Comparative Pharmacological Profiles of Various Bovine, Ovine, and Porcine Heparins

Abstract

Unfractionated heparin is the first anticoagulant drug and has been successfully used clinically for over 80 years. Heparin and its analogues are used during surgery and dialysis and are often used to coat indwelling catheters and other devices where the vascular system is exposed. Most of the heparins used clinically are derived from porcine intestinal mucosa. However, heparins have also been manufactured from tissues of other mammalian species such as cows and sheep. Recently there have been attempts to generate bioengineered heparin in order to overcome contamination and antigenicity problems. Currently there are some concerns about the shortage of the porcine heparins as they are widely used in the manufacturing of the low-molecular-weight heparins. Moreover, due to cultural and religious reasons in some countries, alternative sources of heparins are needed. The Food and Drug Administration and other regulatory agencies have considered alternative sourcing of heparin for potential substitution of porcine heparin and are currently reviewing this matter. Numerous studies are ongoing to understand the structure-activity relationships of these various heparins. In this article, heparins from different animal sources were studied to determine the extent of biosimilarity between them. For these investigations, 10 batches each of bovine mucosal heparin (BMH), ovine mucosal heparin (OMH), and porcine mucosal heparin (PMH) were studied. These studies have demonstrated that OMH and PMH have comparable anticoagulant and antiproteases activities. However, BMH exhibited somewhat a lower potency compared to OMH and PMH in functional assays.

ZNF263 is a transcriptional regulator of heparin and heparan sulfate biosynthesis

“…However, it should be noted that heparin contains other 3-O-sulfated sequences that might constitute lower-affinity sequences, which we suggest might have anticoagulant activity when present at high concentration. It is also notable that the nature of the antithrombin-binding sequence varies according to species and the organ from which the heparin was isolated (39)(40)(41).…”

Protamine Sulfate Neutralization Profile of Various Dosages of Bovine, Ovine and Porcine UFHs and Their Depolymerized Derivatives in Non-Human Primates

“…A previous publication has reported on the comparison of UFHs and LMWHs produced by using mucosal tissue of bovine, ovine and porcine origins. 18 Additional publication provide evidence of the equivalence of bovine and porcine UFHs at potency-adjusted levels. 32 It is noteworthy that, the bovine heparin preparations exhibit a lower potency in comparison to porcine heparin at equivalent mass levels.…”

“…As the U.S. heparin supply is dependent on Chinese manufacturers and up to 70% of the U.S. heparin is imported from China, the U.S. government is concerned on the dependence on one source and the potential impact of its shortage on patient usage. 18 In this study, we projected that, BMH, OMH and PMH have comparable PS neutralization profiles when administered at equi-gravimetric dosages. However, potency equated BMH may require higher amount of PS to be completely neutralized.…”

“…As the U.S. heparin supply is dependent on Chinese manufacturers and up to 70% of the U.S. heparin is imported from China, the U.S. government is concerned on the dependence on one source and the potential impact of its shortage on patient usage. 18 …”

Potential Mechanisms of Cancer-Related Hypercoagulability

“…Mutations affecting the biosynthesis of heparan sulphate proteoglycans are implicated in multiple diseases including Simpson-Golabi-Behmel syndrome and Ehlers-Danlos syndrome [42]. Most commercial heparin production is derived from pig intestine or bovine lungs [44,45]. Multiple studies have shown that heparin and low-molecular-weight heparin (LMWH) appear to prolong survival in patients with cancer [46][47][48][49].…”