- Blood clotting (thrombosis) is an ongoing and necessary natural process: without it, even minor injuries could cause fatal bleeding.
- However, a clot (thrombus) forming inside an artery can block off the blood supply to, for example, the heart and brain, thus causing a heart attack or stroke.
- The formation of thrombi is not a random event: it occurs in response to a triggering event or circumstance. Certain conditions, such as atherosclerosis and hypertension, predispose towards thrombus formation and certain lifestyle risk factors, such as smoking and obesity, can increase the chances of developing a blood clot.
- Diagnosis of a blood clot begins with a complete medical history and physical examination.
- Provided diagnosis is made and treatment begun within three hours of the onset of symptoms, thrombi can be managed successfully.
Blood clotting is a natural process that allows the blood to thicken and form a clot of blood cells and fibrin, to stop the bleeding when a blood vessel is severed or damaged. If the body did not have the ability to clot blood, then people would bleed to death after even a minor cut.
However, when a blood clot (thrombus) forms in an artery, blocking the blood flow to the heart muscle or the brain, a heart attack or stroke can follow. Or when blood lingers in one of the heart’s chambers (due to certain heart conditions), a clot may form and a piece of the blood clot can be pumped from the heart, travel through the bloodstream, and lodge in either an organ or an artery, cutting off the blood supply from that point. This travelling clot is called an "embolus".
There are many other conditions related to blood clots, for example:
- Coronary thrombosis that involves a blood clot in coronary arteries leading to a heart attack
- Deep-vein thrombosis that involves a blood clot in the leg veins
- Pulmonary embolism that involves a blood clot lodged in the pulmonary artery (lungs)
- Retinal vein occlusion that involves a blood clot in a vein of the eye
To prevent excess clot formation, the body has a system whereby clot formation ceases once the clot has served its purpose, and the formed clot is then gradually dissolved. If this controlling system fails, clots may form excessively and persist, causing complications.
There are certain conditions necessary for the formation of clots:
- Platelets are special blood cells which clump together to form a "plug", helping to stop bleeding from a site.
- Clotting factors are proteins in the blood that are involved, along with the platelets, in clot formation.
- Endothelial damage - damage to the lining of the blood vessels and heart may determine where the clots are formed.
- Slow flow or turbulence of blood flow will predispose towards clot formation.
Disturbance in the balance of any of these factors will lead to the development of clots, and subsequent complications, as detailed in the following section.
How are clots formed?
The formation of thrombi is not a random event: it occurs in response to a triggering event or circumstance.
The inner lining (endothelium) of blood vessels or of the heart itself may be damaged by, for example, the deposition of cholesterol plaques, turbulence in blood flow or infection - all of which can expose the collagen fibres underneath the endothelium. The exposed collagen acts as a trigger, attracting platelets to the site and activating the clotting factors in the blood. A thrombus is thus formed exactly where it is needed.
Once the thrombus seals off the damaged site, the process stops, and when the damaged endothelium is healed, the thrombus is slowly dissolved and removed. However, the thrombus that forms may be large enough to partially or even completely obstruct the blood vessel concerned, shutting off the normal blood supply.
If this happens in a coronary artery, heart muscle is totally deprived of oxygenated blood, and the result is a heart attack. If this happens in an artery to the brain, the result is a stroke.
Certain circumstances result in slow flow and turbulence. This may permit thrombi to form in much the same way a slow-flowing river gets clogged up, whereas one with a strong flow seems clean and with clear water. Atherosclerotic plaques (cholesterol) can cause turbulence, triggering thrombi.
Patients with atrial fibrillation have a sluggish flow in their atria, and are at high risk for thrombus formation inside the heart. These also have a high risk of embolising to the lungs or brain.
After a heart attack, portions of the heart may no longer contract normally, causing slow flow of blood and permitting thrombus formation within the heart. The same applies in any aneurysm.
Damage to heart valves, especially the mitral valve, can also promote thrombus formation because of endothelial damage and slow flow.
An excess of platelets and clotting factors can occur in some conditions affecting the bone marrow, and sometimes in association with underlying malignancy. These thrombi tend to form mainly in veins. Some genetic disorders of blood clotting are known, e.g. Factor V Leiden.
A temporary increase in platelets and clotting factors can occur after surgery and trauma of any kind.
