# Exercise as it relates to Disease/Exercise and Thrombosis

Thrombosis is the formation of a clot in the blood that either blocks, or partially blocks a blood vessel. The thrombus may lead to infarction, or death of tissue, due to a reduced blood supply. When a blood vessel is damaged, the body prevents blood loss by using platelets and fibrin to form a clot. A clot that detaches itself from the site and travels throughout the circulatory system is known as an embolus. Thrombosis can occur in arteries (arterial thrombosis) and veins (venous thrombosis).

### Prevalence

Thrombosis effects about 1 in 1000 individuals worldwide. This rate rises rapidly in individuals over 45 years of age and appears to slightly effect men more than women.

## Causes

Thrombosis is thought to be induced by one or a combination of the below factors, known as Virchow’s Triad:
* Disturbed blood flow
* Endothelial cell damage
* Hypercoagulability
| Factor | Causes |
| Disturbed blood flow | Blood flow can be disturbed or interrupted by many different ways such as venous stasis, varicose veins, mitral stenosis and prolonged immobility (travelling or bed ridden), impaired vasodilation / vasoconstriction. |
| Endothelial cell damage | The one-cell thick endothelial lining of the blood vessels may be damaged by hypertension, chronic inflammation, hyperinsulemia, dyslipidemia and turbulent blood flow. |
| Hypercoagulability | An increase in the coagulability of the blood may be the cause of a genetic deficiency, an autoimmune disease and some forms of cancer treatment (radiation, chemotherapy) |

## Complications

Complications of thrombosis are often ischemic-related that lead to a significant reduction or complete restriction of blood flow resulting in damage or potential death to a particular tissue. The most common complications are pulmonary embolism, myocardial infarction, stroke and cor pulmonale.
| Complication | Explanation | Symptoms |
| Pulmonary Embolism (PE) | PE occurs when an embolism travels through the heart and into the lunges. It lodges itself in an artery and obstructs blood flow. Depending on the size of the embolism, PE can remain asymptomatic or be life-threatening. | Dizziness, lightheadedness Acute shortness of breath Chest pain Coughing up blood |
| Myocardial Infarction (MI) | MI occurs when a clot lodges itself in a coronary artery and obstructs the blood flow to the heart. As a consequence the tissue becomes starved of oxygen and potentially dies. | Squeezing or pressure pain in chest Referred pain into arms, shoulders, back or jaw Shortness of breath Profuse sweating Nausea and vomiting |
| Stroke | Stroke occurs when a clot becomes lodged in an artery of the brain or an artery supplying blood to the brain. Severely reduced blood flow (ischemia) can result in damage and/or death to brain cells. | Acute numbness, weakness or paralysis particularly on one side of the body Sudden confusion Vision problems in one or both eyes Loss of balance and coordination Severe headache Difficulty speaking or understanding speech |
| Cor Pulmonale | Typically a chronic disease, Cor Pulmonale is failure of the right side of the heart due to prolonged hypertension within the pulmonary artery and right ventricle. The ventricle becomes enlarged and weaker and often occurs from a pulmonary embolism. | Fatigue Shortness of breath Wheezing or coughing Chest pain Dizziness |

## Exercise

It is well documented that individuals engaging in regular physical activity are less likely to experience a cardiovascular event. Changes in lipid profile, insulin sensitivity and other physiological mechanisms in conjunction with lifestyle habits are thought to reduce this likelihood. There are a number of mechanisms of how exercise alone can reduced the likelihood of suffering a cardiovascular event.

### Mechanisms

The hemostatic and fibrinolytic systems appear to play an important role in cardiovascular health. Fibrin is an insoluble, fibrous protein involved in the formation of a blood clot. Elevated levels of fibrin pose an increased risk of thrombosis. Fibrinolysis or the fibrinolytic system is the enzymatic breakdown of the fibrin in blood clots. Chronic exercise may decrease coagulation potential and increase fibrinolytic potential in healthy individuals and cardiovascular disease (CVD) patients. It can be concluded that chronic aerobic exercise may induce favourable adaptations that reduce the likelihood of an ischemic event occurring both at rest and during physical exertion.
Exercise may also reduce thrombotic tendency due to an increase in nitric oxide (NO). This increase in NO is the result of enhanced expression of endothelial nitric oxide synthase (eNOS) mRNA by which exercise is thought to induce. The synthesis of NO results in the phosphorylation of several proteins that cause smooth muscle relaxation and subsequent vasodilation. Lower blood pressure as a result of vasodilation is a favourable outcome in reducing thrombotic likelihood as well as other cardiovascular diseases.
It is also well-documented that exercise improves one's insulin sensitivity. This is favourable in that individuals possessing poor insulin sensitivity can often lead to too much insulin being released from the pancreas, this is known as hyperinsulinemia. Hyperinsulinemia as an independent factor, has been shown to contribute to endothelial damage and initiate an atherosclerotic process, which can subsequently lead to thrombosis. Therefore improving one's insulin sensitivity through exercise may reduce thrombotic tendency.
Changes in lipid profile is another favourable outcome by which exercise causes. A reduction in low-density lipoproteins (LDL) is important in decreasing the likelihood of atherosclerosis. Atherosclerosis and thrombosis are closely related vascular problems and a reduction in atherosclerosis is likely to reduce thrombotic tendency.

