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1

Greene, Lindsey A., Connie Law, Mike Jung, Sara Walton, and Leslie J. Raffini. "Lack Of Anti-Xa Assay Standardization Results In Significant Dose Variation In Neonates and Children Receiving Enoxaparin." Blood 122, no. 21 (2013): 2379. http://dx.doi.org/10.1182/blood.v122.21.2379.2379.

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Abstract Introduction Due to favorable pharmacokinetic properties, enoxaparin is the most frequently used anticoagulant in children. Unlike adults, a developing hemostatic system provides rationale for therapeutic monitoring with an anti-Xa goal of 0.5-1 units/ml. However, accepted therapeutic ranges are not well correlated with clinical outcomes (i.e. thrombosis or hemorrhage) and there is no assay standardization. In 2011 the coagulation laboratory at the Children's Hospital of Philadelphia (CHOP) changed anti-Xa laboratory assays resulting in anti-Xa levels that were on average, 33% higher
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2

Billoir, Paul, Virginie Barbay, Luc Marie Joly, Marielle Fresel, Marie Hélène Chrétien, and Véronique Le Cam Duchez. "Anti-Xa Oral Anticoagulant Plasma Concentration Assay in Real Life: Rivaroxaban and Apixaban Quantification in Emergency With LMWH Calibrator." Annals of Pharmacotherapy 53, no. 4 (2018): 341–47. http://dx.doi.org/10.1177/1060028018811657.

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Background: Oral anti-Xa inhibitors have demonstrated noninferiority to vitamin K antagonists (VKAs) for the prevention of stroke in patients with atrial fibrillation and recurrent venous thromboembolism. They are associated with a decrease in major bleeding. In contrast with VKA, no coagulation monitoring is required. However, in clinical practice, determination of drug concentration is sometimes necessary. Objective: The objective of this study was to evaluate a low-molecular-weight heparin (LMWH) calibrated anti-Xa assay for the quantification of rivaroxaban and apixaban plasma concentratio
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3

Iampietro, R., A. M. Woolley, F. E. Preston, and S. Kitchen. "Anti Xa Monitoring during Treatment with Low Molecular Weight Heparin or Danaparoid: Inter-assay Variability." Thrombosis and Haemostasis 82, no. 10 (1999): 1289–93. http://dx.doi.org/10.1055/s-0037-1614377.

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SummaryIf laboratory monitoring of low molecular weight heparin (LMWH) therapy is required the test of choice is the anti Xa activity assay. The relationship between anti Xa results obtained using different techniques is unknown. The aim of the present study was to compare anti Xa results obtained with eight different commercially available anti Xa activity assays (five chromogenic and three clotting based assays) in samples from patients receiving either therapeutic or prophylactic LMWH (enoxaparin or dalteparin) or danaparoid.We have demonstrated that highly significant differences exist bet
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4

Siddiqui, Fakiha, Debra Hoppensteadt, Walter Jeske, Omer Iqbal, Alfonso Tafur, and Jawed Fareed. "Factor Xa Inhibitory Profile of Apixaban, Betrixaban, Edoxaban, and Rivaroxaban Does Not Fully Reflect Their Biologic Spectrum." Clinical and Applied Thrombosis/Hemostasis 25 (January 1, 2019): 107602961984752. http://dx.doi.org/10.1177/1076029619847524.

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The currently available oral anti-Xa agents are claimed to produce their anticoagulant and antithrombotic effects solely by the inhibition of factor Xa. This study profiled various anti-Xa drugs in routinely used laboratory assays to demonstrate that their effects are not solely related to the anti-Xa activities. Apixaban, betrixaban, edoxaban, and rivaroxaban were obtained commercially. Native and citrated whole blood was used for the activated clotting time (ACT) and thromboelastography (TEG). Citrated plasma was used for monitoring the prothrombin time (PT), activated partial thromboplastin
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5

Wang, Zhaoqing, Charles Frost, Andrew Shenker, and Yu Chen Barrett. "Clinical laboratory measurement of direct factor Xa inhibitors: Anti-Xa assay is preferable to prothrombin time assay." Thrombosis and Haemostasis 104, no. 12 (2010): 1263–71. http://dx.doi.org/10.1160/th10-05-0328.

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SummaryApixaban and other factor Xa (FXa) inhibitors are in late-stage clinical development for prevention and treatment of thromboembolic diseases. Although routine monitoring will not be required, in certain situations assessment of drug level may be helpful. This study evaluated the suitability of commercially available prothrombin time/international normalised ratio (PT/INR) and anti-FXa activity assays to measure FXa inhibitors in plasma. Twelve PT (ISI 0.89ﺹ1.88) and three anti-Xa assays were evaluated in vitro using human plasma spiked with four FXa inhibitors (0ﺹ2,000 ng/ml). Assay var
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6

Bessekaar, A. M. H. P. van den, J. Meeuwisse-Braun, and R. M. Bertina. "Monitoring Heparin Therapy: Relationships between the Activated Partial Thromboplastin Time and Heparin Assays Based on Ex-Vivo Heparin Samples." Thrombosis and Haemostasis 63, no. 01 (1990): 016–23. http://dx.doi.org/10.1055/s-0038-1645678.

