Enoxaparin

Mechanism of action

Enoxaparin belongs to antithrombin III-dependent anticoagulants. This means that the drug has no intrinsic activity of its own — to exert its effect, it must bind to endogenous antithrombin III.

Like all low-molecular-weight heparins, enoxaparin inhibits factor Xa and thrombin (factor IIa). However, the degree of this inhibition varies. The main pharmacodynamic feature of enoxaparin is its high anti-Xa to anti-thrombin activity ratio, which is 3.8:1. For comparison, this ratio is lower in other agents of the group: 3.2–3.5:1 for nadroparin and reviparin, and 2.2–2.7:1 for dalteparin.

Position in the anticoagulant classification

Enoxaparin is part of the extensive group of antithrombin III-dependent agents. To understand its role in therapy, it is important to remember the full classification:

1. Standard (unfractionated) heparin: heparin sodium and heparin calcium (calciparine).
2. Low-molecular-weight heparins (LMWHs): enoxaparin sodium, nadroparin calcium, dalteparin sodium, reviparin sodium.
3. Factor Xa inhibitors: fondaparinux sodium.
4. Heparinoids: sulodexide, danaparoid sodium. These are sulfated glycosaminoglycans derived from porcine intestinal mucosa. Structurally, they are related to heparins and have a similar mechanism of action, but are classified in a separate group due to differences in physicochemical characteristics.

Pharmacological features of the LMWH group

It is important to understand that LMWH preparations in domestic practice (such as enoxaparin, nadroparin, dalteparin) are heterogeneous. They represent different fractions, are therefore not identical, and cannot replace one another in equivalent doses.

Differences between the drugs concern:

• Composition and physicochemical properties.
• Molecular weight (MW). For instance, the MW of dalteparin sodium is 5,000–6,000 D, whereas other agents (reviparin, nadroparin) have a weight ranging from 3,900 to 4,500 D.
• Biological activity (varying anti-Xa to anti-IIa activity ratios).

At the same time, despite structural heterogeneity, pharmacokinetics within the group differ only slightly.

Drug interactions

When prescribing anticoagulant therapy, it is necessary to consider the influence of concomitant drugs, especially in patients with endocrine pathology.

Heparins can cause attenuation of the hypoglycemic effect of insulin therapy. This counter-regulatory action creates a risk of hyperglycemia.

For differential memorization: attenuation of the insulin effect is also caused by thiazide diuretics, glucocorticoids, and thyroid hormones. Conversely, enhancement of the hypoglycemic effect (risk of hypoglycemia) is promoted by $\beta$-blockers (which additionally mask the symptoms of hypoglycemia), sulfonamides, anabolic steroids, and MAO inhibitors.

Dosage form and prescription rules

In Russian practice, enoxaparin sodium is most commonly known under the trade name Clexane.

Dosage form: Solution in syringes containing 10,000 anti-Xa IU/ml. Available volumes of pre-filled syringes: 0.2, 0.4, and 0.8 ml.

Dose calculation for a prescription:

• 1 ml of the solution contains 0.1 g (100 mg) of enoxaparin.
• 0.001 g (1 mg) of enoxaparin equals 100 anti-Xa IU.

Administration: The drug is administered strictly subcutaneously (s.c.). The standard prophylactic dosage is 20–40 mg once daily. In terms of activity, this is equivalent to 2,000–4,000 anti-Xa IU, which corresponds to a volume of 0.2–0.4 ml of the standard syringe solution.

Class and exam questions

What else to study on this topic

• Unfractionated (standard) heparin: mechanism and differences from LMWHs
• Other LMWH representatives: nadroparin calcium, dalteparin sodium
• Factor Xa inhibitors (fondaparinux sodium)
• Heparinoids (sulodexide, danaparoid sodium)
• Coagulation cascade and the physiological role of antithrombin III

Other topics in the «Drugs and Prescriptions» section

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