[Sub capsular splenic hematoma in a sickle cell trait carrier. Case report].

PubMed

Ugalde, Diego; Conte, Guillermo; Ugalde, Héctor; Figueroa, Gastón; Cuneo, Marianela; Muñoz, Macarena; Mayor, Javiera

2011-09-01

Drepanocytic anemia is an uncommon hereditary disease in Chile. The heterozygous state of drepanocytic anemia or "sickle trait" has a frequency of 8% among Afro-Americans. A small number of patients carrying hemoglobin S are homozygous, with clinical manifestations of hemolytic anemia and thrombotic disease. Sickle trait is usually asymptomatic. We report a 59-year-old male who presented an acute abdominal pain and dyspnea while staying at high altitude. Six days later, an angio CAT scan showed the presence of a subcapsular splenic hematoma that was managed conservatively. Sickle cell induction with sodium metabisulphite was positive. Hemoglobin electrophoresis confirmed the sickle trait.

Sickle cell trait and sudden death--bringing it home.

PubMed Central

Mitchell, Bruce L.

2007-01-01

Sickle cell trait continues to be the leading cause of sudden death for young African Americans in military basic training and civilian organized sports. The syndrome may have caused the death of up to 10 college football players since 1974 and, as recently as 2000, was suspected as the cause of death of three U.S. Army recruits. The penal military-style boot camps in the United States and the recent death of two teenagers with sickle cell trait merits renewed vigor in the education of athletic instructors, the military and the public about conditions associated with sudden death in individuals with sickle cell trait. Images Figure 1 Figure 2 PMID:17393956

Vocational options for those with sickle cell trait : questions about hypoxemia and the industrial environment.

DOT National Transportation Integrated Search

1980-11-01

This report is based on an oral presentation to physicians interested in the treatment of patients with sickle cell disease. Many patients have parents and siblings who possess the sickle cell trait (SCT), and who often require not only genetic couns...

Optimal haematocrit in subjects with normal haemoglobin genotype (HbAA), sickle cell trait (HbAS), and homozygous sickle cell disease (HbSS).

PubMed

Bowers, A S; Pepple, D J; Reid, H L

2011-01-01

The determination of an optimal haematocrit (H0) has important clinical implications if such a level can be attained, and more importantly, maintained. This is defined as a haematocrit level, above or below which oxygen delivery is deleteriously affected. This study is designed to determine an optimal haematocrit in normal (AA), sickle cell trait (AS) and sickle cell disease (SS) subjects. Twenty-seven apparently healthy subjects having normal haemoglobin genotype, 24 with sickle cell trait and 42 with homozygous sickle cell disease were recruited into the study. Whole blood viscosity (WBV) was measured by a Wells Brookfield Cone and Plate Viscometer at a shear rate of 230 sec-1. Haematocrit was determined by an AC.Tron Coulter Counter. The optimal haematocrit was calculated as the inverse of a constant, K, which was derived from the haematocrit and viscosity data. Our findings showed that the H0 varied significantly among the 3 haemoglobin genotypes, in the order AA vs SS and AS vs SS. Additionally, the data indicated an increased H0 in subjects with sickle cell trait, suggesting a possible impairment in oxygen delivery in these individuals.

Splenic infarction associated with sickle cell trait at low altitude.

PubMed

Seegars, Mary Beth; Brett, Allan S

2015-12-01

Sickle cell trait is widely known to be associated with splenic infarction at high altitudes. Although textbooks and reviews imply that this complication does not occur at low altitudes, we encountered such a case and identified several previous cases in the literature. An 18-year-old woman with sickle cell trait who resided near sea level presented with left upper quadrant abdominal pain and was found to have multiple splenic infarcts. She was otherwise well, with no comorbidities that would predispose to hypoxemia or vascular injury. A review of the literature revealed 12 previously published cases of low-altitude splenic infarction in patients with sickle trait; 7 of those patients had comorbidities that likely predisposed to splenic infarction. None. Spontaneous splenic infarction can occur in patients with sickle trait who live at low altitudes. It is unclear whether this complication is rare, or whether it is relatively common but under-recognized.

Sickle Cell Trait and Fatal Exertional Heat Illness: Implications for Exercise-Related Death of Young Ddults

DTIC Science & Technology

2008-10-22

athletes who utilize ordinary weather reports? Alpha- Thalassemia Protects Against Exertional Mortality with Sickle Cell Trait • 30% of African...Americans have alpha- thalassemia (2-3 alpha genes instead of 4). In those with sickle cell trait the main effect is to lower the Hb S fraction below 36...expected 15 cases with alpha- thalassemia & ប% S • Two cases had Hb S < 36% , implying about a 7.5-fold protection for those with alpha thalassemia

Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait.

PubMed

Kim, Lisa; Garfinkel, Marc R; Chang, Anthony; Kadambi, Pradeep V; Meehan, Shane M

2011-07-01

Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss. Copyright © 2011 Elsevier Inc. All rights reserved.

Sickle cell trait: what are the costs and benefits of screening?

PubMed

Shephard, Roy J

2016-12-01

Eight percent of African Americans are carriers of the sickle cell trait. Some regard this as a benign anomaly, but others point to incidents of sudden exercise-related death, calling for a preliminary screening of either all athletes or those of African-American ancestry. This brief review considers the costs and benefits of such screening. The Ovid/Health Star data-base was searched from 1996 to June 2015. 2014. The terms "exercise", "exercise therapy", "sports", "athletes", "physical activity/motor activity" and "physical fitness" were combined to yield 227,120 citations. Likewise, the terms "sickle cell trait", "sickle cell disease", "splenic infarction", "hemoglobin S" and "rhabdomyolysis" identified 12,325 citations. A combination of the 2 searches yielded 416 abstracts. Excluding items relating to animal research or forms of rhabdomyolysis other than sickling left 375 abstracts; 115 papers merited full examination. This material covered the risks of sickle cell trait and of screening (55 items), effects upon physical performance (31 items), cellular mechanisms (23 items), nutrition (4 items), and other topics (2 items). Supplemented material was drawn from reference lists and personal files. The tendency to sickling was provoked by excessive exercise relative to physical condition in hot or hypoxic conditions, and by local tissue acidosis, conditions that were best avoided by all athletes. The condition had little impact upon physical performance, but the relative risks of heat illness, exertional rhabdomyolysis, splenic infarction and sudden death were all increased by the sickle cell trait. The absolute number of critical incidents was nevertheless small, calling for close assessment of the costs and putative benefits of widespread screening. Sports physicians should be aware of the clinical picture of sickling and be prepared to treat it. Screening may be cost-effective if targeted to black athletes involved in certain sports, although it has yet to be demonstrated how far the diagnosis of sickle cell trait reduces the risk of death when exercising in an adverse environment. A better tactic may be to reduce risks for all competitors by educating athletes and their coaches to adopt an intensity of training appropriate to the individual's physical condition, to maintain full hydration, and to avoid exposure to excessive heat and hypoxia.

Genetic modulation of sickle cell anemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinberg, M.H.

1995-05-01

Sickle cell anemia, a common disorder associated with reduced life span of the red blood cell and vasoocclusive events, is caused by a mutation in the {Beta}-hemoglobin gene. Yet, despite this genetic homogeneity, the phenotype of the disease is heterogeneous. This suggests the modulating influence of associated inherited traits. Some of these may influence the accumulation of fetal hemoglobin, a hemoglobin type that interferes with the polymerization of sickle hemoglobin. Another inherited trait determines the accumulation of {alpha}-globin chains. This review focuses on potential genetic regulators of the phenotype of sickle cell anemia. 125 refs., 6 figs., 3 tabs.

The Splenic Syndrome in Individuals with Sickle Cell Trait

PubMed Central

Hassell, Kathryn; Irwin, David; Witkowski, Ewa H.; Nuss, Rachelle

2014-01-01

Abstract Goodman, Jessica, Kathryn Hassell, David Irwin, Ewa H. Witkowski, and Rachelle Nuss. The splenic syndrome in individuals with sickle cell trait. High Alt Med Biol 15:468–471, 2014.—The medical records of 25 individuals with sickle cell trait and altitude-associated splenic infarct, reported to two Colorado physicians, were reviewed. Electrospray mass spectroscopy was performed on blood samples from a cohort of 10 of the individuals to rapidly confirm beta hemoglobin phenotype. Only males were identified with a 1.4:1 ratio of non-African Americans to African Americans, and 44% of African Americans and 85% of non-African Americans were unaware they had sickle cell trait. Left upper quadrant pain and an elevated bilirubin were nearly uniformly present. Either abdominal CT or ultrasound was confirmatory. Conservative treatment at a lower altitude generally resulted in a favorable outcome. PMID:25361178

Congolese children with sickle cell trait may exhibit glomerular hyperfiltration: A case control study.

PubMed

Aloni, Michel Ntetani; Ngiyulu, René Makwala; Nsibu, Célestin Ndosimao; Ekulu, Pépé Mfutu; Makulo, Jean Robert; Gini-Ehungu, Jean-Lambert; Nseka, Nazaire Mangani; Lepira, François Bompeka

2017-11-01

The prevalence of sickle cell trait is extremely high in sub-Saharan Africa. Recent studies have reported the impact of sickle cell carriers on renal function. However, data on renal abnormalities in children with sickle cell trait in this part of the world are unknown. In this report, we assess the glomerular function of children with sickle cell trait (SCT). A case control study was conducted to assess the glomerular function in 43 Congolese children with sickle cell trait (Hb-AS) matched for age to 65 children with sickle cell anemia in steady state (Hb-SS) and 67 normal controls (Hb-AA). There was a significant difference in the blood pressure levels between the Hb-AS group vs Hb-SS group (P<.05). The estimated glomerular filtration rate (eGFR) corrected for body surface area was increased in Hb-AS group compared to Hb-AA group, but there was no significant difference between the two groups (P=.48). At the same time, the eGFR was decreased, but no significantly so, in the Hb-AS group compared to the Hb-SS group (P=.19). The proportion of children with Hb-AS (16.3%) who had hyperfiltration was higher compared to the proportion (6.1%) found in the Hb-AA group, but lower compared to the proportion found in the Hb-SS group (30%). However, in both situations, the difference was not statistically significant. No case of proteinuria was detected in children with Hb-AS. It appears that at least one of six children with SCT had hyperfiltration. The findings could form a basis for further studies on this renal physiology among SCT individuals in Africa. © 2017 Wiley Periodicals, Inc.

Proposed low-cost premarital screening program for prevention of sickle cell and thalassemia in Yemen

PubMed Central

Al-Nood, Hafiz; Al-Hadi, Abdulrahman

2013-01-01

In Yemen, the prevalence of sickle cell trait and β-thalassemia trait are high. The aim of this premarital program is to identify sickle cell and thalassemia carrier couples in Yemen before completing marriages proposal, in order to prevent affected birth. This can be achieved by applying a low-cost premarital screening program using simple blood tests compatible with the limited health resources of the country. If microcytosis or positive sickle cell is found in both or one partner has microcytosis and the other has positive sickle cell, so their children at high risk of having sickle cell or/and thalassemia diseases. Carrier couples will be referred to genetic counseling. The outcomes of this preventive program are predicted to decrease the incidence of affected birth and reduce the health burden of these disorders. The success of this program also requires governmental, educational and religious supports. PMID:25003062

Renal Cell Carcinoma, Unclassified with Medullary Phenotype and Synchronous Renal Clear Cell Carcinoma Present in a Patient with No Sickle Cell Trait/Disease: Diagnostic and Therapeutic Challenges.

PubMed

Lai, Jenny Z; Lai, H Henry; Cao, Dengfeng

2018-06-01

Renal medullary carcinoma (RMC) is an aggressive high-grade renal cell carcinoma (RCC) associated almost exclusively with sickle cell trait or sickle cell disease. However, RCC with RMC features has rarely been reported in patients with no sickle cell trait or disease. Renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) is a newly-coined term used by an international panel of experts to describe renal cell carcinoma showing morphologic and immunohistochemical features of renal medullary carcinoma in patients without sickle cell trait/disease. So far, only one study in the English literature has described five such cases. Here, we report a case with unique clinical and pathological features in a 76-year-old male patient without sickle cell trait. The patient had a history of colon cancer with liver and lung metastases and was found to have a new renal mass in his right kidney during the follow up. A right nephrectomy was performed and showed two separate masses (tumor 1 and tumor 2). Tumor 1 had histologic features of RMC and the tumor cells were positive for CK7, Pax8, and OCT4 and showed loss of nuclear INI1 expression. Tumor 1 was diagnosed as RCCU-MP (6.3 cm, pT3aNx, WHO/ISUP nuclear grade 3). Tumor 2 showed features of clear cell type of RCC (0.6 cm, pT1aNx, WHO/ISUP grade 2) with intact nuclear INI1 expression. Three-months post-nephrectomy, the patient developed lung metastasis of RCCU-MP. To the best of our knowledge, this was the first documented case with synchronous RCCU-MP and clear cell RCC presenting in a patient without sickle cell trait. Careful histologic assessment with a panel of immunohistochemical biomarkers was helpful to render a correct diagnosis for early aggressive treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Recreational Diver Responses to 600-2500 Hz Waterborne Sound

DTIC Science & Technology

2002-06-13

other conditions such as sickle cell disease, polycythemia , leukemia, claustrophobia, psychosis, panic disorder, drug or alcohol abuse? If yes please...Absolute Contraindications: 49 Sickle cell trait Sickle cell disease Acute anemia Polycythemia Leukemia ORTHOPEDIC Relative impairment in mobility

Exertional sickling deaths in Army recruits with sickle cell trait.

PubMed

Ferster, Kenneth; Eichner, E Randy

2012-01-01

Exertional sickling from sickle cell trait (SCT) can pose a grave risk for some military recruits and is a troubling cause of death in college athletes. We report the cases of two U.S. Army recruits with undetected SCT who collapsed and soon died from metabolic complications of exertional sickling as they struggled to finish in time the 2-mile run of the Army Physical Fitness Test, having failed this test on prior attempts. These cases are similar to other military cases and to recent sickling deaths in college track and football. Research shows how and why, in the face of SCT, during intense exercise bouts, sickle cells can quickly form and lead to fulminant rhabdomyolysis that can be fatal. Increasing evidence suggests that, in the military and in sports, the proximate trigger for most cases of fatal sickling collapse is intensity. If this hypothesis is correct, that sickling collapse is an intensity syndrome, it raises vital questions about how best to train military recruits with SCT.

The splenic syndrome in individuals with sickle cell trait.

PubMed

Goodman, Jessica; Hassell, Kathryn; Irwin, David; Witkowski, Ewa H; Nuss, Rachelle

2014-12-01

The medical records of 25 individuals with sickle cell trait and altitude-associated splenic infarct, reported to two Colorado physicians, were reviewed. Electrospray mass spectroscopy was performed on blood samples from a cohort of 10 of the individuals to rapidly confirm beta hemoglobin phenotype. Only males were identified with a 1.4:1 ratio of non-African Americans to African Americans, and 44% of African Americans and 85% of non-African Americans were unaware they had sickle cell trait. Left upper quadrant pain and an elevated bilirubin were nearly uniformly present. Either abdominal CT or ultrasound was confirmatory. Conservative treatment at a lower altitude generally resulted in a favorable outcome.

Acute appendicitis in patients with sickle cell disease.

PubMed

Al-Nazer, Mona A; Al-Saeed, Hussain H; Al-Salem, Ahmed H

2003-09-01

Patients with sickle cell disease (SCD) often present with abdominal pain, usually attributed to vaso-occlusive crisis, but not rarely, it may be caused by other surgical conditions. Acute appendicitis although common in patients with SCD, it is rare and has a rapid course with a high incidence of perforation. Over a period of 7 years from 1995 to 2001, only 8 patients with SCD out of 1563 (0.5%) patients with acute appendicitis underwent operation at Qatif Central Hospital, Qatif, Kingdom of Saudi Arabia. Their histological slides were reviewed and the findings were compared to those with sickle cell trait (9 patients) and control group (28 patients). All patients with SCD and in spite of a short duration of symptoms had a moderate to severe inflammation and the vessels were packed with sickle red blood cells (RBCs) except one who had an intact mucosa, extensive transmural hemorrhage and congested blood vessels with sickled RBCs without inflammatory cell infiltrate. The mucosa was intact in only one patient with SCD when compared to 5 (55.6%) in those with sickle cell trait and 6 (21.4%) in the control group and in the majority (87.5%) of those with SCD there were moderate to severe mucosal ulcerations when compared to those with sickle cell trait (44.4%) or controls (64.3%). In patients with SCD, acute appendicitis is rare, and these appendicular changes were a sequelae of blockage of appendiceal vessels by sickled RBCs leading to congestion, edema, and ischemia with subsequent mucosal ulceration and marked inflammatory cell infiltrate.

Reversal of retinal and optic disc ischemia in a patient with sickle cell trait and glaucoma secondary to traumatic hyphema.

PubMed

Wax, M B; Ridley, M E; Magargal, L E

1982-07-01

A 14-year-old black boy with sickle cell trait, who sustained a traumatic hyphema, developed moderately elevated intraocular pressure that failed to respond to carbonic anhydrase inhibitors and osmotic agents. On the tenth postinjury day, a sudden increased cupping of the optic disc and partial central retinal artery obstruction caused painless loss of vision. Reversal of the cupping, the retinal ischemia, and the intraocular pressure was documented following anterior chamber paracentesis, and visual acuity returned to 6/6. Pathophysiology of the posterior ischemia is discussed. This case documents the potentially debilitating course of traumatic hyphema in "benign" sickle cell trait and its avoidance with proper management. The authors endorse recent suggestions for careful observation of any sickle cell patient with traumatic hyphema, and recommend anterior chamber paracentesis, supplemental oxygen, and avoidance of osmotic agents, if secondary glaucoma develops following the initial trauma.

Sickle Cell Trait and Scholastic Achievement

ERIC Educational Resources Information Center

Jackson, Yvonne; Ayrer, James

1974-01-01

In a preliminary study, no significant interaction effects were found between scholastic achievement and sickle cell trait in black children currently in eight and ninth grades, as measured by the Iowa Tests of Basic Skills over a consecutive period of four years, 1968 through 1971, grades four through seven. (EH)

[Presentation of 2 cases of sudden deafness in patients with sickle-cell anemia and trait].

PubMed

García Callejo, F J; Sebastián Gil, E; Morant Ventura, A; Marco Algarra, J

2002-05-01

We report two cases of sudden deafness which appeared during vaso-occlusive crisis of a sickle cell anaemia (homozygous form of disease) and a sickle cell trait (heterozygous form) in two males aged sixteen and twenty-two, respectively. A high erythrocyte aggregability and low deformability were proved in both young men. Although hearing disorders have been reported in this disease, a sudden onset is not common. The treatment used was useful in the removal of painful crisis and infections, but deafness did not improve in either of then.

Evaluation of a neonatal screening program for sickle-cell disease.

PubMed

Eller, Rodrigo; da Silva, Denise Bousfield

2016-01-01

Evaluate the Neonatal Screening Program of the Health Secretariat of the State of Santa Catarina for sickle-cell disease, from January 2003 to December 2012, regarding program coverage and disease frequency. Descriptive, observational, cross-sectional study with retrospective data collection. The variables analyzed were: number of live births in the State of Santa Catarina; number of screened children; number of children diagnosed with sickle-cell trait and sickle-cell disease; type of sickle-cell disease diagnosed; age at the time of sample collection, ethnicity/skin color, gender, and origin of children with sickle-cell disease. Descriptive measures and frequency tables were used for data analysis. During the study period, there were 848,833 live births and 730,412 samples were screened by the program, resulting in a coverage of 86.0%. There were 6173 samples positive for sickle-cell trait and 39 for sickle-cell disease. Among children with sickle-cell disease, the median age at the time of sample collection was 6 days. Regarding the ethnicity/skin color, 25 (64.1%) children were white, seven were black, and seven others were not specified. The Midwest and the Highland (Planalto Serrano) of Santa Catarina were the regions with the highest incidence of sickle-cell disease. Coverage by the Neonatal Screening Program of Santa Catarina is good, but did not demonstrate an improvement trend over the years. The frequency of sickle-cell disease is low and lower than in the North, Northeast, and Midwest regions. The median age in days at the time of collection is older than the age recommended by the Ministry of Health. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Anaesthesia in Sickle-cell States: A Plea for Simplicity

PubMed Central

Oduro, K. A.; Searle, J. F.

1972-01-01

505 patients with various haemoglobinopathies were given a general anaesthetic between January 1970 and February 1972. One patient with haemoglobin SC disease and one patient with sickle-cell trait (HbAS) died postoperatively. Four other patients who were sickling positive, but whose genotypes were unknown, died, one from sickle-cell crisis precipitated by haemorrhage. A simple anaesthetic technique together with good postoperative care can provide safe general anaesthesia for patients with sickle-cell states. A plea is made for simplicity in the anaesthetic management of these patients. PMID:4643397

A rare case of avascular necrosis in sickle cell trait: a case report.

PubMed

Sanders, William J

2018-01-01

Sickle cell trait is usually an asymptomatic presentation of a patient with slightly different hemoglobin molecule makeup than normal. It is similar to a more serious disease, sickle cell disease, in which a person's hemoglobin is mutated in such a way that causes their red blood cells to easily change shape in certain environmental and internal states; this causes red blood cells to adhere to the walls and occlude the lumen of the arteries in which they travel, leading to downstream effects secondary to ischemia. Sickle cell trait does not have these ischemic effects, usually. In this case, a young African American female patient presents to the clinic with severe right hip pain. Her past medical history includes sickle cell trait and asthma. She has not been symptomatic of her asthma for years and is not on therapy for it. The pain has lasted for several months and has not improved with anti-inflammatory medication. There is severe pain with internal and external rotation of the hip. The neurovascularity of the lower extremities is intact bilaterally. MRI of the femur shows stage 2 or 3 avascular necrosis of the femoral head, while X-rays of the femur are unremarkable. Non weight-bearing for several weeks was unsuccessful; shortly thereafter, the patient underwent core decompression of the right femoral head as well as starting bisphosphonates. The patient improved temporarily but regressed shortly thereafter. Her avascular necrosis worsened radiographically over the next several months. At this point, the only other option would be to do a total hip arthroplasty, but the patient may need several more throughout her lifetime due to the lifespan of the artificial replacement. There have only been scarce reports of avascular necrosis in patients with sickle cell trait. This manuscript presents such a case and includes the trials and tribulations associated with its management.

Athletes' Perceptions of National Collegiate Athletic Association--Mandated Sickle Cell Trait Screening: Insight for Academic Institutions and College Health Professionals

ERIC Educational Resources Information Center

Lawrence, Raymona H.; Shah, Gulzar H.

2014-01-01

Objective: The study objective was to explore athletes' perspectives of National Collegiate Athletic Association (NCAA)--mandated sickle cell trait (SCT)--screening policy by examining race- and gender-related differences in athletes' perceptions regarding risk of having SCT and concern about loss of playing time. Participants: Participants were…

Learning about Sickle Cell Disease

MedlinePlus

... used in conjunction with in vitro fertilization, called pre-implantation genetic diagnosis (PGD), enables parents who carry the sickle cell trait to test embryos for the defective gene before implantation, and ...

Sickle Cell Trait, Rhabdomyolysis, and Mortality among U.S. Army Soldiers

PubMed Central

Nelson, D. Alan; Deuster, Patricia A.; Carter, Robert; Hill, Owen T.; Wolcott, Vickee L.; Kurina, Lianne M.

2016-01-01

Background Studies have suggested that sickle cell trait elevates the risks of exertional rhabdomyolysis and death. We conducted a study of sickle cell trait in relation to these outcomes, controlling for known risk factors for exertional rhabdomyolysis, in a large population of active persons who had undergone laboratory tests for hemoglobin AS (HbAS) and who were subject to exertional-injury precautions. Methods We used Cox proportional-hazards models to test whether the risks of exertional rhabdomyolysis and death varied according to sickle cell trait status among 47,944 black soldiers who had undergone testing for HbAS and who were on active duty in the U.S. Army between January 2011 and December 2014. We used the Stanford Military Data Repository, which contains comprehensive medical and administrative data on all active-duty soldiers. Results There was no significant difference in the risk of death among soldiers with sickle cell trait, as compared with those without the trait (hazard ratio, 0.99; 95% confidence interval [CI], 0.46 to 2.13; P = 0.97), but the trait was associated with a significantly higher adjusted risk of exertional rhabdomyolysis (hazard ratio, 1.54; 95% CI, 1.12 to 2.12; P = 0.008). This effect was similar in magnitude to that associated with tobacco use, as compared with no use (hazard ratio, 1.54; 95% CI, 1.23 to 1.94; P<0.001), and to that associated with having a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30.0 or more, as compared with a BMI of less than 25.0 (hazard ratio, 1.39; 95% CI, 1.04 to 1.86; P = 0.03). The effect was less than that associated with recent use of a statin, as compared with no use (hazard ratio, 2.89; 95% CI, 1.51 to 5.55; P = 0.001), or an antipsychotic agent (hazard ratio, 3.02; 95% CI, 1.34 to 6.82; P = 0.008). Conclusions Sickle cell trait was not associated with a higher risk of death than absence of the trait, but it was associated with a significantly higher risk of exertional rhabdomyolysis. (Funded by the National Heart, Lung, and Blood Institute and the Uniformed Services University of the Health Sciences.) PMID:27518662

Relative deformability of red blood cells in sickle cell trait and sickle cell anemia by trapping and dragging

NASA Astrophysics Data System (ADS)

Solomon, Rance; Cooper, James; Welker, Gabriel; Aguilar, Elaura; Flanagan, Brooke; Pennycuff, Chelsey; Scott, David; Farone, Anthony; Farone, Mary; Erenso, Daniel; Mushi, Robert; del Pilar Aguinaga, Maria

2013-06-01

Genetic mutation of the β-globin gene or inheritance of this mutated gene changes the chemical composition of the oxygen-carrying hemoglobin molecule that could lead to either the heterozygote genotype, resulting in sickle cell trait (SCT), or the homozygote genotype, resulting in sickle cell anemia (SCA). These mutations could affect the reversible elastic deformations of the red blood cells (RBCs) which are vital for biological functions. We have investigated this effect by studying the differences in the deformability of RBCs from blood samples of an individual with SCT and an untreated patient with SCA along with hemoglobin quantitation of each blood sample. Infrared 1064 nm laser trap force along with drag shear force are used to induce deformation in the RBCs. Ultra2-High Performance Liquid Chromatography (UHPLC) is used for the hemoglobin quantitation.

Pressurized flight immediately after splenic infarction in two patients with the sickle cell trait.

PubMed

Norii, Tatsuya; Freeman, Theresa Hess; Alseidi, Adnan; Butler, William P; Gelford, Brendon L

2011-01-01

Splenic infarction in individuals harboring the sickle cell trait can occur in the setting of exposure to low oxygen tension at high altitudes. While this is a concern in unpressurized aircraft flight, it has not been well documented in pressurized flight. What has not been addressed is whether this relative safety of pressurized flight extends to the postinfarction period and whether or not pressurized flight in the immediate post-infarction period, especially air evacuation, would change the patient's outcome. We present two cases of splenic infarction suffered during climbing Mt. Fuji (12,388 ft, 3776 m) in patients harboring the sickle cell trait. Both patients were initially assessed and misdiagnosed by a local hospital. They then voluntarily took a 2-h, 30-min pressurized commercial flight [cruising altitude 40,000 ft (12,192 m), minimal cabin pressure: 0.73 atmospheric pressure] within 48 h of their initial presentation. Shortly after their arrival in their final destination they underwent a full workup, including a contrast enhanced CT scan, and were found to have the above-mentioned diagnosis. In both cases, supportive care was sufficient; both patients recovered without sequelae and did not deviate from what would be considered the standard, expected natural history of splenic infarction in patients with the sickle cell trait. It would seem from this anecdotal experience that pressurized commercial flights undertaken in the immediate post-splenic infarction period by individuals with the sickle cell trait may not change either the disease course or the patient's outcome and might be safe.

Progressive glomerular and tubular damage in sickle cell trait and sickle cell anemia mouse models.

PubMed

Saraf, Santosh L; Sysol, Justin R; Susma, Alexandru; Setty, Suman; Zhang, Xu; Gudehithlu, Krishnamurthy P; Arruda, Jose A L; Singh, Ashok K; Machado, Roberto F; Gordeuk, Victor R

2018-02-02

Homozygosity for the hemoglobin (Hb) S mutation (HbSS, sickle cell anemia) results in hemoglobin polymerization under hypoxic conditions leading to vaso-occlusion and hemolysis. Sickle cell anemia affects 1:500 African Americans and is a strong risk factor for kidney disease, although the mechanisms are not well understood. Heterozygous inheritance (HbAS; sickle cell trait) affects 1:10 African Americans and is associated with an increased risk for kidney disease in some reports. Using transgenic sickle mice, we investigated the histopathologic, ultrastructural, and gene expression differences with the HbS mutation. Consistent with progressive glomerular damage, we observed progressively greater urine protein concentrations (P = 0.03), glomerular hypertrophy (P = 0.002), and glomerular cellularity (P = 0.01) in HbAA, HbAS, and HbSS mice, respectively. Ultrastructural studies demonstrated progressive podocyte foot process effacement, glomerular basement membrane thickening with reduplication, and tubular villous atrophy with the HbS mutation. Gene expression studies highlighted the differential expression of several genes involved in prostaglandin metabolism (AKR1C18), heme and iron metabolism (HbA-A2, HMOX1, SCL25A37), electrolyte balance (SLC4A1, AQP6), immunity (RSAD2, C3, UBE2O), fatty acid metabolism (FASN), hypoxia hall-mark genes (GCK, SDC3, VEGFA, ETS1, CP, BCL2), as well as genes implicated in other forms of kidney disease (PODXL, ELMO1, FRMD3, MYH9, APOA1). Pathway analysis highlighted increased gene enrichment in focal adhesion, extracellular matrix-receptor interaction, and axon guidance pathways. In summary, using transgenic sickle mice, we observed that inheritance of the HbS mutation is associated with glomerular and tubular damage and identified several candidate genes and pathways for future investigation in sickle cell trait and sickle cell anemia-related kidney disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Traumatic central retinal artery occlusion with sickle cell trait.

PubMed

Sorr, E M; Goldberg, R E

1975-10-01

An 8-year-old black boy with sickle cell trait struck his left brow and globe on the edge of a table and had immediate blurring of vision. Six days later visual acuity was light projection, and traumatic iritis with secondary glaucoma and perimacular edema were present. Fluorescein angiography indicated obstructed peripheral and perimacular arterioles and dye leakage from the disk.

Sickle cell in Latin America and the United States [corrected].

PubMed

Huttle, Alexandra; Maestre, Gladys E; Lantigua, Rafael; Green, Nancy S

2015-07-01

Latin Americans are an underappreciated population affected by sickle cell disease (SCD). Sickle trait and SCD exist throughout Latin America and U.S. Latino communities. We describe the epidemiology and genetic heterogeneity of SCD among Latin Americans, and fetal hemoglobin expression. National population-based newborn screening for SCD is limited to Brazil, Costa Rica, and the U.S. Available and extrapolated data suggest that over 6,000 annual births and 100,000-150,000 Latin Americans are affected by SCD. This comprehensive review highlights the substantial numbers and population distribution of SCD and sickle trait in Latin America, and where national newborn screening programs for SCD exist. © 2015 Wiley Periodicals, Inc.

Chromatographic measurements of hemoglobin A2 in blood samples that contain sickle hemoglobin.

PubMed

Shokrani, M; Terrell, F; Turner, E A; Aguinaga, M D

2000-04-01

In the sickle cell syndromes, Hb A2 measurements aid in the differential diagnosis of sickle cell anemia from sickle-beta-thalassemia. The purpose of this study is to assess the Hb A2 levels in samples containing sickle hemoglobin (Hb S) by the use of an automated high performance liquid chromatography system (HPLC-Variant beta-thalassemia Short Program). The blood samples analyzed were from individuals of African descent living in the state of Tennessee who had either sickle cell trait (Hb AS), sickle cell disease (Hb SS), or sickle cell-hemoglobin C disease (Hb SC). Interestingly, the Hb A2 levels determined by HPLC were found elevated in samples containing Hb S. The Hb A2 mean in Hb AS samples (n=146) is 4.09% (SD +/- 0.42, range 2.20 to 5.20%); in Hb SS samples (n=33) it is 3.90% (SD +/- 1.08, range 0.60 to 5.90%); and in Hb SC samples (n=27) it is 4.46% (SD +/- 0.70, range 2.30 to 5.91%). The Hb A2 mean by HPLC in normal individuals (Hb AA, n=70) is 2.57% (SD +/- 0.25, range 2.1 to 3.0%), and the Hb A2 range in beta-thalassemia carriers is 4 to 9%. Our results show that the Hb A2 levels in Hb S-containing samples partially overlap with those expected from beta-thalassemia carriers. The hemoglobinopathy laboratory should be aware of this apparent elevation in Hb A2 levels determined by HPLC in individuals carrying Hb S. Other factors, such as family history and clinical symptoms, should be taken into account before a diagnosis of sickle cell trait, sickle-beta-thalassemia, or sickle cell anemia is made.

Impact of Sickle Cell Trait and Naturally Acquired Immunity on Uncomplicated Malaria after Controlled Human Malaria Infection in Adults in Gabon.

PubMed

Lell, Bertrand; Mordmüller, Benjamin; Dejon Agobe, Jean-Claude; Honkpehedji, Josiane; Zinsou, Jeannot; Mengue, Juliana Boex; Loembe, Marguerite Massinga; Adegnika, Ayola Akim; Held, Jana; Lalremruata, Albert; Nguyen, The Trong; Esen, Meral; Kc, Natasha; Ruben, Adam J; Chakravarty, Sumana; Lee Sim, B Kim; Billingsley, Peter F; James, Eric R; Richie, Thomas L; Hoffman, Stephen L; Kremsner, Peter G

2018-02-01

Controlled human malaria infection (CHMI) by direct venous inoculation (DVI) with 3,200 cryopreserved Plasmodium falciparum sporozoites (PfSPZ) consistently leads to parasitemia and malaria symptoms in malaria-naive adults. We used CHMI by DVI to investigate infection rates, parasite kinetics, and malaria symptoms in lifelong malaria-exposed (semi-immune) Gabonese adults with and without sickle cell trait. Eleven semi-immune Gabonese with normal hemoglobin (IA), nine with sickle cell trait (IS), and five nonimmune European controls with normal hemoglobin (NI) received 3,200 PfSPZ by DVI and were followed 28 days for parasitemia by thick blood smear (TBS) and quantitative polymerase chain reaction (qPCR) and for malaria symptoms. End points were time to parasitemia and parasitemia plus symptoms. PfSPZ Challenge was well tolerated and safe. Five of the five (100%) NI, 7/11 (64%) IA, and 5/9 (56%) IS volunteers developed parasitemia by TBS, and 5/5 (100%) NI, 9/11 (82%) IA, and 7/9 (78%) IS by qPCR, respectively. The time to parasitemia by TBS was longer in IA (geometric mean 16.9 days) and IS (19.1 days) than in NA (12.6 days) volunteers ( P = 0.016, 0.021, respectively). Five of the five, 6/9, and 1/7 volunteers with parasitemia developed symptoms ( P = 0.003, NI versus IS). Naturally adaptive immunity (NAI) to malaria significantly prolonged the time to parasitemia. Sickle cell trait seemed to prolong it further. NAI plus sickle cell trait, but not NAI alone, significantly reduced symptom rate. Twenty percent (4/20) semi-immunes demonstrated sterile protective immunity. Standardized CHMI with PfSPZ Challenge is a powerful tool for dissecting the impact of innate and naturally acquired adaptive immunity on malaria.

Nutcracker Syndrome and Sickle Cell Trait: A Perfect Storm for Hematuria.

PubMed

Ahmad, Amier; McElwee, Samuel K; Kraemer, Ryan R

2017-05-01

We describe the case of a 27-year-old woman with a history of sickle cell trait (SCT) who presented with several months of hematuria and was found to have nutcracker syndrome (NCS). While SCT is a common cause of hematuria resulting from renal papillary necrosis, our patient had concomitant abdominal pain and anemia, prompting further evaluation and the subsequent diagnosis of NCS. Interestingly, the anoxia in the left renal vein from NCS predisposes patients with SCT to sickling. Our case highlights key clinical features of both NCS and SCT and the relationship between the two disease processes.

