The Antiheparin Effect of α1-Acid Glycoprotein, Evaluated by the Activated Partial Thromboplastin Time and by a Factor Xa Assay for Heparin

1980 ◽  
Vol 9 (5) ◽  
pp. 303-309
Author(s):  
P. Andersen
Keyword(s):  
Partial Thromboplastin Time ◽  
Factor Xa ◽  
Activated Partial Thromboplastin Time ◽  
Acid Glycoprotein

scholarly journals Discordance in activated partial thromboplastin time and anti-factor Xa levels in COVID-19 patients on heparin therapy

2021 ◽  
Vol 198 ◽  
pp. 79-82
Author(s):  
Matthew Lawlor ◽  
Aakriti Gupta ◽  
Lauren S. Ranard ◽  
Mahesh V. Madhavan ◽  
Jianhua Li ◽  
...  
Keyword(s):  
Partial Thromboplastin Time ◽  
Factor Xa ◽  
Heparin Therapy ◽  
Activated Partial Thromboplastin Time

scholarly journals Clinical outcomes with unfractionated heparin monitored by anti‐factor Xa vs. activated partial Thromboplastin time

2019 ◽  
Vol 94 (9) ◽  
pp. 1015-1019 ◽  
Author(s):  
James C. Coons ◽  
Carlo J. Iasella ◽  
Megan Thornberg ◽  
Mary Grace Fitzmaurice ◽  
Kimberly Goehring ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Clinical Outcomes ◽  
Partial Thromboplastin Time ◽  
Factor Xa ◽  
Activated Partial Thromboplastin Time

Impact of Apixaban On a Large Panel of Routine or More Specific Coagulation Assays.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2275-2275
Author(s):  
Jonathan Douxfils ◽  
François Mullier ◽  
Christian Chatelain ◽  
Bernard Chatelain ◽  
Dogné Jean-Michel
Keyword(s):  
Atrial Fibrillation ◽  
Drug Concentration ◽  
Partial Thromboplastin Time ◽  
Factor Xa ◽  
Activated Partial Thromboplastin Time ◽  
Plasma Drug Concentration ◽  
Thrombin Time ◽  
Plasma Drug ◽  
Clotting Time

Abstract Abstract 2275 Introduction: Apixaban is direct factor-Xa inhibitor that reached the market for the prevention of venous thromboembolism in patients undergoing major orthopaedic surgery. It is also being evaluated in the reduction of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome and in the prevention of stroke in patients with non-valvular atrial fibrillation. Thanks to its predictable pharmacokinetic profile, biological monitoring is not required. Nevertheless, evaluation of plasma drug concentration may be valuable in specific situations such as recurrent thrombosis, bleedings, before urgent surgery, in case of bridging and in case of at least two risk factors among the following ones: drug interactions with caution, moderate renal impairment and moderate hepatic impairment; Monitoring may also be useful in infants, pregnant women or in extreme body weights, although no relevant data on drug levels associated with approximate therapeutic and harmful ranges are currently available. Material and Methods: Apixaban was spiked at increasing concentrations (0, 5, 10, 20, 50, 100, 200 and 500 ng/mL) in pooled citrated normal human platelet poor plasma (PPP) to measure Prothrombin Time (PT) and dilute PT with different thromboplastin, Thrombin Generation Assay (TGA) with different inducers and activity on different anti-Xa chromogenic assays. Activated Partial Thromboplastin Time with different reagents, Thrombin Time (TT), Ecarin Clotting Time (ECT) and Reptilase Time (RT), measurement of fibrinogen (Clauss method and PT-derived method) and antithrombin (anti-IIa and anti-Xa based chromogenic assays) were also tested. We also evaluated the impact of apixaban on assays used for the determination of lupus anticoagulant such as the DRVV-T.. (Screen and Confirm) as well as the PTT-LA.. and the Staclot-LA.. . Results and Discussion: As mentioned in previous studies, PT showed a weak sensitivity towards apixaban in comparison with the plasma range obtained in short pharmacokinetic studies. Indeed, the concentration needed to double the clotting time was 154 ng/mL with the most sensitive reagent while the mean Cmax obtained in a short PK study after one oral intake of 5 mg apixaban (dose given in atrial fibrillation) was 96 ng/mL. Therefore, the sensitivity of PT is not strong enough to allow accurate quantitative measurement of the plasma drug concentration (Table 1). Activated Partial Thromboplastin Time presented a better sensitivity but showed a plateau after 100 ng/mL reflecting the uselessness of this test for the quantification of apixaban. Thrombin Time, ECT and RT were logically not affected while DRVV-T.. showed a sensitivity of 205 ng/mL (Screen), which is once again not enough sensitive. On the opposite, chromogenic anti-Xa assays seemed to be very sensitive (Figure 2 and Table 1). Nevertheless, the relation was not always linear and some methodologies needed to be adapted to ensure a broader range of application. TGA (Figure 1) may be useful to assess the pharmacodynamics effects of apixaban on the coagulation process. Nevertheless, the turn around time and the lack of standardisation are currently limitations that restrict the use of this method. In the case of the exploration of an haemorrhagic event, specific tests such as RT, fibrinogen (Clauss and PT-derived method (dFib)), TT and clotting factor activity may be used. Apixaban did not interfere with these tests. Antithrombin determination if also of importance and chromogenic anti-IIa based assays should be used in face of patients treated with apixaban to avoid misdiagnosis since an overvaluation of 12% by 100 ng/mL was shown using one chromogenic anti-Xa based assay. Conclusion: PT may not be used as screening test to assess the risk of bleedings. A more specific and sensitive assay such as chromogenic anti-Xa assays using calibrators should be used to correctly assess the concentration of apixaban. Determination of lupus anticoagulant using DRVV-T.. and PTT-LA.. or Staclot LA.. as well as the determination of antithrombin using factor-Xa based chromogenic assays, were influenced by apixaban. Finally, standardization of the time between the last intake of apixaban and the sampling is mandatory. Figures: Disclosures: No relevant conflicts of interest to declare.

