Iron is an essential mineral that is needed by the body for many vital functions. It helps transport oxygen around the body, supports energy production, and plays a role in immune function. While iron is important, having too much iron in the body can also be problematic and has been linked to an increased risk of blood clots. This article will examine the evidence surrounding the question of whether high iron levels can contribute to blood clot formation.
What are blood clots?
Blood clots, also known as thromboses, form when blood platelets and proteins in the plasma stick together at the site of blood vessel damage or abnormal blood flow. This clumping helps stop bleeding from an injury by forming a plug. However, blood clots can also form inside intact blood vessels for a variety of reasons and cause blockages. These clots are dangerous because if they become lodged in blood vessels in the heart, lungs, or brain, they can cut off blood supply and cause heart attacks, pulmonary embolisms, or strokes.
There are two main types of problematic blood clots in the circulatory system:
Arterial clots
Arterial clots form in the arteries and obstruct blood flow. They often form due to atherosclerosis which is the buildup of plaque on artery walls. Plaque rupture can trigger clot formation.
Venous clots
Venous clots occur in the veins, usually in the deep veins of the leg (known as deep vein thrombosis or DVT). Part of the clot can break off and travel to the lungs causing a pulmonary embolism. Prolonged inactivity, injury, surgery, and some inherited blood disorders increase venous clot risk.
What causes blood clots to form?
Blood clotting is a complex process involving multiple clotting factors in the blood. Anything that shifts the balance towards increased clotting can raise the risk of thrombosis. Contributing factors include:
- Endothelial injury – damage to the lining of blood vessels
- Abnormal blood flow – stagnant or turbulent flow
- Hypercoagulability – increased clotting ability of the blood
- Genetic factors – inherited clotting disorders
- Lifestyle factors – smoking, obesity, inactivity
- Medical conditions – cancer, sepsis, inflammatory diseases
- Medications – birth control pills, hormone replacement therapy
- Pregnancy
- Advanced age
How might iron affect blood clot risk?
Iron has been shown to influence several parts of the clotting process and could potentially shift the body towards a prothrombotic state in some circumstances. Possible mechanisms by which iron may promote blood clots include:
Increasing thrombin generation
Thrombin is an enzyme central to the coagulation cascade. It converts fibrinogen into fibrin strands that form the backbone of a clot. Iron may increase production of thrombin.
Oxidative stress
Excess iron in cells can lead to oxidative stress – an imbalance between free radicals and antioxidants. This stress environment can damage blood vessels and has been linked to atherosclerosis and arterial thrombosis.
Promoting platelet aggregation
Platelets are blood cell fragments vital for clot formation. Iron may enhance platelet reactivity and aggregation, increasing their clumping at sites of vascular injury.
Altering blood flow
By promoting atherosclerosis and inflammation, high iron levels can negatively impact blood vessel structure and function. This disturbs normal laminar flow and makes the blood more likely to clot.
Interfering with anticoagulants
Iron can bind to and inhibit natural anticoagulant proteins in the blood such as antithrombin III. This tips the scales towards clotting.
What is the evidence linking high iron and blood clots?
A number of clinical studies have investigated the association between elevated iron levels and thrombosis risk. Some key findings are:
People with hereditary hemochromatosis at risk
Hereditary hemochromatosis is a genetic disorder that leads to excessive absorption of dietary iron and iron overload. Studies show these patients have 2-4 times higher risk of venous thromboembolism (VTE) like DVT.
| Study | Sample Size | Main Findings |
|---|---|---|
| Ellervik et al 2007 | 903 patients | 2x higher VTE risk if homozygous for high-iron gene mutation |
| D’Agnolo et al 2018 | 504 patients | 4x higher VTE incidence compared to controls |
Association found with high ferritin
Ferritin is the protein that stores iron in the body. Studies show a link between high ferritin levels and arterial clots.
| Study | Sample Size | Main Findings |
|---|---|---|
| Wolff et al 2004 | 19,500 patients | Highest ferritin quartile had 2x risk of myocardial infarction |
| Tuomainen et al 1998 | 1,931 men | High ferritin increased heart attack risk by 2.2x |
Iron reduction lowers risk
Removing excess iron through phlebotomy has been found to lower cardiovascular events and thrombosis. This suggests high iron is causative.
| Study | Intervention | Main Findings |
|---|---|---|
| Zacharski et al 2007 | Phlebotomy | 37% lower risk of myocardial infarction and stroke |
| Houschyar et al 2012 | Phlebotomy | Lower thrombin generation and platelet aggregation |
Who is most at risk from high iron-induced clotting?
The impact of high iron on thrombosis risk appears most relevant in certain populations:
Individuals with pre-existing risks
If other clotting risk factors are present e.g. age, family history, smoking, the added thrombotic effect of high iron is amplified.
People with undiscovered hemochromatosis
Those with mild or early hemochromatosis that is undetected and untreated may face increased clot risk before iron levels get extremely high.
Users of high-dose iron supplements
Consuming supplemental iron far exceeding needs, especially in fortified foods, could potentially tip some people towards iron excess.
Frequent blood donors
Frequent blood donation can lead to high iron levels as the body ramps up absorption to compensate for losses. One study found increased thrombosis incidence in men donating 2-3 times per year.
Can high iron levels directly cause blood clots?
Based on the current research, it seems that high iron is unlikely to single-handedly trigger clots in an otherwise healthy person with no clotting risks. However, there is compelling evidence that iron overload shifts the blood to a prothrombotic state and contributes to clot risk alongside other factors. Iron excess acts as an additive risk factor rather than a sole causative agent. It tips vulnerable individuals over the edge into thrombosis but likely does not directly cause clots in isolation.
How is iron-induced thrombosis treated and prevented?
Strategies to reduce thrombosis risk driven by high iron levels center on normalizing iron through removal and reducing absorption.
Phlebotomy
Phlebotomy or bloodletting is the most direct way to rapidly lower iron levels. This therapy is used to treat hemochromatosis and has been shown to reduce cardiovascular complications.
Lower dietary iron intake
Reducing consumption of iron-rich foods and beverages can help prevent excess iron buildup over time. Limiting red meat and vitamin C-rich foods that enhance absorption may be beneficial.
Iron chelation
Medications called chelators bind to excess iron and promote its excretion. Iron chelators may be used if phlebotomy is not an option.
Limit iron supplements
Iron supplements should be avoided in those at risk of iron overload and taken only to treat confirmed deficiencies. Indiscriminate use of fortified foods high in iron should also be limited.
Manage other clotting risks
Steps should be taken to minimize all other thrombosis risk factors as much as possible through lifestyle changes and medical management.
Conclusion
In summary, there is strong evidence linking high body iron stores to an increased risk of both arterial and venous blood clots. Iron appears to act by enhancing processes of coagulation, platelet aggregation, and vascular dysfunction. Individuals with pre-existing clotting risks, mild hemochromatosis, or frequent transfusions seem most susceptible. Normalizing elevated iron levels through phlebotomy and dietary changes can potentially lower thrombosis risk. However, high iron alone is unlikely to directly cause clots – it requires other clotting risk factors also being present. A prudent approach for those vulnerable to iron overload is to be aware it may amplify their clotting risk and take steps to prevent iron excess.
