Warfarin Institute of America
DEDICATED TO YOUR HEALTH SINCE 2000
LUPUS ANTICOAGULANT AND ITS TREATMENT
by
Bethanie Lan Tran, Pharm D. Candidate
University of Colorado School of Pharmacy
Antiphospholipid syndrome or Hughes’ disease is an autoimmune disease which often associates with recurrent thrombosis either in venous or arterial circulation, thrombocytopenia, or fetal loss after the 1st trimester1. The mechanism of action may involve antibody-induced platelet activation producing phosphtidyleserine-rich procoagulant surfaces and thrombocytopenia2. There are three types of antiphospholipid antibody involved in antiphospholipid syndrome1:
1) anti-cardiolipin antibodies
2) lupus anticoagulant
3) antibody that is associated with a biologic false + test for syphillis
What is lupus anticoagulant?
Lupus anticoagulant is an IgM or IgG antibody that produces a prolong plasma thromboplastin time (PTT) assay in vitro resulting in an artificially long protime. Clinically, this does not result in a bleeding disorder. Instead, lupus anticoagulant has been associated with an increased risk of thrombosis and recurrent spontaneous fetal loss1. Therefore, the name lupus anticoagulant is considered a misnomer. Lupus anticoagulant should be suspected in patients with remarkably prolonged PTT without any clinical bleeding. However, bleeding can occur if a secondary disorder is present. Patients do not need to be diagosed with lupus in order to have lupus anticoagulant. Only 5-10% of patients with systemic lupus erythematosus have lupus anticoagulant. It is much more commonly seen in patients without any underlying disorders but who continue having recurrent throbosis events or in patients who are taking phenothiazines1.
How is lupus anticoagulant detected in patients?
According to Proven et al 3, the dilute Russell viper venom time (DRVVT) test is the only test that can identify patients with lupus anticoagulant (LA) other than an LA test. However, more than one LA test was required to identify all patients with LA and none of the LA test can be used to correlate with thrombosis or systemic disease in this patient population. In addition, according to the International Society on Thrombosis and Haemostasis, patients who are lupus anticoagulant positive need to have three consistent laboratory results from three different LA tests 4.
What are the risks of having lupus anticoagulant?
As mentioned above, lupus anticoagulant has been associated with an increased risk of thrombosis events. In patients with systemic lupus erythematosus who also have lupus anticoagulant alone or in combination with anti-cardiolipin antibodies, the risk of VTE is 20 to 30 fold higher compared to the general population 5.
What are the treatment options?
Prednisone, which is an immunosuppressive agent, can be use to rapidly eliminate the lupus anticoagulant. However, it is not clear whether prednisone has any impact on reducing thromoembolic risk or events1. There are no specifc guidelines for lupus anticoagulant treatment; therefore, the guidelines used are under a broader category of antiphospholipid syndrome. According to the CHEST guidelines, every patient with antiphospholipid antibodies and a history of venous thromboses should receive long term anticoagulants due to high risk of recurrence. The treatment course usually begins with IV heparin or low-molecular weight heparin following by (usually) life long warfarin therapy. That the INR range for these patients should be 2-3 is supported by Crowther et al 7, who compared standard-intensity warfarin therapy (INR 2-3) to high-intensity warfarin thereapy (INR 3.1 to 4) in patients with positive antiphospholipid antibodies and a history of thromboembolism. High intensity warfarin therapy did not improve antithrombotic protection but added an increased risk of bleeding. In patients with antiphospholipid antibodies, there is an increased risk of developing VTE or pregnancy loss. Surveillance, mini-dose heparin, prophylactic LMWH, and/ or low dose aspirin (75 to 162 mg daily) can be used but the level of recommendation is intermediate, based on observational studies.
Due to the prolonged PTT caused by lupus anticoagulant mentioned earlier, both heparin and warfarin therapy can be difficult to monitor. Low molecular weight heparin can be used as an alternative but can be quite expensive and the efficacy is not proven to be better compare to other treatment options in clinical trials.
According to Pierangeli et al 8, other treatment options included 81 mg aspirin or immunosuppressive medications in combination with anticoagulants. However, these results are variable. In patients with systemic lupus erythematosus, hydroxychloroquine can be used as a treatment for lupus and may be beneficial in decrease risk of thrombosis. According to Edwards and Espinola et al 9, 10, hydroxychloroquine significantly decrease both thrombus size and total time of thrombus formation in mice that previously were injected with purified immunoglobulin G from patients with antiphospholipid syndrome. More clinical trials are needed to establish the benefits and efficacy of using hydroxychloroquine as treatment of antiphospholipid-mediated thrombosis.
References:
1. Current Medical Diagnosis & Treatment-45th Ed. (2006) [book on CD-rom]. Jackson: Teton Data System; 1993. Based on: Tierney L, Papadakis M, McPhee S, editors. Current Medical Diagnosis & Treatment. New York: Lange Medical Books/McGraw-Hill, Medical Publishing Division; 2006. STAT!-Ref Electronic Medical Library
2. Merk Manual-17th Ed. (1999) Centennial Edition [book on CD-rom]. Jackson: Teton Data Systems; 1993. Based on: Beers M, Berkow R, editors. Merk Manual. West Point: Merck & Co., Inc; 1999. STAT!-Ref Electronic Medical Library.
3. Proven A, Bartlett RP, Moder KG, Chang MA, Cardel LK, Heit JA. Clinical importance of positive test results for lupus anticoagulant and anticardiiolipin antibodies [validation studies]. Mayo Clinic Proc 2004, April; Page: 1.
4. Exner T, Triplett DA, Taberner D, Machin SJ. Guidelines for testing and revised criteria for lupus anticoagulants. SSC Subcommittee for the Standardization of Lupus Anticoagulants. ThromHaemost. 1991: 65:320-322.
5. Brouwer J, Bijl M, Veeger N, Kluin-Nelemans H, Meer J. The Contribution of inherited and acquired thrombophilic defects, alone or combined with antiphospholipid antibodies, to venous and arterial thromboembolism in patients with systemic lupus erythematosus. Journal of the American Society of Hematology. 2004, July [9/6/06]; Vol. 104; pp 143-148. Available from URL: http://0-www.bloodjournal.org.library.uchsc.edu/cgi/content/full/104/1/143.
6. Buller HR, Agmelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy [15383479] 2004 September [date look at 9/6/06]; 130 (1) [401S-428S]. Available from: http://www.chestjournal.org/cgi/content/full/126/3_suppl/401S?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=antiphospholipid&searchid=1&FIRSTINDEX=0&volume=126&issue=3_suppl&resourcetype=HWCIT
7. Crowther, MA, Ginsberg, JS, Julian, J, et al A comparison of two intensities of warfarin for the prevention of recurrent thrombosis in patients with the antiphospholipid antibody syndrome. N Engl J Med 2003;349, 1133-1138.
8. Pierangeli S, Chen P, Gonzalez E. Antiphospholipid antibodies and the antiphospholipid syndrome: an update on treatment and pathogenic mechanisms. Current Opinion in Hematology 2006 September: volume 13 (5), p 366-375.
9. Edwards MH, Pierangeli S, Liu X, et al. Hydroxychloroquine reverses thrombogenic properties of antiphospholipid antibodies in mice. Circulation 1997; 96:4380–4384
10. Espinola RG, Pierangeli SS, Harris EN. Hydroxychloroquine reverses platelet activation induced by human IgG Antiphospholipid antibodies. Thromb Haemost 2002; 87:518–522
©2006 Bethanie Lan Tran Used by permission.
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Last updated June 13, 2007
