Chronic organ failure in adult sickle cell disease

Abstract

Sickle cell disease is now a chronic adult illness characterized by progressive multiorgan failure, particularly involving the brain and kidney. The etiology is multifactorial; it includes hemolysis and nitric oxide deficiency. As patients age, most experience neurologic insult. Twenty-five percent of older adults have had a clinical stroke and at least half of the population have had a silent infarct, cortical atrophy, and neurocognitive impairment. Periodic screening with neuroimaging and neurocognitive testing is recommended. Identification and correction of modifiable risk factors such as nocturnal hypoxemia, obstructive sleep apnea, and physical exercise programs should be implemented. Patients with neurocognitive impairment require cognitive remediation and educational accommodations. Chronic renal disease occurs in 25% of older adults and results in 50% of their deaths. Renal failure often develops insidiously. It can be prevented or minimized by early screening and treatment of modifiable risk factors including hypertension and microalbuminuria. There is an increasing number of therapeutic options, including inhibitors of the renin angiotensin system, angiotensin-II receptor blockers, endothelin-1 receptor antagonist, and haptoglobin therapy. Patients with sickle cell disease have increased mortality rates from renal failure compared with nonsickle cell patients, in part from a lack of access to early multidisciplinary care, including timely initiation of dialysis and renal transplantation.

Serum albumin is independently associated with higher mortality in adult sickle cell patients: Results of three independent cohorts

“…Renal dysfunction, as measured by higher serum creatinine and lower eGFR, was a strong predictor of low serum albumin in walk-PHaSST and OMG cohorts. Renal insufficiency is a frequent comorbidity in SCD patients, with a prevalence of >25% in adult patients [22]. It is also an important prognostic factor in these patients [23].…”

How I treat the older adult with sickle cell disease

“…There is no current consensus guidance on appropriate screening or interventions for diagnosing or treating cognitive decline in SCD but memory concerns should be part of the comprehensive review. 56 We do not routinely perform magnetic resonance imaging/angiography (MRI/A) scans in adults but would have a low threshold for this investigation in patients with headaches, poor memory, or other neurological symptoms. Patients with intracranial aneurysms or moya moya should be referred for neurosurgical review.…”

Cardiac expression of HMOX1 and PGF in sickle cell mice and haem‐treated wild type mice dominates organ expression profiles via Nrf2 (Nfe2l2)

“…The role of Hmox1 in the heart is controversial. Cardioprotective roles of Hmox1 in the heart includes reduction in oxidative stress (van Berlo et al , ), improved mitochondrial function (Hull et al , ), prevention of vascular remodelling (Mito et al , ), inhibition of apoptosis (Wang et al , ; Vichinsky, ) and prevention of atherosclerosis. Increased Hmox1 expression and activity is also linked to diabetes‐induced oxidative stress in the heart via accumulation of iron (Farhangkhoee et al , ).…”

“…Products of intravascular haemolysis contribute to impaired nitric oxide (NO) bioavailability, endothelial dysfunction and organ damage in SCD (Kato et al, 2007;Kato et al, 2017;Vichinsky, 2017). In addition, excess haem (iron protoporphyrin IX) released from damaged sickle red blood cells also acts as a damage-associated molecular pattern (DAMP), thereby activating inflammatory pathways (Ghosh et al, 2013;Belcher et al, 2014;Gladwin & Ofori-Acquah, 2014).…”