Fondaparinux (Arixtra) is an
anticoagulantAn anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders...
medication.
It is marketed by
GlaxoSmithKline GlaxoSmithKline plc is a United Kingdom-based pharmaceutical, biological, and healthcare company. GSK is the world's second largest pharmaceutical company and a research-based company with a wide portfolio of pharmaceutical products covering anti-infectives, central nervous system, respiratory,...
.
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
glycosaminoglycanGlycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit.-Production:...
s
heparinHeparin, a highly-sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule. It can also be used to form an inner anticoagulant surface on various experimental and medical devices such as test tubes and...
and
heparan sulfateHeparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins...
(HS).
Fondaparinux (Arixtra) is an
anticoagulantAn anticoagulant is a substance that prevents coagulation; that is, it stops blood from clotting. A group of pharmaceuticals called anticoagulants can be used in vivo as a medication for thrombotic disorders...
medication.
It is marketed by
GlaxoSmithKline GlaxoSmithKline plc is a United Kingdom-based pharmaceutical, biological, and healthcare company. GSK is the world's second largest pharmaceutical company and a research-based company with a wide portfolio of pharmaceutical products covering anti-infectives, central nervous system, respiratory,...
.
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
glycosaminoglycanGlycosaminoglycans or mucopolysaccharides are long unbranched polysaccharides consisting of a repeating disaccharide unit.-Production:...
s
heparinHeparin, a highly-sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule. It can also be used to form an inner anticoagulant surface on various experimental and medical devices such as test tubes and...
and
heparan sulfateHeparan sulfate is a linear polysaccharide found in all animal tissues. It occurs as a proteoglycan in which two or three HS chains are attached in close proximity to cell surface or extracellular matrix proteins...
(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 thrombosisIn medicine, deep vein thrombosis is the formation of a blood clot in a deep vein...
in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and
pulmonary embolismPulmonary embolism is a blockage of the main artery of the lung or one of its branches by a substance that has travelled from elsewhere in the body through the bloodstream . Usually this is due to embolism of a thrombus from the deep veins in the legs, a process termed venous thromboembolism...
.
Comparison to other agents
One potential advantage of fondaparinux over LMWH or unfractionated heparin is that the risk for
heparin-induced thrombocytopeniaHeparin-induced thrombocytopenia without or with thrombosis is the development of thrombocytopenia due to the administration of the anticoagulant heparin, either in its "unfractionated" or "low molecular weight" form. It predisposes to thrombosis, the formation of abnormal blood clots inside a...
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 inhibitorDirect factor Xa inhibitors are a new class of antithrombotics which act directly upon Factor X in the coagulation cascade, without using antithrombin as a mediator.Examples include:* rivaroxaban* apixaban* otamixaban* YM466...
s, it mediates its effects indirectly through antithrombin III, but unlike
heparinHeparin, a highly-sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule. It can also be used to form an inner anticoagulant surface on various experimental and medical devices such as test tubes and...
, it is selective for
factor XFactor X, also known by the eponym Stuart-Prower factor or as thrombokinase, is an enzyme of the coagulation cascade. It is a serine endopeptidase .-Physiology:...
a.
Uses
Fondaparinux is similar to
enoxaparinEnoxaparin is a low molecular weight heparin marketed as Lovenox or Clexane.It is used to prevent and treat deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection...
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
streptokinaseStreptokinase is a protein produced by beta-haemolytic streptococcus and is used as an effective and inexpensive clot-dissolving medication in some cases of myocardial infarction and pulmonary embolism....
.
Abbreviations
- GlcNS(6S) = 2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside
- GlcA = β-D-glucopyranuronosyl
Glucuronic acid is a carboxylic acid. Its structure is similar to that of glucose. However, glucuronic acid's sixth carbon is oxidized to a carboxylic acid...
- GlcNS(3S,6S) = 2-deoxy-3,6-di-O-sulfo-2-(sulfoamino)-α-D-glucopyranosyl
- IdoA(2S) = 2-O-sulfo-α-L-idopyranuronosyl
L-Iduronic acid is the major uronic acid component of the glycosaminoglycans dermatan sulfate and heparin. It is also present in heparan sulfate although here in a minor amount relative to its carbon-5 epimer glucuronic acid....
- GlcNS(6S)OMe = methyl-O-2-deoxy-6-O-sulfo-2-(sulfoamino)-α-D-glucopyranoside