Latest News on Sickle Cell Disease : Nov 2020

Latest News on Sickle Cell Disease : Nov 2020

Sickle-cell disease

Sickle-cell disease is one of the most common severe monogenic disorders in the world. Haemoglobin polymerisation, leading to erythrocyte rigidity and vaso-occlusion, is central to the pathophysiology of this disease, although the importance of chronic anaemia, haemolysis, and vasculopathy has been established. Clinical management is basic and few treatments have a robust evidence base. One of the main problems of sickle-cell disease in children is the development of cerebrovascular disease and cognitive impairment, and the role of blood transfusion and hydroxycarbamide for prevention of these complications is starting to be understood. Recurrent episodes of vaso-occlusion and inflammation result in progressive damage to most organs, including the brain, kidneys, lungs, bones, and cardiovascular system, which becomes apparent with increasing age. Most people with sickle-cell disease live in Africa, where little is known about this disease; however, we do know that the disorder follows a more severe clinical course in Africa than for the rest of the world and that infectious diseases have a role in causing this increased severity of sickle-cell disease. More work is needed to develop effective treatments that specifically target pathophysiological changes and clinical complications of sickle-cell disease. [1]

Mortality In Sickle Cell Disease — Life Expectancy and Risk Factors for Early Death

BACKGROUND

Information on life expectancy and risk factors for early death among patients with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, and the sickle cell-β-thalassemias) is needed to counsel patients, target therapy, and design clinical trials.

METHODS

We followed 3764 patients who ranged from birth to 66 years of age at enrollment to determine the life expectancy and calculate the median age at death. In addition, we investigated the circumstances of death for all 209 adult patients who died during the study, and used proportional-hazards regression analysis to identify risk factors for early death among 964 adults with sickle cell anemia who were followed for at least two years.

RESULTS

Among children and adults with sickle cell anemia (homozygous for sickle hemoglobin), the median age at death was 42 years for males and 48 years for females. Among those with sickle cell-hemoglobin C disease, the median age at death was 60 years for males and 68 years for females. Among adults with sickle cell disease, 18 percent of the deaths occurred in patients with overt organ failure, predominantly renal. Thirty-three percent were clinically free of organ failure but died during an acute sickle crisis (78 percent had pain, the chest syndrome, or both; 22 percent had stroke). Modeling revealed that in patients with sickle cell anemia, the acute chest syndrome, renal failure, seizures, a base-line white-cell count above 15,000 cells per cubic millimeter, and a low level of fetal hemoglobin were associated with an increased risk of early death.

CONCLUSIONS

Fifty percent of patients with sickle cell anemia survived beyond the fifth decade. A large proportion of those who died had no overt chronic organ failure but died during an acute episode of pain, chest syndrome, or stroke. Early mortality was highest among patients whose disease was symptomatic. A high level of fetal hemoglobin predicted improved survival and is probably a reliable childhood forecaster of adult life expectancy. [2]

Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease

Although the deleterious vasoconstrictive effects of cell-free, hemoglobin-based blood substitutes have been appreciated, the systemic effects of chronic hemolysis on nitric oxide bioavailability have not been considered or quantified. Central to this investigation is the understanding that nitric oxide reacts at least 1,000 times more rapidly with free hemoglobin solutions than with erythrocytes. We hypothesized that decompartmentalization of hemoglobin into plasma would divert nitric oxide from homeostatic vascular function. We demonstrate here that plasma from patients with sickle-cell disease contains cell-free ferrous hemoglobin, which stoichiometrically consumes micromolar quantities of nitric oxide and abrogates forearm blood flow responses to nitric oxide donor infusions. Therapies that inactivate plasma hemoglobin by oxidation or nitric oxide ligation restore nitric oxide bioavailability. Decompartmentalization of hemoglobin and subsequent dioxygenation of nitric oxide may explain the vascular complications shared by acute and chronic hemolytic disorders. [3]

Sickle Cell Disease in Pregnancy: Maternal and Fetal Outcome in Port Harcourt, Nigeria

Background: Medical experts for many years have daunted the occurrence of pregnancy in homozygote sickle cell patients. This is because of associated high risk for mother and fetus.

