PRP and Chronic Venous Insufficiency

Chronic Venous Insufficiency is a significant public health problem not only in the United States but world -wide. It is estimated that 2-5% of all Americans have changes in their legs associated with chronic venous insufficiency. Published estimates of the prevalence of varicosities range from 6-60% of the adult population with most studies demonstrating clinical disease in 40% of the population. Venous insufficiency is the major cause of venous ulcers. These stasis ulcers affect approximately 500,000 people. 92 out of 100,000 hospital admissions is due to venous disease.

In most cases the cause of the ulcers is chronic venous insufficiency. Each year approximately 150,000 new patients are diagnosed with CVI and nearly $500 million is used in the care of these new patients alone.

Chronic leg ulcer is a chronic wound of the lower leg that shows no tendency to heal after 3 months of appropriate treatment.

Etiology of leg ulceration

• Venous ulcers most commonly occur above the medial or lateral malleoli
• Arterial ulcers often affect the toes, shin or pressure points
• Neuropathic ulcers tend to occur on the sole of the foot or over pressure points

Patients with reduced mobility or obesity may develop ulceration because of venous hypertension resulting from inadequate functioning of the calf muscle pump.

Other causes

Microcirculatory and vascular disorders such as Raynaud’s can lead to ulceration.

Vasculitis ulcers such as rheumatoid arthritis, systemic lupus, and polyarteritis nodosa.

Blood dyscrasias such as sickle cell disease, thalassemia and thrombocythemia.

Hematologic disorders that lead to microcirculatory disorders such as leukemia, thrombotic thrombocytopenic purpura, granulocytopenia and polyclonal dysproteinemia.

Since 80% or more of these chronic wounds of the lower limbs are due to venous disease, this article will focus on that etiology.

Venous circulation of the lower extremities progresses from the superficial to the perforating to the deep vessels. There are valves in each section to ensure unidirectional flow of blood. As the calf muscles contract, the pumping action causes the blood flow from these veins into the inferior vena cava. Any disease in these pathways leads to venous insufficiency.

Of the approximately 7 million people in the United States with venous insufficiency, approximately 1 million will develop legs ulcers.

Primary Risk Factors for Ulcers

• Prevalence increases with age
• Obesity
• Smoking
• Women greater than men
• Diabetes
• Hypertension
• Previous traumatic injuries
• History of deep vein thrombosis or phlebitis

Mechanism of Development of Ulcers

In venous disease the ulcers are normally located between the ankle and calf. Venous ulcers arise from venous valve incompetence. Valvular incompetence in the deep veins cause the vessels to become distended and then stretching occurs to accommodate the increased volume of blood. The valve cannot close which causes a retrograde blood flow and venous hypertension. The venous hypertension causes the leakage of blood into the surrounding tissues causing the brownish pigment in these areas. These areas are easily damaged, predisposing to ulceration.

Management of Leg Ulcers

History of the etiology is paramount. Is this a venous ulcer, arterial ulcer or diabetic ulcer? Is this a pressure ulcer? Management should be started immediately.

Pressure ulcers are normally seen in the geriatric population approximately 70%. They usually are over bony prominences such as the hip, sacrum and heel. Prevention of pressure damage to the skin and underlying tissue is the essential part of these patients.

Diabetes should be tightly controlled.  Ulcers affect 15% of all diabetic individuals during their lifetime. 18% of diabetic patients over the age of 65 have chronic ulceration.

Arterial leg disease occur as a result of diminished arterial blood flow to an area. Arterial or arteriolar occlusion due to any cause can result in tissue ischemia and ulceration. Treatment is directed toward restoration of blood flow to the area.

Examination

Examination should include palpation of the pulses and a search for signs of venous hypertension that include varicose veins, hemosiderin pigmentation, varicose eczema and atrophic blanching.

Pictures should ALWAYS be taken and saved in the patient record

Ulcer exam should include site, size, appearance, wound base, exudates, surrounding tissues and odor.

The surrounding tissues should be examined for pain, edema, erythema, warmth, discoloration, dryness, hair growth, clubbing of digits, scarring from previous disease and capillary refill.

Venous ulcers are considerably different from arterial ulcers.

Both types of ulcers and etiologies can co-exist in the same patient

Testing

Arterial and venous ultrasound to obtain accurate hemodynamic information on the site.

When indicated MRI, CT or angiography to obtain further detailed information.

Blood count and analysis including chemical profile and clotting.

Plain x-rays of the area to rule of bony infection.

Wound culture if infected and treatment with antibiotics on if quantitative cultures are greater than 10 to the 5^th organisms.

Treatment

• Cleaning and dressing the ulcer- remove any dead tissue and apply appropriate dressing.
• Dressing can be changed weekly.
• Compression is used to improve overall vein circulation
• Bandage or elastic stockings
• Not to be used or monitored closely in situation with coexisting arterial disease
• Elevate the leg when possible

Infection when severe needs treatment with appropriate antibiotics

Debridement

• Autolytic
• Biological
• Enzymatic
• Surgical Mechanical

Can be done with sharp instruments or live maggots, special dressings or ointments that soften tissue and mechanical forces when the dressings are removed. In most cases natural enzymes will dissolve and phagocytize necrotic tissue. This is called Autolytic Debridement. The majority of newer wound dressings, such as the hydrogels, hydrocolloids and hydrofibres debride by the process of autolysis.

Types of Dressings

• Thin Films
• Honey
• Hydrocolloids
• Alginates
• Hydrogels
• Hydrocolloids

A hydrogel is a hydrophilic polymer that does not dissolve in water. They are highly absorbent. They have many applications in the biomedical field. Many hydrogels are synthetic but some are derived from nature.

