Arixtra and Leiden – pro
Factor V Leiden, or factor V G1691A, is a single-point mutation in the gene that codes for coagulation factor V.2 It involves a G (guanine)-to-A (adenine) substitution at nucleotide 1691 (G1691A) in exon 10, which predicts the replacement of arginine at amino acid residue 506 by glutamine (Arg506Gln). The mutation, transmitted through autosomal dominant inheritance, renders factor V resistant to inactivation by APC (a natural anticoagulant protein). Factor V Leiden accounts for 92% of cases of APC resistance (APC-R), with the remaining 8% of cases resulting from pregnancy, oral contraceptive use, cancer, selected APA, and other factor V point mutations. It is a well accepted indication for life-long anti-coagulation after a DVT or PE.
Low molecular weight heparin (LMWH) is an anticoagulant drug used in both the prevention of clot formation in the blood vessels (thrombosis) and in the treatment of conditions caused by clot formation or embolization. It is an injectable drug that may be administered by the patient or by a health care practitioner. LMWH may be used in some circumstances as an alternative to oral warfarin or injectable unfractionated heparin therapy (UFH). Fondaparinux (Arixtra®) is a synthetic pentasaccharide selective inhibitor of factor Xa used in a similar fashion and for some similar indications as LMWHs.
An extensive literature review and evaluation of the evidence regarding the use of LMWH, fondaparinux and other forms of antithrombotic therapy and prophylaxis was conducted by the Seventh American College of Chest Physicians (ACCP) Conference on Antithrombotic and Thrombolytic Therapy and published in “Chest” in September, 2004.
Fondaparinux (Arixtra®), is a factor Xa inhibitor with some similar indications and activity as the LMWHs. It may in some cases be used as an alternative to LMWHs for certain indications. Despite the fact LMWH has different indications and dosing regimens, and has been studied for different uses, there is considerable overlap for use in similar clinical circumstances as an alternative to UFH. When there is a choice between long term UFH and LMWH/fondaparinux, LMWH/fondaparinux has advantages in terms of frequency of administration, predictability of response, and decreased incidence of complications such as osteoporosis or heparin induced thrombocytopenia. Given these two options, it is reasonable that LMWH/fondaparinux would be the drug(s) of choice.
ANTITHROMBOTIC THERAPY AND PREVENTION OF THROMBOSIS, 9TH ED: AMERICAN COLLEGE OF CHEST PHYSICIANS EVIDENCE-BASED CLINICAL PRACTICE GUIDELINES
Chest February 2012 141:2 suppl 1S;
David Bergqvist Review of fondaparinux sodium injection for the prevention of venous thromboembolism in patients undergoing surgery. Vasc Health Risk Manag. 2006 ;2 (4):365-70
Colleen M. Johnson, MD Hypercoagulable States: A Review Vascular and Endovascular Surgery, Vol. 39, No. 2, 123-133 (2005)
Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med. 2001;344:1222-1231.