Overview

The mechanism of blood clotting is a safety measure provided by the body to prevent blood loss and promote healing of the breach in the epithelium. But there are times when this clot starts forming within the blood vessels, creating a blockage (partial or complete) which in turn affects the oxygen supply to the end organ.

This inflammation due to the presence of a clot or thrombus in a vein is called thrombophlebitis. It can affect the superficial veins as well as deep veins. The deep veins of the lower extremities are the most affected. Women are more affected than men. The mean age of incidence is above 40 years of age. The involvement may be unilateral or bilateral.

Signs and symptoms of thrombophlebitis

Thrombophlebitis is usually a manifestation of some underlying health issues which need thorough investigation. A patient with thrombophlebitis usually presents with:^13,19

• Pain
• Swelling
• Redness along the length of the vein
• Eschars or nodules along the length of the vein
• Itching and pruritus of the affected area

Causes of thrombophlebitis

As mentioned earlier, thrombophlebitis is usually a symptom of an underlying disease state whose prompt diagnosis and treatment are imperative to prevent fatal complications.

According to Davidson and Boone, the causes of thrombophlebitis can be grouped under patient factors, surgical factors, and autoimmune factors.¹ A brief classification is as follows:¹⁶

Patient factors

• Age
• Usage of oral contraceptives
• Obesity
• Pregnancy/ puerperium
• Varicose veins
• Dehydration
• Immobility due to lifestyle or prolonged hospitalisation

Surgical conditions

• Knee arthroplasty
• Hip fracture 
• Abdominal or pelvic surgery

Medical conditions

• Malignancy
• Myocardial infarction or heart failure
• Atherosclerosis of the arteries
• Inflammatory bowel disease
• Nephrotic syndrome
• Pneumonia
• Blood disorders: thrombophilia
• Deficiency of anticoagulants: protein C or protein S

Investigations

Before a detailed physical examination of the patient is attempted, a thorough history investigation is mandatory to understand the underlying cause of thrombophlebitis and establish the further course of investigations and treatment planning.

A detailed patient history

A comprehensive patient history is taken. This includes the presenting complaint, the current symptoms, aggravating and relieving factors.

A thorough past medical and surgical history is taken to understand whether there were any venous episodes in the past.

Current medications help a physician understand the current health status of the patient. The use of oral contraceptives, the number of pregnancies and/or miscarriages is an indicator of the vulnerability of a person to thrombophlebitis. 

A detailed family history can be used to understand the likelihood of a person having a venous episode. Thrombophilia or a deficiency of Protein C or Protein S make a person more susceptible to venous disease.

Lifestyle choices that include the degree of daily physical activity, alcohol and tobacco consumption and travel patterns indicate the propensity of an individual for a venous episode.

Physical examination

A typical case of thrombophlebitis would show some common symptoms of the affected vein itself whilst also exhibiting some symptoms of the underlying cause. The common symptoms include:^{5, 6, 7}

• Pain, swelling, induration (skin thickening/hardening), and redness along the course of the affected vein
• Pitting oedema or temporary indentationin the affected limb when pressed
• The physician can palpate/feel the thrombus which is partly or completely occluding the lumen of the blood vessel
• The vein feels cord-like on palpation
• Itching/pruritus along the length of the vein
• Mobility of the affected limb may be restricted
• Cerebral vein and sinus thrombosis (CVST) can present itself in young and middle-aged patients as an unusual recent headache, stroke-like symptoms in patients without the usual risk factors, intracranial hypertensions, bleeding, cerebral infarcts etc.
• Retinal vein occlusion characterised by acute, painless, loss of vision in one eye. This usually occurs in males who are more than 60 years old
• Subclavian vein thrombosis seen as face or neck swelling, swelling of the arms and hands plus difficulty breathing as blood flow from the chest is obstructed
• Portal vein thrombosis presenting as acute or chronic symptoms. Acute symptoms can be abdominal pain, fever and nausea. Chronic symptoms include varices (abnormally dilated blood vessels), portal hypertension (high blood pressure in the portal vein) and ascites (abdomen fluid accumulation)
• Renal vein thrombosis patients present with flank pain and hematuria. If the involvement is bilateral, the patient can go into acute renal failure
• Prolonged compromised blood circulation leadingd to venous ulcers, especially in the lower extremities

Definitive tests for diagnosing thrombophlebitis

Only physical examination is inadequate in making a definitive diagnosis of thrombophlebitis. The other investigations which can be very useful in identifying thrombophlebitis are:^{2, 3, 4}

• Venography
• Ultrasonography
• Computed tomography (CT scan)
• Magnetic resonance imaging (MRI)

Venography

Venography is considered the gold standard in diagnosing thrombophlebitis and thrombosis. It is an invasive procedure which entails injecting a contrast dye in the affected vein for a definitive diagnosis. 

