Monitoring Anticoagulant Therapy by Activated Partial Thromboplastin Time: Hirudin Assessment

1994 ◽  
Vol 72 (05) ◽  
pp. 685-692 ◽  
Author(s):  
Michael T Nurmohamed ◽  
René J Berckmans ◽  
Willy M Morriën-Salomons ◽  
Fenny Berends ◽  
Daan W Hommes ◽  
...  
Keyword(s):  
Whole Blood ◽  
Partial Thromboplastin Time ◽  
Ex Vivo ◽  
Fold Increase ◽  
Heparin Therapy ◽  
Activated Partial Thromboplastin Time ◽  
Recombinant Hirudin ◽  
Interindividual Differences ◽  
The Relationship

SummaryBackground. Recombinant hirudin (RH) is a new anticoagulant for prophylaxis and treatment of venous and arterial thrombosis. To which extent the activated partial thromboplastin time (APTT) is suitable for monitoring of RH has not been properly evaluated. Recently, a capillary whole blood device was developed for bed-side monitoring of the APTT and it was demonstrated that this device was suitable to monitor heparin therapy. However, monitoring of RH was not evaluated.Study Objectives. To evaluate in vitro and ex vivo the responsiveness and reproducibility for hirudin monitoring of the whole blood monitor and of plasma APTT assays, which were performed with several reagents and two conventional coagulometers.Results. Large interindividual differences in hirudin responsiveness were noted in both the in vitro and the ex vivo experiments. The relationship between the APTT, expressed as clotting time or ratio of initial and prolonged APTT, and the hirudin concentration was nonlinear. A 1.5-fold increase of the clotting times was obtained at 150-200 ng/ml plasma. However, only a 2-fold increase was obtained at hirudin levels varying from 300 ng to more than 750 ng RH/ml plasma regardless of the assays. The relationship linearized upon logarithmic conversion of the ratio and the hirudin concentration. Disregarding the interindividual differences, and presuming full linearity of the relationship, all combinations were equally responsive to hirudin.Conclusions. All assays were equally responsive to hirudin. Levels up to 300 ng/ml plasma can be reliably estimated with each assay. The manual device may be preferable in situations where rapid availability of test results is necessary.

Monitoring Heparin Therapy: Relationships between the Activated Partial Thromboplastin Time and Heparin Assays Based on Ex-Vivo Heparin Samples

1990 ◽  
Vol 63 (01) ◽  
pp. 016-023 ◽  
Author(s):  
A M H P van den Bessekaar ◽  
J Meeuwisse-Braun ◽  
R M Bertina
Keyword(s):  
Partial Thromboplastin Time ◽  
Plasma Sample ◽  
Ex Vivo ◽  
Correlation Coefficients ◽  
Heparin Therapy ◽  
Thromboembolic Disease ◽  
Activated Partial Thromboplastin Time ◽  
Venous Thromboembolic Disease ◽  
Venous Thromboembolic

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 coefficients: 0.92-0.97). However, the amidolytic anti-Xa activity was significantly higher (p <0.001) than the two amidolytic anti-IIa activities. Less good correlations were observed between the log-transformed APTTs and the anti-Xa or anti-IIa activities (correlation coefficients: 0.64-0.78). The correlations were improved by transforming the APTT into APTT-ratio, i.e. the ratio of the patient’s APTT to the same patient’s APTT after removal of heparin from the plasma sample by means of ECTEOLA-cellulose treatment. The correlation coefficients of log (AFTT-ratio) with anti-Xa or anti-IIa ranged from 0.76 to 0.87.For both APTT and amidolytic heparin assay, the response to in vitro heparin was different from the response to ex vivo heparin.Therefore, equivalent therapeutic ranges should be assessed by using ex vivo samples rather than in vitro heparin. Because of the response differences between the APTT reagents, it is not adequate to define a therapeutic range for heparin therapy without specification of the reagent.

scholarly journals Inhibition of Stimulated Interleukin-2 Production in Whole Blood: A Practical Measure of Cyclosporine Effect

1999 ◽  
Vol 45 (9) ◽  
pp. 1477-1484 ◽  
Author(s):  
C Michael Stein ◽  
John J Murray ◽  
Alastair JJ Wood
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Interleukin 2 ◽  
Major Effect ◽  
Biologically Relevant ◽  
Maximum Inhibition ◽  
Before And After ◽  
Dose Dependent Fashion ◽  
The Relationship

