scholarly journals Resolving Interference of Direct Oral Anticoagulants (DOACs) on Routine Coagulation, Thrombophilia, and Lupus Anticoagulant Testing Using Activated Carbon

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 830-830
Author(s):  
Pierre Toulon ◽  
Mathilde Vannini ◽  
Anny Appert-Flory ◽  
Florence Fischer ◽  
Didier Jambou ◽  
...  

Abstract Background: Direct (anti-IIa and anti-Xa) oral anticoagulants (DOACs) have a significant impact on various coagulation test results. As the correct interpretation of these tests is mandatory to prevent misclassification and subsequent clinical consequences, withholding treatment could be necessary, with the associated risk of thrombosis. Aims: To evaluate the performance of the activated carbon DOAC-Remove (5-Diagnostics, Basel, Switzerland) in extracting DOACs from plasma samples and its effect on various routine and esoteric coagulation test results. Patients, Materials and Methods: Left-over plasmas from patients treated or not with DOAC obtained in the routine laboratory workload were evaluated. Briefly, 0.8 mL of plasma sample was incubated with 1 tablet of the activated carbon for 10 min at room temperature using a rotating shaker. After a 2 min-centrifugation at 2000x g and room temperature, the supernatant was pipetted before being analyzed. Tests were performed before and after such incubation. DOACs were measured using either a specific direct thrombin inhibitor or an anti-Xa assay with specific calibrations. Routine coagulation tests (PT, aPTT, and factor(F)V, FVIII:C, FIX, fibrinogen, and D-dimer) were performed, as well as thrombophilia panel [antithrombin, protein C (PC, chromogenic and clotting assays), PS (free PS antigen and clotting assays)], and lupus anticoagulant (LA) panel [silica clotting time (SCT), and dilute Russell venom clotting time (dRVVT)]. All assays were performed using reagents from Werfen (Bedford, MA, USA) on the ACL TOP 700 analyzer. As the distribution of data was not normal, test results were compared using non-parametric tests. Results: We evaluated a total of 756 plasma samples, obtained from patients treated with dabigatran (n=139, median concentration 129 ng/mL [range:18-905]), rivaroxaban (n=157, median concentration 159 ng/mL [range:19-815]), or apixaban (n=155, median concentration=154 ng/mL (range:11-510), and from 305 patients with various disease states and not on DOAC including 35 patients on coumadin and 32 patients on heparin (UFH: n=18 ; LMWH: n=14). In untreated patients, the DOAC-Remove had no significant impact on test results (n>30 for each parameter), except for D-dimer, free PS and FVIII:C. However, the mean biases, evaluated according to Bland-Altman, were below the accepted limits, and changes would not have had any clinical relevance. In the plasma from patients treated on DOAC, the DOAC-Remove eliminated all the three DOACs, with levels far below the detection limit of the techniques after a 10 min-incubation, leading to a dramatic correction of the DOAC-induced prolongations of PT and APTT, as well as of their lowering effect on FV, FVIII and FIX activities. The same applied to the DOAC-induced elevation of PC and PS anticoagulant activities (clotting assays), and antithrombin activity in the plasma from patients on rivaroxaban and apixaban. DRVVT screen/confirm ratios, which were above the normal ranges in 45% of the patients on dabigatran (n=31), and 78% of the patients on rivaroxaban (n=32), were normalized in most samples after a 10 min-incubation with the carbon and remained positive in only 10% of the patients on dabigatran and 12% of the patients on rivaroxaban. The impact of the DOACs on the SCT screen/confirm ratio was less noticeable with baseline positive test results in only one of the samples from patients on dabigatran (n=31), and in 2 patients on rivaroxaban (n=32). Treatment with the carbon leaded to a correction in the positive sample from patient on dabigatran and in one of the two positive samples from patients on rivaroxaban. Both dRVVT and SCT test results were within the normal range in the plasma from 32 patients on apixaban before and after treatment with the activated carbon. As expected, fibrinogen, PC activity evaluated using a chromogenic assay, free PS antigen concentration, VWF:RCo and VWF:Ag were not affected by any of the 3 DOACs, and test results were not significantly different before and after incubation with the activated carbon. Conclusion: The DOAC-Remove had no effect on test results obtained in the plasma from untreated patients and from patients on traditional anticoagulants. It effectively removed all 3 tested DOACs from the plasma of treated patients, allowing an accurate measurement of routine and esoteric coagulation tests in DOAC treated patients without withholding the treatment. Disclosures No relevant conflicts of interest to declare.