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SummaryFive different APTT reagents, two amidolytic anti-ITa assays, one amidoiytic anti-Xa assay, and one coagulometric anti-Xa/ anti-IIa assay were used to assess the effect of heparin in patients treated for venous thromboembolic disease. Good correlations were observed between lug-transformed APYE> determined with the various reagents (correlation coefficients: 0.92-0.96).Nevertheless there were important differences in the slopes of the lines of relationship between the APTT reagents.Good correlations were observed between the anti-Xa and anti-IIa assay results (correlation coefficient
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7

Vera-Aguilera, Jesus, Hindi Yousef, Diego Beltran-Melgarejo, et al. "Clinical Scenarios for Discordant Anti-Xa." Advances in Hematology 2016 (2016): 1–6. http://dx.doi.org/10.1155/2016/4054806.

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Anti-Xa testmeasuresthe activity ofheparinagainst the activity of activated coagulation factor X; significant variability of anti-Xa levels in common clinical scenarios has been observed.Objective. To review the most common clinical settings in which anti-Xa results can be bias.Evidence Review. Guidelines and current literature search: we used PubMed, Medline, Embase, and MEDION, from 2000 to October 2013.Results. Anti-Xa test is widely used; however the assay underestimates heparin concentration in the presence of significant AT deficiency, pregnancy, end stage renal disease, and postthrombol
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8

Gilbert, M., V. Goret, N. Rolland, M. Samama, and F. Depasse. "Anti-Xa Monitoring: Inter-assay Variability." Thrombosis and Haemostasis 84, no. 12 (2000): 1122–23. http://dx.doi.org/10.1055/s-0037-1614183.

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9

Gilbert, M., V. Goret, N. Rolland, M. Samama, and F. Depasse. "Anti-Xa Monitoring: Inter-assay Variability." Thrombosis and Haemostasis 84, no. 12 (2000): 1122–23. http://dx.doi.org/10.1055/s-0037-1614184.

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10

Barrowcliffe, T. W., A. D. Curtis, T. P. Tomlinson, A. R. Hubbard, E. A. Johnson, and D. P. Thomas. "Standardization of Low Molecular Weight Heparins : A Collaborative Study." Thrombosis and Haemostasis 54, no. 03 (1985): 675–79. http://dx.doi.org/10.1055/s-0038-1660095.

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SummaryA collaborative study was carried out, in which eight laboratories each assayed eight low molecular weight (LMW) heparins against the International Standard (IS) for heparin. APTT assays and three types of anti-Xa method were used. The results of this study showed that:1. LMW heparins cannot be validly assayed against the IS by APTT or anti-Xa methods.2. Potencies of LMW heparins vs. the IS differed considerably between the four types of assay method used and also between different laboratories using the same type of method.3. Adoption of a single LMW heparin standard would improve vali
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11

Williams-Norwood, Tanya, Megan Caswell, Barbara Milner, et al. "Design and Implementation of an Anti–Factor Xa Heparin Monitoring Protocol." AACN Advanced Critical Care 31, no. 2 (2020): 129–37. http://dx.doi.org/10.4037/aacnacc2020132.

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Background: The VA Northeast Ohio Healthcare System introduced a new nurse-driven anti–factor Xa (anti-Xa) protocol for monitoring unfractionated heparin to replace the previous activated partial thromboplastin time protocol. Objective: To design, implement, and evaluate the efficacy of the anti-Xa monitoring protocol. Methods: An interdisciplinary team of providers collaborated to develop and implement a nurse-driven, facility-wide anti–factor Xa protocol for monitoring unfractionated heparin therapy. The effectiveness of this protocol was evaluated by retrospective analysis. Results: We revi
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12

Kostousov, Vadim, Kim Nguyen, Shilpa G. Hundalani, and Jun Teruya. "The Influence of Free Hemoglobin and Bilirubin on Heparin Monitoring by Activated Partial Thromboplastin Time and Anti-Xa Assay." Archives of Pathology & Laboratory Medicine 138, no. 11 (2014): 1503–6. http://dx.doi.org/10.5858/arpa.2013-0572-oa.

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Context Elevated free hemoglobin (Hb) and bilirubinemia complicate extracorporeal membrane oxygenation and could affect unfractionated heparin (UH) therapy monitoring by anti-Xa assay and activated partial thromboplastin time (aPTT). Objectives To compare in vitro response of anti-Xa and aPTT assays to UH in samples with artificial hyperbilirubinemia and hyperhemoglobinemia and to estimate if this interference is also observed in vivo in pediatric extracorporeal membrane oxygenation. Design Measurement of aPTT and anti-Xa activity in plasma spiked with UH and increased concentration of free Hb
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13

Hoppensteadt, Debra, Angel Gray, Josephine Cunanan, Walter Jeske, Jeanine M. Walenga, and Jawed Fareed. "Comparative Studies on An Anti-Xa Enriched Ultra Low Molecular Weight Heparin with Bemiparin." Blood 116, no. 21 (2010): 4394. http://dx.doi.org/10.1182/blood.v116.21.4394.4394.

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Abstract Abstract 4394 Most low molecular weight heparins (LMWHs) have a mean molecular weight in the range of 4–6 kDa and anti-Xa/IIa ratios of 3–6. Further depolymerization of porcine mucosal heparin results in the generation of Ultra low molecular weight heparins (ULMWHs) with a molecular weight range of 2–4 kDa with proportionately decreased anti-Xa and anti-IIa activities. Bemiparin (Rovi, Madrid, Spain) represents one such ULMWH. AVE 5026 (Sanofi-Aventis, Paris, France) is a unique ULMWH (2.5 kDa) which exhibits higher affinity to antithrombin (AT) and therefore, enhanced anti-Xa activit
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14

Olson, Guy, Walter Jeske, Omer Iqbal, et al. "USP Standardized Mixtures of Bovine, Ovine and Porcine Heparin Exhibit Comparable Biologic Effects to Referenced Single Sourced Heparins and May be Interchangeable,." Blood 138, Supplement 1 (2021): 1067. http://dx.doi.org/10.1182/blood-2021-147995.

