Activated Partial Thromboplastin Time vs Heparin Concentration

Mungall, Dennis

doi:10.1001/archinte.158.11.1273

Archives of Internal Medicine

1998

DOI: 10.1001/archinte.158.11.1273

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Activated Partial Thromboplastin Time vs Heparin Concentration

Dennis Mungall¹

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1999

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“…As the role of heparin levels in patient monitoring continues to evolve, so must the analytical considerations in appropriate interpretation. 3,21,22 The equivalency between heparin levels by protamine titration and antifactor Xa stated in the consensus guidelines requires further evaluation. But for now, we feel that the most prudent approach is for clinicians to follow the recent consensus recommendations.…”

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Heparin Monitoring: The Confusion Continues

Smythe

Koerber

1999

Pharmacotherapy

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Earlier this year in Pharmacotherapy, Dr. Henry Bussey reviewed the numerous considerations and limitations of using the activated partial thromboplastin time (aPTT) for heparin monitoring. 1 The recommendations of two recent consensus papers on heparin monitoring from the American College of Chest Physicians and the College of American Pathologists were presented in his article.2, 3 Both organizations suggested that individual laboratories define their own aPTT therapeutic range. Samples from patients receiving heparin should be analyzed to determine the aPTT range that corresponds to a "therapeutic" heparin level of either 0.2-0.4 U/ml by protamine titration or 0.3-0.7 U/ml by antifactor Xa analysis.Since Dr. Bussey' s review, clinical investigations of unfractionated heparin have cited significantly different end points for heparin levels using antifactor Xa analysis. [4][5][6] The varying end points highlight another area of controversy surrounding heparin monitoring-the use of heparin levels. What is a therapeutic heparin level, and is 0.2-0.4 U/ml by protamine titration equivalent to 0.3-0.7 U/ml by antifactor Xa analysis?To attempt to answer the above questions, one must have a minimal understanding of the different heparin assays. The two most common are neutralization and functional assays. Neutralization assays estimate heparin activity by identifying the lowest amount of a substance (protamine sulfate or polybrene) that blocks prolongation of a coagulation test (i.e., thrombin) by heparin. The amount of protamine needed in the test plasma then is compared with the protamine required in a standard sample with a known heparin concentration.Functional assays measure the activity of heparin by inhibiting specific coagulation factors such as Xa or thrombin. This type of assay is based on the binding of heparin, antithrombin, and the activated coagulation factor. Residual activated coagulation factor is measured using enzyme-specific chromogenic or fluorogenic substrates.3, 7 Functional assays using antifactor Xa typically report a higher therapeutic range compared with thrombin-based protamine titration assays. This is due to the differential clearance of high-and low-molecular-weight heparin molecules. Low-molecular-weight molecules that inhibit factor Xa are cleared more slowly and thus accumulate.3 In general, antifactor Xa assays are more automated and are therefore less labor intensive to perform.The majority of data supporting a heparin concentration of 0.2 U/ml as the lower limit of the therapeutic range by protamine titration is limited to animal studies and subanalysis of clinical trials. One study reported inhibition of thrombus progression in a rabbit model with heparin concentrations of approximately 0.2 U/ml by protamine titration.8 A clinical trial comparing continuous intravenous heparin infusion with intermittent subcutaneous heparin in 115 patients found that 13 of 14 episodes of recurrent venous thromboembolism occurred during the first 24 hours in patients with a heparin concentration < ...

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confidence: 99%

Heparin Monitoring: The Confusion Continues

Smythe

Koerber

1999

Pharmacotherapy

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Activated Partial Thromboplastin Time vs Heparin Concentration

Cited by 1 publication

References 12 publications

Heparin Monitoring: The Confusion Continues

Heparin Monitoring: The Confusion Continues

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