Blood Clots

What are blood clots?

Blood is a liquid that flows within blood vessels. It is constantly in motion as the heart pumps blood through arteries to the different organs and cells of the body. The blood is returned back to the heart by the veins. Veins are squeezed when muscles in the body contract and push the blood back to the heart.
Blood clotting is an important mechanism to help the body repair injured blood vessels. Blood consists of:

• red blood cells containing hemoglobin that carry oxygen to cells and remove carbon dioxide (the waste product of metabolism),
  
• white blood cells that fight infection,
  
• platelets that are part of the clotting process of the body, and
  
• blood plasma, which contains fluid, chemicals and proteins that are important for bodily functions.

Complex mechanisms exist in the bloodstream to form clots where they are needed. If the lining of the blood vessels becomes damaged, platelets are recruited to the injured area to form an initial plug. These activated platelets release chemicals that start the clotting cascade, using a series of clotting factors produced by the body. Ultimately, fibrin is formed, the protein that crosslinks with itself to form a mesh that makes up the final blood clot.
The medical term for a blood clot is a thrombus (plural= thrombi). When a thrombus is formed as part of a normal repair process of the body, there is little consequence. Unfortunately, there are times when a thrombus (blood clot) will form when it is not needed, and this can have potentially significant consequences.

What does a blood clot look like?

Picture of a how blood clot is formed

What causes blood clots?

Blood clots form when there is damage to the lining of a blood vessel, either an artery or a vein. The damage may be obvious, such as a laceration, or may occur on the microscopic level. As well, blood will begin to clot if it stops moving and becomes stagnant.
Venous thrombosis or blood clots in a vein occur when a person becomes immobilized and muscles are not contracting to push blood back to the heart. This stagnant blood begins to form small clots along the walls of the vein. This initial clot can gradually grow to partially or completely occlude or block the vein and prevent blood from returning to the heart. An analogy to this process is a slow moving river. Over time, weeds and algae start to accumulate along the banks of the river where the water flows more slowly. Gradually, as the weeds start to grow, they begin to invade the center of the river because they can withstand the pressure of the oncoming water flow.
Arterial thrombi (blood clots in an artery) occur by a different mechanism. For those with atherosclerotic disease, plaque deposits form along the lining of the artery and grow to cause narrowing of the vessel. This is the disease process that may cause heart attack, stroke, or peripheral artery disease. If a plaque ruptures, a blood clot can form at the site of that rupture and can completely or partially occlude the blood flow at that point.
Blood clots in the heart. In atrial fibrillation, the atrium or upper chamber of the heart does not beat in an organized manner. Instead, it jiggles, and blood tends to become stagnant along the walls of the atrium. Over time, this may cause small blood clots to form. Clots can also form in the ventricle after a heart attack when part of the heart muscle is injured and unable to contract normally. Since the damaged area doesn't contract with the rest of the heart, blood can start to pool or stagnate, leading to clot formation.
Blood leaking out of a blood vessel.  Blood clots can form when blood leaks out of a blood vessel. This is very beneficial when a person gets a cut or scrape wound, because the clot helps stop further bleeding at the wound site. The clotting mechanism works well following trauma as well. Broken bones, sprains and strains, and nosebleeds all result in bleeding that is controlled by the body's clotting mechanism.
Blood clots causing other medical problems. Sometimes, normal blood clotting can cause medical problems because of its location. For example, if bleeding occurs in the urine from any of a variety of reasons (such as infection, trauma, or tumor) clots may form and prevent the bladder from emptying, causing urinary retention. Clot formation in the uterus may cause pain when the clots are passed through the cervix and can lead to vaginal bleeding, either as part of menstruation or as abnormal vaginal bleeding (menorrhagia, dysmenorrhea).

What are the risk factors for blood clots?

The risk factors for arterial clots are those that are common to all diseases that cause narrowing of blood vessels, cholesterol plaque formation, and plaque rupture.

• High blood pressure
  
• High cholesterol levels
  
• Diabetes
  
• Smoking
  
• Family history

Venous clots are formed due to one of two main reasons: 1) immobility, and 2) genetic errors in the clotting mechanism.

1. Immobility: Most commonly, when the body stops moving, the risk of blood clots increases, since muscle movement is required to pump blood towards the heart. Stagnant blood in a vein is prone to clot.

• This may occur when a person is hospitalized or bedridden after illness or surgery.
  
• It may also occur with long trips (such as in a car, train, or plane) where hours may pass without a person getting up to walk or stretch.
  
• Orthopedic injuries and casting also put the person at risk.
  
• Pregnancy is a risk factor for forming blood clots in the legs and pelvis, since the growing uterus may slow blood flow back to the heart to a sufficient extent that blood clots may form.