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Abstract Introduction: Unfractionated heparin (UFH) is the first line anticoagulant for the management of medical indications. UFH complexes with antithrombin to produce strong inhibition of thrombin and factor Xa. The UFHs are standardized using USP compliant amidolytic anti-Xa and IIa methods in defined conditions. Clinically used UFH is solely sourced from porcine mucosal tissue. Because of the shortage of porcine tissue and the African Swine Fever, the supply chain of this anticoagulant is compromised. Thus, there is a need for resourcing of this anticoagulant. Bovine and ovine mucosal sou
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15

Hubbard, A. R., and C. A. Jennings. "Neutralisation of Heparan Sulphate and Low Molecular Weight Heparin by Protamine." Thrombosis and Haemostasis 53, no. 01 (1985): 086–89. http://dx.doi.org/10.1055/s-0038-1661242.

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SummaryThe neutralisation by protamine sulphate (PS) of heparan sulphate (HS), a low molecular weight heparin (LMWH), and a reference preparation of unfractionated heparin (UH), was studied by activated partial thromboplastin time (APTT) and anti-Xa clotting assays. UH was most easily neutralised in the APTT assay by PS (on a weight for weight basis), followed by LMWH and HS. The neutralisation of APTT activity by PS closely followed the loss of activity in the anti-Xa clotting assay, when plasma was used as the source of At III. When the anti-Xa clotting assay was carried out using purified A
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16

Smith, Alex R., William E. Dager, and Michael P. Gulseth. "Transitioning hospitalized patients from rivaroxaban or apixaban to a continuous unfractionated heparin infusion: A retrospective review." American Journal of Health-System Pharmacy 77, Supplement_3 (2020): S59—S65. http://dx.doi.org/10.1093/ajhp/zxaa143.

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Abstract Purpose To determine a patient’s clinical course based on the use of an activated partial thromboplastin time (aPTT) or heparin anti-Xa assay when transitioning from rivaroxaban or apixaban to an unfractionated heparin infusion. Methods A retrospective chart review was conducted to investigate how unfractionated heparin infusions were managed at a tertiary care hospital in the setting of recent apixaban or rivaroxaban administration. Patients were separated into 2 cohorts based on the chosen heparin infusion monitoring assay: heparin anti-Xa or aPTT. The primary composite outcome was
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17

Manco-Johnson, Marilyn J., Neil Goldenberg, Lesley G. Mitchell, and Linda J. Jacobson. "Can Heparin-Based Therapy in Children Be Monitored on Samples Drawn Through Ports? An Analysis From Clinical Trials Data,." Blood 118, no. 21 (2011): 3365. http://dx.doi.org/10.1182/blood.v118.21.3365.3365.

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Abstract Abstract 3365 Background: Based on preliminary data, children clear heparins more rapidly than adults, and thus most pediatric hematologists monitor heparin therapy. Many pediatric deep vein thrombosis patients have indwelling central venous lines (CVLs) due to co-morbid conditions and patients and clinicians desire to use these CVLs for blood sampling. Standard protocols are used to flush and clear CVLs prior to sample collection, but validated approaches to exclude contamination of heparin in dwell-volume (i.e., hep-lock) from systemic anticoagulant have not been established. Aims:
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18

Siddiqui, Fakiha, Debra Hoppensteadt, Jeanine Walenga, et al. "Assay Dependent Reversal of the Oral and Parenteral Anti-Xa Agents By Andexanet Alfa." Blood 136, Supplement 1 (2020): 39–40. http://dx.doi.org/10.1182/blood-2020-142653.

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Introduction: Andexanet alfa (AA, Portola Pharmaceuticals, San Francisco, USA) is an approved reversal agent for the control of potential bleeding associated with apixaban and rivaroxaban. Beside the oral anti-Xa agents, parenteral forms of the inhibitors of factor Xa such as otamixaban (Sanofi Aventis, Paris, France) and DX9065a (Mitsubishi Pharmaceuticals, Tokyo, Japan) have also been developed. These agents represent synthetic organo-mimerics with comparable selectivity and inhibitory profile to the currently available oral anti-Xa agents. Parenteral anti-Xa agents are considered for clinic
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19

Siddiqui, Fakiha, Alfonso J. Tafur, Debra Hoppensteadt, et al. "Andexanet Alpha Differentially Neutralizes the Anticoagulant, Antiprotease and Thrombin Generation Inhibitory Effects of Unfractionated Heparin, Enoxaparin and Fondaparinux." Blood 134, Supplement_1 (2019): 1158. http://dx.doi.org/10.1182/blood-2019-127072.

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Introduction: Andexanet Alpha (Coagulation factor Xa recombinant, inactivated Zh-zo; AA, Portola Pharmaceuticals) is a recombinant factor Xa decoy protein which is designed to reverse the effects of apixaban and rivaroxaban and is approved for the control of bleeding complications associated with their use. The molecular modification in this recombinant protein involves the substitution of serine active site by alanine and the removal of the gamma-carboxyglutamic acid (GLA) domain to restrict its assemblage into prothrombinase complex. Beside the reversal of the effects of anti-Xa agents AA is
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20

Rohde, Gabriele, Gertrud Stratmann, Christian Hesse, et al. "Accurate determination of rivaroxaban levels requires different calibrator sets but not addition of antithrombin." Thrombosis and Haemostasis 108, no. 07 (2012): 191–98. http://dx.doi.org/10.1160/th11-12-0832.

