A dose–response study in animals to evaluate the anticoagulant effect of the stage 2 unfractionated heparin USP monograph change

Honchel, Ronald; Carraway, Jeff; Gopee, Neera V.; Callicott, Ralph; Chen, J.; Patton, Ralph E.; Xu, Qinzhu; Zalkkar, J.; Laniyonu, Adebayo; Krefting, Ira; Cato, M.; Robie‐Suh, Kathy; Rieves, R. D.

doi:10.1016/j.yrtph.2011.04.008

Cited by 5 publications

(3 citation statements)

References 7 publications

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“…Utilization of purified reagents, including factor IIa, factor Xa, and specific polypeptide-based chromogenic substrates, in the assay allows the measurement of specific effects from heparin, avoiding the potential for interference from plasma proteins or the presence of OSCS (Supplementary Note 5 and Supplementary Table 2). Over the past 30 years, there has been a 10% drift in potency definition between USP unit and international unit (IU) due to the improved quality of reference materials and potency assay changes 32 . The employment of the new potency assay and new USP Heparin Sodium for Assays reference standard aligned both units, and brought minimum potency requirements in line with expectations for modern heparin products.…”

Section: Methods Establishing Heparin Identificationmentioning

confidence: 99%

The US regulatory and pharmacopeia response to the global heparin contamination crisis

et al. 2016

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The contamination of the widely used lifesaving anticoagulant drug heparin in 2007 has drawn renewed attention to the challenges that are associated with the characterization, quality control and standardization of complex biological medicines from natural sources. Heparin is a linear, highly sulfated polysaccharide consisting of alternating glucosamine and uronic acid monosaccharide residues. Heparin has been used successfully as an injectable antithrombotic medicine since the 1930s, and its isolation from animal sources (primarily porcine intestine) as well as its manufacturing processes have not changed substantially since its introduction. The 2007 heparin contamination crisis resulted in several deaths in the United States and hundreds of adverse reactions worldwide, revealing the vulnerability of a complex global supply chain to sophisticated adulteration. This Perspective discusses how the US Food and Drug Administration (FDA), the United States Pharmacopeial Convention (USP) and international stakeholders collaborated to redefine quality expectations for heparin, thus making an important natural product better controlled and less susceptible to economically motivated adulteration.

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Section: Methods Establishing Heparin Identificationmentioning

confidence: 99%

The US regulatory and pharmacopeia response to the global heparin contamination crisis

et al. 2016

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“….it is essential that health care professionals be aware of the potential difference in potency between the old and new vials of heparin when administering the drug," because the new UFH has a 10% decrease in potency (3). This decrease in heparin potency was suggested to have minimal to no effect, unless administered through an intravenous bolus or when immediate anticoagulation is needed, both of which pertain to operating room procedures (1)(2)(3)(4)(5).…”

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confidence: 99%

Effect of New Heparin Potency on Activated Clotting Time during Pediatric Cardiac Surgery: A Retrospective Chart Review

Thompson¹,

Alred²,

Deyo³

et al. 2014

J Extra Corpor Technol

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In 2009, the U.S Food and Drug Administration (FDA) announced a two-phase change in unfractionated heparin to reduce contamination and create a new potency reference. The FDA announced the change would bring about a 10% decrease in potency from the old heparin (OH) to new heparin (NH). The purpose of this article is to compare heparin in pediatric patients undergoing cardiac surgery before and after the FDA changes. After Institutional Review Board approval, a retrospective chart review was conducted with pediatric patients (n = 266) undergoing cardiac surgery. All patients received a heparin loading dose of 400 IU/kg and data collected included patient demographics, baseline activated clotting time (ACT), ACT after initial heparin dose, and heparin dose–response. These data were then further broken down into age blocks consisting of neonates (<1 month), 1–12 months, 1–5 years old, and older than 5 years old. In 17.3% of cases in the NH group, the ACT after the initial heparin dose did not reach the critical value of 400 seconds necessary for initiation of cardiopulmonary bypass (CPB). This is significantly higher than the 8.9% of cases in the OH group (p < .05). There was an overall trend among age groups that the NH was less potent than OH. However, only the 1–5 years of age group showed significance at p < .05. Given the median ACTs 591 seconds for OH and 484 seconds for NH, the calculated percentage difference was 18.1%. The results from this retrospective pediatric chart review indicate that the change in heparin potency greatly deviates from the 10% change reported by the FDA. In conclusion, NH has a trend of lower potency and frequent monitoring is necessary to maintain a safe level of anticoagulation during CPB.

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“…The conclusion was that there was a modest reduction in the anticoagulant response with the new heparin. The author noted that the variability of the animal's response to heparin demonstrates the importance of monitoring the heparin effect (7).…”

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confidence: 99%

Has the New USP Assay for Heparin Affected Dosage for Patients Undergoing Cardiopulmonary Bypass?

Anderson¹,

Holt²

2013

J Extra Corpor Technol

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In October 2009, the U.S. Pharmacopoeia (USP) changed the monograph for heparin to bring USP units in line with international units for heparin. The result was a 10% decrease in potency as measured by in vitro laboratory tests. This decrease led to questions regarding dosing guidelines. There existed a need for an in vivo study to determine the practical changes that may need to be implemented in regard to heparin administration for cardiopulmonary bypass in the clinical setting. A retrospective study was conducted to determine the heparin dose administered and the corresponding effect on patients undergoing coronary artery bypass grafting surgery using cardiopulmonary bypass. The study compared the heparin dose requirements and activated clotting time (ACT) results using the heparin before and after the USP changes. An analysis of the data was performed to determine the increased heparin dose required to achieve the same effect as before the USP change. This new heparin dosing protocol was instituted at Concord Hospital, Concord, NH. A prospective study was then preformed to verify the effects of the dosing change. In the new heparin group, the postheparin ACT fell by 9.1% (p = .028) and the patients achieving an ACT > 479 seconds fell by 12.8% as compared with the old heparin group. After adjustment of the loading dose calculation for heparin, the prospective study demonstrated the postheparin ACT (p = .684) and the percentage of patients achieving an ACT > 479 seconds (p = 1.000) to be similar to the values obtained before the USP change. An increase of the loading dose of approximately 12% is needed to achieve the patient effects seen before the UPS change.

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A dose–response study in animals to evaluate the anticoagulant effect of the stage 2 unfractionated heparin USP monograph change

Cited by 5 publications

References 7 publications

The US regulatory and pharmacopeia response to the global heparin contamination crisis

The US regulatory and pharmacopeia response to the global heparin contamination crisis

Effect of New Heparin Potency on Activated Clotting Time during Pediatric Cardiac Surgery: A Retrospective Chart Review

Has the New USP Assay for Heparin Affected Dosage for Patients Undergoing Cardiopulmonary Bypass?

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