Abstract Background: Prediction of cyclosporine (CSA) efficacy and toxicity in individual patients is difficult. There is no practical, biologically relevant, pharmacodynamic measure of CSA effect. A major effect of CSA is to decrease interleukin-2 (IL-2) production; however, measurement of this effect in isolated lymphocytes as a marker of response to CSA has been problematic. Methods: CSA inhibition of phytohemagglutinin-P (PHA)-stimulated IL-2 production, measured by ELISA, was studied ex vivo in whole blood drawn before, and after subjects received 4 mg/kg oral CSA. Results: Four hours after CSA was administered, the mean (± SD) CSA concentration was 702 ± 196 μg/L and PHA-stimulated IL-2 production decreased by 68.7% ± 17.2% (P &lt;0.0001; n = 17). Twenty-four hours after CSA was administered, concentrations were low (64 ± 24 μg/L), with no inhibition of IL-2 production. A rapid, concentration-dependent response occurred. Maximum CSA concentrations (944 ± 187 μg/L) and maximum inhibition of IL-2 production (86.9% ± 13.7%) occurred 90 min after subjects received CSA. In vitro, 32.5–1200 μg/L CSA also inhibited PHA-stimulated IL-2 production in whole blood in a dose-dependent fashion with a similar IC50 (∼300–400 μg/L) ex vivo and in vitro. Conclusion: In the search for a pharmacodynamic marker to better guide immunosuppressive therapy, the relationship between this simple, biologically relevant measure of CSA effect and clinical outcome should be determined.

State-of-the-Art Review : Activated Partial Thromboplastin Time in Heparinized Plasma: Influence of Reagent, Acute-Phase Reaction, and Interval Between Sampling and Testing

1996 ◽  
Vol 2 (3) ◽  
pp. 169-176 ◽  
Author(s):  
Finn G. Strekerud ◽  
Ulrich Abildgaard
Keyword(s):  
Acute Phase ◽  
State Of The Art ◽  
Ex Vivo ◽  
Heparin Therapy ◽  
Activated Partial Thromboplastin Time ◽  
Acute Phase Reaction ◽  
Phase Reaction ◽  
Prolonged Aptt ◽  
Healthy Persons

Plasma samples from 10 healthy persons and 10 patients with acute-phase reaction were heparinized in vitro to obtain up to 0.70 U/ml. Activated partial throm boplastin time (APTT) was then determined using an op tical method (Automated Coagulation Laboratory or ACL Machine) and four different reagents (Actin, Ceph otest, Platelin, and Thrombosil). Heparin sensitivity var ied between individuals, and it was lower in acute-phase plasma than in healthy plasma. There was also a marked difference in heparin sensitivity among the different re agents; Actin was the least sensitive reagent, while Plate lin was the most sensitive reagent in healthy plasma and Thrombosil the most sensitive reagent in acute-phase plasma. Delay in testing prolonged the APTT values both in acute-phase and healthy heparinized plasma. With Ac tin and Cephotest, a delay of 90 min at 22°C resulted in 30-50% prolongation of APTT. A delay of 150 min caused a prolongation of 75-110% with Actin. Cephotest, Plate lin, and Thrombosil were less prolonged. Ex vivo samples from heparinized plasma showed similar degrees of pro longation. Storage at 4°C resulted in less prolongation. Assuming a therapeutic range of 0.35-0.70 U/ml of hep arin, the therapeutic APTT ratios in heparinized acute- phase plasma were 1.5-3.0 for Actin and 2.5-4.5 for Cephotest, Platelin, and Thrombosil. These results un derscore certain limitations in monitoring heparin therapy with the APTT system. Unless the assay is performed within 30 min after sampling, unduly prolonged APTT values will be recorded, which may lead to giving the patient an inappropriately small dose of heparin.

