28 diseases - Venous thromboembolism

DNA test for genetic predisposition to venous thromboembolism

Venous thromboembolism is a group of diseases caused by the formation of a thrombus and the disruption of blood flow along the affected vessel. Thromboembolism is a dangerous condition that threatens the health and the life of the patient.

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Venous thromboembolism

Thromboembolic conditions are the third most frequent type of cardio-vascular disorder (after coronary heart disease and cerebral circulation disorders), and the most common undetected cause of death in in-patient hospital settings.

Essentially, thromboembolism involves the activation of intravascular coagulation, which leads to the formation of a thrombus - a blood clot created by the blood cells sticking together. The thrombus narrows the vascular lumen, impeding the flow of blood, and if it undergoes progressive growth it may completely block the blood supply to part of the corresponding organ.

An embolism occurs when fluctuations in blood pressure and changes in vascular wall tone lead to the thrombus becoming detached, travelling along the blood vessels to distant organs, and obstructing the blood supply. The most dangerous site for an embolism is the pulmonary artery: mortality in such patients is as high as 50%, while the majority of surviving patients develop persistent lung function disorders.

The concept of venous thromboembolism thus includes two conditions:

deep vein thrombosis (DVT);

Pulmonary embolism (PE).

Morbidity from deep vein thrombosis is quite high: in elderly people, the figure is as much as 20%. The incidence of the severe complication of thrombosis, pulmonary embolism, is substantially lower: for this disease, the figure fluctuates between 1 and 3 per 1,000 people per year.

Causes of venous thromboembolism

No single cause of thromboembolic diseases has been established. The formation of a thrombus is known to occur when three physiopathological conditions are present:

poor circulation;
high blood clottability;
Damage to the internal
lining (endothelium) of the blood vessel.

The following risk factors for thromboembolism have been identified:

prolonged immobility (e.g. as a result of severe illness);

injury, especially fractures in large bones;

major surgical operations;

insertion of vascular catheters;

taking of hormone drugs (oral contraceptives are especially significant);

pregnancy and the first 1,5 months after giving birth;

malignant tumors;

systemic lupus erythematosus;


severe cardiac conditions leading to cardiovascular insufficiency;

chronic obstructive pulmonary disease (COPD);

chronic inflammations of the digestive tract;



signs of venous insufficiency (e.g. on the background of varicose veins);

frequent airplane flights;

Advanced age.

Among external risk factors for thromboembolic diseases, oral contraceptives are especially significant. These drugs are very popular with women of childbearing age; they are often not perceived as serious medical agents and are taken unsupervised, without taking contraindications into account. Nevertheless, the effect of hormonal contraceptives on the frequency of thromboembolism is fairly strong, so before starting to take them it is necessary to consult a specialist, who will be able to identify the risk factors and recommend the best way to avoid becoming pregnant.
The genetic factor in the development of venous thromboembolism

It is well established that people whose relatives suffer from thrombotic diseases have a consistently higher risk of thromboembolism than the population at large. Genetic peculiarities and mutations coding for the blood’s clotting and anticoagulant mechanisms are particularly significant in the development of the disease.

The clotting factor V gene mutation (the Leiden mutation) is one of the most studied and most important genetic markers for a high risk of thrombosis. The replacement of one amino acid with another in the structure of Factor V causes the blood to clot more readily, which affects susceptibility to thrombus formation. A statistical study has shown that the risk of thromboembolism in women who are positive for the Leiden mutation and who are taking oral contraceptives is between 40 and 50 times higher than for the general population. By way of comparison, prolonged ingestion of hormonal contraceptives increases the risk of thrombosis between six- and eightfold on average. In view of this, some American scientists are studying whether it may be appropriate to conduct a genetic test for the Leiden mutation before prescribing any oral contraceptive; to date, however, this question remains open.

are taking oral contraceptives is between 40 and 50 times higher than for the general population. By way of comparison, prolonged ingestion of hormonal contraceptives increases the risk of thrombosis between six- and eightfold on average. In view of this, some American scientists are studying whether it may be appropriate to conduct a genetic test for the Leiden mutation before prescribing any oral contraceptive; to date, however, this question remains open.