### Recommendations

There is a lack of evidence for exercise recommendations for thrombosis as a stand-alone disease. Thrombosis however is considered a cardiovascular disease and thrombotic individuals are advised to follow the same exercise recommendations of:
* 30 minutes or more of moderate-intensity physical activity on most, if not all days of the week,
* Moderate-intensity resistance training on at least two days per week.
It is important to cease exercising if experiencing:
* Feelings of nausea
* Chest pain
* Dizziness
* Headaches
* Numbness
These are potential early signs of a cardiovascular event.

## Further reading

- National Heart Foundation of Australia physical activity recommendations for people with cardiovascular disease

## References

* ↑ Furie B, Furie BC (2008). "Mechanisms of thrombus formation". New England Journal of Medicine 359 (9): 938–949. doi:10.1056/NEJMra0801082. PMID 18753650.
* ↑ Cushman M. Epidemiology and risk factors for venous thrombosis. 2007;44(2):62--69.
* ↑ Cushman M. Epidemiology and risk factors for venous thrombosis. 2007;44(2):62--69.
* ↑ April Wang Armstrong; David E. Golan; Armen H. Tashjian; Ehrin Armstrong (2008). Principles of pharmacology: the pathophysiologic basis of drug therapy. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 396. ISBN 0-7817-8355-0.
* ↑ Lowe GD (2003). "Virchow's triad revisited: abnormal flow". Pathophysiol. Haemost. Thromb. 33 (5-6): 455–7. doi:10.1159/000083845. PMID 15692260.
* ↑ Pinkney J, Stehouwer C, Coppack S, Yudkin J. Endothelial dysfunction: cause of the insulin resistance syndrome. Diabetes. 1997;46(Supplement 2):9--13.
* ↑ Chung I, Lip GY (2003). "Virchow's triad revisited: blood constituents". Pathophysiol. Haemost. Thromb. 33 (5-6): 449–54. doi:10.1159/000083844. PMID 15692259.
* ↑ Dalen J, Alpert J. Natural history of pulmonary embolism. Progress in cardiovascular diseases. 1975;17(4):259--270.
* ↑ Margolis J, Kannel W, Feinleib M, Dawber T, McNamara P. Clinical features of unrecognized myocardial infarction—silent and symptomatic: eighteen year follow-up: the Framingham study. The American journal of cardiology. 1973;32(1):1--7.
* ↑ Greenlund K, Neff L, Zheng Z, Keenan N, Giles W, Ayala C et al. Low public recognition of major stroke symptoms. American journal of preventive medicine. 2003;25(4):315--319.
* ↑ Weitzenblum E. Chronic cor pulmonale. Heart. 2003;89(2):225--230.
* ↑ Myers J. Exercise and cardiovascular health. Circulation. 2003;107(1):2--5.
* ↑ Imhof A, Koenig W. Exercise and thrombosis. Cardiology clinics. 2001;19(3):389--400.
* ↑ Wada H, Kobayashi T, Abe Y, Hatada T, Yamada N, Sudo A et al. Elevated levels of soluble fibrin or D-dimer indicate high risk of thrombosis. Journal of Thrombosis and Haemostasis. 2006;4(6):1253--1258
* ↑ 11. Koenig W, Ernst E. Exercise and thrombosis. Coronary artery disease. 2000;11(2):123--127
* ↑ 11. Koenig W, Ernst E. Exercise and thrombosis. Coronary artery disease. 2000;11(2):123--127
* ↑ asaki Y, Noguchi T, Yamamoto E, Giddings J, Ikeda K, Yamamoto J et al. Effects of voluntary exercise on cerebral thrombosis and endothelial function in spontaneously hypertensive rats (SHRSP/Izm). Clinical and Experimental Pharmacology and Physiology. 2004;31(s2):47--48.
* ↑ asaki Y, Noguchi T, Yamamoto E, Giddings J, Ikeda K, Yamamoto J et al. Effects of voluntary exercise on cerebral thrombosis and endothelial function in spontaneously hypertensive rats (SHRSP/Izm). Clinical and Experimental Pharmacology and Physiology. 2004;31(s2):47--48.
* ↑ Weller, Richard, Could the sun be good for your heart? TedxGlasgow March 2012, posted January 2013
* ↑ Lip G. Hypertension, Platelets, and the Endothelium The “Thrombotic Paradox” of Hypertension (or “Birmingham Paradox”) Revisited. Hypertension. 2003;41(2):199--200
* ↑ Borghouts L, Keizer H. Exercise and insulin sensitivity: a review. International journal of sports medicine. 2000;21(01):1--12
* ↑ Insulin Causes Endothelial Dysfunction in Humans
* ↑ Ramachandran S, Penumetcha M, Merchant N, Santanam N, Rong R, Parthasarathy S. Exercise reduces preexisting atherosclerotic lesions in LDL receptor knock out mice. Atherosclerosis. 2005;178(1):33--38
* ↑ Holvoet P, Collen D. Oxidized lipoproteins in atherosclerosis and thrombosis. The FASEB journal. 1994;8(15):1279--1284
* ↑ Briffa T, Maiorana A, Allan R, others. of the Executive Working Group and National Forum Participants, 2006, National Heart Foundation of Australia Physical Activity Recommendations for People with Cardiovascular Disease, National Heart Foundation of Australia. Families, Incomes and Jobs, Volume 2. 2007;2002:100
* ↑ Briffa T, Maiorana A, Allan R, others. of the Executive Working Group and National Forum Participants, 2006, National Heart Foundation of Australia Physical Activity Recommendations for People with Cardiovascular Disease, National Heart Foundation of Australia. Families, Incomes and Jobs, Volume 2. 2007;2002:100