Fondaparinux (trade name Arixtra) is an

anticoagulant Anticoagulants, commonly known as blood thinners, are chemical substances that prevent or reduce coagulation of blood, prolonging the clotting time. Some of them occur naturally in blood-eating animals such as leeches and mosquitoes, where the ...

medication chemically related to

low molecular weight heparin Low-molecular-weight heparin (LMWH) is a class of anticoagulant medications. They are used in the prevention of blood clots and treatment of venous thromboembolism (deep vein thrombosis and pulmonary embolism) and in the treatment of myocardial in ...

s. It is marketed by

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...

. A generic version developed by Alchemia is marketed within the US by

Dr. Reddy's Laboratories Dr. Reddy's Laboratories is an Indian multinational pharmaceutical company based in Hyderabad. The company was founded by Kallam Anji Reddy, who previously worked in the mentor institute Indian Drugs and Pharmaceuticals Limited. Dr. Reddy's ...

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 enla ...

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 p ...

. Fondaparinux is similar to

enoxaparin Enoxaparin sodium, sold under the brand name Lovenox among others, is an anticoagulant medication (blood thinner). It is used to treat and prevent deep vein thrombosis (DVT) and pulmonary embolism (PE) including during pregnancy and following c ...

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 Streptokinase (SK) is a thrombolytic medication activating plasminogen by nonenzymatic mechanism. As a medication it is used to break down clots in some cases of myocardial infarction (heart attack), pulmonary embolism, and arterial thromboemboli ...

Comparison to other agents

One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for

heparin-induced thrombocytopenia Heparin-induced thrombocytopenia (HIT) is the development of thrombocytopenia (a low platelet count), due to the administration of various forms of heparin, an anticoagulant. HIT predisposes to thrombosis (the abnormal formation of blood clots ...

(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 Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine (C-X-C motif) ligand 4 (CXCL4) . This chemokine is released from alpha-granules of activated platelets during platelet aggregation, ...

. However, its renal excretion precludes its use in patients with renal dysfunction. Unlike

direct factor Xa inhibitor Direct may refer to: Mathematics * Directed set, in order theory * Direct limit of (pre), sheaves * Direct sum of modules, a construction in abstract algebra which combines several vector spaces Computing * Direct access (disambiguation), a ...

s, 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. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatm ...

, it is selective for

factor X Factor X, also known by the eponym Stuart–Prower factor, is an enzyme () of the coagulation cascade. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for its synthesis. Fa ...

Pharmacology

Mechanism of action

Fondaparinux is a synthetic pentasaccharide

factor Xa Factor X, also known by the eponym Stuart–Prower factor, is an enzyme () of the coagulation cascade. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for its synthesis. Fa ...

inhibitor. Fondaparinux binds

antithrombin Antithrombin (AT) is a small glycoprotein that inactivates several enzymes of the coagulation system. It is a 432-amino-acid protein produced by the liver. It contains three disulfide bonds and a total of four possible glycosylation sites. α-An ...

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

glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case ...

and

heparan sulfate Heparan sulfate (HS) is a linear polysaccharide found in all animal tissues. It occurs as 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

(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 Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...

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