Biological potency evaluation and physicochemical characterization of unfractionated heparins

Abstract

Unfractionated heparins are used clinically as anticoagulants. The biological potency of thirteen samples of raw material and pharmaceutical formulations were assessed utilizing the 5th International Standard of heparin using the sheep plasma coagulation inhibition assay, activated partial thromboplastin time, anti-factor Xa assay, and anti-factor IIa assay, resulting in mean potencies of 101.15%, 96.15%, 98.15% and 99.37%, respectively. The samples were also evaluated by the protamine neutralization test giving results within the range of 92-138 IU/mg. The anti-factor IIa assay was performed showing reproducibility and significant correlation with the pharmacopoeial assays, thus demonstrating it to be a feasible alternative to the sheep plasma coagulation inhibition assay. Moreover, an analysis by nuclear magnetic resonance and capillary electrophoresis showed some peaks attributable to oversulfated chondroitin sulfate. The results show that batch-to-batch variations and the quality of samples contributed to improvements in the quality control of pharmaceutical products and to assure the safe use and clinical efficacy of this biological medicine. Rev. Bras. Hematol. Hemoter.

Birth defects in newborns and stillborns: an example of the Brazilian reality

“…Parental consanguinity was observed in approximately 2% of cases which is higher than the general population of South America (0.96%) However, this is lower than previously reported frequencies of consanguinity among parents of children with BD in Brazil of up to 8.5% [19]. This can be explained by the wide variation of consanguinity in different cities and regions of Brazil.…”

“…Early ages (up to 20 years) are associated with gastroschisis [18] and all the mothers that the child had this BD were aged up to 20 years old. At older ages the risk of numerical chromosomal abnormalities increases progressively [19] and this was a risk factor observed in this study too, in which most mothers of children with these abnormalities were 35 years or older. The cause of gastroschisis is unknown, although possible exogenous causes have been studied.…”

Avaliação comparativa da atividade biológica de heparinas não fracionadas pelas metodologias de inibição da coagulação do plasma ovino (ICPO) e de tempo de tromboplastina parcial ativada (TTPA)

“…Por meio da repetição dos ensaios analíticos que expressaram a variação nos resultados sob as mesmas condições de operação, observamos que o método ICPO apresentou precisão superior (CV entre 0,0% e 2,0%) em relação ao método TTPA (CV entre 1,80% e 4,98%), mas, mesmo assim, podemos considerar o TTPA preciso, pois seus valores de CV foram baixos [22][23][24][25] .…”

“…Ambas as metodologias foram comparadas com o 5º Padrão Internacional de Heparina em relação a ele mesmo e os resultados (100 % ICPO e 99,60 % TTPA) apontaram como capazes de descrever com exatidão o valor da potência biológica de heparina [22][23][24][25] .…”

Desafios na qualidade de heparinas

“…Já no início de 2009, a United States Pharmacopeia, publicou um informativo relatando a ocorrência de duzentas mortes em todo o mundo em razão da adulteração de heparinas com condroitina supersulfatada, e indicando as providências tomadas, através da proposição de metodologias de controle de qualidade para avaliação de potência, identidade e pureza. Tais metodologias encontram-se disponíveis para consulta e, em parte, são as mesmas utilizadas no artigo de Dalmora e col. 4 publicado neste periódico.…”