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Blood Clotting Problems & Heart Risk

What is a hypercoagulable state?

A hypercoagulable state occurs when there is an abnormally high tendency for the blood to thicken and clot. This can be the result of environmental factors (e.g., hormones, illness including surgery, or cancer) or because of inherited blood clotting problems. Blood clotting problems like these are more likely to increase your risk of blood clots in the deep veins of the legs (deep vein thrombosis or DVT) than clots in the arteries that can cause a heart attack. A blood clot or thrombus in the veins of the legs can break off and travel through the bloodstream to block an artery in the lungs causing the life-threatening condition, pulmonary embolism.

What causes blood clotting problems?

There are several causes for blood clotting problems. You are more prone to developing blood clots after surgery (especially hip or knee), if you are immobilized for more than 4 days, or as a result of injuries from a severe accident. Cancer can lead to a hypercoagulable state: 1% to 15% of cancer patients develop blood clots in their veins.1

Hormones, including the estrogen found in hormone therapy and birth control pills, can increase your risk of developing blood clots. During pregnancy, levels of blood clotting proteins rise and blood thinning enzymes fall. In most cases, these changes are not a cause for concern. Some women inherit blood clotting problems that increase their risk for miscarriage. These inherited blood clotting problems also put you at a higher risk of blood clots or DVT when you take oral contraceptives or hormone therapy.

What is Factor V Leiden?

Some people have a higher risk of blood clotting problems because they are born with mutations (mistakes) in the genes for blood clotting proteins. The most common inherited blood clotting problem is called Factor V Leiden (FVL), so-called because it affects the Factor V (five) clotting protein. FVL occurs in about 5% of white men and women; rates are lower for Hispanics and it is rare in people of Asian or African descent.2

Women who have one defective FVL gene have a 30-fold higher risk of developing blood clots while using birth control pills,3 a 15-fold higher risk with postmenopausal hormone therapy, and a 7-fold higher risk during pregnancy compared with women without this mutation.4 While their risks are much higher relative to women without the mutation, the actual risk remains quite low.5 Women who carry two abnormal FVL genes have an even greater risk of developing blood clots.6, 7 It is likely that these women will experience at least one blood clotting event during their lifetime.6

Do blood clotting problems increase my risk of having a heart attack?

Most blood clotting problems are more likely to increase your risk of blood clots in the deep veins of the legs (DVT) than a heart attack. However, some inherited blood clotting problems have been linked to a higher risk of heart attack. Whether a blood clotting mutation increases, decreases, or has no affect on your risk for heart disease seems to change depending on your sex and what other risk factors you have.

Does FVL increase my risk of heart attack?

FVL may increase your risk of having a heart attack at a young age (under 50 years).8 The risk posed seems to depend on what other risk factors you have. In one study of heart attack patients, FVL was 3 times more common in the men than in the women.8 In an all-women study, FVL doubled the risk of having a heart attack at an early age only in women who smoked.9

What other inherited blood clotting problems are linked to heart attack risk?
Another mutation affects a clotting protein called prothrombin. Having either a defective prothrombin or FVL gene has been shown to increase heart attack risk 12-fold in women who smoke.9 In a study of postmenopausal women who had suffered heart attacks, having a prothrombin mutation increased the risk of heart attack 7-fold in women with high blood pressure.10 However, when hormone therapy was added to the mix, these women had an 11-fold increased risk of heart attack compared with women who had high blood pressure but did not have the mutation and were not taking hormones.

A mutation that affects the Factor XIII (thirteen) clotting protein may increase a man’s risk for heart attack, but seems to increase a woman’s risk only if she also has a prothrombin mutation.8 In another study, having 2 or more factor XIII mutations appeared to decrease the risk of heart attack in postmenopausal women taking hormones compared with women who had fewer than 2 mutations and were not taking hormones.11

Can pregnancy increase my risk for a heart attack?

Women of childbearing age have a relatively low risk of heart attack to begin with. While it is well recognized that pregnant women have a higher risk of developing clots in the veins, the risk of heart attack was largely ignored. A study published in 2006 addressed this knowledge gap. Researchers searched pregnancy-related discharge records from around 1,000 hospitals nationwide.12 During 2000 to 2002, there were more than 850 cases of heart attack, making it a rare event—about 6 heart attacks per 100,000 deliveries. The risk was about 30-fold higher for women 40 years and older compared with much younger mothers. Women with inherited blood clotting problems had a 25-fold higher risk of heart attack. High blood pressure increased the risk almost 22-fold and pregnant smokers were 8 times more likely to have a heart attack than nonsmokers. Black women older than 35 years appeared to have the highest risk, but this was largely because they were more likely to have high blood pressure.

Are pregnant women treated for heart attack?

In the study mentioned above, pregnant women who had heart attacks were largely undertreated: fewer than half received cardiac catheterization—an important diagnostic test that pinpoints blockages in the arteries of the heart. This may reflect a lack of awareness among physicians that heart attack can occur during pregnancy. Increased awareness should lead to preventive screening and appropriate treatment of pregnant women at risk.

What is fibrinogen and how does it affect my heart attack risk?

High blood levels of clotting proteins, including fibrinogen, are linked to an increased risk of heart disease. The ARIC study tracked nearly 14,500 largely healthy middle-aged adults for about 5 years. It showed that high levels of fibrinogen slightly increased the risk of heart disease in women.13 It was once thought that testing for fibrinogen could help predict your risk of heart disease. However, fibrinogen has largely fallen out of favor because it’s not clear whether it tells you any more about your risk for heart disease than the traditional risk factors (such as high blood pressure).13-15 Fibrinogen levels increase with older age, menopause, pregnancy, and use of birth control pills.16, 17 Postmenopausal hormone therapy lowers fibrinogen.18

Should I be tested for blood clotting problems?