scholarly journals Performance of Anti-Factor Xa Versus Activated Partial Thromboplastin Time for Heparin Monitoring Using Multiple Nomograms

2017 ◽  
Vol 24 (2) ◽  
pp. 310-316 ◽  
Author(s):  
Emily Whitman-Purves ◽  
James C. Coons ◽  
Taylor Miller ◽  
Jeannine V. DiNella ◽  
Andrew Althouse ◽  
...  
Keyword(s):  
Partial Thromboplastin Time ◽  
Factor Xa ◽  
Activated Partial Thromboplastin Time ◽  
Heparin Monitoring

Effectiveness of a Calculation-Free Weight-Based Unfractionated Heparin Nomogram With Anti-Xa Level Monitoring Compared With Activated Partial Thromboplastin Time

2020 ◽  
pp. 106002802096150
Author(s):  
Nicole M. Kindelin ◽  
Ananth M. Anthes ◽  
Sarah M. Providence ◽  
Xinhua Zhao ◽  
Sherrie L. Aspinall
Keyword(s):  
Unfractionated Heparin ◽  
Partial Thromboplastin Time ◽  
Adverse Drug Events ◽  
Factor Xa ◽  
Primary Objective ◽  
Activated Partial Thromboplastin Time ◽  
Historical Control ◽  
Dose Calculations ◽  
Free Weight ◽  
Therapeutic Anticoagulation

Background Accurate monitoring of intravenous unfractionated heparin (UFH) is essential to mitigate the risk of adverse drug events associated with dosing errors. Although recent data support anti-factor Xa (anti-Xa) monitoring preferentially over activated partial thromboplastin time (aPTT) to improve time to therapeutic anticoagulation, the utility of incorporating anti-Xa monitoring with a calculation-free weight-based UFH nomogram has not been formally evaluated. Objective The primary objective of this study was to evaluate the time to therapeutic anticoagulation of a calculation-free weight-based UFH nomogram integrated with anti-Xa monitoring versus a historical control of aPTT monitoring utilizing manual dose calculations. Methods This was a retrospective analysis of patients with anti-Xa monitoring and a novel calculation-free weight-based UFH nomogram compared with a historical control with aPTT monitoring and manual calculations. Results A total of 103 patients in the aPTT cohort and 100 patients in the anti-Xa cohort were analyzed. The anti-Xa cohort achieved goal therapeutic target 3.8 hours sooner than the aPTT cohort ( P = 0.03). Patients with anti-Xa monitoring required 1 fewer adjustment per 2.5 patient-days of UFH with the venous thromboembolism nomogram ( P = 0.02). Patients in the aPTT cohort required more infusion interruptions because of supratherapeutic values ( P = 0.007) and boluses because of subtherapeutic values ( P = 0.044). There were no differences in rates of thromboembolism, major bleeding, or clinically relevant nonmajor bleeding between the cohorts. Conclusion and Relevance This study demonstrated that anti-Xa UFH monitoring integrated with a calculation-free nomogram results in faster time to therapeutic anticoagulation and fewer dose adjustments compared with aPTT monitoring with manual calculations.