2. Genetic errors in the clotting mechanism: There may be a genetic or inborn error in the clotting mechanism, making a person hypercoagulable (hyper=more + coagulation= clotting) and at greater risk for forming clots.

   What types of conditions are caused by blood clots?

   Blood clots may cause life-threatening medical conditions, and are always considered in the differential diagnosis of any symptoms or signs. Differential diagnosis is the list of potential causes of a patient's condition, that is considered by the health care practitioner when caring for a patient.
   Deep venous thrombosis and pulmonary embolism
   Deep venous thrombosis may lead to a pulmonary embolism. If there is a blood clot or thrombus in a deep vein, it has the potential to break off (embolize) and flow through the veins back through the heart, and into the lung where it can become lodged in a small blood vessel, which prevents the lung from functioning. Pulmonary embolism is a medical emergency and can cause serious illness or death.
   An embolus is the medical term for a blood clot that has moved with the bloodstream to a different location. With pulmonary embolus (pulmonary embolism), two issues occur.
   
3. The lungs' blood supply is comprised and the affected area of lung tissue may infarct, or die.
   
4. Because of the blockage, the ability of the lung to provide oxygen to the body is decreased and hypoxia (decreased levels of oxygen in the blood and throughout the body) may occur.

Even if venous blood clots do not embolize, they may cause significant local problems with swelling and pain. Since blood cannot return to the heart if a vein is blocked by a clot, the limbs may chronically swell and have decreased function in a condition called chronic thrombophlebitis.
Arterial thrombus
An arterial thrombus stops the blood supply to the tissues beyond the blockage, depriving cells of oxygen and nutrients. This quickly leads to tissue death. Arterial thrombus is the mechanism that causes:

• heart attack (when it occurs in the coronary arteries that supply blood to the heart)
  
• stroke (when it occurs in arteries within the brain), or
  
• peripheral vascular disease (occurring in the arteries of the legs).

Atrial fibrillation
In atrial fibrillation, small clots may form along the walls of the atrium or the upper chambers of the heart. Should one of these clots break off, it may embolize, or travel in the bloodstream to the brain, blocking an artery and causing a stroke. Other arteries may also be involved by this process, including those that supply the bowel. This can cause mesenteric ischemia (mesentery=lining of the bowel + ischemia=loss of blood supply) and potential necrosis (tissue death) of the intestine. Clots can also affect blood supply to fingers and toes.
Blood should clot anytime it becomes stagnant. This also means that clots will form when blood leaks out of blood vessels.
Examples include some of the following:

• With bleeding peptic ulcers, patients may vomit liquid blood mixed with clot.
  
• Patients with rectal bleeding may also have clot mixed with the bloody stool if there has been time for the clot to form.
  
• Sometimes patients with urinary tract or bladder infections develop associated bleeding in their urine, and small clots can form. On occasion these clots may be so big that they cannot be passed and block the urethra, preventing urination and causing urinary retention.
  
• Vaginal bleeding is a normal event for most women in the reproductive years and occasionally, blood can pool in the vagina and form clots before being expelled. If clots form in the uterus, they may cause significant pain and pressure as they pass through the cervix while being expelled.

  What are the symptoms of blood clots?

  Venous clots do not allow blood to return to the heart and symptoms occur because of this damming effect. Most often occurring in the legs or the arms, symptoms include:
  
• swelling,
  
• warmth,
  
• redness, and
  
• pain.

Arterial clots do not allow blood get to the affected area. Body tissue that is deprived of blood and oxygen begins to die and becomes ischemic (isch=to restrain + emia = blood)

• Pain is the initial symptom of the ischemia, or oxygen deprivation due to loss of blood supply.
  
• Other symptoms depend upon the location of the clot, and often the effect will be a loss of function. Heart attack and stroke are self-explanatory.
  
• In an arm or leg, in addition to pain, the limb may appear white, and weakness, loss of sensation, or paralysis may occur.
  
• If the blood supply is lost to an area of the bowel, in addition to intense pain, there may be bloody diarrhea.

How are blood clots diagnosed?

The initial step in making the diagnosis of a blood clot is obtaining a patient history. The blood clot itself does not cause a problem. It's the location of the blood clot and its effect on blood flow that causes symptoms and signs. If a blood clot or thrombus is a consideration, the history may expand to explore risk factors or situations that might put the patient at risk for forming a clot.
Venous blood clots often develop slowly with a gradual onset of swelling, pain, and discoloration. Symptoms of a venous thrombus will often progress over hours.
Arterial thrombi occur as an acute event. Tissues need oxygen immediately, and the loss of blood supply creates a situation in which symptoms begin immediately.
There may be symptoms that precede the acute artery blockage, that may be warning signs of the potential future complete occlusion of the blood vessel.

