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A-PRP CAN FACILITATE WOUND HEALING AND CARE IN CHRONIC DIABETIC AND VARICOSE LOWER LEG AND FOOT ULCERATION.


PRP or autologous platelet-rich plasma, biostimulates chronic wounds and ulcers , improves wound healing, by the release of platelet-derived growth factors such as PDGF, TGF, EGF and VEGF. This cascade activates the healing process and stimulates cells such as keratinocytes and fibroblasts. It does not replace conventional dressings entirely, but is a strong adjuvant to wound healing and care. The pioneer in the field, and more specifically oro-facial surgery, is Professor Robert Marx, of Miami, United States of America. He co-authored an excellent textbook on the use of autologous platelet rich plasma ( A-PRP).

For chronic lower limb ulceration ( ischaemic, diabetic, venous and traumatic) and care, there are more than 55 different types of wound care dressings on the market in South Africa. And new ones appear every month. Some assist wound healing, others do nothing. These may include iodine, honey, antibiotic creams, silver-based to mention but a few. A few commercial products available in South Africa are listed ( Gauze-Swabs®, Gelanet®, L-Mesitran®, Melloderm®, Acticoat®, Betadine®, Granuflex®, Tegaderm®, Granugel®, Iruxol®, Aserbine®, Intrasite®, Aquacel® and Aquacel AG®, Bactroban®, Allevyn®, Opsite®, Actico®, IV3000®, Promogram®, Cultimed Gel®, Apligraft®, Biobrane®, Integra®, Matriderm®, Cultimed Sorbact Gel®, Bio-Oil®, ReCell®, Silvercel®).

ABC…CLINICAL APPROACH TO MANAGEMENT OF CHRONIC WOUND HEALING AND LIMB ULCERATION

  • Make a clinical diagnosis and rule out associated skin diseases by considering a differential diagnosis. Rule out chronic arterial insufficiency due to atherosclerosis, diabetes mellitus, burns, venous ulceration, pressure sores, skin diseases, trauma, steroid-therapy, underlying systemic disorders such as lupus, heart, liver and renal failure, local cancerous growths, malnutrition and a-vitaminosis.

  • Do a comprehensive wound assessment using the WHASA wound assessment form ( see www.whasa.org or peruse Wound Healing Southern Africa 2008 Volume 1 no 1, by Sr. L. Naude, pp 16-24).

  • Check urine to pick up diabetes mellitus or do a blood test. X-rays may be needed to rule out osteomyelitis.

  • Palpate for the presence, absence or attenuation of the two important foot pulses of both feet ( dorsal pedal and posterior tibial). A palpable perforating peroneal pulse usually means up stream arterial occlusion or stenosis and the development of collaterals.

  • Rule out infection by sending a puswab off to the pathologist laboratory. Give appropriate antibiotics to reduce surrounding cellulitis.

  • Absolute foot arterial pressure studies may be indicated as well as the ABI. This will give guidance and prognosticate. Don’t forget to compare with the other leg. Falsely high values may be detected in diabetics. Absolute pressures below 50 mm are a bad sign and healing is going to be prolonged and amputation stumps may not heal. Wound healing sometimes can be affected, but not always. A failed leg bypass operation, due to excessive calcification without reversal of rest pain, usually means an amputation. And the patient should be counselled regarding this issue and that it is the only humane way to relieve the pain. No doctor wants to do an amputation, but sometimes this is the only way out. Some patients suffer after an amputation, but many become rehabilitated on a pylon , lead a fruitful life and still make positive contributions. A good rehabilitation team is needed to achieve maximum rehabilitation, and should include a podiatrist.