Chemorheological Studies of the Effect of Heparin on the Course of Coagulation

1976 ◽  
Vol 35 (02) ◽  
pp. 447-459
Author(s):  
K. A Overholser ◽  
C. B Baysinger ◽  
T. R Harris ◽  
T Deveau
Keyword(s):  
Whole Blood ◽  
Partial Thromboplastin Time ◽  
Time Course ◽  
Normal Subjects ◽  
Activated Partial Thromboplastin Time ◽  
Weissenberg Rheogoniometer ◽  
Rheological Measurements ◽  
Kinetics Of

SummaryThe influence of sodium heparin on viscoelastic change during coagulation was determined in vitro for whole blood samples from ten normal subjects at heparin concentrations ranging from 0 to 1.45 units/(ml whole blood). A four-parameter chemorheological model was used to describe the time course of coagulation as measured by the Weissenberg Rheogoniometer. One parameter compares closely with the whole blood activated partial thromboplastin time, while the other three may be related to the chemical kinetics of clotting.The chemorheological model and experimental techniques were then tested in a dog preparation. It was found that rheological measurements are more self-consistent than either thrombelastography or the activated partial thromboplastin time for the assay of in vivo heparin in two dogs.

Use of the Activated Partial Thromboplastin Time in the Control of Heparin Administration

1966 ◽  
Vol 12 (5) ◽  
pp. 263-268 ◽  
Author(s):  
Jane G Lenahan ◽  
Sheldon Frye ◽  
George E Phillips
Keyword(s):  
Therapeutic Range ◽  
Whole Blood ◽  
Partial Thromboplastin Time ◽  
Blood Clotting ◽  
Heparin Therapy ◽  
Activated Partial Thromboplastin Time ◽  
Clotting Time ◽  
Heparin Administration ◽  
Blood Clotting Time

Abstract The activated partial thromboplastin time (APTT) was compared to the whole blood clotting time (WBCT) as a control of heparin administration. The APTT was shown to be a sensitive system for the control of heparin therapy, with the added advantage that the blood can be drawn and taken to the laboratory for assay. The effective therapeutic range in man remains to be established.

The Therapeutic Range for Heparin Therapy: Relationship between Six Activated Partial Thromboplastin Time Reagents and Two Heparin Assays

1996 ◽  
Vol 75 (05) ◽  
pp. 734-739 ◽  
Author(s):  
S Kitchen ◽  
F E Preston
Keyword(s):  
Unfractionated Heparin ◽  
Therapeutic Range ◽  
Partial Thromboplastin Time ◽  
Warfarin Therapy ◽  
Normal Subjects ◽  
Heparin Therapy ◽  
Thromboembolic Disease ◽  
Activated Partial Thromboplastin Time ◽  
Therapy Relationship ◽  
The Relationship

SummaryThe 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.

aPTT in Heparinized Plasma: Influence of Reagent, Acute-Phase Reaction, and Interval Between Sampling and Testing

1996 ◽  
Vol 2 (4) ◽  
pp. 250-257 ◽  
Author(s):  
Finn G. Strekerud ◽  
Ulrich Abildgaard
Keyword(s):  
Acute Phase ◽  
Ex Vivo ◽  
Heparin Therapy ◽  
Activated Partial Thromboplastin Time ◽  
Acute Phase Reaction ◽  
Phase Reaction ◽  
Normal Plasma ◽  
Prolonged Aptt ◽  
Healthy Persons

Plasma samples from 10 healthy persons and 10 patients with acute-phase reaction were heparinized in vitro to obtain 0.00-0.70 U/ml. The activated partial thromboplastin time (aPTT) was then determined, using an optical method (Automated Coagulation Laboratory) and four reagents (actin, Cephotest, Platelin, and Throm bosil). The heparin sensitivity showed variation between individuals and was lower in acute-phase plasma than in normal plasma. There was also a marked difference in heparin sensitivity among the different reagents; actin was the least sensitive reagent, while Platelin was the most sensitive reagent in normal plasma and Thrombosil the most heparin-sensitive reagent in acute-phase plasma. Delay in testing prolonged the aPTT values in both acute- phase and normal heparinized plasma. With actin and Ce photest, a delay of 90 min at 22°C resulted in 30-50% prolongation of the aPTT. A delay of 150 min caused a prolongation of 75-110% with actin. Cephotest, Platelin, and Thrombosil were less prolonged. Ex vivo samples from heparinized plasma showed similar degrees of pro longation. Storage at 4°C resulted in less prolongation. Assuming a therapeutic range of 0.35-0.70 U/ml of hep arin, the therapeutic aPTT ratio ranges in heparinized, acute-phase plasma were 1.5-3.0 for actin and 2.5-4.5 for Cephotest, Platelin, and Thrombosil. These results un derscore certain limitations in monitoring heparin therapy with the aPTT system. Unless the assay is performed within 30 min after sampling, unduly prolonged aPTT val ues will be recorded. This may lead to underdosing of the patient.

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