Blood Clots (Arterial & Venous)


Blood clotting can be and is a very important natural process in which platelets, fibrin, blood cells and various components of blood clump together to stop bleeding after a blood vessel or your skin has been injured.  Eventually, the clot forms a protective seal over an injury.  If the body did not have the ability to clot blood, people would bleed to death after just a minor cut.

There are two distinct forms of clots.  One is in the arteries and the second is in the veins and these will each be discussed below under their separate heading. 

Blood flow is much more susceptible to abnormal clotting when it moves slowly.  Flow in the arteries moves rapidly, flow in the veins moves slowly and even slower if you are bedridden or sitting.

Abnormalities of the blood clotting system are more manifest in the veins (which are already at higher risk of clotting because the blood flow is slow).  Other factors affecting the increased tendency to clot may not be as manifest in the arteries.  These abnormal clotting problems will also be further discussed below. 

The arteries and veins are like two separate tree trunks with the flow in the tree trunk going in the arteries to your feet and arms and in the veins the flow goes to your lungs.  The arterial and venous flow goes in opposite directions.   When arterial blood flow gets to the end of the limbs, it goes through tiny capillaries that keep blood clots from going into the venous side.  Clots in the veins travel up the trunk to the end, which is the lungs.  The lungs filter out clots to keep them from going back around to the arterial side.  A large blood clot if untreated can kill the tissue distal to where it lodges in the limb–arterial side, your feet, etc., venous side, the lungs and also affects the heart if it is very large.

Blood clots can form without there being an obvious injury.  Most of these clots tend to dissolve on their own without any problem, but sometimes blood clots can become large and fail to dissolve properly and block blood flow through an artery or a vein.  When a blood clot forms and stays where it forms, it is called a thrombus whether that be in an artery or vein.  A thrombus that breaks loose and travels from where it formed and goes to another location in the body is called an embolus and these can occur in both arteries and veins.

Arterial blood clots (stroke)

What are causes and risks?

When blood clots form in an artery, including the heart, they tend to break loose and travel distally through the arteries in a somewhat random fashion and can involve the arteries to your arms or your brain or your kidneys or your bowel or your legs and feet creating an emergency.

Blood clots in the arteries can form in areas of atherosclerotic buildup where this plaque tends to ulcerate with clots forming in the ulceration and the clots travel distally to whatever part of the body is distal to the ulcer and clot.  The most common areas where we see this are when this buildup is in the arteries of your neck to your brain and the clots go to your brain or the artery to your eye.  When these are in the arteries somewhere above the level of your legs, they can go to just your toes or can block larger sections of the artery again causing an emergency.

As atherosclerotic plaque builds up in an artery and as it narrows and becomes very tight then the blood flows very slowly and blood can clot at these areas of slow flow totally occluding the artery or they can break loose and travel distally.  They can also occlude the entire vessel at the level of the narrowing and progress on down the leg without breaking loose.

If there are extensive areas of atherosclerotic blockage throughout an artery to your legs, flow rates to your foot can become critical and this slow-flowing blood can thrombose and this is called a “low-flow thrombosis.”

Among the most common clots that we see are those that occur with atrial fibrillation or other forms of irregular heart rhythm when clots form in the heart and can break loose and can travel to any artery in your body.  They can travel to and lodge in any artery in your body.

They can also occur after a myocardial infarction where the muscle inside the wall of the heart is injured.  This triggers clot to form on this site and it can break loose and can go to any artery in your body.  When the clots in the heart break loose or clots break loose in an ulcerated plaque or a narrowed area break loose and go to another part of your body, they are called emboli even though they started as a thrombus.

Occasionally an atherosclerotic plaque can undergo acute degeneration and showers of cholesterol emboli can go to either your brain or feet or hands causing sudden changes.  These have a characteristic appearance and appear as little scattered purple or purple and red blotches.  If this area continues to be a problem, it will form a blood clot on the ulceration where the plaque degenerated and then shower blood clots distally.

Emboli can also come from aneurysms which are ballooned out areas on the artery like boots on an old-time tire where they tend to blow out.  These aneurysms may have a clot that laminates inside them filling some of the excess space.  These clots can break loose and go to the arteries distal to the aneurysm, most notably your legs, from your abdominal aorta and iliac arteries in your lower abdomen but can be the aorta in your chest, the femoral arteries in your groin and the popliteal arteries behind your knees.  They can occur at the site of an injured subclavian artery with aneurysm formation secondary to thoracic outlet syndrome.  This clot will go to your fingers and hand.