Sickle cell disease and venous thromboembolism in pregnancy and the puerperium.

PubMed

Noubouossie, Denis; Key, Nigel S

2015-02-01

Recent data strongly suggest an increased risk of venous thromboembolism in subjects with sickle cell disease and to a lesser extent, sickle cell trait. However, most studies have been retrospective, case-control or cross-sectional based on data obtained from administrative databases. More data from adequately powered prospective studies that include matched controls are needed to definitely establish the link between venous thromboembolism during pregnancy and sickle hemoglobin disorders. Similarly, there remains a need for properly designed randomized control trials to establish the safety of various hormonal contraceptive methods in women with sickle cell disorders. © 2015 Elsevier Ltd. All rights reserved.

Perception of young adults with sickle cell disease or sickle cell trait about participation in the CHOICES randomized controlled trial.

PubMed

Hershberger, Patricia E; Gallo, Agatha M; Molokie, Robert; Thompson, Alexis A; Suarez, Marie L; Yao, Yingwei; Wilkie, Diana J

2016-06-01

To gain an in-depth understanding of the perceptions of young adults with sickle cell disease and sickle cell trait about parenthood and participating in the CHOICES randomized controlled trial that used computer-based, educational programmes. In the USA, there is insufficient education to assure that all young adults with sickle cell disease or sickle cell trait understand genetic inheritance risks and reproductive options to make informed reproductive decisions. To address this educational need, we developed a computer-based, multimedia program (CHOICES) and reformatted usual care into a computer-based (e-Book) program. We then conducted a two-year randomized controlled trial that included a qualitative component that would deepen understanding of young adults' perceptions of parenthood and use of computer-based, educational programmes. A qualitative descriptive approach completed after a randomized controlled trial. Sixty-eight men and women of childbearing age participated in semi-structured interviews at the completion of the randomized controlled trial from 2012-2013. Thematic content analysis guided the qualitative description. Three main themes were identified: (1) increasing knowledge and new ways of thinking and behaving; (2) rethinking parenting plans; and (3) appraising the program design and delivery. Most participants reported increased knowledge and rethinking of their parenting plans and were supportive of computer-based learning. Some participants expressed difficulty in determining individual transmission risks. Participants perceived the computer programs as beneficial to their learning. Future development of an Internet-based educational programme is warranted, with emphasis on providing tailored education or memory boosters about individual transmission risks. © 2015 John Wiley & Sons Ltd.

Renal medullary carcinoma and sickle cell trait: A systematic review.

PubMed

Alvarez, Ofelia; Rodriguez, Maria M; Jordan, Lanetta; Sarnaik, Sharada

2015-10-01

Sickle cell trait (SCT) carries a small risk of renal medullary carcinoma (RMC). We conducted a systematic literature review and reported new four RMC cases (total N = 217). Eighty eight percent had SCT and 8% had sickle cell disease; 50% were children. Males had 2.4× risk than females. Isolated hematuria or in combination with abdominal or flank pain was the presenting sign in 66% cases. Tumor-related mortality was 95%. Four non-metastatic patients were long-term disease-free survivors. Although risk appears to be very low, individuals with SCT should be informed about the low risk of RMC with the hope of early diagnosis. Hematuria should prompt immediate investigation. © 2015 Wiley Periodicals, Inc.

A Policy Impact Analysis of the Mandatory NCAA Sickle Cell Trait Screening Program

PubMed Central

Tarini, Beth A; Brooks, Margaret Alison; Bundy, David G

2012-01-01

Objective To estimate the impact of the mandatory National Collegiate Athletic Association (NCAA) sickle cell trait (SCT) screening policy on the identification of sickle cell carriers and prevention of sudden death. Data Source We used NCAA reports, population-based SCT prevalence estimates, and published risks for exercise-related sudden death attributable to SCT. Study Design We estimated the number of sickle cell carriers identified and the number of potentially preventable sudden deaths with mandatory SCT screening of NCAA Division I athletes. We calculated the number of student-athletes with SCT using a conditional probability based upon SCT prevalence data and self-identified race/ethnicity status. We estimated sudden deaths over 10 years based on published attributable risk of exercise-related sudden death due to SCT. Principal Findings We estimate that over 2,000 NCAA Division I student-athletes with SCT will be identified under this screening policy and that, without intervention, about seven NCAA Division I student-athletes would die suddenly as a complication of SCT over a 10-year period. Conclusion Universal sickle cell screening of NCAA Division I student-athletes will identify a substantial number of sickle cell carriers. A successful intervention could prevent about seven deaths over a decade. PMID:22150647

Assessment of factors possibly contributing to the susceptibility of sickle trait erythrocytes to mild hypoxia. I., Design considerations and research protocol.

DOT National Transportation Integrated Search

1978-08-01

This report continues a review (see FAA-AM-76-15) of the evidence for mixed dominance of the Hbs beta gene in people with the sickle cell trait. These individuals, whose erythrocytes contain a mixture of hemoglobins (HbA/HbS), are healthy and have a ...

Malaria hidden in a patient with diffuse large-B-cell lymphoma and sickle-cell trait.

PubMed

Linares, María; Albizua, Enriqueta; Méndez, Darío; Rubio, José M; Martínez-Serna, Alejandra; Martínez, Miguel A; Salto, Efren; Puyet, Antonio; Diez, Amalia; Martinez-López, Joaquin; Bautista, José M

2011-12-01

We report a case of an African patient with sickle cell trait who was diagnosed in Spain with B-cell lymphoma. Blood smears were negative for malaria, and no plasmodium antigens were detected in the blood. To treat his lymphoma, the patient underwent chemotherapy and autologous stem cell transplantation. Following a splenectomy due to a worsening condition, he developed clinical malaria with detectable parasitemia. This case suggests that the humoral response and parasite removal by the spleen may afford protection from overt disease and may even help maintain subclinical human reservoirs of the disease.

Sickle Cell: A Selected Resource Bibliography.

ERIC Educational Resources Information Center

National Center for Education in Maternal and Child Health, Washington, DC.

This annotated, selective bibliography lists the following types of educational and informational material on both sickle cell disease and trait: (1) professional education materials; (2) fact sheets, pamphlets, and brochures; and (3) audiovisual material. A selected list of references is provided for the following topic areas: (1) genetic…

Sudden death due to sickle cell crisis during law enforcement restraint.

PubMed

Channa Perera, S D; Pollanen, Michael S

2007-07-01

We report a case of vaso-occlusive sickle cell crisis in a young schizophrenic man with undiagnosed sickle cell trait who was restrained. Prior to being restrained he had locked himself in his apartment for two days without food or water. He was subsequently restrained, and transferred to hospital while handcuffed to the stretcher. He died suddenly during restraint. At autopsy, there was acute vaso-occlusive sickle cell crisis associated with hypernatremic dehydration. There were no injuries present. We conclude that the death was due to vaso-occlusive sickle cell crisis secondary to dehydration. It is important for the forensic pathologist to remember that death may occur suddenly during restraint from an unexpected mechanism other than excited delirium leading to cardiac arrhythmia or restraint asphyxia.

Massive gross hematuria in a sickle cell trait patient with renal papillary necrosis. Conservative approach using a balloon ureteral catheter to tamponade the papilla bleeding.

PubMed

Herard, A; Colin, J; Youinou, Y; Drancourt, E; Brandt, B

1998-08-01

We report the case of a patient with heterozygous sickle cell trait presenting with massive gross hematuria. Ureteroscopy revealed bleeding from the tip of papilla of the inferior calica and allowed us to tamponade the bleeding with a balloon ureteral dilator set (Cook(R) Urology). We show the value of the endourological approach in the conservative management of these patients at high risk of recurrent hematuria.

Sickle cell crisis leading to extensive necrosis in a low-grade glioma and masquerading high-grade lesion.

PubMed

Agrawal, Amit; Balpande, D N; Khan, A; Vagh, S J; Shukla, Samarth; Chopra, Sumit

2008-01-01

A 9-year-old female child presented with rapid neurological deterioration. Clinical features and imaging findings were suggestive of high-grade malignancy, and hematological investigations were suggestive of sickle cell trait. Histopathology showed features of low-grade malignancy and extensive intratumoral sickling. We hypothesize that the vicious cycle of hypoxia, sickling, thrombosis, ischemia and infarction resulted in the extensive tumor necrosis in the present case causing the initial symptoms and rapid deterioration in the condition of the patient. Copyright 2008 S. Karger AG, Basel.

NCAA Football Off-Season Training: Unanswered Prayers… A Prayer Answered

PubMed Central

Anderson, Scott

2017-01-01

Off-season training in year-round collegiate football is purported to be performance enhancing. Absent principles of exercise physiology, excesses in sport-training regimens pose risk to the participant athletes. Since 2000, 33 National Collegiate Athletic Association (NCAA) football players have died in sport: 27 nontraumatic deaths and 6 traumatic deaths, a ratio of 4.5 nontraumatic deaths for every traumatic death. On average, 2 NCAA football players die per season. Best practices, consensus guidelines, and precautions are ignored, elevating the risk. However, standards exist that will, if heeded, prevent nontraumatic death in athletes training for sport. Sickle cell trait status knowledge and tailored precautions are preventing deaths from exertional collapse associated with sickle cell trait. Adherence to established principles of exercise physiology and best-practice training standards, which is long overdue, will help to prevent not only deaths from exertional collapse associated with sickle cell trait but also sudden cardiac, exertional heat stroke, and asthma deaths. PMID:28140625

Modulation of sickle cell crisis by naturally occurring band 3 specific antibodies -- a malaria link.

PubMed

Kennedy, James Randall

2002-05-01

This paper's focus is prevention of sickle cell adhesion resulting from the erythrocyte's prematurely denatured hemoglobin. This denatured hemoglobin causes a molecule called band 3 to cluster on the erythrocyte's surface and adhere to the CD36 molecule located on the microvascular endothelium. Natural antibodies recognize these clusters on senescent erythrocytes and prevent their endothelial adhesion and target them for reticuloendothelial elimination. Band 3 is also displayed on the erythrocytes of individuals with falciparum malaria and the vaso-occlusive pathology in these patients is prevented in individuals with sickle trait. The hypothesis is that prematurely denatured sickle hemoglobin results in an up regulation of natural antibodies which control erythrocyte adhesion in both malaria and sickle cell disease.

Recommendations for the management of sickle cell disease in South Africa.

PubMed

Alli, N A; Patel, M; Alli, H D; Bassa, F; Coetzee, M J; Davidson, A; Essop, M R; Lakha, A; Louw, V J; Novitzky, N; Philip, V; Poole, J E; Wainwright, R D

2014-11-01

The spectrum of sickle cell disease (SCD) encompasses a heterogeneous group of disorders that include: (I) homozygous SCD (HbSS), also referred to as sickle cell anaemia; (ii) heterozygous SCD (HbAS), also referred to as sickle cell trait; and (iii) compound heterozygous states such as HbSC disease, HbSβ thalassaemia, etc. Homozygous or compound heterozygous SCD patients manifest with clinical disease of varying severity that is influenced by biological and environmental factors, whereas subject with sickle cell trait are largely asymptomatic. SCD is characterized by vaso-occlusive episodes that result in tissue ischaemia and pain in the affected region. Repeated infarctive episodes cause organ damage and may eventually lead to organ failure. For effective management, regular follow-up with support from a multidisciplinary healthcare team is necessary. The chronic nature of the disease, the steady increase in patient numbers, and relapsing acute episodes have cost implications that are likely to impact on provincial and national health budgets. Limited resources mandate local management protocols for the purposes of consistency and standardisation, which could also facilitate sharing of resources between centres for maximal utility. These recommendations have been developed for the South African setting, and it is intended to update them regularly to meet new demands and challenges.

Frequency of haemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency in Basra.

PubMed

Hassan, M K; Taha, J Y; Al-Naama, L M; Widad, N M; Jasim, S N

2003-01-01

Basra, southern Iraq, was mapped for haemoglobinopathies and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Of 1064 couples aged 14-60 years recruited from the Public Health Laboratory, 49 had beta-thalassaemia trait, 69 had sickle-cell trait, 2 had haemoglobin D trait, 2 had haemoglobin C trait and 1 had high persistent fetal haemoglobin. Carriers of major beta-globin disorders comprised 11.48%. G6PD deficiency was detected in 133 individuals (12.5%). Only 10 couples (0.94%) were at risk of having children affected with either sickle-cell disease or beta-thalassaemia major. These defects constitute a real health problem and necessitate a management plan and public health education for early diagnosis and therapy.

Sickle-cell hip necrosis and intraosseous pressure.

PubMed

Mukisi, M M; Bashoun, K; Burny, F

2009-04-01

Osteonecrosis of the femoral head (ONFH) is a frequent complication of sickle-cell disease. Numerous studies have demonstrated increased intraosseous pressure (IOP) in idiopathic necrosis and necrosis secondary to corticotherapy or alcohol poisoning. Several reports have testified to the clinical interest of decompression by drilling which, when performed in the early course of the pathology, can arrest or slow evolution. To the best of our knowledge, no studies have reported IOP increase in sickle-cell ONFH. The present study sought to show that intraosseous hyperpressure plays a role in the physiopathology of sickle-cell, like idiopathic, ONFH. Sixteen intraosseous pressure (IOP) measurements were taken: eight in adult sickle-cell disease patients, four in sickle-cell trait carrying ONFH patients (AS) and four in non-sickle-cell ONFH patients (AA). Arterial blood-pressure equipment with bone-puncture needle was used to measure IOP in the great trochanter body. Three IOP measurements were made after zero calibration: before drilling (direct pressure: IOP-1), after hyperpressure test but before drilling (IOP-2), and after drilling (IOP-3). The present, admittedly short, series displayed elevated predrilling IOP-1 and IOP-2, reduced after drilling (IOP-3). Abnormal IOP fell after drilling performed for evolutive symptomatic ONFH. Significant differences in IOP-1 and IOP-2 were found, these being higher in the "sickle-cell disease" and "sickle-cell trait carriers" groups (p<0.05). Only in the sickle-cell groups was there a significant correlation between pain score and hyperpressure level, with significantly reduced pain after drilling. The elevated IOP levels found in symptomatic sickle-cell hips were comparable to those reported in the literature. Ischemia due to femoral head sinusoid occlusion by falciform globules with secondary intraosseous hyperpressure is the cause of the pain and of the onset and evolution of ONFH. The drilling tunnel acts as a safety valve, achieving real decompression of the segment involved and immediate postoperative reduction in or disappearance of pain. Measuring pressure is of diagnostic interest in sickle-cell disease patients with symptomatic hips. Manometry can be performed independently of surgery, under local anesthesia, and provides early confirmation of ONFH in geographic regions in which MRI is not readily available. It can be carried out very straightforwardly, without pressure sensor, using a simple water column (physiological saline) and three-way tap. Peroperative comparison of IOP-1 and IOP-3 is a means of assessing the effectiveness of decompression drilling.

Red blood cell aggregation, aggregate strength and oxygen transport potential of blood are abnormal in both homozygous sickle cell anemia and sickle-hemoglobin C disease.

PubMed

Tripette, Julien; Alexy, Tamas; Hardy-Dessources, Marie-Dominique; Mougenel, Daniele; Beltan, Eric; Chalabi, Tawfik; Chout, Roger; Etienne-Julan, Maryse; Hue, Olivier; Meiselman, Herbert J; Connes, Philippe

2009-08-01

Recent evidence suggests that red blood cell aggregation and the ratio of hematocrit to blood viscosity (HVR), an index of the oxygen transport potential of blood, might considerably modulate blood flow dynamics in the microcirculation. It thus seems likely that these factors could play a role in sickle cell disease. We compared red blood cell aggregation characteristics, blood viscosity and HVR at different shear rates between sickle cell anemia and sickle cell hemoglobin C disease (SCC) patients, sickle cell trait carriers (AS) and control individuals (AA). Blood viscosity determined at high shear rate was lower in sickle cell anemia (n=21) than in AA (n=52), AS (n=33) or SCC (n=21), and was markedly increased in both SCC and AS. Despite differences in blood viscosity, both sickle cell anemia and SCC had similar low HVR values compared to both AA and AS. Sickle cell anemia (n=21) and SCC (n=19) subjects had a lower red blood cell aggregation index and longer time for red blood cell aggregates formation than AA (n=16) and AS (n=15), and a 2 to 3 fold greater shear rate required to disperse red blood cell aggregates. The low HVR levels found in sickle cell anemia and SCC indicates a comparable low oxygen transport potential of blood in both genotypes. Red blood cell aggregation properties are likely to be involved in the pathophysiology of sickle cell disease: the increased shear forces needed to disperse red blood cell aggregates may disturb blood flow, especially at the microcirculatory level, since red blood cell are only able to pass through narrow capillaries as single cells rather than as aggregates.

Reversible second degree atrioventricular block after a severe sickle cell crisis.

PubMed

Jaeggi, E; Bolens, M; Friedli, B

1998-01-01

Despite the high prevalence of sickle cell disease and trait in the black population and its serious potential for microinfarction, there are only a few reports on acute myocardial damage during vasoocclusive crisis. We report a unique case of transient second degree atrioventricular (A-V) block of Mobitz I and II type during a severe sickle cell crisis. Localized high ventricular septum hypoperfusion demonstrated by a 99mTc-MIBI radionuclide study and reversible echocardiographic wall motion abnormalities in the same area were strong indicators for a local ischemic event in the A-V node and His bundle area, explaining the observed transient conduction abnormalities. The present report draws attention to a potentially lethal complication of sickle cell crisis.

[Acute abdominal pain due to splenic infarction in a patient with heterozygous sickle cell disease exposed to high altitude].

PubMed

Ruiz Semba, Edgar; Garavito Rentería, Jorge; Jiménez Bustamante, Jorge; Arteaga Caro, Ronal; García Del Aguila, José Luis; Chávez Gil, Vannya

2006-01-01

Hemoglobinopathy S, Depranocytosis or Sickle Cell Disease is the most common hemoglobinopathy in the world. In its heterozygous form (Sickle Cell Trait), it affects 8% of the black population in the U.S. and 25% of the black population in Africa, and is found less frequently in the Mediterranean area, India, Middle East and Latin America. The basic alteration is a substitution of glutamic acid by valin in the sixth position of the beta globin chain, which causes polymerization at low oxygen tension thereby distorting the structure of erythrocytes and increasing blood viscosity, which, in turn, generates obstructions of the capillary arterial blood flow to different areas of the body thus causing microinfarctions. Although Splenic Infarction is rare, it is recognized as a serious complication of Heterozygous Sickle Cell Disease (Sickle Cell Trait). We present the case of a 21 year-old mestizo male patient who came in with an acute case of abdominal pain after arriving to work in the Casapalca mining city (located in the Peruvian Andes at 4200 m.a.s.l.) and was referred to our Hospital in Lima for exams. We present the case because it is an unusual cause of acute abdominal pain, and because this condition is rare in Peru and there are few publications about it.

Evaluation of high performance liquid chromatography (HPLC) pattern and prevalence of beta-thalassaemia trait among sickle cell disease patients in Lagos, Nigeria.

PubMed

Adeyemo, Titilope; Ojewunmi, Oyesola; Oyetunji, Ajoke

2014-01-01

Sickle cell disease (SCD) is the most common inherited disorder of haemoglobin worldwide. This study evaluated the chromatographic patterns and red blood cell indices of sickle cell patients to determine the co-inheritance of other haemoglobin(Hb) variants and β-thalassaemia trait. Red cell indices, blood film, sickle solubility test, Hb electrophoresis using alkaline cellulose acetate membrane, and chromatographic patterns using Bio Rad HPLC Variant II were evaluated for 180 subjects. Based on low MCV <76fL and MCH<25 pg, in the presence of elevated A₂ >4.0% on HPLC and Hb variants eluting outside the S and C windows, at least four haemoglobin phenotypes (SS: 87.7%; SC: 1.1%; SD Punjab: 0.6%; Sβ-thalassemia: 10.6%) were identified. Mean Hb F% was 8.1±5.1 (median 7.65) for Hb SS and 6.03±5.2 (median 3.9) for Hb Sβ-thalassemia trait. Majority of Hb SS (69.1%) had Hb F% less than 10 while 27.6% had 10-19.9 and 3.2% had ≥ 20. Mean Hb F% was higher in female Hb SS (9.55±5.09; mean age 7.4±3.8 years) than the males (7.63±4.80; mean age 6.9±3.8 years) (P=0.02). A borderline significant negative correlation between age and Hb F levels among Hb SS subjects (r= -0.169 P=0.038) was also observed. Our data suggests that α and β- thalassaemia traits, and other haemoglobin variants co-exist frequently with SCD in our population.

Effectiveness of antenatal screening for sickle cell trait: the impact on women's self-report of sickle cell trait status.

PubMed

Knight-Madden, J M; Reid, M; Younger, N; Francis, D; McFarlane, S; Wilks, R

2012-03-01

The sickle gene frequency in the Jamaican population has not changed over a generation. It is unknown whether routine antenatal screening for sickle cell trait (SCT) has affected women's knowledge of their SCT status. The aim of this study was to compare the prevalence of self-reported SCT in parous women to the prevalence in nulliparous women, men and to the observed prevalence of SCT measured in an antenatal clinic. All participants in the nationally representative Jamaica Health and Lifestyle Survey 2008 were asked whether they had the SCT. The impact of gender, age, educational attainment, geographical location, and pregnancy on self-reported SCT were assessed. The prevalence of SCT in women attending a large antenatal clinic concurrently was compared to that reported by women of child-bearing age in the lifestyle survey. Self-report significantly underestimated the prevalence of SCT (2·9% versus 10·1%, P<0·001). Those with secondary education were more likely than those with presecondary education (P = 0·01) and women more likely than men (3·2% versus 1·1%, P = 0·001) to report having SCT. Women who had been pregnant were no more likely than other women to report having SCT (3·1% versus 4·1%, P = 0·4). Attendance at antenatal clinic where SCT screening is routine, is not associated with increased self-report of SCT. Screening programs must ensure that, as well as technically accurate screening, there is effective communication of the results of screening for SCT to those tested to help reduce the public health burden of sickle cell disease in tropical countries.

Association between sickle cell and β-thalassemia genes and hemoglobin concentration and anemia in children and non-pregnant women in Sierra Leone: ancillary analysis of data from Sierra Leone's 2013 National Micronutrient Survey.

PubMed

Wirth, James P; Ansumana, Rashid; Woodruff, Bradley A; Koroma, Aminata S; Hodges, Mary H

2018-01-17

By measuring the associations between the presence of sickle cell and β-thalassemia genes, we assessed the extent to which these hemoglobinopathies contribute to the high prevalence of anemia observed in preschool-aged children and women of reproductive age in Sierra Leone. The prevalence of anemia was statistically significantly higher in children with homozygous sickle cell genes (HbSS) than in children with normal hemoglobin genes (HbAA or HbAC), but there was no difference in anemia prevalence in those with heterozygous sickle cell trait (HbAS or HbSC) compared with those with normal hemoglobin genes. In women, there was no difference in anemia prevalence by sickle cell status. In both children and women, there was no difference in the anemia prevalence for individuals with or without the β-thalassemia gene. For both sickle cell and β-thalassemia, there was no significant difference in hemoglobin concentrations by sickle cell or β-thalassemia status. Anemia prevalence was higher in children and women with homozygous sickle cell (HbSS). However, as the prevalence of HbSS children (5.4%) and women (1.6%) was quite small, it is unlikely that these hemoglobinopathies substantially contributed to the high anemia prevalence found in the 2013 national micronutrient survey.

[Targeted newborn screening for sickle-cell anemia: Sickling test (Emmel test) boundaries in the prenatal assessment in West African area].

PubMed

Diallo, D A; Guindo, A; Touré, B A; Sarro, Y S; Sima, M; Tessougué, O; Baraika, M A; Guindo, P; Traoré, M; Diallo, M; Dorie, A

2018-05-01

Newborn screening for sickle cell anemia is necessary in Africa where the disease is more frequent. Hemoglobin electrophoresis is used for screening, but is limited by a high cost and difficult access. Sickling test (Emmel test), which is more affordable and technically more accessible, is often requested for prenatal assessment of pregnant women in West African areas to reserve screening for newborns from mothers in whom the positive sickling test attests the presence of hemoglobin S. This study aims to evaluate the number of undetected sickle cell anemia newborns by a screening policy targeting only newborns from mothers in whom a sickling test would have been positive. From 2010 to 2012, in Bamako, Mali, West Africa, 2489 newborns were routinely screened for sickle cell anemia at the umbilical cord or heel by isoelectrofocusing and, if necessary, by high-performance liquid chromatography. These newborns were born from 2420 mothers whose hemoglobin was studied by isoelectrofocusing. The data was recorded and processed using Excel software version 14.0.0. We calculated the frequency of the sickle cell gene in mothers and newborns as well as the number of SCA newborns from heterozygous or C homozygous mothers. Of the 2489 newborns, 16 had sickle cell anemia (6 SS and 10 SC); 198 had the sickle cell trait; 139 were AC and 1 was CC. Of the 10 newborns with SC profile, 3 were born from mothers not carrying the S gene but the C gene of hemoglobin and in which an Emmel test would have been negative. Targeted newborn screening, based on the results of sickling test in pregnant women, would misdiagnose more than one of six sickle cell anemia newborns who would not benefit from early care. Cost-effectiveness studies of routine newborn screening for sickle cell anemia should lead to a better screening strategy in contexts where hemoglobin S and other hemoglobin defect genes coexist. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Alpha thalassemia among sickle cell anaemia patients in Kampala, Uganda.

PubMed

Lubega, Irene; Ndugwa, Christopher M; Mworozi, Edison A; Tumwine, James K

2015-06-01

Sickle cell anaemia is prevalent in sub Saharan Africa. While α+-thalassaemia is known to modulate sickle cell anaemia, its magnitude and significance in Uganda have hitherto not been described. To determine the prevalence of α+thalassaemia among sickle cell anaemia patients in Mulago Hospital and to describe the clinical and laboratory findings in these patients. A cross sectional study was carried out on patients with sickle cell anaemia in Kampala. Dried blood spots were used to analyze for the deletional α+ thalassaemia using multiplex polymerase chain reaction. Of the 142 patients with sickle cell anaemia, 110 (77.5%) had the αα+thalassaemia deletion. The gene frequency of (-α) was 0.425. Ninety one percent (100/110) of those with α+thalassaemia were heterozygous (αα/α-). Amongst the patients older than 60 months, 15 (83.3%) of those without αα+thalassaemia had significant hepatomegaly of greater than 4 cm compared to 36 (45.6%) of those with α+thalassaemia (p=0.003). The gene frequency of (-α) of 0.425 noted in this study is higher than that reported from many places in Africa. Concurrent alpha thalassemia might be a protective trait against significant hepatomegaly in sickle cell anaemia patients more than 60 months of age at Mulago hospital.

Detection of Sickle Cell Hemoglobin in Haiti by Genotyping and Hemoglobin Solubility Tests

PubMed Central

Carter, Tamar E.; von Fricken, Michael; Romain, Jean R.; Memnon, Gladys; St. Victor, Yves; Schick, Laura; Okech, Bernard A.; Mulligan, Connie J.

2014-01-01

Sickle cell disease is a growing global health concern because infants born with the disorder in developing countries are now surviving longer with little access to diagnostic and management options. In Haiti, the current state of sickle cell disease/trait in the population is unclear. To inform future screening efforts in Haiti, we assayed sickle hemoglobin mutations using traditional hemoglobin solubility tests (HST) and add-on techniques, which incorporated spectrophotometry and insoluble hemoglobin separation. We also generated genotype data as a metric for HST performance. We found 19 of 202 individuals screened with HST were positive for sickle hemoglobin, five of whom did not carry the HbS allele. We show that spectrophotometry and insoluble hemoglobin separation add-on techniques could resolve false positives associated with the traditional HST approach, with some limitations. We also discuss the incorporation of insoluble hemoglobin separation observation with HST in suboptimal screening settings like Haiti. PMID:24957539

Validation of a Low-Cost Paper-Based Screening Test for Sickle Cell Anemia

PubMed Central

Piety, Nathaniel Z.; Yang, Xiaoxi; Kanter, Julie; Vignes, Seth M.; George, Alex; Shevkoplyas, Sergey S.

2016-01-01

Background The high childhood mortality and life-long complications associated with sickle cell anemia (SCA) in developing countries could be significantly reduced with effective prophylaxis and education if SCA is diagnosed early in life. However, conventional laboratory methods used for diagnosing SCA remain prohibitively expensive and impractical in this setting. This study describes the clinical validation of a low-cost paper-based test for SCA that can accurately identify sickle trait carriers (HbAS) and individuals with SCA (HbSS) among adults and children over 1 year of age. Methods and Findings In a population of healthy volunteers and SCA patients in the United States (n = 55) the test identified individuals whose blood contained any HbS (HbAS and HbSS) with 100% sensitivity and 100% specificity for both visual evaluation and automated analysis, and detected SCA (HbSS) with 93% sensitivity and 94% specificity for visual evaluation and 100% sensitivity and 97% specificity for automated analysis. In a population of post-partum women (with a previously unknown SCA status) at a primary obstetric hospital in Cabinda, Angola (n = 226) the test identified sickle cell trait carriers with 94% sensitivity and 97% specificity using visual evaluation (none of the women had SCA). Notably, our test permits instrument- and electricity-free visual diagnostics, requires minimal training to be performed, can be completed within 30 minutes, and costs about $0.07 in test-specific consumable materials. Conclusions Our results validate the paper-based SCA test as a useful low-cost tool for screening adults and children for sickle trait and disease and demonstrate its practicality in resource-limited clinical settings. PMID:26735691

Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications.

PubMed

Goldsmith, Jonathan C; Bonham, Vence L; Joiner, Clinton H; Kato, Gregory J; Noonan, Allan S; Steinberg, Martin H

2012-03-01

Sickle Cell Trait (HbAS), the heterozygous state for the sickle hemoglobin beta globin gene is carried by as many as 100 million individuals including up to 25% of the population in some regions of the world (World Health Organization, Provisional agenda item 4.8, EB117/34 (22 December 2005) or World Health Organization, Provisional agenda item 11.4 (24 April 2006)). Persons with HbAS have some resistance to falciparum malaria infection in early childhood (Piel FB, Patil AP, Howes RE, et al., Nat Commun 2010;1104:1-7 and Aidoo M, Terlouw DJ, Kolczak M, et al., Lancet 2002;359:1311-1312) and as a result individuals with HbAS living in malarial endemic regions of Africa have a survival advantage over individuals with HbAA. Reports from the US emphasize possible health risks for individuals with HbAS including increased incidence of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. The National Heart, Lung, and Blood Institute, National Institutes of Health convened a workshop in Bethesda, Maryland on June 3-4, 2010, Framing the Research Agenda for Sickle Cell Trait, to review the clinical manifestations of HbAS, discuss the exercise-related sudden death reports in HbAS, and examine the public health, societal, and ethical implications of policies regarding HbAS. The goal of the workshop was to identify potential research questions to address knowledge gaps.

Autonomic nervous system involvement in sickle cell disease.

PubMed

Coates, Thomas D; Chalacheva, Patjanaporn; Zeltzer, Lonnie; Khoo, Michael C K

2018-01-01

Sickle cell disease (SCD) is a genetic disorder of hemoglobin producing hemoglobin-S (HbS) and resulting in recurrent severe episodes of pain, organ damage and premature death due to vaso- occlusion. Deoxy HbS polymerizes, causing red cells to become rigid and lodge in the microvasculature if they do not escape into larger vessels before this transformation occurs. The mechanism that triggers this transition from steady state to vaso-occlusive crisis (VOC) is not known. Patients state that cold, emotional stress, and pain itself can trigger these events. In spite of the connection between these symptoms and the autonomic nervous system (ANS), and the fact that the ANS regulates regional microvascular blood flow, the role of the ANS in sickle pathophysiology has not been significantly investigated. We will briefly review the mechanism of SCD vaso-occlusion, the dysautonomia associated with SCD and sickle trait, and the role that the ANS may play in the genesis of sickle vaso-occlusive crisis.

New pulmonary infiltrates in a 19 year-old with sickle cell crisis.

PubMed

Islam, Tasbirul; Usman, Md Haris Umer; Rahman, Fahd

2005-10-01

Sickle cell anemia (SCA) is the most common inherited blood disorder. Sickle cell crisis is characterized by episodes of pain, chronic hemolytic anemia and severe infections, usually beginning in early childhood. Sickle cell disease primarily affects those of African descent and Hispanics of Caribbean ancestry, but the trait has also been found in those with Middle Eastern, Indian, Latin American, Native American, and Mediterranean heritage. Recent studies indicate that more than 12,500 people in England have sickle cell disorders. The acute chest syndrome is the leading cause of death and the second most common cause of hospitalization among patients with sickle cell disease. The acute chest syndrome (ACS) is characterized by chest pain with dyspnea and recent radiological abnormalities. Since its cause is largely unknown, rapid recognition and early institution of therapy is paramount as with timely and appropriate intervention majority of these patients survive. The treatment of ACS rests on controlled hydration, antibiotic therapy, oxygen therapy, controlled analgesic therapy, blood transfusion and exchange transfusion. A better understanding of the disease and a close collaborative approach between a primary care physician and a specialist may be the key to improve the quality of care rendered. Research studies, review articles, and published scientific meeting abstracts were reviewed.

Sickle cell disease: renal manifestations and mechanisms

PubMed Central

Nath, Karl A.; Hebbel, Robert P.

2015-01-01

Sickle cell disease (SCD) substantially alters renal structure and function, and causes various renal syndromes and diseases. Such diverse renal outcomes reflect the uniquely complex vascular pathobiology of SCD and the propensity of red blood cells to sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions. Renal complications and involvement in sickle cell nephropathy (SCN) include altered haemodynamics, hypertrophy, assorted glomerulopathies, chronic kidney disease, acute kidney injury, impaired urinary concentrating ability, distal nephron dysfunction, haematuria, and increased risks of urinary tract infections and renal medullary carcinoma. SCN largely reflects an underlying vasculopathy characterized by cortical hyperperfusion, medullary hypoperfusion, and an increased, stress-induced vasoconstrictive response. Renal involvement is usually more severe in homozygous disease (sickle cell anaemia, HbSS) than in compound heterozygous types of SCD (for example HbSC and HbSβ+-thalassaemia), and is typically mild, albeit prevalent, in the heterozygous state (sickle cell trait, HbAS). Renal involvement contributes substantially to the diminished life expectancy of patients with SCD, accounting for 16–18% of mortality. As improved clinical care promotes survival into adulthood, SCN imposes a growing burden on both individual health and health system costs. This Review addresses the renal manifestations of SCD and focuses on their underlying mechanisms. PMID:25668001

Neonatal Screening and the Clinical Outcome in Children with Sickle Cell Disease in Central India

PubMed Central

Upadhye, Dipti S.; Jain, Dipty L.; Trivedi, Yogesh L.; Nadkarni, Anita H.; Ghosh, Kanjaksha; Colah, Roshan B.

2016-01-01

Background Sickle cell disease (SCD) is a major health burden in India. The objective of the study was to establish a neonatal screening program and to understand the clinical course of children with SCD in central India. Methods and Findings Pregnant mothers were screened for sickle hemoglobin using the solubility test. Babies were screened by high performance liquid chromatography if the mother was positive for sickle hemoglobin. The diagnosis was confirmed by molecular analysis. They received early prophylactic treatment and vaccination. Of 2134 newborns screened, 104 were sickle homozygous (SS), seven had sickle β-thalassemia (S-β thal) and 978 were sickle heterozygous (AS). The other hemoglobin abnormalities detected included HbS -δβ thalassemia-1, HbSD disease-2, HbE traits-5, β-thalassemia traits-4, alpha chain variants-3 and HbH disease-1.These babies were followed up regularly for hematological and clinical evaluation. Pain, severe anemia requiring blood transfusions and acute febrile illness were the major complications with 59.7, 45.1 and 42.6 cases per 100 person years. Fetal hemoglobin (HbF) levels were inversely associated with vaso-oclussive crisis (VOC) and severe anemia while presence of alpha thalassemia increased the rate of painful events and sepsis. Six early deaths occurred among the SS babies. Conclusion A systematic follow up of this first newborn SCD cohort in central India showed that 47% of babies presented within 1 year of age. In spite of the presence of the Arab-Indian haplotype many babies had severe manifestations. PMID:26785407

Cellular function reinstitution of offspring red blood cells cloned from the sickle cell disease patient blood post CRISPR genome editing.