Natural polymers

• Hyaluronic acid
• Chitosan
• Heparin
• Alginate
• Fibrin

Synthetic polymers

• Polyvinyl alcohol
• Polyethylene glycol
• Sodium polyacrylate
• Acrylate polymers

Chemical hydrogels have irreversible gels due to their covalent bonding and they may possess harmful properties which makes them unfavorable for medical applications.

Therefore, natural hydrogels are used in medical applications. Hydrogels are beneficial in treating pressure ulcers because when used as a wound dressing, the hydrogel not only forms a physical barrier and removes excess exudate but also provides a moisture environment that promotes the wound healing process. They promote the removal of infected or necrotic tissue via autolysis.

The mechanical properties of hydrogels can be fine tuned in many ways with attention to their properties. Other biologics can be added and then the hydrogel matrix can be polymerized in a layer- by- layer fashion.

In this method, photoinitiators, compounds that cleave from the absorbtion of photons, are added to the solution which will become the hydrogel. When the precursor solution is exposed to a concentrated source of light, the photoinitiators will cleave and form free radicals which will begin a polymerization reaction that forms crosslinks between the polymer strands. This reaction will cease if the light source is removed allowing the amount of crosslinks formed in the hydrogel to be controlled. The properties of a hydrogel are highly dependent on the type and quality of its crosslinks, making photopolymerization a popular choice for fine tuning hydrogels. This technique has seen considerable use in cell and tissue engineering applications due to the ability to inject or mold a precursor solution loaded with cells into a wound site and solidify it in situ.

Platelet Rich Plasma and Platelet Rich Fibrin has been studied extensively in the field of wound care and management. There are many studies published with proven results of lower infection rates, less scar formation and augmented healing as apposed to normal would treatment protocols.

Both Platelet Rich Plasma and Platelet Rich Fibrin are autologous and support the three phases of wound healing:

• Inflammatory Phase
• Proliferative Phase
• Remodeling Phase

Platelet Rich Plasma stimulates the “clastic activity” phase. Where tissue is debrided by an autologous process mediated the leukocytes in the environment. This is a hyper- inflammatory response stimulated by pro-inflammatory cytokines, triggering apoptosis of abnormal tissue. The PRP stimulates the activity of the macrophages and releases cytokines IL-1b, IL-6 and TNF-alpha (all known for their inflammatory stimulation)

This phase is ideal for the inception of the wound healing process. However, the limitation is its liquid state. However, if added to the natural hydrogel, hyaluronic acid, then photobiomodulated to start a polymerization, the non-cross linked HA would then become cross linked and the PRP would benefit from a prolonged relationship on the wound site.

Platelet Rich Fibrin stimulates a “blastic activity” phase. Where tissue is remodeled and regenerated. This is a hyper anti-inflammatory response stimulated by a completely different set of cytokines from the platelet Rich Plasma. IL-1 receptor antagonist, IL-4, IL-10, Il-11, Il-13 reduce swelling and pain in the wound area while promoting growth of new tissue. It also recruits the patient’s own stem cells.  Again, this process can be augmented and solidified for a prolonged duration at the wound site with the addition of the hyaluronic acid hydrogel that is polymerized by the photobiomodulation process.

Since wound dressing changes are usually accomplished once a week, the initial application in week one should be the PRP application and depending on the amount of dead tissue could be continued weekly where clinically indicated.

Dressing could be adaptic over the area  and occlusive pressure dressing or compression garment

CAUTION IF THERE IS ARTERIAL DISEASE AS COMPRESSION MAY WORSEN THIS CONDITION

Once debridement is relatively complete, the process should be continued weekly with the application of Platelet Rich Fibrin until healing is complete.

Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our Platelet Rich Plasma Kits are FDA approved and designed for safety and effectiveness. They are cost effective and very easy to use. Our kits provide consistency of concentrated product when obtained from the same source.

Juventix Regenerative Medical offers a patent pending LED Photo- Activator to activate the platelets and begin the regenerative process. The activation, a critical step in the release of cytokines and growth factors, is accomplished with light and not with the addition of other chemicals such as Calcium Chloride or Thrombin.

Juventix Regenerative Medical supplies a Bio-Incubator that transforms the Platelet Rich Plasma into an Injectable Platelet Rich Fibrin. The PRF, commonly called the “second generation of platelet products, has a broader range of clinical applications while providing outstanding outcomes.

Juventix Regenerative Medical is proud to announce the addition of a Photobiomodulator System. The “Domed “configuration of this system allows easy application over the wound care sites. The process not only augments healing but starts the polymerization process transitioning the hydrogel hyaluronic acid to a stronger more dense covering over the wound area. Therefore, the cytokines, growth factors, bio-active proteins and leukocytes have a prolonged time in association with the wound site which will keep the area moist, fight infection while the healing occurs.

Juventix Regenerative Medical has met the challenge of wound care and offers our solutions to the health care professional to provide solutions to the rapidly expending medical condition.

 

RESTORE, REVIVE, REGENERATE- JUVENTIX REGENERATIVE MEDICAL

 

Regenerative Regards,

 

Dr. Robert McGrath

 

Studies

• Recent Advances in Photocrosslinkable Hydrogels for Biomedical Applications

Bio Techniques 66(1): 40-53  PMID 30730212

• Biomedical Applications of Hydrogels: A Review of Patents and Commercial Products

European Polymer Journal 65:252-267  doi:10.1016/jeurpolymj .2014.11.024

• Bioinspired mechanically Active Adhesive Dressings to Accelerate Wound Closure

Science Advances 2019 Jul 24. 5(7): eaaw3963  PMID 31355332