If blood clots go to your brain and you have a stroke, you need to be seen in an emergency room immediately because in the first approximate 3 to 4 hours these can be lysed (broken up) and have a good chance of saving part of your brain function. 

What are the symptoms?

If blood clots go to your brain, they can affect your speech, your facial expression, use of your arms or legs and cause loss of vision in an eye or double vision.  There may be confusion and not being able to understand or speak, trouble walking, dizziness and loss of balance and possible sudden severe headaches.

If these blood clots go to your legs, you also need to be seen in the emergency room or in your physician’s office immediately.

When the blood clots go to your legs and block the artery, the legs tend to become very painful and then develop numbness, tend to be pale in color, tend to be cool and have no pulses, and you have just a few hours to get these diagnosed and treated as well before there is loss of tissue or parts of your limb distal to this.

How are these diagnosed?

The first and most obvious is a clinical examination.

An ECG to check your heart rhythm and blood work to check cardiac enzymes to be sure you have not had a heart attack that you did or did not know about and with CT angiograms or regular angiograms to be sure you do not have an aneurysm of arteries at any level in your body.  The angiogram will show the level of the blockage.

Prevention (Arterial)

This includes all the things important for arterial health such as:

  • Stop smoking immediately
  • Statins which are used to lower your blood cholesterol levels
  • Control your heart rhythm.  If it cannot be controlled, you may need anticoagulation.
  • Anticoagulant medicines such as warfarin, antiplatelet medicines such as low-dose aspirin and Plavix and then newer medications such as Pradaxa or similar to Pradaxa which decrease your likelihood of clotting.  Which is used depends on the diagnosis of your risk factors
  • Angiotensin-converting enzyme or ACE inhibitors to treat high blood pressure
  • Other medicines to control blood pressure
  • Screening for carotid artery atherosclerotic disease, heart rhythm, abdominal aortic aneurysm, femoral artery aneurysm, popliteal artery aneurysm and PAD

Treatment of emboli

First is to manage the acute problem and get flow re-established by whatever means is appropriate.  The next most important thing in treatment is to prevent it from happening again by controlling or treating the continued cause, such as abnormal heart rhythm or PAD or abdominal aortic aneurysm and management with additional interventional cardiology or surgical means as deemed necessary.  Lifestyle modifications with management of your smoking and cholesterol and triglycerides and diabetes problems.

Venous blood clots (DVT)

What are causes and risks?

Blood clots can occur in the veins which return blood to your heart and lungs.  They have the regular thrombus that form on sites of injury, such as from a contusion.  The large varicosities where flow is slow are easily bruised.  Blood clots can form in areas of chronic low flow because of being in a sitting position too long.  Flow in the normal veins, which are much larger in diameter than the arteries, is already much slower.  Veins tend to hold blood longer and flow is never fast moving.

Inherited or genetic clotting abnormalities cause much more trouble in veins than in arteries because of the fact they are more inclined to clot.  If you have a family member with a history of forming blood clots, please read more below (inherited thrombophilia).  If you have an acquired thrombophilia, you are more sensitive to clotting abnormalities that go with autoimmune diseases such as rheumatoid arthritis, lupus anticoagulant and antiphospholipid syndrome or ulcerative colitis.

Patients with cancer also are more likely to clot because these patients are hypercoagulable and because of  the body’s reaction to the cancer and, in addition, may be dehydrated.  Veins are also more sensitive to changes in coagulation with birth control pills, hormones and pregnancy.  When vessels are relaxed and dilated late in pregnancy due to higher hormone levels, they are also more prone to clot.  If one is immobile for any period of time, whether it be after surgery, riding long distance in a car or flying long distance in an airplane, or if you are paralyzed, you have a cast on your leg, your ankle joints become frozen and do not work or anything that prevents you from using your feet and ankles normally and ambulating normally leaves you at increased likelihood to clot.  Being grossly overweight impedes some of the blood flow return again further slowing blood flow from your legs.  Sitting with your legs hanging down or horizontal 90 degrees to your body on a footstool all decrease velocity of return toward your heart.  Also anytime you are very ill and dehydrated, you have a decreased cardiac output either from a heart attack, sepsis or other problems, you are more likely to develop clots in your veins.