2009 ◽  
Vol 79-82 ◽  
pp. 377-380
Author(s):  
Hong Yun Zhao ◽  
Guo Dong Wang ◽  
Chun Hua Xu ◽  
Feng Yuan Shu

After reheated at different temperatures for 5 minutes, the 400MPa Ultrafine Grained Steel specimens were air-cooled to room temperature, and then carried out the mechanical nanocrystallization surface treatment and structure performance testing. On the basis of comparing the test results on the specimens before and after the mechanical nanocrystallization surface treatment, the process of mechanical nanocrystallization was analyzed briefly. The results show that: as the reheating temperature rising, the trend of grain size growing increases markedly, and the mechanical properties also drop down to different degrees; when the reheating temperature is around 800°C, because of the pearlite spheroidized significantly, its mechanical properties drop the most seriously; after the mechanical nanocrystallization surface treatment, not only its surface form a layer of fine nano-layer (about 100 nm) structure, but also its mechanical properties rise obviously, and the yield strength is over 450MPa.


2020 ◽  
Vol 65 (10) ◽  
pp. 607-610
Author(s):  
O. V. Petrova ◽  
O. V. Dymova ◽  
D. K. Tverdokhlebova ◽  
E. V. Smeltsova ◽  
E. V. Panova ◽  
...  

Comparative analysis of the impact of blood collection systems on the results of routine coagulation tests. The aim of this study was to conduct comparative analysis of the effects of blood collection systems on the results of routine coagulation tests. The study involved practically healthy women over 18 years of age female (n=30). Inclusion criteria: practically healthy individuals. Exclusion criteria: taking non-steroidal anti-inflammatory drugs, or oral contraceptives. Blood collection was carried out in the following systems: 1 system-Vacuette Premium,2 system- Improvacuter, 3 system- BD Vacutainer® Plus. Before and after centrifugation, visual assessment of tubes was performed.No signs for the presence of clots, hemolysis, or insufficient filling was observed. In each sample we measured prothrombin time (PV, sec), activated partial thromboplastin time (APTT, sec), and fibrinogen (F, g/l) by clotting method on the automatic coagulometer «Sta Compact» («Diagnostica Stago», France). The results of laboratory analyses were processed using parametric and non - parametric statistics using The Statistica 12.0 software. At the preanalytical laboratory stage, there were no differences when using systems for blood sampling: the clots and hemolysis were not detected in the samples, the level of filling of the sistems was sufficient. Comparative analysis revealed small, though statistically significant, differences for: PT when comparing Improvacuter wiht Vacuette Premium or BD Vacutainer®; APPT when comparing Improvacuter wiht Vacuette Premium. No differences were observed for Fg levels. Our results support the data available in the literature on the effects of blood-taking systems on hemostasis , which should be taken into account when purchasing blood collection systems.


2017 ◽  
Vol 43 (04) ◽  
pp. 423-432 ◽  
Author(s):  
Paolo Bianchi ◽  
Marco Ranucci ◽  
Ekaterina Baryshnikova ◽  
Giacomo Iapichino

AbstractDirect oral anticoagulants (DOACs) exert similar anticoagulant effects to vitamin K antagonists and are increasingly used worldwide. Nevertheless, an evidence-based approach to patients receiving DOACs when any unplanned urgent surgery or bleeding (either spontaneous or traumatic) occurs is still missing. In this review, we investigate the role of point-of-care coagulation tests when other, more specific tests are not available. Indeed, thromboelastography and activated clotting time can detect dabigatran-induced coagulopathy, while their accuracy is limited for apixaban and rivaroxaban, mostly in cases of low drug plasma concentrations. These tests can also be used to guide the reversal of DOAC-induced coagulopathy providing a quick, before-and-after picture in case of therapeutic use of hemostatic compounds.