The aim of this study is to determine the prevalence and maternal and fetal outcome of pregnant mothers with sickle cell disease at the University of Port Harcourt Teaching Hospital, Nigeria.

Materials and Methods: This was a retrospective descriptive study of medical case files of all booked pregnant mothers who attended the antenatal clinic of the University of Port Harcourt Teaching Hospital, Nigeria from January 2007 to December 2011. The parameters extracted from the folders included: age, level of education, hemoglobin genotype, full blood count, malaria parasite, urine analysis and culture, complications of pregnancy, Apgar scores and birth weight.

Results: A total of 4,650 mothers were booked for antenatal care. Eight hundred and forty (18.1%) of them were HbAS, five (0.1%) were HbAC, nine (0.2%) were HbSS and 1(0.02%) HbSC. Age and gestation at booking were 18–42 years (mean 28.6± 2.1) and 9–34 weeks gestation (mean 16.6±3.3), respectively. Malaria and vaso-occlusive crisis were the commonest complications encountered in pregnancy. Twenty percent of women had induction of labour and 60% were delivered by emergency caesarean section. Twenty percent had postpartum haemorrhage. Forty four percent of women delivered before 37 completed weeks. Birth weight below 2500 g occurred in 50% of singleton pregnancies. Two neonates developed transient complications related to maternal opiate exposure postnatally. There were 2(20%) maternal and fetal losses from toxaemia of pregnancy.

Conclusion: Pregnancy is uncommon among females with sickle cell disease in Port Harcourt, Nigeria. Sickle cell disease remains a severe complicating factor to pregnancy and associated with increased fetal and maternal losses. [4]

Trace Elements Deficiency in Patients with Homozygous Sickle Cell Disease

Aim: The serum trace elements statuses of sickle cell patients attending at General Hospital Owerri, Nigeria were investigated to determine whether or not the serum levels of these elements were normal.

Materials and Methods: One hundred confirmed sickle cell patients (HbSS) age 5–30 years were selected. One hundred normal subjects (HbAA) age 5–30 years were used as control.

Results: The levels of trace elements were significantly decreased in sickle cell anemia (p<0.05), except copper, when compared with the control.

Conclusion: The result suggests, but not conclusively, that supplementation of sickle cell patients with food and drug containing trace elements might be helpful, particularly if diminished mineral levels predispose patients to crises. [5]

Reference

[1] Rees, D.C., Williams, T.N. and Gladwin, M.T., 2010. Sickle-cell disease. The Lancet, 376(9757), pp.2018-2031.

[2] Platt, O.S., Brambilla, D.J., Rosse, W.F., Milner, P.F., Castro, O., Steinberg, M.H. and Klug, P.P., 1994. Mortality in sickle cell disease–life expectancy and risk factors for early death. New England Journal of Medicine, 330(23), pp.1639-1644.

[3] Reiter, C.D., Wang, X., Tanus-Santos, J.E., Hogg, N., Cannon, R.O., Schechter, A.N. and Gladwin, M.T., 2002. Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease. Nature medicine, 8(12), pp.1383-1389.

[4] Ugboma, H. A. A. and George, I. O. (2015) “Sickle Cell Disease in Pregnancy: Maternal and Fetal Outcome in Port Harcourt, Nigeria”, Journal of Advances in Medicine and Medical Research, 7(1), pp. 40-44. doi: 10.9734/BJMMR/2015/11602.

[5] Nnodim, J., Samuel, M., Dioka, C. E., Onah, C., Ihim, A. and Atuegbu, C. (2014) “Trace Elements Deficiency in Patients with Homozygous Sickle Cell Disease”, Journal of Advances in Medicine and Medical Research, 4(21), pp. 3878-3883. doi: 10.9734/BJMMR/2014/7489.

Editor 251News

leave a comment

Create Account



Log In Your Account