A rational approach to heparins.

Area of Science:

• Pharmacology
• Biochemistry
• Analytical Chemistry

Background:

• Current heparin activity measurement using International Units is insufficient for low molecular weight heparins (LMWHs).
• LMWHs exhibit complex interactions with antithrombin III, necessitating a more precise quantification method.
• Understanding the distinct components of LMWHs is crucial for accurate therapeutic monitoring.

Purpose of the Study:

• To demonstrate the inadequacy of International Units for LMWH activity assessment.
• To propose an alternative method for quantifying specific LMWH components.
• To establish a quantitative measure for heparin fractions based on their biological activity.

Main Methods:

• Characterization of LMWH fractions based on chain length and binding affinity to antithrombin III.
• Differentiation between components with dual (anti-factor Xa and antithrombin) and single (anti-factor Xa) activities.
• Development of a method to determine the levels of these distinct components in plasma samples.

Main Results:

• The study identifies two key components in high-affinity binding LMWH fractions: ACLM (above 17 sugar units) and BCLM (below 17 sugar units).
• ACLM possesses both anti-factor Xa and antithrombin activities, while BCLM has only anti-factor Xa activity.
• A method was successfully developed to quantify ACLM and BCLM levels in micrograms/ml.

Conclusions:

• The current practice of using International Units for heparin activity is inadequate for LMWHs.
• The proposed method allows for the precise determination of ACLM and BCLM, offering a more accurate assessment of LMWH activity.
• Quantifying heparin fractions in micrograms/ml provides a superior alternative for managing LMWH therapy.