As well as the Factor V gene mutation, the G20210A prothrombin gene, the gene for antithrombin and the genes for proteins C and S (the anticoagulation proteins), amongst others, are studied to determine the risk of thromboembolic diseases.

Lower-extremity deep vein thrombosis: symptoms and complications

In some cases of lower-extremity deep vein thrombosis, symptoms may be absent: compensation mechanisms come into play that divert the blood from the obstructed deep vein into superficial collaterals, eventually forming collateral vascular pathways that wholly or partially restore circulation.

In more serious cases, however, expressed symptoms appear:

  • a bursting sensation;

  • pain that intensifies on squeezing the affected limb and on pressing in the region of the thrombosed vein;

  • edemas;

  • raised local skin temperature;

  • cyanosis of the skin;

  • dilated, filled subcutaneous veins.

The lower extremities are a favored site of thrombosis, accounting for over 90% of all diagnoses. Deep vein thrombosis occurs less frequently in the upper limbs, internal organs and pelvic vessels.

Functional tests are used for express diagnosis. The most popular such test is the Perthes test, which involves tightly bandaging the affected leg with an elastic band, followed by exertion. If an intense pain appears after a few minutes of walking with the bandage on, and the subcutaneous veins do not collapse, this indicates thrombosis. To confirm the diagnosis, ultrasound tests (Doppler test and duplex ultrasonography), phlebography (contrast x-ray), rheovasography and radionuclide methods are prescribed.

Many patients fully recover the function of the affected limb after suffering a deep vein thrombosis, but without supporting treatment there is a high risk of the following complications:

  • 1

    Pulmonary embolism:
    in many cases, this develops when part of a thrombus located in the deep veins becomes detached.

  • 2

    Repeat thromboses:
    these develop in nearly ¼ of patients.

  • 3

    Post-thrombotic syndrome:
    this arises in over half of cases, often after a relatively short interval of 1 or 2 years. The thrombosis damages the venous valves, causing increasing venous insufficiency and blood congestion. Post-thrombotic syndrome manifests in thinning, peeling skin, the formation of non-healing trophic ulcers, susceptibility to infection in micro-injuries, muscle pain and swelling of the whole limb.

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Every year, millions of patients have their first encounter with the severe symptoms of thromboembolic disease. Hundreds of thousands of dollars are spent on diagnosis and treatment, but assistance is by no means always prompt or effective.

Don't wait for the disease to find you! Take a DNA test for genetic predisposition to venous thromboembolism.

Pulmonary embolism (PE): symptoms and outcome

A PE is an acute condition that occurs suddenly, usually against a background of complete health. The severity of the clinical picture depends principally on the diameter of the obstructed vessel and the degree of occlusion of the lumen.

Pulmonary embolism presents the following symptoms:

  • a sensation of lack of air or shortness of breath;

  • cyanosis and skin pallor;

  • dizziness;

  • cold, clammy sweat;

  • rapid pulse;

  • dry cough;

  • subfebrile temperature (up to 38°C).

An embolism in a small-caliber pulmonary artery may initially show no symptoms, but the interruption of blood supply to an area of tissue nevertheless causes a pulmonary micro-infarction. An inflammation – secondary pneumonia with raised temperature, coughing, weakness and breathing difficulty – will then develop on the site of the tissue necrosis.

The diagnosis of PE is very complex, as the majority of widely used investigative techniques are uninformative. The diagnosis can be confirmed by means of computed tomography, echocardiography, pulmonary angiography and a laboratory analysis of D-dimer, a raised level of which indicates widespread fibrin degradation and thrombosis.

