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Jack Hirsh - One of the best experts on this subject based on the ideXlab platform.
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relationship of activated Partial Thromboplastin Time to coronary events and bleeding in patients with acute coronary syndromes who receive heparin
Circulation, 2003Co-Authors: Sonia S Anand, Jeffrey S Ginsberg, Salim Yusuf, Janice Pogue, Jack HirshAbstract:Background— Antithrombotic therapy with intravenous heparin in conjunction with aspirin reduces negative cardiovascular (CV) outcomes in patients with acute coronary syndromes. The need for a therapeutic range with the activated Partial Thromboplastin Time (APTT) has not been validated in patients with arterial thrombosis who receive heparin. Therefore, it is unclear whether there is an association between recurrent CV events and low APTT values and between bleeding and high APTT values. Methods and Results— We examined the relationship between the APTT and recurrent cardiovascular events and bleeding among 5058 patients with an acute coronary syndrome without ST elevation who received intravenous heparin in the OASIS-2 trial. The increase in relative risk of recurrent CV events was 1.54 (95% CI 1.10 to 2.15; P=0.01) among patients with APTT values <60 seconds compared with patients with APTT values ≥60 seconds. When patients had persistently subtherapeutic APTT values for more than 48 hours, the increase...
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use of a fixed activated Partial Thromboplastin Time ratio to establish a therapeutic range for unfractionated heparin
JAMA Internal Medicine, 2001Co-Authors: Shannon M Bates, Jeffrey I Weitz, Marilyn Johnston, Jack Hirsh, Jeffrey S GinsbergAbstract:Background: The commonly recommended therapeutic range for patients receiving unfractionated heparin of 1.5 to 2.5 Times the control activated Partial Thromboplastin Time (aPTT) is not universally applicable. It has been suggested that the therapeutic range for each aPTT reagent should be based on plasma heparin levels. We sought to identify an aPTT ratio that corresponds to therapeutic anti‐factor Xa heparin levels for combinations of several reagents and coagulometers that are commonly used. Methods: Citrated plasma was collected from 126 unselected patients receiving unfractionated heparin. Four automated coagulometers and 6 commercial aPTT reagents were used to measure the aPTT. Plasma anti‐ factor Xa levels were measured by means of a commercially available assay. The relationship between the aPTT results and anti‐factor Xa heparin levels for each reagent-coagulometer combination was determined by linear regression analysis, and the aPTT results corresponding to therapeutic anti‐factor Xa heparin levels were calculated. Results: For all reagent-coagulometer combinations studied, an aPTT ratio of 1.5 resulted in anti‐factor Xa heparin levels considerably below the lower limit of the therapeutic range. When the aPTT was performed on any of the coagulometers assessed with the use of Actin (Dade Diagnostics, Aguada, Puerto Rico) and IL Test (Instrumentation Laboratories, Fisher Scientific, Unionville, Ontario) reagents, aPTT ratios necessary to achieve therapeutic anti‐ factor Xa heparin levels approximated 2.0 to 3.5. Conclusion: For laboratories that cannot perform heparin levels, the use of less responsive reagents and any of the coagulometers studied, along with target aPTT ratio between 2.0 and 3.5, appears to be a reasonable alternative.
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activated Partial Thromboplastin Time and outcome after thrombolytic therapy for acute myocardial infarction results from the gusto i trial
Circulation, 1996Co-Authors: Christopher B Granger, Jack Hirsh, Harvey D White, Robert M Califf, Jacques Col, Amadeo Betriu, Lynn H Woodlief, Kerry L Lee, Edwin G Bovill, John R SimesAbstract:Background Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated Partial Thromboplastin Time (aPTT) in 29 656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes. Methods and Results Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P<.00001) as well as older age, female sex, and lack of cigarette smoking (all P<.0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rater; was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of rt infarction in the first 10 hours after discontinuation of intravenous heparin. Conclusions Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should oo consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy.
Samuel Weinstein - One of the best experts on this subject based on the ideXlab platform.
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anti factor xa assay is a superior correlate of heparin dose than activated Partial Thromboplastin Time or activated clotting Time in pediatric extracorporeal membrane oxygenation
Pediatric Critical Care Medicine, 2014Co-Authors: Anna Liveris, Ricardo Bello, Patricia Friedmann, Melissa Duffy, Deepa Manwani, James S Killinger, Daniel Rodriquez, Samuel WeinsteinAbstract:Objective:To assess the utility of activated clotting Time, activated Partial Thromboplastin Time, and anti-Factor Xa assay for the monitoring and dosing of heparin in pediatric patients requiring support with extracorporeal membrane oxygenation.Design:Retrospective chart review.Setting:PICU in a si
Peter D Wearden - One of the best experts on this subject based on the ideXlab platform.
