Critical Reviews: How we treat sickle cell patients with leg ulcers

Abstract

The past five decades have seen an improvement in the mortality and morbidity of sickle cell disease (SCD) because of prophylaxis against infectious complications, improved and expanded red cell transfusions, implementation of hydroxyurea therapy, and advances in supportive care. Now that the majority of patients in the western hemisphere reaches adulthood, end organ diseases are frequent, which include vasculopathic complications such as chronic leg ulcers. The management of patients with leg ulcers requires the hematologist to lead a team of health care professionals, and investigates the presence of associated, but potentially still occult signs of vasculopathy, such as pulmonary hypertension, renal disease, priapism and retinopathy. These complications may be asynchronous, and long term careful screening is indicated, in order to ensure early diagnosis and intervention. It is crucial to address both the immediate consequences of pain, infection and disability, and long term effects on quality of life, employment and stigma associated with chronic ulceration. Recent insights into their pathophysiology may have practical implications. We propose a holistic approach to the management of patients' physical and emotional problems and mechanisms of ulcers formation and delayed healing. An overview of topical and systemic therapies for chronic ulcers is given, with the understanding that wound care therapy is best left to the wound specialists, medical and surgical, with whom the hematologist must keep an open line of communication. In the absence of evidence-based guidelines, our opinion is based on both a critical review of the literature and our personal clinical and research experience. Am. J. Hematol. 91:22-30, 2016. V C 2015 Wiley Periodicals, Inc. Clinical CasesCase 1. A 49 year old African American woman with sickle cell anemia, bilateral hip replacements for avascular necrosis of the femoral head, pulmonary arterial hypertension documented by pulmonary artery catheterization, and history of laser treatment and vitrectomy for proliferative retinopathy and vitreous hemorrhage, presented with a very painful ulcer at the right malleolus. She has had three previous ulcers, on both legs, the first at age 32 years, attributed to excessive standing at her job, no trauma, which had responded to topical care and healed within few months of presentation. At that time she was not taking hydroxyurea, but has been taking it now for longer than 10 years with good fetal hemoglobin response: 17%. This current ulcer developed while she was experiencing high personal stress but no physical trauma. She rarely experiences vaso-occlusive pain crisis and has very infrequent hospitalizations. She was referred to the wound care service and after 7 months of unfruitful therapies, including surgical debridement, MIST ultrasound therapy, antibiotics, and compressions, she was started on monthly transfusions and her ulcer healed 5 months later. She has had consistently elevated serum lactate dehydrogenase (LDH) (>600 IU/L), serum dire...

Factors predictive of leg-ulcer healing in sickle cell disease: a multicentre, prospective cohort study

“…The benefit of repeated blood transfusions to increase the haemoglobin level above 8 g dL −1 to promote the healing process is not supported by the results of prospective studies . Venous compression therapy and standard local wound care, including modern dressings and sharp debridement, are used to treat SCD‐LUs, by analogy with venous LU treatment protocols, but without any strong evidence . Thus, it is important to stimulate SCD‐LU healing to a level that is not presently possible with standard care.…”

“…The pathophysiology of SCD‐LUs is poorly understood, including haemolysis‐induced decreased nitric oxide availability, endothelial dysfunction, venous insufficiency and genetic factors . LUs occur almost exclusively in adults, and are associated with elevated haemolytic parameters, increased percentage of dense dehydrated red blood cells and a clinical pattern of organ damage, including pulmonary hypertension, renal dysfunction and priapism . SCD‐LUs are responsible for disabilities and heavy social burden, related to their chronic course, high risk of recurrence and intense chronic pain, with repeated loss of time at work …”

Sickle cell disease: a natural model of acute and chronic pain

“…[40] The mean age of death for patients with HbSS disease is 38 for males and 42 for females (55 years for all SCD genotypes). [31].…”

Autologous stem cell‐based therapy for sickle cell leg ulcer: a pilot study

“…SCLUs affect quality of life, work productivity and overall morbidity in SCD patients (Serjeant et al , ; Sebastiani et al , ). The prevalence of SCLU is variable among SCD patients, depending on the origin of the cohort, with an estimate of 29·5% in Jamaica, and 9–22% in North America (Minniti & Kato, ). In Brazil, SCLUs prevalence ranges from 23·4–50% of adult patients and is considered a marker of SCD severity (Belini Junior et al , ).…”