  • Critical limb ischaemia must be detected and is characterised by rest pain and tissue loss ( ulceration and gangrene). Rest pain, especially at night, is a bad symptom and means critical ischaemia. It keeps the patient out of sleep, and wears down the patient mentally, who becomes despondent and dejected with time because of the knawing pain. In these cases if the circulation to the lower limb is not restored ( and it is not always possible, because the blood vessels are not reconstructable by a bypass), means that the limb is eventually lost to amputation. This may mean, toe, forefoot, below-knee and often above-knee amputation. Don’t forget that BKA has a wound healing failure rate of 15% at 3-years, and that often means a conversion or re-amputation to AKA ie the stump has to be revised and the BKA converted to a AKA. Rest pain wares out the patient and loss of sleep with the leg hanging over the side of the bed, leads to severe psychological trauma. Usually, only opiates, sleeping pills and hospitalization can temporarily relieve the issue and amputation is usually inevitable or mandatory because of intolerable pain. Amputation is usually the only route, and last resort, especially if the angiogram of the lower limb vessels show that bypass is not possible/feasible and the patient has severe rest pain.

  • Regular dressings initially may be indicated to get rid of excessive secretions and pus discharge. This can take weeks in some cases and debriding agents are effective if correctly applied. The slough and necrotic tissue must be debrided to expose healthy granulation tissue. Sometimes repeated surgical debridement is needed in theatre under general anaesthesia to clean up the necrotic and dead tissue. Then the wound must be kept moist to promote healing ( see WHASA recommendations). Allowing the wound to dry out causes a scab or eschar to form and scarring is worse. In the “old days”, the wound was allowed to dry out and mercurochrome was applied. Condemned to-day by many, it still has a small place in clinical practice, especially in poverty stricken areas where bandages are not available.

Not all dressings promote healing despite their antimicrobial properties. OMNIMED® provide a comprehensive wound care service in South Africa and the head-office in Randburg can be contacted. Recalcitrant wounds can be treated by the biological route, supplemented by standard ulcer care. Some wounds take longer to heal than others and factors such as diabetes, underlying chronic arterial insufficiency, pressure, size, position ( location) , malnutrition play a role. But infection must be brought under control and slough must be debrided ( either surgically or chemically) before the application of REGENLAB® autologous platelet-rich plasma ( A-PRP). Once the burden of infection has been reduced and granulations “ripen”, then A-PRP together with skin-grafting is a good option, provided the underlying circulation status is reasonable. But it does not have to be perfect for wound healing. The process is as follows.

  • Patient is selected for topical REGENLAB® PRP treatment either on an ambulent out-patient basis or in–hospital treatment.

  • Pusswab cultures are important and appropriate antibiotics must be given. Therefore basic principles of wound-care remain in place and must be adhered to.

  • All slough must be removed.

  • Topical A-PRP is applied weekly or twice weekly until the wound is ready for skin grafting. Sometimes the wound closes fast with no need for skin grafting. In most cases topical treatment will be necessary for 6-8 treatments over 8-12 weeks. Sometimes more, in very extensive chronic wounds, and in bedridden patients.

  • 16 ml venous blood is obtained per visit, centrifuged, the A-PRP separated and the platelets are activated with calcium chloride. The alpha granules in the A-PRP are then activated to release the wound healing growth factors PDGF, TGF, EGF. REGEN-LAB® PRP renders the best platelet yield and GF concentration. The PRP GEL is applied topically to the ulcerated surface. To avoid spillage the gel can be placed in hydrocolloid, which keeps it closely applied to the raw ulcer bed. It is advisable to apply a second A-PRP enriched dressing later in the afternoon so that the patient benefits from two applications on the day. Topical application is weekly until the ulcer is healed. In rare cases up to 20 applications may be needed. In the interim days, standard care of dressings is applied to keep the wound moist. Silver tends to cauterise and forms eschars, whilst honey-based dressings facilitate wound healing. In the management of lower limb varicose ulcers, special compression dressings are needed to keep the superficial varicose veins collapsed. In chronic arterial insufficiency, bandages and dressings must not be tight so as to occlude capillary flow in the skin. A tight dressing in this situation can worsen pain and may even precipitate skin gangrene.

  • At all times one should adhere to the classification of TIME and address tissue, infection, moisture and wound edge. More details can be obtained from www.whasa.org or www.woundhealingsa.co.za. Both REGEN-PRP and L-Mesitran are distributed by Omnimed ( PTY), LTD.,Randburg, Gauteng.

