Background: Unfractionated heparins (UFH) of mucosal origin are currently obtained from bovine, ovine, and porcine sources (BMH, OMH, and PMH respectively). Besides molecular and structural differences, these heparins have differential interactions with serpins such as antithrombin (AT) and heparin cofactor II (HCII).

Aims: The purpose of this study is to compare the inhibitory profiles of various heparins in systems enriched with AT and HCII.

Methods: All heparins (UFH’s and LMWH’s) were supplemented to AT and HCII enriched buffer systems at various gravimetric and potency equated concentrations. The relative inhibition of thrombin (IIa) was measured in terms of percent inhibition, which was calculated for each concentration in both systems for each of the three heparins. Inhibitory concentrations required to inhibit 50% of thrombin (IC-50) was calculated for each UFH and LMWH.

Results: In the AT supplemented system using gravimetric concentrations of various UFH’s, PMH and OMH showed comparable values, whereas BMH exhibited much higher IC-50’s. However, the LMWH’s of various origins showed comparable IC-50 values. The potency adjusted heparins exhibited comparable results for all UFH’s (Figure 1). In the HCII supplemented system, all UFH’s exhibited similar IC-50 values in both gravimetric and USP potency adjusted studies. Similarly, all LMWH’s demonstrated similar IC-50 values (Figure 2). The relative IC-50 values of the LMWH’s in both the AT and HCII enriched systems were higher than the UFH’s.

Conclusion(s): These results show that potency adjusted UFH’s exhibit comparable inhibition of IIa in AT and HCII enriched systems. The differing BMH results observed may partly be due to differences in charge density and AT-binding consensus sequences. The nearly identical results of all LMWH’s may be due to the chemical modifications that occur during the manufacturing of these agents. Future studies may be warranted to further investigate these cofactors and their impacts on the function of various heparins.

Figure 1

Potency -IC50- comparison for various heparins and LMWHs when supplemented in purified AT system as measured by the amidolytic anti-IIa assay -n=3-. All heparins were supplemented in AT system over a concentration range of -0–10- μg/ml -A- or -0–1- U/ml -B-. All LMWHs were supplemented in AT system over a concentration range of -0–20- μg/ml -C-. Significance was set at -*p ≤ 0.05-. All results represent the mean ± SD.

Figure 2

Potency -IC50- comparison for various heparins and LMWHs when supplemented in purified HCII as measured by the amidolytic anti-IIa assay -n=3-. All heparins were supplemented in HCII system over a concentration range of -0–20- μg/ml -A- or -0–2- U/ml -B-. All LMWHs were supplemented in HCII system over a concentration range of -0–20- μg/ml -C-. Significance was set at -*p ≤ 0.05-. All results represent the mean ± SD.

« Back to ISTH 2022 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/comparative-studies-on-the-interaction-of-heparins-from-various-origins-with-heparin-cofactor-ii-and-antithrombin/