Fondaparinux (Arixtra) is an anticoagulant medication.

It is marketed by GlaxoSmithKline.

Structure and mechanism

Fondaparinux is a synthetic pentasaccharide as evident by its chemical structure on the right. Apart from the O-methyl group at the reducing end of the molecule, the identity and sequence of the five monomeric sugar units contained in fondaparinux is identical to a sequence of five monomeric sugar units that can be isolated after either chemical or enzymatic cleavage of the polymeric glycosaminoglycans heparin and heparan sulfate (HS). Within heparin and heparan sulfate this monomeric sequence is thought to form the high affinity binding site for the anti-coagulant factor antithrombin III (ATIII). Binding of heparin/HS to ATIII has been shown to increase the anti-coagulant activity of antithrombin III 1000 fold.

Administration

Fondaparinux is given subcutaneously daily. Clinically, it is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism.

Comparison to other agents

One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for heparin-induced thrombocytopenia is substantially lower. Furthermore, there have been case reports of fondaparinux being used to anticoagulate patients with established HIT as it has no affinity to PF-4. However, its renal excretion precludes its use in patients with renal dysfunction.

Unlike direct factor Xa inhibitors, it mediates its effects indirectly through antithrombin III, but unlike heparin, it is selective for factor Xa.

Uses

Fondaparinux is similar to enoxaparin in reducing the risk of ischemic events at nine days, but it substantially reduces major bleeding and improves long term mortality and morbidity.
It has been investigated for use in conjunction with streptokinase.

Chemical structure

Abbreviations

• GlcNS(6S) = 2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside

• GlcA = β-D-glucopyranuronosyl

• GlcNS(3S,6S) = 2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-α-D-glucopyranosyl

• IdoA(2S) = 2-O-sulfo-α-L-idopyranuronosyl

• GlcNS(6S)OMe = methyl-O-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside