Lower Sensitivity ◽  
Vein Thrombosis ◽  
Deep Vein ◽  
D Dimer

SummaryThe current D-Dimer ELISA methods provide high sensitivity and negative predictive value for the diagnosis of deep vein thrombosis but these methods are not suitable for emergency or for individual determination. We have evaluated the performance of 3 newly available fast D-Dimer assays (Vidas D-Di, BioMerieux; Instant IA D-Di, Stago; Nycocard D-Dimer, Nycomed) in comparison with 3 classic ELISA methods (Stago, Organon, Behring) and a Latex agglutination technique (Stago). One-hundred-and-seventy-one patients suspected of presenting a first episode of deep vein thrombosis were investigated. A deep vein thrombosis was detected in 75 patients (43.8%) by ultrasonic duplex scanning of the lower limbs; in 11 of them the thrombi were distal and very limited in size (<2 cm). We compared the performance of the tests by calculating their sensitivity, specificity, positive and negative predictive value for different cut-off levels and by calculating the area under ROC curves. The concordance of the different methods was evaluated by calculating the kappa coefficient. The performances of the 3 classic ELISA and of the Vidas D-Di were comparable and kappa coefficients indicated a good concordance between the results provided by these assays. Their sensitivity slightly declined for detection of the very small thrombi. Instant IA D-Di had a non-significantly lower sensitivity and negative predictive value than the 4 previous assays; however its performance was excellent for out-patients. As expected, the Latex assay had too low a sensitivity and negative predictive value to be recommended. In our hands, Nycocard D-Dimer also exhibited low sensitivity and negative predictive value, which were significantly improved when the plasma samples were tested by the manufacturer. Thus significant progress has been made, allowing clinical studies to be planned to compare the safety and cost-effectiveness of D-Dimer strategy to those of the conventional methods for the diagnosis of venous thrombosis.

Rapid Quantitative D-dimer Assay and Clinical Evaluation for the Diagnosis of Clinically Suspected Deep Vein Thrombosis

1997 ◽  
Vol 77 (03) ◽  
pp. 602-603 ◽  
Author(s):  
J Y Borg ◽  
H Lévesque ◽  
N Cailleux ◽  
C Franc ◽  
M F Hellot ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Clinical Evaluation ◽  
Vein Thrombosis ◽  
Deep Vein ◽  
D Dimer

scholarly journals Performance of age-adjusted D-dimer values for predicting DVT before the knee and hip arthroplasty

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jian Xiang Wu ◽  
Jiang Hui Qing ◽  
Yao Yao ◽  
Dong Yang Chen ◽  
Qing Jiang
Keyword(s):  
Deep Vein Thrombosis ◽  
Odds Ratio ◽  
Joint Arthroplasty ◽  
Receiver Operating Curve ◽  
Multiple Logistic Regression ◽  
Vein Thrombosis ◽  
Specificity And Sensitivity ◽  
Knee And Hip Arthroplasty ◽  
Deep Vein ◽  
D Dimer

Abstract Purpose To compare the specificity and sensitivity of preoperative D-dimer and age-adjusted D-dimer value for predicting the incidence of the DVT preoperatively in total joint arthroplasty (TJA) patients. Methods We enrolled 406 patients finally above 50 years old. Everyone had done ultrasonography bedside, and D-dimer concentrations were collected before surgery. The D-dimer and age-adjusted D-dimer cut-off was calculated by multiple logistic regression and receiver operating curve (ROC) analyses. Results A total of 39 patients had found asymptomatic deep vein thrombosis (DVT) by ultrasonography. The age (odds ratio [OR] 1.067; p = 0.003) and D-dimer (OR 1.331; p = 0.025) were related to the existence of DVT. For conventional D-dimer and age-adjusted D-dimer value, the area under the curves (AUCs) were 0.685 (0.499–0.696) and 0.795 (0.611–0.881), respectively. Conclusion Compared to traditional D-dimer, age-adjusted D-dimer showed better performance in screening DVT, which was useful clinically.

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