PubMed

Wen, Jianguo; Tao, Wenjing; Hao, Suyang; Zu, Youli

2017-06-13

Sickle cell disease (SCD) is a disorder of red blood cells (RBCs) expressing abnormal hemoglobin-S (HbS) due to genetic inheritance of homologous HbS gene. However, people with the sickle cell trait (SCT) carry a single allele of HbS and do not usually suffer from SCD symptoms, thus providing a rationale to treat SCD. To validate gene therapy potential, hematopoietic stem cells were isolated from the SCD patient blood and treated with CRISPR/Cas9 approach. To precisely dissect genome-editing effects, erythroid progenitor cells were cloned from single colonies of CRISPR-treated cells and then expanded for simultaneous gene, protein, and cellular function studies. Genotyping and sequencing analysis revealed that the genome-edited erythroid progenitor colonies were converted to SCT genotype from SCD genotype. HPLC protein assays confirmed reinstallation of normal hemoglobin at a similar level with HbS in the cloned genome-edited erythroid progenitor cells. For cell function evaluation, in vitro RBC differentiation of the cloned erythroid progenitor cells was induced. As expected, cell sickling assays indicated function reinstitution of the genome-edited offspring SCD RBCs, which became more resistant to sickling under hypoxia condition. This study is an exploration of genome editing of SCD HSPCs.

Frequency and origin of haplotypes associated with the beta-globin gene cluster in individuals with trait and sickle cell anemia in the Atlantic and Pacific coastal regions of Colombia

PubMed Central

Fong, Cristian; Lizarralde-Iragorri, María Alejandra; Rojas-Gallardo, Diana; Barreto, Guillermo

2013-01-01

Sickle cell anemia is a genetic disease with high prevalence in people of African descent. There are five typical haplotypes associated with this disease and the haplotypes associated with the beta-globin gene cluster have been used to establish the origin of African-descendant people in America. In this work, we determined the frequency and the origin of haplotypes associated with hemoglobin S in a sample of individuals with sickle cell anemia (HbSS) and sickle cell hemoglobin trait (HbAS) in coastal regions of Colombia. Blood samples from 71 HbAS and 79 HbSS individuals were obtained. Haplotypes were determined based on the presence of variable restriction sites within the β-globin gene cluster. On the Pacific coast of Colombia the most frequent haplotype was Benin, while on the Atlantic coast Bantu was marginally higher than Benin. Eight atypical haplotypes were observed on both coasts, being more diverse in the Atlantic than in the Pacific region. These results suggest a differential settlement of the coasts, dependent on where slaves were brought from, either from the Gulf of Guinea or from Angola, where the haplotype distributions are similar. Atypical haplotypes probably originated from point mutations that lost or gained a restriction site and/or by recombination events. PMID:24385850

Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications

PubMed Central

Goldsmith, Jonathan C.; Bonham, Vence L.; Joiner, Clinton H.; Kato, Gregory J.; Noonan, Allan S.; Steinberg, Martin H.

2012-01-01

Sickle Cell Trait (HbAS), the heterozygous state for the sickle hemoglobin beta globin gene is carried by as many as 100 million individuals including up to 25% of the population in some regions of the world (World Health Organization, Provisional agenda item 4.8, EB117/34 (22 December 2005) or World Health Organization, Provisional agenda item 11.4 (24 April 2006)). Persons with HbAS have some resistance to falciparum malaria infection in early childhood (Piel FB, Patil AP, Howes RE, et al., Nat Commun 2010;1104:1–7 and Aidoo M, Terlouw DJ, Kolczak M, et al., Lancet 2002;359:1311–1312) and as a result individuals with HbAS living in malarial endemic regions of Africa have a survival advantage over individuals with HbAA. Reports from the US emphasize possible health risks for individuals with HbAS including increased incidence of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. The National Heart, Lung, and Blood Institute, National Institutes of Health convened a workshop in Bethesda, Maryland on June 3–4, 2010, Framing the Research Agenda for Sickle Cell Trait, to review the clinical manifestations of HbAS, discuss the exercise-related sudden death reports in HbAS, and examine the public health, societal, and ethical implications of policies regarding HbAS. The goal of the workshop was to identify potential research questions to address knowledge gaps. PMID:22307997

Malaria Hidden in a Patient with Diffuse Large-B-Cell Lymphoma and Sickle-Cell Trait▿

PubMed Central

Linares, María; Albizua, Enriqueta; Méndez, Darío; Rubio, José M.; Martínez-Serna, Alejandra; Martínez, Miguel A.; Salto, Efren; Puyet, Antonio; Diez, Amalia; Martinez-López, Joaquin; Bautista, José M.

2011-01-01

We report a case of an African patient with sickle cell trait who was diagnosed in Spain with B-cell lymphoma. Blood smears were negative for malaria, and no plasmodium antigens were detected in the blood. To treat his lymphoma, the patient underwent chemotherapy and autologous stem cell transplantation. Following a splenectomy due to a worsening condition, he developed clinical malaria with detectable parasitemia. This case suggests that the humoral response and parasite removal by the spleen may afford protection from overt disease and may even help maintain subclinical human reservoirs of the disease. PMID:21976762

Prevalence of the β(S) gene among scheduled castes, scheduled tribes and other backward class groups in Central India.

PubMed

Shrikhande, Anuradha V; Arjunan, Aishwarya; Agarwal, Amit; Dani, Aarti; Tijare, Jayashri; Gettig, Elizabeth; Krishnamurti, Lakshmanan

2014-01-01

Sickle cell disease is an inherited disorder of the blood, and characterized by vasoocclusive crises (VOC), risks for pneumococcal infections and organ toxicities, is associated with morbidity and premature mortality. India, with a population of 1.2 billion individuals, is estimated to be home to over 50.0% of the world's patients with sickle cell disease. The β(S) gene [β6(A3)Glu→Val; HBB: c.20A>T] has the highest prevalence in three socio-economically disadvantaged ethnic categories: the Scheduled Castes (SC), the Scheduled Tribes (ST), and Other Backward Class (OBC) groups in India. The tradition of endogamy practiced by the ethnic groups in India provides the rationale for the screening of individual populations to better understand the distribution of the β(S) gene, guide counseling and awareness programs and aid development of public policy. We undertook a study to describe the prevalence of the β(S) gene in these ethnic groups in the district of Nagpur, Maharashtra in Central India. Through community screening and subsequent targeted screening of high risk individuals, 35,636 individuals were screened, of whom 5466 were found to have sickle cell trait and 1010 were identified with sickle cell disease. Community screening revealed a sickle cell trait prevalence of 13.0% in the SC, 12.0% in the ST and 3.4% in the OBC population. This study describes the prevalence of the β(S) gene within these groups in Central India determined by large scale community screening. This program has uncovered previously undiagnosed cases, provided detailed information to guide population-based disease counseling, prevention and comprehensive care programs.

Glucose-6-Phosphate Dehydrogenase Deficiency and Sickle Cell Trait among Prospective Blood Donors: A Cross-Sectional Study in Berekum, Ghana.

PubMed

Adu, Patrick; Simpong, David Larbi; Takyi, Godfred; Ephraim, Richard K D

2016-01-01

Background. Blood transfusion is a therapeutic procedure usually undertaken in patients with severe anaemia. In Ghana, severe anaemia is mostly due to malaria caused by severe Plasmodium falciparum infection, road traffic accidents, and haemoglobinopathy-induced acute haemolysis. Method. This cross-sectional study evaluated coinheritance of sickle cell haemoglobin variant and G6PD enzymopathy among individuals that donated blood at the Holy Trinity Hospital, Berekum, in the Brong-Ahafo Region, Ghana. Demographic data and other pertinent information were captured using questionnaire. Sickle cell haemoglobin variants were determined using cellulose acetate electrophoresis (pH 8.6). Qualitative G6PD status and quantitative G6PD enzyme activity were determined using methaemoglobin reduction and Trinity Biotech G6PD test kit, respectively. Results. Prevalence of sickle cell trait (SCT) and G6PD enzymopathy coinheritance was 7%. In addition, 19.5% of the donors had 10%-60% of normal G6PD enzyme activity suggesting that these donor units are prone to stressor-induced acute haemolysis when given to recipients. Mild G6PD activity ( p = 0.03, OR: 2.410 (CI: 1.049-5.534)), commercial ( p = 0.020, OR: 5.609 (CI: 1.309-24.035)), and voluntary ( p = 0.034, OR: 2.404 (CI: 1.071-5.397)) donors were significantly associated with SCT. Conclusion. Screening for red cell pathologies must be incorporated into existing protocols for populations with high incidence of haemoglobinopathies to protect high-risk recipients.

Perinatal implications of sickle cell disease.

PubMed

MacMullen, Nancy J; Dulski, Laura A

2011-01-01

Sickle cell disease (SCD) affects millions of people across the globe. In the United States, approximately 70,000 to 100,000 people have the disease, and 2 million have the sickle cell trait. SCD occurs once in every 500 African American births, and once in 36,000 Hispanic American births. Women with SCD can have more adverse maternal outcomes such as preeclampsia, eclampsia, preterm labor, placental abruption, intrauterine growth restriction, and low birthweight. Providing comprehensive nursing care to women with SCD is a challenge, particularly during labor and birth, with nursing management aimed at attaining healthy birth outcomes while preventing or treating manifestations of the disease. Labor and delivery nurses are responsible for specific knowledge and care practices for these women, including differentiating the pain of sickle cell crisis from contraction pain and monitoring maternal and fetal oxygenation, as oxygenation is jeopardized in laboring sickle cell patients. Intrapartum nursing care also requires vigilance in the need for emergency cesarean birth. Nursing interventions include symptom management, pain management, ensuring patient safety, and educating patients. Coordination of care and clear communication between the members of the healthcare team, patient, and family are essential elements to ensure a positive outcome for perinatal patients with SCD.

[Evaluation of coverage by a neonatal screening program for hemoglobinopathies in the Recôncavo region of Bahia, Brazil].

PubMed

Silva, Wellington dos Santos; Lastra, Angel; de Oliveira, Silviene Fabiana; Klautau-Guimarães, Nazaré; Grisolia, Cesar Kope

2006-12-01

In 2001, government ruling n. MS 822/01 by the Brazilian Ministry of Health made neonatal screening mandatory for hemoglobinopathies, with special focus on sickle cell disease, the most common hemoglobinopathy in Brazil. Bahia is the State of Brazil with the highest prevalence of this disease. The current paper reports on the prevalence of hemoglobin variants HbS and HbC, which cause sickle cell disease, in the cities of Cachoeira, Maragogipe, and São Félix, Bahia State. The overall proportion of carriers for the two forms of hemoglobin was 13%. From 2001 to 2003, the neonatal screening rate decreased from 82.6% to 46.4% in Cachoeira and increased from 37.0% to 56.2% in Maragogipe. Thus, only about one-half of children are being tested in these cities. The findings show that the public health care system in these cities is poorly prepared to screen for sickle cell disease in newborns and that there was a lack of health care personnel to follow up on newly diagnosed sickle cell patients or carriers of the sickle cell trait.

Red blood cell-derived microparticles: An overview.

PubMed

Westerman, Maxwell; Porter, John B

2016-07-01

The red blood cell (RBC) is historically the original parent cell of microparticles (MPs). In this overview, we describe the discovery and the early history of red cell-derived microparticles (RMPs) and present an overview of the evolution of RMP. We report the formation, characteristics, effects of RMP and factors which may affect RMP evaluation. The review examines RMP derived from both normal and pathologic RBC. The pathologic RBC studies include sickle cell anemia (SCA), sickle cell trait (STr), thalassemia intermedia (TI), hereditary spherocytosis (HS), hereditary elliptocytosis (HE), hereditary stomatocytosis (HSt) and glucose-6-phosphate dehydrogenase deficiency (G6PD). Copyright © 2016 Elsevier Inc. All rights reserved.

Dental infections increase the likelihood of hospital admissions among adult patients with sickle cell disease

PubMed Central

Laurence, B.; Haywood, C; Lanzkron, S.

2014-01-01

The objective To determine if dental infections increase the likelihood of hospital admission among adult patients with sickle cell disease (SCD). Basic Research Design Cross-sectional analysis of data from the Nationwide Emergency Department Sample (NEDS) pooled for the years 2006 through 2008. Prevalence ratios (PR) for the effects of interest were estimated using Poisson regression with robust estimates of the variance. Participants Adults, aged 18 and over, diagnosed with SCD using ICD-9-CM codes excluding participants discharged with a code for sickle cell trait. Main outcome measure Emergency department (ED) visit disposition, dichotomised to represent whether or not the ED visit ended in admission versus being treated and released. Results Among patients having a sickle cell crisis, those with dental infections were 72% more likely to be admitted compared to those not having dental infections (PR=1.72, 95%CI 1.58-1.87). No association was observed among adult SCD patients not having a sickle crisis event. Based on preliminary data from this analysis, prevention of dental infection among patients with SCD could result in an estimated cost saving of $2.5 million dollars per year. Conclusions Having a dental infection complicated by a sickle cell crisis significantly increases the likelihood of hospital admission among adult SCD patients presenting to the ED. PMID:24151791

Biochemical and immunological mechanisms by which sickle cell trait protects against malaria.

PubMed

Gong, Lauren; Parikh, Sunil; Rosenthal, Philip J; Greenhouse, Bryan

2013-09-11

Sickle cell trait (HbAS) is the best-characterized genetic polymorphism known to protect against falciparum malaria. Although the protective effect of HbAS against malaria is well known, the mechanism(s) of protection remain unclear. A number of biochemical and immune-mediated mechanisms have been proposed, and it is likely that multiple complex mechanisms are responsible for the observed protection. Increased evidence for an immune component of protection as well as novel mechanisms, such as enhanced tolerance to disease mediated by HO-1 and reduced parasitic growth due to translocation of host micro-RNA into the parasite, have recently been described. A better understanding of relevant mechanisms will provide valuable insight into the host-parasite relationship, including the role of the host immune system in protection against malaria.

Biochemical and immunological mechanisms by which sickle cell trait protects against malaria

PubMed Central

2013-01-01

Sickle cell trait (HbAS) is the best-characterized genetic polymorphism known to protect against falciparum malaria. Although the protective effect of HbAS against malaria is well known, the mechanism(s) of protection remain unclear. A number of biochemical and immune-mediated mechanisms have been proposed, and it is likely that multiple complex mechanisms are responsible for the observed protection. Increased evidence for an immune component of protection as well as novel mechanisms, such as enhanced tolerance to disease mediated by HO-1 and reduced parasitic growth due to translocation of host micro-RNA into the parasite, have recently been described. A better understanding of relevant mechanisms will provide valuable insight into the host-parasite relationship, including the role of the host immune system in protection against malaria. PMID:24025776

A new gene deletion in the alpha-like globin gene cluster as the molecular basis for the rare alpha-thalassemia-1(--/alpha alpha) in blacks: HbH disease in sickle cell trait.

PubMed

Steinberg, M H; Coleman, M B; Adams, J G; Hartmann, R C; Saba, H; Anagnou, N P

1986-02-01

A novel deletion of at least 26 kilobase of DNA, including both alpha-globin genes, the psi alpha- and psi zeta-globin genes, but sparing the functional zeta-gene was found in a 10-year-old black boy with HbH disease and sickle cell trait. This particular deletion has not previously been described in blacks. Its existence makes it likely that the absence of Hb Barts hydrops fetalis in blacks is due to the rarity of the chromosome lacking two alpha-globin genes rather than a result of early embryonic death due to the failure to synthesize embryonic hemoglobins because of deletion of functional zeta-globin genes.

Prevalence of polymorphisms in glucose-6-phosphate dehydrogenase, sickle haemoglobin and nitric oxide synthase genes and their relationship with incidence of uncomplicated malaria in Iganga, Uganda.

PubMed

Lwanira, Catherine Nassozi; Kironde, Fred; Kaddumukasa, Mark; Swedberg, Göte

2017-08-09

Host genetics play an important role in Plasmodium falciparum malaria susceptibility. However, information on host genetic factors and their relationships with malaria in the vaccine trial site of Iganga, Uganda is limited. The main objective of this study was to determine the prevalence of selected host genetic markers and their relationship to malaria incidence in the vaccine trial site of Iganga, Uganda. In a 1-year longitudinal cohort study, 423 children aged below 9 years were recruited and their malaria episodes were investigated. Host genetic polymorphisms were assessed by PCR-RFLP, haemoglobin electrophoresis and DNA sequencing. Using a multivariate negative binomial regression model, estimates of the impact of human genetic polymorphisms on malaria incidence were performed. In all statistical tests, a P value of <0.05 was considered as significant. The prevalences of sickle cell haemoglobin trait, G6PD c.202 G>A (rs 1050828) and NOS2 -954 G>C (rs 1800482) variants were 26.6, 22.7 and 17.3%, respectively. Inducible nitric oxide synthase 2 (NOS2 -954 G>C; rs 1800482) heterozygosity was associated with lower incidence of malaria in all age groups {Adjusted incident rates ratio (aIRR) 0.59; 95% CI [0.386-0.887]; P = 0.012)}. About 4% of study subjects had co-existence of sickle cell Hb trait and G6PD deficiency. Sickle cell Hb heterozygotes (Hb AS) aged less than 1 year experienced significantly more malaria episodes annually than children with normal haemoglobin (Hb AA) {aIRR = 1.98; 95% CI [1.240-3.175]; P = 0.004}. There was no significant influence of the sickle cell trait on malaria incidence among older children of 1-9 years. Mutation (NOS2 -954 G>C; rs 1800482) of nitric oxide synthase 2 gene promoter was associated with a lower incidence of acute malaria. The normal haemoglobin (wild genotype; HbAA) was associated with reduced malaria incidence rates during the first year of life. More understanding of the interplay between host genetics and malaria susceptibility is required.

Sickle Cell Trait

MedlinePlus

... muscle breakdown when doing intense exercise, such as competitive sports or military training under unfavorable temperatures( very ... during training. People with SCT who participate in competitive or team sports (i.e. student athletes) should ...

Increasing hemoglobin oxygen saturation levels in sickle trait donor whole blood prevents hemoglobin S polymerization and allows effective white blood cell reduction by filtration.

PubMed

Stroncek, David F; Byrne, Karen M; Noguchi, Constance T; Schechter, Alan N; Leitman, Susan F

2004-09-01

BACKGROUND Red blood cell (RBC) components from donors with sickle cell trait (Hb AS) often occlude white blood cell (WBC) reduction filters. Techniques were investigated to successfully filter Hb AS donor blood by increasing the Hb oxygen saturation with storage bags and conditions suitable for transfusion products. Oxygenation kinetics were measured over 3 days in whole-blood units stored in standard-sized 600-mL polyvinylchloride (PVC) bags and whole-blood units divided into three equal parts and stored in standard-sized blood bags made from PVC, tri-2-(ethylhexyl)trimellitate (CLX) plastic, or Teflon. The filterability of Hb AS blood stored for 3 days was tested with whole-blood filters. Oxygen saturation levels did not increase in full whole-blood units from donors without sickle cell trait during 3 days of storage in 600-mL PVC bags. In divided Hb AS whole-blood units stored for 3 days, oxygen saturation levels increased from baseline levels of 45 to 56, 66, and 94 percent after storage in 600-mL PVC, CLX, and Teflon bags, respectively (n = 5, p < 0.02), and all components filtered completely. When full Hb AS whole-blood units from eight donors were stored for 3 days in 1.5-L CLX bags, all units filtered completely, but one had a high residual WBC count. Storage of Hb AS whole blood in large-capacity oxygen-permeable bags increases oxygen tension and allows more effective WBC reduction by filtration.

[Cardiac manifestations of sickle cell anemia].

PubMed

Gacon, P H; Donatien, Y

HEMOGLOBINS S AND C: Drepanocytosis, the occurrence of sickle cells (drepanocytes) in the blood, is an inherited condition. Electrophoresis demonstrates hemoglobin SS in homozygous subjects who present the typical clinical features of severe hemolytic sickle-cell anemia. Heterozygous subjects have sickle-cell anemia trait, an asymptomatic condition associated with a 50% hemoglobin S and 50% hemoglobin C at electrophoresis. Hemoglobin S and C are transmitted by Mendelian inheritance. CARDIAC DISORDERS: Well-known, cardiac disorders occur in more than 82% of homozygous subjects while only 2% of heterozygous subjects are affected. Heart murmur, radiological cardiomegaly, or eletrocardiographic anomalies are often the only signs. There is a risk of fatal heart failure in children and neonates. Acute rheumatic fever or infectious endocarditis, particularly due to pneumococcal or Haemophilus influenzae infection, may trigger heart failure. CARDIAC ANOMALIES: Patients with sickle-cell anemia can develop an "anemic heart" expressed by an elevated cardiac output and systemic ejection volume at rest and a fall in arteriolar peripheral resistance. Patients who develop cor pulmonae have an elevated pulmonary pressure at exercise and experience venous occlusive events with a progressive reduction in the pulmonary vascular bed and development of a left-right shunt. Myocardiopathy leads to left ventricular dysfunction contrasting with the dilated right heart seen at echocardiography and rare cases of transmural infarction.

Candidate Sequence Variants and Fetal Hemoglobin in Children with Sickle Cell Disease Treated with Hydroxyurea

PubMed Central

Green, Nancy S.; Ender, Katherine L.; Pashankar, Farzana; Driscoll, Catherine; Giardina, Patricia J.; Mullen, Craig A.; Clark, Lorraine N.; Manwani, Deepa; Crotty, Jennifer; Kisselev, Sergey; Neville, Kathleen A.; Hoppe, Carolyn; Barral, Sandra

2013-01-01

Background Fetal hemoglobin level is a heritable complex trait that strongly correlates swith the clinical severity of sickle cell disease. Only few genetic loci have been identified as robustly associated with fetal hemoglobin in patients with sickle cell disease, primarily adults. The sole approved pharmacologic therapy for this disease is hydroxyurea, with effects largely attributable to induction of fetal hemoglobin. Methodology/Principal Findings In a multi-site observational analysis of children with sickle cell disease, candidate single nucleotide polymorphisms associated with baseline fetal hemoglobin levels in adult sickle cell disease were examined in children at baseline and induced by hydroxyurea therapy. For baseline levels, single marker analysis demonstrated significant association with BCL11A and the beta and epsilon globin loci (HBB and HBE, respectively), with an additive attributable variance from these loci of 23%. Among a subset of children on hydroxyurea, baseline fetal hemoglobin levels explained 33% of the variance in induced levels. The variant in HBE accounted for an additional 13% of the variance in induced levels, while variants in the HBB and BCL11A loci did not contribute beyond baseline levels. Conclusions/Significance These findings clarify the overlap between baseline and hydroxyurea-induced fetal hemoglobin levels in pediatric disease. Studies assessing influences of specific sequence variants in these and other genetic loci in larger populations and in unusual hydroxyurea responders are needed to further understand the maintenance and therapeutic induction of fetal hemoglobin in pediatric sickle cell disease. PMID:23409025

Renal cell carcinoma, unclassified with medullary phenotype: poorly differentiated adenocarcinomas overlapping with renal medullary carcinoma.

PubMed

Sirohi, Deepika; Smith, Steven C; Ohe, Chisato; Colombo, Piergiuseppe; Divatia, Mukul; Dragoescu, Ema; Rao, Priya; Hirsch, Michelle S; Chen, Ying-Bei; Mehra, Rohit; Amin, Mahul B

2017-09-01

Renal medullary carcinoma (RMC) is a highly aggressive renal cell carcinoma arising in the collecting system and requiring careful correlation with status of sickle cell trait. A panel of international experts has recently proposed provisional diagnostic terminology, renal cell carcinoma, unclassified, with medullary phenotype, based on encountering an extraordinarily rare tumor with RMC morphology and immunophenotype in an individual proven not to have a hemoglobinopathy. Herein, we extend this observation to a cohort of 5 such tumors, morphologically similar to RMC, lacking SMARCB1 expression by immunohistochemistry, but each without evidence of a hemoglobinopathy. The tumors arose in 4 men and 1 woman with a mean age of 44 years, occurring in 3 left and 2 right kidneys. Clinically, aggression was apparent with involvement of perinephric adipose tissue in all 5 cases, nodal metastasis in 4 of 5 cases, and death of disease in 4 of 5 cases within 3-27 months. Histologic sections showed poorly differentiated adenocarcinoma, often with solid and nested growth patterns, as well as infiltrative glandular, tubulopapillary, cribriform, or reticular growth. Rhabdoid and sarcomatoid cytomorphology was seen in a subset. All tumors showed PAX8 nuclear positivity and SMARCB1 loss, with OCT3/4 expression in 4 of 5 cases. In summary, this first series of renal cell carcinoma, unclassified, with medullary phenotype documents tumors with morphologic, immunophenotypic, and prognostic features of RMC occurring in individuals without sickle cell trait. Although greater biologic and molecular understanding is needed, the available evidence points to these cases representing a sporadic counterpart to sickle cell trait-associated RMC. Copyright © 2017 Elsevier Inc. All rights reserved.

Anemia Offers Stronger Protection Than Sickle Cell Trait Against the Erythrocytic Stage of Falciparum Malaria and This Protection Is Reversed by Iron Supplementation.

PubMed

Goheen, M M; Wegmüller, R; Bah, A; Darboe, B; Danso, E; Affara, M; Gardner, D; Patel, J C; Prentice, A M; Cerami, C

2016-12-01

Iron deficiency causes long-term adverse consequences for children and is the most common nutritional deficiency worldwide. Observational studies suggest that iron deficiency anemia protects against Plasmodium falciparum malaria and several intervention trials have indicated that iron supplementation increases malaria risk through unknown mechanism(s). This poses a major challenge for health policy. We investigated how anemia inhibits blood stage malaria infection and how iron supplementation abrogates this protection. This observational cohort study occurred in a malaria-endemic region where sickle-cell trait is also common. We studied fresh RBCs from anemic children (135 children; age 6-24months; hemoglobin <11g/dl) participating in an iron supplementation trial (ISRCTN registry, number ISRCTN07210906) in which they received iron (12mg/day) as part of a micronutrient powder for 84days. Children donated RBCs at baseline, Day 49, and Day 84 for use in flow cytometry-based in vitro growth and invasion assays with P. falciparum laboratory and field strains. In vitro parasite growth in subject RBCs was the primary endpoint. Anemia substantially reduced the invasion and growth of both laboratory and field strains of P. falciparum in vitro (~10% growth reduction per standard deviation shift in hemoglobin). The population level impact against erythrocytic stage malaria was 15.9% from anemia compared to 3.5% for sickle-cell trait. Parasite growth was 2.4 fold higher after 49days of iron supplementation relative to baseline (p<0.001), paralleling increases in erythropoiesis. These results confirm and quantify a plausible mechanism by which anemia protects African children against falciparum malaria, an effect that is substantially greater than the protection offered by sickle-cell trait. Iron supplementation completely reversed the observed protection and hence should be accompanied by malaria prophylaxis. Lower hemoglobin levels typically seen in populations of African descent may reflect past genetic selection by malaria. National Institute of Child Health and Development, Bill and Melinda Gates Foundation, UK Medical Research Council (MRC) and Department for International Development (DFID) under the MRC/DFID Concordat. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Annual Progress Report Fiscal Year 1990

DTIC Science & Technology

1991-03-25

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Newborn Screening for Sickle Cell Disease in Liberia: A Pilot Study

PubMed Central

Tubman, Venée N; Marshall, Roseda; Jallah, Wilhemina; Guo, Dongjing; Ma, Clement; Ohene-Frempong, Kwaku; London, Wendy B; Heeney, Matthew M

2015-01-01

Background In malaria-endemic countries in West Africa, sickle cell disease (SCD) contributes to childhood mortality. Historically, Liberia had regions wherein hemoglobin S and beta-thalassemia trait were mutually exclusive. Data on hemoglobinopathies in the Monrovia, the capital, are outdated and do not reflect urban migration. Updating the epidemiology of SCD is necessary to plan a public health and clinical agenda. Neither newborn screening (NBS) nor screening tools were available in-country. This pilot study aimed to determine the feasibility of NBS using a South-South partnership and define the incidence of sickle cell trait (SCT) and SCD in Monrovia. Procedure This descriptive epidemiologic feasibility study collected dried blood spots from 2785 consecutive newborns delivered at a hospital in Monrovia. Samples were analyzed by isoelectric focusing at a regional reference laboratory. Infants with SCD were referred for preventive care. Results SCT occurred in 10.31% of infants screened. SCD occurred in 33 infants screened [1.19% (95% CI: 0.79%–1.59%)](FS: 28/33, FSB: 2/33, FSA: 2/33, FSX 1/33). There were no infants with FSC phenotype observed. Non-sickling hemoglobin phenotypes ‘FC’ and ‘F’ were each present in 3 infants screened. Seventy-six percent of infants with SCD were brought to care, demonstrating the feasibility of our approach. Conclusions The incidence of SCD and other hemoglobinopathies remain high in Liberia. Additional studies are needed to clarify sickle genotypes and identify the contribution of silent beta-thalassemia alleles. By developing regional partnerships, countries similar to Liberia can acquire current data to inform NBS as an important public health initiative toward improving child health. PMID:26739520

Sickle cell protection from malaria.

PubMed

Eridani, Sandro

2011-10-19

A linkage between presence of Sickle Haemoglobin (HbS) and protection from malaria infection and clinical manifestations in certain areas was suspected from early observations and progressively elucidated by more recent studies. Research has confirmed the abovementioned connection, but also clarified how such protection may be abolished by coexistence of sickle cell trait (HbS trait) and alpha thalassemia, which may explain the relatively low incidence of HbS trait in the Mediterranean. The mechanisms of such protective effect are now being investigated: factors of genetic, molecular and immunological nature are prominent. As for genetic factors attention is given to the role of the red blood cell (RBC) membrane complement regulatory proteins as polymorphisms of these components seem to be associated with resistance to severe malaria; genetic ligands like the Duffy group blood antigen, necessary for erythrocytic invasion, and human protein CD36, a major receptor for P. falciparum-infected RBC's, are also under scrutiny: attention is focused also on plasmodium erythrocyte-binding antigens, which bind to RBC surface components. Genome-wide linkage and association studies are now carried out too, in order to identify genes associated with malaria resistance. Only a minor role is attributed to intravascular sickling, phagocytosis and haemolysis, while specific molecular mechanisms are the object of intensive research: among these a decisive role is played by a biochemical sequence, involving activation of haeme oxygenase (HMO-1), whose effect appears mediated by carbon monoxide (CO). A central role in protection from malaria is also played by immunological factors, which may stimulate antibody production to plasmodium antigens in the early years of life; the role of agents like pathogenic CD8 T-cells has been suggested while the effects of molecular actions on the immunity mechanism are presently investigated. It thus appears that protection from malaria can be explained by interaction of different factors: the elucidation of such mechanisms may prove valuable for the prevention and treatment strategy of a disease which still affects large parts of the world.

Comparative haematological parameters of HbAA and HbAS genotype children infected with Plasmodium falciparum malaria in Yemen.

PubMed

Albiti, Anisa H; Nsiah, Kwabena

2014-04-01

Sickle haemoglobin (HbS) is known to offer considerable protection against falciparum malaria. However, the mechanism of protection is not yet completely understood. In this study, we investigate how the presence of the sickle cell trait affects the haematological profile of AS persons with malaria, in comparison with similarly infected persons with HbAA. This study is based on the hypothesis that the sickle cell trait plays a protective role against malaria. Children from an endemic malaria transmission area in Yemen were enrolled in this study. Hematological parameters were estimated using manual methods, the percentage of parasite density on stained thin smear was calculated, haemoglobin genotypes were determined on paper electrophoresis, ferritin was measured using enzyme-linked immunosorbent assay, serum iron and TIBC were assayed using spectrophotometer, transferrin saturation index was calculated by dividing serum iron by TIBC and expressing the result as a percentage. Haematological parameters were compared in HbAA- and HbAS-infected children. Falciparum malaria parasitaemia was confirmed in the blood smears of 62 children, 44 (55.7%) of AA and 18 (37.5%) AS, so there was higher prevalence in HbAA children (P = 0.047). Parasite density was lower in HbAS- than HbAA-infected children (P = 0.003). Anaemia was prominent in malaria-infected children, with high proportions of moderate and severe forms in HbAA (P = 0.001). The mean levels of haemoglobin, packed cell volume, reticulocyte count, platelets count, lymphocytes, eosinophils, and serum iron were significantly lower while total leukocytes, immature granulocytes, monocytes, erythrocyte sedimentation rate, transferrin saturation, and serum ferritin were significantly higher in HbAA-infected children than HbAS-infected children. Infection with Plasmodium falciparum malaria caused more significant haematological alterations of HbAA children than HbAS. This study supports the observation that sickle cell trait seems to be a beneficial genetic factor that resists malaria, since inheriting it protects against significant haematological consequences of malaria.

Exercise collapse associated with sickle cell trait (ECAST): case report and literature review.

PubMed

Quattrone, Richard D; Eichner, E Randy; Beutler, Anthony; Adams, W Bruce; O'Connor, Francis G

2015-01-01

Sickle cell trait (SCT) has been associated with exertional collapse (ECAST) and exercise-related sudden death in athletes and military warfighters. The mechanisms underlying ECAST remain controversial in the sports medicine community. Multiple case presentations and anecdotal reports postulate the role of extraordinary exercise intensity, but other risk factors including dehydration, heat, previous exertional rhabdomyolysis, genetic cofactors, and dietary supplements have been cited as potential contributors. Others have hypothesized some of the aforementioned factors combining in a "perfect storm" to trigger ECAST with a resultant potentially fatal "metabolic crisis." This case report provides a brief review of SCT as it pertains to exercise in warfighters and athletes, identifies known and postulated risk factors associated with ECAST, and introduces the potential mechanistic role of the "double hit" as a contributor to ECAST.

Rhabdomyolysis in a Sickle Cell Trait Positive Active Duty Male Soldier.

PubMed

Saxena, Pulkit; Chavarria, Christopher; Thurlow, John

2016-01-01

Exertional rhabdomyolysis is a complication of sickle cell trait (SCT) likely first reported in the military population over 40 years ago. Although commonly a benign condition, numerous studies and case reports have identified SCT positive patients to be at increased risk for rhabdomyolysis, compartment syndrome and sudden cardiac death. We report a recent case of an SCT positive African American active duty male Soldier who suffered exertional rhabdomyolysis following an Army Physical Fitness Test. His course was complicated by acute renal failure requiring hemodialysis, and he eventually recovered renal function. The diagnosis was significantly delayed despite a typical clinical presentation and available SCT screening results. The case highlights the importance of the recognition of SCT as a risk factor for severe rhabdomyolysis, and suggests more must be done for an effective SCT screening program for the active duty military population.

Non-invasive imaging of oxygen extraction fraction in adults with sickle cell anaemia.

PubMed

Jordan, Lori C; Gindville, Melissa C; Scott, Allison O; Juttukonda, Meher R; Strother, Megan K; Kassim, Adetola A; Chen, Sheau-Chiann; Lu, Hanzhang; Pruthi, Sumit; Shyr, Yu; Donahue, Manus J

2016-03-01

Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2-56.8 ml/100 g/min; oxygen extraction fraction = 0.39-0.50) relative to controls (interquartile range cerebral blood flow = 40.8-46.3 ml/100 g/min; oxygen extraction fraction = 0.33-0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the premise that magnetic resonance imaging-based assessment of elevated oxygen extraction fraction might be a viable screening tool for evaluating stroke risk in adults with sickle cell anaemia. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Non-invasive imaging of oxygen extraction fraction in adults with sickle cell anaemia

PubMed Central

Gindville, Melissa C.; Scott, Allison O.; Juttukonda, Meher R.; Strother, Megan K.; Kassim, Adetola A.; Chen, Sheau-Chiann; Lu, Hanzhang; Pruthi, Sumit; Shyr, Yu; Donahue, Manus J.

2016-01-01

Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2–56.8 ml/100 g/min; oxygen extraction fraction = 0.39–0.50) relative to controls (interquartile range cerebral blood flow = 40.8–46.3 ml/100 g/min; oxygen extraction fraction = 0.33–0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the premise that magnetic resonance imaging-based assessment of elevated oxygen extraction fraction might be a viable screening tool for evaluating stroke risk in adults with sickle cell anaemia. PMID:26823369

Does repeated and heavy exercise impair blood rheology in carriers of sickle cell trait?

