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Physiologic Changes of Clotting Factors During Pregnancy - Risk factors for DVT in pregnancy

 

 

Physiologic changes of clotting factors during pregnancy include:

 

 

Elevated circulating levels of Factor VII, Factor VIII, Factor X and Factor XII during pegnancy increase risk of developing venous thromboembolism. This risk is highest right after delivery of the baby (the puerperium).

 

There are also a reduction in sensitivity to activated protein C and functional protein S levels during pregnancy.

 

The risk of develoing venous thromboembolism during pregnancy is 0.66 per 100.

 

This data is from P Kesteven and colleagues and the article is published in Phlebology 2012; volume 27 Supplement: pages 73-80.

 

 

 

 

 

 

 

 

 

 

Endoscopic view of blood clot across a vein valve (venous endoscopy):

 

 

 

courtesy of Prof Alberto Caggiati (Rome, Italy)

 

 

 

 

 

 

Deep venous thrombosis (DVT) is the formation of blood clots in the deep veins of the leg or arms (rarely). This potentially life threatening condition has an incidence of about 5 to 20 million cases per year in the United States.

 

 

The main clinical concern with DVT is the potential of a thrombus (blood clot) to break free, travel through the inferior vena cava, through the heart, and get lodged in the vessels of the lungs. This event, called pulmonary embolism, carries a mortality rate of roughly 20 to 30%.

 

The formation of DVT’s can be attributed to one or more of the following factors: venous stasis (sluggish blood flow), injury of the blood vessel wall, or hypercoaguability (increased tendency of blood to clot).

 

Risk factors for DVT formation include age >40, obesity, smoking, pregnancy, trauma, IV drug use, or prolonged immobilization - such as due to chronic illness or long trips in cars or airplanes.

 

People with cancer, congestive heart failure, lupus, or recent heart attack or stroke are also prone to DVT’s. Recent surgery, chemotherapy, and hormone replacement therapy are risk factors as well.

 

Patients with DVT’s of the lower extremities have pain and swelling of the affected leg about 75% of the time. Other symptoms may include increased warmth and redness of the leg and occasionally low grade fever. DVT’s usually occur in the mid to upper leg.

 

The most commonly used test to check for DVT is duplex ultrasonography, which has very good sensitivity and specificity in certain patients. It is most reliable when used on patients who are symptomatic, especially when the symptoms are localized above the knee and below the groin. The most accurate test for DVT is venography, in which dye is injected into the veins of the involved leg. A blood test can also be done, which checks for D-dimer fragments. This test is of limited usefulness, however, as it has a high rate of false positives.

 

DVT’s are treated by administering anticoagulants (blood thinners) such as heparin or warfarin. Patients are generally started on heparin for immediate anticoagulation, and then continued on warfarin for 6 weeks to 6 months. Patients who are anticoagulated for 3 to 6 months have roughly on half the DVT recurrence rate of those who are anticoagulated for only 4 to 6 weeks. Anticoagulants are contraindicated in patients with active bleeding or bleeding disorders. These patients may benefit from placement of a Greenfield filter in the inferior vena cava. By placing a filter in the vessel which returns blood from the legs, any thrombi are screened out before they can get lodged in the vessels of the lungs.

 

Unless one succumbs to the complication of DVT, such as a massive pulmonary embolism, the outcomes in patients are good.

 

 

 

Deep venous thrombosis (DVT) in Cancer Patients

 

 

The annual incidence of venous thromboembolism in cancer patients is 1 in 200.

 

It has been shown that tissue proteases and tissue factor have procoagulant effects.  There is also activation of platelets when tumor cells interact with tissue macrophages (white blood cells).

 

Chemotheray is also associated with a 6.5 fold increasein the risk of thrombosis.

 

Cancers involving bone, brain, ovary, pancreas and lymphomas are associated with the highest risk of developing DVT and venous thromboembolism.  

 

We recommend walking and leg exercizes in bedridden patients. Foot pedal exercizes are ideal and significantly decrease the risk of developing DVT from immobility.

 

Any swelling of the calf or leg or leg pain should prompt immediate scanning of the venous system to exclude deep vein thrombosis.  

 

Epidemiology, risk factors and sequelae of venous thromboembolism. P Wong and colleagues, Phlebology 2012; Suplement 2: pages 2-11.

 

 

 

Deep venous thrombosis (DVT) and surgery

 

 

 

Immobility following surgery is a risk factor for the development of venous thromboembolism.

  

 Surgery creates a hypercoagulable state and increases likelihood of thrombosis.

 

 Immobility following surgery (bed rest) results in venous stasis (sluggish blood flow) due to lack of use of the calf muscle pump.

 

 General anesthesia decreases vascular tone and increases vein size resulting in damage of the inside lining of vein (endothelial cells).

