Fondaparinux (trade name Arixtra) is an

anticoagulant An anticoagulant, commonly known as a blood thinner, is a chemical substance that prevents or reduces the coagulation of blood, prolonging the clotting time. Some occur naturally in blood-eating animals, such as leeches and mosquitoes, which ...

medication chemically related to low molecular weight heparins. It is marketed by Viatris. A generic version developed by Alchemia is marketed within the US by Dr. Reddy's Laboratories.

Medical uses

Clinically, it is used for the prevention of

deep vein thrombosis Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enl ...

in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and

pulmonary embolism Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain ...

. 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.

Comparison to other agents

One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for heparin-induced thrombocytopenia (HIT) is substantially lower. Furthermore, there have been case reports of fondaparinux being used to anti-coagulate patients with established HIT as it has no affinity for PF4. 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 Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Heparin is a blood anticoagulant that increases the activity of antithrombin. It is used in the treatment of myocardial infarction, ...

, it is selective for

factor X Coagulation factor X (), or Stuart factor, is an enzyme of the coagulation cascade, encoded in humans by ''F10'' gene. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for i ...

Pharmacology

Mechanism of action

Fondaparinux is a synthetic pentasaccharide factor Xa inhibitor. Fondaparinux binds antithrombin and accelerates its inhibition of factor Xa. 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

and

heparan sulfate Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs in a proteoglycan (HSPG, i.e. Heparan Sulfate ProteoGlycan) in which two or three HS chains are attached in close proximity to cell surface or extracellular ma ...

(HS). Within heparin and heparan sulfate this monomeric sequence is thought to form the high-affinity binding site for the anti-coagulant factor antithrombin (AT). Binding of heparin or HS to AT has been shown to increase the anti-coagulant activity of antithrombin 1000 fold. In contrast to heparin, fondaparinux does not inhibit thrombin.

Chemistry

Abbreviations

* GlcNS6S = 2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside * GlcA = β-D-glucopyranuronoside * GlcNS3,6S = 2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-α-D-glucopyranosyl * IdoA2S = 2-O-sulfo-α-L-idopyranuronoside * GlcNS6SOMe = methyl-O-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside Fondaparinux is only accessible by chemical synthesis. Recently, Supriya Dey ''et al''. reported an effective and scalable one-pot synthesis of Fondaparinux. The sequence of monosaccharides is D-GlcNS6S-α-(1,4)-D-GlcA-β-(1,4)-D-GlcNS3,6S-α-(1,4)-L-IdoA2S-α-(1,4)-D-GlcNS6S-OMe, as shown in the following structure:

References

External links

* {{Portal bar , Medicine Heparins Sulfamates