2011 ◽  
Vol 201-203 ◽  
pp. 1774-1779
Author(s):  
Ze Biao Zhang ◽  
Wan Kun Wang ◽  
Jin Hui Peng

The leaching tests of nickel supported activated carbon under normal pressure in (NH4)2SO4were studied. The effects of experimental condition, such as initial concentration of (NH4)2SO4, liquid-to-solid ratio, leaching time and leaching temperature on the leaching rate of nickel, were investigated. The results show that the leaching rate of nickel is 96.12% with initial concentration of (NH4)2SO4of 7.5%, liquid-to-solid ratio of 2, leaching time of 5h and leaching temperature of 25°C. The morphology of nickel supported activated carbon before and after leaching was characterized by XRD, which proved the effective separation of nickel and activated carbon. The leaching rate of nickel was also shown better at room temperature and atmospheric pressure. Moreover, it needn’t equipments enduring high-pressure and high temperature in the leaching process, thus reducing the costs of leaching equipments greatly. This work provides a new way to the comprehensive utilization of nickel-containing activated carbon.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jianguo Zhang ◽  
Xing Huang ◽  
Daoyin Ding ◽  
Zhimin Tao

Abstract Background One year into the coronavirus diseases 2019 (COVID-19) pandemic we analyzed the blood coagulopathy in severe and non-severe COVID-19 patients and linked to those of influenza patients for a comparative study. Methods We reported 461 COVID-19 patients and 409 seasonal influenza patients admitted at separated medical centers. With their demographic data and medical history, hematological profiles with coagulation characters were emphasized, and compared between two cohorts before and after treatment. Results For 870 patients included in this study, their median age was (64.0, 51.0–76.0), and among them 511 (58.7%) were male. Hypertension, diabetes, cardiovascular diseases, and bronchitis constituted the leading comorbidities. Upon hospital admission blood test results differentiated COVID-19 patients from influenza cases, and for COVID-19 patients, leukocytosis, neutrophilia, lymphocytopenia, and thrombocytopenia were associated with disease severity and mortality. In addition, COVID-19 cohort demonstrated a prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), increased INR, shortened thrombin time and decreased fibrinogen, compared to those in influenza cohort, leaving D-dimer levels indistinguishably high between both cohorts. Platelet hyperreactivity in COVID-19 is more evident, associated with worse hyper-inflammatory response and more refractory coagulopathy. For severe COVID-19 patients administered with anticoagulants, bleeding incidence was substantially higher than others with no anticoagulant medications. Conclusions Comparison of coagulation characteristics between COVID-19 and influenza infections provides an insightful view on SARS-CoV-2 pathogenesis and its coagulopathic mechanism, proposing for therapeutic improvement.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2091-2091
Author(s):  
Pierre A. Toulon ◽  
Lién Abecassis ◽  
Motalib Smahi ◽  
Catherine Ternisien