Effect of Fondaparinux on Coagulation Assays: Results of College of American Pathologists Proficiency Testing

2006 ◽  
Vol 130 (11) ◽  
pp. 1605-1611 ◽  
Author(s):  
Agata Smogorzewska ◽  
John T. Brandt ◽  
Wayne L. Chandler ◽  
Mark T. Cunningham ◽  
Timothy E. Hayes ◽  
...  
Keyword(s):  
Factor Viii ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Factor Xa ◽  
Cost Effective ◽  
Activated Partial Thromboplastin Time ◽  
Thrombin Time ◽  
Standard Curve ◽  
Relevant Effect ◽  
Clinically Significant

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. Design.—Samples with different concentrations of fondaparinux (0, 0.4, 0.8, and 2.0 μg/mL) were sent to laboratories participating in the College of American Pathologists Comprehensive Coagulation proficiency survey (N = 898). Laboratory-specific methods were used to assay coagulation parameters. Results.—Prophylactic or therapeutic fondaparinux prolonged the prothrombin time by approximately 1 second and the activated partial thromboplastin time by 4 to 5 seconds, and reduced factor VIII from 119% to 107% and 102%, respectively. Supratherapeutic fondaparinux reduced factor VIII to 85%. The activated partial thromboplastin time was prolonged in 19%, 29%, and 52% of laboratories with prophylactic, therapeutic, and supratherapeutic fondaparinux levels, respectively. Fibrinogen, antithrombin, and thrombin time assays did not show clinically significant changes. When measuring fondaparinux concentration using an anti–factor Xa assay, the most accurate results were obtained when fondaparinux was used as the calibrator. Conclusions.—Fondaparinux, even in prophylactic doses, slightly prolongs the prothrombin time and activated partial thromboplastin time and can interfere with factor VIII assays, but it has no clinically relevant effect on fibrinogen, antithrombin, or thrombin time. A fondaparinux standard curve should be used for reporting fondaparinux levels using an anti–factor Xa assay.

Interlaboratory Precision in the Monitoring of Unfractionated Heparin Using the Anti-Factor Xa-Correlated Activated Partial Thromboplastin Time

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 435-435
Author(s):  
Adam Cuker ◽  
Beverly Ptashkin ◽  
Barbara A. Konkle ◽  
Steven W. Pipe ◽  
Herbert C. Whinna ◽  
...  
Keyword(s):  
Unfractionated Heparin ◽  
Therapeutic Range ◽  
Partial Thromboplastin Time ◽  
Factor Xa ◽  
Correlation Method ◽  
Activated Partial Thromboplastin Time ◽  
Laboratory Monitoring ◽  
Upper Limit ◽  
Accuracy And Precision ◽  
Therapeutic Category

Abstract Although the activated partial thromboplastin time (aPTT) remains the most widely used method for monitoring unfractionated heparin (UFH) therapy, it is affected by a number of preanalytic, analytic, and biological variables, which undermine both its accuracy and precision. In an effort to improve the accuracy and precision of laboratory monitoring of UFH, the College of American Pathologists (CAP) and the American College of Chest Physicians (ACCP) have issued guidelines recommending that the therapeutic range of the aPTT be defined in each laboratory through correlation with a direct measurement of heparin activity such as the factor Xa inhibition assay (anti-FXa). Whether and to what extent this approach enhances the precision of UFH monitoring has not been reported. We conducted a cross-validation study among 4 CAP-accredited coagulation laboratories to assess the interlaboratory precision of the anti-FXa-correlation method. An aPTT and anti-FXa were performed in each laboratory on plasma samples from 44 inpatients receiving UFH. Interlaboratory precision of the anti-FXa-correlation method was compared to that of the traditional 1.5–2.5 times the upper limit of normal (ULN) method for defining the therapeutic aPTT range. Modest to poor intralaboratory correlation between the aPTT and anti-FXa was observed in each of the 4 laboratories. The coefficients of determination (R2) ranged from 0.1962 to 0.6964. In accordance with CAP guidelines, the anti-FXa-derived therapeutic aPTT range was defined by linear regression corresponding to a range of anti-FXa activity of 0.3 – 0.7 units/ml. In each laboratory, the range defined by this method was broader than that defined using the ULN method. In 3 of the laboratories, the therapeutic range defined by the anti-FXa-correlation method extended more than 20 seconds beyond the upper limit of the therapeutic range defined by the ULN approach. Based on the laboratory-specific therapeutic ranges defined by both methods, samples were segregated into therapeutic category [i.e. below therapeutic (BT), therapeutic (T), or above therapeutic (AT)]. Using the ULN method, there was agreement among all 4 laboratories regarding the therapeutic category in 22 (50%) samples, whereas consensus was achieved in only 7 (16%) samples with the anti-FXa-correlation method. Furthermore, 3 (7%) samples were simultaneously determined to be BT and AT in different laboratories by the anti-FXa-correlation method, suggesting that the dose of UFH might be increased in one center and decreased in another for the same patient encounter. This striking discrepancy was not observed with the ULN method. In conclusion, the anti-FXa-correlation method for defining the therapeutic range of the aPTT does not enhance the interlaboratory precision of UFH laboratory monitoring and may be inferior to the ULN method in this regard. Clinical studies are needed to assess the impact of these findings on patient safety.

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