Effects of Heparin Therapy on Hexagonal Lipid Neutralization Test

SummaryThe activated partial thromboplastin time test (aPTT) represents one of the most commonly used diagnostic tools in order to monitor patients undergoing heparin therapy. Expression of aPTT coagulation time in seconds represents common practice in order to evaluate the integrity of the coagulation cascade. The prolongation of the aPTT thus can indicate whether or not the heparin level is likely to be within therapeutic range. Unfortunately aPTT results are highly variable depending on patient properties, manufacturer, different reagents and instruments among others but most importantly aPTT’s dose response curve to heparin often lacks linearity. Furthermore, aPTT assays are insensitive to drugs such as, for example, low molecular weight heparin (LMWH) and direct factor Xa (FXa) inhibitors among others. On the other hand, the protrombinase-induced clotting time assay (PiCT®) has been show to be a reliable functional assay sensitive to all heparinoids as well as direct thrombin inhibitors (DTIs). So far, the commercially available PiCT assay (Pefakit®-PiCT®, DSM Nutritional Products Ltd. Branch Pentapharm, Basel, Switzerland) is designed to express results in terms of units with the help of specific calibrators, while aPTT results are most commonly expressed as coagulation time in seconds. In this report, we describe the results of a pilot study indicating that the Pefakit PiCT UC assay is superior to the aPTT for the efficient monitoring of patients undergoing UFH therapy; it is also suitable to determine and quantitate the effect of LMWH therapy. This indicates a distinct benefit when using this new approach over the use of aPPT for heparin monitoring.

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

Thrombosis and Haemostasis ◽

10.1055/s-0038-1645678 ◽

1990 ◽

Vol 63 (01) ◽

pp. 016-023 ◽

Cited By ~ 41

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.

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Monitoring Anticoagulant Therapy by Activated Partial Thromboplastin Time: Hirudin Assessment

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648943 ◽

1994 ◽

Vol 72 (05) ◽

pp. 685-692 ◽

Cited By ~ 43

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.

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The Clinical Usefulness of the Platelet Aggregation Test for the Diagnosis of Heparin-Induced Thrombocytopenia

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651610 ◽

1993 ◽

Vol 69 (04) ◽

pp. 344-350 ◽

Cited By ~ 175

Author(s):

B H Chong ◽

J Burgess ◽

F Ismail

Keyword(s):

Platelet Aggregation ◽

Heparin Therapy ◽

Serotonin Release ◽

Point System ◽

Control Groups ◽

Heparin Induced Thrombocytopenia ◽

Heparin Concentration ◽

Release Test ◽

The Mean ◽

Normal Controls

SummaryThe platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platelet aggregation test was found to vary with the heparin concentration and the donor of the platelets used in the test. The optimal heparin concentrations were between 0.1 and 1.0 U/ml. Using these heparin concentrations, the mean sensitivity varied from 39% (with the least reactive platelets) to 81% (with the most reactive platelets). In comparison, the sensitivity of the release test ranged from 65% to 94%. The specificities of the platelet aggregation test were 82%, 90% and 100% for the following control groups: (1) non-thrombocytopenic patients given heparin, (2) patients with thrombocytopenia due to other causes, and (3) normal controls not given heparin, respectively. The corresponding specificities for the release test was 94%, 90% and 100%. The specificities can be further increased to 100% for all controls with the adoption of a two-point system which defines a positive result as one in which platelet aggregation occurs with a low heparin concentration (0.5 U/ml) but not with 100 U heparin/ml. For optimal results, a two-point platelet aggregation test should be performed with heparin concentrations of 0.5 and 100 U/ml and using platelets of more reactive donors.

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Low Molecular Weight Heparin Therapy: Is Monitoring Needed?

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648866 ◽

1994 ◽

Vol 72 (03) ◽

pp. 330-334 ◽

Cited By ~ 72

Author(s):

B Boneu

Keyword(s):

Molecular Weight ◽

Clinical Trials ◽

Plasma Proteins ◽

Bleeding Risk ◽

Heparin Therapy ◽

Low Molecular Weight ◽

Vein Thrombosis ◽

Meta Analyses ◽

Deep Vein ◽

Initial Check

SummaryRecent meta-analyses indicate that low molecular weight heparins (LMWH) are more effective than unfractionated heparin (UH) in preventing and treating deep vein thrombosis. This article presents the arguments for and against the need for laboratory monitoring. At the present time, the only tests currently available for monitoring LMWH therapy are those which measure the anti Xa activity in the plasma. Due to lower binding to plasma proteins and to cell surfaces,the plasma anti Xa activity generated by a given dose of LMWH is more predictable than for UH.Some clinical trials suggest that LMWH delivered at the recommended dose expose the patient to less bleeding risk than UH. Several . meta-analyses indicate comparable risk while any overdose unaccept-ably increases the haemorrhagic risk. The lowest dose of LMWH still effective in treating established DVT is presently unknown; some reports indicate that inadequate doses of LMWH are associated with a lack of efficacy for prevention. An overview of the published clinical trials indicates that the LMWH dose has never been monitored for prevention of DVT. In the treatment of established DVT, several trials have been performed without any monitoring, while in others the dose was adapted to target a given anti Xa activity. These considerations suggest that in prevention of DVT, monitoring the dose is not required. In the treatment of established DVT, considering the haemorrhagic risk of LMWH, the risk of undertreating the patient and the absence of large clinical trials comparing the advantages of monitoring the dose or not, it might be useful to check anti Xa activity at least once at the beginning of the treatment but the need for this initial check remains to be established. Because a large proportion of patients will be in the desired range, dose adjustments will be far less frequent than for UH.