Superficial vein thrombosis and deep vein thrombosis.

Superficial vein thrombosis means veins under the skin such as your great saphenous vein, small saphenous vein and the large tributary veins from any of these.  All the factors we have mentioned can cause them to be susceptible to thrombophlebitis (blood clots in your veins).  If you have a spontaneous superficial thrombosis with no apparent cause, there may be a 4% to 5% chance of an unknown cancer.  For this reason many times you will undergo a chest CT scan and an abdominal and pelvis CT scan with IV and p.o. contrast.  Cancers trigger clotting mechanisms (cause hypercoagulability) until they are under control or in remission thus requiring long periods of anticoagulation.

Deep vein thrombosis  has its highest risk 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 where, 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.

If your deep veins have had a thrombophlebitis or clots in the past, they may be scarred shut leaving you with impaired outflow to your legs thus leaving you more susceptible to your next blood clot.

Embolization from veins is totally different than in your arteries.  Embolization from veins usually occurs from the veins in the pelvis, thighs, groin or from the knee level.  When these clots break loose they go through the heart into the lungs blocking off blood flow and this pulmonary embolism (PE) can cause death with the first event though some will shower smaller clots over a period of time.  The warning sign of smaller clots is a sudden feeling of impending doom, shortness of breath or pain in your chest when you breathe in and out (pleuritic).  If you have any symptoms, your physician needs to know immediately and not two days later.

What are symptoms of blood clots in the legs or arms?

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
  • Pain

Venous blood clots often develop slowly with a gradual onset of swelling, pain, and discoloration and symptoms will often progress over hours.

Deep vein thrombosis symptoms are not always obvious.  The classic signs of a blood clot are swollen and tender calf or calves.  Unfortunately, these classic signs are not always present and you should be aware of other possible symptoms of DVT that include:

  • Red areas on the leg
  • Swelling in one area or on one leg
  • Pain or tenderness in one leg
  • Temperature differences between the two legs (a leg with a clot may be warmer to the touch)

Since not everyone with DVT experiences the above symptoms, you should be aware of the signs and symptoms of a pulmonary embolism, which can occur as the result of a blood clot.  Because pulmonary embolisms are blood clots in the lungs, the signs will be related to your breathing.  These include:

  • Shortness of breath
  • Feeling of impending doom
  • Sharp pain described as stabbing, burning, aching, dull and heavy under your breastbone or to the side of your chest
  • Increase in pain when you take a deep breath, cough, bend, or stoop
  • Increase in breathing rate
  • Increase in heart rate
  • Sudden cough
  • Coughing up blood or blood-streaked sputum (phlegm or mucus)

Certain types of blood clots, called superficial thrombophlebitis, have symptoms similar to those of DVT but are typically less serious.  One way to tell the difference is that with superficial thrombophlebitis the redness and warmth is located along a vein just beneath the skin and you can feel the tenderness and a ropey feeling.

How are they diagnosed?

When your family physician is suspicious of a clot in your veins, a referral will most frequently be made to a vascular specialist or diagnostic radiologist.  Venous blood clots may be detected in a variety of ways.

Venous ultrasound (venous duplex Doppler) is the most widely used method for evaluating suspected DVT.  This is a safe, non-invasive test and more detailed information can be read by clicking here

CT venography is a radiographic technique that uses a computer to assimilate multiple X-ray images into a two-dimensional cross-sectional image.  Veins are not normally visible on an X-ray image, so a special dye is injected into your blood to make them stand out.  In the past venography (a catheter was placed in your vein) was considered to be the “gold standard” test for diagnosing and investigating vein disease. However, today venography has mostly been replaced by duplex ultrasound to examine the health of the veins and look for blood clots

Magnetic resonance imaging (MRI) employs a powerful magnetic field to generate a high-resolution image of anatomic structures.  This non-invasive study may be used to diagnose DVT.  Unlike CT venography, MRI does not involve radiation exposure.

Blood testing can also be 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.  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.

What is the treatment?

Treatment is most often individualized for each patient depending upon the clinical situation and other medical conditions that may be present.