PubMed

Tripette, Julien; Hardy-Dessources, Marie-Dominique; Sara, Fagnété; Montout-Hedreville, Mona; Saint-Martin, Christian; Hue, Olivier; Connes, Philippe

2007-11-01

To determine if the time courses of hemorheologic parameters are different between carriers of sickle cell trait (SCT) and subjects with normal hemoglobin in response to exercise. Observational and comparative study. Testing was conducted in a laboratory of exercise physiology. Nine carriers of sickle cell trait (SCT group) and 7 subjects with normal hemoglobin (CONT group) performed an exercise protocol of the repetition of 3 successive maximal ramp exercise tests. Blood was sampled at rest (TR), at the end of each of the 3 tests (T1, T2, T3), and during the immediate (T2h) and late (T24h, T48h) recovery periods. Blood and plasma viscosity (etab and etap, respectively), hematocrit (Hct), and red blood cell (RBC) rigidity (Tk and k indexes) were determined. In both groups, etab significantly increased in response to exercise but the SCT group had significantly higher etab at T3 and T2h. etab then returned to baseline value at T2h in the CONT group and at T24h in the SCT group. Tk and k were not changed by exercise but significantly increased above baseline value in both groups at T24h and T48h. The increase in Tk and k during late recovery was higher in the SCT group than in the CONT group, indicating that SCT carriers had significantly higher RBC rigidity than the CONT group at that time. The hemorheologic changes induced by exercise in the SCT carriers could trigger microcirculatory disorders during the recovery.

Association between wind speed and the occurrence of sickle cell acute painful episodes: results of a case-crossover study

PubMed Central

Nolan, Vikki G.; Zhang, Yuqing; Lash, Timothy; Sebastiani, Paola; Steinberg, Martin H.

2015-01-01

Summary The role of the weather as a trigger of sickle cell acute painful episodes has long been debated. To more accurately describe the role of the weather as a trigger of painful events, we conducted a case-crossover study of the association between local weather conditions and the occurrence of painful episodes. From the Cooperative Study of Sickle Cell Disease, we identified 813 patients with sickle cell anaemia who had 3570 acute painful episodes. We found an association between wind speed and the onset of pain, specifically wind speed during the 24-h period preceding the onset of pain. Analysing wind speed as a categorical trait, showed a 13% increase (95% confidence interval: 3%, 24%) in odds of pain, when comparing the high wind speed to lower wind speed (P = 0.007). In addition, the association between wind speed and painful episodes was found to be stronger among men, particularly those in the warmer climate regions of the United States. These results are in agreement with another study that found an association between wind speed and hospital visits for pain in the United Kingdom, and lends support to physiological and clinical studies that have suggested that skin cooling is associated with sickle vasoocclusion and perhaps pain. PMID:18729854

Association between wind speed and the occurrence of sickle cell acute painful episodes: results of a case-crossover study.

PubMed

Nolan, Vikki G; Zhang, Yuqing; Lash, Timothy; Sebastiani, Paola; Steinberg, Martin H

2008-11-01

The role of the weather as a trigger of sickle cell acute painful episodes has long been debated. To more accurately describe the role of the weather as a trigger of painful events, we conducted a case-crossover study of the association between local weather conditions and the occurrence of painful episodes. From the Cooperative Study of Sickle Cell Disease, we identified 813 patients with sickle cell anaemia who had 3570 acute painful episodes. We found an association between wind speed and the onset of pain, specifically wind speed during the 24-h period preceding the onset of pain. Analysing wind speed as a categorical trait, showed a 13% increase (95% confidence interval: 3%, 24%) in odds of pain, when comparing the high wind speed to lower wind speed (P = 0.007). In addition, the association between wind speed and painful episodes was found to be stronger among men, particularly those in the warmer climate regions of the United States. These results are in agreement with another study that found an association between wind speed and hospital visits for pain in the United Kingdom, and lends support to physiological and clinical studies that have suggested that skin cooling is associated with sickle vasoocclusion and perhaps pain.

Community engagement to inform the development of a sickle cell counselor training and certification program in Ghana.

PubMed

Anie, Kofi A; Treadwell, Marsha J; Grant, Althea M; Dennis-Antwi, Jemima A; Asafo, Mabel K; Lamptey, Mary E; Ojodu, Jelili; Yusuf, Careema; Otaigbe, Ayo; Ohene-Frempong, Kwaku

2016-07-01

Sickle cell disease (SCD) and sickle cell trait (SCT) are highly prevalent in Africa. Despite public health implications, there is limited understanding of community issues for implementing newborn screening and appropriate family counseling. We conducted a 3-day workshop in Kumasi, Ghana, with community leaders as lay program development advisors to assist the development and implementation of a Sickle Cell Counselor Training and Certification Program. We employed qualitative methods to understand cultural, religious, and psychosocial dimensions of SCD and SCT, including the advisors' attitudes and beliefs in relation to developing a culturally sensitive approach to family education and counseling that is maximally suited to diverse communities in Ghana. We collated advisors' discussions and observations in order to understand community issues and potential challenges and guide strategies for advocacy in SCD family education and counseling. Results from the workshop revealed that community leaders representing diverse communities in Ghana were engaged constructively in discussions about developing a culturally sensitive counselor training program. Key findings included the importance of improved knowledge about SCD among the public and youth in particular, the value of stakeholders such as elders and religious and traditional leaders, and government expectations of reduced SCD births. We submitted a report to the Ministry of Health in Ghana with recommendations for the next steps in developing a national sickle cell counselor training program. We named the program "Genetic Education and Counseling for Sickle Cell Conditions in Ghana" (GENECIS-Ghana). The first GENECIS-Ghana Training and Certification Program Workshop was conducted from June 8 to 12, 2015.

Blood bank issues associated with red cell exchanges in sickle cell disease.

PubMed

Sarode, Ravindra; Altuntas, Fevzi

2006-12-01

Sickle cell disease (SCD) patients are prone to develop complications that include stroke, acute chest syndrome, and other crises. Some of these complications require chronic transfusion therapy or red cell exchange (RCE), either for therapeutic or prophylactic reasons. Due to a discrepancy of red cell antigens between African Americans and Caucasians (majority blood donors), the incidence of alloantibody formation is very high, which makes it difficult to find compatible red cell units, especially for urgent RCE. Some of the above conditions require immediate oxygen delivery to the tissues. Thus, SCD patients undergoing RCE should receive red blood cells with special attributes that include matching for Rh and Kell blood group antigens; RBCs should be fresh in order to provide (1) immediate oxygen delivery and (2) longer surviving cells to reduce the interval between RCE. Also, these units should be pre-storage leukoreduced to prevent febrile non-hemolytic reactions and screened for sickle cell traits to avoid transfusing red cells containing HbS. This requires a concerted effort between the apheresis unit, the local blood bank, and the central blood supplier.

ACSM and CHAMP summit on sickle cell trait: mitigating risks for warfighters and athletes.

PubMed

O'Connor, Francis G; Bergeron, Michael F; Cantrell, Joyce; Connes, Philippe; Harmon, Kimberly G; Ivy, Edward; Kark, John; Klossner, Dave; Lisman, Peter; Meyers, Bryce K; O'Brien, Karen; Ohene-Frempong, Kwaku; Thompson, Alexis A; Whitehead, James; Deuster, Patricia A

2012-11-01

An estimated 300 million people worldwide have sickle cell trait (SCT). Although largely benign, SCT has been associated with exertional rhabdomyolysis and exercise-related sudden death in warfighters/athletes (WA). The National Collegiate Athletic Association's policy to confirm a student athlete's SCT status during their preparticipation medical examination prompted reaction from some organizations regarding the rationale and ethical justification of the policy. On September 26 and 27, 2011, a summit, composed of military and civilian experts in sports medicine and SCT, was convened at the Uniformed Services University in Bethesda, MD. The expert panel was charged with two objectives: 1) to provide specific recommendations to further mitigate the apparent risk with strenuous exercise in WA with SCT and 2) to develop clinical guidelines to identify, treat, and return to duty/play WA suspected to have incurred nonfatal sickle cell collapse. New terminology is introduced, areas of current controversy are explored, consensus recommendations for mitigating risk and managing the WA with SCT are reviewed, and important areas for future research are identified. Further research is needed before conclusions can be drawn regarding the etiology of the increased death rate observed in WA with SCT, and the possibility exists that SCT is a surrogate for as yet another contributing factor for the unexplained deaths.

Current issues with blood transfusions in sickle cell disease.

PubMed

Vichinsky, E P

2001-01-01

With increased recognition of the profound morbidity of sickle cell disease and with growing evidence of the efficacy of transfusion therapy in prevention and treatment of sickle cell complications, most patients now receive intermittent transfusion therapy. The purpose of this report is to review blood component therapy and Its risks for sickle cell patients. Packed red cells are the preferred blood component. Leukocyte-reduced units should be standard because of their beneficial effects in reducing alloimmunization, transfusion reactions, platelet refractoriness, and infection transmission. The use of washed, frozen, or Irradiated units is limited to specific problems. Sickle trait-positive units function normally, but because of difficulties with calculating hemoglobin S percentages and leukocyte filters, they are not routinely used. Transfusion-acquired infections have shown a marked decrease but still present a major risk. Viral hepatitis transmission is currently low, but at least 10% of adult sickle cell patients are hepatitis C positive, and they often have liver damage. Although bacterial infections are rare, they account for 16% of transfusion-related fatalities. Patients who are iron overloaded are particularly vulnerable to Yersina enterocolitica. Red cell alloimmunization is a serious problem that could potentially affect 50% of transfused patients. However, preventive phenotypic matching for common antigens can minimize alloimmunization; limited matching for at least E, C, and K has become the standard of care. Recently, more patients are being identified who have developed red cell autoantibodies, which can mask alloantibodies and occasionally are hemolytic. Careful laboratory evaluation of all cases is essential. Transfusions also may trigger sickle cell events, including pain crises, stroke, and acute pulmonary deterioration. In part, these are induced by blood viscosity and increased blood pressure. Diuretic therapy and close monitoring of transfusion volume and vital signs can minimize these events. In summary, transfusion therapy carries risks, but the routine use of leukocyte-reduced, phenotypically matched units in conjunction with close monitoring of patients can make transfusion therapy safer.

Factor V Leiden G1691A and prothrombin G20210A mutations among Palestinian patients with sickle cell disease.

PubMed

Samarah, Fekri; Srour, Mahmoud A

2018-01-01

Vascular thrombosis is an important pathophysiological aspect of sickle cell disease (SCD). This study aimed to investigate the prevalence and clinical impact of factor V Leiden G1691A (FVL) and prothrombin G20210A mutations among Palestinian sickle cell disease (SCD) patients. A total of 117 SCD patients, including 59 patients with sickle cell anemia (SS), 33 patients with sickle β-thalassemia and 25 individuals with sickle cell trait (AS) were studied. The control group consisted of 118 healthy individuals. FVL and prothrombin G20210A mutations were determined by RFLP PCR. Analysis of the clinical history of SCD patients revealed that seven patients have had vascular complications such as ischemic stroke or deep vein thrombosis. In SCD patients, the inheritance of the FVL mutation showed a significantly higher incidence of pain in joints, chest and abdomen as well as regular dependence on blood transfusion compared to SCD with the wild type. Age- and sex-adjusted logistic regression analysis revealed a significant association between FVL and sickle cell anemia with an odds ratio (OR) of 5.6 (95% confidence intervals [CI] of 1.91-39.4, P  = 0.039) in SS patients. However, increased prevalence of the FVL in AS subjects and sickle β-thalassemia patients was not statistically significant compared to controls (OR 3.97, 95% CI 0.51-28.6, P  = 0.17 and OR 3.59, 95% CI 0.35-41.6, P  = 0.26, respectively). The distribution of prothrombin G20210A mutation among SCD patients compared to controls was not significantly different, thus our findings do not support an association of this mutation with SCD. FVL was more prevalent among SS patients compared to controls and it was associated with higher incidence of disease complications among SCD patients.

Microcytic hypochromic anemia: should high performance liquid chromatography be used routinely for screening anemic and antenatal patients?

PubMed

Philip, Joseph; Sarkar, Ravi Shankar; Kushwaha, Neerja

2013-01-01

Hemoglobinopathies are the most common inherited red cell disorders worldwide. Identification of these disorders is immensely important epidemiologically and for improved management protocols. Our aim was to determine the prevalence of hemoglobinopathies in patients with microcytic hypochromic anemia and to assess the suitability of using high performance liquid chromatography (HPLC) routinely for screening antenatal cases and patients with anemia. A total of 4335 cases received from Mar 2007 to Nov 2011 were studied for various hemoglobinopathies and variants on BIO RAD 'VARIANT' analyzer. Of the 4335 cases studied, 2119 were antenatal cases, 1710 patients with other disorders and 506 family studies. Of these, 688 cases displayed abnormal hemoglobin fractions on HPLC of which 140 were antenatal women. There were 455 cases of β thalassemia trait, 24 β thalassemia major, 20 thalassemia inter-media, 54 sickle cell trait, fivesickle cell disease, 21 double heterozygous β thalassemia-sickle cell trait, nineand 4 Hb D- Punjab heterozygous and homozygous respectively, three Hb D β Thalassemia trait, 20 and 37 Hb E homozygous and heterozygous respectively, three Hb E β Thalassemia trait and four cases of Hb Q India. Twenty nine adults had isolated HbF elevation. Our study found a high prevalence (15.8%) of hemoglobinopathies amongst microcytic hypochromic anemia and antenatal cases. An accurate diagnosis helps in preventing unnecessary iron loading. Screening all antenatal cases with anemia helps in timely antenatal counseling, thus preventing the psychological trauma of bearing a transfusion dependent child for life.

Sickle-Cell Trait as a Risk Factor for Sudden Death in Physical Training

DTIC Science & Technology

1987-09-24

8 percent for black and 0.08 ->We conclude that recruits in basic training with the percent for nonblack recruits), death rates (per 100,000) sickle...there is no for calculation of death rates . means of distinguishing histologically between incon- We investigated the risk of sudden death in conipa...from alter- pt 00)renddrtn iit ida prto exhubitd an (Fig.s tIt. gic epgottsadth teFa ondda nbd able 2 summarizes the death rates for subjects Thirty

Reproductive health choices for young adults with sickle cell disease or trait: randomized controlled trial immediate posttest effects.

PubMed

Wilkie, Diana J; Gallo, Agatha M; Yao, Yingwei; Molokie, Robert E; Stahl, Christine; Hershberger, Patricia E; Zhao, Zhongsheng; Suarez, Marie L; Labotka, Robert J; Johnson, Bonnye; Angulo, Rigo; Angulo, Veronica; Carrasco, Jesus; Shuey, David; Pelligra, Stephanie; Wang, Edward; Rogers, Dennie T; Thompson, Alexis A

2013-01-01

People with sickle cell disease (SCD) or sickle cell trait (SCT) may not have information about genetic inheritance needed for making informed reproductive health decisions. CHOICES is a Web-based, multimedia educational intervention that provides information about reproductive options and consequences to help those with SCD or SCT identify and implement an informed parenting plan. Efficacy of CHOICES compared with usual care must be evaluated. The purpose was to compare immediate posttest effects of CHOICES versus an attention-control usual care intervention (e-Book) on SCD-/SCT-related reproductive health knowledge, intention, and behavior. In a randomized controlled study, we recruited subjects with SCD/SCT from clinics, community settings, and online networks with data collected at sites convenient to the 234 subjects with SCD (n = 136) or SCT (n = 98). Their ages ranged from 18 to 35 years; 65% were women, and 94% were African American. Subjects completed a measure of sickle cell reproductive knowledge, intention, and behavior before and immediately after the intervention. Compared with the e-Book group, the CHOICES group had significantly higher average knowledge scores and probability of reporting a parenting plan to avoid SCD or SCD and SCT when pretest scores were controlled. Effects on intention and planned behavior were not significant. The CHOICES group showed significant change in their intention and planned behavior, whereas the e-Book group did not show significant change in their intention, but their planned behavior differed significantly. Initial efficacy findings are encouraging but warrant planned booster sessions and outcome follow-ups to determine sustained intervention efficacy on reproductive health knowledge, intention, and actual behavior of persons with SCD/SCT.

Are sickle cell anaemia and sickle cell trait predictive factors for periodontal disease? A cohort study.

PubMed

de Carvalho, H L C C; Thomaz, E B A F; Alves, C M C; Souza, S F C

2016-10-01

Periodontal diseases are associated with bacterial challenge and the host immune response, and are also modulated by genetic factors. There is evidence that sickle cell anaemia (SCA) does not represent a risk factor for periodontal diseases. However, it is still unclear whether the heterozygous condition [sickle cell trait (SCT)] is associated with periodontal diseases. SCT is a genetic condition that can cause vaso-occlusive events, which may be associated with a propensity to bacterial infections. The aim of this study was to investigate the association of SCA and SCT with periodontal diseases by evaluating clinical and radiographic characteristics. The sample (n = 369) was selected and divided into two groups: exposed groups [HbSS (SCA genotype) and HbAS (SCT genotype) = 246] and a nonexposed group (HbAA = 123). HbAA consisted of individuals without SCA and SCT. The clinical parameters evaluated were plaque index, gingival index, calculus index, clinical probing depth, clinical attachment level, gingival recession, tooth mobility and furcation involvement. The percentage of alveolar bone loss was measured using a Schei ruler. Binomial and Poisson regressions were used to estimate correlations of interest (α = 0.05). None of the periodontal parameters was associated with SCA. SCT was associated with gingivitis (p = 0.041) and periodontitis (p = 0.002). Individuals with SCT had a lower plaque index (p = 0.044) but a higher calculus index (p = 0.003) and greater alveolar bone loss (p = 0.010) compared with subjects in the HbAA group. SCT can act as a predictor for establishment of periodontal diseases. There was no correlation between SCA and periodontal diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reproductive Health CHOICES for Young Adults with Sickle Cell Disease or Trait: Randomized Controlled Trial Immediate Posttest Effects

PubMed Central

Wilkie, Diana J; Gallo, Agatha M.; Yao, Yingwei; Molokie, Robert E.; Stahl, Christine; Hershberger, Patricia E.; Zhao, Zhongsheng; Suarez, Marie L.; Labotka, Robert J.; Johnson, Bonnye; Angulo, Rigo; Angulo, Veronica; Carrasco, Jesus; Shuey, David; Pelligra, Stephanie; Wang, Edward; Rogers, Dennie T.; Thompson, Alexis A.

2013-01-01

Background People with sickle cell disease (SCD) or sickle cell trait (SCT) may not have information about genetic inheritance needed for making informed reproductive health decisions. CHOICES is a web-based, multimedia educational intervention that provides information about reproductive options and consequences to help those with SCD or SCT identify and implement an informed parenting plan. Efficacy of CHOICES compared with usual care must be evaluated. Objective The purpose was to compare immediate posttest effects of CHOICES versus an attention control usual care intervention (e-Book) on SCD/SCT-related reproductive health knowledge, intention, and behavior. Methods In a randomized controlled study, we recruited subjects with SCD/SCT from clinics, community settings, and online networks with data collected at sites convenient to the 234 subjects with SCD (n = 136) or SCT (n = 98) (age ranged from18-35 years, 65% were female, and 94% were African American). Subjects completed a measure of sickle cell reproductive knowledge, intention, and behavior before and immediately after the intervention. Results Compared to the e-Book group, the CHOICES group had significantly higher average knowledge scores and probability of reporting a parenting plan to avoid SCD or SCD and SCT when pretest scores were controlled. Effects on intention and planned behavior were not significant. The CHOICES group showed significant change in their intention and planned behavior; the e-Book group did not show significant change in their intention, but their planned behavior differed significantly. Discussion Initial efficacy findings are encouraging but warrant planned booster sessions and outcome follow-ups to determine sustained intervention efficacy on reproductive health knowledge, intention, and actual behavior of persons with SCD/SCT. PMID:23995469

Community expansion and gene geography of sickle cell trait and G6PD deficiency, and natural selection against malaria: experience from tribal land of India.

PubMed

Balgir, R S

2012-03-01

Malaria is globally endemic in tropical and subtropical regions and so is the hemoglobinopathies, thalassemias and glucose-6-phosphate dehydrogenase (G6PD) deficiency. This biological dogma of hyper-endemic all over the tribal land in India leads to high morbidity and mortality. The directed genetic abnormalities of human erythrocytes have found to decrease the susceptibility towards malaria parasites and the heterozygotes of abnormalities probably confer protection against the Plasmodium falciparum infection. A fascinating trend for an inverse relationship between sickle cell disorders and G6PD deficiency in scheduled caste and tribal communities of Central-Eastern India has been observed. When the frequency of sickle cell allele decreases in malaria endemic cross-section of the tribal population, the frequency of G6PD deficiency allele increases and vice versa. This medical aspect is important from an evolutionary biological background and could be an excellent point for molecular analyses to determine the signature of selection in the genomic regions of β- globin and G6PD genes. Since the selection favors the mutation with least cost to the population [as the clinical manifestations of G6PD deficiency are mild and do not result in a complete loss of enzyme activity against the sickle cell disease with high morbidity and mortality in the region] and the predominant frequency of G6PD deficiency over the sickle cell disorders in some tribal communities, it seems that the replacement of sickle cell allele for G6PD deficiency is occurring in the scheduled castes/tribes of Chhattisgarh, Madhya Pradesh, Maharashtra and Odisha states in Central India. These findings are consistent with our previous studies carried out in Central-Eastern India.

Clinical features of sickle cell anaemia in northern nigerian children.

PubMed

Ambe, J P; Mava, Y; Chama, R; Farouq, G; Machoko, Y

2012-01-01

Sickle cell disease (SCD) is a more common and severe disease in Africa. Nigeria the most populous black nation in Africa has the largest number of sickle cell anaemia (SCA) patients in the world. Borno and Yobe State has the largest number of sickle cell trait in Nigeria with prevalence of 27.9% and 32.6% respectively. Sickle cell anaemia survival to adulthood in Africa was reported to be 10-15% in the first decade of life, with the death rate of about 5% during subsequent decades. Large portion that died have shown no overt chronic organ failure but died during acute episodes of pain, infections, acute chest syndrome, stroke and anaemic crises. To review the morbidity pattern among SCA children in the University of Maiduguri Teaching Hospital, North-Eastern Nigeria. This was a retrospective study of SCA patients seen from 1994 to 2003. There were 333 case notes retrieved and reviewed with their age, sex, clinical features at diagnosis and other morbidities documented and analysed. Sickle cell anaemia is commonly diagnosed in infants aged 6-11 months, with hand-foot swelling and jaundice being the commonest symptoms at presentation. Anaemic and vaso-occlusive crises were seen more common in children aged 1-5 years. The over-all morbidity pattern is same in both sexes with diseases such as bronchopneumonia, malaria, osteomyelitis, urinary tract infections, septicaemia and septic arthritis being common. Age has been found to influence morbidity pattern in our studied patients. There is need for early diagnosis and counseling, so that mothers or caregivers will be able to assist in prompt identification of these morbidities and to seek for prompt and appropriate treatment in the health facilities.

Do tribal communities show an inverse relationship between sickle cell disorders and glucose-6-phosphate dehydrogenase deficiency in malaria endemic areas of Central-Eastern India?

PubMed

Balgir, R S

2006-01-01

Tribal communities in India constitute the largest tribal population in the world. There are about 635 biological isolates (tribes and subtribes), which constituted 8.08% (about 84.3 million) of the total population of India as per the 2001 census. Out of 635 scheduled tribes (aborigines), 62 live in the state of Orissa alone forming about 10.8% of the tribal population of India. Orissa state occupies an important place, being the 3rd in rank for the highest concentration of tribal population in the country. In India, tribal communities are highly vulnerable to hereditary diseases and have a high degree of malnutrition, morbidity and mortality. The sickle cell haemoglobinopathy and glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency are important genetic and public health problems in Central-Eastern part of India. In order to map out these genetic disorders among the tribal people, a cross-section of 15 major tribal communities from different parts of Orissa was randomly screened for haemoglobin variants and G6PD deficiency. The high frequency of sickle cell haemoglobinopathy (0-22.4%) and G6PD deficiency (4.3-17.4%), with beta-thalassemia trait (0-8.5%) taking almost an intermediate position, was observed. For G6PD deficiency, hemizygous males as well as female heterozygotes and female homozygotes were detected. Twelve cases showed compound heterozygosity for sickle cell haemoglobinopathy and G6PD deficiency. There seems to be a trend towards an inverse relationship between the sickle cell allele and G6PD deficiency, and sickle cell and beta-thalassemia allele in a cross-section of malaria endemic (Plasmodium falciparum) tribal communities in Orissa. When the frequency of sickle cell allele decreases in a cross-section of malaria endemic tribal population, the frequency of G6PD enzyme deficiency and beta-thalassemia allele increases and vice versa. Natural selection had played a major role in favour of sickle cell, beta-thalassemia and G6PD mutation alleles so that they had probably evolved as a protective mechanism against the lethal effects of malaria in this part of the country. However, the calculated values of 0.074, 0.218 and 0.337, respectively, of Pearson's correlation co-efficient (r), showed no correlation between sickle cell disorders and G6PD deficiency, sickle cell disorders and beta-thalassemia, and G6PD deficiency and beta-thalassemia.

Hashimoto's thyroiditis and acute chest syndrome revealing sickle cell anemia in a 32 years female patient.

PubMed

Igala, Marielle; Nsame, Daniela; Ova, Jennie Dorothée Guelongo Okouango; Cherkaoui, Siham; Oukkach, Bouchra; Quessar, Asmae

2015-01-01

Sickle cell anemia results from a single amino acid substitution in the gene encoding the β-globin subunit. Polymerization of deoxygenated sickle hemoglobin leads to decreased deformability of red blood cells. Hashimoto's thyroiditis is a common thyroid disease now recognized as an auto-immune thyroid disorder, it is usually thought to be haemolytic autoimmune anemia. We report the case of a 32 years old women admitted for chest pain and haemolysis anemia in which Hashimoto's thyroiditis and sickle cell anemia were found. In our observation the patient is a young woman whose examination did not show signs of goitre but the analysis of thyroid function tests performed before an auto-immune hemolytic anemia (confirmed by a high level of unconjugated bilirubin and a Coombs test positive for IgG) has found thyroid stimulating hormone (TSH) and positive thyroid antibody at rates in excess of 4.5 times their normal value. In the same period, as the hemolytic anemia, and before the atypical chest pain and anguish they generated in the patient, the search for hemoglobinopathies was made despite the absence of a family history of haematological disease or painful attacks in childhood. Patient electrophoresis's led to research similar cases in the family. The mother was the first to be analyzed with ultimately diagnosed with sickle cell trait have previously been ignored. This case would be a form with few symptoms because the patient does not describe painful crises in childhood or adolescence.

Reproductive Health CHOICES for Young Adults with Sickle Cell Disease or Trait: Randomized Controlled Trial Outcomes over Two Years.

PubMed

Gallo, Agatha M; Wilkie, Diana J; Yao, Yingwei; Molokie, Robert E; Stahl, Christiane; Hershberger, Patricia E; Zhao, Zhongsheng; Suarez, Marie L; Johnson, Bonnye; Angulo, Rigoberto; Carrasco, Jesus; Angulo, Veronica; Thompson, Alexis A

2016-04-01

Interventions to assist reproductive health decision-making in populations affected by sickle cell disease (SCD) or trait (SCT) lack proven efficacy over time. Our aim was to compare effects of CHOICES, a Web-based multimedia education program on implementing informed reproductive plans, and usual care education (e-Book) on reproductive knowledge, intention, and behavior over 24 months. We randomized 234 participants with SCD (n = 138) or SCT (n = 96) (age 18-35 years, 35 % male, 94 % African American) to CHOICES and e-Book groups. Participants completed a sickle cell-specific reproductive measure before and four times after the intervention (6, 12, 18 and 24 months). Compared to the e-Book group the CHOICES group had significantly more improvement in knowledge over time (p = .004) but not intention (p = .18) or behavior (p = .69). At baseline, 114 (48.7 %) participants reported having partners who would not put the couple at risk for their children inheriting SCD. Of the 116 (49.6 %) at-risk participants, a higher poroportion of those who were in the CHOICES group chose partners that reduced their risk by the last visit than the e-Book group (p = .04). Study findings provide important insights for designing a national trial of the CHOICES intervention focusing on subjects whose partner status puts them at risk for having a child with SCD.

A GCH1 haplotype confers sex-specific susceptibility to pain crises and altered endothelial function in adults with sickle cell anemia

PubMed Central

Belfer, Inna; Youngblood, Victoria; Darbari, Deepika S.; Wang, Zhengyuan; Diaw, Lena; Freeman, Lita; Desai, Krupa; Dizon, Michael; Allen, Darlene; Cunnington, Colin; Channon, Keith M.; Milton, Jacqueline; Hartley, Stephen W.; Nolan, Vikki; Kato, Gregory J.; Steinberg, Martin H.; Goldman, David; Taylor, James G.

2014-01-01

GTP cyclohydrolase (GCH1) is rate limiting for tetrahydrobiopterin (BH4) synthesis, where BH4 is a cofactor for nitric oxide (NO) synthases and aromatic hydroxylases. GCH1 polymorphisms are implicated in the pathophysiology of pain, but have not been investigated in African populations. We examined GCH1 and pain in sickle cell anemia where GCH1 rs8007267 was a risk factor for pain crises in discovery (n = 228; odds ratio [OR] 2.26; P = 0.009) and replication (n = 513; OR 2.23; P = 0.004) cohorts. In vitro, cells from sickle cell anemia subjects homozygous for the risk allele produced higher BH4. In vivo physiological studies of traits likely to be modulated by GCH1 showed rs8007267 is associated with altered endothelial dependent blood flow in females with SCA (8.42% of variation; P = 0.002). The GCH1 pain association is attributable to an African haplotype with where its sickle cell anemia pain association is limited to females (OR 2.69; 95% CI 1.21–5.94; P = 0.01) and has the opposite directional association described in Europeans independent of global admixture. The presence of a GCH1 haplotype with high BH4 in populations of African ancestry could explain the association of rs8007267 with sickle cell anemia pain crises. The vascular effects of GCH1 and BH4 may also have broader implications for cardiovascular disease in populations of African ancestry. PMID:24136375

Newborn Screening for Sickle Cell Disease in Liberia: A Pilot Study.

PubMed

Tubman, Venée N; Marshall, Roseda; Jallah, Wilhemina; Guo, Dongjing; Ma, Clement; Ohene-Frempong, Kwaku; London, Wendy B; Heeney, Matthew M

2016-04-01

In malaria-endemic countries in West Africa, sickle cell disease (SCD) contributes to childhood mortality. Historically, Liberia had regions wherein hemoglobin S and beta-thalassemia trait were mutually exclusive. Data on hemoglobinopathies in the Monrovia, the capital, are outdated and do not reflect urban migration. Updating the epidemiology of SCD is necessary to plan a public health and clinical agenda. Neither newborn screening (NBS) nor screening tools were available in country. This pilot study aimed to determine the feasibility of NBS using a South-South partnership and define the incidence of sickle cell trait (SCT) and SCD in Monrovia. This descriptive epidemiologic feasibility study collected dried blood spots from 2,785 consecutive newborns delivered at a hospital in Monrovia. Samples were analyzed by isoelectric focusing at a regional reference laboratory. Infants with SCD were referred for preventive care. SCT occurred in 10.31% of infants screened. SCD occurred in 33 infants screened [1.19% (95% confidence interval [CI]: 0.79-1.59%)] (FS: 28/33, FSB: 2/33, FSA: 2/33, FSX: 1/33). There were no infants with FSC phenotype observed. Nonsickling hemoglobin phenotypes "FC" and "F" were each present in three infants screened. Seventy-six percent of infants with SCD were brought to care, demonstrating the feasibility of our approach. The incidence of SCD and other hemoglobinopathies remains high in Liberia. Additional studies are needed to clarify sickle genotypes and identify the contribution of silent beta-thalassemia alleles. By developing regional partnerships, countries similar to Liberia can acquire current data to inform NBS as an important public health initiative toward improving child health. © 2016 Wiley Periodicals, Inc.

Sickle cell disease caused by heterozygosity for Hb S and novel LCR deletion: Report of two patients.

PubMed

Koenig, Sara C; Becirevic, Esmira; Hellberg, Miriam S C; Li, Michael Y; So, Jason C C; Hankins, Jane S; Ware, Russell E; McMahon, Lillian; Steinberg, Martin H; Luo, Hong-Yuan; Chui, David H K

2009-09-01

The b-globin gene LCR is located approximately 6 kb upstream of the embryonic epsilon-globin gene, and is made up of five DNase I hypersensitive sites (HSs), HS 1-5. LCR plays a pivotal role in regulating the expression of downstream epsilon-, (G)gamma-, (A)gamma-, delta-, and beta-globin genes in cis [1]. Deletions removing the LCR and parts of the downstream beta-globin gene cluster in patients have been described [2]. These individuals present with a (gammadeltabeta)0-thalassemia carrier phenotype. We now report two patients with severe sickle cell disease who were compound heterozygous for Hb S mutation and novel LCR deletion. In one case, HS 1-3 were deleted; in the other, HS 1-5 were deleted. In both cases, the b-like globin genes in cis to the LCR deletions were intact. Genotypically, both patients appeared to have sickle cell trait. Coinherited with either LCR deletion, these individuals presented as sickle cell disease patients. The breakpoints of these LCR deletions were defined. These results affirm that HS 2 and 3 are primarily responsible for conferring erythroid specific high-level expression of cis-linked beta-like globin genes. Furthermore, LCR deletions might cause hemolytic disease of newborns.

Sickle cell trait and development of microvascular complications in diabetes mellitus.

PubMed

Bleyer, Anthony J; Reddy, Sri V; Sujata, Leon; Russell, Gregory B; Akinnifesi, Damilola; Bleyer, Anthony J; Hire, Donald; Shihabi, Zak; Knovich, Mary Ann; Daeihagh, Pirouz; Calles, Jorge; Freedman, Barry I

2010-06-01

Many African Americans (AA) have both sickle cell trait (SCT) and diabetes mellitus. The objective of this study was to determine whether individuals with diabetes mellitus and SCT have higher rates of microvascular complications relative to those without SCT. This was a retrospective study comparing albuminuria, estimated GFR (eGFR), and microvascular complications in AA with diabetes on the basis of presence of SCT. The study included 821 outpatients who underwent hemoglobin A1c (HbA1c) testing, and presence of SCT was determined using the HbA1c assay. Medical record review and telephone interviews were performed for AA participants. Data were obtained on 376 AA patients (110 with SCT, 245 with neither SCT nor hemoglobin C trait, and 21 with hemoglobin C trait) and 445 European Americans. The mean eGFR and urinary protein excretion were similar between the three AA subgroups. Analysis revealed that 36.3% of AA nontrait and 22.7% of AA SCT participants had retinopathy, peripheral vascular disease, or end-stage kidney disease (P = 0.01). After adjustment for diabetes duration, age, insulin use, and gender, differences in the prevalence of microvascular complications were not observed. SCT does not increase the risk of microvascular complications in AA with diabetes mellitus.

Sickle Cell Trait and Development of Microvascular Complications in Diabetes Mellitus

PubMed Central

Bleyer, Anthony J.; Reddy, Sri V.; Sujata, Leon; Russell, Gregory B.; Akinnifesi, Damilola; Hire, Donald; Shihabi, Zak; Knovich, Mary Ann; Daeihagh, Pirouz; Calles, Jorge; Freedman, Barry I.

2010-01-01

Background and objectives: Many African Americans (AA) have both sickle cell trait (SCT) and diabetes mellitus. The objective of this study was to determine whether individuals with diabetes mellitus and SCT have higher rates of microvascular complications relative to those without SCT. Design, setting, participants, & measurements: This was a retrospective study comparing albuminuria, estimated GFR (eGFR), and microvascular complications in AA with diabetes on the basis of presence of SCT. The study included 821 outpatients who underwent hemoglobin A1c (HbA1c) testing, and presence of SCT was determined using the HbA1c assay. Medical record review and telephone interviews were performed for AA participants. Results: Data were obtained on 376 AA patients (110 with SCT, 245 with neither SCT nor hemoglobin C trait, and 21 with hemoglobin C trait) and 445 European Americans. The mean eGFR and urinary protein excretion were similar between the three AA subgroups. Analysis revealed that 36.3% of AA nontrait and 22.7% of AA SCT participants had retinopathy, peripheral vascular disease, or end-stage kidney disease (P = 0.01). After adjustment for diabetes duration, age, insulin use, and gender, differences in the prevalence of microvascular complications were not observed. Conclusions: SCT does not increase the risk of microvascular complications in AA with diabetes mellitus. PMID:20299376

Impact of sickle cell trait on physical growth in tribal children of Mandla district in Madhya Pradesh, India.

