PB0382 - Does Activity Standardization Suffice for Equivalence Among Heparins from Different Sources?

Background: Heparin, a valuable anticoagulant, remains essential for treating venous thromboembolism. Composed mainly of 2-sulfated α-iduronic acid and N,6-disulfated α-glucosamine, heparins from distinct animal sources, such as bovine intestinal heparin (HBI) and porcine intestinal heparin (HPI), display notable compositional differences affecting their anticoagulant properties (120 and 180 UI/mg, respectively). Despite HPI being the predominant source of unfractionated heparin (UFH) globally, some regions use bovine mucosa-derived products. Varied biological activities prompt clinical protocols to standardize based on activity rather than mass, compensating for HBI's lower activity with increased mass administration. However, chemical and pharmacological disparities between HPI and HBI raise concerns about their interchangeable use as UFHs.

Aims: This study aims to assess if activity-based standardization yields similar biological responses for these heparins.

Methods: Specific activity (IU/mg) was determined using aPTT, anti-Xa, and anti-IIa assays. Antithrombotic potential was assessed in an experimental model of venous thrombosis with intravital microscopy. Heparins adjusted on an activity basis were added to platelet-rich plasma and whole blood for aPTT assays.

Results: HBI exhibited approximately 40% lower activity than HPI in all in vitro assays, emphasizing compositional distinctions. Evaluating antithrombotic efficacy standardized by mass (mg/kg) revealed both heparins effectively prevented thrombus formation, with HPI showing superior efficacy at lower doses. Surprisingly, when comparing antithrombotic effects using anti-Xa adjusted doses, HBI demonstrated higher efficacy than HPI at all concentrations. Testing heparins on activity-basis with aPTT revealed coincident curves. However, pre-adding heparin to blood components resulted in higher activity for HBI than HPI.

Conclusion(s): Contrary to in vitro findings, dosage standardization was not efficient to ensure interchangeability of different heparins in inhibiting thrombosis i. Our findings suggest a greater bioavailability of HBI in whole blood. This suggests that standardizing the commercialization of heparins from different sources based on activity in purified systems may not guarantee may not guarantee consistent performance in biological systems.