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activated Partial Thromboplastin Time is a better trending tool in pediatric extracorporeal membrane oxygenation
Pediatric Critical Care Medicine, 2012Co-Authors: Timothy M Maul, Erin L Wolff, Bradley A Kuch, Adam Rosendorff, Victor O Morell, Peter D WeardenAbstract:OBJECTIVES To determine whether activated Partial Thromboplastin Times are a better heparin management tool than activated clotting Times in pediatric extracorporeal membrane oxygenation. DESIGN A single-center retrospective analysis of perfusion and patient records. SETTING Academic pediatric tertiary care center. PATIENTS Pediatric patients (<21 yrs old) requiring extracorporeal membrane oxygenation support initiated at Children's Hospital of Pittsburgh. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Point-of-care activated clotting Time and activated Partial Thromboplastin Time values, clinical laboratory activated Partial Thromboplastin Time values, weight-normalized heparin administration (units/kg/hr), and reported outcomes were collected for pediatric patients treated for cardiac and/or respiratory failure with extracorporeal membrane oxygenation. Spearman's ranked correlations were performed for each coagulation test compared to heparin dosage. The Bland-Altman test was used to determine the validity of the point-of-care activated Partial Thromboplastin Time. Hazard analysis was conducted for outcomes and complications for patients whose heparin management was based on the clinical laboratory activated Partial Thromboplastin Time or the activated clotting Time. Only the clinical laboratory activated Partial Thromboplastin Time showed a correlation (ρ = 0.40 vs. ρ = -0.04 for activated clotting Time) with the heparin administration (units/kg/hr). Point-of-care activated Partial Thromboplastin Time and activated Partial Thromboplastin Time values correlated well (ρ = 0.76), with <5% of samples showing a difference outside 2 SDs, but differences in their absolute values (Δactivated Partial Thromboplastin Time = 100 secs) preclude them from being interchangeable measures. Furthermore, despite no effective change in the mean activated clotting Time, cardiac patients showed a significantly improved correlation to heparin dose for all coagulation tests (e.g., point-of-care activated Partial Thromboplastin Time ρ = 0.60). Management of patients with the clinical laboratory activated Partial Thromboplastin Time did not significantly affect patient survival rates but did significantly reduce bleeding complications and significantly increased clotting in the extracorporeal membrane oxygenation circuit. A hazard analysis demonstrated that bleeding complications were associated with an increased risk of mortality, whereas clotting complications in the extracorporeal membrane oxygenation circuit were not. CONCLUSIONS The activated clotting Time is not an accurate monitoring tool for heparin management in pediatricextracorporeal membrane oxygenation. The point-of-care activated Partial Thromboplastin Time correlates well with the clinical laboratory activated Partial Thromboplastin Time but cannot be substituted for the clinical laboratory activated Partial Thromboplastin Time values. Management of pediatric extracorporeal membrane oxygenation patients with the clinical laboratory activated Partial Thromboplastin Time reduced bleeding complications which are associated with increases in mortality.
S Kitchen - One of the best experts on this subject based on the ideXlab platform.
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limitation of the activated Partial Thromboplastin Time as a monitoring method of the direct thrombin inhibitor argatroban
International Journal of Laboratory Hematology, 2015Co-Authors: Susan Guy, S Kitchen, Rhona Maclean, J J Van VeenAbstract:SummaryBackground Argatroban is licensed for patients with heparin-induced thrombocytopenia and monitoring is conventionally by activated Partial Thromboplastin Time (APTT) ratio with a target of 1.5–3.0 and not exceeding 100 s. The APTT may be influenced by coagulopathies, lupus anticoagulant and raised FVIII levels. Variable but not clinically significant sensitivity of APTT reagents to argatroban has been highlighted in other studies. Methods Residual plasma of 15 patients (n = 124 samples) was tested on Sysmex™ CS series using the Hemoclot® thrombin inhibitor assay (HTI) and APTT ratio (Actin FS and SynthASil). A subgroup from four patients (n = 31) were tested on ACL TOP™ to compare the different platforms with the HTI. Spiked normal pooled plasma was tested with Actin FS, Actin FSL, SynthASil and APTT-SP on their respective platforms (CS5100™ and ACL TOP™) to assess reagent sensitivity. Results Mean concentration of argatroban by HTI assay for patient plasma was 0.47 μg/mL; the mean APTT ratio using Actin FS was 1.89 and for SynthASil 1.56. There was a poor correlation between APTT and the HTI. In the spiked normal pooled plasma, Actin FS gave a significantly higher APTT ratio than the other three reagents for the various argatroban concentrations. Conclusions Hemoclot ® thrombin inhibitor assay should be considered in patients on argatroban, particularly if there is concern the APTT may not be reflective of the degree of anticoagulation with argatroban due to other factors including coagulopathies in critically ill patients, the presence of a lupus anticoagulant or very high FVIII levels.