Ultrasonography

Doppler

When an electric current passes through the ultrasound probes, the piezoelectric crystals around the probe generate sound waves with specific frequencies. When these waves travel through tissue, they encounter various types of hindrances. Due to these, they are either reflected, refracted or absorbed by the tissues. The waves that make their way back to the transducer produce vibrations that are picked up by the crystals around the probe, generating an electric current which is relayed back to the machine. The speed of sound in soft tissue is known. The time taken by these waves to come back to the transducer determines the depth of the tissue to which the waves have travelled.

The different modalities of doppler are:

• Colour doppler: This shows the shift in the velocities of sound displayed as different colours. The lighter colours indicate fast flow and darker colours indicate a slower flow. This is used to understand the blood circulation in an organ
• Power doppler: This shows the amplitude (strength) of the waves, representing the blood flow amount. This does not give information about the direction or velocity of blood flow but is more sensitive and thus is used in smaller vessels
• Spectral doppler: This shows the change in blood flow velocity over a given time by generating a visual wave signal. This can show velocity, direction and narrowing of blood flow

Venous function and physiology assessment

Patient venous function needs to be assessed by a screening procedure. This is is cost-effective and eradicatesthe need for imaging. There are two types of screening tests:

D dimer tests

1. Laboratory tests: ELISA (Enzyme Linked Radioimmunoassay) 
2. Near patient Tests : SimiRED and Simplify

Plethysmography

1. Digital plethysmography
2. Strain gauge plethysmography
3. Impedance plethysmography

Plethysmography

This is the recording of the changes in the size of the limbs which occur due to pooling of venous blood or tissue fluids.

• Digital photoplethysmography: This takes into consideration the amount of light absorbed by haemoglobin in the blood. The digital probe is placed 10 cm above the affected area and the patient is asked to move the limb 10 times before resting for 45 seconds. The type of reflected light determines the venous inflow which is presented as a graph
• Computerised strain gauge plethysmography: This measures the change in calf size when the venous return is blocked by a thigh cuff. Ideally, faster filling suggests a normal venous function. It is an easy test to perform with minimal training and can be completed in 15 minutes
• Impedance plethysmography: This is technique and operator sensitive, hence is coupled with D-dimer tests. In this case, the venous outflow is restricted but the arterial inflow remains the same with the help of a thigh cuff. The blood starts pooling below the calf. This pooled blood has the capacity to send an electric signal after the cuff is removed and the blood circulation resumes. In the case of a thrombus, the emptying is slower

Magnetic Resonance Imaging (MRI)

MRI is the method of choice for diagnosis of venous disease in young patients where multiple/serial imaging is required, due to lack of ionising radiation. It is not operator sensitive and is more accurate than a CT scan to measure the proximal length of deep vein thrombosis.

The disadvantages of MRI include the presence of a strong magnetic field which is detrimental for pacemakers. MRI is also more expensive and less available.

Computed Tomography (CT)

Computed tomography is the ideal imaging modality where ultrasound is difficult to use, for example, stent thrombosis in a deeper vein like the vena cava. The disadvantage of CT is the high levels of ionising radiation. In addition, the contrast agent should be used sparingly in people with kidney disease. Repeat scans should be done only when absolutely necessary.

Laboratory investigations

• Routine blood tests like the complete blood count and haematocrit, routine urine tests, microbiology work up and other investigations can help identify the underlying cause for thrombophlebitis
• Clotting tests and clotting factor assays plus platelet function assays, can help determine any significant absence of the required anti coagulants and enzymes
• Laboratory markers for thrombophilia help identify genetic predisposition to the disease
• Family member screening and genetic counselling can help understand the predisposition to thrombophlebitis allowing precautions to be taken to prevent any episodes

Tumour markers in blood can help identify the presence of any malignancies.

Summary

With the advent of AI, there seems to be a promise of better diagnostic tools, more accurate diagnoses and faster treatment outcomes for thrombophlebitis. A minimally invasive yet accurate diagnostic tool would make management of this complicated phenomenon that much easier.