A Comparison of two Heparin-Neutralizing Agents: Protamine and Polybrene

Hc, Godal

doi:10.3109/00365516009065409

Cited by 71 publications

(21 citation statements)

References 18 publications

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“…Although metachromatic assay methods are usefui for in vitro studies, they are not" suitable for measuring heparin concentrations in biological fluids (johnson and Mulloy, 1976); unpublished data from my laboratory suggest that the difficulty lies in the varied protein binding properties of heparin. A similar methodological approach is inherent in the more successful polybrene (hexadimethrine bromide, a synthetic polymerised quaternary amine salt) neutralisation assay, the principle of which is similar to that of protamine titration (Godal, 1960). More direct methods that are based on the ability of heparin to inhibit known amounts of activated factor X are becoming more widely used for the measurement of heparin concentrations (Denson and Bonnar, 1973;Odegard et al, 1976;Yin et aI., 1973).…”

Section: Methods For Measuring the Anticoagulant Effect Of Heparinmentioning

confidence: 96%

Clinical Pharmacokinetics of Heparin

1980

Clinical Pharmacokinetics

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Heparin binds reversibly to its target sites of action, antithrombin and the other serine proteases involved in coagulation, especially activated factor X. It also binds to other plasma proteins, including fibrinogen, plasmin, albumin, and lipases. The volume of distribution of heparin is then, under most circumstances, limited to the plasma volume. Heparin has a very short half-life, about 1.5 hours, which is dose-dependent and varies with the assay method employed for its measurements. It is not eliminated enzymatically nor by glomerular filtration or renal tubular secretion. In all likelihood, the anticoagulant is transferred to reticuloendothelial cells, which may also provide the means for its degradation. Many of the difficulties inherent in assessing the kinetic properties of heparin, as well as its clinical efficacy, may be attributed to: (1) its molecular heterogeneity; (2) its wide spectrum of binding sites and their respective kinetic properties and dissociation constants; (3) differences among methods for measuring heparin effect and concentration; (4) the dose dependence of the drug's half-life; (5) variation in patient response to heparin; (6) the specific cation associated with it; and (7) the presence of hypercoagulation syndromes associated with deficits of antithrombin. Neither renal nor hepatic disease, nor the biological tissues from which heparins are extracted commercially, seem to influence the drug's kinetic properties as much as variations in clearance and response to heparin among individual patients. Many comparisons among available studies are difficult because of the wide variation in the assay methods employed in them. It would appear that optimum therapy with heparin can be achieved only when the individual patient's response to, and rate of elimination of, heparin are taken into account concurrently.

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Section: Methods For Measuring the Anticoagulant Effect Of Heparinmentioning

confidence: 96%

Clinical Pharmacokinetics of Heparin

1980

Clinical Pharmacokinetics

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“…Polybrene is a positively charged quaternary nitrogen poly mer, used as a safe alternative heparin neu tralizer in patients with a protamine allergy [12,13], in spite of its reported nephrotoxicity [14], Polybrene is mainly used for in vitro heparin titration experiments [15,16]. In the late 60s, several articles reported polybrene to be superior to protamine [17][18][19]. This was based on experiments using thrombin time determination and now antiquated methods like the clotting time according to Lee and White.…”

Section: Introductionmentioning

confidence: 99%

Influence of Heparin, Protamine and Polybrene on the Time Integral of Thrombin Generation (Endogenous Thrombin Potential)

Rotteveel¹,

Roozendaal

Weijers³

et al. 1996

Pathophysiol Haemos Thromb

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We investigated the anticoagulating and heparin-neutralizing properties of protamine and polybrene (hexadimethrine bromide), using the endogenous thrombin potential (ETP) as the parameter to access plasma coagulability. The hypocoagulability induced by high doses of heparin (3 IU/ml) could be reversed by addition of protamine to a very limited extent only. Polybrene on the other hand did neutralize heparin at the equivalent concentration and a two-fold excess did not influence the ETP parameters. In vivo neutralization of high-dose heparin with protamine should therefore be reconsidered. Our experiments suggest polybrene to be superior over protamine with respect to neutralization of high doses of heparin.

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“…The first of these tests involved HA neutralization by polycationic substances, protamine 31 or Polybrene. 32 Because both of these neutralization assays were based on the thrombin time, they measured antithrombin activity. When compared with standard thrombin time and APTT tests in the ability to predict the amount of UH added in vitro to plasma, the neutralization assays were more accurate.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Anti–Factor Xa Heparin Activity and Activated Partial Thromboplastin Time in 2,773 Plasma Samples From Unfractionated Heparin–Treated Patients

Rosborough

1997

Am J Clin Pathol

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C o m p a r i s o n o f A n t i -F a c t o r X a H e p a r i n A c t i v i t y a n dA c t i v a t e d P a r t i a l T h r o m b o p l a s t i n T i m e i n 2 , 7 7 3 P l a s m a S a m p l e s F r o m U n f r a c t i o n a t e d H e p a r i n -T r e a t e d P a t i e n t s TERRY K. ROSBOROUGH, MDThis study was conducted to evaluate two methods of determining the "therapeutic range" of the activated partial thromboplastin time (APTT) during unfractionated heparin treatment. Multiple fresh plasma samples from 694 patients treated with unfractionated heparin were tested simultaneously for APTT and anti-factor Xa heparin activity. The data were analyzed by linear regression and by a minimization-of-error technique to determine the more accurate APTT therapeutic range. The best-fit linear regression equation was obtained using logarithmically transformed APTT values. Using this equation, the

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A Comparison of two Heparin-Neutralizing Agents: Protamine and Polybrene

Cited by 71 publications

References 18 publications

Clinical Pharmacokinetics of Heparin

Clinical Pharmacokinetics of Heparin

Influence of Heparin, Protamine and Polybrene on the Time Integral of Thrombin Generation (Endogenous Thrombin Potential)

Comparison of Anti–Factor Xa Heparin Activity and Activated Partial Thromboplastin Time in 2,773 Plasma Samples From Unfractionated Heparin–Treated Patients

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