Probably not. There is no standard test for fibrinogen and no clear definition of a high or low reading because levels vary with age, hormones, and other risk factors. Tests that measure blood clotting proteins do not help predict whether you will develop heart disease any better than the well established risk factors (such as high blood pressure and high cholesterol).13-15 It has also not been shown that lowering fibrinogen will reduce your risk for heart disease.

Tests for inherited blood clotting problems are not usually done, but you may be sent for one if you meet any of the following criteria:19

How are blood clotting problems treated?

If you had a blood clot and were diagnosed with an inherited blood clotting problem, you may have to take blood thinning medications for the rest of your life. Some people at risk take blood thinning medications during high-risk situations (e.g., pregnancy or surgery).19, 20

There is no established treatment for high levels of blood clotting proteins such as fibrinogen. Some of the risk factors that increase your likelihood of blood clotting problems include smoking, physical inactivity, higher body mass index (BMI), and diabetes or early signs of diabetes ( insulin resistance).16 Quitting smoking and getting more exercise helps lower levels of blood clotting proteins and has also been proven to lower your risk of heart disease and heart attack.


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2. Ridker PM, Miletich JP, Hennekens CH, Buring JE. Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening. JAMA. 1997;277:1305-1307.
3. Vandenbroucke JP, Koster T, Briet E, et al. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet. 1994;344:1453-1457.
4. Ornstein DL, Cushman M. Factor V Leiden. Circulation. 2003;107:94e-97.
5. Vandenbroucke JP, van der Meer FJM, Helmerhorst FM, Rosendaal FR. Factor V Leiden: should we screen oral contraceptive users and pregnant women? BMJ. 1996;313:1127-1130.
6. Rosendaal F, Koster T, Vandenbroucke J, Reitsma P. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance) [see comments]. Blood. 1995;85:1504-1508.
7. Juul K, Tybjaerg-Hansen A, Schnohr P, Nordestgaard BG. Factor V Leiden and the risk for venous thromboembolism in the adult Danish population. Ann Intern Med. 2004;140:330-337.
8. Butt C, Zheng H, Randell E, et al. Combined carrier status of prothrombin 20210A and factor XIII-A Leu34 alleles as a strong risk factor for myocardial infarction: evidence of a gene-gene interaction. Blood. 2003;101:3037-3041.
9. Tanis BC, Bloemenkamp DG, van den Bosch MA, et al. Prothrombotic coagulation defects and cardiovascular risk factors in young women with acute myocardial infarction. Br J Haematol. 2003;122:471-478.
10. Psaty BM, Smith NL, Lemaitre RN, et al. Hormone Replacement Therapy, Prothrombotic Mutations, and the Risk of Incident Nonfatal Myocardial Infarction in Postmenopausal Women. JAMA. 2001;285:906-913.
11. Reiner AP, Heckbert SR, Vos HL, et al. Genetic variants of coagulation factor XIII, postmenopausal estrogen therapy, and risk of nonfatal myocardial infarction. Blood. 2003;102:25-30.
12. James AH, Jamison MG, Biswas MS, et al. Acute Myocardial Infarction in Pregnancy: A United States Population-Based Study. Circulation. 2006;113:1564-1571.
13. Folsom AR, Wu KK, Rosamond WD, Sharrett AR, Chambless LE. Prospective Study of Hemostatic Factors and Incidence of Coronary Heart Disease : The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 1997;96:1102-1108.
14. Cooper JA, Miller GJ, Bauer KA, et al. Comparison of Novel Hemostatic Factors and Conventional Risk Factors for Prediction of Coronary Heart Disease. Circulation. 2000;102:2816-2822.
15. Pankow JS, Folsom AR, Province MA, et al. Family history of coronary heart disease and hemostatic variables in middle-aged adults. Atherosclerosis Risk in Communities Investigators and Family Heart Study Research Group. Thromb Haemost. 1997;77:87-93.
16. Stefanick ML, Legault C, Tracy RP, et al. Distribution and correlates of plasma fibrinogen in middle-aged women. Initial findings of the Postmenopausal Estrogen/ Progestin Interventions (PEPI) study. Arterioscler Thromb Vasc Biol. 1995;15:2085-2093.
17. Vorster HH. Fibrinogen and women's health. Thromb Res. 1999;95:137-154.
18. Effects on haemostasis of hormone replacement therapy with transdermal estradiol and oral sequential medroxyprogesterone acetate: a 1-year, double-blind, placebo-controlled study. The Writing Group for the Estradiol Clotting Factors Study. Thromb Haemost. 1996;75:476-480.
19. Grody WW, Griffin JH, Taylor AK, Korf BR, Heit JA. American College of Medical Genetics Consensus Statement on Factor V Leiden Mutation Testing. Accessed May 18, 2005.
20. Hirsh J, Hoak J. Management of Deep Vein Thrombosis and Pulmonary Embolism : A Statement for Healthcare Professionals From the Council on Thrombosis (in Consultation With the Council on Cardiovascular Radiology), American Heart Association. Circulation. 1996;93:2212-2245.

Filed in Am I at Risk? > Blood Clotting Problems

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