  • A-PRP can be used for arterial, venous, traumatic and pressure ulcers. The advantage of this biological treatment is that the patients own plasma is used, that excludes the possibility of anaphylaxis.

TREATMENT GUIDELINES FOR THE MANAGEMENT OF LOWER LEG VARICOSE ULCERATION

  • In the vast majority of cases, ambulant treatment, on an out-patient basis with compression occlusive dressings suffices. Most ulcers heal in about 12 weeks, but some take up to 5 years or 500+ days. Sometimes ulcers persist for 20 years and are incurable even with modern wound care. Recalcitrant lower leg ulceration in octogenarians ( due to mixed arterial and venous disease) is a huge challenge to the wound care team, especially if there is underlying diabetes mellitus. In these cases, the underlying microangiopathy, neuropathy, impaired immunology and autosympathectomy provides for a poor prognosis regarding wound healing. Malnutrition in bedridden obese patients, and low serum albumin makes matters worse. For an overview on management of venous leg ulcers , the reader is referred to an article by Dr G Weir, that appeared in the first edition of Wound Healing Southern Africa. See www.whasa.org and www.woundhealingsa.co.za.

  • Remmember the WHASA WOUND ASSESSMENT FORM: see www.whasa.org.

  • The principles of wound healing based on the TIME CLASSIFICATION are applicable in varicose ulceration.

  • Varicose ulceration is often refractory to treatment.

  • Diabetes and varicose ulceration sited at the medial malleolus pose special challenges especially in the aged with ischaemia and neuropathy.

  • These persons are prone to dressing sensitivity.

  • “ Sustained graduated compression overcomes the effects of venous hypertension”. ( Weir G 2008).

  • Compression dressings or bandages can heal venous ulcers.

  • The most effective level of compression to overcome venous hypertension at the ankle is about 40 mm HG. ( Weir 2008). Iatrogenic pressure ulcers at bony prominences must be avoided due to excess dressings that are too tight.

  • The correct sizing of compression hosiery is also important.

  • Despite getting ulcers healed, the recurrent ulceration rate of venous ulcers is about 31% at 18 months and 26% at 12 months. ( Weir 2008). So, it is common. This is why supportive hosiery after the ulcer is healed, is very important. The reason for the recurrence is that the underlying condition, and deep venous insufficiency, is often not correctable, and the venous hypertension persists.

  • Leg elevation in hospital, enhances healing in venous ulcers, but may reduce healing in patients with co-existing arterial ulcers.

  • Walking exercises are important ( if the patient is able to get out of bed), to improve the circulation in the deep system.

  • Skin grafting of venous ulcers has a place, but means hospitalization, costs and the dangers of recurrence are not reduced. The skin grafts are known to lift-off after a few months, and is frustrating for the surgeon.

  • PRP and hyperbaric oxygen treatment have a small and definitive role to play in venous ulceration.

  • The role of varicose vein surgery in the aged remains problematical, but is indicated for bleeding from a venous ulcer that can be fatal.

