Venous thromboembolism

Venous thromboembolism (VTE) refers to a thrombus which originates in a vein. The most important types are deep vein thrombosis and pulmonary embolism.

VTE is a major source of mortality and morbidity, and its incidence is increasing. In the US alone it causes > 200 000 deaths annually, more than HIV, motor vehicle accidents, and breast cancer combined. VTE is preventable, and a major cause of preventable death. Many patients with VTE develop recurrent VTE later.

Etiology

VTE occurs due to Virchow’s triad, three categories of factors which contribute to thrombosis:

Stasis (alteration in normal blood flow)
Hypercoagulability (alteration in the constitution of blood predisposing to thrombosis)
Endothelial injury

There are many risk factors for VTE, which we can categorise according to Virchow’s triad:

Stasis
- Old age
- Recent immobility (especially after surgery or trauma)
- Heart failure
- Paralysis
- Obesity
- Varicose veins
Hypercoagulability
- Cancer
- Smoking
- High oestrogen state
- Pregnancy
- Thrombophilia
- Sepsis
Endothelial damage
- Surgery
- Previous VTE
- Trauma

Deep vein thrombosis

Deep vein thrombosis (DVT) is a form of venous thromboembolism which occurs in deep veins, most commonly in the legs or groin. Its main importance is the risk of the deep venous thrombosis dislodging and traveling to the lungs, causing pulmonary embolism (PE). DVT mostly affects the distal deep veins, but may affect the larger, proximal veins as well, including the iliac, femoral, or popliteal veins. PE is a serious complication which can lead to death in 30 – 60% of cases, and is more common in case of proximal DVT.

Etiology

See venous thromboembolism.

Clinical features

DVT presents as a unilaterally swollen leg which is warm and erythematous. The leg may be tender or painful. Homans sign refers to calf pain on dorsiflexion of the foot, which may be positive in case of DVT. In distal DVT, symptoms are confined to the calf. Proximal DVT may cause symptoms of the whole leg.

Upper extremity DVT is rare and usually due to central catheters or cancer.

Diagnosis and evaluation

Wells score for DVT

When DVT is suspected, we calculate the pre-test probability of DVT to determine how to proceed. The pre-test probability of DVT can be calculated with the Wells score:

Item	Points
Active or recent cancer	+ 1
Paralysis or recent cast	+ 1
Recent bed rest or surgery	+ 1
Pain on palpation of deep veins	+ 1
Swelling of entire leg	+ 1
Diameter difference compared to other calf of > 3 cm	+ 1
Pitting oedema on affected side only	+ 1
Dilated superficial veins on affected side	+ 1
Alternative diagnosis at least as probably as DVT (cellulitis, Baker cyst, etc.)	– 2

If the Wells score is 0, the pre-test probability is low (3%). If 1 – 2, the probability is intermediate (17%). If 3 or more, the probability is high (> 50%). The Wells score is then used to guide further evaluation.

Wells score 0
- -> measure D-dimer
  - D-dimer negative: DVT excluded
  - D-dimer positive: perform ultrasound
Wells score 1 – 2
- -> perform ultrasound
  - Ultrasound negative: measure D-dimer
  - Ultrasound positive: diagnostic of DVT

D-dimer

D-dimer is a fibrin degradation product. Its level in the blood correlates with the activity of coagulation and fibrinolysis. It’s highly sensitive for VTE and DIC, in which case the level is increased., D-dimer is not specific. It can be elevated due to other conditions, like pregnancy, cancer, infection, kidney disease, surgery, etc. Thus, D-dimer is used to rule out VTE (if the pre-test probability is low), rather than diagnose it. If D-dimer is normal, VTE is effectively ruled out (high negative predictive value). It should not be measured in those with conditions known to cause positive D-dimer.

Imaging

Ultrasound is important in the evaluation of DVT, and is the first choice. When applying pressure to the vein with the ultrasound probe and the vein is not completely compressible, a thrombus is lodged in the vein. Examining in this manner is called compression Doppler ultrasound. Ultrasound may also rarely show the thrombus as a hyperechoic mass in the venous lumen. Doppler imaging may show absent blood flow. If any of these findings are present, the diagnosis of DVT is made.

If D-dimer and ultrasound are inconclusive, venography with CT or MRI may be used.

Screening for etiology

Patients with VTE without clear risk factors, especially if recurrent, should be considered for screening for a hypercoagulable state (thrombophilia) and malignancy.

Treatment

DVT should be treated with anticoagulants for 3 months, preferably DOACs like rivaroxaban or apixaban. Very low-risk patients with distal DVT may be managed with regular surveillance rather than anticoagulants, but in almost all cases patients with DVT should receive anticoagulant therapy.

After three months, the patient should be reassessed for whether they require longer therapy. If the underlying risk factor(s) which are suspected to have caused the DVT are irreversible, indefinite anticoagulant therapy may be appropriate. If the risk factor(s) was reversible and is now reversed, anticoagulant therapy should be stopped after these three months.

If anticoagulants are contraindicated, IVC filters may be used. These filters are placed in the IVC and aim to prevent embolisms from reaching the heart and lungs.

Complications

Pulmonary embolism
Post-thrombotic syndrome
Phlegmasia cerulea dolens

Phlegmasia cerulea dolens is a severe form of DVT where all veins of one extremity is obstructed, leading to necrosis. It’s an emergency with high mortality, which causes severe swelling, pain, cyanosis, and pulselessness. It requires emergency thrombectomy surgery to prevent shock, gangrene, and limb loss.