  

The risk of venous thromboembolism is lower after spinal or epidural anesthesia than after general anesthesia.

 

 Fatal pulmonary embolism rates are less than 1% (as low as 0.2%) after general anesthesia.

 

data from Epidemiology, risk factors and sequelae of venous thromboembolism. P Wong and colleagues, Phlebology 2012; Suplement 2: pages 2-11.

 

 

 

Deep venous thrombosis (DVT) and air travel

 

 

 

Immobility during travel is a risk factor for the development of venous thromboembolism.

  

All types of travel (air, bus, car) predisposes you to develop deep vein thrombosis and thromboembolism.

 

Researchers have shown that travel for more than 4 hours increases the risk of thromboembolism two-fold for two weeks after the traveling ends ! 

 

It has been calculated that 1 person in every 7 planes that leave JFK airport will develop a deep vein clot before than plane lands at its destination.  

 

data from Epidemiology, risk factors and sequelae of venous thromboembolism. P Wong and colleagues, Phlebology 2012; Suplement 2: pages 2-11.

 

 

 

Deep venous thrombosis (DVT) and risk of having a 2nd, 3rd deep vein clot (DVT recurrence)

 

 

Researchers have shown that after developing DVT, patients have an increased risk of having further DVT and thromboembolism.  

 

Recurrence risks are 5% to 7% annually for another episode of DVT.

 

Compared to previously unaffected patients (patients without DVT), patients with DVT have a 40 fold increase in the risk of getting another episode of DVT and thromboembolism.

 

An abnormal D-Dimer at one month following discontinuation of anticoagulation after DVT treatment is an independent risk factor for recurrent DVT.

 

data from Epidemiology, risk factors and sequelae of venous thromboembolism. P Wong and colleagues, Phlebology 2012; Suplement 2: pages 2-11.

 

 

 

What are inherited conditions that predispose one to deep vein thrombosis (DVT)?

 

 

 

 

 

 

How common is the factor V Leiden mutation ?

 

 

The Factor V Leiden imutation is the most common inherited form of thrombophilia affecting 3% to 8% of people with Northern European ancestry who carry one copy of the mutated gene. One in 5,000 individuals carry mutations in 2 genes. 

 

 

 

 

 

What is the likelihood of developing blood clots with the Factor V Leiden mutation ?

 

 

Individuals that carry one copy of the Factor V Leiden mutation are 7 more likely than individuals that don't have this mutation to develop clotting complications, like DVT and thromboembolism.

 

Individuals with 2 mutated copies of Factor V Leiden are 80 times more likely than individuals in the normal population (that don't have this mutation) to develop DVT and thromboembolism.

 

 

 

 

How does Factor V Leiden mutations increase the likelihood of blood clotting ?

 

 

Factor V (of the coagulation cascade) in patients with Factor V Leiden mutations cannot be normally inactivated by activated protein C (APC). As a result, the normal clotting process is altered, thus increasing the likelihood of developing blood clots, DVT and thromboembolism. 

 

 

 

Can you direct me to some resources for Factor V Leiden mutations and tests ?

 

 

 

http://www.acmg.net/StaticContent/StaticPages/Factor_V.pdf

 

 

 

 

What are the 7 most common acquired conditions that lead to DVT and thromboembolism ? 

 

 

Antihospholipid syndrome

 

Anticardiolipin antibodies

 

Lupus antibodies

 

Hyperhomocysteinemia

 

Activated protein C resistance

 

Malignancy

 

Autoimmune disorders

 

 

 

 

Sometimes, the first clinical presentation of a deep vein clot is a malignancy that has hereto yet to be diagnosed. Patients are investigated and found to have a malignant tumor, such as breast cancer, lung cancer or colon cancer ! 

 

 

 

 

What is Congenital dysfibrinogenemia ? 

 

 

 

Dysfibrinogenia can be aquired or congenital. Congenital dysfibrinogenemia is inherited in an autosomal dominant fashion. There is associated arterial and venous thrrombosis.

 

40% of patients with congenital dysfibrinogenemia have no symptoms while 50% of patients with dysfibrinogenemia have a bleeding disorder. Ten per cent of patients with dysfibrinogenemia have a thrombotic disorder or combined thrombotic and bleeding tendencies.

 

 

  

What is the prothrombin mutation G20210 ?  

 

 

 

 

This is a mutation in the prothrombin gene with replacement of guanidine with adenine at the 20210 nucleotide position. Prothrombin, also known as factor II is the precurson to thrombin, which is the end product of the coagulation cascade. Heterozygous carriers of this gene mutation have a 30% elevated risk of developing venous thromboembolism. The presence of associated factor V Leiden mutations increases the risk of thrombosis in patients with the prothrombin G20210 mutation.

 

 

 

 What is the antiphospholipid syndrome ?