Superficial system:  Clots in the superficial system are often treated symptomatically with warm compresses and NSAIDS (ibuprofen, Motrin, Aleve) since there is usually no risk for clots in the superficial veins to embolize to the lung.  Superficial veins are connected to the deep system by perforator veins.  If a clot is in the superficial vein near a perforating vein, it may propagate through the perforating vein into your calf or thigh and become a DVT.  A clot in a superficial vein can propagate up the great saphenous vein to the saphenofemoral junction and into the common femoral vein.  A clot can propagate up the small saphenous vein into the popliteal vein and become a DVT.  If a clot is propagating into a perforating vein, in the great saphenous vein within 8 cm of the saphenofemoral junction or nearly into the popliteal vein, these are no longer treated as a superficial system blood clot.

Deep venous thrombosis:  DVT usually requires anticoagulation to prevent the clot from growing and causing a pulmonary embolus.  Most cases of DVT can be successfully treated with a combination of medications, including heparin or Lovenox and then Coumadin (warfarin) or possibly one of the newer drugs such as or similar to Pradaxa.  Once these medications are started, most people take them for 3 to 6 months or longer (one year if there is a pulmonary embolus) and must see their doctor regularly for monitoring.  You will also have periodic duplex venous Doppler studies.  The treatments will be individualized.  In more severe cases, or when other health conditions keep people from being able to take these medications, alternative interventions (inferior vena cava filter) and surgeries are possible.

Monitoring:  Blood clots below the knee are at lower risk for embolization to the lung.  All clots once they are found and treatment initiated should be re-evaluated with venous duplex Doppler in 2 to 14 days to monitor the clot to see if it is growing or propagating.  Clots in the femoral and common femoral vein should be restudied to be sure they are not propagating in the veins in the pelvis.

Pulmonary emboli:  PE are treated similarly to deep venous thrombosis but more emergently and aggressively.  Admission to the hospital for treatment and observation is mandatory.  You are given IV anticoagulant with some form of heparin (such as Lovenox) and then started on long-term anticoagulation with warfarin (Coumadin) or one of the newer anticoagulants.  If you have had a pulmonary embolus, you will be on anticoagulation for six months to a year at least.  Your blood thinner will be checked frequently to be sure the levels are adequate.  If lung function is compromised and the patient is short of breath or is experiencing hypoxia, or low oxygen levels, or has heart enzyme changes, a clot buster may be used to decrease the size of the clot in the lung.  Surgery may be required to get the clot out of your chest, but you do not want to wait until you are in this kind of shape before seeking medical attention.  You may also need a filter placed in your inferior vena cava because the second blood clot on top of this problem could again be life-threatening.

Routinely thrombolysis of clot in the common femoral vein at the groin, iliac vein up to the inferior vena cava and some into the inferior vena cava is relatively standard providing you meet certain criteria.  (If you have had a recent stroke or recent surgery, or other health problems, you may not meet criteria.)  Many times prior to doing this an inferior vena cava filter is placed to prevent large clots from breaking loose and going to your lungs.  Thrombolysis of clot from your groin to your knee is so far not recommended.  An iliofemoral vein thrombosis that does not resolve is a life-changing event.  Blood that goes into the leg in an artery must come back out of the leg.  You normally flow 300 to 400 cc per minute into the leg through the femoral artery in your groin.  If you walk fast,  you can increase this two to four times.  Your leg will become tight, swollen and painful and you will have to stop and rest until the blood slowly drains out of your leg.  With a walking exercise program, you can develop some new collateral veins, but they are never as good as the first ones.  A progressive walking exercise program is a very important part of your rehabilitation.

Occasionally the iliac veins have to be dilated and stented and again you will be on long-term anticoagulation of six months to a year at least.  Sometimes a thrombosed iliac vein can be dilated and stented if it is less than 3 to 6 months old.  The age of the thrombus does not always correlate with age in days and weeks.

Surgery:  Although surgery is rarely recommended as a treatment for DVT, venous thrombectomy is an option but is not without controversy as many times the patient will form new clots and, therefore, is on anticoagulation therapy afterwards.