Abstract Abstract 2091 Poster Board II-68 Collecting small volumes of blood may be necessary, particularly in pediatrics, or in case of difficult or recurrent sampling. The aim of this multicenter study, involving four hemostasis laboratories, was to compare hemostasis test results in plasma samples obtained using partial- and full-draw evacuated polymer collection tubes containing 0.109 M sodium citrate (1 vol./9 vol.) as the anticoagulant solution (VenoSafeTM, Terumo Europe, Leuven, Belgium). For that purpose, blood was collected into one full- and one partial-draw tube from patients on vitamin K antagonists (VKA, n=100), unfractionated heparin (UFH, n=89), or a low molecular weight derivative (LMWH, n=52), as well as from 136 untreated patients, including 13 hemophiliacs. Routine coagulation tests i.e. PT/INR, aPTT, fibrinogen, and factor V, as well as factor VIII and anti-FXa activity when applicable, were measured using the routine techniques at each participating center. In addition, plasma PF-4 level, evaluated using an ELISA, was investigated in a subset of 36 healthy controls. In untreated patients incl. hemophiliacs as well as in those on either VKA or LMWH, no significantly relevant discrepancy (Bland-Altman) was found between tests results obtained using full- and partial-draw tubes. In contrast, anti-FXa activity in patients on UFH was significantly lower in partial- than in full-draw tubes [median=0.33 IU/mL (range: 0.00-1.11) vs. 0.39 (range: 0.05-1.32) respectively, p<0.0001]. Similarly, aPTT was significantly shorter in partial- than in the full-draw tubes, whereas other test results were not significantly different in the two tubes. That discrepancy was likely to be related to higher amount of PF4 released in plasma after increased platelet activation in partial-draw than in full-draw tubes [392 U/mL (range: 138-971) vs. 177 (range: 52-460) respectively, n=36; p<0.005)]. To further support that hypothesis, blood was collected, from 101 patients on UFH and from 104 untreated patients, into one partial-draw collection tube containing CTAD, a mixture of citrate and inhibitors of platelet activation, as the anticoagulant solution and one full-draw citrated tube, obtained from the same manufacturer. Comparison performed according to Bland-Altman of anti-FXa obtained in the two tubes failed to demonstrate any relevant difference, with a mean bias of +0.02 IU/mL that was identical throughout the measuring range of values [median=0.22 IU/mL (range: 0.06-1.16) vs. 0.20 (range: 0.03-1.15) respectively, n=101]. Moreover, in those patients on UFH, aPTT and other routine coagulation tests were not significantly different in the two tubes and the same applied to test results obtained in the plasma from untreated patients. These results suggest that samples collected into partial-draw citrated tubes allow accurate routine coagulation testing in all patients but those requiring UFH assessment, in which their use could lead to a significant underestimation of anticoagulation. In such cases, partial-draw tubes containing CTAD could be validly used to monitor heparin therapy, as well as to perform routine coagulation testing. Disclosures: No relevant conflicts of interest to declare.


2019 ◽  
Vol 25 ◽  
pp. 107602961983505 ◽  
Author(s):  
Vanessa M. Silva ◽  
Maurício Scanavacca ◽  
Francisco Darrieux ◽  
Cyrillo Cavalheiro ◽  
Celia C. Strunz

Dabigatran and rivaroxaban, direct oral anticoagulants (DOACs), affect coagulation tests, and knowledge of their effects is important for therapeutic monitoring. Our aim was to examine the association between DOAC levels and routine coagulation tests in patients with nonvalvular atrial fibrillation. Samples from patients receiving dabigatran (150 mg) and patients receiving rivaroxaban (20 mg) were collected 2 hours after drug intake. Direct oral anticoagulant concentrations were determined using direct Hemoclot thrombin inhibitor (HTI) assay (HTI test) and a direct Xa inhibitor (Anti Xa-Riva). The routine coagulation measured included activated partial thromboplastin time (aPTT) and prothrombin time (PT). The median plasmatic dabigatran was 128.3 ng/mL (95% confidence interval [CI]: 93.7-222.6 ng/mL). The HTI exhibited a good correlation with aPTT ( R2 = 0.74; P < .0001). The median plasmatic rivaroxaban was 223.9 ng/mL (95% CI: 212.3-238.9 ng/mL). Anti-Xa-Riva correlated with PT ( R2 = 0.69, P< .0001) and aPTT (R2 = 0.36, P < .001), but prolonged PT results were obtained, even below the rivaroxaban therapeutic range (20%). The routine coagulation tests were able to identify out of therapeutic range concentrations for dabigatran and rivaroxaban. We suggest the use of these screening tests to better understand and monitor the subtherapeutic concentrations of these DOACs.


2020 ◽  
Vol 26 ◽  
pp. 107602962097550
Author(s):  
Xuemei Quan ◽  
Qixiong Qin ◽  
Xianting Que ◽  
Ya Chen ◽  
Yunfei Wei ◽  
...  

