DOES HUMAN RECOMBINANT ERYTHROPOIETIN IMPROVE WOUND HEALING? (1995)

To the Editor: An 81-year-old male on hemodialysis for end stage renal disease was admitted to the nursing home after undergoing removal of an infected loop graft fistula of the left forearm. He required assistance with his activities of daily living (ADL) and care of his surgical wounds, which were left open and treated only with wet to dry normal saline dressings. His other medical problems included chronic obstructive pulmonary disease, peptic ulcer disease, hypertension, osteoarthritis, and atrial fibrillation. On admission to the nursing home, his medications were famotidine, aspirin, digoxin, a phosphate binder, a multivitamin, and human recombinant erythropoietin, 8000 units three times a week. Significant laboratory results consisted of an albumin of 2.6 mg/dL, total protein of 5.6 mg/dL, hemoglobin of 10.1 g/dL, hematocrit of 31.2%, BUN of 48 mg/dL, creatinine of 8.3 mg/dL, and a potassium of 4.0 mEq/L. The patient had two surgical wounds on admission to the nursing home. One was 15 cm long by 3 cm wide by 1 cm deep to the muscular fascia on the volar aspect of the left forearm. The second wound was described as a 3-cm diameter “stage III” wound of the left antecubital fossa. As stated, these wounds were not closed after surgery and were treated with normal saline wet to dry dressings. All measurements were performed by the same nurse. The healing of the wounds in this frail, older gentleman with multiple medical conditions, impaired ADL's and poor nutritional status seemed rather dramatic to the nursing home staff. The nursing staff and I wondered if the erythropoietin had any role in the healing process inasmuch as this rapid a resolution of similar wounds had not been observed previously with normal saline wet to dry dressings. Human recombinant erythropoietin is a 165 amino acid glycoprotein that stimulates the division and differentiation of committed erythroid progenitors in the bone marrow.1 Erythropoietin's mechanism of action at a molecular level is through activation of globin gene transcription and enhancement of the enzymatic activities for hemoglobin synthesis.1 Erythropoietin is approved for use in chronic renal failure, zidovudine-treated HIV patients, and cancer patients on chemotherapy for nonmyeloid malignancies. Recent publications have reported its use for the anemia of myelodysplastic syndrome.2 A Medline literature search did not revel any publications on erythropoietins use in wound healing or in association with accelerated wound healing. Reported side effects of erythropoietin are hypertension, seizures, polycythemia and thrombotic events. The recommended dose for the above indications is 50–300 units/kg three times a week. A great deal of interest has arisen in the use of growth factors in the treatment of chronic wounds, particularly chronic pressure ulcers.3 Basic fibroblast growth factor (BFGF), platelet-derived growth factor (PDGF), and transforming growth factor beta 1 have been reported to improve wound healing. Although erythropoietin is a hematopoietic mitogen and survival factor, could it also have a role as a growth factor in promoting epithelialization and fibroblast proliferation and, thus, have accounted for the rapid healing of this patient's surgical wounds? A potential use of erythropoietin would be for stage III and IV, full thickness, pressure ulcers. Pressure ulcers are present in 11% of patients admitted to nursing homes and develop in 22% of nursing home residents within 2 years.4 The cost of treating chronic pressure ulcers is staggering, averaging $27,000 per patient in 1984.5 The human cost is even greater, with the presence of a pressure ulcer conferring a fourfold increase in mortality.4 The cost of the above patient's erythropoietin was $267 per week. Although normal saline wet to dry dressings are inexpensive, they are labor intensive. If short-term administration of erythropoietin can hasten the healing of full thickness wounds with minimal side effects, its use in chronic wounds may be justified and cost effective. It must be stressed that this case report is a single observation. A pilot study and, if warranted, a randomized, controlled trial would certainly be necessary before any definitive conclusions could be made about the use of erythropoietin in wound healing. Regardless of the possible association with erythropoietin, the healing of this patient's wounds were much more rapid than expected.