Vasculopathy, inflammation, and blood flow in leg ulcers of patients with sickle cell anemia

Minniti, Caterina P.; Delaney, Kara; Gorbach, Alexander M.; Xu, Dihua; Lee, Chyi‐Chia Richard; Malik, Nasir S. A.; Koroulakis, Antony; Antalek, Matthew; Maivelett, Jordan; Peters-Lawrence, Marlene; Novelli, Enrico M.; Lanzkron, Sophie; Axelrod, Karen C.; Kato, Gregory J.

doi:10.1002/ajh.23571

Cited by 70 publications

(88 citation statements)

References 42 publications

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“…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. 3 and 4) [44]. Hypoxia is well known to induce angiogenesis, therefore it is conceivable that chronic hypoxia in ulcerated skin leads to increase in capillary proliferation and recruitment, with higher measured blood flow.…”

Section: Pathophysiologymentioning

confidence: 99%

“…3, panel C), but whether this leads to an effective increase in perfusion and oxygen delivery needs to be determined by further analysis. A possible role for in situ thrombosis is supported by plasma markers of thrombophilia [44][45][46] and 44% prevalence of venous thromboembolism in SCD ulcer patients [44], and by results of a pilot study of antithrombin use in treatment of SCD leg ulcer [47]. Oxidative stress plays an important pathogenic role in the development of SCD related complications, and patients with glutathione S-transferase polymorphism (GSTM1 and GSTT1 null phenotype) have recently been shown to have a high risk of developing ulcers [48].…”

Section: Pathophysiologymentioning

confidence: 99%

“…The first ulcer often occurs in the second decade of life. About 40-50% of patients recall prior trauma [44,56], often seemingly insignificant, and/or pruritus that provoke scratching and skin breakage. Half of patients will have two or more ulcers at the same time.…”

Section: Medical Historymentioning

confidence: 99%

“…The size of the ulcer has no relationship to the intensity of the pain and very small ulcerations can be extremely painful. Most patients take chronic opioids for ulcer pain and often this is their only indication for opioids [44]. Exposure to air often intensifies the pain.…”

Section: Medical Historymentioning

confidence: 99%

“…Urinalysis often will show microalbuminuria. Serum C-reactive protein (CRP) and/or erythrocyte sedimentation rate are frequently elevated [44]. Patients with and without past history of venous thromboembolic disease may have low levels of antithrombin III, protein C or S, high level of factor VIII or positive lupus anticoagulant.…”

Section: Laboratory Testing and Imagingmentioning

confidence: 99%

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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%