PubMed

Qamra, Suneel; Roy, Jyotirmoy; Srivastava, Praval

2011-11-01

Reliable reports on growth impairment in sickle cell trait (SCT) children in India are lacking despite contradictory findings reported earlier. The present study assessed the impact of SCT on physical growth of tribal children of Mandla district. Weight, height, circumferences, breadths, lengths and skinfolds were recorded on 6190 children, inclusive of 732 SCT children, from birth to 12 years of age using a cross-sectional design. The sickle test was conducted in the field using 2% sodium metabisulphite followed by electrophoresis. No significant difference in mean values was observed in the majority of the age groups between SCT and normal children for all 11 body measurements. However, inconsistent growth patterns in these measurements among SCT children were evident. Body weight was more deficient than height or other body measurements in the children when compared to Indian and National Centre for Health Statistics (NCHS) standards, while bicristal breadth was comparable with Indian standards. There was no significant impact of SCT observed on growth of children irrespective of sex. Notably, growth of SCT girls was comparable to their normal counterparts. The actual growth difference between normal and SCT children may have been masked on account of poor attainment of annual gain in each successive age group.

78 FR 16514 - Secretary's Advisory Committee on Heritable Disorders in Newborns and Children; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-15

... screening activities, technologies, policies, guidelines, and programs for effectively reducing morbidity... recommendations related to sickle cell trait testing; (2) a presentation on the Affordable Care Act and the impact... comments and present them through a single representative. No audiovisual presentations are permitted...

Significant prevalence of sickle cell disease in Southwest Germany: results from a birth cohort study indicate the necessity for newborn screening.

PubMed

Kunz, Joachim B; Awad, Saida; Happich, Margit; Muckenthaler, Lena; Lindner, Martin; Gramer, Gwendolyn; Okun, Jürgen G; Hoffmann, Georg F; Bruckner, Thomas; Muckenthaler, Martina U; Kulozik, Andreas E

2016-02-01

Children with sickle cell disease (SCD) benefit from newborn screening, because life-threatening complications can be prevented by pre-symptomatic diagnosis. In Germany, the immigration of people from endemic countries is steadily growing. Comprehensive data about the epidemiology and prevalence of SCD in Germany are however lacking, and SCD is not included in the national newborn screening program. We provide data on the prevalence of SCD in a population from both urban and rural areas in Southwest Germany. Anonymized dried blood spots from 37,838 unselected newborns were analyzed by allele-specific PCR for the HbS mutation. Samples tested positive were subjected to Sanger sequencing of the entire β-globin coding sequence firstly to validate the screening and secondly to identify compound heterozygous SCD patients with other mutations of the β-globin gene. We identified 83 carriers of the sickle cell trait, three compound heterozygous SCD patients (two with sickle cell-β-thalassemia, one with sickle cell-Hb Tianshui) but no homozygous SCD patients. The novel molecular method and strategy for newborn screening for SCD presented here compares favorably in terms of sensitivity (1.0 for homozygous HbS, 0.996 for heterozygous HbS), specificity (0.996), practicability, and costs with conventional biochemical screening. Our results demonstrate a significant prevalence of SCD of approximately 1:12,000 in an unselected urban and rural population in Southwest Germany. Together with previously published even higher results from exclusively urban populations in Berlin and Hamburg, our data provide the basis for the decision on a newborn screening program for SCD in Germany.

Emergency Blood Transfusions in Combat Theaters and Impact on HIV Testing Policy

DTIC Science & Technology

2008-06-02

or sickle cell traits, an approximate 8.6% misidentification of blood type is thought to have occurred, further indicating the importance of thorough...Military Medicine. 149:55-62. o. Spinella PC, Perkins JG, Gathwohl KW et al. (2007) Risks Associated with Fresh Whole Blood and Red Blood Cell ...administering trauma care in theater, tested packed red blood cells (PRBC) are the only blood component therapy available to the Forward Surgical Team

Consulting communities on feedback of genetic findings in international health research: sharing sickle cell disease and carrier information in coastal Kenya

PubMed Central

2013-01-01

Background International health research in malaria-endemic settings may include screening for sickle cell disease, given the relationship between this important genetic condition and resistance to malaria, generating questions about whether and how findings should be disclosed. The literature on disclosing genetic findings in the context of research highlights the role of community consultation in understanding and balancing ethically important issues from participants’ perspectives, including social forms of benefit and harm, and the influence of access to care. To inform research practice locally, and contribute to policy more widely, this study aimed to explore the views of local residents in Kilifi County in coastal Kenya on how researchers should manage study-generated information on sickle cell disease and carrier status. Methods Between June 2010 and July 2011, we consulted 62 purposively selected Kilifi residents on how researchers should manage study-generated sickle cell disease findings. Methods drew on a series of deliberative informed small group discussions. Data were analysed thematically, using charts, to describe participants’ perceptions of the importance of disclosing findings, including reasoning, difference and underlying values. Themes were derived from the underlying research questions and from issues emerging from discussions. Data interpretation drew on relevant areas of social science and bioethics literature. Results Perceived health and social benefits generated strong support for disclosing findings on sickle cell disease, but the balance of social benefits and harms was less clear for sickle cell trait. Many forms of health and social benefits and harms of information-sharing were identified, with important underlying values related to family interests and the importance of openness. The influence of micro and macro level contextual features and prioritization of values led to marked diversity of opinion. Conclusions The approach demonstrates a high ethical importance in many malaria endemic low-to-middle income country settings of disclosing sickle cell disease findings generated during research, alongside provision of effective care and locally-informed counselling. Since these services are central to the benefits of disclosure, health researchers whose studies include screening for sickle cell disease should actively promote the development of health policy and services for this condition in situations of unmet need, including through the prior development of collaborative partnerships with government health managers and providers. Community consultation can importantly enrich ethical debate on research practice where in-depth exploration of informed views and the potential for difference are taken into account. PMID:24125465

Consulting communities on feedback of genetic findings in international health research: sharing sickle cell disease and carrier information in coastal Kenya.

PubMed

Marsh, Vicki; Kombe, Francis; Fitzpatrick, Raymond; Williams, Thomas N; Parker, Michael; Molyneux, Sassy

2013-10-14

International health research in malaria-endemic settings may include screening for sickle cell disease, given the relationship between this important genetic condition and resistance to malaria, generating questions about whether and how findings should be disclosed. The literature on disclosing genetic findings in the context of research highlights the role of community consultation in understanding and balancing ethically important issues from participants' perspectives, including social forms of benefit and harm, and the influence of access to care. To inform research practice locally, and contribute to policy more widely, this study aimed to explore the views of local residents in Kilifi County in coastal Kenya on how researchers should manage study-generated information on sickle cell disease and carrier status. Between June 2010 and July 2011, we consulted 62 purposively selected Kilifi residents on how researchers should manage study-generated sickle cell disease findings. Methods drew on a series of deliberative informed small group discussions. Data were analysed thematically, using charts, to describe participants' perceptions of the importance of disclosing findings, including reasoning, difference and underlying values. Themes were derived from the underlying research questions and from issues emerging from discussions. Data interpretation drew on relevant areas of social science and bioethics literature. Perceived health and social benefits generated strong support for disclosing findings on sickle cell disease, but the balance of social benefits and harms was less clear for sickle cell trait. Many forms of health and social benefits and harms of information-sharing were identified, with important underlying values related to family interests and the importance of openness. The influence of micro and macro level contextual features and prioritization of values led to marked diversity of opinion. The approach demonstrates a high ethical importance in many malaria endemic low-to-middle income country settings of disclosing sickle cell disease findings generated during research, alongside provision of effective care and locally-informed counselling. Since these services are central to the benefits of disclosure, health researchers whose studies include screening for sickle cell disease should actively promote the development of health policy and services for this condition in situations of unmet need, including through the prior development of collaborative partnerships with government health managers and providers. Community consultation can importantly enrich ethical debate on research practice where in-depth exploration of informed views and the potential for difference are taken into account.

Fast-track cardiac anesthesia in patients with sickle cell abnormalities.

PubMed

Djaiani, G N; Cheng, D C; Carroll, J A; Yudin, M; Karski, J M

1999-09-01

We conducted a retrospective review of 10 patients with sickle cell trait (SCT) and 30 patients (cohort control) without SCT undergoing first-time coronary artery bypass graft surgery with cardiopulmonary bypass. Demographic, perioperative management, and outcome data were collected. Both groups were matched according to age, weight, duration of surgery, and preoperative hemoglobin (Hb) concentration. Distribution of gender, medical conditions, pharmacological treatment, and preoperative left ventricular function were similar between the groups. The comparisons were analyzed in respect to postoperative blood loss and transfusion rates, as well as duration of intubation, intensive care unit, and hospital length of stay (LOS). All patients underwent fast-track cardiac anesthesia. A combination of cold crystalloid and blood cardioplegia was used. The lowest nasopharyngeal temperature was 33 degrees C. There were no episodes of significant hypoxemia, hypercarbia, or acidosis. None of the patients had sickling crisis during the perioperative period. The postoperative blood loss was 687 +/- 135 vs 585 +/-220 mL in the SCT and control groups, respectively. The trigger for blood transfusion during cardiopulmonary bypass was hematocrit <20% and Hb <75 g/L postoperatively. Three SCT patients (30%) and 10 control patients (33%) received a blood transfusion. Median extubation time was 4.0 vs 3.9 h; intensive care unit LOS was 27 vs 28 h; and hospital LOS was 6.0 vs 5.5 days in the SCT and control groups, respectively. There were no intraoperative deaths. One patient in the SCT group died from multiorgan failure 2 mo after surgery. Fast-track cardiac anesthesia can be used safely in patients with sickle cell trait undergoing first-time coronary artery bypass graft surgery. Extubation time and intensive care unit and hospital length of stay are comparable to those of matched controls, and blood loss and transfusion requirements are not increased. A hematocrit of 20% seems to be a safe transfusion trigger during cardiopulmonary bypass in these patients.

Prevalence of -alpha(3.7) and alpha alpha alpha(anti3.7) alleles in sickle cell trait and beta-thalassemia patients in Mexico.

PubMed

Nava, María Paulina; Ibarra, Bertha; Magaña, María Teresa; de la Luz Chávez, María; Perea, F Javier

2006-01-01

The aim of this study was to determine the frequency of alpha-globin gene mutations in three groups of Mexican unrelated individuals. The first two groups were normal and sickle cell trait individuals from the Costa Chica region, a place with a 12.8% frequency of HbS carriers, and the third group comprised of Mexican mestizo patients with beta-thalassemia. We searched for -alpha(3.7) and -alpha(4.2) alpha(+)-thalassemia deletion alleles, as well as the alpha alpha alpha(anti3.7) triplication through long-gap PCR. The alleles -alpha(3.7) and alpha alpha alpha(anti3.7) were found in the heterozygote state only; 19% of the normal subjects had the -alpha(3.7) allele, and 2% showed the alpha alpha alpha(anti3.7) allele. In individuals with the sickle cell trait, 17% had the -alpha(3.7) deletion, and the alpha alpha alpha(anti3.7) triplication was observed in 3% of these individuals. We revealed that 16% of the subjects with beta-thalassemia showed the -alpha(3.7) deletion and 28% the alpha alpha alpha(anti3.7) triplication. The -alpha(4.2) deletion was not detected in any individual. The frequency of the -alpha(3.7) allele was roughly the same in the three groups studied; this can be explained by the fact that the three groups have common genes from Africa and the Mediterranean, where a high prevalence of alpha(+)-thalassemia has been observed. To our knowledge, the frequency of alpha alpha alpha(anti3.7) triplication observed in the Mexican beta-thalassemia patients is the highest reported. As the -alpha(3.7) and alpha alpha alpha(anti3.7) alleles are very common in our selected populations, we believe that there is a need to investigate systematically the alpha-globin gene mutations in all hemoglobinopathies in the Mexican population.

Vocational Options for Those with Sickle Cell Trait: Questions about Hypoxemia and the Industrial Environment,

DTIC Science & Technology

1980-11-01

Infectious mononucleosis associated with rhabdomyolysis and renal failure. South Med J 71:346-348, 1978 31. Schreir RW, Henderson HS, Tisher CC, et...might just as likely have been associated with some infectious agent. Organisms capable of causing DIC and RML are known to be endemic or epidemic in

Red blood cell indices and prevalence of hemoglobinopathies and glucose 6 phosphate dehydrogenase deficiencies in male Tanzanian residents of Dar es Salaam.

PubMed

Mwakasungula, Solomon; Schindler, Tobias; Jongo, Said; Moreno, Elena; Kamaka, Kasimu; Mohammed, Mgeni; Joseph, Selina; Rashid, Ramla; Athuman, Thabit; Tumbo, Anneth Mwasi; Hamad, Ali; Lweno, Omar; Tanner, Marcel; Shekalaghe, Seif; Daubenberger, Claudia A

2014-01-01

Hemoglobinopathies, disorders of hemoglobin structure and production, are one of the most common monogenic disorders in humans. Glucose 6 phosphate dehydrogenase deficiency (G6PD) is an inherited enzymopathy resulting in increased oxygen stress susceptibility of red blood cells. The distributions of these genetic traits in populations living in tropical and subtropical regions where malaria has been or is still present are thought to result from survival advantage against severe life threatening malaria disease. 384 male Tanzanian volunteers residing in Dar es Salaam were typed for G6PD, sickle cell disease and α-thalassemia. The most prominent red blood cell polymorphism was heterozygous α(+)-thalassemia (37.8%), followed by the G6PD(A) deficiency (16.4%), heterozygous sickle cell trait (15.9%), G6PD(A-) deficiency (13.5%) and homozygous α(+)-thalassemia (5.2%). 35%, 45%, 17% and 3% of these volunteers were carriers of wild type gene loci, one, two or three of these hemoglobinopathies, respectively. We find that using a cut off value of 28.6 pg. for mean corpuscular hemoglobin (MCH), heterozygous α(+)-thalassemia can be predicted with a sensitivity of 84% and specificity of 72% in this male population. All subjects carrying homozygous α(+)-thalassemia were identified based on their MCH value < 28.6 pg.

In vivo studies of sickle red blood cells.

PubMed

Kaul, Dhananjay K; Fabry, Mary E

2004-03-01

The defining clinical feature of sickle cell anemia is periodic occurrence of painful vasoocclusive crisis. Factors that promote trapping and sickling of red cells in the microcirculation are likely to trigger vasoocclusion. The marked red cell heterogeneity in sickle blood and abnormal adhesion of sickle red cells to vascular endothelium would be major disruptive influences. Using ex vivo and in vivo models, the authors show how to dissect the relative contribution of heterogeneous sickle red cell classes to adhesive and obstructive events. These studies revealed that (1) both rheological abnormalities and adhesion of sickle red cells contribute to their abnormal hemodynamic behavior, (2) venules are the sites of sickle cell adhesion, and (3) sickle red cell deformability plays an important role in adhesive and obstructive events. Preferential adhesion of deformable sickle red cells in postcapillary venules followed by selective trapping of dense sickle red cells could result in vasoocclusion. An updated version of this 2-step model is presented. The multifactorial nature of sickle red cell adhesion needs to be considered in designing antiadhesive therapy in vivo.

Sickle Cell Anemia Disease (For Kids)

MedlinePlus

... Safe Videos for Educators Search English Español Sickle Cell Disease KidsHealth / For Kids / Sickle Cell Disease What's ... to stay in the hospital. What Causes Sickle Cell Disease? Sickle cell disease is an inherited (say: ...

High birth prevalence of sickle cell disease in Northwestern Tanzania

PubMed Central

Ambrose, Emmanuela E.; Makani, Julie; Chami, Neema; Masoza, Tulla; Kabyemera, Rogatus; Peck, Robert N.; Kamugisha, Erasmus; Manjurano, Alphaxard; Kayange, Neema; Smart, Luke R.

2017-01-01

Background Worldwide, hemoglobinopathies affect millions of children. Identification of hemoglobin disorders in most sub-Saharan African countries is delayed until clinical signs of the disease are present. Limited studies have been conducted to understand their prevalence and clinical presentation among newborns in resource-limited settings. Methodology This was a prospective cohort study. Newborns (aged 0–7 days) at two hospitals in Northwestern Tanzania were enrolled and followed prospectively for 6 months. Clinical and laboratory information were collected at baseline. Participants were screened for hemoglobinopathies using high-performance liquid chromatography. Clinical and laboratory follow-up was performed at 3 and 6 months for those with hemoglobinopathies as well as a comparison group of participants without hemoglobinopathies. Results A total of 919 newborns were enrolled. Among these, 1.4% (13/919) had sickle cell anemia or Hb S/β0-thalassemia (Hb FS), and 19.7% (181/919) had sickle cell trait or Hb S/β+ thalassemia (Hb FAS). Furthermore, 0.2% (two of 919) had β+-thalassemia. Red cell indices compared between Hb FS, Hb FAS, and Hb FA were similar at baseline, but hemoglobin was lower and red cell distribution width was higher in children with Hb FS at 3- and 6-month follow-up. Febrile episodes were more common for children with Hb FS at 3- and 6-month follow-up. Conclusion The prevalence of sickle cell disease among neonates born in Northwestern Tanzania is one of the highest in the world. Newborn screening is needed early in life to identify neonates with hemoglobinopathies so that clinical management may commence and morbidity and mortality related to hemoglobinopathies be reduced. PMID:28766840

Evaluation of nucleated red blood cell count by Sysmex XE-2100 in patients with thalassaemia or sickle cell anaemia and in neonates.

PubMed

Buoro, Sabrina; Vavassori, Mauro; Pipitone, Silvia; Benegiamo, Anna; Lochis, Eleonora; Fumagalli, Sabina; Falanga, Anna; Marchetti, Marina; Crippa, Alberto; Ottomano, Cosimo; Lippi, Giuseppe

2015-10-01

Current haematology analysers have variable sensitivity and accuracy for counting nucleated red blood cells in samples with low values and in all those conditions characterised by altered sensitivity of red blood cells to the lysing process, such as in beta-thalassaemia or sickle-cell diseases and in neonates. The aim of our study was to evaluate the performance of the automated analyser XE-2100 at counting nucleated red blood cells in the above-mentioned three categories of subjects with potentially altered red blood cell lysis sensitivity and yet a need for accurate nucleated red blood cell counts. We measured nucleated red blood cell count by XE-2100 in peripheral blood samples of 187 subjects comprising 55 patients with beta-thalassaemia (40 major and 15 traits), 26 sickle-cell patients, 56 neonates and 50 normal subject. Results were compared with those obtained by optical microscopy. Agreement between average values of the two methods was estimated by means of Pearson's correlation and bias analysis, whereas diagnostic accuracy was estimated by analysis of receiver operating characteristic curves. The comparison between the two methods showed a Pearson's correlation of 0.99 (95% CI; 0.98-0.99; p<0.001) and bias of -0.61 (95% CI, -1.5-0.3). The area under the curve of the nucleated red blood cell count in all samples was 0.98 (95% CI, 0.96-1.00; p<0.001). Sub-analysis revealed an area under curve of 0.99 (95% CI, 0.98-1.00; p<0.001) for patients with thalassaemia, 0.94 (95% CI, 0.85-1.00; p<0.001) for patients with sickle cell anaemia, and 1.00 (95% CI, 1.0-1.0) for neonates. XE-2100 has excellent performance for nucleated red blood cell counting, especially in critical populations such as patients with haemoglobinopathies and neonates.

Sickle Cell Crisis (For Teens)

MedlinePlus

... Safe Videos for Educators Search English Español Sickle Cell Crisis (Pain Crisis) KidsHealth / For Teens / Sickle Cell ... drepanocíticas (Crisis de dolor) What Is a Sickle Cell Crisis? Sickle cell disease changes the shape of ...

Sickle Cell Disease (For Parents)

MedlinePlus

... Safe Videos for Educators Search English Español Sickle Cell Disease KidsHealth / For Parents / Sickle Cell Disease What's ... español Enfermedad de células falciformes What Is Sickle Cell Disease? Sickle cell disease is a condition in ...

Paclitaxel-induced sickle cell crisis.

PubMed

Wilson, Nicole M; Espirito, Janet L; Valero, Vicente; Pusztai, Lajos

2008-07-15

A case of paclitaxel-induced painful crisis in a patient with breast cancer and hemoglobin sickle cell disease (SCD) is reported. A 55-year-old postmenopausal African-American woman had stage IIB invasive ductal carcinoma of the left breast. She was not taking any medications and did not report a history of cancer or other diseases. She had mild microcytic anemia, but the rest of her blood counts and liver function test values were normal. Bone scans and computed tomography scans of her chest and abdomen did not reveal any metastatic disease. She underwent a routine left segmental mastectomy and axillary lymph node dissection that revealed a 4-cm invasive cancer with 1 of 10 axillary lymph nodes positive for metastatic disease. Her treatment plan included chemotherapy with weekly paclitaxel, followed by fluorouracil, epirubicin, and cyclophosphamide and radiation. The first cycle of paclitaxel was well tolerated until one week after initiation when the patient woke up in the middle of the night with a sudden onset of excruciating back pain and muscle spasms. Other symptoms that developed included fatigue, left-sided rib pain, and shortness of breath. The patient recalled being told that she had sickle cell trait but said that she never had a sickle cell crisis. Laboratory tests during her 13-day hospitalization revealed hemolysis. The patient was diagnosed with hemoglobin SCD and later discharged with as-needed, low-dose oxycodone and baclofen, antibiotics, and folic acid. A patient with breast cancer and SCD had a painful crisis after receiving paclitaxel as part of her chemotherapy regimen.

Acquisition of natural humoral immunity to P. falciparum in early life in Benin: impact of clinical, environmental and host factors.

PubMed

Dechavanne, Célia; Sadissou, Ibrahim; Bouraima, Aziz; Ahouangninou, Claude; Amoussa, Roukiyath; Milet, Jacqueline; Moutairou, Kabirou; Massougbodji, Achille; Theisen, Michael; Remarque, Edmond J; Courtin, David; Nuel, Gregory; Migot-Nabias, Florence; Garcia, André

2016-09-27

To our knowledge, effects of age, placental malaria infection, infections during follow-up, nutritional habits, sickle-cell trait and individual exposure to Anopheles bites were never explored together in a study focusing on the acquisition of malaria antibody responses among infants living in endemic areas.Five hundred and sixty-seven Beninese infants were weekly followed-up from birth to 18 months of age. Immunoglobulin G (IgG), IgG1 and IgG3 specific for 5 malaria antigens were measured every 3 months. A linear mixed model was used to analyze the effect of each variable on the acquisition of antimalarial antibodies in 6-to18-month old infants in univariate and multivariate analyses. Placental malaria, nutrition intakes and sickle-cell trait did not influence the infant antibody levels to P. falciparum antigens. In contrary, age, malaria antibody levels at birth, previous and present malaria infections as well as exposure to Anopheles bites were significantly associated with the natural acquisition of malaria antibodies in 6-to18-month old Beninese infants. This study highlighted inescapable factors to consider simultaneously in an immuno-epidemiological study or a vaccine trial in early life.

Red cell 2,3-diphosphoglycerate levels in children with hereditary haemolytic anaemias.

PubMed

Haidas, S; Zannos-Mariolea, L; Matsaniotis, N

1975-12-01

The role of red cell 2,3-diphosphoglycerate (2,3-DPG) in increasing the availability of haemoglobin oxygen in neonatal jaundice and hereditary haemolytic anaemias was investigated. Measurements of 2,3-DPG were carried out on 58 normal children and six normal adults, 18 full-term newborns with neonatal jaundice and 57 cases (51 children and six adults) with hereditary haemolytic anaemias. In normal children and adults, with a mean haemoglobin of 12.69 g/dl, mean 2,3-DPG was 14.90 mumol/g Hb. In jaundiced newborns with a mean haemoglobin of 16.04 g/dl mean 2,3-DPG levels were 14.51 mumol/g Hb, i.e. normal. 2,3-DPG levels were increased in patients with beta-thalassaemia major, alpha-thalassaemia, sickle-cell disease, favism, hereditary spherocytosis and in heterozygotes for beta-thalassaemia with increased haemoglobin F. In heterozygotes for beta-thalassaemia with increased haemoglobin A2 only and in sickle cell trait 2,3-DPG levels were normal.

Sickle Cell Research: Yesterday, Today, and Tomorrow | NIH MedlinePlus the Magazine

MedlinePlus

... this page please turn Javascript on. Special Section: Sickle Cell Disease Sickle Cell Research: Yesterday, Today, and Tomorrow Past ... live productively. Sickle cell disease (also known as sickle cell anemia) is a serious disease in which the body ...

Comparison of oxidative stress and the frequency of polymorphisms in the HFE gene between hemoglobin S trait blood donors and sickle cell disease patients.

PubMed

Viana-Baracioli, L M S; Tukamoto Junior, N C; Ricci Junior, O; Mattos, L C; Ângulo, I L; Bonini-Domingos, C R

2011-12-08

It is well documented that Hb S and iron affect blood cells, and trigger oxidative processes and generation of free radicals with potential for lipid peroxidation. We evaluated the frequency of polymorphisms in the HFE gene in Hb AS blood donors and how these polymorphisms influenced lipid peroxidation and antioxidant capacity. Blood samples were collected from 211 Hb AS blood donors, 119 Hb AA blood donors as a control group, and 28 sickle cell disease patients (Hb SS). The H63D allele was found at a frequency of 10.5% in the Hb AS samples, and the C282Y allele frequency was 0.7%. In the control group, the frequencies of the H63D and C282Y alleles were 13.4 and 2.1%, respectively. In the sickle-cell disease patients, the H63D and the C282Y allele frequencies were 10.7 and 3.5%, respectively. The frequencies of the C282Y and H63D polymorphisms in Hb AS blood donors are similar to those reported for the Brazilian population. Serum malondialdehyde values, indicative of lipid peroxidation, were highest in sickle cell patients, independent of the polymorphisms in the HFE gene, with significant differences, showing the influence of Hb S allele in the levels of lipid peroxidation. However, the trolox equivalent antioxidant capacity average levels, indicative of the antioxidant capacity, were reduced with significant differences, indicating that in spite of a lipid peroxidation raise, this is not followed by the increased of the antioxidant capacity, leading to oxidative stress.

Sickle cell anemia

MedlinePlus

Anemia - sickle cell; Hemoglobin SS disease (Hb SS); Sickle cell disease ... Sickle cell anemia is caused by an abnormal type of hemoglobin called hemoglobin S. Hemoglobin is a protein inside red blood cells ...

When Blood Cells Bend: Understanding Sickle Cell Disease

MedlinePlus

... Subscribe April 2012 Print this issue When Blood Cells Bend Understanding Sickle Cell Disease Send us your ... Diabetes? Sound Health Wise Choices Living with Sickle Cell Disease See a sickle cell disease expert regularly. ...

Sickle cell anemia - resources

MedlinePlus

Resources - sickle cell anemia ... The following organizations are good resources for information on sickle cell anemia : American Sickle Cell Anemia Association -- www.ascaa.org US National Library of Medicine -- ghr.nlm. ...

21 CFR 864.7825 - Sickle cell test.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Sickle cell test. 864.7825 Section 864.7825 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7825 Sickle cell test. (a) Identification. A sickle cell test is a device used to determine the sickle cell hemoglobin content of human...

21 CFR 864.7825 - Sickle cell test.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Sickle cell test. 864.7825 Section 864.7825 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7825 Sickle cell test. (a) Identification. A sickle cell test is a device used to determine the sickle cell hemoglobin content of human...

21 CFR 864.7825 - Sickle cell test.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Sickle cell test. 864.7825 Section 864.7825 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7825 Sickle cell test. (a) Identification. A sickle cell test is a device used to determine the sickle cell hemoglobin content of human...

21 CFR 864.7825 - Sickle cell test.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Sickle cell test. 864.7825 Section 864.7825 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7825 Sickle cell test. (a) Identification. A sickle cell test is a device used to determine the sickle cell hemoglobin content of human...

21 CFR 864.7825 - Sickle cell test.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Sickle cell test. 864.7825 Section 864.7825 Food... DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7825 Sickle cell test. (a) Identification. A sickle cell test is a device used to determine the sickle cell hemoglobin content of human...

Analysis of hemoglobin electrophoresis results and physicians investigative practices in Saudi Arabia.

PubMed

Mehdi, Syed Riaz; Al Dahmash, Badr Abdullah

2013-07-01

Riyadh and central province falls in a moderate prevalent zone of hemoglobinopathies in Saudi Arabia. However, it has been observed that the physicians working in Saudi Arabia invariably advise all cases of anemia for hemoglobin electrophoresis (HE). The present work was carried out to study the yield of the HE in Riyadh and the investigative practices of the physicians advising HE. The study was carried out in the hospitals of King Saud University from 2009 to 2011 in order to assess the yield of HE in referred cases of clinical anemia. A total of 1073 cases divided in two groups of males and females had undergone complete blood count and red blood cell morphology. Cellulose acetate HE was performed and all the positive results were reconfirmed on the high performance liquid chromatography (HPLC). The results were analyzed for the type of hemoglobinopathies. For statistical analysis Statistical Package for Social Sciences 15 version (SPSS Inc., Chicago, IL, USA) was used. A total of 405 males and 668 females blood samples were included in the present study. 116 (28.5%) males and 167 (25%) females showed an abnormal pattern on HE. The incidence of beta thalassemia trait was higher in females while sickle cell trait was predominantly seen in males. Red cell indices were reduced considerably in thalassemias, but were unaffected in sickle cell disorders, except those which had concurrent alpha trait. The total yield of HE was 26.6% which was much less than expected. The physicians are advised to rule out iron deficiency and other common causes of anemia before investigating the cases for hemoglobinopathies, which employs time consuming and expensive tests of HE and HPLC.

Analysis of hemoglobin electrophoresis results and physicians investigative practices in Saudi Arabia

PubMed Central

Mehdi, Syed Riaz; Al Dahmash, Badr Abdullah

2013-01-01

BACKGROUND AND OBJECTIVES: Riyadh and central province falls in a moderate prevalent zone of hemoglobinopathies in Saudi Arabia. However, it has been observed that the physicians working in Saudi Arabia invariably advise all cases of anemia for hemoglobin electrophoresis (HE). The present work was carried out to study the yield of the HE in Riyadh and the investigative practices of the physicians advising HE. SETTINGS AND DESIGN: The study was carried out in the hospitals of King Saud University from 2009 to 2011 in order to assess the yield of HE in referred cases of clinical anemia. MATERIALS AND METHODS: A total of 1073 cases divided in two groups of males and females had undergone complete blood count and red blood cell morphology. Cellulose acetate HE was performed and all the positive results were reconfirmed on the high performance liquid chromatography (HPLC). The results were analyzed for the type of hemoglobinopathies. For statistical analysis Statistical Package for Social Sciences 15 version (SPSS Inc., Chicago, IL, USA) was used. RESULTS: A total of 405 males and 668 females blood samples were included in the present study. 116 (28.5%) males and 167 (25%) females showed an abnormal pattern on HE. The incidence of beta thalassemia trait was higher in females while sickle cell trait was predominantly seen in males. Red cell indices were reduced considerably in thalassemias, but were unaffected in sickle cell disorders, except those which had concurrent alpha trait. The total yield of HE was 26.6% which was much less than expected. CONCLUSION: The physicians are advised to rule out iron deficiency and other common causes of anemia before investigating the cases for hemoglobinopathies, which employs time consuming and expensive tests of HE and HPLC. PMID:24339548

Effect of health education on the knowledge and attitude to sickle cell disorder and screening practices among school of nursing students in Sokoto, Nigeria.

PubMed

Abiola, A O; Ojika, B O; Mannir, B; Abba, S K; Muhammad, M; Ibrahim, M T O; Aschcroft, B N; Akanmu, S S

2013-01-01

Sickle cell disorder is the most important genetic hematological disease that affects people of black African descent. The years of young adulthood present a good opportunity for screening and counseling for this genetic blood disorder. To assess effect of health education and provision of free sickle cell haemoglobin screening on knowledge of sickle cell disorder, attitude towards sickle cell haemoglobin screening, and uptake of sickle cell haemoglobin screening among students of a School of Nursing. Study design was a quasi-experimental noncontrolled study. Self-administered questionnaire was used for pre- and post-intervention data collection. Implemented interventions were seminar on sickle cell disorder combined with free sickle cell haemoglobin screening. The data was analyzed with Epi-info version 3.5.1 statistical software package. Respondents who participated in all the study phases were 104. Mean knowledge score (%) was high (80.9 +/- 22.8%) at baseline and improved significantly to 91.8 +/- 9.4% (p < 0.001) at post intervention. 91.3% were willing to screen fiancée before getting married while 72.1% were willing not to go ahead with marriage if self and fiancée are carriers of sickle cell haemoglobin. Phenotype of the respondents that volunteered to be screened for sickle cell haemoglobin were: A (70.5%), AC (6.8%) and AS (22.7%). Implemented interventions, seminar on sickle cell disorder combined with free sickle cell haemoglobin screening service yielded significant impact on respondents' knowledge, attitude and uptake of sickle cell haemoglobin screening.

Red Blood Cell Immune Complex Binding Capacity in Children with Sickle Cell Trait (HbAS) Living in P. falciparum Malaria Holoendemic Region of Western Kenya

DTIC Science & Technology

2012-12-08

the erythrocytes in normal individuals and also in certain disease states such as systemic lupus erythematosus, HIV and some hemolytic anemia. In these...chronic conditions including malaria, HIV infection and others are known to interfere with the parameters under investigation such as complement...Craig M, Deichmann U, Marsh K. Estimating mortality, morbidity and disability due to malaria among Africa’s non- pregnant population. Bull World Health

Vascular occlusion and infarction in sickle cell crisis and the sickle chest syndrome.

PubMed Central

Athanasou, N A; Hatton, C; McGee, J O; Weatherall, D J

1985-01-01

A young adult with homozygous sickle cell anaemia (Hb SS) suffered a fatal sickle cell crisis complicated by the sickle chest syndrome. At necropsy multiple large infarcts of the lung, bone marrow, and pituitary gland were found. The large majority of pulmonary infarcts were not associated with either gross or microscopic vaso-occlusion. These findings are discussed and correlated with past and current opinions of sickle cell crisis and the sickle chest syndrome. Images PMID:4008666

Sickle cell, habitual dys-positions and fragile dispositions: young people with sickle cell at school

PubMed Central

Dyson, Simon M; Atkin, Karl; Culley, Lorraine A; Dyson, Sue E; Evans, Hala

2011-01-01

The experiences of young people living with a sickle cell disorder in schools in England are reported through a thematic analysis of forty interviews, using Bourdieu’s notions of field, capital and habitus. Young people with sickle cell are found to be habitually dys-positioned between the demands of the clinic for health maintenance through self-care and the field of the school, with its emphases on routines, consistent attendance and contextual demands for active and passive pupil behaviour. The tactics or dispositions that young people living with sickle cell can then employ, during strategy and struggle at school, are therefore fragile: they work only contingently, transiently or have the unintended consequences of displacing other valued social relations. The dispositions of the young people with sickle cell are framed by other social struggles: innovations in school procedures merely address aspects of sickle cell in isolation and are not consolidated into comprehensive policies; mothers inform, liaise, negotiate and advocate in support of a child with sickle cell but with limited success. Reactions of teachers and peers to sickle cell have the enduring potential to drain the somatic, cultural and social capital of young people living with sickle cell. PMID:21375541

Multiorgan failure during a sickle cell crisis in sickle/beta-thalassemia.

PubMed

Tedla, Fasika M; Friedman, Eli A

2003-08-01

In contrast to the chronic nephropathy associated with sickle cell syndromes, acute renal failure and multiorgan dysfunction caused by acute sickling crisis are encountered infrequently. The authors present the first case of extensive multiorgan failure during a sickling episode in a patient with sickle/beta+thalassemia. The authors also review the interaction of the thalassemias with sickle cell disease and outline the distinctive course of their patient in comparison with previous reports.

Intravenous support for the patient in sickle cell crisis.