Lung cancer related hypercoagulability could increase the risk of ischemic stroke. Routine coagulation tests may have limited capacity in evaluating hypercoagulability. The aim of this study was to investigate the ability of thromboelastography (TEG) in the identification of hypercoagulability in patients with lung cancer and cryptogenic ischemic stroke (LCIS). Between January 2016 and December 2018, whole citrated blood from LCIS patients (n = 35) and age- and gender-matched lung cancer patients and healthy volunteers were used for TEG and routine coagulation tests. The coagulation indicator and clinical data were compared among the 3 groups. There were 27/35 (77.14%) on TEG and 18/35 (51.43%) on routine coagulation tests of LCIS patients who had evidence of hypercoagulability. The detection rate of hypercoagulability by TEG in LCIS patients was higher than routine coagulation tests ( P = 0.018). Comparing with lung cancer patients and healthy controls, LCIS patients have a significantly higher maximum amplitude (MA), fibrinogen, and D-dimer. Multivariate analysis showed that D-dimer and MA were significantly associated with ischemic stroke in lung cancer patients. ROC curve showed that the area under the curve of TEG (0.790 ± 0.048, 95% CI: 0.697-0.864) was significantly higher than routine coagulation tests (0.673 ± 0.059, 95% CI: 0.572-0.763) ( P = 0.04) in identifying hypercoagulability in LCIS patients. Therefore, TEG could identify hypercoagulability in LCIS patients and healthy controls. Identification of hypercoagulability in lung cancer patients by TEG may be helpful to prevent the occurrence of LCIS.


2018 ◽  
Vol 56 (3) ◽  
pp. 454-462 ◽  
Author(s):  
Ana Mlinaric ◽  
Marija Milos ◽  
Désirée Coen Herak ◽  
Mirjana Fucek ◽  
Vladimira Rimac ◽  
...  

AbstractBackground:The need to satisfy high-throughput demands for laboratory tests continues to be a challenge. Therefore, we aimed to automate postanalytical phase in hematology and coagulation laboratory by autovalidation of complete blood count (CBC) and routine coagulation test results (prothrombin time [PT], international normalized ratio [PT-INR], activated partial thromboplastin time [APTT], fibrinogen, antithrombin activity [AT] and thrombin time [TT]). Work efficacy and turnaround time (TAT) before and after implementation of automated solutions will be compared.Methods:Ordering panels tailored to specific patient populations were implemented. Rerun and reflex testing rules were set in the respective analyzers’ software (Coulter DxH Connectivity 1601, Beckman Coulter, FL, USA; AutoAssistant, Siemens Healthcare Diagnostics, Germany), and sample status information was transferred into the laboratory information system. To evaluate if the automation improved TAT and efficacy, data from manually verified results in September and October of 2015 were compared with the corresponding period in 2016 when autovalidation was implemented.Results:Autovalidation rates of 63% for CBC and 65% for routine coagulation test results were achieved. At the TAT of 120 min, the percentage of reported results increased substantially for all analyzed tests, being above 90% for CBC, PT, PT-INR and fibrinogen and 89% for APTT. This output was achieved with three laboratory technicians less compared with the period when the postanalytical phase was not automated.Conclusions:Automation allowed optimized laboratory workflow for specific patient populations, thereby ensuring standardized results reporting. Autovalidation of test results proved to be an efficient tool for improvement of laboratory work efficacy and TAT.


Perfusion ◽  
1995 ◽  
Vol 10 (1) ◽  
pp. 13-16 ◽  
Author(s):  
M. Wallock ◽  
C. Arentzen ◽  
J. Perkins

Factor XII initiates the intrinsic coagulation cascade and may affect the fibrinolytic system. Routine coagulation tests used during cardiopulmonary bypass (CPB) are abnormal in factor-XII-deficient patients and are useless for monitoring anticoagulation in these patients. A factor-XII-deficient patient requiring CPB is described. The baseline celite activated clotting time (ACT) was greater than 1400 seconds and the thrombin time was 12.4 seconds (control, 11.9 seconds). Two units of plasma were given resulting in an ACT of 173 seconds. Following 300 units/kg of heparin and during CPB, the ACT ranged from 670-596 seconds with the thrombin time greater than 200 seconds. Plasma provides exogenous factor XII allowing an endpoint on the ACT test and may protect against possible postoperative hypofibrinolytic complications. A commercially available modified thrombin time may also be useful and provide an endpoint during high-dose heparinization.


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