• Patients with an acute heart attack (myocardial infarction) may experience angina in the days and weeks prior to the heart attack.
• Patients with peripheral artery disease may have pain with walking (claudication), and a TIA (transient ischemia attack, mini-stroke) may precede a stroke.

Physical examination can assist in providing additional information that may increase the suspicion for a blood clot.

• Venous thrombi may cause swelling of an extremity. It may be red, warm, and tender; sometimes the appearance is difficult to distinguish from cellulitis or an infection of the extremity. If there is concern about a pulmonary embolus, the clinician may examine the lungs, listening for abnormal sounds caused by an area of inflamed lung tissue.
  
• Arterial thrombus symptoms are much more dramatic. If a leg or arm is involved, the tissue may be white because of the lack of blood supply. As well, it may be cool to touch and there may be loss of sensation and movement. The patient may be writhing in pain.

Arterial thrombus is also the cause of heart attack (myocardial infarction) and stroke (cerebrovascular accident) and their associated symptoms.
Testing for venous blood clots
Venous blood clots may be detected in a variety of ways, though ultrasound is most commonly used. Occasionally, the patient's size and shape limit the ability for ultrasound to provide a definitive answer.
Venography is an alternative test to look for a clot. In this test, a radiologist injects contrast dye into a small vein in the hand or foot and using fluoroscopy (video X-ray), watches the dye fill the veins in the extremity as it travels back to the heart. The area of clot or obstruction can thus be visualized.
Sometimes, a blood test is used to screen for blood clots. D-Dimer is a breakdown product of a blood clot, and its levels in the bloodstream may be measured. Blood clots are not stagnant; the body tries to dissolve them at the same time as new clot is being formed. D-Dimer is not specific for a blood clot in a given area and cannot distinguish a "good” or needed blood clot, one that forms after surgery or due to bruising from a fall, from one that is causing medical problems. It is used as a screening test with hopes that the result will be negative and show that there is no need to look further for blood clots.
The D-dimer blood test is usually ordered with the expectation that it will be negative. It is a useful test in patients who have a low probability of having a blood clot, and the health care practitioner usually counsels the patient that a positive blood test will likely require additional tests being ordered.
Should a blood clot embolize to the lung, this may be a medical emergency. There are a variety of tests to look for pulmonary emboli. A plain chest X-ray will not show blood clots, but it may be done to look for other conditions that can cause chest pain and shortness of breath, which are the symptoms of a pulmonary embolus. An electrocardiogram (EKG) may show abnormalities suggestive of a pulmonary embolus and also may reveal other causes of chest pain.
Computerized tomography (CT scan) is often the test of choice when suspicion of pulmonary embolus is high. Contrast material is injected intravenously, and the radiologist can determine whether a clot is present in the pulmonary vessels. The contrast material injected into the body can be irritating to the kidney(s) and should not be used in patients who have impaired kidney function. In older patients, screening blood tests (serum creatinine) to check kidney function may be required before a dye study is considered.
On occasion, a ventilation perfusion (V/Q) scan is performed to look for pulmonary emboli. This test uses labeled chemicals to identify inhaled air into the lungs and match it with blood flow in the arteries. If a mismatch occurs, meaning that there is lung tissue that has good air entry but no blood flow, it may be indicative of a pulmonary embolus. It is less accurate and more subjective than a CT scan, and requires the skill and experience of a radiologist to interpret. Two radiologist may interpret a VQ scan differently and come to different conclusions.
Testing for arterial blood clots
Arterial thrombosis is an emergency, since tissue cannot survive long without blood supply before there is irreversible damage. When this occurs in an arm or leg, often a surgeon is consulted on an emergency basis. Arteriography may be considered, a test in which contrast material is injected into the artery in question to look for blockage on imaging studies. Sometimes, if there is a large artery that is occluded, this test is done in the operating room with the presumption that a surgical procedure will be needed to open the vessel and restore blood flow.
For a heart attack (acute myocardial infarction, MI), the EKG may establish the diagnosis, although blood tests may be used to look for enzymes (troponin, myoglobin, CPK) that leak into the bloodstream from irritated heart muscle. In an acute heart attack, the diagnostic and therapeutic procedure of choice is a heart catheterization.
For an acute stroke (cerebrovascular accident, CVA), the test of choice is a computerized tomography (CT) scan of the head to look for bleeding or tumor as the cause of stroke symptoms. If the symptoms resolve, the diagnosis is a transient ischemic attack (TIA, mini-stroke), and further tests may include carotid ultrasound to look for blockages in the major arteries of the neck and echocardiography to look for blood clots in the heart that may embolize to the brain.

How are blood clots treated?

