Blended Heparin: A new Perspective to Guarantee the Supply of a Life-Saving Drug?

Abstract

The risk of heparin shortage opens up the possibility of diversifying the sources of heparin by introducing products of other animal/organ origins. In addition to bovine heparin, already used in the past in the United States and Europe, ovine heparin can become another alternative to the widely used pig source. It is therefore appropriate to compare the anticoagulant activity of pig heparin with that of products of different animal origin and to verify whether blended heparin obtained from different sources can give rise to anticoagulant effects comparable to those of heparin of a single origin.

Dear Sirs

Originally extracted from dog liver, in 1939 the first heparin product to be approved for medical practice was obtained from bovine lung or intestine, a safer and less expensive source compared to the liver. Due to the increased demand of heparin, from the 1950s porcine intestine has largely replaced the bovine source. About two decades later, US supplies of porcine crude material was flanked and then largely replaced by products imported from China, that now represents more than 70% of the US market. The outbreak of bovine spongiform encephalopathy (BSE) in 1990s led the porcine mucosa to be the sole source of heparin for US and Europe, confining the bovine heparin market mainly to South America and some Muslin countries. In 2015, the global increase in demand for heparin and its shortage due to African swine fever of 2018, induced the US Food and Drug Administration (FDA) to discuss the possibility of diversifying heparin sources by the reintroduction of heparin from bovine, as it provides a more reliable supply than other sources. ¹ The production of heparin from other animal sources requires that crude heparin must be processed using the most up-to-date processing capabilities to ensure a high-quality of finished product and to maintain the highest safety standards possible. Recently, scientists of the Agency confirmed that current heparin manufacturing is likely to remove substantial amounts of BSE agent, supporting the BSE risk for bovine heparin sourced from cattle in the north America to be very low. ²

In 2016 Gomes and colleagues demonstrated that potency adjusted bovine heparin presented comparable efficacy and safety of porcine heparin in open-heart surgery, ³ while few years later, Kouta and colleagues showed that ovine and porcine heparins exhibit comparable anticoagulant and antiprotease activities. ⁴ This opened the question of whether potency adjusted bovine heparin might show a similar pharmacological and biological profiles as referenced porcine and ovine single sources. In the present issue of this Journal, the group of Professor Fareed at Loyola University not only confirmed this hypothesis but also showed that potency adjusted blended heparin, comprised of one third PMH, one third OMH and one third BMH, exhibits comparable biochemical and pharmacological profiles to that of referenced, single sourced heparin. Although further investigations will be necessary, this study supports the concept that the interchangeably of BMH and OMH with the widely used PMH, can counteract the possible heparin shortage due to swine fever epidemics, in addition to the current vast changes in geopolitical equilibria.