Blood Viscosity and the Expression of Inflammatory and Adhesion Markers in Homozygous Sickle Cell Disease Subjects with Chronic Leg Ulcers

Bowers, Andre; Reid, H. L.; Greenidge, Andre; Landis, Clive; Reid, Marvin

doi:10.1371/journal.pone.0068929

Cited by 39 publications

(44 citation statements)

References 53 publications

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“…Elevated levels of fetal hemoglobin are generally protective [9,29,41], although this has not been true in all studies [33,42]. SCD ulcer patients have higher levels of soluble ICAM-1 and the key inflammatory cytokine IL-1beta [43]. We have found that the active ulcer and peri-ulcer area have higher blood flow than distant, non-ulcerated areas of the leg, are characterized histopathologically by venostasis, inflammation, and vasculopathy, with activated endothelium and evidence of thrombosis/recanalization (Figs.…”

Section: Pathophysiologymentioning

confidence: 99%

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

Minniti

Kato

2015

American J Hematol

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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...

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Section: Pathophysiologymentioning

confidence: 99%

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

Minniti

Kato

2015

American J Hematol

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“…2,7 Etiologic factors include the sickling of red blood cells in blood vessels, causing vaso-occlusion and impairing oxygen delivery to tissues; as well as the binding of hemolysis-freed hemoglobin to nitric oxide, deactivating it and subsequently resulting in vasoconstriction. 1,8,11 Blood viscosity and inflammatory factors are also being studied to determine whether these are increased in patients manifesting chronic leg ulcers and whether they have an impact on the development of ulcer. Recent evidence also indicates that there is an element of venous incompetence in sickle cell patients.…”

Section: Pathophysiologymentioning

confidence: 99%

“…Recent evidence also indicates that there is an element of venous incompetence in sickle cell patients. 1,2,8 All the earlier mechanisms can either occur spontaneously in a patient with SCD, or alternatively be caused by trauma, which may start a cascade of the aforementioned mechanisms, leading to ulcer formation.…”

Section: Pathophysiologymentioning

confidence: 99%

“…2,7 Prominent locations are the malleoli, with the medial malleolus being more frequently affected than the lateral. 2,4,7,8 Hallmark features of sickle cell leg ulcers are their indolent clinical courses and high recurrence rates despite appropriate therapy, 2,9 with some studies quoting the recurrence at 80%-97% 2 years after wound closure, 2,3 thereby making this a prominent problem and a cause of morbidity, decreased functionality, and low quality of life. 10 These features makes chronic wound care an important adjunct in sickle cell patient care.…”

Section: Introductionmentioning

confidence: 99%

“…Many physicians also use compression therapy; and although evidence is scarce, it may be of use in modifying the role venous congestion plays in leg ulcer pathophysiology. 1,2,8 The use of a triple antibiotic cream has been advocated for the treatment of ulcers in patients with SCD after a prospective trial showed a statistically significant decrease in ulcer size. 19 The study population, however, had only 15 patients.…”

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confidence: 99%

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Leg ulcers in sickle cell patients: management challenges

Khatib¹,

Hayek²

2016

CWCMR

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Sickle cell disease is an autosomal recessive hemoglobinopathy caused by an amino acid substitution from glutamic acid to valine in the beta hemoglobin chain. One of the common symptoms occurring in sickle cell patients are leg ulcers, which are notoriously painful, difficult to treat, and frequently recurrent. These ulcers pose a therapeutic challenge with multiple modalities proposed for treatment, but with scarce evidence of efficacy of any single modality. Ulcer prevention, rigorous wound care, pain control, and surgery are the current mainstays of sickle cell leg ulcer treatment.

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