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Comparison of Progressive Antithrombin Activity and the Concentration of Three Thrombin Inhibitors in Nephrotic Syndrome

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653432 ◽

1981 ◽

Vol 46 (03) ◽

pp. 623-625 ◽

Cited By ~ 25

Author(s):

B Boneu ◽

F Bouissou ◽

M Abbal ◽

P Sie ◽

C Caranobe ◽

...

Keyword(s):

Nephrotic Syndrome ◽

Antithrombin Iii ◽

Heparin Therapy ◽

Thrombin Inhibitors ◽

Compensatory Mechanism ◽

Dramatic Reduction ◽

Antithrombin Activity ◽

Α2 Macroglobulin ◽

At Iii ◽

A Prospective Study

SummaryIn order to compare the plasmatic progressive antithrombin activity to the concentration of three thrombin inhibitors, antithrombin III (AT III), α2 macroglobulin (α2, M), α1 anti-trypsin (α1 AT) in nephrotic syndrome, a prospective study was carried out on a group of 28 children affected with the disease. A dramatic reduction of the level of AT III and of α1 AT, two inhibitors of molecular weight close to that of albumin, was observed. The decreased level of AT III was counterbalanced by an increase in α2 M. This phenomenon accounts for the increased progressive antithrombin activity observed in all the affected children. It is suggested that the above compensatory mechanism explains the absence of thrombotic accidents in this series and that the benefit of heparin therapy is doubtful in these conditions.

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The Measurement of Heparin and Other Therapeutic Sufphated Polysaccharides in Plasma, Serum and Urine

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660086 ◽

1985 ◽

Vol 54 (03) ◽

pp. 630-634 ◽

Cited By ~ 19

Author(s):

J Dawes ◽

C V Prowse ◽

D D Pepper

Keyword(s):

Biological Fluids ◽

Anticoagulant Activity ◽

Dose Range ◽

Plasma Concentrations ◽

Heparin Therapy ◽

Competitive Binding Assay ◽

First Order Kinetics ◽

Activity Measurements ◽

Heparin Activity ◽

Dose Dependent

SummaryThe competitive binding assay described will specifically and accurately measure concentrations of administered heparin in biological fluids with a sensitivity of 60 ng ml-1. Neither endogenous glycosaminoglycans, nor plasma proteins such as ATIII and PF4 interfere in the assay. Semi-synthetic highly sulphated heparinoids and LMW heparin can also be measured. Using this assay heparin clearance followed simple first-order kinetics over the dose range 100-5,000 units, but the half-life was strongly dose-dependent. There was good correlation with heparin activity measurements by APTT and anti-Xa clotting assays. Plasma concentrations were measurable for at least 5 h following subcutaneous injection of 10,000 units of heparin. Excretion in the urine could be followed after all but the lowest intravenous dose. This assay, used in conjunction with measurements of heparin anticoagulant activity, will be valuable in the elucidation of mechanisms of action of heparin and the heparinoids, and in the assessment and management of problems related to heparin therapy.

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How Useful is the Monitoring of (Low Molecular Weight) Heparin Therapy by Anti-Xa Assay? A Laboratory Perspective

Laboratory Hematology ◽

10.1532/lh96.05028 ◽

2005 ◽

Vol 11 (3) ◽

pp. 157-162 ◽

Cited By ~ 18

Author(s):

EMMANUEL J. FAVALORO ◽

ROSLYN BONAR ◽

MARGARET ABOUD ◽

JOYCE LOW ◽

JOHN SIOUFI ◽

...

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Heparin Therapy ◽

Low Molecular Weight

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Heparin therapy during extracorporeal circulation

Journal of Thoracic and Cardiovascular Surgery ◽

10.1016/s0022-5223(19)41500-6 ◽

1975 ◽

Vol 69 (5) ◽

pp. 685-689 ◽

Cited By ~ 246

Author(s):

Brian S. Bull ◽

Wilfred M. Huse ◽

Floyd S. Brauer ◽

Ralph A. Korpman

Keyword(s):

Extracorporeal Circulation ◽

Heparin Therapy

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Need for Confirmatory Neutralization Tests for Hepatitis B Surface Antigen Tests in Populations with Intermediate Prevalence

Laboratory Medicine ◽

10.1093/labmed/lmab006 ◽

2021 ◽

Author(s):

Min Young Lee ◽

So Young Kang ◽

Woo In Lee ◽

Myeong Hee Kim

Keyword(s):

Hepatitis B ◽

Surface Antigen ◽

Neutralization Test ◽

Hepatitis B Surface Antigen ◽

False Negative ◽

Confirmatory Test ◽

Negative Group ◽

Positive Group ◽

Test Kit ◽

Antigen Tests

Abstract Objective Hepatitis B surface antigen (HBsAg) is known as the hallmark of hepatitis B virus (HBV) infection. This study aimed to determine whether an HBsAg neutralization test is necessary to accurately interpret HBsAg test results. Methods Initially reactive HBsAg specimens from a 5-year period, with cutoff index values between 1.0 and 2.0, were subjected to neutralization confirmatory testing using an Elecsys HBsAg Confirmatory test kit (Roche Diagnostics GmbH. Mannheim, Germany). Results The neutralization test showed 46.1% positive (confirmed positive group) and 53.9% negative (confirmed negative group) results from the total specimens. Among the confirmed negative group, 79.5% of patients were confirmed to be negative for the current infection, whereas 4 patients in the chronic hepatitis B subgroup showed a neutralization percentage close to 40%. More than half of patients in the confirmed positive group were considered to be in the hepatitis B e antigen-negative inactive HBsAg carrier phase. Conclusion In populations with intermediate HBV prevalence, a neutralization test is necessary to confirm an HBsAg result and reduce the false positive and false negative rates of initial HBsAg tests.

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