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What is the association between lipoprotein a
[Lp(a)] and venous thrombosis (VTE)?

Henry I. Bussey, Pharm.D., FCCP, FAHA
July, 2007

Lp(a) is a subgroup or a sub-type of the cholesterol that is in the blood. The relationship between high Lp(a) and arterial atherosclerosis and arterial thrombotic events is well established. Such an association with venous thrombosis is less clear. In other words, it is generally accepted that high levels of Lp(a) are associated with hardening of the arteries (atherosclerosis) and with the development of clots in the arteries, but it is not clear if high levels of Lp(a) have anything to do with clots in the veins. Arteries are the blood vessels that carry blood away from the heart to other areas of the body. Veins are the blood vessels that carry blood back to the heart from other parts of the body.

Although some investigators have found that high levels of Lp(a) are associated with approximately a two-fold increase in the risk of venous thrombosis, others have found no such association.(1-4) Those who have suggested that a relationship exists point to data that high Lp(a) may result in an anti-fibrinolytic effect.(1) An anti-fibrinolytic effect helps blood clots to develop and/or grow in a vein. The body has its own clot dissolving system that breaks up fibrin. Fibrin is the main component of a blood clot in a vein. Therefore, the "fibrinolytic" system works to breakup clots and keep them from growing. Anything that works against this fibrinolytic process is "anti-fibrinolytic," and thus promotes clotting in the veins.

Others have reported that various thrombophilias (blood clotting disorders) and high Lp(a) often occur together in the same individual. (2) Therefore, it is possible that the presence of Lp(a) may be a marker or "flag" for patients who have other causes to be at increased risk for blood clots. It has also been suggested that Lp(a) may be more likely to cause venous blood clots in children than adults.(3,4) Even if there is an association, the question still remains as to whether the association is coincidental or whether high Lp(a) actually causes blood clots in the veins.

Additionally, I know of no data to show that altering the Lp(a) level alters the risk of venous thrombosis. Also, there are very few medications that have been shown to reduce Lp(a). In fact, the only agent I know of is niacin, which, according to a nice review by McKenney (5), can achieve a 20% to 38% reduction in Lp(a) in doses that are commonly used to treat high cholesterol levels. Even so, the potential exists that the situation between high Lp(a) levels and venous thrombosis is similar to that of high homocysteine levels and venous thrombosis. For years clinicians recognized a relationship between high homocysteine levels and thrombosis, and evidence indicated that the homocysteine levels could be lowered at little cost with folic acid and vitamin B supplements. Only recently, however, it was demonstrated that such a reduction in homocysteine does not consistently reduce the incidence of thrombosis. (see http://www.clotcare.com/clotcare/
homocysteinevasculardisease.aspx
) So, even if there is a relationship between clots in the veins and high Lp(a), we do not know if lowering the Lp(a) would reduce the risk of clotting. Clearly, more information is needed on the relationship between high Lp(a) and venous thrombosis in order for clinicians to know the best way to manage such patients.

References

  1. Vormittag, R, et al. Lipoprotein (a) in patients with spontaneous venous thromboembolism. Thrombosis Research 2007; 120(1):15-20. [doi:10.1016/j.thromres.2006.03.002]

  2. Kosch A, et al. Prothrombotic risk factors in children with spontaneous venous thrombosis and their asymptomatic parents. Thrombosis Research 2000; 99(6):531-537.[doi:10.1016/S0049-3848(00)00287-5]

  3. Nowak-Gottl U, et al. Increased lipoprotein(a) is an important risk factor for venous thormboembolism in childhood. Circulation 1999; 100:743-748. [http://www.circ.ahajournals.org/cgi/
    content/abstract/100/7/743
    ]

  4. Marcucci R, et al. Increased plasma levels of lipoprotein(a) and the risk of idiopathic and recurrent venous thromboembolism. American Journal of Medicine 2003; 115(8):601-605.

  5. McKenney J. New perspectives on the use of niacin in the treatment of lipid disorders. Archives of Internal Medicine 2004;164:697-705.
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