Depending upon their location, blood clots may be aggressively treated or may need nothing more than symptomatic care.
Venous blood clots
Venous thrombosis in the leg may occur in the superficial or deep systems of veins.
Clots in the superficial system are often treated symptomatically with warm compresses and acetaminophen or ibuprofen since there is no risk for clots in the superficial veins to embolize to the lung. They are connected to the deep system by perforator veins that have valves that act like a sieve to strain and prevent any clots form getting to the lung.
Deep venous thrombosis usually requires anticoagulation to prevent the clot from growing and causing a pulmonary embolus. Initial therapy with injectable enoxaparin (Lovenox) is used to immediately "thin" the blood. Meanwhile, warfarin (Coumadin) is prescribed as an anti-coagulation pill. It takes a few days for warfarin to reach therapeutic levels and in this time frame, both the injectable and oral medications are used. Most often, patients with DVTs are treated as an outpatient and taught how to give themselves enoxaparin (Lovenox) injections. Occasionally, depending upon circumstances, patients may be admitted to the hospital for an unfractionated heparin intravenous (IV) injection.
Blood clots below the knee are at lower risk for embolization to the lung, and an alternative to anti-coagulation treatment is serial ultrasound examinations to monitor the clot to see if it is growing or being resorbed by the body.
Pulmonary emboli are treated similarly to deep venous thrombosis, but depending on the severity of the symptoms, amount of clot formation, and the underlying health of the patient, admission to the hospital for treatment and observation may be needed. This is especially the case if lung function is compromised and the patient is short of breath or is experiencing hypoxia, or low oxygen levels in the blood.
Arterial blood clots
Arterial blood clots are often managed more aggressively. Surgery may be attempted to remove the clot, or medication may be administered directly into the clot to try to dissolve it. Alteplase (Activase, TPA) or tenecteplase (TNKase) are examples of medications that may be used in peripheral arteries to try to restore blood supply.
This is the same approach that is used for heart attack. If possible, cardiac catheterization is performed to locate the blocked blood vessel and a balloon is used to open the occluded area, restore blood flow, and place a stent to keep it open. This is a time-sensitive procedure and if a hospital is not available to do the procedure emergently, TPA or TNK is used intravenously to try to dissolve the thrombus and minimize heart damage.
Stroke is also treated with TPA if the patient is an appropriate candidate for this therapy.

What are the complications of blood clots?

Blood clots prevent proper circulation of blood.
Deep vein thrombosis of the leg or arm may cause permanent damage to the veins themselves and cause persistent swelling of the extremity. The life-threatening issue that may arise from deep venous clots is a clot that breaks off and embolizes to the lungs (pulmonary embolus), causing problems with lung function and oxygenation of the blood.
Arterial thrombus often is a life- or limb threatening event, since organs and cells do not get enough oxygen.

How can blood clots be prevented?

Prevention is key in thrombosis or clot formation.
Arterial thrombosis

• For arterial thrombosis, the most likely precipitating event is a plaque rupture with clot formation in the artery.
  
• Minimizing the risk of vascular disease requires life-long attention to the risk factors that lead to plaque buildup and "hardening" of the arteries.
  
• Blood pressure and cholesterol control, diabetes management, and refraining from smoking all minimize the risk of arterial disease.
  
• Although family history is an important risk factor, one needs to be even more vigilant about the other risk factors if there is a family history of early heart attack or stroke.

Deep vein thrombosis
The main risk factor for deep vein thrombosis risks is immobilization. It is important to move around routinely so that blood can circulate in the venous system. On long trips, it is recommended to get out of the car every couple of hours and in an airplane routinely get up and stretch.
Physicians and nurses work hard at getting people moving after surgery or while in the hospital for medical conditions. Enoxaparin (Lovenox) can also be used in low doses to prevent clot formation. Patients are often given tight stockings to promote blood return from the legs and prevent pooling of blood.
In patients with atrial fibrillation, warfarin (Coumadin) is used to prevent clot formation and minimize the risk of embolus and stroke.

Blood Clots At A Glance

• Blood clots form when blood fails to circulate adequately.
  
• Arterial thrombi form when a plaque ruptures and promotes an acute clot formation.
  
• Venous thrombosis occurs when prolonged immobilization allows blood to pool in an extremity and then clot.
  
• The diagnosis is suggested by the history and physical examination and often confirmed with a radiologic test.
  
• Treatment may require surgery, anti-coagulation medications, or a combination of the two.
  
• Prevention of blood clots involves attention to the risk factors for vascular disease.
  
• Serious complications can arise from blood clots, and individuals should seek medical care if they believe a blood clot exists.

REFERENCE:

eMedicine.com. Deep Vein Thrombosis and Thrombophlebitis.
<http://emedicine.medscape.com/article/758140-overview.>

Fauci, Anthony S., et al. Harrison's Principles of Internal Medicine. 17th ed. United States: McGraw-Hill Professional, 2008.