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SummaryRivaroxaban is a direct factor Xa inhibitor, which can be monitored by anti-factor Xa chromogenic assays. This ex vivo study evaluated different assays for accurate determination of rivaroxaban levels. Eighty plasma samples from patients receiving rivaroxaban (Xarelto®) 10 mg once daily and 20 plasma samples from healthy volunteers were investigated using one anti-factor Xa assay with the addition of exogenous antithrombin and two assays without the addition of antithrombin. Two different lyophilised rivaroxaban calibration sets were used for each assay (low concentration set: 0, 14.5,
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21

Siriez, Romain, Jonathan Evrard, Jean-Michel Dogné, et al. "Betrixaban: Impact on Routine and Specific Coagulation Assays—A Practical Laboratory Guide." Thrombosis and Haemostasis 118, no. 07 (2018): 1203–14. http://dx.doi.org/10.1055/s-0038-1657772.

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Introduction Betrixaban is a novel direct oral factor Xa inhibitor approved by the Food and Drug Administration for prophylaxis of venous thromboembolism in adult patients hospitalized for an acute illness at risk for thromboembolic complications. Assessment of the anti-coagulant effect of betrixaban may be useful in some situations. Also, clinicians need to know how routine coagulation assays are influenced. Objective The aim of this study is to determine which coagulation assay(s) should be used to assess the impact of betrixaban on haemostasis and provide laboratory guidance for their inter
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22

Gatt, Alexander, Anne Riddell, Lesley Lanning, Saman Aghighi, Pamala Kanagasapathy, and Pratima Chowdary. "Thrombin Generation Is a Sensitive Measure of Low Molecular Weight Heparin Anticoagulant Activity." Blood 116, no. 21 (2010): 1099. http://dx.doi.org/10.1182/blood.v116.21.1099.1099.

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Abstract Abstract 1099 Current guidelines recommend monitoring of low molecular weight heparins (LMWHs) using the anti-Xa assay in high risk patients like those with renal impairment, pregnancy or overweight and in children. However, it is well accepted that this test does not accurately predict the anticoagulant effect of these drugs1. This is understandable since the various LMWHs available affect the coagulation cascade in different ways relative to their different molecular structure. Notoriously, the larger LMWHs like Tinzaparin have a higher anti-IIa to anti-Xa ratio that is not detected
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23

McLaughlin, Kevin, Jessica Rimsans, Katelyn W. Sylvester, et al. "Evaluation of Antifactor-Xa Heparin Assay and Activated Partial Thromboplastin Time Values in Patients on Therapeutic Continuous Infusion Unfractionated Heparin Therapy." Clinical and Applied Thrombosis/Hemostasis 25 (January 1, 2019): 107602961987603. http://dx.doi.org/10.1177/1076029619876030.

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Clinical uncertainty exists regarding which assay should be designated as the standard monitoring coagulation test for intravenous unfractionated heparin (UFH). Several studies have compared the use of activated partial thromboplastin time (aPTT) and antifactor-Xa (anti-Xa) and have come out with varying results. The correlation between these 2 tests varied, markedly from strong to weak. Some have demonstrated that monitoring with anti-Xa heparin assay leads to fewer dose adjustments, resulting in fewer laboratory tests, while others have not. In the current study, we evaluated the correlation
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24

Raby, Anne, Karen Moffat, Greg Flynn, Mark Crowther, and Adam Cuker. "Interlaboratory variation in heparin monitoring: Lessons from the Quality Management Program of Ontario coagulation surveys." Thrombosis and Haemostasis 104, no. 10 (2010): 837–44. http://dx.doi.org/10.1160/th10-02-0099.

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SummaryUnfractionated heparin (UFH) monitoring is subject to substantial inter-laboratory variation. We analysed results of annual coagulation surveys administered by the Quality Management Program – Laboratory Services (Toronto, ON, Canada) from 2003 to 2007 to evaluate variation in UFH monitoring across Ontario. Participating laboratories performed an activated partial thromboplastin time (APTT) utilising their local methodology on lyophilised human plasma spiked with UFH. In the 2006 and 2007 surveys, laboratories licensed to perform anti-Xa assays also reported anti-Xa activity results. Th
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25

Billoir, Paul, Thomas Elie, Jerrold H. Levy, et al. "Anticoagulation Monitoring with Activated Partial ThromboPlastin Time and Anti-Xa Activity in Intensive Care Unit Patients: Interest of Thrombin Generation Assay." International Journal of Molecular Sciences 23, no. 19 (2022): 11219. http://dx.doi.org/10.3390/ijms231911219.

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Current guidelines recommend monitoring the anticoagulant effect of unfractionated heparin (UFH) by measuring anti-Xa activity rather than activated partial thromboplastin time (aPTT) in intensive care unit (ICU) patients. The primary objective of this study was to evaluate the correlation of aPTT, anti-Xa activity, and thrombin generation in UFH-treated ICU patients. A prospective observational pilot study was conducted in adult surgical ICU patients treated with UFH. aPTT and anti-Xa activity were monitored daily. The therapeutic target was aPTT between 50 s and 84 s, and/or anti-Xa between
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26

Hoppensteadt, D., M. Tobu, R. Wahi, et al. "Comparative Study on the Anticoagulant Effects of Low Molecular Weight Heparins as Measured by Whole Blood Act, Anti-Xa and a Newly Developed Prothrombinase Induced Clotting Time (PiCT) Assay." Blood 106, no. 11 (2005): 4148. http://dx.doi.org/10.1182/blood.v106.11.4148.4148.

