Venous Thromboembolism: An investigation into the causes, effects and current treatment options of this fatal but preventable clinical condition. Word Count: 1067 Venous Thromboembolism (VTE) is one of the leading causes of hospital related death as well as the third most common cardiovascular illness.
Each year in the UK alone 250,000 people die from hospital related VTE. (1) There are two types of VTE, the first is Deep Vein Thrombosis (DVT) which is a blood clot developed in a deep vein, this generally occurs in the lower extremities, usually in the leg but can also occur in the upper extremities. (2) If untreated DVT can lead to the second type of VTE, Pulmonary Embolism (PE). This causes a piece to break off from the blood clot and travel around the blood stream, eventually blocking the pulmonary arteries which can cause a range of respiratory problems.
(1) Table 1 shows the morbidity and mortality of VTE in 6 European countries (France, Germany, Italy, Spain, Sweden and the UK) in 2004 (3) Causes: There are thought to be 3 main abnormalities that lead to thrombosis, these are depicted in Virchow’s triad. (4) Figure 1 shows the 3 elements Virchow’s triad is composed of. (4) Figure 2 shows how the 3 components of Virchow’s triad can cause venous thrombosis. (4) There are many different causes of VTE including cancer, combined oral contraceptives, psychiatric disorder treatments, trauma and surgery, these are known as risk factors. (5) A risk factor is anything which increases the likeliness of developing a disease or injury. (6) The reasons behind why many identified risk factors can lead to VTE is unkown however, they are all linked to at least one aspect of Virchow’s Triad. (5) Table 2: Risk factors observed in 1231 consecutive patients treated for acute DVT and/or PE.
(5) Risk Factor Patients (%) Explanation Age > 40 years 88.5 Aging causes prevalence of other risk factors to increase. (7) Obesity 37.8 Although it isn’t known how obesity contributes towards VTE, it is known that it interacts with other risk factors for VTE such as inherited factors and hormonal contraception. (8) History of VTE 26.0 Patients who have previously suffered from VTE have been found to be approximately 8 times more likely to suffer from reccurent VTE. (5) Cancer 22.
3 The risk of VTE is increased in patients with cancer as tumours constitutively produce the transmembrane glycoprotein tissue factor (TF) which is a procoagulant, activating blood clotting. The constitutive production of this molecule means it is produced constantly without consideration of the cells environment. (5,9) Bed rest > 5 days 12.0 Decreased ability to move from one place to the other causes the formation of blood clots, this can increase the risk of VTE in patients with mental health disorders and other illnesses. (10) Major surgery 11.2 Major surgery is a risk factor due anaesthesia paralysing the muscles, this slows blood flow so it is more likely to clot. (10) Congestive heart failure 8.2 Congestive heart failure causes blood flow to slow down, this makes the blood more likely to clot thus, making it a risk factor for VTE.
(11) Varicose veins 5.8 Varicose veins are a weak risk factor for VTE due to the fact that the severity of varicose veins is a subjective matter and there are only a small number of studies that have looked into the link between varicose veins and VTE (5) Fracture (hip or leg) 3.7 Immobilization of the joint after the fracture to aid healing can cause VT, fractures of the femur and pelvis are also risk factors for VTE. (5) Oestrogen treatment 2.0 Taking combined oral contraceptives increases the chance of VTE in women who have inherited thrombollic defects, however there is only a slight risk in healthy women. The type of progesterone and dosage of oestrogen affects the risk level.
This type of contraception increases risk of VTE as it can lead to an increase in coagulation and decrease in fibrinolytic activity, so blood clots are more likely to form and the enzymes which dissolve fibrin in the clots are not as active. (12) Stroke 1.8 VTE commonly occurs after stroke.
(13) Multiple trauma 1.1 Deep vein thrombosis is a common complication in patients who have suffered from trauma. (14) Childbirth 1.1 VTE often occurs in the left leg during pregnancy due to compression of the left iliac vein by the right iliac artery, also pregnant women can only lie in the supine position (with the face and torso up) which causes decreased blood flow velocity, leading to more chance of clotting. (15) Myocardial infarction 0.7 Myocardial infarction often leads to bed rest and venous stasis as well as often being linked to age, these are all risk factors for VTE and are the reason myocardial infarction is considered a risk factor.
