top of page
  • Writer's pictureCork Medical

Factors That Delay Wound Healing in Venous Leg Ulcers

Article originally featured on WoundSource


Approximately 2.5 million Americans are diagnosed with chronic venous insufficiency, and approximately 20% will go on to develop venous leg ulcerations.1 Chronic venous leg ulcers (VLUs) account for 90% of all chronic ulcers of the lower limb region.2 Wound chronicity takes place in wounds that are stalled and/or remain unhealed after four to six weeks. Although evidence-based care has been established, it has been reported that 30% of patients still experience delayed healing, with wounds often failing to heal within a 24-week time frame. Identifying risk factors for VLUs is imperative in best outcomes.3

What Are Venous Lug Ulcers?

VLUs, sometimes referred to as stasis ulcers, are primarily caused by poor blood flow in the leg veins normally located along the medial or lateral distal lower limbs. Veins that become impaired or malfunctioned cause increased pressure in these blood vessels, a condition called venous hypertension. Increased pressure causes the vein walls to stretch, and this stretching then allows proteins in the blood and cell to saturate the subcutaneous tissues, thus resulting in edema. Venous hypertension causes the blood to pool when it cannot move back toward the heart. This condition is called venous insufficiency.4

Evidence-based treatment for VLUs may consist of a variety of treatment options, including compression therapy, advanced wound care dressings, medications (pentoxifylline, statins, etc.), endovenous interventions, debridement, and advanced wound care therapies (cellular and/or tissue-based products [CTPs], skin grafting, etc.).

Venous Leg Ulcer Complicating Factors


Managing VLUs can be extra challenging in the presence of heavy, malodorous exudate. The patient becomes uncomfortable because of the smell of exudate and frequent dressing changes. Exudate management can be better achieved using absorbent dressing technologies that prevent exudate leakage and extend dressing wear time. Dressings that are water resistant and lock exudate inside the dressing will reduce dressing changes and decrease the risk of breakdown of the periwound and surrounding skin.5


VLU infection can be caused by a variety of sources, including bacterial, viral, fungal, and protozoal bacteria. Clinical presentation of infection in VLUs may include fever, increased exudate, increased pain, cellulitis, necrosis, and purulent exudate with or without odor. VLUs that are critically colonized with bacteria or biofilm may be treated with a variety of approaches such as the use of topical antibiotics.6

Chronic Inflammation and Cellular Abnormalities

Complex wounds are characterized by a multitude of factors that impede healing, including biofilm, excess matrix metalloproteinases and extracellular matrix degradation, inflammation, fibrosis, unresponsive keratinocytes and fibroblasts, and atypical growth factor signaling. CTPs play an important role in treatment of full-thickness wounds of various etiologies.7,8

Molecular and cellular abnormalities in VLUs lock in chronic inflammation. Venous hypertension causes disrupted microcirculation and pathological changes of the capillaries. Proinflammatory cytokines and proteases prevent the healing progress as a result of their non-stop elevated levels and activities. The longer the duration of the VLU, the less responsive fibroblasts, senescence, and growth factors become. Growth factors show an unfavorable distribution, proteolytic enzyme imbalances, and endogenous inhibitors in chronic VLUs.6

Extensive and chronic inflammation plays a major role in suspending the normal healing process. The goal in most chronic wounds is to move inflammatory characteristics from chronic to acute, allowing the healing process to continue. In VLUs, the underlying pathogenesis creates prolonged inflammation that is related to critical microbial colonization and early localized infection.9 Treating VLUs in this prolonged inflammatory state may include a variety of therapies such as biologics, extracellular matrices, non-biological products, growth factors, silver dressings, matrix metalloproteinase inhibitors, modulators of reactive oxygen or nitrogen, immune response, and tissue metabolites. Compression therapy and venotonics can also be used to reduce the risk of chronic venous insufficiency progression.10

Bioengineered CTPs comprise a type of skin replacement technology used in wounds of various etiologies, including diabetic foot ulcers, VLUs, pressure injuries, and acute burns. CTPs are designed to help hard-to-heal wounds by providing support and stimulating the wound healing process by mirroring the extracellular matrix.7,8

Comorbid Factors

Uncontrolled comorbid factors increase the risk of developing VLUs. These comorbid factors may include obesity, previous deep vein thrombosis, varicose veins, previous surgery (hip or knee replacement), decreased mobility, and increased age.2