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Abstract Low Molecular Weight Heparins (LMWHs) are currently developed for anticoagulation in various intravenous indications such as DVT treatment and percutaneous interventions (PCI). Traditionally, these drugs are administered in anti-Xa units. The purpose of this study was to compare the relative levels of anticoagulation produced by different LMWHs in whole blood ACT (Hemochron), an amidolytic anti-Xa method and a plasma-based global anticoagulant assay, the PiCT test (Pentapharm, Basel, Switzerland). Various LMWHs such as dalteparin, enoxaparin, reviparin and a synthetic pentasaccharide
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27

Burger, Annika, Jan-Dirk Studt, Adriana Mendez, et al. "Determination of Anti-Xa Inhibitor Plasma Concentrations Using a Universal Edoxaban Calibrator." Diagnostics 13, no. 12 (2023): 2128. http://dx.doi.org/10.3390/diagnostics13122128.

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A universal calibrator for the determination of all anti-Xa inhibitors would support laboratory processes. We aimed to test the clinical performance of an anti-Xa assay utilizing a universal edoxaban calibrator to determine clinically relevant concentrations of all anti-Xa inhibitors. Following a pilot study, we enrolled 553 consecutive patients taking rivaroxaban, edoxaban, or apixaban from nine study centers in a prospective cross-sectional study. The Technochrom® anti-Xa assay was conducted using the Technoview® edoxaban calibrator. Using ultra-high-performance liquid chromatography-tandem
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28

Siddiqui, Fakiha, Siddharth Mehrotra, Vishnu Venkitasubramony, et al. "Factor Xa Inhibitory Profile of Apixaban, Betrixaban, Edoxaban and Rivaroxaban Does Not Fully Reflect Their Biologic Spectrum." Blood 132, Supplement 1 (2018): 2520. http://dx.doi.org/10.1182/blood-2018-99-116993.

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Abstract Introduction: There are four oral anti-Xa drugs currently available for clinical use in various indications. These drugs are claimed to mediate their therapeutic effects by solely targeting factor Xa. While these agents are structurally similar, their biochemical properties and their effects on blood coagulation differ. Such differences may impact their safety and efficacy profile. The purpose of this study was to demonstrate the differences among factor Xa inhibitors in terms of their in vitro anticoagulant activity and other biochemical effects. Materials and Methods: Commercially o
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Gosselin, Robert C., Dorothy M. (Adcock) Funk, J. Michael Taylor, et al. "Comparison of Anti-Xa and Dilute Russell Viper Venom Time Assays in Quantifying Drug Levels in Patients on Therapeutic Doses of Rivaroxaban." Archives of Pathology & Laboratory Medicine 138, no. 12 (2014): 1680–84. http://dx.doi.org/10.5858/arpa.2013-0750-oa.

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Context Rivaroxaban is a new oral anticoagulant that functions as a direct anti-Xa inhibitor. Although routine monitoring is not required, measurement of plasma concentrations may be necessary in certain clinical situations. Routine coagulation assays, such as the prothrombin time and, to a lesser degree, activated partial thromboplastin time, correlate with drug concentration, but because of reagent variability, these methods are not reliable for determining rivaroxaban anticoagulation. Objective To compare different methods and calibrators for measuring rivaroxaban, including the chromogenic
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30

Opoku, Akwasi, Kenneth Iwuji, Brendon Clough, et al. "Discordance between aPTT and anti-factor Xa levels and implications in patients receiving intravenous unfractionated heparin therapy." Southwest Respiratory and Critical Care Chronicles 7, no. 30 (2019): 12–18. http://dx.doi.org/10.12746/swrccc.v7i30.559.

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Heparin, one of the world’s oldest anticoagulation medications, accelerates the rate ofinhibition of previously activated clotting factors. It is most often used in the prophylaxis andtreatment of thromboembolic disorders and complications associated with atrial fibrillation.The two most common ways to monitor plasma heparin levels and anticoagulation therapyare the activated partial thromboplastin time (aPTT) and anti-factor Xa assay (anti-Xa). Thisarticle assesses the performance of aPTT and anti-Xa monitoring protocols and analyzes thediscordance between aPTT and anti-Xa levels and its clin
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31

Aubron, Cécile, Xavier Chapalain, Michael Bailey, et al. "Anti-Factor-Xa and Activated Partial Thromboplastin Time Concordance and Outcomes in Adults Undergoing Extracorporeal Membrane Oxygenation: A Secondary Analysis of the Pilot Low-Dose Heparin in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation Randomized Trial." Critical Care Explorations 5, no. 11 (2023): e0999. http://dx.doi.org/10.1097/cce.0000000000000999.

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OBJECTIVES: To determine the concordance between activated partial thromboplastin time (aPTT) and anti-factor-Xa (anti-Xa) in adults undergoing extracorporeal membrane oxygenation (ECMO) and to identify the factors associated with discordant paired aPTT/anti-Xa. DESIGN: Pre-planned secondary analysis of the Low-Dose Heparin in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation pilot randomized unblinded, parallel-group controlled trial. SETTING: Two ICUs in two university hospitals. PATIENTS: Thirty-two critically ill patients who underwent ECMO and who had at least one pai
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32

Hellstern, Peter, Juergen Bach, Melanie Simon, and Werner Saggau. "Heparin Monitoring During Cardiopulmonary Bypass Surgery Using the One-Step Point-of-Care Whole Blood Anti-Factor-Xa Clotting Assay Heptest-POC-Hi." Journal of ExtraCorporeal Technology 39, no. 2 (2007): 81–86. http://dx.doi.org/10.1051/ject/200739081.