The complex clinical picture of pulmonary embolism frequently hinders diagnosis, leading to delay in starting treatment. Many surviving patients develop persistent disorders of the affected lung; moreover, structural changes often occur in other important organs as a result of prolonged hypoxia (lack of oxygen).
Treatment of venous thromboembolism

When thromboembolic disease is suspected, with a pronounced clinical picture, treatment procedures should start immediately – even before a definitive diagnosis. Treatment aims to restore blood flow (as far as possible), prevent life-threatening complications and maintain organ function.

Treatment of lower-extremity deep vein thrombosis

Until the diagnostic investigation is complete, the patient is prescribed bed rest, which is necessary to reduce the risk of pulmonary embolism. Once the diagnosis is confirmed and the type of thrombus identified, an active regime may be substituted for bed rest.

The following treatments are prescribed for deep vein thrombosis:

  • 1

    Medical-grade (class 2 or 3) compression stockings:
    these help normalize the circulation in the affected limb and reduce the mobility of the thrombus.

  • 2

    Direct anticoagulants:
    unfractionated or low-molecular-weight heparin, or dabigatran. These suppress thrombin activity in the blood, thus inhibiting the process of thrombus formation. They are normally prescribed for a short period and need to be used very carefully.

  • 3

    Indirect anticoagulants:
    warfarin, fondaparinux, rivaroxaban. These act indirectly by inhibiting the formation of prothrombin in the liver. They may be used long-term to prevent post-thrombotic syndrome, PE and recurrence of thrombosis.

  • 4

    Nonsteroidal anti-inflammatory drugs (NSAIDS): aspirin, ibuprofen etc. These reduce edema and pain, and also have a moderate anticoagulant effect.

  • 5

    Thrombolytics (Lovenox, streptokinase):
    these break down the blood clot. They are prescribed in exceptional cases in view of their limited indications and high risk of unfavorable outcomes.

  • 6

    Insertion of vena cava filters:
    a non-invasive endovascular surgical technique involving the implantation of devices to prevent the thrombus or embolism penetrating to the inferior vena cava and from there to the pulmonary artery. Vena cava filters are usually inserted when anticoagulants are ineffective or cannot be used.

Treatment of pulmonary embolism

Treatment for PE is started immediately: the outcome of the disease depends on it. Statistics show that about 85% of all deaths from pulmonary embolism occur within 6 hours of the appearance of the first symptoms. Treatment is carried out in the intensive care unit. In cases of lowered respiratory and cardiac activity, these functions are supported both mechanically and medically.

The following are also prescribed:

  • 1

    Drug therapy:
    anticoagulants and thrombolytics.

  • 2

    Surgical treatments:
    embolectomy. The operation to remove the embolus is performed in a specialized theater using sternotomy access (making an incision along the breastbone). This intervention requires the use of hypothermia and artificial blood-circulation apparatus.

  • 3

    Extracorporeal membrane oxygenation (ECMO):
    a technology for artificially saturating the blood with oxygen. In PE, this treatment is used until the thrombus is resorbed and blood flow along the vessels restored. ECMO can be a substitute for surgical treatment when the latter cannot be performed.


The prevention of venous thromboembolism involves:

a healthy lifestyle with physical exercise and correct diet;

weight and blood pressure control;

prompt treatment of cardiovascular, endocrine and venous disorders;

care in the use of oral contraceptives (only be doctor's prescription and taking one's risk group into account);

wearing of compression hosiery by patients in at-risk groups (pregnant women, patients with a history of varicose veins or thromboses etc.);

Prophylactic use of anticoagulants during major operations and during enforced immobility.

Your future in your hands!

The dangerous nature of the disease makes it necessary to identify patients in the at-risk groups. A DNA test is the only way to diagnose a genetic predisposition to venous thromboembolic diseases. The test results can be used as the basis of an individual protocol for the prevention and early detection of the disease.

Stay alive and stay healthy! For early and effective prevention, take a DNA test for genetic predisposition to venous thromboembolism.