On rare instance the clotting is so extensive in the leg that the venous pressures become so high that they block off arterial flow to the leg causing loss of the extremity.  If this is approaching, the clot will be removed in one form or another and may require opening the skin in the fibrous compartment over the muscles of the lower leg to prevent them from dying.  If clotting is this severe, surgical embolectomy through a gron incision may be necessary.  Usually a vein is anastomosed to the side of an artery to create a high-flow rate on the venous side to help keep this open.  After the swelling in the leg goes down, the incisions over the lower leg can be closed and skin grafted.  In a few months to a year or two when this is stable, the artery-to-vein fistula may be removed.  This may not be very pretty, but it is better than having no leg or a leg on which you cannot lift your toes secondary to nerve injury.

Inferior vena cava filter:  If you cannot take anticoagulant medications, undergo lysis of your clot with TPA, and decide against venous thrombectomy, you may have implanted a special metal device called a vena cava filter into your largest vein (the vena cava) to protect you from the blood clot.  The vena cava is located in your abdomen and works to carry blood back to your lungs and heart.  The filter is designed to catch any large clots that break free and head toward your lungs where they can cause a pulmonary embolism.

Compression therapy:  The use of compression stockings is a main consideration in conservative treatment.  The use of support stockings will be discussed with you by your vascular specialist and testing will be done to assure that you have appropriate arterial flow for wearing compression. 

With hospitalization:  Compression therapy is started when you are in the hospital and should be of moderately high compression and you should wear this for at least a year.  At that time your veins will have to be reassessed to see if this is going to be a lifelong commitment or whether the veins have cleared enough that these will not have to be continued past one year.  During  your stay or shortly thereafter if this is your second deep vein thrombosis or even superficial clot and you have a strong family history of clots, you will be evaluated for inherited and acquired thrombophilia and discussion of that follows:  Learn more about compression stocking therapy by clicking here.

Prevention (Venous)

The best prevention is to reverse your risk factors in regard to lifestyle changes. 

  • Do not smoke.
  • Develop an exercise program and healthy diet to control your weight. 
  • Avoid long periods of immobility at work, on long airplane or car trips and periodically get up or stop and walk around or pump your feet up and down 20 times every 30 minutes to keep your calf muscle pump working and blood flowing. 
  • Avoid sitting with crossed legs and wearing tight garments below the waist. 
  • Women should avoid wearing high-heeled shoes.
  • Reconsider your use of birth control pills or hormone replacement therapy.

To reduce the risk of blood clot formation after surgery (particularly knee or hip surgery but also shoulder surgery) during the recovery period, your doctor may prescribe anti-clotting medication to prevent blood clots.

The use of compression stockings is helpful in the prevention of future clot formation.

Inherited and Acquired Thrombophilia

What is thrombophilia?

Thrombophilia is a term used to describe a group of conditions in which there is an increased tendency, often repeated and often over an extended period of time, for excessive clotting. These break down into two types:

  1. An inherited thrombophilia is a family history of clotting or a diagnosis based on a demonstrated genetic mutation such as factor V Leiden, protein C and S deficiencies, antithrombin, MTHFR gene mutation C677T and prothrombin 20210A mutations.
  2. An acquired thrombophilia such as lupus inhibitor, antiphospholipid antibody, inflammatory bowel disease and systemic lupus erythematosus.  The antiphospholipid antibody should be rechecked in six months to see if it is still positive.

Both children and adults may have thrombophilia, but it is more commonly diagnosed during the adolescent and adult years due to normal changes that occur with growth and aging.  Both men and women may have thrombophilia.  In fact, women who have thrombophilia may have a greater tendency to show symptoms due to the contributing effects of pregnancy or use of hormones (birth control pills or hormone replacement therapy).  The first event of thrombophilia may not be identified until times of surgery or periods of immobilization.

Thrombophilia is just the reverse of the process of blood clotting compared to hemophilia.  While people with hemophilia have an increased tendency to bleed, people with thrombophilia have an increased tendency to clot. 

What are the differences between inherited and acquired thrombophilia?

Inherited thrombophilia is a genetic abnormality, meaning you are born with it, that leads to an increased risk of thrombosis throughout a person’s life. The most common inherited thrombophilic disorder is factor V Leiden.  

Acquired thrombophilia refers to a group of disorders that an individual is not born with, but they may develop throughout life due to illness or situation.  The most common acquired thrombophilias are commonly encountered during surgery (particularly hip and knee), injury, or medical conditions including congestive heart failure and certain respiratory conditions, and these are called antiphospholipid antibodies (APLA).  These represent a family of several different individual antibodies which may, as a group or independently, lead both to clotting events and also recurrent miscarriages.