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The activated clotting time (ACT) generally used for monitoring heparinization during cardiopulmonary bypass (CPB) surgery does not specifically measure heparin anticoagulant activities. This may result in heparin over- or under-dose and subsequent severe adverse events. A new point-of-care whole blood clotting assay (Heptest POC-Hi [HPOCH]) for quantifying heparin anticoagulant activity specifically was compared with ACT and anti-factor Xa (anti-Xa) heparin plasma levels (Coatest heparin) in 125 patients undergoing CPB surgery. The analytical reliability of the HPOCH and the influence of prea
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33

Ranucci, Marco, Mauro Cotza, Giuseppe Isgrò, Giovanni Carboni, Andrea Ballotta, and Ekaterina Baryshnikova. "Anti-Factor Xa–Based Anticoagulation during Extracorporeal Membrane Oxygenation: Potential Problems and Possible Solutions." Seminars in Thrombosis and Hemostasis 46, no. 04 (2019): 419–27. http://dx.doi.org/10.1055/s-0039-1697950.

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AbstractChoices for monitoring of unfractionated heparin (UFH) anticoagulation in extracorporeal membrane oxygenation (ECMO) patients include activated clotting time, activated partial thromboplastin time, reaction times of viscoelastic tests, and anti-factor Xa activity (between 0.3 and 0.7 IU/mL). Recent studies propose the anti-factor Xa to be the gold standard for monitoring UFH anticoagulation in ECMO. However, many extraneous factors combined question the utility of anti-factor Xa as the sole method of monitoring of UFH effects in ECMO. Anti-factor Xa is a chromogenic assay, which may be
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34

Delmas, Clément, Aemilia Jacquemin, Fanny Vardon-Bounes, et al. "Anticoagulation Monitoring Under ECMO Support: A Comparative Study Between the Activated Coagulation Time and the Anti-Xa Activity Assay." Journal of Intensive Care Medicine 35, no. 7 (2018): 679–86. http://dx.doi.org/10.1177/0885066618776937.

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Purpose: Extra Corporeal Membrane Oxygenation (ECMO) is used in cases of severe respiratory and/or circulatory failure over periods of several days to several weeks. Its circuitry requires a closely monitored anticoagulation therapy that is empirically supported by activated clotting time (ACT)—a method often associated with large inter- and intraindividual variability. We aimed to compare the measurement of heparin activity with ACT and the direct measurement of the heparin activity (anti-Xa) in a large ECMO population. Methods: All patients treated by venoarterial or venovenous ECMO in our i
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35

Martinoli, Jean-Luc, Léna LeFlem, Céline Guinet, et al. "Assessment of laboratory assays to measure rivaroxaban – an oral, direct factor Xa inhibitor." Thrombosis and Haemostasis 103, no. 04 (2010): 815–25. http://dx.doi.org/10.1160/th09-03-0176.

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SummaryAlthough there is no need for routine coagulation monitoring with rivaroxaban – an oral, direct factor Xa inhibitor – a haemostasis assay might be valuable to measure its pharmacodynamic effects. This study aimed to find assays, among those commercially available, to measure rivaroxaban pharmacodynamics. Several global conventional clotting tests, as well as clotting or chromogenic assays to measure anti-factor Xa activity, were studied. A thrombin generation test using calibrated automated thrombogram was also done. Tests were performed with the indirect factor Xa inhibitor fondaparinu
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36

Thakkar, Nikunj, Kannan Meganathan, Yash Gupta, et al. "Unfractionated Heparin Resourced from Bovine, Ovine, and Porcine Origin Is Bioequivalent." Blood 144, Supplement 1 (2024): 5577. https://doi.org/10.1182/blood-2024-211016.

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Introduction: Unfractionated heparin (UFH) in the United States is sourced from porcine mucosa and is mainly supplied from China. This sole dependence on one source can potentially lead to a serious health crisis for this essential medicine if there is a shortage of UFH due to any supply chain disruption. A realistic solution would be to develop bovine and ovine mucosa as alternate sources to porcine mucosa to produce UFH. In this study, the pharmacologic profile of single-sourced bovine, ovine, and porcine heparins were evaluated to demonstrate and validate their bio-equivalence. The immunolo
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Smogorzewska, Agata, John T. Brandt, Wayne L. Chandler, et al. "Effect of Fondaparinux on Coagulation Assays: Results of College of American Pathologists Proficiency Testing." Archives of Pathology & Laboratory Medicine 130, no. 11 (2006): 1605–11. http://dx.doi.org/10.5858/2006-130-1605-eofoca.

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Abstract Context.—Fondaparinux, a factor Xa inhibitor, is approved for thromboprophylaxis after orthopedic surgery and for treatment of venous thromboembolism. It may also be efficacious, safe, and cost-effective for other patients; thus, more widespread use of fondaparinux is likely. The effect of fondaparinux on coagulation testing needs to be thoroughly examined. Objective.—To report the effects of fondaparinux on coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, factor VIII, thrombin time, anti–factor Xa) across diverse methodologies. Des
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38

Siddiqui, Fakiha, Alfonso Tafur, Emily Bontekoe, et al. "Assay-Based Differentiation in the Neutralization Profile of Unfractionated Heparin, Enoxaparin, and Fondaparinux by Andexanet Alfa." Clinical and Applied Thrombosis/Hemostasis 26 (January 1, 2020): 107602961989512. http://dx.doi.org/10.1177/1076029619895120.