(5) 1 or more risks 96.3 2 or more risks 76.0 3 or more risks 39.0 As well as acquired risk factors, inherited traits can also contribute towards the development of VTE. Antithrombin deficiency is the inherited trait with the greatest contribution towards VTE, Heterozygous Protein C and Protein S deficiency is also a trait that can contribute to VTE as these are part of the natural anticoagulant system.
A mutation in the factor V gene can cause APC resistance, this is a weaker risk factor and is especially prevalent in women with VTE who take oral contraceptives. An inherited mutation in factor II can also increase risk of VTE. Elevated levels of coagulants including factors VIII, IX and XI can cause an increased risk of VTE due to the higher chance of clots forming. Hyperhomocysteinemia has been identified as an independent risk for VTE however, the reason it causes VTE is unknown.
Incidence of VTE is higher in men than women and in black populations in comparison to white populations. (5) Effects: PE occurs when DVT is left untreated therefore, the symptoms of DVT will show first; these are swelling, tenderness and pain in the area of the clot (usually the leg). The affected area will also have warm skin and a heavy ache. If PE does develop, the symptoms for this are gradual or sudden breathlessness, chest pains which may worsen when breathing in and collapse. (2) After DVT there are three main long-term effects which can occur, firstly there is a higher risk of re-occurrence of VTE. (16) Another of the long-term effects which occurs in just under 50% of patients after DVT in the leg is Post-Thrombotic Syndrome, this is the formation of an ulcer due to poor blood flow caused by a blood clot that didn’t fully heal; this causes pain and swelling.
(16,10) The third long-term consequence is death. (16) Prevention: People with risk factors for VTE can prevent the development of blood clots by taking blood-thinning or anti-clotting medications as well as using mechanical devices such as compression stockings. (17) Compression stockings work by inducing a pressure gradient in the leg thus, increasing blood flow velocity. (13) As surgery is one of the biggest risk factors for VTE, to prevent VTE from occurring patients should try to get out of bed as soon as possible after surgery. (17) Diagnosis: VTE is difficult to diagnose just from the symptoms due to the fact there could be a range of different causes.
The first test to be carried out is the D-Dimer test, D-Dimer is a protein formed when a blood clot is degraded; patients with VTE will have an increased amount of D-Dimer in the blood. This test is used as a first indication as to whether the patient could have VTE however, an increased level of D-Dimer doesn’t mean they have VTE as this increase also occurs in other scenarios such as after major surgery, if a tumour is present and during pregnancy. If the D-Dimer test comes back showing an elevated amount of D-Dimer, then the next stage of diagnosis is compression ultrasound imaging.
In this type of imaging test an ultrasound probe is used to produce an image of the suspected vein. Pressure is then applied to the area by the probe being pressed onto the vein, if there is nothing wrong the vein will compress but if a clot is present this will prevent the vein from compressing; the second ultrasound image will show whether the vein compressed when pressure was applied or not. (18,19) Treatment: There are two main treatment paths that can be taken to treat VTE, the first is anticoagulant therapy, this is recommended over the second type of treatment, thrombolytic therapy, as it causes less major bleeding with the same recurrence rate of VTE.
Anticoagulant therapy usually uses a combination of a parenteral anticoagulant called Heparin and Warfarin, a Vitamin K antagonist which prevents the blood from clotting by reducing the action of Vitamin K. (20) Heparin is used initially because it acts immediately. (21) Anticoagulants reduce the blood’s clotting ability, prevent any clots already in the blood from getting bigger and can also stop parts of the clot breaking off, preventing PE. Thrombolytic therapy has a lower risk of causing post thrombotic syndrome but gives a higher risk of major bleeding, hence why anticoagulant therapy is more widely used. (20) There are two main complications associated with anticoagulant therapy, these are recurrence of VTE and major bleeding. If clinically required there is also surgical treatment where a filter is placed in the inferior vena cava to prevent clots from travelling to the lungs, large blood clots can also be removed surgically and clot busting medicines can be injected into the veins to disperse clots. (17) VTE is a fatal condition, causing over 250,000 deaths per year in the UK however, it is a very treatable condition once diagnosed, especially with new anticoagulants being produced with less serious side effects. There can be many causes of VTE so people showing risk factors such as hospitalised patients, cancer patients and women taking oral contraceptives should be monitored for warning signs regularly to ensure a quick diagnosis in order to prevent PE from forming.