Congenital, Acquired and Situational Thrombophilias
CongenitalAcquiredSituationalCongenital or Acquired
Factor V Leiden
Prothrombin G20210A
Antithrombin deficiency
Protein C deficiency
Protein S deficiency
Factor VII excess
MTHFR gene C677T
Antiphospholipid antibodies
HIV infection
Polycythemia vera
Paroxysmal nocturnal hemoglobinuria
Heparin-induced thrombocytopenia
Behçet disease
Nephrotic syndrome
Inflammatory bowel disease
Oral contraceptives
Hormone replacement therapy
Factor VII, IX, XI excess
Inherited thrombophilia

Genetic errors in the clotting mechanism:  People with inherited thrombophilia tend to form clots due to a genetic predisposition inherited from their parents.  People with inherited thrombophilia may have a family history of relatives with abnormal or excessive blood clotting.

One common cause is a defect in the blood clotting protein called factor V.  The second most commonly inherited cause of venous thrombosis is a mutation in the prothrombin (factor II) gene, named prothrombin gene 20210 G/A.

Inherited hypercoagulable conditions include:

  • Factor V Leiden (the most common)
  • Prothrombin gene mutation
  • Deficiencies of natural proteins that prevent clotting (such as antithrombin, protein C and protein S)
  • Elevated levels of homocysteine
  • Elevated levels of fibrinogen or dysfunctional fibrinogen (dysfibrinogenemia)
  • Elevated levels of factor VIII (still being investigated as an inherited condition) and other factors including factor IX and XI
  • Abnormal fibrinolytic system, including hypoplasminogenemia, dysplasminogenemia and elevation in levels of plasminogen activator inhibitor (PAI-1 )
  • Homozygous MTHFR gene C677T with hyperhomocysteinemia
Situational thrombophilia

Situational thrombophilia includes:

  • Pregnancy
  • Supplemental estrogen use, including oral contraceptive pills (birth control pills)
  •  Hormone replacement therapy
  •  Recent trauma or surgery
  •  Prolonged bedrest
  •  Immobility such as with lengthy airplane travel, also known as “economy class syndrome”

Pregnancy is a special situation.  From the Handbook of Venous Disorders, 3rd Ed. and Guidelines of American Venous Forum, it states: 

Venous thromboembolism is secondary only to abortion as a cause of pregnancy associated death.  Increased thrombotic risks during pregnancy contribute to an acquired prethrombotic state in combination with impaired venous outflow due to uterine compression.  Pregnancy is associated with a variety of changes in the coagulation system including increases in fibrinogen and factors II, VII, VIII, and X; decreases in protein S levels; and diminished fibrolytic activity.

From venous ultrasound studies, instances of thrombophlebitis are approximately 75 per 100,000 deliveries.  The instance of DVT postpartum time period is twofold to fourfold higher than during the pregnancy.  (The overall instances of 351 per 100,000—for DVT occurring within three months of delivery compared with 85.2 per 100,000 women-years during pregnancy.  Recurrent thromboembolism may complicate 4 to 15 percent of subsequent pregnancies.)

 Again, from the Handbook of Venous Disorders:

Among women with thrombophilia, those with antithrombin deficiency are at very high risk for pregnancy-associated thrombosis; those with protein C or protein S deficiency or homozygous or combined factor V and prothrombin mutations are at high risk: those with heterozygous factor V or prothrombin mutations are at moderate risk.  The factor V Leiden mutation has been associated with up to 59 percent of cases of pregnancy-associated thromboembolism.

 Fortunately, thrombophlebitis can be treated during pregnancy with Lovenox (low molecular weight heparin) injections, subcutaneous injections twice daily during the pregnancy.  Lovenox does not cross the placental barrier.  Coumadin or warfarin cannot be used because it does cross the placental barrier.