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Andexanet alfa is a recombinant factor Xa decoy protein, designed to reverse bleeding associated with oral anti-Xa agents. Andexanet alfa is also reported to neutralize the effects of heparin-related drugs. This study focused on the neutralization profiles of unfractionated heparin (UFH), enoxaparin, and, a chemically synthetic pentasaccharide, fondaparinux by andexanet alfa. Whole blood clotting studies were carried out using thromboelastography (TEG) and activated clotting time (ACT). The anticoagulant profile of UFH, enoxaparin, and fondaparinux was studied using the activated partial throm
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Lewis, Joseph, Omer Iqbal, Walter Jeske, Debra Hoppensteadt, Fakiha Siddiqui, and Jawed Fareed. "Differential Neutralization of Unfractionated Heparin and Enoxaparin by Andexanet Alfa." Clinical and Applied Thrombosis/Hemostasis 28 (January 2022): 107602962210999. http://dx.doi.org/10.1177/10760296221099934.

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Introduction Andexanet alfa (andexanet) is an approved antidote used to reverse the bleeding effects of Direct Oral Anticoagulant (Direct-Xa agents) agents because it reverses anti-Xa activity. Unfractionated heparin (UFH) and low molecular weight heparins (LMWHs) exhibit anti-Xa activity. The purpose is to investigate the neutralization of UFH and LMWH by andexanet in activated clotting time (ACT), thrombelastography (TEG), and anti-Xa due to the protamine sulfate shortage. Methods UFH and LMWH were studied with andexanet, PS, or saline as potential reversal agents/controls at varying concent
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Dalmora, Sérgio Luiz, Liberato Brum Júnior, Cleber Alberto Schmidt, Silvana Ferreira Vaccari, Paulo Renato Oliveira, and Cristiane Franco Codevilla. "Validation of the Anti-Factor Xa Assay for the Potency Assessment of Enoxaparin in Pharmaceutical Formulations." Journal of AOAC INTERNATIONAL 87, no. 6 (2004): 1305–8. http://dx.doi.org/10.1093/jaoac/87.6.1305.

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Abstract Enoxaparin is a low-molecular weight heparin used clinically for the prevention and treatment of venous and arterial thrombosis. An anti-factor Xa assay was used to evaluate the potency of the final drug preparation. Method validation investigated parameters such as the range, linearity (r2 = 0.9971), precision, accuracy, and robustness; the biological assay incorporated a chromogenic endpoint and detection at 405 nm. The method yielded good results with a quantitation limit of 0.037 IU/mL and a detection limit of 0.011 IU/mL. The results demonstrated the validity of the anti-factor X
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41

Bhagirath, Vinai, John Eikelboom, Jack Hirsh, et al. "Apixaban-Calibrated Anti-FXa Activity in Relation to Outcome Events and Clinical Characteristics in Patients with Atrial Fibrillation: Results from the AVERROES Trial." TH Open 01, no. 02 (2017): e139-e145. http://dx.doi.org/10.1055/s-0037-1613679.

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Background In patients with nonvalvular atrial fibrillation (AF), apixaban is given in doses of 5 or 2.5 mg twice daily, according to clinical characteristics. The usual on-treatment range of apixaban drug levels, as determined by apixaban-calibrated anti-factor Xa (anti-Xa) activity, has previously been measured in small cohorts; however, the association between anti-Xa activity and clinical outcomes and the predictors of variability in anti-Xa activity have not been well studied in the AF population. Methods and Results Anti-Xa activity was measured before taking the morning dose, 3 months a
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Triantos, Christos, Emmanuel Louvros, Maria Kalafateli, et al. "Endogenous Heparinoids Detected by anti-Xa Activity are Present in Blood during Acute Variceal Bleeding in Cirrhosis. A Prospective Study." Journal of Gastrointestinal and Liver Diseases 23, no. 2 (2014): 187–94. http://dx.doi.org/10.15403/jgld.2014.1121.232.cht1.

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Background & Aims: Endogenous heparinoids have been detected by thromboelastography and quantified by clotting based anti-Xa activity assays in patients with cirrhosis, but their presence in variceal bleeding has not been established yet.Methods: Clotting based anti-Xa activity was measured in A) 30 cirrhotics with variceal bleeding, B) 15 noncirrhotics with peptic ulcer bleeding, C) 10 cirrhotics without infection or bleeding, and D) 10 cirrhotics with hepatocellular carcinoma (HCC).Results: Anti-Xa activity was not detected in ulcer bleeders or in cirrhotics without infection or bleeding
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43

Keeney, Michael, and Michael Kovacs. "Inter-assay and Instrument Variability of Anti-Xa – Results." Thrombosis and Haemostasis 84, no. 07 (2000): 138. http://dx.doi.org/10.1055/s-0037-1613982.

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44

Grimaudo, V., A. Omri, E. K. O. Kruithof, J. Hauert, and F. Bachmann. "Fibrinolytic and Anticoagulant Activity After a Single Subcutaneous Administration of a Low Dose of Heparin or a Low Molecular Weight Heparin-Dihydroergotamine Combination." Thrombosis and Haemostasis 59, no. 03 (1988): 388–91. http://dx.doi.org/10.1055/s-0038-1647501.