PubMed

Odesina, V

2001-01-01

Sickle cell episodes (otherwise known as crises) are inevitable complications of sickle cell disease (SCD). Successful management of these episodes includes hydration, medication administration, and blood transfusion. Intravenous support is an essential component in the management of sickle cell-related complications. This article gives an overview of SCD and its complications and treatments, focusing on infusion therapy support of the patient during a sickle cell episode.

Sickle cell trait and incident ischemic stroke in the Atherosclerosis Risk in Communities study.

PubMed

Caughey, Melissa C; Loehr, Laura R; Key, Nigel S; Derebail, Vimal K; Gottesman, Rebecca F; Kshirsagar, Abhijit V; Grove, Megan L; Heiss, Gerardo

2014-10-01

Numerous case reports describe stroke in individuals with sickle cell trait (SCT) in the absence of traditional risk factors for cerebrovascular disease. To date, no prospective epidemiological studies have investigated this association. A population-based sample of blacks (n=3497; mean age=54 years; female=62%) was followed from 1987 to 2011 in the Atherosclerosis Risk in Communities (ARIC) study, contributing a total of 65 371 person-years. Hazard ratios and incidence rate differences for ischemic stroke were estimated, contrasting SCT to homozygous hemoglobin A. Models were adjusted for age, sex, smoking, diabetes mellitus, hypertension, total cholesterol, atrial fibrillation, and coronary heart disease. SCT was identified in 223 (6.4%) participants. During a median follow-up of 22 years, 401 subjects experienced incident stroke (89% ischemic). Incident ischemic stroke was more frequent among those with SCT (13%) than those with homozygous hemoglobin A (10%). SCT was associated with an ischemic stroke hazard ratio of 1.4 (1.0-2.0) and an incidence rate difference amounting to 1.9 (0.4-3.8) extra strokes per 1000 person-years. We observed an increased risk of ischemic stroke in blacks with SCT. Further investigation of the incidence and pathophysiology of stroke in patients with SCT is warranted. © 2014 American Heart Association, Inc.

Latest Sickle Cell Research | NIH MedlinePlus the Magazine

MedlinePlus

... Special Section: Sickle Cell Disease Latest Sickle Cell Research Past Issues / Winter 2011 Table of Contents In ... treatment on brain function. Other current and future research efforts include studies of: Genetic factors affecting sickle ...

The frequency and severity of epistaxis in children with sickle cell anaemia in eastern Uganda: a case-control study.

PubMed

Nardo-Marino, Amina; Williams, Thomas N; Olupot-Olupot, Peter

2017-01-01

There are a paucity of data on epistaxis as it pertains to sickle cell anaemia. Some case studies suggest epistaxis to be a significant complication in patients with sickle cell anaemia in sub-Saharan Africa; however, no robust studies have sought to establish the epidemiology or pathophysiology of this phenomenon. We conducted a case-control study with the aim of investigating the importance of epistaxis among children presenting with sickle cell anaemia at the Mbale Regional Referral Hospital in eastern Uganda. Cases were children aged 2-15 years with an existing diagnosis of laboratory confirmed sickle cell anaemia, while controls were children without sickle cell anaemia who were frequency matched to cases on the basis of age group and gender. The frequency and severity of epistaxis was assessed using a structured questionnaire developed specifically for this study. Odds ratios controlled for age group and gender were calculated using unconditional logistic regression. A total of 150 children were included, 73 children with sickle cell anaemia and 77 children without sickle cell anaemia. The overall prevalence of epistaxis among children with sickle cell anaemia and children without sickle cell anaemia was 32.9 and 23.4% respectively. The case-control odds ratios for epistaxis, recurrent epistaxis and severe epistaxis were, 1.6 (95%CI 0.8-3.4; p  = 0.2), 7.4 (1.6-34.5; 0.01), and 8.3 (1.0-69.8; 0.05) respectively. Our results suggest that in eastern Uganda, children with sickle cell anaemia experience epistaxis more frequently and with greater severity than children without sickle cell anaemia. Further studies are indicated to confirm this conclusion and investigate aetiology.

Sickle red cell adhesion: many issues and some answers.

PubMed

Kaul, D K

2008-01-01

Among multiple pathologies associated with sickle cell disease, sickle red cell-endothelial interaction has been implicated as a potential initiating mechanism in vaso-occlusive events that characterize this disease. Vast literature exists on various aspects of sickle red cell adhesion, but many issues remain unresolved, especially pertaining to the role of sickle red cell heterogeneity, the relative role of multiple adhesion mechanisms and targets of antiadhesive therapy. This review briefly analyzes these issues.

78 FR 44575 - Sickle Cell Disease Treatment Demonstration Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Sickle Cell... Extension: Sickle Cell Disease Treatment Demonstration Program (U1E) Awards to Three Currently Funded... the Sickle Cell Disease Treatment Demonstration Program. Three of these awards will end on August 31...

Legal, Ethical, Social and Economic Issues in Sickle Cell Program

ERIC Educational Resources Information Center

Bowman, James E.

1973-01-01

Urges that mandatory sickle cell screening laws be repealed, and that all screening programs be voluntary; bogus sickle cell organizations are a major crisis in black communities and must be eliminated; research and education in sickle cell disease is badly needed. (Author/JM)

Elevated IL-8 levels during sickle cell crisis.

PubMed

Duits, A J; Schnog, J B; Lard, L R; Saleh, A W; Rojer, R A

1998-11-01

The vaso-occlusive process (VOC) in sickle cell disease is of a complex nature. It involves intricate interactions between sickle red blood cells, endothelium and probably also leukocytes. As these interactions are regulated by cytokines, we analyzed the role of the potent neutrophil chemokine IL-8 by measuring serum levels in sickle cell patients during sickle cell crisis. These results were compared to nonsymptomatics and healthy controls. In patients having a vaso-occlusive crisis both HbSS and HbSC patients showed significantly enhanced serum IL-8 levels compared to healthy controls. Several of these patients showed extremely elevated serum IL-8 levels which were independent of the crisis inducing factor. Furthermore, a sickle cell patient with VOC as a complication of rhGM-CSF treatment similarly showed high IL-8 serum levels at crisis onset. Nonsymptomatic sickle cell patients serum IL-8 levels were comparable to healthy controls. These results implicate a role for IL-8 at or during (the initiation of) sickle cell crisis.

Sickle red cell-endothelium interactions.

PubMed

Kaul, Dhananjay K; Finnegan, Eileen; Barabino, Gilda A

2009-01-01

Periodic recurrence of painful vaso-occlusive crisis is the defining feature of sickle cell disease. Among multiple pathologies associated with this disease, sickle red cell-endothelium interaction has been implicated as a potential initiating mechanism in vaso-occlusive events. This review focuses on various interrelated mechanisms involved in human sickle red cell adhesion. We discuss in vitro and microcirculatory findings on sickle red cell adhesion, its potential role in vaso-occlusion, and the current understanding of receptor-ligand interactions involved in this pathological phenomenon. In addition, we discuss the contribution of other cellular interactions (leukocytes recruitment and leukocyte-red cell interaction) to vaso-occlusion, as observed in transgenic sickle mouse models. Emphasis is given to recently discovered adhesion molecules that play a predominant role in mediating human sickle red cell adhesion. Finally, we analyze various therapeutic approaches for inhibiting sickle red cell adhesion by targeting adhesion molecules and also consider therapeutic strategies that target stimuli involved in endothelial activation and initiation of adhesion.

Human genome project and sickle cell disease.

PubMed

Norman, Brenda J; Miller, Sheila D

2011-01-01

Sickle cell disease is one of the most common genetic blood disorders in the United States that affects 1 in every 375 African Americans. Sickle cell disease is an inherited condition caused by abnormal hemoglobin in the red blood cells. The Human Genome Project has provided valuable insight and extensive research advances in the understanding of the human genome and sickle cell disease. Significant progress in genetic knowledge has led to an increase in the ability for researchers to map and sequence genes for diagnosis, treatment, and prevention of sickle cell disease and other chronic illnesses. This article explores some of the recent knowledge and advances about sickle cell disease and the Human Genome Project.

[Acute painful crisis in a female Nigerian patient with sickle cell disease].

PubMed

Nin, Sayaka; Seki, Masanori; Maie, Koichiro; Kuroda, Akihiro; Miyamoto, Kana; Ogawa, Shinichi; Ito, Yufu; Kurita, Naoki; Yokoyama, Yasuhisa; Sakata Yanagimoto, Mamiko; Obara, Naoshi; Hasegawa, Yuichi; Ogino, Yasuko; Ito, Takayoshi; Chiba, Shigeru

2015-01-01

We report a 38-year-old Nigerian woman with sickle cell disease. Sickle cell disease had been diagnosed when she experienced her first sickle cell crisis episode at age 8 years. Thereafter, she had infrequent minor episodes. She visited a hospital presenting with fever, anemia, jaundice, and systemic pain, and was then transferred to our hospital. Together with rehydration and red blood cell transfusion, analgesics and antibiotics were prescribed, and produced gradual improvement of all symptoms and signs. The patient was discharged on day 9 of hospitalization. Sickle cell crisis is an acute painful episode caused by occlusion of arterioles. The degree of pain and accompanying symptoms, as well as the frequencies of crises, are variable. Moreover, one third of individuals with sickle cell disease never experience a crisis. As our society becomes increasingly globalized, the probabilities of encountering sickle cell disease patients will be higher.

Granulocyte-colony stimulating factor administration among hemoglobin S trait donors: A single center experience from the Eastern Mediterranean region.

PubMed

Gereklioglu, Cigdem; Asma, Suheyl; Korur, Aslı; Tepebaşı, Songul; Aytan, Pelin; Yeral, Mahmut; Kozanoglu, Ilknur; Boga, Can; Ozdogu, Hakan

2018-02-01

Assessment of Hemoglobin S trait donors has gained importance together with the increased allogeneic peripheral stem cell transplant activity for sickle cell disease in the regions where the disease is prevalent. Outcomes of Granulocyte-Colony Stimulating Factor (G-CSF) administration are obscure for hemoglobin S trait donors. This study aims at investigating the incidence of hemoglobin S carrier status and outcomes of G-CSF administration among donors who live in Eastern Mediterranean region. The cross-sectional, single-center cohort study was performed with 147 donors between January 2013 and March 2017. Prevalence of hemoglobin S trait was estimated and subjects with or without Hemogobin S trait were compared with regard to stem cell characteristics, early and late clinical outcomes after G-CSF administration. Eleven out of 147 donors (7.48%) were found as hemoglobin S trait. G-CSF administration was successfully completed and yielded good harvesting results in hemoglobin S trait donors. No statistically significant difference was found between groups with regard to early and late side effects, stem cell characteristics. Blood pressures and QTc values were within normal ranges in both groups. Groups were similar with regard to CD34 values. G-CSF seems safe in hemoglobin S trait donors. Their being eligible as donors would increase the chance of the patients for allogeneic stem cell transplantation in high prevalence regions. Further studies are required to reveal the safety profile of G-SCF in hemoglobin S carriers in different regions. © 2017 Wiley Periodicals, Inc.

Amelioration of Sickle Cell Pain after Parathyroidectomy in Two Patients with Concurrent Hyperparathyroidism: An Interesting Finding.

PubMed

Muthu, John; Ali, Mir

2016-01-01

Patients with sickle cell disease have high morbidity and healthcare utilization due to repeated painful crises. Some coexisting conditions which cause pain similar to sickle cell disease may go undiagnosed in these patients. We report two adults with concurrent hyperparathyroidism who experienced significant improvement in sickle cell pain following parathyroidectomy thereby pointing to hyperparathyroidism as the principal causative factor for their pain. Meticulous evaluation for parathyroid disorders can be rewarding in sickle cell disease.

Amelioration of Sickle Cell Pain after Parathyroidectomy in Two Patients with Concurrent Hyperparathyroidism: An Interesting Finding

PubMed Central

Muthu, John

2016-01-01

Patients with sickle cell disease have high morbidity and healthcare utilization due to repeated painful crises. Some coexisting conditions which cause pain similar to sickle cell disease may go undiagnosed in these patients. We report two adults with concurrent hyperparathyroidism who experienced significant improvement in sickle cell pain following parathyroidectomy thereby pointing to hyperparathyroidism as the principal causative factor for their pain. Meticulous evaluation for parathyroid disorders can be rewarding in sickle cell disease. PMID:27579039

Gene therapy for sickle cell disease.

PubMed

Olowoyeye, Abiola; Okwundu, Charles I

2016-11-14

Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review. The objectives of this review are:to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 15 August 2016. All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. No trials of gene therapy for sickle cell disease were found. No trials of gene therapy for sickle cell disease were reported. No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Gene therapy for sickle cell disease.

PubMed

Olowoyeye, Abiola; Okwundu, Charles I

2014-10-10

Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. The objectives of this review are:- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 July 2014. All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. No trials of gene therapy for sickle cell disease were found. No trials of gene therapy for sickle cell disease were reported. No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

The "starfield" pattern of cerebral fat embolism from bone marrow necrosis in sickle cell crisis.

PubMed

Dhakal, Laxmi P; Bourgeois, Kirk; Barrett, Kevin M; Freeman, William D

2015-04-01

Sickle cell disease may manifest with cerebrovascular and systemic complications. Sickle crisis that results in avascular necrosis of long bones with resultant cerebral fat embolism syndrome is rare and has a characteristic "starfield" pattern on MRI. This "starfield" MRI pattern should raise suspicion for sickle cell crisis in patients without a known history of the disease, which can lead to earlier sickle cell red blood cell exchange transfusion and treatment. We present a case of a male who presented emergently with acute seizure, coma with a characteristic MRI pattern, which lead to the diagnosis of avascular bone marrow necrosis and cerebral fat embolism syndrome from sickle cell crisis.

Orbital compression syndrome in sickle cell crisis.

PubMed

Mueller, E B; Niethammer, K; Rees, D; Partsch, C J

2009-09-01

This article is about a 9-year-old boy with known homozygous sickle cell disease who developed unilateral exophthalmia and eyelid swelling during a sickle cell crisis. The symptoms were due to a vaso-occlusive event in the orbital bones,known as orbital compression syndrome, which is a rare complication of sickle cell disease.

Sickle Cell Screening: Medical, Legal, Ethical, Psychological and Social Problems; A Sickle Cell Crisis.

ERIC Educational Resources Information Center

Bowman, James E.

In recent years, sickle cell screening programs have been initiated by community groups, health centers, hospitals, medical schools, health departments, school systems, city and State governments, various branches of the Federal Government, fraternal and social clubs, and other organizations. Problems have resulted from mass sickle cell screening,…

The Effects of Conditions of Cerebral Anoxia, on Phospholipids, Metabolism, and Circulation of the Brain.

DTIC Science & Technology

and of patients with sickle cell crisis were examined. It was found that patients with sickle cell anemia show a relative increase of phospholipids in...the ghosts which are enhanced in patients with sickle cell crisis . During sickle cell crisis the concentration of phosphatidylglycerol of blood

78 FR 66747 - Sickle Cell Disease Public Meeting on Patient-Focused Drug Development

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-06

...] Sickle Cell Disease Public Meeting on Patient-Focused Drug Development AGENCY: Food and Drug... Development for sickle cell disease. Patient-Focused Drug Development is part of FDA's performance commitments... intended to allow FDA to obtain patients' perspectives on the impact of sickle cell disease on daily life...

Cannabinoid receptor-specific mechanisms to alleviate pain in sickle cell anemia via inhibition of mast cell activation and neurogenic inflammation.

PubMed

Vincent, Lucile; Vang, Derek; Nguyen, Julia; Benson, Barbara; Lei, Jianxun; Gupta, Kalpna

2016-05-01

Sickle cell anemia is a manifestation of a single point mutation in hemoglobin, but inflammation and pain are the insignia of this disease which can start in infancy and continue throughout life. Earlier studies showed that mast cell activation contributes to neurogenic inflammation and pain in sickle mice. Morphine is the common analgesic treatment but also remains a major challenge due to its side effects and ability to activate mast cells. We, therefore, examined cannabinoid receptor-specific mechanisms to mitigate mast cell activation, neurogenic inflammation and hyperalgesia, using HbSS-BERK sickle and cannabinoid receptor-2-deleted sickle mice. We show that cannabinoids mitigate mast cell activation, inflammation and neurogenic inflammation in sickle mice via both cannabinoid receptors 1 and 2. Thus, cannabinoids influence systemic and neural mechanisms, ameliorating the disease pathobiology and hyperalgesia in sickle mice. This study provides 'proof of principle' for the potential of cannabinoid/cannabinoid receptor-based therapeutics to treat several manifestations of sickle cell anemia. Copyright© Ferrata Storti Foundation.

Microparticles in sickle cell anaemia: promise and pitfalls.

PubMed

Hebbel, Robert P; Key, Nigel S

2016-07-01

Blood from patients with sickle cell disease contains microparticles (MP) derived from multiple cell sources, including red cells, platelets, monocytes and endothelial cells. MPs are of great interest because of their disease associations, their status as promising biomarkers, and the intercellular communications they mediate. To illustrate the likelihood of their relevance in sickle cell disease, we discuss the nature of MP, their profiling in sickle disease, some caveats relevant to their detection, their roles in supporting coagulation and the disparate influences they may exert upon the pathobiology of sickle cell disease. © 2016 John Wiley & Sons Ltd.

Trivalent inactivated influenza vaccine is not associated with sickle cell crises in children.

PubMed

Hambidge, Simon J; Ross, Colleen; Glanz, Jason; McClure, David; Daley, Matthew F; Xu, Stan; Shoup, Jo Ann; Narwaney, Komal; Baggs, James; Weintraub, Eric

2012-01-01

Children with sickle cell disease are considered at high risk for complications from influenza infection and are recommended to receive annual influenza vaccination. However, data on the safety of influenza vaccination in children with sickle cell anemia are sparse. Using a retrospective cohort of children aged 6 months to 17 years in 8 managed care organizations that comprise the Vaccine Safety Datalink and who had a diagnosis of sickle cell anemia from 1999 to 2006, we conducted matched case-control and self-controlled case series studies to examine the association of trivalent inactivated influenza vaccination with hospitalization for sickle cell crisis in the 2 weeks after vaccination. From an original pool of 1085 pediatric subjects with a diagnosis of sickle cell anemia, we identified 179 children with at least 1 sickle cell crisis during any influenza season (October 1-March 31). In the matched case-control study (matching on age category, gender, Vaccine Safety Datalink site, and season), the odds ratio of hospitalization for a crisis in vaccinated compared with unvaccinated children was not significant: 1.3 (95% confidence interval 0.8-2.2). In the self-controlled case series study of hospitalized cases, the incident rate ratio for hospitalization with sickle cell crisis in the 2 weeks after trivalent inactivated influenza vaccination was also not significant: 1.2 (95% confidence interval 0.75-1.95). This large cohort study did not find an association of influenza vaccination and hospitalization for sickle cell crises in children with sickle cell anemia.

Analysis of Retinal Thinning Using Spectral-domain Optical Coherence Tomography Imaging of Sickle Cell Retinopathy Eyes Compared to Age- and Race-Matched Control Eyes.

PubMed

Lim, Jennifer I; Cao, Dingcai

2018-03-17

To determine whether the retina is thinner in sickle cell patients than in race- and age-matched controls, and, if it is thinner, whether there is any association with systemic diseases. Sickle cell and control (age- and race-matched) patients were prospectively enrolled from a university retina clinic into this observational study. Participants underwent visual acuity testing, slit-lamp biomicroscopy, dilated ophthalmoscopy, and spectral-domain optical coherence tomography imaging. Sickle cell retinal lesions, degree of vascular tortuosity, caliber of arteriovenous anastomosis, and stage of retinopathy were noted. Early Treatment Diabetic Retinopathy Study (ETDRS) subfield measurements were compared between sickle cell and control subjects and also among sickle cell hemoglobin subtypes. Associations between ETDRS subfield measurements and hemoglobin subtype, retinopathy stage, and systemic diseases were assessed. A total of 513 sickle cell eyes (260 patients) and 75 control eyes (39 patients) had median visual acuities of 20/20. ETDRS central (P = .002), inner (nasal P = .009, superior P = .021, temporal P < .001, inferior P = .017), and temporal outer (P = .012) subfield measurements were thinner in sickle cell eyes compared to control eyes. Hemoglobin SS eyes had significantly thinner inner ETDRS subfield measurements compared to SC and SThal eyes. Retinal thinning in all subfields was associated with age (P = .017) for sickle cell and control eyes. No association was found between retinal thinning and hydroxyurea use or arteriovenous anastomosis caliber. The macula is thinner in sickle cell eyes compared to control eyes; retinal thickness decreases with increasing age and sickle cell retinopathy stage and is most severe in hemoglobin SS subtypes. Copyright © 2018 Elsevier Inc. All rights reserved.

Relationship between pulmonary and cardiac abnormalities in sickle cell disease: implications for the management of patients

PubMed Central

Maioli, Maria Christina Paixão; Soares, Andrea Ribeiro; Bedirian, Ricardo; Alves, Ursula David; de Lima Marinho, Cirlene; Lopes, Agnaldo José

2015-01-01

Objective To evaluate the association between clinical, pulmonary, and cardiovascular findings in patients with sickle cell disease and, secondarily, to compare these findings between sickle cell anemia patients and those with other sickle cell diseases. Methods Fifty-nine adults were included in this cross-sectional study; 47 had sickle cell anemia, and 12 had other sickle cell diseases. All patients underwent pulmonary function tests, chest computed tomography, and echocardiography. Results Abnormalities on computed tomography, echocardiography, and pulmonary function tests were observed in 93.5%, 75.0%; and 70.2% of patients, respectively. A higher frequency of restrictive abnormalities was observed in patients with a history of acute chest syndrome (85% vs. 21.6%; p-value < 0.0001) and among patients with increased left ventricle size (48.2% vs. 22.2%; p-value = 0.036), and a higher frequency of reduced respiratory muscle strength was observed in patients with a ground-glass pattern (33.3% vs. 4.3%; p-value = 0.016). Moreover, a higher frequency of mosaic attenuation was observed in patients with elevated tricuspid regurgitation velocity (61.1% vs. 24%; p-value = 0.014). Compared to patients with other sickle cell diseases, sickle cell anemia patients had suffered increased frequencies of acute pain episodes, and acute chest syndrome, and exhibited mosaic attenuation on computed tomography, and abnormalities on echocardiography. Conclusion A significant interrelation between abnormalities of the pulmonary and cardiovascular systems was observed in sickle cell disease patients. Furthermore, the severity of the cardiopulmonary parameters among patients with sickle cell anemia was greater than that of patients with other sickle cell diseases. PMID:26969771

Biomechanics and biorheology of red blood cells in sickle cell anemia

PubMed Central

Li, Xuejin; Dao, Ming; Lykotrafitis, George; Karniadakis, George Em

2017-01-01

Sickle cell anemia (SCA) is an inherited blood disorder that causes painful crises due to vaso-occlusion of small blood vessels. The primary cause of the clinical phenotype of SCA is the intracellular polymerization of sickle hemoglobin resulting in sickling of red blood cells (RBCs) in deoxygenated conditions. In this review, we discuss the biomechanical and biorheological characteristics of sickle RBCs and sickle blood as well as their implications toward a better understanding of the pathophysiology and pathogenesis of SCA. Additionally, we highlight the adhesive heterogeneity of RBCs in SCA and their specific contribution to vaso-occlusive crisis. PMID:27876368

Bilateral orbital infarction and retinal detachment in a previously undiagnosed sickle cell hemoglobinopathy African child

PubMed Central

Helen, Onakpoya Oluwatoyin; Ajite, K. O.; Oyelami, O. A.; Asaleye, C. M.; Adeoye, A. O.

2013-01-01

Bone infarction involving the orbit in sickle cell disease is not common. Bilateral orbital infarction in a previously undiagnosed sickle cell hemoglobinopathy has not been previously reported. In this report, we present a case of an 11-year-old previously undiagnosed sickle cell disease Nigerian girl with severe acute bilateral orbital infarction and retinal detachment to highlight that hemoglobinopathy induced orbital infarction should be considered in African children with acute onset proptosis with or without previous history of sickle cell hemoglobinopathy. PMID:23901183

The “Starfield” Pattern of Cerebral Fat Embolism From Bone Marrow Necrosis in Sickle Cell Crisis

PubMed Central

Dhakal, Laxmi P.; Bourgeois, Kirk; Barrett, Kevin M.

2015-01-01

Sickle cell disease may manifest with cerebrovascular and systemic complications. Sickle crisis that results in avascular necrosis of long bones with resultant cerebral fat embolism syndrome is rare and has a characteristic “starfield” pattern on MRI. This “starfield” MRI pattern should raise suspicion for sickle cell crisis in patients without a known history of the disease, which can lead to earlier sickle cell red blood cell exchange transfusion and treatment. We present a case of a male who presented emergently with acute seizure, coma with a characteristic MRI pattern, which lead to the diagnosis of avascular bone marrow necrosis and cerebral fat embolism syndrome from sickle cell crisis PMID:25829988

The Measure of Sickle Cell Stigma: Initial findings from the Improving Patient Outcomes through Respect and Trust study.

PubMed

Bediako, Shawn M; Lanzkron, Sophie; Diener-West, Marie; Onojobi, Gladys; Beach, Mary C; Haywood, Carlton

2016-05-01

Research about the influence of stigma on health outcomes in sickle cell disease is limited. We administered the recently developed Measure of Sickle Cell Stigma to 262 patients in the United States. The Measure of Sickle Cell Stigma yielded very good internal consistency and four interpretable factors. Significant associations among stigma, pain-related healthcare utilization, and perceived disease severity were observed for three of the four stigma factors (F range = 2.78-5.44). The Measure of Sickle Cell Stigma appears to be a useful tool for measuring disease-specific stigma among adults living with sickle cell disease, and further assessment of its clinical utility is warranted. © The Author(s) 2014.

Effects of nitric oxide and its congeners on sickle red blood cell deformability

PubMed Central

Belanger, Andrea M.; Keggi, Christian; Kanias, Tamir; Gladwin, Mark T.; Kim-Shapiro, Daniel B.

2015-01-01

BACKGROUND Sickle cell disease is characterized by hemoglobin (Hb) polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium-activated Gardos channel which dehydrates the cells leading to increased polymerization. In this study effects of NO and its congeners on RBC deformability were examined, focusing on sickle red blood cells. STUDY DESIGN AND METHODS Red blood cells from patients with sickle cell disease and from non-patients were exposed to various compounds that release NO or its congeners. Intracellular calcium was increased using a calcium ionophore or cycling of oxygen tension for sickle red blood cells. Deformability was measured by laser-assisted osmotic gradient ektacytometry. RESULTS Consistent with a previous report, sodium nitroprusside (SNP) was found to protect against calcium-induced loss of deformability in normal red blood cells, but (contrary to some previous reports) no effect of any NO donors was observed when calcium influx was not induced. Importantly, in studies of deoxygenation-induced dehydration of sickle RBCs, SNP resulted in substantial improvements in deformability (p=0.036) and hydration (p=0.024). Sodium nitrite showed similar trends. SNP was shown to have no effect on calcium influx, but reduced potassium efflux. CONCLUSION These data suggest SNP and perhaps certain nitrogen oxides (like nitrite) inhibit the Gardos channel and may be able to protect sickle cells from dehydration and thereby improve outcome in the disease. PMID:25912054

Pathophysiologically based drug treatment of sickle cell disease.

PubMed

Steinberg, Martin H

2006-04-01

Sickle cell disease is a systemic disorder that is caused by a mutation (Glu6Val) in the gene that encodes beta globin. The sickle hemoglobin molecule (HbS) is a tetramer of two alpha-globin chains and two sickle beta-globin chains, and has the tendency to polymerize when deoxygenated. HbS facilitates abnormal interactions between the sickle erythrocyte and leukocytes and endothelial cells, which trigger a complex pathobiology. This multifaceted pathophysiology provides the opportunity to interrupt the disease at multiple sites, including polymerization of HbS, erythrocyte density and cell-cell interactions. For example, it is possible to induce higher concentrations of fetal hemoglobin, which disrupts the pathology-initiating step of HbS polymerization. Furthermore, it is possible to improve the hydration of sickle erythrocytes and it might be feasible to counteract the endothelial, inflammatory and oxidative abnormalities of sickle cell disease. A therapeutic approach that targets several sites of pathobiology might be most promising.

Patient-specific modeling and analysis of dynamic behavior of individual sickle red blood cells under hypoxic conditions

NASA Astrophysics Data System (ADS)

Li, Xuejin; Du, E.; Li, Zhen; Tang, Yu-Hang; Lu, Lu; Dao, Ming; Karniadakis, George

2015-11-01

Sickle cell anemia is an inherited blood disorder exhibiting heterogeneous morphology and abnormal dynamics under hypoxic conditions. We developed a time-dependent cell model that is able to simulate the dynamic processes of repeated sickling and unsickling of red blood cells (RBCs) under physiological conditions. By using the kinetic cell model with parameters derived from patient-specific data, we present a mesoscopic computational study of the dynamic behavior of individual sickle RBCs flowing in a microfluidic channel with multiple microgates. We investigate how individual sickle RBCs behave differently from healthy ones in channel flow, and analyze the alteration of cellular behavior and response to single-cell capillary obstruction induced by cell rheologic rigidification and morphological change due to cell sickling under hypoxic conditions. We also simulate the flow dynamics of sickle RBCs treated with hydroxyurea (HU) and quantify the relative enhancement of hemodynamic performance of HU. This work was supported by the National Institutes of Health (NIH) Grant U01HL114476.

New developments in anti-sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo?

PubMed

Oder, Esther; Safo, Martin K; Abdulmalik, Osheiza; Kato, Gregory J

2016-10-01

The hallmark of sickle cell disease is the polymerization of sickle haemoglobin due to a point mutation in the β-globin gene (HBB). Under low oxygen saturation, sickle haemoglobin assumes the tense (T-state) deoxygenated conformation that can form polymers, leading to rigid erythrocytes with impaired blood vessel transit, compounded or initiated by adhesion of erythrocytes to endothelium, neutrophils and platelets. This process results in vessel occlusion and ischaemia, with consequent acute pain, chronic organ damage, morbidity and mortality. Pharmacological agents that stabilize the higher oxygen affinity relaxed state (R-state) and/or destabilize the lower oxygen affinity T-state of haemoglobin have the potential to delay the sickling of circulating red cells by slowing polymerization kinetics. Relevant classes of agents include aromatic aldehydes, thiol derivatives, isothiocyanates and acyl salicylates derivatives. The aromatic aldehyde, 5-hydroxymethylfurfural (5-HMF) increases oxygen affinity of sickle haemoglobin and reduces hypoxia-induced sickling in vitro and protects sickle cell mice from effects of hypoxia. It has completed pre-clinical testing and has entered clinical trials as treatment for sickle cell disease. A related molecule, GBT440, has shown R-state stabilization and increased oxygen affinity in preclinical testing. Allosteric modifiers of haemoglobin as direct anti-sickling agents target the fundamental pathophysiological mechanism of sickle cell disease. © 2016 John Wiley & Sons Ltd.

Biomechanics and biorheology of red blood cells in sickle cell anemia.

PubMed

Li, Xuejin; Dao, Ming; Lykotrafitis, George; Karniadakis, George Em

2017-01-04

Sickle cell anemia (SCA) is an inherited blood disorder that causes painful crises due to vaso-occlusion of small blood vessels. The primary cause of the clinical phenotype of SCA is the intracellular polymerization of sickle hemoglobin resulting in sickling of red blood cells (RBCs) in deoxygenated conditions. In this review, we discuss the biomechanical and biorheological characteristics of sickle RBCs and sickle blood as well as their implications toward a better understanding of the pathophysiology and pathogenesis of SCA. Additionally, we highlight the adhesive heterogeneity of RBCs in SCA and their specific contribution to vaso-occlusive crisis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Renal Failure in Sickle Cell Disease: Prevalence, Predictors of Disease, Mortality and Effect on Length of Hospital Stay.

PubMed

Yeruva, Sri L H; Paul, Yonette; Oneal, Patricia; Nouraie, Mehdi

2016-09-01

Renal dysfunction in sickle cell disease is not only a chronic comorbidity but also a mortality risk factor. Though renal dysfunction starts early in life in sickle cell patients, the predictors that can identify sickle cell disease patients at risk of developing renal dysfunction is not known. We used the Truven Health MarketScan ® Medicaid Databases from 2007 to 2012. Incidence of new acute renal failure (ARF) and chronic kidney disease (CKD) was calculated in this cohort. There were 9481 patients with a diagnosis of sickle cell disease accounting for 64,201 hospital admissions, during the study period. Both ARF and CKD were associated with higher risk of inpatient mortality, longer duration of the hospital stay and expensive hospitalizations. The yearly incidence of new ARF in sickle cell disease patients was 1.4% and annual CKD incidence was 1.3%. The annual rate of new ARF and CKD in the control group was 0.4 and 0.6%, respectively. The most important predictors of new CKD were proteinuria, ARF and hypertension. Chronic kidney disease, hypertension and sickle cell crisis were the most important predictors of new ARF. The annual rate of incidences of ARF and CKD were 2- to 3-fold higher in sickle cell disease compared to the non sickle cell disease group. Besides the common risk factors for renal disease in the general population, it is imperative to monitor the sickle cell disease patients with more severe disease to prevent them from developing renal dysfunction.

Perceptions of young adults with sickle cell disease concerning their disease experience.

PubMed

Matthie, Nadine; Hamilton, Jill; Wells, Diana; Jenerette, Coretta

2016-06-01

To describe the perceptions of young adults with sickle cell disease concerning their disease experience. Sickle cell disease is a lifelong, genetic condition with both acute and chronic painful exacerbations. Little is known of the experiences of young adults with sickle cell disease. This study used a qualitative, descriptive design with semi-structured, life review interviews. Between August 2010-September 2012, purposive sampling was used to recruit participants with a known sickle cell disease diagnosis who were ages 18-35 years, were being seen in an outpatient sickle cell clinic and were English speaking. Participants provided demographic information and responded to two interviews. A content analysis was then used to interpret participants' narratives of their experiences of living with sickle cell disease. A sample of 29 young adults with sickle cell disease consisted of 79·3% females, 35·6% employed full-time or part-time, 71·6% single/never married and 57·8% with sickle cell anaemia. Their mean age was 25·8 with 13·2 years of education. Four major interview themes were identified: (1) struggles to maintain or achieve good quality of life or life satisfactions; (2) strategies to maintain self-care; (3) interruptions to family, work and social roles; and (4) difficulties accessing needed health care. Young adults face many challenges while living with sickle cell disease. With a better understanding of their disease experience and how it influences their quality of life, researchers can begin tailoring appropriate interventions to improve health outcomes in this vulnerable, minority population. © 2015 John Wiley & Sons Ltd.

Venous thromboembolism in adults with sickle cell disease: A serious and under-recognized complication

PubMed Central

Naik, Rakhi P.; Streiff, Michael B.; Haywood, Carlton; Nelson, Julie A.; Lanzkron, Sophie

2013-01-01

BACKGROUND Sickle cell disease is recognized as a hypercoagulable state; however the frequency and characteristics of venous thromboembolism in sickle cell patients have not been well-defined. PURPOSE To establish the prevalence and risk factors for venous thromboembolism in a large cohort of patients with sickle cell disease and determine the relationship between venous thromboembolism and mortality. METHODS We performed a cross-sectional study of 404 sickle cell disease patients cared for at the Sickle Cell Center for Adults at Johns Hopkins. Demographic, sickle cell disease-specific comorbidity, and venous thromboembolism data were collected on all patients. RESULTS 101 patients (25%) had a history of venous thromboembolism with a median age at diagnosis of 29.9 years. A history of non-catheter-related venous thromboembolism was found in 18.8% of patients. Sickle variant genotypes conferred a higher risk of non-catheter-related venous thromboembolism compared to sickle cell anemia genotypes (SS/Sβ0) (relative risk (RR) 1.77, 95% confidence interval (CI) 1.18–2.66). Tricuspid regurgitant jet velocity ≥ 2.5 m/s was also associated with non-catheter-related venous thromboembolism (RR 1.65, CI 1.12–2.45). Thirty patients (7.4%) died during the study period. Adjusting for all variables, non-catheter-related venous thromboembolism was independently correlated with death (RR 3.63, CI 1.66–7.92). CONCLUSION Venous thromboembolism is common in adults with sickle cell disease. Sickle variant genotypes and tricuspid regurgitant jet velocity ≥ 2.5m/s are associated with non-catheter-related venous thromboembolism. In addition, non-catheter-related venous thromboembolism appears to be an independent risk factor for death in our cohort. These results suggest that disease-specific prophylaxis and treatment strategies for venous thromboembolism should be investigated in sickle cell disease patients. PMID:23582935

Sickle Cell Disease (For Teens)

MedlinePlus

... help relieve the pain of sickle cell crises. Penicillin or other antibiotics can help prevent infections, though doctors usually stop giving penicillin to kids who have sickle cell disease after ...

