A Development of Varicose Vein: Today & Tomorrow

The Latin term "Varix," which meaning "twisted," is where the word "varicose" originates. A "vein with a saccular development tortuous," as defined by the World Health Organization (WHO), is a varicose vein. The word "varicosity" refers generically to lengthy, twisted, pouched, thickened, friable, inelastic vessels that have similarly changed over time and are continuously losing their valvular efficiency. ^[7]. Varicose veins are defined as dilated, tortuous, subcutaneous veins ≥3 mm in diameter measured in the upright position with demonstrable reflux. ^[1-3]

Fig 1.1 Varicose Veins forms in a lower extremity.

The superficial and deep venous systems carry venous blood from the lower limbs back to the right heart against gravity. Great saphenous veins (GSV), small saphenous veins (SSV), and their tributaries make up the superficial venous system. ^{[1, 3]}. The medial end of the dorsal venous arch is where the GSV begins. Veins are blood vessels located throughout the body that collect oxygen-poor blood and return it to the heart. Veins are part of the circulatory system.

ig: 1.2 Anatomical view of Varicose Vein

Varicose veins develop when the valves in the veins fail to function properly, leading to a backward flow of blood. These valves normally act like one-way doors, allowing blood to flow towards the heart and preventing it from flowing backward. ^{[4, 5]}. When these valves become weak or damaged, blood pools in the veins, causing them to swell and become visible. This pooling of blood can also put pressure on the surrounding tissues, leading to symptoms such as pain, fatigue, and swelling. ^[6]. The mechanism of valve failure is complex and can be influenced by factors such as age, genetics, and lifestyle. Factors like prolonged standing or sitting, pregnancy, and obesity can further increase pressure in the veins, contributing to valve dysfunction. The weakened valve system ultimately leads to the characteristic appearance of varicose veins. ^[4]. It is due to the various factors such as, Environmental and Patient factors, Genetic Predisposition, Local Hypoxia, Hemodynamic factors, Alteration in the extracellular matrix

1. Changes in the vein wall & over stretching of veins
2. Increases in size of veins but valve leaflets do not expand
3. Secondary valvular Incompetence & Backflow (Reflux)
4. Pooling and further dilation of veins
5. Varicosity – Dilated Tortuous Veins  

Diagnosis and Evaluation

1. Doppler Ultrasound: 

Doppler ultrasound helps with varicose veins detection and identifying severity. It is a special procedure to examine blood circulation.

   Uses:

• A Doppler ultrasound uses sound waves to produce images of blood moving through circulatory system.    
• Peripheral arterial diseases (PAD), narrow or blocked arteries in our legs or arms. 
• Blood clots, including deep vein thrombosis (DVT), Blood clots usually in the legs.
• Chronic venous insufficiency (CVI).
• Tumors in blood vessels.

2. Venography: 

• A venogram (venography) is an X-ray procedure that shows blood flow in the veins.
• Providers typically use this test to look at veins in the: Legs, Pelvis, Upper arms.

Uses:

• Diagnose deep vein thrombosis (DVT) when ultrasound is inconclusive or can’t provide a good enough view (for example, when there’s swelling around an arm or leg).
• Diagnose blood flow problems in the pelvic area, including pelvic congestion syndrome, nutcracker syndrome and varicoceles. ^[22]. 
• Check blood flow in the leg veins before certain surgeries, like varicose vein stripping and ligation.
• Provide real-time imaging during treatments, like thrombolytic therapy and thrombectomy.

Fig. 2.1 Venogram

This test measures blood pressure in the ankles and arms to determine the severity of arterial blockage and rule out other vascular conditions. ^{[2, 3].} 

Uses:

• The ankle-brachial index test is done to check for PAD [Peripheral Arterial Diseases] — narrowed arteries that reduce blood flow, usually in the legs. 
• Risk factors for PAD include:  History of tobacco use, Diabetes, High blood pressure & Cholesterol.

Treatment of Varicose Vein

The conventional treatments for varicose veins involve compression therapies- employment of particular type of surgeries like cryosurgery, vein stripping, ambulatory phlebectomy. ^[4] The Non-surgical treatments mainly involve sclerotherapy and endothermal ablation. ^{[5, 6].} 

1. Physical Therapy ^[6]

2. Compression Therapy ^[6]

Types of compression therapy device includes: 

• Compression stockings ^[2,7]
• Bandages and wraps
• Inflatable devices

1. Surgical Therapy:

A. Vein Stripping: Vein stripping is a surgical procedure that removes or ties off a large vein in the leg to treat varicose veins and other chronic venous diseases ^{[2, 3]}.The side effects are produced by this therapy that are bleeding, infections, bruishing^{[5, 6]}. Stripping of varicose veins out surgically does not permanently remove veins, as most grow back but without valves, during the healing process, causing the same problem to reoccur. ^{[3, 4]}.  

B. Ambulatory Phlebectomy: In this technique by achieving laceration in the skin the superficial veins are removed. After this treatment the temporary inflammation and swelling may be observed ^[5].  

2. Non-Surgical Treatments: The Non-surgical treatments mainly include Sclerotherapy, Ultrasound guided foam sclerotherapy and Endothermal Ablation. ^[3,7].  

A. Sclerotherapy: By using this therapy, the spider veins or angioectasis are treated. For this treatment some sclerosing agents are used like as sodium salicylate, chromated glycerine they are administered by using small needles^.

Fig.2.3 Sclerotherapy- Injecting a solution directly into varicose vein

In most of the cases, varicose veins can be cured by early preventive measures such as,

• Maintaining a Healthy Weight
• Regular Exercise
• Avoid Prolonged Standing or Sitting

Novel Approach of Varicose Vein

Step 1: Direct Injection into varicose veins

Step 2: Damage to the endothelial cells, leading to disruption of cell membrane integrity

Step 3: Triggers an inflammatory response à WBCs and platelets aggregation

Step 4: Fibrinogen is converted to fibrin, forming a blood clot.

Step 5: Due to replacement of fibrotic tissue à Vein wall thickening and contraction

Step 6: Fibrotic tissue contracts, causing the vein to narrow and close à Blood flow is redirected to adjacent veins.

Step 1: Inhibition of Factor Xa

Step 2: Prevention of Prothrombinase Complex Formation

Step 3: Reduction of Thrombin Generation

Step 4: Inhibition of Fibrin Clot Formation

Step 5: Prevention of Blood Coagulation

Mechanism of Action

Step: 1 Inhibition of Factor Xa

Step: 2 Blockage of Prothrombinase Complex

Step: 3 Decreased Thrombin Formation

Step: 4 Prevention of Platelet Activation

Step: 5 Inhibition of Coagulation Cascade

Mechanism of Action

Step 1: Inhibition of P2Y12 Receptor

Step 2: Increased cAMP Levels

Step 3: Reduced Platelet Activation

Step 4: Endothelial Function Enhancement

Step 5: Prostacyclin (PGI2) Increase

Step 6: Reduced Inflammation and Oxidative Stress