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SummaryThe anticoagulant and potential profibrinolytic effect of a combination of low molecular weight heparin with dihydroergotamine (LMWH-DHE) and of unfractionated heparin was studied in eight healthy volunteers. Each volunteer received a subcutaneous injection of either LMWH-DHE (1,500 U anti-Xa of LMWH + 0.5 mg DHE), unfractionated heparin (5,000 IU) or of placebo (saline) between 7 and 8 h in the morning on three different occasions. Anti-Xa activity, and fibrinolytic activity measured by the euglobulin clot lysis time (ECLT) and by the fibrin plate assay were determined before and at di
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45

Lyon, Sandra G., Elliott C. Lasser, and Rosalyn Stein. "Modification of an Amidolytic Heparin Assay to Express Protein-Bound Heparin and to Correct for the Effect of Antithrombin III Concentration." Thrombosis and Haemostasis 58, no. 03 (1987): 884–87. http://dx.doi.org/10.1055/s-0038-1646008.

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SummaryA modification of an anti-Xa assay for plasma heparin has been devised using a low molecular weight dextran sulfate that competitively binds protein heparin neutralizers and displaces masked heparin. The addition of 0.12 mg dextran sulfate per ml of plasma permits heparin, neutralized by the products of platelet aggregation, to recover full functional activity against Xa. The assay will permit a more accurate assessment of both exogenous plasma heparin and endogenous liepaiin-like activity in blood samples collected with varying techniques. A further modification is proposed employing p
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46

Samama, Meyer Michel, Genevieve Contant, Theodore E. Spiro, et al. "Evaluation of the Anti-Factor Xa Chromogenic Assay for Measuring Rivaroxaban Plasma Concentrations Using Calibrators and Controls." Blood 116, no. 21 (2010): 3330. http://dx.doi.org/10.1182/blood.v116.21.3330.3330.

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Abstract Abstract 3330 Background: Rivaroxaban is an oral, direct Factor Xa inhibitor in an advanced stage of clinical development for the prevention and treatment of thromboembolic disorders. It inhibits Factor Xa activity without requiring cofactors (such as antithrombin) and has been found to have predictable pharmacokinetics and pharmacodynamics in humans. Routine coagulation monitoring is not required, but a quantitative determination of rivaroxaban concentrations might be useful in some cases, such as severe overdose or to measure compliance. Although the prothrombin time assay may be of
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47

Gray, Angel, Evangelos Litinas, Debra Hoppensteadt, et al. "Thrombin Generation Inhibition by Newer Anti Xa and Anti IIa Drugs in Prothrombin Complex Concentrates: Relevance to Endogenous Modulation of Thrombogenesis." Blood 118, no. 21 (2011): 1196. http://dx.doi.org/10.1182/blood.v118.21.1196.1196.

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Abstract Abstract 1196 Several anti-Xa agents (apixaban, otamixaban, rivaroxaban and edoxaban) and anti-IIa agents (dabigatran and melagatran) have been developed for clinical use. These agents are strong inhibitors of factor Xa and IIa and their potency is usually expressed in terms of the inhibitory parameters of these enzymes. These synthetic agents can also modulate thrombin and factor Xa generation in complex systems such as the platelet rich and platelet poor plasma and whole blood. The order of potency differs depending upon the type of matrix used due to cellular and protein binding an
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48

Buchanan, MR, B. Boneu, F. Ofosu, and J. Hirsh. "The relative importance of thrombin inhibition and factor Xa inhibition to the antithrombotic effects of heparin." Blood 65, no. 1 (1985): 198–201. http://dx.doi.org/10.1182/blood.v65.1.198.198.

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Abstract The relative importance of antithrombin and anti-factor Xa activities of heparin fractions required to achieve optimal antithrombotic effects is unknown. To study this, we measured the effects of standard heparin, an octasaccharide heparin fraction (anti-factor Xa activity only), and dermatan sulfate (antithrombin activity only) on the prevention of thrombosis and related this to their anticoagulant effects in vivo in rabbits. Thrombosis was measured as the incorporation of 125I- fibrinogen into tissue thromboplastin-induced thrombi using a Wessler- type model. Ex vivo changes in thro
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Buchanan, MR, B. Boneu, F. Ofosu, and J. Hirsh. "The relative importance of thrombin inhibition and factor Xa inhibition to the antithrombotic effects of heparin." Blood 65, no. 1 (1985): 198–201. http://dx.doi.org/10.1182/blood.v65.1.198.bloodjournal651198.

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The relative importance of antithrombin and anti-factor Xa activities of heparin fractions required to achieve optimal antithrombotic effects is unknown. To study this, we measured the effects of standard heparin, an octasaccharide heparin fraction (anti-factor Xa activity only), and dermatan sulfate (antithrombin activity only) on the prevention of thrombosis and related this to their anticoagulant effects in vivo in rabbits. Thrombosis was measured as the incorporation of 125I- fibrinogen into tissue thromboplastin-induced thrombi using a Wessler- type model. Ex vivo changes in thrombin clot
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50

Wagner, Lieselotte, Martina Leitner, Viktoria Kaufmann, and Jutta Mager. "Evaluation of Assay Performance Monitoring the New Oral Anticoagulants Rivaroxaban and Dabigatran." Blood 120, no. 21 (2012): 3424. http://dx.doi.org/10.1182/blood.v120.21.3424.3424.

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Abstract Abstract 3424 Introduction: Dabigatran etexilate is a new orally direct thrombin inhibitor and rivaroxaban is a new oral direct Factor Xa (FXa) inhibitor. The increasing use of the new oral anticoagulants administered for prevention of VTE in patients after orthopedic surgery creates the need of their measurement in the clinical routine. A modified thrombin time based assay can be used for measurement of thrombin inhibitors like dabigatran and the direct Xa inhibitor rivaroxaban can be measured with a chromogenic anti-Xa assay. The aim of this study was to evaluate the performance of
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