Are there clinical phenotypes of homozygous sickle cell disease?

Alexander, Neal; Higgs, Douglas R.; Dover, George J.; Serjeant, G. R.

doi:10.1111/j.1365-2141.2004.05025.x

Cited by 66 publications

(53 citation statements)

References 13 publications

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“…Sickle cell patients with leg ulcers constitute a relatively distinct sub-phenotype, characterized by less frequent hospitalizations for vaso-occlusive pain crisis [22,23], while they are prone to develop pulmonary hypertension [5,[24][25][26][27][28], suggesting that the two complications share a common pathophysiology. In a cohort of 20 SCD patients with leg ulcer who underwent right hearth catheterization for suspected pulmonary hypertension, 15 had confirmation of PAH (personal data, this cohort has been described in Mehari et al (2013) [24].…”

Section: Epidemiologymentioning

confidence: 99%

See 1 more Smart Citation

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: Epidemiologymentioning

confidence: 99%

“…SCD leg ulcers have been linked to venous incompetence and vasomotor alterations [13,38,39]. Alpha thalassemia trait has been protective [9,29], although this is not always consistent [13,23,40]. Elevated levels of fetal hemoglobin are generally protective [9,29,41], although this has not been true in all studies [33,42].…”

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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“…Indeed, some have suggested that SCA can be split into two sub-phenotypes based on the relative dominance of one or other of these processes in individual patients. [8][9][10] Pulmonary hypertension, a known complication in patients with the hemolytic sub-phenotype of SCD, is thought to be caused by vasculopathy related to the chronic nitric oxide depletion from continuing intravascular hemolysis. 11 Although the markers of SCN are known to predict the presence of pulmonary hypertension, 12 it is still not clear if both conditions share the same pathological process.…”

Section: Introductionmentioning

confidence: 99%

Association between hemolysis and albuminuria in adults with sickle cell anemia

Day

Drašar²,

Fulford³

et al. 2011

Haematologica

104

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We have investigated renal function and markers of hemolysis in a cohort of 424 adult African-British patients with sickle cell disease. While significant associations were found in HbSS and HbSb 0 (sickle cell anemia) patients with and without controlling for covariates between hemolytic markers and albuminuria, the associations were not significant in patients with HbSC. Estimated glomerular filtration rate, a marker of renal function, correlated significantly with reticulocyte count and bilirubin. Alpha thalassemia, present in 34% of the sickle cell anaemia patients, had a protective effect against albuminuria in this group. Altogether, the incidence of hyperfiltration was 71% and microalbuminuria 37%, making nephropathy a common complication of sickle cell anemia. Haematologica 2012;97(2):201-205. doi:10.3324/haematol.2011 This is an open-access paper. ABSTRACTexcluded from the study group if they had a history of diabetes mellitus, HIV infection, malignancy or another cause of chronic kidney disease (CKD) or if they were on a blood transfusion program. Seventeen patients were on ACE (angiotensin converting enzyme) inhibitor or ARB (angiotensin II receptor blocker) therapy; these patients were also excluded from the study. Since 2006, urinary albumin/creatinine ratio (ACR) has been a routine measurement for patients attending the specialist clinic. All patients were routinely genotyped for α thalassemia using a PCR-based methodology on DNA extracted from peripheral blood.17

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“…11,51,54,55 Much of this work is facilitated by very careful observations of the natural history of disease and by the formation of clinical research networks within and between countries. [56][57][58] Nevertheless, there remains an urgent need to extend these networks more effectively to include the large number of African countries where, so far, there is not only limited detailed prevalence data as discussed above, but also very little information about the clinical features of the disease.…”

mentioning

confidence: 99%