Associated risk factors
It is clear from the above description that conditions leading to endothelial damage, sluggish blood flow or changes in platelets and clotting factors will predispose towards thrombus formation. Patients with the following conditions are thus at greater risk of thrombosis:
- High blood pressure
- Recent heart attack/stroke
- Heart-valve disease
- Atrial fibrillation/heart failure
- Trauma to blood vessels, e.g. accidents, surgery or burns
- Raised platelet levels, genetic clotting disorders
- Inflammatory bowel disorders
- Auto-immune disease, e.g. lupus or rheumatoid arthritis
- Certain cancers
- Vascular problems, e.g. varicose veins or aneurysms
- Immobility, e.g. prolonged bedrest after surgery or long-haul flights
- Renal disease, especially nephrotic syndrome
In addition, the following lifestyle risk factors can increase the chances of developing a blood clot:
- Obesity (more than 10kg overweight)
- Lack of exercise
- Use of oral contraceptives, especially high-dose types
- High dosages of oestrogen, or hormone-replacement therapy (HRT)
- Sitting in one position for a prolonged time (as in an aeroplane)
Symptoms and signs
The symptoms of a blood clot depend on where the blood clot is located in the body:
|Where blood clot is lodged||Possible symptoms|
|Lung (pulmonary embolism)||Sharp chest pain, rapid heart rate, blood-tinged coughing, shortness of breath and low-grade fever.|
Arm or leg (e.g. deep-vein thrombosis)
|A blood clot in an artery can cause sudden pain, swelling and a slight blue colouration. If it is in a vein, it could cause swelling and tenderness.|
|Brain (stroke)||Visual disturbances, weakness, seizure, speech impairment, leading to a stroke or a transient ischaemic event. Artherosclerotic plaques in the carotid artery can lead to blood clots lodging in the carotid artery or deep in the brain.|
|Heart (heart attack)||Chest pain could lead to a heart attack. Blood clots forming in the heart can also travel to any organ or artery in the body. Conditions that can lead to blood clots forming in the heart include heart-valve disease, previous heart attack, atrial fibrillation and heart failure.|
|Abdomen||Severe abdominal pain, vomiting and/or diarrhoea.|
Diagnosis of a blood clot begins with a complete medical history and physical examination.
In most cases, the diagnosis is easily made. However, more sophisticated investigations are often needed to make a more specific diagnosis (e.g. exactly where in the lung the thrombus is located), so that treatment can be targeted at the troublespot.
The "gold standard" for diagnosis of thrombi remains contrast venography, or arteriography: in this test, a special dye is injected into the blood vessel after which X-ray studies are done. This gives accurate information, but is an invasive procedure, and not suitable for all patients (e.g. for pregnant patients, unnecessary exposure to radiation is avoided where possible).
There are other less invasive investigations, some of which are more accurate than others, or better suited to certain areas of the body. There are also blood tests that can detect by-products of clot formation and breakdown (specifically, for a substance called D-dimer). These, coupled with imaging studies, can make a firm diagnosis.
For venous thromboses of limbs, other investigations may include:
- Impedance plethysmography
- D-dimmer blood test (a breakdown product of one of the clotting factors)
- Doppler ultrasound
- Magnetic resonance venography
- Computer-assisted scans
Arterial thromboses can require urgent management, especially if they occur in a coronary artery. In this case, coronary angiography may be done as an emergency investigation.
Computerised scans are used often for suspected cerebral thromboses, when it is vital to know whether a stroke is due to a blockage of an artery, or due to a bleed within the brain. The treatment of each of these is very different.
In the diagnosis of pulmonary embolus, other tests (in addition to the basic clinical examination and blood tests) become more important, for example:
- Blood gas estimations>li>Chest X-rays,
- V/Q scans
The treatment for a blood clot will depend on whether the clot has formed in a vein or artery, the location and size of the clot, and the patient’s general health.
The main aims of treatment are to:
- Remove the thrombus where possible
- Reverse or limit damage caused by the thrombus
- Pevent complications, e.g. emboli
- Prevent recurrence of thrombus formation
If it has formed in an artery and has caused a heart attack or stroke, then clot busters (e.g. streptokinase) may be used to dissolve the blood clot. These must be given within three hours of the heart attack or stroke.