 Also from the Handbook of Venous Disorders, antiphospholipid antibody syndrome is characterized by at least one episode of arterial or venous thrombosis and/or history of at least three spontaneous abortions prior to the tenth week, one fetal death after ten weeks, or one premature delivery before 24 weeks.  (Laboratory confirmation requires presence of lupus anticoagulant or moderate to high titers of immunoglobulin (IgG or IgM, anticardiolipin antibody on at least two occasions at least six weeks apart).  These lupus anticoagulant and anticardiolipin antibodies are on most lupus panels.  (Antiphospholipid antibodies may be present in 4 to 20 percent of patients with venous thromboembolism.  Lupus anticoagulant (LA) and anticardiolipin antibody (ACA) may be seen in association with systemic lupus erythematosus; other autoimmune disorders; and non-autoimmune disorders such as syphilis and acute infection; drugs including chlorpromazine, procainamide, hydrolyzing; and elderly people.  They are present in 34 and 44 percent of patients with systemic lupus erythematosus compared with 2 percent and 0.75 percent of the general population.  Among patients with systemic lupus erythematosus, those with LA are at sixfold increase for venous thromboembolism (VTE) while those with ACA are at twofold greater risk.  This risk from lupus anticoagulant activity is increased by the presence of anti-beta-2-glycoprotein 1 or antiprothrombin antibodies.  Again, in the non-pregnant patient anticardiolipin antibodies should be rechecked in six months to see if they have returned to normal or if they are permanently high.

 The risk from birth control pills and post-menopausal hormone replacement are slightly to somewhat increased for thrombophlebitis but, so far, there are no national recommendations for thrombophilia screening prior to starting these unless there is a family history of thrombophlebitis or pulmonary embolus (VTE) or the patient may have a prior history of thrombophlebitis or pulmonary embolus (VTE).

Acquired thrombophilia

In acquired thrombophilia the abnormal clotting is usually related to a specific cause.  The most common acquired thrombophilias are encountered during surgery, injury or medical conditions including congestive heart failure.  Often acquired errors in clotting mechanism are associated with an inflammatory disease such as rheumatoid arthritis, lupus, antiphospholipid syndrome (APLA) or inflammatory bowel disease.  These represent a family of several different individual antibodies which may, as a group or independently, lead both to clotting events and also recurrent miscarriages.  Acquired hypercoagulable conditions include:

  • Cancer
  • Some medications used to treat cancer, such as tamoxifen, bevacizumab, thalidomide and lenalidomide
  • Central venous catheter placement
  • Obesity
  • Heart attack, congestive heart failure, stroke and other illnesses that lead to decreased activity
  • Heparin-induced thrombocytopenia (decreased platelets in the blood due to antibodies to heparin/PF-4 Complex.  These people have usually been exposed to heparin previously or low molecular weight heparin preparations.
  • Antiphospholipid antibody syndrome
  • Previous history of deep vein thrombosis or pulmonary embolism
  • Myeloproliferative disorders such as polycythemia vera or essential thrombocytosis
  • Paroxysmal nocturnal hemoglobinuria
  • Inflammatory bowel syndrome
  • Nephrotic syndrome (too much protein in the urine)

Who needs testing?

The American College of Medical Genetics and the College of American Pathologists and Society of Vascular Surgery, American Venous Forum and American College of Phlebology recommend factor V Leiden screening and other tests, such as prothrombin G20210A, protein S and C deficiencies, antithrombin III, and elevated homocysteine.  Additionally, it is appropriate to consider anticardiolipin antibody and lupus anticoagulant assays in individuals with venous thrombosis, particularly if no other cause is found, autoimmune disease is present, or there is no family history of thrombosis. 

Following are commonly ordered tests for thrombophilia work-up of patients with venous thromboembolism:

  • Factor V Leiden
  • Prothrombin 20210A mutation
  • Protein C activity
  • Protein S activity, free and total protein S antigen
  • Antithrombin activity
  • Anticardiolipin IgG and IgM antibodies
  • Lupus anticoagulant
  • Anti-ß-2-glycoprotein l IgG and IgM antibodies
  • Homocysteine
  • Factor VIII, Factor IX, Factor XI
  • Prothrombin time, activated partial thromboplastin time

With an acute thrombophlebitis, tests for antithrombin III, protein C and protein S should not be ordered following an acute thrombotic event (within three weeks) because of possible “consumption” of these factors leading to false low values. 

Certain tests cannot be accomplished when a patient is already on anticoagulants (particularly protein C and protein S on vitamin K antagonist [VKA] and antithrombin III).  Four to eight weeks after stopping your anticoagulation, these three studies should be obtained.  It is appropriate to obtain those that can be done on anticoagulants and your doctor will discuss those with you.