 

 

 

 

Antiphospholipid antibodies are found in 1% to 5% of the population and the prevalence increases with age.

 

The antihospholipid antibody syndrome is a clinical disorder where patients can develop recurrent episodes of arterial and venous thrombosis. Another name (misnomer) is lupus anticoagulant syndrome. The current terminology is to call it antiphospholipid syndrome with or without associated rheumatologic disease.

 

The procoagulant effects of the antiphospholipid antibodies lead to thrombosis and this is mediated through inhibition of the activated protein C pathway, inhibition of antithrombin activity, inhibition of the anticoagulant activity of beta glycoprotein I, inhibition of fibrinolysis and activation of platelets.

 

The most important complication from the antiphospholipid syndrome is venous clots and thromboembolism and less commonly, arterial clotting. Prophylaxis is achieved with oral aspirin and hydroxychloroquin.

 

 

 

 

How does D-Dimer testing help exclude DVT ?

 

 

 

 

A negative D-dimer test measured by ELISA testing with a normal Doppler ultrasound test has a high negative predictive value for DVT - meaning that it can reliably say that the patient does not have deep vein thrombosis.

 

 

 

 

Can a positive D-Dimer test diagnose DVT ?

 

 

 

 

A positive D-dimer test measured by ELISA testing does not confirm the existence of DVT as there are numerous causes of elevated D-dimer : infection, pregnancy and malignancy. Therefore, it should be used in conjunction with history, physical examination and ultasound study (Duplex) of the venous system. 

 

 

 

 

 

 

 

 

 

What is hyperhomocysteinemia ?  Hyperhomocysteinemia and Clot Formation Buffalo

 

 

 

Hyperhomocysteinemia is a rare condition that is either inherited or an acquired condition. It is inherited as an autosomal dominant manner. Hyperhomocysteinemia results from abnormal metabolism of methionine. This metabolic derangement in hyperhomocysteinemia results in decreased activation of protein C and impaired binding of the plasminogen activator. Hyperhomocysteinemia is associated with venous thromboembolism and arterial clot formation.

 

Acquired hyperhomocysteinemia is from nutritinal deficiencies of folate (folic acid), cobalamine and pyridoxine.

 

 

 

 

 

What is Virchow's Triad for DVT - Buffalo Vein Expert

 

 

 

Rudolph Virchow was the first physician to ecplain how pulmonary embolism develops as it develops from deep vein clots. He described what is now called 'Virchow's Triad' as a triad of circumstances and conditions that predispose patients to the develop deep vein thrombosis. He has been given credit for the triad posthumously and his name is associated with it. What is required for formation of blood clots is:

 

 

1) stasis - venous stasis - turbulence of blood flow and stagnant blood flow in the venous system

 

2) endothelial injury - injury to the inside lining of the vein wall

 

3) hypercoagulability - increased tendency to form blood clots from the elements or components of the blood clotting cascade and coagulation factors

 

 

 

 

 

 

 

 

 

 

Rudolph Virchow Facts for Medical Historians and Medical History Buffs

 

 

Rudolph Virchow (Rudolph Ludwig Karl Virchow) was the first physician who described the phenomenon of cells giving rise to other cells, i.e. "every cell originates from another cell". He called it or phrased this as "omnis cellula e cellula".

 

 

 

 

 

 

 

 

Read the following articles about Deep Vein Thrombosis and Venous Thromboembolism by Dr. Karamanoukian:

 

 

 

Chemotherapy and Radiation Therapy increase the risk of Deep Vein Thrombosis

 

Venous Thromboembolism and Cancer Type

 

Treatment of DVT and Venous Thromboembolism in Patients with Cancer

 

Anticoagulation for DVT thrombophylaxis after hip surgery and knee surgery

 

Antiphospholipid Syndrome and Venous Thromboembolism

 

Hemorrhagic Complications with Anticoagulation for DVT and Venous Thromboembolism

 

Hormone replacement therapy and venous thromboembolism

 

Xarelto for Deep Vein Thrombosis - rivaroxaban for DVT

 

Protein C Deficiency and Deep Vein Thrombosis, mutations PROC gene

 

Thrombophilia and Exercise, Smoking Cessation, Avoiding Immobility, Surgery, Oral Contraceptives, Pregnancy

 

Thrombophilia and Relative Risk for DVT and Venous Thromboembolism

 

Ways to Reduce Risk of Deep Vein Thrombosis (DVT)

 

What is Travelers DVT (Deep Vein Thrombosis)?

 

Deep Vein Thrombosis is Multifactorial

  

Three Ways to Diagnose Deep Vein Thrombosis

 

Are Temporary Vena Cava Filters Really Temporary?

 

Blood Clots During Pregnancy and Risk factors for Deep Vein Thrombosis During pregnancy