Overview

Thrombophlebitis is a condition where a vein becomes inflamed due to the presence of a clot or thrombus in the lumen of the vein that may partially or completely occlude (block) the blood flow in the vein.^2,5,17

When microthrombi (small blood clots) are formed in the blood and spread through the circulatory system, away from the point of origin, the microthrombi,  are termed migratory thrombophlebitis. 

It is characterised by spreading from one group of veins to the next, as it spreads or migrates. The previously affected area is healed.. Sometimes, many veins across different locations may be involved simultaneously.

It is usually seen in

• Thrombophlebitis obliterans
• Factor XII deficiency
• Inflammatory bowel disease
• Behcet disease
• Pancreatic cancer

It occurs between 25-50 years of age, men being affected thrice as much as women.^2,17

Trousseau’s Syndrome

Trousseau's syndrome or Trousseau's sign of malignancy refers to the presence of an occluded vein either before or along with the diagnosis of a malignant cancer. 

Various theories exist as to the mechanism of migratory thrombophlebitis and Trousseau syndrome, but a specific mechanism has not yet been determined.

Pathophysiology

A detailed history needs to be taken to understand the underlying cause of thrombophlebitis. Previous episodes of venous disease are indicative of a deeper cause, and further investigations should promptly be done to rule out migratory thrombophlebitis.^3,2,5,17

The common clinical signs of Trousseau's syndrome are:

• Deep vein thrombosis
• Pulmonary embolism
• Venous thromboembolism 
• Recurrent episodes of infarcts

Cancers that are related to migratory thrombophlebitis:

• Lung cancer
• Pancreatic cancer
• Ovarian cancer
• Brain tumours
• Stomach cancer

The main mechanism of blood clot formation

Blood coagulation or clot formation happens chiefly by two mechanisms: 

• The extrinsic pathway 
• The intrinsic pathway

Mechanisms of blood clot or thrombus formation in cancer patients

The tissue factor helps in the clot formation and accelerates the rate of clot formation. The level of this tissue factor increases whenever there is inflammation. Inflammation is present when tumours secrete mucin. The persistent inflammation in the blood causes clot formation at multiple sites.^2,5

Clinical features

A typical case of thrombophlebitis would show some common symptoms of the affected vein itself, and in addition to that, would also exhibit some symptoms of the underlying cause. Trousseau syndrome clinical features would be the same as thrombophlebitis, but more severe and usually as a complication of the malignancy at the final stages. 

Common symptoms include:^2,5,17

• Pain, swelling, induration and redness along the course of the affected vein
• Pitting oedema of the affected limb
• The physician can palpate the thrombus
• There can be itching and pruritus along the length of the vein
• Mobility of the affected limb may be restricted

Investigations

In addition to the physical examination and detailed family and personal history of the patient, further investigations are essential to determine the cause, extent and prognosis of migratory thrombophlebitis. 

These include: ^{18, 17} 

• VenographyPlethysmography: digital, strain gauge or Impedance
• Ultrasonography
• Computed tomography 
• Magnetic resonance imaging
  • Laboratory tests: Complete blood count
  • Hematocrit
  • Clotting tests
  • Clotting factor assays
  • Platelet function assays
  • D-dimer tests:
  • Liver function tests
  • Urinalysis
  • Tumor markers
  • Autoimmune workup

• Chest X-ray
• Mammography 
• Papanicoleau smear in women

Management

The course of treatment for migratory thrombophlebitis and Trousseau syndrome is from three aspects:^8,9

1. Anticoagulation therapy
2. Treatment of the underlying cancer
3. Symptomatic treatment or adjuvant treatment

Anticoagulation therapy

Low molecular weight heparins are the drug of choice for the treatment of trousseau syndrome as compared to warfarin due to their improved presence at the required site, ability to be given in a single dose and also does not cause thrombocytopenia like heparin does

Oral anticoagulants like apixaban, rivaroxaban and fondaparinux are used for the management of migratory thrombophlebitis

Treatment of the underlying cancer

When the underlying cancer has been determined, prompt treatment is recommended to prevent progression. These include.

• Surgery
• Radiotherapy
• Chemotherapy

Symptomatic treatment or adjunct treatment

• Treatment of pain through compression stockings for deep vein thrombosis
• Follow-up screening to determine the extent of the spread of the disease
• Alternate warm and cold compresses
• Non-steroidal anti-inflammatory drugs for pain control
• Periodic follow-ups to assess progress or regression in treatment modalities

Prognosis

Trousseau’s syndrome is the second leading cause of death in cancer patients, after death from the cancer itself. The risk of venous thromboembolism is 4-7 times higher in patients with cancer than in those without cancer. The prognosis of a cancer patient with trousseau syndrome is poor.^{7,12,13,15,19}

Summary

A confirmed diagnosis of migratory thrombophlebitis, especially in cancer patients, is a red flag as it progresses towards Trousseau’s syndrome. The clinician should be aware of this correlation and should undertake diagnostic screening promptly, as this could be a critical window for the diagnosis of occult cancer. Considering that the complications of Trousseau syndrome and migratory thrombophlebitis- DVT, PE and VTE are potentially fatal, physicians should keep their eyes and ears peeled for any symptom pointing towards these.