Sickle Cell Disease and Your Baby

MedlinePlus

... of SCD are: Sickle cell anemia (also called hemoglobin SS). Hemoglobin is the part of red blood cells that ... one sickle cell gene change from each parent. Hemoglobin SC. This condition is caused when a baby ...

Juvenile fibromyalgia in an adolescent patient with sickle cell disease presenting with chronic pain.

PubMed

Ramprakash, Stalin; Fishman, Daniel

2015-10-01

Juvenile fibromyalgia in children with sickle cell disease has not been reported in the literature. We report an adolescent patient with sickle cell whose pain symptoms progressed from having recurrent acute sickle cell pain crisis episodes to a chronic pain syndrome over several years. He was eventually diagnosed with juvenile fibromyalgia based on the clinical history and myofascial tender points and his pain symptoms responded better to multidisciplinary strategies for chronic fibromyalgia pain. Chronic pain in sickle cell disease is an area of poor research, and in addition there is inconsistency in the definition of chronic pain in sickle cell disease. Central sensitisation to pain is shown to occur after recurrent painful stimuli in a genetically vulnerable individual. In a chronic pain condition such as fibromyalgia central sensitisation is thought to play a key role. Fibromyalgia should be considered as one of the main differential diagnosis in any sickle cell patient with chronic pain. 2015 BMJ Publishing Group Ltd.

Filterability of freshly-collected sickle erythrocytes under venous oxygen pressure without exposure to air.

PubMed

Shah, Siddharth; Acholonu, Rhonda Graves; Ohene-Frempong, Kwaku; Asakura, Toshio

2015-12-01

We previously found that blood samples collected from steady-state patients with sickle cell disease (SCD) without exposure to air contain a new type of reversibly sickled cells (RSCs) with blunt edges at a level of as high as 78%. Since partial oxygenation of once-deoxygenated sickled cells with pointy edges to near venous oxygen pressure generates similar sickled cells with blunt edges in vitro, we named them as partially oxygenated sickled cells (POSCs). On the other hand, partial deoxygenation of once-oxygenated SS cells to venous oxygen pressure generates partially deoxygenated sickled cells (PDSCs) with pointy edges. In this study, we obtained blood samples from 6 steady-state patients with SCD under venous oxygen pressure without exposure to air, subjected them to various oxygenation/deoxygenation/reoxygenation cycles, and studied their filterability through a membrane filter with pore diameter of 3μm, the theoretical minimum diameter of a capillary. Our results indicated that discocytes, POSCs with blunt edges, and irreversibly sickled cells could deform and pass through the filter, while PDSCs with pointy edges were rigid and could not. The filterability of SS cells seems to be related to the length and amount of deoxy-hemoglobin S fibers in the cells. Copyright © 2015. Published by Elsevier Inc.

Sickle Cell Screening: Emphasis on Education

ERIC Educational Resources Information Center

Valente, Carmine; Frank, William

1972-01-01

This article relates the sickle cell education program, the personnel training and the screening procedures of a pilot sickle cell screening program by the Prince George's County Health Department. (JA)

Interplay between coagulation and vascular inflammation in sickle cell disease

PubMed Central

Sparkenbaugh, Erica; Pawlinski, Rafal

2013-01-01

Sickle cell disease is the most common inherited hematologic disorder that leads to the irreversible damage of multiple organs. Although sickling of red blood cells and vaso-occlusion are central to the pathophysiology of sickle cell disease the importance of hemolytic anemia and vasculopathy has been recently recognized. Hypercoagulation state is another prominent feature of sickle cell disease and is mediated by activation of both intrinsic and extrinsic coagulation pathways. Growing evidence demonstrates that coagulation may not only contribute to the thrombotic complications, but also to vascular inflammation associated with this disease. This article summarizes the role of vascular inflammation and coagulation activation, discusses potential mechanisms responsible for activation of coagulation and reviews recent data demonstrating the crosstalk between coagulation and vascular inflammation in sickle cell disease. PMID:23593937

Cardiac troponin I in sickle cell crisis.

PubMed

Aslam, Ahmad K; Rodriguez, Carlos; Aslam, Ahmed F; Vasavada, Balendu C; Khan, Ijaz A

2009-03-20

Gross and microscopic findings consistent with acute and healed myocardial injury without coronary artery disease have been described in autopsy studies of patients with sickle cell crisis. The present study was designed to determine whether serum levels of cardiac troponin I are elevated in sickle cell crisis. Cardiac troponin I levels were measured in 32 patients age>18 years with the admission diagnosis of sickle cell crisis. All patients had cardiac troponin I level drawn >24 h after the onset of symptoms. The clinical profile and electrocardiograms were analyzed. Out of 32 patients, 2 patients had serum cardiac troponin I elevated, both had presented with acute chest syndrome. Serum cardiac troponin I may be elevated during sickle cell crisis, possibly by myocardial ischemia resulting from microvascular coronary obstruction during sickle cell crisis.

Pulmonary hypertension in children with sickle cell disease.

PubMed

Zuckerman, Warren A; Rosenzweig, Erika B

2011-04-01

Pulmonary hypertension and cor pulmonale have long been known to be complications of sickle cell disease, thought mostly to affect the adult population. Recently, pediatric studies in sickle cell patients have uncovered a similar prevalence of elevated tricuspid regurgitation jet velocities, a finding consistent with increased right-sided pressures, when compared with adult counterparts. Implications on mortality to date, while significant in the adult sickle cell population, appear to be unsubstantiated in children and adolescents. We review the recent literature in an attempt to discuss the prevalence, etiology and implications of an elevated tricuspid regurgitation jet velocity in pediatric sickle cell patients. We also suggest screening, diagnostics, treatment and follow-up plans that may improve the disease burden of pulmonary hypertension in both pediatric and adult sickle cell populations.

Sickle red cell dehydration: mechanisms and interventions.

PubMed

Bookchin, Robert M; Lew, Virgilio L

2002-03-01

A critical link between the single molecular defect in sickle cell anemia and the extensive pathology of this disease is the reversible increase in red cell membrane permeability generated by hemoglobin S polymers in the deoxygenated state. This permeability, usually described as P (sickle), triggers a chain of events in which two constitutive transporters of the red cell membrane become activated-the recently cloned intermediate conductance, Ca 2+ -sensitive K channel, and the electroneutral K:Cl cotransporter-leading to sickle cell dehydration. This article reviews knowledge of the dehydration mechanism, stressing the marked heterogeneity of dehydration rates in sickle cell populations, and discusses recent contributions to understanding of the function and regulation of P (sickle), Ca 2+ -sensitive K channel, and K:Cl cotransporter, and of therapies targeted at these transporters.

Coinheritance of B-Thalassemia and Sickle Cell Anaemia in Southwestern Nigeria.

PubMed

Vincent, Osunkalu; Oluwaseyi, Bamisaye; James, Babatunde; Saidat, Lawal

2016-11-01

Genes for haemoglobin S are found in high frequencies in Nigeria. However, there is little information on beta thalassemia in sickle cell anaemia in this population. The clinical presentation of HbS- β thalassemia is enormously variable, ranging from an asymptomatic state to a severe disorder similar to homozygous sickle cell disease. Haemoglobin A 2 and HbF were determined in sickle cell anaemia patients attending LAUTECH Teaching Hospital, Osogbo, by elution after electrophoresis and alkaline denaturation methods respectively. Haematological parameters were estimated using Sysmex KX-21N and percentage target cells using Leishman's staining technique. Exactly 6% f the SCA patients were found to have elevated HbA 2 (>3.3%) and HbF (>1.3%). These patients also had normal erythrocyte indices, increased platelet count, a significantly higher HCT and an increased % target cell. These findings confirm that the frequency of beta thalassaemia in sickle cell patients in Nigeria is higher than previously thought. It is therefore important to consider the possibility of this variant in patients with sickle cell anaemia since their course may differ from that of patients with homozygous sickle cell anaemia.

CD4+ T Lymphocytes count in sickle cell anaemia patients attending a tertiary hospital.

PubMed

Ojo, Omotola Toyin; Shokunbi, Wuraola Adebola

2014-05-01

Sickle cell haemoglobin (HbS) is the commonest abnormal haemoglobin and it has a worldwide distribution. Reports have shown that patients with sickle cell anaemia (HbSS) have an increased susceptibility to infection leading to increased morbidity and mortality. Impaired leucocyte function and loss of both humoral and cell-mediated immunity are some of the mechanisms that have been reported to account for the immunocompromised state in patients with sickle cell disease. This study was carried out to determine the CD4+ T lymphocytes count in patients with sickle cell anaemia. A comparative cross-sectional study of 40 sickle cell anaemia patients in steady state (asymptomatic for at least 4 weeks) attending haematology clinic and 40 age and sex-matched healthy HbA control were recruited into the study. Both HbS patients and the controls were HIV negative. The blood samples obtained were analyzed for CD4+ T cell by Flow cytometry. The study found that there was no significant difference in the number of CD4+ T lymphocyte count between individuals with sickle cell anaemia and HbA (1016 ± 513 cells/μL vs 920 ± 364cells/μL). It is recommended that the functionality of CD4+ T lymphocyte should be considered rather than the number in further attempt to elucidate the cellular immune dysfunction in patients with sickle cell anaemia.

An Hepatic Abscess in a Patient With Sickle Cell Anemia.

PubMed

Marolf, Marissa D; Chaudhary, Manu; Kaplan, Sheldon L

2016-11-01

We present a case of hepatic abscess in a transfusion-dependent 16-year-old patient with sickle cell disease. There have been 10 such cases in sickle cell disease patients reported, with the last report published greater than a decade ago. The diagnosis of hepatic abscess merits consideration in sickle cell disease patients presenting with fever without a source and/or abdominal pain.

Sickle cell disease in Madhya Pradesh, Central India: A comparison of clinical profile of sickle cell homozygote vs. sickle-beta thalassaemia individuals.

PubMed

Yadav, Rajiv; Lazarus, Monica; Ghanghoria, Pawan; Singh, Mpss; Gupta, Rasik Behari; Kumar, Surendra; Sharma, Ravendra K; Shanmugam, Rajasubramaniam

2016-10-01

The clinical manifestation in sickle cell disease (SCD) patients varies from one individual to another due to factors like the presence of alpha-thalassaemia mutation, foetal haemoglobin, and β-globin gene haplotype. The present study enumerates the clinical profile of sickle cell anaemia patients from Central India. Seven hundred seventy-six SCD patients from Jabalpur and surrounding districts (Madhya Pradesh) in central India were registered with the sickle cell clinic of NIRTH, Jabalpur. The present study reveals recorded signs and symptoms of genetically confirmed sickle cell anaemia (404) and sickle beta thalassaemia (92) patients. Majority of the patients were from scheduled caste communities (47.9%) and Gond tribal community (13.8%). Splenomegaly was the most common clinical manifestation observed (71.4%). Overall, 63.5% patients had a history of blood transfusion. The most frequent signs and symptoms observed were Pallor, Icterus, Joint pain, Fever, and Fatigue. Majority of the patients revealed onset of disease prior to attaining the age of 3 years (sickle cell anaemia 44.3% and sickle beta thalassaemia 35.9%). Mean haemoglobin levels among SCA individuals were marginally higher than SBT patients. On the other hand, mean foetal haemoglobin levels among SBT individuals showed the reverse trend. Notably, the present study reports the first incidence of priapism recorded in Central India. The study revealed a high prevalence of SCD among scheduled caste, backward caste, and tribal communities. Dissemination of study findings, screening, pre-marriage counselling, and pre-natal diagnosis are fundamental to preventing or lowering of birth of sickle cell anaemia children in the affected populations.

Translocation Renal Cell Carcinoma t(6;11)(p21;q12) and Sickle Cell Anemia: First Report and Review of the Literature.

PubMed

Chaste, Damien; Vian, Emmanuel; Verhoest, Gregory; Blanchet, Pascal

2014-02-01

Translocation renal cell carcinoma (RCC) is a family of rare tumors recently identified in the pediatric and young adult population. We report the first case of a young woman from French West Indies with sickle cell anemia who developed a translocation RCC t(6;11)(p21;q12). Usually people with the sickle cell condition are known to develop renal medullary carcinoma (RMC). To our knowledge, this is the first case described in the literature of a translocation RCC associated with sickle cell disease. Here we discuss the relation between translocation RCC, RMC, and sickle cell disease.

Cross-stream distribution of red blood cells in sickle-cell disease

NASA Astrophysics Data System (ADS)

Zhang, Xiao; Lam, Wilbur; Graham, Michael

2017-11-01

Experiments revealed that in blood flow, red blood cells (RBCs) tend to migrate away from the vessel walls, leaving a cell-free layer near the walls, while leukocytes and platelets tend to marginate towards the vessel walls. This segregation behavior of different cellular components in blood flow can be driven by their differences in stiffness and shape. An alteration of this segregation behavior may explain endothelial dysfunction and pain crisis associated with sickle-cell disease (SCD). It is hypothesized that the sickle RBCs, which are considerably stiffer than the healthy RBCs, may marginate towards the vessel walls and exert repeated damage to the endothelial cells. Direct simulations are performed to study the flowing suspensions of deformable biconcave discoids and stiff sickles representing healthy and sickle cells, respectively. It is observed that the sickles exhibit a strong margination towards the walls. The biconcave discoids in flowing suspensions undergo a so-called tank-treading motion, while the sickles behave as rigid bodies and undergo a tumbling motion. The margination behavior and tumbling motion of the sickles may help substantiate the aforementioned hypothesis of the mechanism for the SCD complications and shed some light on the design of novel therapies.

Sickle cell disease incidence among newborns in New York State by maternal race/ethnicity and nativity.

PubMed

Wang, Ying; Kennedy, Joseph; Caggana, Michele; Zimmerman, Regina; Thomas, Sanil; Berninger, John; Harris, Katharine; Green, Nancy S; Oyeku, Suzette; Hulihan, Mary; Grant, Althea M; Grosse, Scott D

2013-03-01

Sickle cell disease is estimated to occur in 1:300-400 African-American births, with higher rates among immigrants from Africa and the Caribbean, and is less common among Hispanic births. This study determined sickle cell disease incidence among New York State newborns stratified by maternal race/ethnicity and nativity. Newborns with confirmed sickle cell disease born to New York State residents were identified by the New York State newborn screening program for the years 2000-2008 and matched to birth records to obtain birth and maternal information. Annual incidence rates were computed and bivariate analyses were conducted to examine associations with maternal race/ethnicity and nativity. From 2000 to 2008, 1,911 New York State newborns were diagnosed with sickle cell disease and matched to the birth certificate files. One in every 1,146 live births was diagnosed with sickle cell disease. Newborns of non-Hispanic black mothers accounted for 86% of sickle cell disease cases whereas newborns of Hispanic mothers accounted for 12% of cases. The estimated incidence was 1:230 live births for non-Hispanic black mothers, 1:2,320 births for Hispanic mothers, and 1:41,647 births for non-Hispanic white mothers. Newborns of foreign-born non-Hispanic black mothers had a twofold higher incidence of sickle cell disease than those born to US-born non-Hispanic black mothers (P < 0.001). This study provides the first US estimates of sickle cell disease incidence by maternal nativity. Women born outside the United States account for the majority of children with sickle cell disease born in New York State. Such findings identify at-risk populations and inform outreach activities that promote ongoing, high-quality medical management to affected children.

Mortality of New York children with sickle cell disease identified through newborn screening.

PubMed

Wang, Ying; Liu, Gang; Caggana, Michele; Kennedy, Joseph; Zimmerman, Regina; Oyeku, Suzette O; Werner, Ellen M; Grant, Althea M; Green, Nancy S; Grosse, Scott D

2015-06-01

Long-term follow-up of newborn screening for conditions such as sickle cell disease can be conducted using linkages to population-based data. We sought to estimate childhood sickle cell disease mortality and risk factors among a statewide birth cohort with sickle cell disease identified through newborn screening. Children with sickle cell disease identified by newborn screening and born to New York residents in 2000-2008 were matched to birth and death certificates. Mortality rates were calculated (using numbers of deaths and observed person-years at risk) and compared with mortality rates for all New York children by maternal race/ethnicity. Stratified analyses were conducted to examine associations between selected factors and mortality. Among 1,911 infants with sickle cell disease matched to birth certificates, 21 deaths were identified. All-cause mortality following diagnosis was 3.8 per 1,000 person-years in the first 2 years of life and 1.0 per 1,000 person-years at ages 2-9 years. The mortality rate was significantly lower among children of foreign-born mothers and was significantly higher among preterm infants with low birth weight. The mortality rates were not significantly higher for infants after 28 days with sickle cell disease than for all New York births, but they were 2.7-8.4 times higher for children 1 through 9 years old with homozygous sickle cell disease than for those of all non-Hispanic black or Hispanic children born to New York residents. Estimated mortality risk in children with homozygous sickle cell disease remains elevated even after adjustment for maternal race/ethnicity. These results provide evidence regarding the current burden of child mortality among children with sickle cell disease despite newborn screening.Genet Med 17 6, 452-459.

Acute soft head syndrome in children with sickle cell anaemia in lagos, Nigeria.

PubMed

Akodu, Samuel Olufemi; Njokanma, Olisamedua Fidelis; Diaku-Akinwumi, Ijeoma Nnenna; Ubuane, Peter Odion; Adediji, Uchechukwu Okwudili

2014-09-01

Acute soft head syndrome is rare complications seen in children with sickle cell anaemia. A case report of a child with sickle cell anaemia who developed acute soft head syndrome. A 12-year old known sickle cell anaemia patient presented with acute, rapidly progressive skull pain and swelling, manifestations indicative of the rare complication of SCD which is called acute soft head syndrome. Conservative treatment with intravenous fluids and analgesics and empirical use of broad-spectrum antibiotics resulted in recovery. Acute soft head syndrome is a rare complication in children with sickle cell anaemia probably related to skull infarction. It further draws attention to the importance of acute soft head syndrome as a differential to be considered for pains in the head and skull swellings in children with sickle cell anaemia.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heck, L.L.; Brittin, G.M.

A 19-year-old black woman with sickle cell beta degrees thalassemia had experienced more than 100 hospital admissions for sickle cell crisis and aseptic necrosis of both femoral heads. Her spleen was enlarged threefold and accumulated both radiocolloid and bone-seeking agent on two occasions, demonstrating an exception to the rule in sickle cell anemia that spleens that take up bone-seeking agents demonstrate functional asplenia. In the context of fever, left upper quadrant pain, and splenomegaly, the pattern of calcification in the patient's spleen as revealed in ultrasound and CT studies suggested possible abscess and led to unnecessary splenectomy. The nuclear medicinemore » studies did not support this diagnosis. Nuclear medicine physicians should not be misled by splenic findings of sickle cell thalassemia (and possibly of other heterozygous sickle cell disorders) that differ from those of the more familiar homozygous sickle cell anemia.« less

In-vivo neutrophil migration and nitroblue tetrazolium reduction in sickle cell disease.

PubMed

Akinyanju, O O

1985-01-01

In order to determine the contribution of neutrophil malfunction to the phenomenon of enhanced susceptibility of sickle cell disease patients to bacterial infection, the in-vivo neutrophil migration capacity in 23 sickle cell patients and in 14 normal controls; and the neutrophil reduction of nitroblue tetrazolium dye in 74 sickle cell patients and in 78 normal controls were studied. Secondarily the usefulness of the NBT test in distinguishing between osteomyelitis and uncomplicated bone pain was examined. No impairment of neutrophil migratory capacity was evident as no significant difference was observed between the mean migrated neutrophil count in the sickle cell subjects (1.99 X 10(9)/1) and that in normal controls (2.08 X 10(9)/1). The mean NBT scores were 19.9 +/- 8.9% in non-infected controls and 41.3 +/- 14.6% in infected controls (P less than 0.001). In sickle cell disease they were 23.6 +/- 6% in steady state subjects, 29.2 +/- 16.4% in sterile painful crises, 42.9 +/- 15% in non-osteomyelitic bacterial infection (P less than 0.001) and 18.9 +/- 4.2% during osteomyelitis. Thus all sickle cell subjects apart from those with osteomyelitis showed significant increases in the NBT scores during bacterial infection. The low score in sickle cell osteomyelitis is possibly associated with a relative neutrophil phagocytic defect which requires further elucidation. The NBT test was not useful in distinguishing uncomplicated painful crisis from early osteomyelitis in sickle cell disease.

Visualizing red blood cell sickling and the effects of inhibition of sphingosine kinase 1 using soft X-ray tomography

DOE PAGES

Darrow, Michele C.; Zhang, Yujin; Cinquin, Bertrand P.; ...

2016-08-09

Sickle cell disease is a destructive genetic disorder characterized by the formation of fibrils of deoxygenated hemoglobin, leading to the red blood cell (RBC) morphology changes that underlie the clinical manifestations of this disease. Here, using cryogenic soft X-ray tomography (SXT), we characterized the morphology of sickled RBCs in terms of volume and the number of protrusions per cell. We were able to identify statistically a relationship between the number of protrusions and the volume of the cell, which is known to correlate to the severity of sickling. This structural polymorphism allows for the classification of the stages of themore » sickling process. Recent studies have shown that elevated sphingosine kinase 1 (Sphk1)-mediated sphingosine 1-phosphate production contributes to sickling. Here, we further demonstrate that compound 5C, an inhibitor of Sphk1, has anti-sickling properties. Additionally, the variation in cellular morphology upon treatment suggests that this drug acts to delay the sickling process. SXT is an effective tool that can be used to identify the morphology of the sickling process and assess the effectiveness of potential therapeutics.« less

Visualizing red blood cell sickling and the effects of inhibition of sphingosine kinase 1 using soft X-ray tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darrow, Michele C.; Zhang, Yujin; Cinquin, Bertrand P.

Sickle cell disease is a destructive genetic disorder characterized by the formation of fibrils of deoxygenated hemoglobin, leading to the red blood cell (RBC) morphology changes that underlie the clinical manifestations of this disease. Here, using cryogenic soft X-ray tomography (SXT), we characterized the morphology of sickled RBCs in terms of volume and the number of protrusions per cell. We were able to identify statistically a relationship between the number of protrusions and the volume of the cell, which is known to correlate to the severity of sickling. This structural polymorphism allows for the classification of the stages of themore » sickling process. Recent studies have shown that elevated sphingosine kinase 1 (Sphk1)-mediated sphingosine 1-phosphate production contributes to sickling. Here, we further demonstrate that compound 5C, an inhibitor of Sphk1, has anti-sickling properties. Additionally, the variation in cellular morphology upon treatment suggests that this drug acts to delay the sickling process. SXT is an effective tool that can be used to identify the morphology of the sickling process and assess the effectiveness of potential therapeutics.« less

Association between Oxidative Stress, Genetic Factors, and Clinical Severity in Children with Sickle Cell Anemia.

PubMed

Renoux, Céline; Joly, Philippe; Faes, Camille; Mury, Pauline; Eglenen, Buse; Turkay, Mine; Yavas, Gokce; Yalcin, Ozlem; Bertrand, Yves; Garnier, Nathalie; Cuzzubbo, Daniela; Gauthier, Alexandra; Romana, Marc; Möckesch, Berenike; Cannas, Giovanna; Antoine-Jonville, Sophie; Pialoux, Vincent; Connes, Philippe

2018-04-01

To investigate the associations between several sickle cell disease genetic modifiers (beta-globin haplotypes, alpha-thalassemia, and glucose-6-phosphate dehydrogenase deficiency) and the level of oxidative stress and to evaluate the association between oxidative stress and the rates of vaso-occlusive events. Steady-state oxidative and nitrosative stress markers, biological variables, genetic modulators, and vaso-occlusive crisis events requiring emergency admissions were measured during a 2-year period in 62 children with sickle cell anemia (58 SS and 4 Sβ 0 ). Twelve ethnic-matched children without sickle cell anemia also participated as healthy controls (AA) for oxidative and nitrosative stress level measurement. Oxidative and nitrosative stress were greater in patients with sickle cell anemia compared with control patients, but the rate of vaso-occlusive crisis events in sickle cell anemia was not associated with the level of oxidative stress. The presence of alpha-thalassemia, but not glucose-6-phosphate dehydrogenase deficiency or beta-globin haplotype, modulated the level of oxidative stress in children with sickle cell anemia. Mild hemolysis in children with alpha-thalassemia may limit oxidative stress and could explain the protective role of alpha-thalassemia in hemolysis-related sickle cell complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Chaos in an Eulerian Based Model of Sickle Cell Blood Flow

NASA Astrophysics Data System (ADS)

Apori, Akwasi; Harris, Wesley

2001-11-01

A novel Eulerian model describing the manifestation of sickle cell blood flow in the capillaries has been formulated to study the apparently chaotic onset of sickle cell crises. This Eulerian model was based on extending previous models of sickle cell blood flow which were limited due to their Lagrangian formulation. Oxygen concentration, red blood cell velocity, cell stiffness, and plasma viscosity were modeled as system state variables. The governing equations of the system were expressed in canonical form. The non-linear coupling of velocity-viscosity and viscosity- stiffness proved to be the origin of chaos in the system. The system was solved with respect to a control parameter representing the unique rheology of the sickle cell erythrocytes. Results of chaos tests proved positive for various ranges of the control parameter. The results included con-tinuous patterns found in the Poincare section, spectral broadening of the Fourier power spectrum, and positive Lyapunov exponent values. The onset of chaos predicted by this sickle cell flow model as the control parameter was varied appeared to coincide with the change from a healthy state to a crisis state in a sickle cell patient. This finding that sickle cell crises may be caused from the well understood change of a solution from a steady state to chaotic could point to new ways in preventing and treating crises and should be validated in clinical trials.

ENERCA clinical recommendations for disease management and prevention of complications of sickle cell disease in children.

PubMed

de Montalembert, Mariane; Ferster, Alina; Colombatti, Raffaella; Rees, David C; Gulbis, Beatrice

2011-01-01

Universal neonatal screening is performed in the United States, England, the Netherlands, and several cities in Belgium, with selective screening targeted on "high-risk" population in France (globally, one quarter of all the babies born in France are screened). Newborns diagnosed with a major sickle cell syndrome (SCD) should be referred to a designated pediatric sickle cell centre, and the parents are informed that their child has SCD; this may be in the sickle cell centre by an expert physician or in the community by an experienced nurse counsellor. The pediatric sickle cell centre should organize the care of the baby.

Partial Red Blood Cell Exchange in Children and Young Patients with Sickle Cell Disease: Manual Versus Automated Procedure.

PubMed

Escobar, Carlos; Moniz, Marta; Nunes, Pedro; Abadesso, Clara; Ferreira, Teresa; Barra, António; Lichtner, Anabela; Loureiro, Helena; Dias, Alexandra; Almeida, Helena

2017-10-31

The benefits of manual versus automated red blood cell exchange have rarely been documented and studies in young sickle cell disease patients are scarce. We aim to describe and compare our experience in these two procedures. Young patients (≤ 21 years old) who underwent manual- or automated-red blood cell exchange for prevention or treatment of sickle cell disease complications were included. Clinical, technical and hematological data were prospectively recorded and analyzed. Ninety-four red blood cell exchange sessions were performed over a period of 68 months, including 57 manual and 37 automated, 63 for chronic complications prevention, 30 for acute complications and one in the pre-operative setting. Mean decrease in sickle hemoglobin levels was higher in automated-red blood cell exchange (p < 0.001) and permitted a higher sickle hemoglobin level decrease per volume removed (p < 0.001), while hemoglobin and hematocrit remained stable. Ferritin levels on chronic patients decreased 54%. Most frequent concern was catheter outflow obstruction on manual-red blood cell exchange and access alarm on automated-red blood cell exchange. No major complication or alloimunization was recorded. Automated-red blood cell exchange decreased sickle hemoglobin levels more efficiently than manual procedure in the setting of acute and chronic complications of sickle cell disease, with minor technical concerns mainly due to vascular access. The threshold of sickle hemoglobin should be individualized for clinical and hematological goals. In our cohort of young patients, the need for an acceptable venous access was a limiting factor, but iron-overload was avoided. Automated red blood cell exchange is safe and well tolerated. It permits a higher sickle hemoglobin removal efficacy, better volume status control and iron-overload avoidance.

Mental nerve anaesthesia; a complication of sickle cell crisis during childbirth.

PubMed

Stevenson, Helen; Boardman, Charlotte; Chu, Patrick; Field, Anne

2004-10-01

This report describes the case of an Afro-Caribbean lady diagnosed with sickle cell anaemia, who presented with permanent mental nerve anaesthesia as a result of a sickle cell crisis during childbirth.

Exploring parent-sibling communication in families of children with sickle cell disease.

PubMed

Graff, J Carolyn; Hankins, Jane S; Hardy, Belinda T; Hall, Heather R; Roberts, Ruth J; Neely-Barnes, Susan L

2010-01-01

Communication within families of children with sickle cell disease is important yet has not been adequately investigated. Focus group interviews were conducted with parents of children with sickle cell disease to explore parent-sibling communication about sickle cell disease. Communication was influenced by attributes and behaviors of the parent, the child with sickle cell disease, and the sibling; extended family, neighbors, friends, and church members or social networks; and available, accessible resources related to the child's health, child's school, and parent employment. Outcomes that influenced and were influenced by factors within and outside the parent-sibling dyad and nuclear family included parent satisfaction, parent roles, family intactness, and status attainment. These findings support previous research with African-American families and expand our views of the importance of educating parents, family members, and others about sickle cell disease. The findings suggest a need to explore sibling perception of this communication, parent and sibling perception of the impact of frequent hospitalizations and clinic visits on the sibling and family, and variations within families of children with sickle cell disease.

Cholecystectomy in patients with sickle cell disease: experience at a regional hospital in southeast Georgia.

PubMed Central

Rudolph, R.; Williams, J. S.

1992-01-01

The treatment of patients with sickle cell disease and cholelithiasis is controversial. This retrospective study assesses the outcome of preoperative transfusion and timely cholecystectomy in symptomatic sickle cell disease patients. Fourteen patients who had undergone cholecystectomy were determined to have sickle cell disease. The patients' mean age was 17.9 years. Eleven patients were female. Thirteen patients had complained of abdominal pain. Ultrasound confirmed the diagnosis of cholelithiasis in 12 of 13 patients tested. Hemoglobin before treatment averaged 7.7 g/dL. Transfusion or exchange transfusion was given to 12 patients, raising the average hemoglobin to 10.3 g/dL. Postoperative morbidity was 14%: one patient had a urinary tract infection and another a left-lower-lobe pneumonia. No sickle cell crises or deaths occurred. Postoperative hospital stay averaged 4.4 days. With judicious use of preoperative transfusion, early cholecystectomy for symptomatic gallstones was well tolerated by sickle cell disease patients and is advisable to avoid the morbid sequelae of acute cholecystitis and peroperative sickle cell crisis. PMID:1507260

Knowledge of and attitudes to sickle cell disease and sickle carrier screening among new graduates of Nigerian tertiary educational institutions.

PubMed

Adewuyi, J O

2000-09-01

Six hundred and ten new graduates of Nigerian tertiary institutions were studied for their knowledge of and attitude to sickle cell disorders. A questionnaire was administered to assess knowledge and attitudes. Then a two-hour educational seminar on the basic genetics, transmission, and implications for the affected individuals and their families, of sickle cell disease (SCD) and carrier states was conducted. Sickle carrier screening was undertaken by cellulose acetate haemoglobin electrophoresis. A sickle carrier frequency of 21.6% was found and the questionnaires revealed severely deficient knowledge of the transmission of SCD among the 20-32 year old graduates. After the seminar there was eagerness among the graduates to know their sickle status. It is concluded that unmarried youths in, or graduating from, higher educational institutions may be a most suitable target for information, carrier detection and genetic counselling in the prevention and control of sickle cell disorders.

Incidence and Predictors of Bacterial infection in Febrile Children with Sickle Cell Disease.

PubMed

Morrissey, Benita J; Bycroft, Thomas P; Almossawi, Ofran; Wilkey, Olufunke B; Daniels, Justin G

2015-01-01

Children with sickle cell disease are at increased risk of developing bacteremia and other serious bacterial infections. Fever is a common symptom in sickle cell disease and can also occur with sickle cell crises and viral infections. We aimed to evaluate the incidence and predictors of bacteremia and bacterial infection in children with sickle cell disease presenting with fever to a district hospital and sickle cell center in London. A retrospective analysis was performed on all attendances of children (aged under 16 years) with sickle cell disease presenting with a fever of 38.5 °C or higher over a 1-year period. Confirmed bacterial infection was defined as bacteremia, bacterial meningitis, urinary tract infection (UTI), pneumonia, osteomyelitis or other bacterial infection with positive identification of organism. Children were defined as having a suspected bacterial infection if a bacterial infection was suspected clinically, but no organism was identified. Over a 1-year period there were 88 episodes analyzed in 59 children. Bacteremia occurred in 3.4% of episodes and confirmed bacterial infection in 7.0%. Suspected bacterial infection occurred in 33.0%. One death occurred from Salmonella typhirium septicemia. C-reactive protein (CRP) level and white blood cell (WBC) count were both significantly associated with bacterial infection (p = 0.004 and 0.02, respectively.) In conclusion, bacterial infections continue to be a significant problem in children with sickle cell disease. C-reactive protein was significantly associated with bacterial infections, and could be included in clinical risk criteria for febrile children with sickle cell disease.

Non-invasive estimation of pulmonary artery pressures in patients with sickle cell anaemia in Ibadan, Nigeria: an echocardiographic study.

PubMed

Enakpene, Evbu O; Adebiyi, Adewole A; Ogah, Okechukwu S; Olaniyi, John A; Aje, Akinyemi; Adeoye, Moshood A; Falase, Ayodele O

2014-10-01

Pulmonary hypertension is emerging as one of the causes of morbidity and mortality in adults with sickle cell disease. The prevalence of pulmonary hypertension in Nigerian adults with sickle cell anaemia is unknown. We decided to estimate the pulmonary artery systolic and diastolic pressures in subjects with sickle cell anaemia seen at the University College Hospital, Ibadan, Nigeria, and to determine the frequency of pulmonary hypertension among them. Ninety patients (38 males and 52 females) with sickle cell anaemia in steady state and comparable age- and sex-matched normal controls had a clinical evaluation and echocardiographic examination. The mean age of the subjects with sickle cell anaemia was 24.0 (9.00) years while the mean age for the control group was 24.0 (7.00) years. The frequency of pulmonary hypertension as assessed by a tricuspid regurgitant jet velocity of > 2.5 m/s in this study was 12.2%. Larger left ventricular dimensions and volumes, higher stroke volume and increased left ventricular mass indexed by body surface area were found to be associated with pulmonary hypertension. A multivariate analysis of the potential predictors of pulmonary hypertension in this study showed that male sex and lower packed cell volume (PCV) were independent predictors of pulmonary hypertension in patients with sickle cell anaemia. We conclude that pulmonary artery systolic and diastolic pressures are higher in subjects with sickle cell disease than normal controls. Male sex and low PCV are independent determinants of pulmonary arterial pressure in subjects with sickle cell anaemia in Nigeria.

Update: new guidelines for the treatment of infants with sickle cell disease. Agency for Health Care Policy and Research.

