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Gene & Protein in Disease Sickle cell disease’s journey

the peak incidence occurs in the second to fourth year of to SCD, and cardiopulmonary complications were cited as
life. ACS in affected adults is most often (around 78% of the most common cause of death in SCD adults. ACS has
affected cases) secondary to vaso-occlusive pain episodes. been already discussed in a separate subsection above. In
ACS is the most common cause of death in SCD patients addition, eccentric hypertrophy, diastolic dysfunction, left
(nearly 25% of all deaths in SCD), with a mortality rate of ventricular dysfunction, and right ventricular dysfunction
4.3% in adults and 1.1% in children. 51 due to pulmonary hypertension are commonly reported
ACS results from vaso-occlusion within the pulmonary cardiac complications of SCD. 73-80 Compared to age- and
vasculature in SCD patients, followed by deoxygenation race-matched children, SCD children have lower lung
of hemoglobin, sickling of RBCs, further vaso-occlusion capacity and expiratory flows in general. Compromised
(by fat and bone marrow released into venous circulation pulmonary function, asthma, wheezing, and sleep-
due to vaso-occlusion and traveling to the lungs), disordered breathing are associated with increased
ischemia and endothelial injury. Pulmonary infarction episodes of vaso-occlusive crisis and ACS. Sleep-disordered
and fat embolism are large contributors to ACS. Infection, breathing along with chronic pulmonary disease and
asthma, factors causing hypoxemia, and post-operative hypoxemia is also associated with the development of
complications are other known causes that incite ACS pulmonary hypertension and ventricular dysfunction.
in SCD patients. Patients hospitalized for vaso-occlusive Most treatments in SCD patients are administered per
pain in the spine, ribs, and abdomen are at a greater risk guidelines for the general population and need to be
of developing ACS because the pain in these regions can monitored in a multidisciplinary setting by specialists. 76
lead to hypoventilation and hence alveolar hypoxia when 5.7. Genitourinary complications
opioids are used. 49,51 Children affected by ACS present
with wheezing, coughing, shortness of breath, and fever, The kidney is one of the most commonly affected organs
whereas adults affected by the same condition present with in SCD. Ischemia-reperfusion injury to the kidney
chest pain, pain in extremities, dyspnea, or vaso-occlusive due to vaso-occlusion leads to hematuria, proteinuria,
signs in other parts of the body. 49,51,52-65 tubular disturbances, and complications, namely, sickle
cell nephropathy, painful priapism, papillary necrosis,
5.4. Infections and renal medullary carcinoma. 81-89 Microalbuminuria
SCD patients are highly likely to contract bacterial is the earliest sign of sickle cell nephropathy, and its
infections such as pneumonia, urinary tract infections, prevalence increases with the age of the SCD patients.
osteomyelitis, meningitis, and septicemia, probably due to Hyperphosphatemia, hyperuricemia, and increased GFR
hyposplenism, defective opsonization, decreased immune are seen in SCD patients. Acute kidney injury due to the
response and complement pathway, defective leukocyte resulting volume depletion, rhabdomyolysis, renal vein
function, and cellular immunity. S. aureus, Salmonella, and thrombosis, papillary necrosis, and clot obstructions of the
Gram-negative enteric bacteria are reported to be the most urinary tract are reported in 10% of SCD patients. Chronic
common causative organisms. Children under the age of kidney injury is reported in 30% of SCD patients, whereas
five are at increased risk of life-threatening pneumococcal 4 – 12% of the patients develop end-stage renal disease,
infection due to hyposplenism. 48,66,67 whose mortality rate is thrice as high as in patients without
SCD. 82-86
5.5. Neurological complications Ischemic priapism is not common in sickle cell trait but
Neurological complications in SCD are not uncommon. has a prevalence rate of as high as 42% in SCD males. It is
There have been reports that silent cerebral infarcts were characterized by a rigid, painful erection lasting more than
seen in 39% of patients by 18 years of age, acute and chronic 4 h, unrelated to orgasm and not involving the glans penis,
headaches in 36% of children with SCD, ischemic strokes is often seen in SCD children and adults, and is a medical
in 9 – 11% of children with sickle cell anemia without emergency that needs to be treated even before treating the
screening, hemorrhagic stroke affected 3% of children disease itself. 83
and 10% of adults with SCD. Intracranial hemorrhage
and aneurysms are also seen in SCD. Asymptomatic silent 5.8. Hepatobiliary complications
cerebral infarcts in early life can progress to neurocognitive Liver dysfunction is estimated to be prevalent in about 10%
impairments and reduced academic performance. 68-72 of SCD adults, and the prevalence is expected to increase
with age. Acute manifestations of hepatic dysfunction in
5.6. Cardiopulmonary complications SCD include hepatic crisis, intrahepatic cholestasis, and
Studies have indicated that 60% of SCD patients exhibited hepatic sequestration. Cholelithiasis, cholangiopathy,
some cardiac abnormality, 40% succumbed prematurely auto-immune hepatitis, viral hepatitis, and iron overload

Volume 4 Issue 1 (2025) 5 doi: 10.36922/gpd.4361