Repeat testing of a genetic cause of thrombophilia whether positive or negative is not indicated.  (Factor V Leiden and prothrombin gene mutation 20210A are inherited.)

Warfarin-induced skin necrosis is usually caused by the patient having a protein C deficiency and high-dose warfarin is started without the patient already being on heparin.  To prevent this, the patient is started on heparin and after 24 hours is started on warfarin.

The Handbook of Venous Disorders indicates some circumstances that would require a person to be tested for possible inherited thrombophilia which include:

Guidelines for Thrombophilia Screening
A first episode of idiopathic VTEVTE occurring at <50 years of age, even in the presence of transient risk factorsVTE occurring during pregnancy or oral contraceptive/hormone replacement therapyChildren with VTERecurrent VTERecurrent superficial thrombophlebitis in the absence of cancer or varicose veinsVTE at unusual sites (cerebral sinus, mesenteric/hepatic veins)Warfarin-induced skin necrosis and infants with purpura fulminans in the absence of sepsisFemales of child-bearing age with documented symptomatic thrombophilia in a first-degree relativeTwo consecutive/three non-consecutive abortions at any gestational age:  One fetal death after the 20th weekSevere pre-eclampsia
VTE, venous thromboembolis (or PE, pulmonary embolus)

Some circumstances that would require a person to be tested for possible inherited thrombophilia include:

  • Venous thrombosis before 40-50 years of age
  • Unprovoked thrombosis at any age
  • Recurrent thromboses at any age
  • Unusual sites such as cerebral (brain), mesenteric (small bowel), portal vein (coming together of superior mesenteric and splenic veins), or hepatic veins (moves blood from the liver)
  • Positive family history for thrombosis
  • Thrombosis during pregnancy, oral contraceptives, or hormone replacement therapy (HRT)
  • Unexplained abnormal laboratory test such as prolonged PTT (partial thromboplastin time)

If it is determined that you are genetically disposed to thrombophilia, your doctor will discuss this with you in depth so it can be best understood in your individual situation.  Any and all tests will be discussed and you will be given every opportunity to ask any and all questions and are encouraged to do so.  Many times a referral to a doctor who specializes in genetics or hematology may be made.

Thromboembolic Risk Factors
Risk FactorPrevalence& %Risk
Age1.9 x per 10 year increase
Surgery18-394-5.9 x(General surgery 25%; retropubic prostatectomy 32%; gynecology (benign disease) 1.4%; neurosurgery 22%; hip/knee arthroplasty 51% (47%)
Trauma3-1220.5 x
Malignancy18-51Without chemotherapy 4.4-6.9 xWith chemotherapy 6.5-9.9 x
Hospital/nursing home18.4 x
History of venous thromboembolism15.6 x
Primary hypercoagulable states
Antithrombin, protein C & S deficiency5.5-9.510 x
Factor V Leiden20
Heterozygous3-8 x
Homozygous50-80 x
Prothrombin 20210A4-72-4 x
Increased Factor VIII256x
Hyperhomocysteinemia    MTHFR gene C677T homozygous02-4 x
Family history2.9 x
Oral contraceptives16†2.9 x(30-50 x with Factor V Leiden)
Estrogen replacement2-4 x
Immobilization10-172 x (preoperative) – 5.6 x (medical patients)
Long distance travel13.32.4 x – 3 x
Pregnancy and puerperium25-30†4.3 x
Central venous catheter11.8 x
Antiphospholipid antibodies3.1Lupus anticoagulant 6 xAnticardiolipin antibody 2 x
Inflammatory bowel disease1.2 – 7.1% of patients
Varicose veinsVariable
Myocardial infarction/CHF11Variable
* Prevalence of risk factor among patients with deep vein thrombosis or venous thromboembolism (population attributable risk)† Among women <45 years of age, CHF, congestive heart failure


We hope the information on these pages is both informative and helpful, but it is intended for education only.  Please do note that no web site, no matter how much information is shared, can replace a consultation with your doctor and a vascular specialist.  Medical technology and treatment are continually improving and evolving so before making any decision on treatment, it is always advisable to see your doctor first for a comprehensive evaluation of your vascular disease and other medical conditions.

At the Vascular Center of Wichita Falls, we work closely with your other physicians.  If you have concerns about your arteries or veins, contact us.  A referral is not necessary to make an appointment.