Diabetes, peripheral arterial disease (PAD), peripheral venous disease, and peripheral neuropathy impact vital tissues and nerves negatively secondary to a compromised blood supply. Therefore, tissue begins to break down and ulcerate. Diabetes is known to increase the risk of PAD, whereas PAD in persons with diabetes often is known to result in the development of a foot or toe ulceration.11 Given the aging population, the prevalence of diabetic foot ulcers and VLUs is increasing.7

Patient Education

Educating patients can be very challenging for health care professionals. Clinicians should evaluate and identity the learning style that is best for each patient because this knowledge can be most beneficial in ensuring the effectiveness of learning. In patients with conditions that create a gap in knowledge, encourage a family member or caregiver to be present during education. Utilizing various methods of education to increase adherence should be at the forefront of VLU treatment and management. Involving patients in their care is shown to optimize healing outcomes.

Patients’ adherence to treatment is imperative in managing VLUs. Non-adherence is often is the reason for failure in treatment. One report found that 63% of patients did not adhere to prescribed regulations of graded-elastic compression therapy after a period of time.12 Non-adherence can worsen venous disease and exacerbate secondary edema, lead to recurrence of healed VLUs, and cause new venous ulcerations. Non-adherence to compression can be caused by a multitude of factors, including gaps in knowledge, sociopsychological and socioeconomic factors, side effects (burning, itching, pain), and lack of motivation.13


Health care professionals should have practical knowledge of prognostic indicators and risk factors associated with hard-to-heal VLUs. There are various causes of stalled healing in wound chronicity. It is paramount to treat underlying conditions, as well as to perform regular monitoring and re-evaluation throughout the healing trajectory. Although there is a high risk of new-onset VLUs or recurrence, clinicians providing education to their patients in prevention and management will help overall outcomes. Therefore, early identification and proper diagnosis and management are key in wound healing outcomes.



  1. DiMuzio P. Venous ulceration: a minimally invasive treatment of a big problem. Society for Vascular Surgery; 2017. Accessed August 9, 2021.

  2. NHS Inform. Venous leg ulcer. National Health Service (Scotland); updated July 2019. Accessed August 9, 2021.

  3. Parker CN, Finlayson KJ, Shuter P, Edwards HE. Risk factors for delayed healing in venous leg ulcers: a review of the literature. Int J Clin Pract. 2015;69(9):967-977. doi: 10.1111/ijcp.12635 PMID: 25831965

  4. Cleveland Clinic. Leg and foot ulcers. Cleveland Clinic. Accessed August 9, 2021.

  5. Rai R, Dogra S. Venous leg ulcer: topical treatment, dressings and surgical debridement. Indian Dermatol Online J. 2014;5(3):371. doi:10.4103/2229-5178.137820

  6. Agren MS, Eaglstein WH, Ferguson MW, et al.. Causes and effects of the chronic inflammation in venous leg ulcers. Acta Derm Venereol Suppl (Stockh). 2000;210:3-17.

  7. Hayes, Inc. Skin Substitutes for Chronic Foot Ulcers in Adults With Diabetes Mellitus: A Review of Reviews. Lansdale, PA; Hayes, Inc Directory Publication; 2017.

  8. Liu Y, Panayi AC, Bayer LR, Orgill DP. Current available cellular and tissue-based products for treatment of skin defects. Adv Skin Wound Care. 2019;32(1):19-25. doi: 10.1097/01.ASW.0000547412.54135.b7

  9. Davies CE, Hill KE, Newcombe RG, et al. A prospective study of the microbiology of chronic venous leg ulcers to reevaluate the clinical predictive value of tissue biopsies and swabs. Wound Repair Regen. 2007;15(1):17–22.

  10. Raffetto JD, Ligi D, Maniscalco R, Khalil RA, Mannello F. Why venous leg ulcers have difficulty healing: overview on pathophysiology, clinical consequences, and treatment. J Clin Med. 2020;10(1):29. doi:10.3390/jcm10010029

  11. American Endovascular & Amputation Prevention. What is peripheral arterial disease and why does it affect so many patients with diabetes? Accessed August 9, 2021.

  12. Raju S, Hollis K, Neglen P. Use of compression stockings in chronic venous disease: patient compliance and efficacy. Ann Vasc Surg. 2007;21(6):790-795.

  13. Gong JM, Du JS, Han DM, Wang XY, Qi SL. Reasons for patient non-compliance with compression stockings as a treatment for varicose veins in the lower limbs: a qualitative study. PLoS One. 2020;15(4):e0231218. doi:10.1371/journal.pone.0231218


bottom of page