More invasive procedures may be indicated, where a catheter is inserted to deliver thrombolytic enzymes directly to the blood clot, or used to treat the blood clot by angioplasty or a stent procedure. Higher concentrations of enzymes can be used. This medication is followed by treatment with anti-clotting medication (e.g. heparin or warfarin) to prevent more blood clots from forming.
This treatment is not without risks or side effects, and not all patients are suitable candidates (e.g. those allergic to the enzymes). Excessive – and even fatal – bleeding has been reported as a result of “clot-busting” therapy.
If a blood clot forms in a vein, there is a risk that the blood clot may travel to the lungs and cause a life-threatening pulmonary embolism. In this case, blood clots are usually treated with a combination of painkilling medication, anti-clotting medication and elevation/bandaging of the affected area (e.g. the leg) to reduce swelling. Special anti-embolism stockings may be used instead of bandages.
In extreme situations, surgery may be required to remove a clot before it starts to travel to the lungs.
An important part of the treatment concerns identifying and treating underlying conditions, which may predispose to recurrent thrombosis in the future, e.g. avoiding oral contraceptives, stopping smoking, managing atrial fibrillation and treating heart-valve disease.
In some patients, no underlying cause can be found. A minority of these patients may still have recurrent thromboses. For recurring deep-vein thromboses of the legs with emboli, a special filter may need to be inserted into the inferior vena cava. This is a tricky and hazardous procedure, not undertaken lightly. This special umbrella-like device is surgically implanted, and traps any emboli coming from the lower extremeties, preventing pulmonary emboli.
All patients with documented thromboses will be placed on some form of anti-clotting medication to prevent a recurrence. Aspirin is widely used. For specific ongoing medical conditions, e.g. atrial fibrillation, warfarin is necessary.
Provided diagnosis is made and treatment begun within three hours of the onset of symptoms, thrombi can be managed successfully. The most important factor here is an astute doctor who asks the right questions.
Early, appropriate treatment can stop the thrombus from enlarging, and prevent emboli occurring. Thrombosis in a coronary artery can be treated with clot-busting enzymes, and may prevent a heart attack. Emboli to the brain may also be treated, but because the brain is so sensitive to oxygen deprivation, there may be some permanent damage, even once the clot is dissolved and blood flow re-established if there is a delay in starting the therapy.
Thrombosis in the legs is common, especially among air travellers. The treatment is highly successful, and emboli can easily be prevented.
There may be some long-term consequences of clot formation, but this is usually due to a delay in treatment, with subsequent less-than-ideal results. Dissolving most of a coronary artery clot may avert a major heart attack, but the patient may still have a smaller heart attack. Brain damage may be minimised after a brain clot, but the patient may have some residual neurological problems, e.g. a weak arm, or minor speech slurring. A common residual problem after a leg clot is persistent swelling of the leg.
If there is an underlying cause for the clot formation, e.g. atrial fibrillation, the patient may need to use warfarin permanently, which creates several problems of its own.
A brief look at the section on associated risk factors will clearly show the conditions which predispose towards clot formation. It is therefore logical that any steps taken to counter these risk factors will help prevent clots forming, especially in high-risk patients and situations.
Patients with known cardiovascular conditions, e.g. atherosclerosis, high blood pressure, valve disease, heart failure, atrial fibrillation, varicose veins and aneurysms are at risk. These conditions require correct treatment, which often includes anti-clotting medication.
Patients undergoing surgery, after which prolonged immobilisation is expected, may need specific types of anti-clotting medication to be started within a day or two of surgery, and are often also given support stockings to wear during and/or immediately after surgery.
Air travellers (long flights) may benefit from aspirin and support stockings, but the best prevention is adequate hydration and regular movement.
Patients with recent physical trauma must be carefully monitored for clot formation, as should patients with known cancers or some auto-immune diseases.
Pregnancy may also be a high-risk period, but an equally high index of suspicion is needed for patients using an oral contraceptive, especially if combined with varicose veins and smoking.
In general, weight loss, not smoking and regular exercise are of benefit to everyone. Patients over 50 often use aspirin for other reasons, and this may also help prevent clots.
When to see your doctor
If you have – or suspect you may have – any of the symptoms or risk factors outlined in this article, please see your doctor as soon as possible. Patients with known heart disease are at special risk.
Reviewed by Dr A.G. Hall (B.Soc.Sc.(SW), MB,Ch.B), December 2008