Thrombophlebitis

Thrombophlebitis is the inflammation of a vein due to the presence of a thrombus (blood clot), obstructing the lumen of the vein.

It obstructs the flow of blood, which can present itself clinically as pain, swelling, redness and local or systemic increase in body temperature. 

It can affect the veins that are towards the surface of the skin or the deeper veins. It is called superficial vein thrombosis or deep vein thrombosis, respectively. Deep vein thrombosis can lead to pulmonary embolism, which can pose a significant risk. This makes it imperative to understand the risk factors and underlying conditions that cause thrombophlebitis.

The process of blood clot formation

It starts with an injury to the blood vessel lining. The damaged lining releases tissue factor. In the presence of calcium ions, thromboplastin converts prothrombin to thrombin. Thrombin converts fibrinogen to fibrin. The fibrin aggregates to form a net which houses red blood cells, platelets, and collagen fibres to form a clot. This is a protective mechanism of the body to prevent blood loss whenever there is trauma. But when this process starts within the blood vessels, obstructing the blood flow, it becomes a health hazard.

Risk factors for thrombophlebitis

Patient factors

• Age : 
  • Superficial venous thrombosis usually affects women who are older than 60 years of age and whose body mass index is greater than 25¹
• Obesity: 
  • Obesity is a chronic inflammatory condition wherein the adipocytes secrete larger amounts of inflammatory cytokines, and the impaired fibrinolytic activity predisposes a patient to intravascular thrombus formation. This leads to migration of macrophages to the adipose tissue. This tissue is found more in the visceral areas than the superficial areas of the body. Tumour necrosis factors, interleukin 6, are in turn increased and contribute to maintaining the chronic inflammatory state of the body
• Chronic Inflammation
  • Chronic inflammation causes dysfunction of the inherent anticoagulant pathways of the body, like the tissue factor pathway inhibitor, protein C, etc and increases the possibility of thrombus formation
• Varicose veins
  • Studies show that varicose veins and increased height are contributing factors for deep vein thrombosis²¹
• Previous Deep Vein Thrombosis
  • Patients with previous thromboembolic episodes are more prone to have a repeat occurrence
• Oral contraceptives
  • The use of oestrogen and progesterone creates hypercoagulation states in the body by promoting transcription of genes for multiple coagulation factors.²³ In addition to this, non-aspirin NSAIDs also cause deep vein thrombosis, and the patients who are prescribed these medications should be informed of the side effects of the same.
• Pregnancy /Puerperium
  • Pregnancy is associated with increased coagulability of blood and lessened destruction of fibrin. While this ensures that there is limited blood loss during the delivery, it also carries a greater risk of deep vein thrombosis, which can be potentially life-threatening. Altered platelet function during pregnancy and triggered response to inflammatory mediators like ADP leads to increased platelet aggregation at the injury site. There is venous stasis due to dilation of the veins in response to oestrogen and progesterone. The rate of blood flow is reduced, and the uterus compresses the iliac veins. This completes Virchow's triad. Pertinent measures need to be taken at this time to reduce deep vein thrombosis
• Dehydration
  • Dehydration does not cause thromboembolism and thrombophlebitis by itself, but in compromised patients, it does increase the risk of superficial or deep vein thrombosis.^27,28
• Immobility 
  • Patients who are confined to their beds for prolonged periods, especially after a stroke, heart failure, respiratory failure etc are at an increased risk of deep vein thrombosis.²⁸

Surgical risk factors

The incidence of deep vein thrombosis in patients who have had surgery done recently depends upon the age, the type of surgery done, obesity, underlying risk factors like coagulation defects or comorbidities like myocardial infarction or stroke.

Patients who undergo surgery on the lower extremities, like knee arthroplasty or hip fracture surgery, are at increased risk for deep vein thrombosis.

Underlying medical conditions contributing to thrombophlebitis

• Myocardial infarction or heart failure:
  • Myocardial infarction occurs when one of the coronary arteries is occluded by a thrombus, leading to impaired cardiac muscle function. Atherosclerosis of the arteries is the underlying risk factor wherein the atherosclerotic plaque in the walls of the affected artery, inflammation and unstable nature of the plaque can lead to dislodging of the plaque and formation of the thrombus, which will move further down to occlude an artery
  • The mortality rate is 5% -10% in patients with myocardial infarction. The only alternative to restore the cardiac muscle is to revascularise it as soon as possible. It cannot be revived otherwise
• Inflammatory bowel disease
  • It includes Crohn's disease, ulcerative colitis, etc
  • Virchow's triad is present during inflammatory bowel disease, too. The coagulation irregularities seen in Inflammatory Bowel Disease are:
    • Elevated levels of coagulation factors- V, VIII, Von Willebrand and fibrinogen
    • Products of fibrin and thrombin production
    • Increased markers of vascular endothelial activation
    • Dysfunction and deficiencies of natural anticoagulants
    • Defects in fibrinolytic pathways
    • Elevated levels of platelets
    • Decreased levels of anti-inflammatory bacteria like Faecalibacterium prausnitzii. An altered microbiome in the intestine leads to improper digestion of food, which further increases the inflammation³⁵
• Malignancy:
  • Thrombosis during chemotherapy and due to malignancy is due to mucin-producing carcinomas. These mucins are secreted in the blood after defective glycosylation. The liver gets rid of almost all these mucins, but some are resistant. These act on the L-selection adhesion molecules on leukocytes and P-selectin adhesion molecules on platelets and endothelial cells, producing microthrombi. Cancer cells secrete abnormally high tissue factor( which is highly procoagulant) and also induce monocytes and macrophages to release tissue factor. The Tissue Factor converts factor VII to VIIa. Cysteine proteinase (also a form of cancer procoagulant) induces the conversion of factor X to Xa. This leads to coagulation
• Nephrotic syndrome
  • Nephrotic syndrome is defined by the presence of nephrotic proteinuria, peripheral edema, hypoalbuminemia, hyperlipidemia and venous thrombo-embolic complications.³⁷ There is damage to the glomerular membrane, which increases its permeability to proteins like antithrombin III, plasminogen, protein C, and protein S, which increases coagulability. Also, the loss of albumin makes the liver secrete more fibrinogen, which increases the possibility of thrombus formation
• Pneumonia
  • Pneumonia is caused by mycoplasma pneumoniae. It causes thrombosis after about 3 days to 3 weeks of infection. The mechanism of action also seems to be hypercoagulability and vascular injury. M. pneumoniae harbors itself in the atherosclerotic plaques and travels with the dismembered clot from the blood vessel wall. Patients with familial thrombophilia are more at risk of developing a thrombus due to increased homocysteine level and decreased folic acid levels. The infection also increases the factors of the intrinsic pathway, increases cold agglutinins and increases levels of protein C and protein S.
• Other hematologic disorders
  • Deficiencies of the following factors can cause thrombosis:
    • Antithrombin deficiency
    • Protein C and S deficiency
    • Factor V Leiden
    • Prothrombin G20210A
    • Antiphospholipid antibody syndrome

Conclusion

Thrombophlebitis is a condition occurring due to multiple risk factors, which may or may not be modified. The lifestyle choices, medications and preventive measures can help in controlling the disease a bit. Healthcare personnel should keep a constant lookout for these symptoms so that a major medical emergency can be averted.