Figure 1: A-PRP. Pre-operative before. Chronic venous ulceration of the lower limb showing extensive eschar formation. Permission by Dr W. Kleintjes, plastic surgeon, Louis Leipoldt Hospital, Bellville 2008. Figure 1: A-PRP. Pre-operative before. Chronic venous ulceration of the lower limb showing extensive eschar formation. Permission by Dr W. Kleintjes, plastic surgeon, Louis Leipoldt Hospital, Bellville 2008.
FIGURE 2: A-PRP. Post-operative, after. Skin graft of the ulcerated surface combined with pre and intra-operative treatment with autologous platelet-rich plasma. ( Permission from Dr W Kleintjes, plastic surgeon from Louis Leipoldt Hospital 2008) FIGURE 2: A-PRP. Post-operative, after. Skin graft of the ulcerated surface combined with pre and intra-operative treatment with autologous platelet-rich plasma. ( Permission from Dr W Kleintjes, plastic surgeon from Louis Leipoldt Hospital 2008)
FIGURE 3: A-PRP.Before. Prior to skin grafting the wound bed under went debridement and topical pre-treatment with autologous platelet-rich plasma ( Permission from Dr W. Kleintjes, plastic surgeon, from Louis Leipoldt Hospital, Bellville, 2008). FIGURE 3: A-PRP.Before. Prior to skin grafting the wound bed under went debridement and topical pre-treatment with autologous platelet-rich plasma ( Permission from Dr W. Kleintjes, plastic surgeon, from Louis Leipoldt Hospital, Bellville, 2008).
Figure 4: A-PRP. Rapid healing of recurrent varicose ulcer with platelet-rich plasma. Note vein in close proximity of ulcer. Figure 4: A-PRP. Rapid healing of recurrent varicose ulcer with platelet-rich plasma. Note vein in close proximity of ulcer.
Figure 5: A-PRP. Varicose ulcer closure with PRP. Permission from Dr W. Kleintjes, specialist plastic surgeon, Louis Leipoldt Hospital, Bellville. Figure 5: A-PRP. Varicose ulcer closure with PRP. Permission from Dr W. Kleintjes, specialist plastic surgeon, Louis Leipoldt Hospital, Bellville.

AFRIKAANS: Skakel uit kritiese ledemaat iskemie, wat gekenmerk word deur ulserasie, gangreen en ruspyn. Dit is opvallend as die pasient slaap met die voet oor die kant van die bed. As die spesifieke persoon in ‘n rystoel sit verkleur die voete en laer been donker rooi of pers. Dit word genoem “ dependant rubor” en is ‘n gevorderde teken van chroniese arteriele inkorting. As die reguit bene 45 grade opgelig word, verkleur die voetsole bleek, wat ook sterk aanduiding is van betekenisvolle arteriele inkorting. Meeste van die gevalle gaan gepaard met afwesige voet polse. Arteriele vloeistudies, enkel drukke is belangrik, en in pasiente wat kwalifiseer vir omleiding chirurgie is arteriografie sterk aan te bevel ( RT-MNR van die ledemaat arteries). Bloedvat-omleidings in diabete is nie altyd suksesvol nie, bied tydelike verligting, en baie van die omleidings gaan toe ( stol toe, weens gevorderde diabetiese arteriosklerose) na ‘n paar maande, wat dikwels ‘n amputasie beten sodra die gangreen van die toon, web, sool en voorvoet versprei. In alle gevalle is dit belangrik om ‘n sonaar te verkry van die knie gebied om ‘n politeale aneurisme uit te skakel. In ‘n klein persentasie van pasiente wat nie operasie wil ondergaan nie vir arteriele inkorting, kan arteriele toevoer na die onderbene verbeter word deur die inplaas van ‘n intraluminale, arteriele “stent” of “ veer”. Dit word genoem nie-ingrypende chirurgie en die endovaskulere tegnologie is beskikbaar in die private sektor. Soos met oop chirurgie, in gevorderde gevalle, kan die been sirkulasie nie beredder word en is ‘n amputasie die enigste uitweg, veral met ‘n nie-lewens vatbare ledemaat en dreigende gangreen. Onderskei altyd tussen akute en chroniese arteriele inkorting, sovel as tussen trombose en embolisme. Maak seker dat die pasient nie atrium-fibrillasie onderliggend het ( hartritme akwyking), want die toestand dra by tot serebrale( beroerte), buik ( derm- sirkulasie afsluiting) en ledemaat embolisme ( gangreen). ‘n EKG is sterk aan te bevel. DFDT. Outeur van: Dokter in die Huis ( voorheen, Jan Van Elfin, Tafelberg Uitgewers, Kaapstad 2002).


REFERENCES: WOUND HEALING SOUTHERN AFRICA 2008, VOL1, NO 1. See www.woundhealingsa.co.za or www.whasa.org. Robert Marx’s textbook on platelet rich plasma 2005.


Posted 21 May 2008

 

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