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dabigatran effects on the international normalized ratio activated Partial Thromboplastin Time thrombin Time and fibrinogen a multicenter in vitro study
Annals of Pharmacotherapy, 2012Co-Authors: William E Dager, Robert C Gosselin, S Kitchen, Denis M DwyreAbstract:Background:Patients receiving the direct thrombin inhibitor dabigatran may have selected anticoagulation assays performed as part of routine care. The effect of dabigatran on the international normalized ratio (INR), activated Partial Thromboplastin Time (aPTT), thrombin Time (TT), and fibrinogen requires clarification.Objective:To describe the effect of dabigatran on selected assays in North America and the United Kingdom.Methods:Pooled normal plasma enriched with dabigatran at concentrations of 25, 50, 75, 100, 125, 150, 200, 300, 400, and 500 ng/mL were sent blinded to 19 centers in the US, the UK, and Canada to assess the effect of dabigatran on routine coagulation screening tests, the INR, aPTT, TT, and fibrinogen.Results:Data were returned from 16 centers. For effects on INR, Neoplastine CI Plus and Simplastin HTF were the most sensitive and Thromborel S the least sensitive to increasing dabigatran concentrations. For the aPTT, all reagents demonstrated decreasing sensitivity to increasing dabigatra...
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the therapeutic range for heparin therapy relationship between six activated Partial Thromboplastin Time reagents and two heparin assays
Thrombosis and Haemostasis, 1996Co-Authors: S Kitchen, F E PrestonAbstract:The activated Partial Thromboplastin Time (APTT) is the most commonly used test for laboratory monitoring of unfractionated heparin therapy. Since there are differences between APTT reagents in respect of responsiveness to heparin the widely used therapeutic range of 1.5-2.5 (APTT ratios) may not be appropriate for all reagents. The aim of this study was to assess the relationship between 6 different APTT reagents using a manual technique, 2 of these reagents used in combination with a coagulometer, a heparin assay by protamine titration and a chromogenic anti-Xa assay. Samples from 42 patients treated with unfractionated heparin for thromboembolic disease were studied, 12 of whom were receiving warfarin therapy with International Normalised Ratios (INR) of > 1.3. For normal subjects, APTT results were highly dependent on the method used and statistically significant differences were noted. The ratio of patient to mean normal APTT was calculated for each APTT method. When 30 samples from heparinised patients (with INRs of < 1.3) were analysed manually, the APTT ranges equivalent to 0.2-0.4 u/ml heparin by protamine titration (by regression analysis) were 1.6-1.9 for Boehringer reagent (the least responsive) up to 2.2-2.9 for Instrumentation Laboratory reagent (the most responsive). The concentration of heparin associated on average with APTT ratios of 1.5-2.5 varied approximately twofold to threefold between reagents.
Marc Zumberg - One of the best experts on this subject based on the ideXlab platform.
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activated Partial Thromboplastin Time versus antifactor xa heparin assay in monitoring unfractionated heparin by continuous intravenous infusion
Annals of Pharmacotherapy, 2011Co-Authors: David J Guervil, Amy F Rosenberg, Almut G Winterstein, Neil S Harris, Thomas E Johns, Marc ZumbergAbstract:Background:Unfractionated heparin (UFH) has been used clinically for 5 decades. Despite being a cornerstone of anticoagulation, UFH is limited by its unpredictable pharmacokinetic profile, which makes close laboratory monitoring necessary. The most common methods for monitoring UFH are the activated Partial Thromboplastin Time (aPTT) and antifactor Xa heparin assay (anti-Xa HA), but both present challenges, and the optimal method to monitor UFH remains unclear.Objective:To compare the performance of the aPTT with the anti-Xa HA for efficiency and safety of monitoring intravenous UFH infusions.Methods:This was a single-center, retrospective, observational cohort study conducted in an 852-bed academic medical center.Results:One hundred patients receiving intravenous UFH for a variety of indications were enrolled in the study; 50 were assigned to each group. The mean (SD) Time to achieve therapeutic anticoagulation was significantly less in the anti-Xa HA group compared with the aPTT group (28 [16] vs 48 [26...