Treatment of leg ulcers with platelet‐derived wound healing factor (pdwhfs) in a patient with beta thalassaemia intermedia

Leg ulcers are a well-recognized complication of beta thalassaemia intermedia, occurring frequently in patients with untreated or poorly controlled disease (Weatherall & Clegg, 1981). Poor tissue repair may be owing, at least in part, to the poor oxygen delivery to the peripheral tissues resulting from the high oxygen affinity of haemoglobin F, which may comprise more than 50% of the total haemoglobin in these patients. Increased knowledge of the biology of wound healing has led to a new understanding of the role of tissue growth factors in tissue repair (Ross et al, 1986; Kunimoto, 1999). Numerous trials of (recombinant) growth factor administration as adjunctive therapy to enhance the rate and quality of acute and chronic wound repair have been reported (Miller, 1999; Rees et al, 1999), but the outcomes have not been consistently reproducible in terms of wound healing. We postulated that a combination of platelet-derived growth factors, also called platelet-derived wound healing factors/formula (PDWHFs), could potentially promote better healing than either one used alone. We used PDWHFs to treat the chronic ulcer of one patient with beta thalassaemia intermedia. It was prepared from a pooled platelet concentrate of a matching blood group. The platelets were aliquoted into sterile single-dose vials under aseptic conditions and then placed in a freezer at a temperature of −25°C. At this temperature, the platelet membrane ruptures, leading to a release of the growth factors contained within the platelet alpha granules. The growth factor preparation was kept frozen until the time of use and thawed at room temperature prior to application. The patient was a 43-year-old woman with beta thalassaemia intermedia (β+IVS2-1A/β+IVS1-6C compound heterozygote) with a history of intractable ankle ulcers lasting nearly 20 years. Her general health was good and she had mild features of beta thalassaemia consistent with her underlying genotype. The patient was not on a regular transfusion programme nor had she been splenectomized. Her average haemoglobin was ≈9·0 g/dl, mean corpuscular volume (MCV) = 65 fl, HbA2 = 5·4% and HbF = 59%. At the onset of therapy, an ulcer was present on the left medial ankle area (Fig 1) that did not appear to be infected. Wound culture was negative. The surrounding skin exhibited blue-purple discoloration with scarring and scaling. There were no clinical signs of vascular disease on her legs with preserved distal pulses bilaterally. Doppler examination of the arteries and veins of her lower limbs and the ankle–brachial index were normal. Wound appearance before (left) and after (right) the treatment. Every evening, the patient applied a sterile gauze swab moistened with the thawed PDWHF, covered this with a paraffin-impregnated dressing (Jelonet) and bandaged the area. On alternate days, a dressing of saline-moistened gauze was applied in the morning. On d 1, baseline assessment of ulcer dimensions as well as wound culture was performed. At each visit, the ulcer area was assessed visually and measured by means of a graph acetate template (Opsite; Flexigrid). The extent of granulation tissue was assessed with a granulometer and swabs for culture were performed. The application of PDWHF resulted in a remarkable change in ulcer appearance. Within a few days, the border exhibited swelling and increasing perfusion. Granulation tissue developed in the ulcer base. No exudate or other signs of infection were observed. The surface area decreased from 10 cm2, measured on d 1 to 7·50 cm2 on d 18 and 3·95 cm2 on d 95. Complete healing was achieved by d 141 (Fig 1). The patient was treated with Ciprofloxacin orally for 14 d 6 weeks after therapy with PDWHF commenced, owing to a superficial wound infection associated with a decreased rate of healing. Three months later the condition remained stable. Further prospective studies on thalassaemic patients with leg ulcers seem justified to elucidate the wound healing potential of PDWHF compared with the recombinant platelet-derived growth factor (rPDGF).