PubMed

Selekman, J

1993-01-01

These clinical practice guidelines set forth a comprehensive program for identifying, diagnosing, and treating newborns and infants with sickle cell disease and recommend education and counseling strategies for their parents. Sickle cell disease comprises a group of genetic disorders characterized by the production of hemoglobin S, anemia, and acute and chronic tissue damage secondary to the blockage of blood flow by abnormally shaped red cells. Sickle cell anemia is the most common form of the disease, and it affects approximately 1 in 375 African-American infants. Although in the United States sickle cell disease is most commonly found in persons of African ancestry, it also affects other populations. The panel recommends screening of all newborns for sickle cell disease, since targeting specific groups will miss some infected infants. Samples of dried blood on filter paper or liquid blood samples should be used for hemoglobinopathy screening. Hemoglobin electrophoresis, isoelectric focusing, and high performance liquid chromatography are acceptable, reliable, and accurate testing methods. Infants identified on initial screening must be retested to establish a definitive diagnosis. Affected infants must be given twice-daily oral penicillin beginning at 2 months of age to reduce pneumococcal, conjugated Haemophilus influenzae, and hepatitis B vaccines. Infants with sickle cell disease require the same well-child care as infants without the disease. Education and nondirective genetic counseling should be offered to all parents of infants with sickle cell disease. The guidelines stress the need for a comprehensive and fully integrated approach to reduce morbidity and mortality from sickle cell disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Phytomedicines and Nutraceuticals: Alternative Therapeutics for Sickle Cell Anemia

PubMed Central

Imaga, Ngozi Awa

2013-01-01

Sickle cell anemia is a genetically inherited disease in which the “SS” individual possesses an abnormal beta globin gene. A single base substitution in the gene encoding the human β-globin subunit results in replacement of β6 glutamic acid by valine, leading to the devastating clinical manifestations of sickle cell disease. This substitution causes drastic reduction in the solubility of sickle cell hemoglobin (HbS) when deoxygenated. Under these conditions, the HbS molecules polymerize to form long crystalline intracellular mass of fibers which are responsible for the deformation of the biconcave disc shaped erythrocyte into a sickle shape. First-line clinical management of sickle cell anemia include, use of hydroxyurea, folic acid, amino acids supplementation, penicillinprophylaxis, and antimalarial prophylaxis to manage the condition and blood transfusions to stabilize the patient's hemoglobin level. These are quite expensive and have attendant risk factors. However, a bright ray of hope involving research into antisickling properties of medicinal plants has been rewarding. This alternative therapy using phytomedicines has proven to not only reduce crisis but also reverse sickling (in vitro). The immense benefits of phytomedicines and nutraceuticals used in the management of sickle cell anemia are discussed in this paper. PMID:23476125

Sickle cell crisis associated with hemophagocytic lymphohistiocytosis.

PubMed

Kio, Ebenezer; Onitilo, Adedayo; Lazarchick, John; Hanna, Maged; Brunson, Chris; Chaudhary, Uzair

2004-11-01

Sickle-beta(+) (beta(+)) thalassemia is a double heterozygous genetic disorder characterized by both a qualitative and quantitative abnormality. We present a case of an African American male who was first diagnosed with sickle cell disease (SCD) at the age 23 years when he presented with generalized bone pain, fever, and hepatosplenomegaly. Laboratory findings included thrombocytopenia, microcytic anemia, and markedly elevated ferritin. He was subsequently diagnosed with a sickle-beta thalassemia hemoglobinopathy. Findings in the bone marrow aspirate and biopsy were consistent with hemophagocytic lymphohistiocytosis (HLH). HLH resolved with the resolution of sickle cell bone pain crisis without use of immunosuppressive therapy. To the best of our knowledge this is the first documented case of HLH associated with sickle cell bone pain crisis.

Measuring sickle cell morphology in flow using spectrally encoded flow cytometry (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kviatkovsky, Inna; Zeidan, Adel; Yeheskely-Hayon, Daniella; Dann, Eldad J.; Yelin, Dvir

2017-02-01

During a sickle cell crisis in sickle cell anemia patients, deoxygenated red blood cells may change their mechanical properties and block small blood vessels, causing pain, local tissue damage and even organ failure. Measuring these cellular structural and morphological changes is important for understanding the factors contributing to vessel blockage and developing an effective treatment. In this work, we use spectrally encoded flow cytometry for confocal, high-resolution imaging of flowing blood cells from sickle cell anemia patients. A wide variety of cell morphologies were observed by analyzing the interference patterns resulting from reflections from the front and back faces of the cells' membrane. Using numerical simulation for calculating the two-dimensional reflection pattern from the cells, we propose an analytical expression for the three-dimensional shape of a characteristic sickle cell and compare it to a previous from the literature. In vitro spectrally encoded flow cytometry offers new means for analyzing the morphology of sickle cells in stress-free environment, and could provide an effective tool for studying the unique physiological properties of these cells.

Acute pancreatitis during sickle cell vaso-occlusive painful crisis.

PubMed

Ahmed, Shahid; Siddiqui, Anita K; Siddiqui, Rina K; Kimpo, Miriam; Russo, Linda; Mattana, Joseph

2003-07-01

Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to microvascular occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease. Copyright 2003 Wiley-Liss, Inc.

The significance of gallstones in children with sickle cell anemia.

PubMed Central

Alexander-Reindorf, C.; Nwaneri, R. U.; Worrell, R. G.; Ogbonna, A.; Uzoma, C.

1990-01-01

Infection is the most common cause of high morbidity, hospitalization, and mortality in children with sickle cell anemia. In this study of pediatric sickle cell anemia patients, aged 1 to 19, we explore the hypothesis that gallstones (usually pigment stones) create a nidus of infection, predisposing the affected patients to high morbidity. Our study involved 86 children with sickle cell anemia at the Howard University Center for Sickle Cell Disease, who had been followed at the clinic for a total of 602 patient years. Review of their records revealed that patients with gallstones had a mean number of 10.24 hospitalizations and 25.35 ambulatory visits; those without gallstones had a mean number of only 4.26 hospitalizations and 13.41 ambulatory visits. In children with sickle cell anemia and gallstones, elective cholecystectomy (or, in the future, cholelithotripsy) could reduce the high morbidity caused by infection. PMID:2213913

Influence of sickle hemoglobin polymerization and membrane properties on deformability of sickle erythrocytes in the microcirculation.

PubMed Central

Dong, C; Chadwick, R S; Schechter, A N

1992-01-01

The rheological properties of normal erythrocytes appear to be largely determined by those of the red cell membrane. In sickle cell disease, the intracellular polymerization of sickle hemoglobin upon deoxygenation leads to a marked increase in intracellular viscosity and elastic stiffness as well as having indirect effects on the cell membrane. To estimate the components of abnormal cell rheology due to the polymerization process and that due to the membrane abnormalities, we have developed a simple mathematical model of whole cell deformability in narrow vessels. This model uses hydrodynamic lubrication theory to describe the pulsatile flow in the gap between a cell and the vessel wall. The interior of the cell is modeled as a Voigt viscoelastic solid with parameters for the viscous and elastic moduli, while the membrane is assigned an elastic shear modulus. In response to an oscillatory fluid shear stress, the cell--modeled as a cylinder of constant volume and surface area--undergoes a conical deformation which may be calculated. We use published values of normal and sickle cell membrane elastic modulus and of sickle hemoglobin viscous and elastic moduli as a function of oxygen saturation, to estimate normalized tip displacement, d/ho, and relative hydrodynamic resistance, Rr, as a function of polymer fraction of hemoglobin for sickle erythrocytes. These results show the transition from membrane to internal polymer dominance of deformability as oxygen saturation is lowered. More detailed experimental data, including those at other oscillatory frequencies and for cells with higher concentrations of hemoglobin S, are needed to apply fully this approach to understanding the deformability of sickle erythrocytes in the microcirculation. The model should be useful for reconciling the vast and disparate sets of data available on the abnormal properties of sickle cell hemoglobin and sickle erythrocyte membranes, the two main factors that lead to pathology in patients with this disease. PMID:1420913

Sickle cell-induced ischemic colitis.

PubMed

Stewart, Camille L; Ménard, Geraldine E

2009-07-01

Sickle cell-induced ischemic colitis is a rare yet potentially fatal complication of sickle cell anemia. Frequent pain crises with heavy analgesia may obscure and prolong this important diagnosis. Our patient was a 29-year-old female with sickle cell disease who was admitted with left lower quadrant abdominal pain. A diagnostic workup, including chemistries, complete blood count, blood cultures, chest x-ray, computerized tomography scanning, and colonoscopy, was performed to identify the etiology of her symptoms. This case highlights the importance of differentiating simple pain crisis from more serious and life-threatening ischemic bowel. A review of the literature compares this case to others reported and gives a method for diagnosing and treating this complication of sickle cell disease.

Blood mononuclear cell gene expression profiles characterize the oxidant, hemolytic, and inflammatory stress of sickle cell disease

PubMed Central

Jison, Maria L.; Munson, Peter J.; Barb, Jennifer J.; Suffredini, Anthony F.; Talwar, Shefali; Logun, Carolea; Raghavachari, Nalini; Beigel, John H.; Shelhamer, James H.; Danner, Robert L.; Gladwin, Mark T.

2016-01-01

In sickle cell disease, deoxygenation of intra-erythrocytic hemoglobin S leads to hemoglobin polymerization, erythrocyte rigidity, hemolysis, and microvascular occlusion. Ischemia-reperfusion injury, plasma hemoglobin-mediated nitric oxide consumption, and free radical generation activate systemic inflammatory responses. To characterize the role of circulating leukocytes in sickle cell pathogenesis we performed global transcriptional analysis of blood mononuclear cells from 27 patients in steady-state sickle cell disease (10 patients treated and 17 patients untreated with hydroxyurea) compared with 13 control subjects. We used gender-specific gene expression to validate human microarray experiments. Patients with sickle cell disease demonstrated differential gene expression of 112 genes involved in heme metabolism, cell-cycle regulation, antioxidant and stress responses, inflammation, and angiogenesis. Inducible heme oxygenase-1 and downstream proteins biliverdin reductase and p21, a cyclin-dependent kinase, were up-regulated, potentially contributing to phenotypic heterogeneity and absence of atherosclerosis in patients with sickle cell disease despite endothelial dysfunction and vascular inflammation. Hydroxyurea therapy did not significantly affect leukocyte gene expression, suggesting that such therapy has limited direct anti-inflammatory activity beyond leukoreduction. Global transcriptional analysis of circulating leukocytes highlights the intense oxidant and inflammatory nature of steady-state sickle cell disease and provides insight into the broad compensatory responses to vascular injury. PMID:15031206

Sickle Cell Crisis and the Acute Abdomen

PubMed Central

Nazem, Ahmad; Walker, Mark

1986-01-01

Abdominal pain is one of the most common symptoms in sickle cell crisis, and its cause remains controversial. Simple vaso-occlusive crisis may be an explanation. The abdominal pain may also reflect an acute surgical abdomen. A patient presented with sickle cell crisis and abdominal pain; he had a periappendiceal abscess at the site of an appendiceal stump five months after appendectomy. The role of sickle cell anemia in the pathogenesis of this abscess is uncertain. PMID:3531534

Cholelithiasis in a toddler with sickle cell disease.

PubMed

Schinasi, Dana Aronson; Mistry, Rakesh D; Mistry, Rakesh

2011-06-01

Cholelithiasis is rarely seen in toddlers and school-aged children, even in the setting of sickle cell anemia. In addition to more common etiologies, such as gastroenteritis, constipation, and urinary tract infection, the differential diagnoses of acute abdominal pain in young children with sickle cell disease include vaso-occlusive pain crisis and splenic sequestration. We describe a case of a toddler with sickle cell disease initially presenting with abdominal pain who was found to have symptomatic cholelithiasis.

Deficiencies in school readiness skills of children with sickle cell anemia: a preliminary report.

PubMed

Chua-Lim, C; Moore, R B; McCleary, G; Shah, A; Mankad, V N

1993-04-01

Patients with sickle cell anemia often express myriad clinical signs and symptoms that affect their life-style and academic performance. Certain psychoeducational and psychosocial factors have been shown to influence the academic achievement of older patients with sickle cell anemia. However, studies evaluating the school readiness skills of younger children have not been published. To determine whether sickle cell anemia delays preschool development in children aged 4 to 6 years, we studied 10 affected children and 10 normal subjects matched for age, sex, and race. School readiness was evaluated by the Pediatric Examination of Educational Readiness (PEER), which assess a child's performance in areas of developmental attainment such as visual input, verbal output, and short-term memory. The presence of associated movements (minor neurologic signs) and other areas of behavior such as selective attention, activity level, adaptive behavior, and processing efficiency are also observed. The children with sickle cell anemia scored significantly lower than their normal counterparts in several parameters of the PEER. The McCarthy Scales of Children's Abilities, a standardized psychometric test, showed that these children with sickle cell anemia were within the normal range of intelligence. Magnetic resonance imaging done on three children with sickle cell anemia who scored lowest on the PEER revealed no cerebrovascular infarcts. These preliminary studies demonstrate significant differences in school readiness skills between children with sickle cell anemia and normal subjects.

The super sickling haemoglobin HbS-Oman: a study of red cell sickling, K+ permeability and associations with disease severity in patients heterozygous for HbA and HbS-Oman (HbA/S-Oman genotype).

PubMed

Al Balushi, Halima W M; Wali, Yasser; Al Awadi, Maha; Al-Subhi, Taimoora; Rees, David C; Brewin, John N; Hannemann, Anke; Gibson, John S

2017-10-01

Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K + permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S-Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K + was markedly abnormal with elevated activities of P sickle , Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca 2+ entry and Mg 2+ loss via P sickle stimulating Gardos channel and KCC activities. The abnormal red cell behaviour was similar to that in the commonest genotype of SCD, HbSS, in which the level of mutated Hb is considerably higher. Although activities of all three K + transporters also correlated with the level of HbS-Oman, there was no association between transport phenotype and disease severity. The super sickling behaviour of HbS-Oman may obviate the need for solute loss and red cell dehydration to encourage Hb polymerisation, required in other SCD genotypes. Disease severity was reduced by concurrent α thalassaemia, as observed in other SCD genotypes, and represents an obvious genetic marker for prognostic tests of severity in young SCD patients of the HbA/S-Oman genotype. © 2017 John Wiley & Sons Ltd.

Hearing Loss and Auditory Function in Sickle Cell Disease

ERIC Educational Resources Information Center

Burch-Sims, G.P.; Matlock, V.R.

2005-01-01

Sickle cell disease was first reported in 1910 by J. Herrick, and since then, various associated conditions and complications have been described. Sickle cell disease is a hereditary disorder characterized by abnormality of the hemoglobin in the red blood cell. During periods of decreased oxygen tension in the red blood cell's environment, the…

The triumph of good over evil: protection by the sickle gene against malaria.

PubMed

Bunn, H Franklin

2013-01-03

The mechanisms underlying Plasmodium falciparum resistance in persons with sickle trait have been under active investigation for more than a half century. This Perspective reviews progress in solving this challenging problem, including recent studies that have exploited the genomics and proteomics of the parasite. The formation of Hb S polymer in the parasitized AS RBC leads to impaired parasite growth and development along with enhanced clearance from the circulation and reduced deposition in deep postcapillary vascular beds. Enhanced generation of reactive oxygen species in sickled AS RBCs is a pathogenetic feature shared by parasitized thalassemic and G6PD-deficient RBCs, triggering abnormal topology of the RBC plasma membrane with decreased and disordered display of PfEMP-1, a P falciparum adhesion protein critical for endothelial adherence. A mouse model of Hb S confers host tolerance to P berghei, through inhibition of pathogenic CD8(+) T cells and induction of heme oxygenase-1. An additional and apparently independent mode of protection is provided by the selective expression in AS RBCs of 2 species of microRNA that integrate into P falciparum mRNAs and inhibit translation and parasite growth.

Blood and Diversity

MedlinePlus

... blood. About Sickle Cell Disease Sickle cell disease is a common, inherited red blood disorder. Throughout their lives, sickle cell disease patients ... more time, consider a Power Red donation . Power Red is similar to a whole blood donation, except a special machine is used to ...

Anisotropic light scattering of individual sickle red blood cells.

PubMed

Kim, Youngchan; Higgins, John M; Dasari, Ramachandra R; Suresh, Subra; Park, YongKeun

2012-04-01

We present the anisotropic light scattering of individual red blood cells (RBCs) from a patient with sickle cell disease (SCD). To measure light scattering spectra along two independent axes of elongated-shaped sickle RBCs with arbitrary orientation, we introduce the anisotropic Fourier transform light scattering (aFTLS) technique and measured both the static and dynamic anisotropic light scattering. We observed strong anisotropy in light scattering patterns of elongated-shaped sickle RBCs along its major axes using static aFTLS. Dynamic aFTLS analysis reveals the significantly altered biophysical properties in individual sickle RBCs. These results provide evidence that effective viscosity and elasticity of sickle RBCs are significantly different from those of the healthy RBCs.

Electocardiographic findings in adult Nigerians with sickle cell anaemia.

PubMed

Oguanobi, N I; Onwubere, B J C; Ike, S O; Anisiuba, B C; Ejim, E C; Ibegbulam, O G

2010-09-01

Cardiovascular system abnormalities are common causes of morbidity and mortality in sickle cell anaemia. The study aims at determining the pattern of electrocardiographic changes in adult Nigerian sickle cell anaemia patients. A descriptive cross sectional study was done on sixty sickle cell anaemia patients seen at the adult sickle cell clinic of University of Nigeria Teaching Hospital (UNTH) Enugu, and sixty age and sex matched normal controls. All the subjects had clinical evaluation as well as electrocardiographic examination. The mean heart rate, P-wave duration, P-wave dispersion, PR interval, QRS duration, QRS dispersion, QTc interval and QTc dispersion were significantly higher in the patients than in the control group. Electrocardiographic abnormalities identified by this study were: left ventricular hypertrophy (75%; 1.7%), left atrial enlargement (40%; 0%), biventricular hypertrophy (11%; 0), ST-segment elevation (10%; 0%) and increased P-wave and QTc dispersions. ST segment elevation was found more in patients with moderate and severe anaemia (P= 0.02, Spearman correlation r= 0.342; P= 0.007), Sickle cell anaemia is associated with significant electrocardiographic abnormalities. Further prospective studies are recommended to evaluate the prognostic significance of the electrocardiographic intervals dispersion on the long term disease outcome in sickle cell anaemia.

Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease

PubMed Central

Pushkaran, Suvarnamala; Konstantinidis, Diamantis G.; Koochaki, Sebastian; Malik, Punam; Mohandas, Narla; Zheng, Yi; Joiner, Clinton H.; Kalfa, Theodosia A.

2013-01-01

Chronic inflammation has emerged as an important pathogenic mechanism in sickle cell disease (SCD). One component of this inflammatory response is oxidant stress mediated by reactive oxygen species (ROS) generated by leukocytes, endothelial cells, plasma enzymes, and sickle red blood cells (RBC). Sickle RBC ROS generation has been attributed to sickle hemoglobin auto-oxidation and Fenton chemistry reactions catalyzed by denatured heme moieties bound to the RBC membrane. In this study, we demonstrate that a significant part of ROS production in sickle cells is mediated enzymatically by NADPH oxidase, which is regulated by protein kinase C, Rac GTPase, and intracellular Ca2+ signaling within the sickle RBC. Moreover, plasma from patients with SCD and isolated cytokines, such as transforming growth factor β1 and endothelin-1, enhance RBC NADPH oxidase activity and increase ROS generation. ROS-mediated damage to RBC membrane components is known to contribute to erythrocyte rigidity and fragility in SCD. Erythrocyte ROS generation, hemolysis, vaso-occlusion, and the inflammatory response to tissue damage may therefore act in a positive-feedback loop to drive the pathophysiology of sickle cell disease. These findings suggest a novel pathogenic mechanism in SCD and may offer new therapeutic targets to counteract inflammation and RBC rigidity and fragility in SCD. PMID:23349388

Hyperfibrinogenaemia and hyperviscosity in sickle-cell crisis.

PubMed Central

Richardson, S G; Breeze, G R; Stuart, J

1976-01-01

Plasma fibrinogen concentration and whole-blood viscosity, the latter measured at two shear rates (23 and 230 sec-1), were estimated during eight episodes of sickle-cell crisis and compared with values in 26 sickle-cell anaemia patients who were not in crisis. Painful crisis was associated with a significant increase in both plasma fibrinogen and whole-blood viscosity. Increased fibrinogen-erythrocyte interaction in vivo may be a significant contributory factor to raising blood viscosity and precipitating vaso-occlusive crisis in sickle-cell disease. PMID:977763

Neutrophil chemotaxis in sickle cell anaemia, sickle cell beta zero thalassaemia, and after splenectomy.

PubMed Central

Donadi, E A; Falcão, R P

1987-01-01

Neutrophil chemotaxis was evaluated in 28 patients with sickle cell anaemia, 10 patient with sickle cell beta zero thalassaemia, 25 patients who had undergone splenectomy, and 38 controls. The mean distance migrated by patients' neutrophils was not significantly different from that of neutrophils from controls. Although several immunological variables have been reported to be changed after loss of splenic function, we were unable to show a defect in neutrophil chemotaxis that could account for the increased susceptibility to infection. PMID:3611395

A case of recurrent psychosis during sickle cell disease crisis treated successfully with ziprasidone.

PubMed

Spiegel, David R; Messerschmidt, Cory; Morewitz, Jerry; Akintola, Morakinyo

2013-01-01

We present and follow a series of three consecutive hospitalizations of a 36-year-old, African-American male with sickle cell anemia disease who presented with sickle cell crises and a new onset psychotic episode. After multiple hospitalizations for prior episodes of sickle cell crisis-induced pain, treated with rehydration, blood transfusions, and opiate medication, this hospitalization was the first time he developed psychosis. As such, we discuss the differential diagnosis of the latter, and effective adjunctive treatment with ziprasidone.

Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea

PubMed Central

Lopes, Flavia C. M.; Traina, Fabiola; Almeida, Camila B.; Leonardo, Flavia C.; Franco-Penteado, Carla F.; Garrido, Vanessa T.; Colella, Marina P.; Soares, Raquel; Olalla-Saad, Sara T.; Costa, Fernando F.; Conran, Nicola

2015-01-01

As hypoxia-induced inflammatory angiogenesis may contribute to the manifestations of sickle cell disease, we compared the angiogenic molecular profiles of plasma from sickle cell disease individuals and correlated these with in vitro endothelial cell-mediated angiogenesis-stimulating activity and in vivo neovascularization. Bioplex demonstrated that plasma from patients with steady-state sickle cell anemia contained elevated concentrations of pro-angiogenic factors (angiopoietin-1, basic fibroblast growth factor, vascular endothelial growth factor, vascular endothelial growth factor-D and placental growth factor) and displayed potent pro-angiogenic activity, significantly increasing endothelial cell proliferation, migration and capillary-like structure formation. In vivo neovascularization of Matrigel plugs was significantly greater in sickle cell disease mice than in non-sickle cell disease mice, consistent with an up-regulation of angiogenesis in the disease. In plasma from patients with hemoglobin SC disease without proliferative retinopathy, anti-angiogenic endostatin and thrombospondin-2 were significantly elevated. In contrast, plasma from hemoglobin SC individuals with proliferative retinopathy had a pro-angiogenic profile and more significant effects on endothelial cell proliferation and capillary formation than plasma from patients without retinopathy. Hydroxyurea therapy was associated with significant reductions in plasma angiogenic factors and inhibition of endothelial cell-mediated angiogenic mechanisms and neovascularization. Thus, individuals with sickle cell anemia or hemoglobin SC disease with retinopathy present a highly angiogenic circulating milieu, capable of stimulating key endothelial cell-mediated angiogenic mechanisms. Combination anti-angiogenic therapy to prevent the progression of unregulated neovascularization and associated manifestations in sickle cell disease, such as pulmonary hypertension, may be indicated; furthermore, the benefits and drawbacks of the potent anti-angiogenic effects of hydroxyurea should be clarified. PMID:25769545

ARQ 092, an orally-available, selective AKT inhibitor, attenuates neutrophil-platelet interactions in sickle cell disease

PubMed Central

Kim, Kyungho; Li, Jing; Barazia, Andrew; Tseng, Alan; Youn, Seock-Won; Abbadessa, Giovanni; Yu, Yi; Schwartz, Brian; Andrews, Robert K.; Gordeuk, Victor R.; Cho, Jaehyung

2017-01-01

Previous studies identified the Ser/Thr protein kinase, AKT, as a therapeutic target in thrombo-inflammatory diseases. Here we report that specific inhibition of AKT with ARQ 092, an orally-available AKT inhibitor currently in phase Ib clinical trials as an anti-cancer drug, attenuates the adhesive function of neutrophils and platelets from sickle cell disease patients in vitro and cell-cell interactions in a mouse model of sickle cell disease. Studies using neutrophils and platelets isolated from sickle cell disease patients revealed that treatment with 50–500 nM ARQ 092 significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets. Treatment of isolated platelets and neutrophils with ARQ 092 inhibited heterotypic cell-cell aggregation under shear conditions. Intravital microscopic studies demonstrated that short-term oral administration of ARQ 092 or hydroxyurea, a major therapy for sickle cell disease, diminishes heterotypic cell-cell interactions in venules of sickle cell disease mice challenged with tumor necrosis factor-α. Co-administration of hydroxyurea and ARQ 092 further reduced the adhesive function of neutrophils in venules and neutrophil transmigration into alveoli, inhibited expression of E-selectin and intercellular adhesion molecule-1 in cremaster vessels, and improved survival in these mice. Ex vivo studies in sickle cell disease mice suggested that co-administration of hydroxyurea and ARQ 092 efficiently blocks neutrophil and platelet activation and that the beneficial effect of hydroxyurea results from nitric oxide production. Our results provide important evidence that ARQ 092 could be a novel drug for the prevention and treatment of acute vaso-occlusive complications in patients with sickle cell disease. PMID:27758820

Systematic review of interventional sickle cell trials registered in ClinicalTrials.gov.

PubMed

Lebensburger, Jeffrey D; Hilliard, Lee M; Pair, Lauren E; Oster, Robert; Howard, Thomas H; Cutter, Gary R

2015-12-01

The registry ClinicalTrials.gov was created to provide investigators and patients an accessible database of relevant clinical trials. To understand the state of sickle cell disease clinical trials, a comprehensive review of all 174 "closed," "interventional" sickle cell trials registered at ClinicalTrials.gov was completed in January 2015. The majority of registered sickle cell disease clinical trials listed an academic center as the primary sponsor and were an early phase trial. The primary outcome for sickle cell disease trials focused on pain (23%), bone marrow transplant (BMT) (13%), hydroxyurea (8%), iron overload (8%), and pulmonary hypertension (8%). A total of 52 trials were listed as terminated or withdrawn, including 25 (14% of all trials) terminated for failure to enroll participants. At the time of this review, only 19 trials uploaded results and 29 trials uploaded a manuscript in the ClinicalTrials.gov database. A systematic review of pubmed.gov revealed that only 35% of sickle cell studies completed prior to 2014 resulted in an identified manuscript. In comparison, of 80 thalassemia trials registered in ClinicalTrials.gov, four acknowledged failure to enroll participants as a reason for trial termination or withdrawal, and 48 trials (60%) completed prior to 2014 resulted in a currently identified manuscript. ClinicalTrials.gov can be an important database for investigators and patients with sickle cell disease to understand the current available research trials. To enhance the validity of the website, investigators must update their trial results and upload trial manuscripts into the database. This study, for the first time, quantifies outcomes of sickle cell disease trials and provides support to the belief that barriers exist to successful completion, publication, and dissemination of sickle cell trial results. © The Author(s) 2015.

Myonecrosis in Sickle Cell Anemia: Case Study

PubMed Central

Turaga, Lalita Prabha; Boddu, Prajwal; Kipferl, Steve; Basu, Anupam; Yorath, Martin

2017-01-01

Patient: Male, 27 Final Diagnosis: Myonecrosis of sickle cell anaemia Symptoms: Pain • redness to feet • swelling foot Medication: — Clinical Procedure: MRI Specialty: Podiatry Objective: Rare disease Background: Myonecrosis is one of the more poorly studied, painful manifestations of sickle cell crisis. Medical literature is sparse detailing the manifestations and management of such symptoms. In myonecrosis, red cells containing sickle hemoglobin become rigid, resulting in reduced blood flow and myonecrosis. Case Report: We present a case study of a patient in sickle cell crisis with an episode of acute pain and swelling to the intrinsic muscles of the foot as a prominent feature of the crises. Although muscle biopsy is considered the gold standard for the diagnosis of myositis or myonecrosis, a low intensity signal on T1 and high intensity signal on T2 at the affected muscle belly can be as conclusive as imaging studies. In an actively sickling patient any invasive intervention should be avoided as it can result in ischemic necrosis of the tissues, due to interruption of capillary flow in end-arteries. Conclusions: Early recognition is critical in sickle cell disease management, allowing for prompt and aggressive fluid resuscitation which remains a cornerstone in the management of most sickle cell vaso-occlusive crises. In this instance, off loading the extremity and early fluid resuscitation resolved the pain and swelling and prevented myonecrosis. PMID:28133359

Fanconi's Anemia Effect or Sickle Cell Anemia Effect: That is the Question.

PubMed

Unal, Sule; Chui, David H K; Gumruk, Fatma

2015-01-01

A 16-year-old boy who was diagnosed to have sickle cell anemia was referred to our center. The parental consanguinity, growth retardation and dysmorphic features prompted a search for possible Fanconi's Anemia (FA). The diepoxybutane (DEB) test was positive, confirming FA. The interaction of both diseases might account for his relatively mild phenotype in terms of both sickle cell anemia (or Hb S, HBB: c.20A > T) and FA. The high Hb F level that might be related to concomitant FA, may have caused a milder phenotype of sickle cell anemia, whereas nitric oxide (NO) depletion as a consequence of sickle cell anemia, may have caused a delay in the bone marrow failure of FA.

Reproductive endocrine issues in men with sickle cell anemia.

PubMed

Huang, A W; Muneyyirci-Delale, O

2017-07-01

In patients with sickle cell anemia, the sickling of red blood cells is known to cause end-organ damage by infarction. In some men who are affected by sickle cell anemia, the obstruction of venous outflow of the penis causes priapism, which could lead to erectile dysfunction. There is also evidence that the disease is linked to other reproductive issues in men-specifically delayed puberty, low testosterone, and sperm abnormalities-although the causes of these problems are less clear. Treatment of sickle cell anemia can have effects on the reproductive system as well. This review summarizes the findings from various publications pertaining to reproductive endocrinology, along with their conclusions and discrepancies. © 2017 American Society of Andrology and European Academy of Andrology.

A successful education program for parents of infants with newly diagnosed sickle cell disease.

PubMed

Day, S; Brunson, G; Wang, W

1992-02-01

The most dramatic recent advance in the care of young children with sickle cell disease was the demonstration by a cooperative study that the use of oral penicillin prophylaxis is highly effective in decreasing the risk of pneumococcal sepsis. Subsequently, the need for more comprehensive education of the parents of these children to ensure compliance with penicillin administration has become apparent. Over the past 4 years, the Mid-South Sickle Cell Disease Program has used a seven-phase educational process for the parents of more than 200 infants with newly diagnosed sickle cell disease. This has resulted in excellent compliance and a marked decrease in the incidence of pneumococcal sepsis among sickle cell patients at our center.

Alternative Etiologies for Stroke In Sickle Cell Anemia

PubMed Central

Dowling, Michael Morgan; Quinn, Charles T.; Rogers, Zora R.; Journeycake, Janna M.

2009-01-01

Stroke is common in children with sickle cell anemia but is rarely attributed to the traditional causes of stroke identified in other children. We report an 11 year-old girl with sickle cell anemia who presented with severe headache and was found to have recurrent bilateral multifocal strokes in a cardioembolic pattern. Evaluation revealed the presence of a patent foramen ovale, antiphospholipid antibodies, and elevations in factor VIII and lipoprotein a. Sickle cell anemia is itself a hypercoaguable state with potential for increased right heart pressures, both of which predispose to paradoxical embolization via right-to-left intracardiac shunting of emboli causing stroke. This case suggests that the more traditional etiologies for pediatric stroke may also cause stroke in children with sickle cell anemia. PMID:19589461

Pitfalls in the biological diagnosis of common hemoglobin disorders.

PubMed

Wajcman, Henri; Moradkhani, Kamran

2015-01-01

In West-European countries, hemoglobin disorders are no more rare diseases. Programs for diagnosis of heterozygous carriers have been established to prevent cases with major sickle cell disease or thalassemias. These studies have been done essentially by high performance liquid chromatography on cation-exchange columns and electrophoresis (mostly capillary electrophoresis). They have been done through systematic population studies or premarital diagnosis. We describe in this work the frequent or rare pitfalls encountered, which led to false negative or positive diagnosis both in the field of sickle cell disease and thalassemias. In the absence of a well identified hemoglobin disorder in the proband's family, it is a rule that the use of a single test is insufficient to identify formally HbS. The presence of HbS could also be masked by another hemoglobin abnormality. The sole measurement of HbA2 level is insufficient to characterize a thalassemic trait: this level needs always to be interpreted considering RBC parameters and iron metabolic status. In difficult cases, the definitive answer may require a family study and/or a molecular genetic characterization.

38 CFR 1.464 - Minor patients.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Or Alcohol Abuse, Infection with the Human Immunodeficiency Virus (hiv), Or Sickle Cell Anemia § 1... alcohol abuse, infection with the HIV, or sickle cell anemia, any written consent for disclosure... for drug abuse, alcoholism or alcohol abuse, infection with the HIV, or sickle cell anemia, any...

38 CFR 1.464 - Minor patients.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Or Alcohol Abuse, Infection with the Human Immunodeficiency Virus (hiv), Or Sickle Cell Anemia § 1... alcohol abuse, infection with the HIV, or sickle cell anemia, any written consent for disclosure... for drug abuse, alcoholism or alcohol abuse, infection with the HIV, or sickle cell anemia, any...

38 CFR 1.464 - Minor patients.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Or Alcohol Abuse, Infection with the Human Immunodeficiency Virus (hiv), Or Sickle Cell Anemia § 1... alcohol abuse, infection with the HIV, or sickle cell anemia, any written consent for disclosure... for drug abuse, alcoholism or alcohol abuse, infection with the HIV, or sickle cell anemia, any...

38 CFR 1.464 - Minor patients.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Or Alcohol Abuse, Infection with the Human Immunodeficiency Virus (hiv), Or Sickle Cell Anemia § 1... alcohol abuse, infection with the HIV, or sickle cell anemia, any written consent for disclosure... for drug abuse, alcoholism or alcohol abuse, infection with the HIV, or sickle cell anemia, any...

38 CFR 1.464 - Minor patients.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Or Alcohol Abuse, Infection with the Human Immunodeficiency Virus (hiv), Or Sickle Cell Anemia § 1... alcohol abuse, infection with the HIV, or sickle cell anemia, any written consent for disclosure... for drug abuse, alcoholism or alcohol abuse, infection with the HIV, or sickle cell anemia, any...

Y-chromosome R-M343 African Lineages and Sickle Cell Disease reveal structured assimilation in Lebanon

PubMed Central

Haber, Marc; Platt, Daniel E; Khoury, Simon; Badro, Danielle A; Abboud, Miguel; Smith, Chris Tyler; Zalloua, Pierre A

2012-01-01

We have sought to identify signals of assimilation of African male lines in Lebanon by exploring the association of sickle cell disease in Lebanon with Y-chromosome haplogroups that are informative of the disease origin and its exclusivity to the Muslim community. A total of 732 samples were analyzed including 33 sickle cell disease patients from Lebanon genotyped for 28 binary markers and 19 short tandem repeats on the non-recombinant segment of the Y chromosome. Genetic organization was identified using populations known to have influenced the genetic structure of the Lebanese population, in addition to African populations with high incidence of sickle cell disease. Y-chromosome haplogroup R-M343 sub-lineages distinguish between sub-Saharan African and Lebanese Y chromosomes. We detected a limited penetration of sickle cell disease into Lebanese R-M343 carriers, restricted to Lebanese Muslims. We suggest that this penetration brought the sickle cell gene along with the African R-M343, probably with the Saharan caravan slave trade. PMID:20981037

Cerebrovascular accidents in sickle cell disease. Risk factors and blood transfusion influence. French Study Group on Sickle Cell Disease.

PubMed

de Montalembert, M; Beauvais, P; Bachir, D; Galacteros, F; Girot, R

1993-03-01

This study presents a series of 34 sickle cell patients with one or more cerebrovascular accidents (CVA). Risk factors were studied in a subgroup of 19 patients whose clinical and biological characteristics were compared to those of a group of 444 sickle cell patients without CVA. The only risk factor discovered was a past history of purulent meningitis, which was significantly more frequent in sickle cell patients than in those without CVA (P < 0.0001). No biological or radiological factor affecting the risk of recurrence was found. The risk of recurrence, neurological defects or death after subsequent CVA justify long-term transfusion treatment in patients presenting with a second CVA. However our study shows that 10 patients who were not transfused after their first CVA had no recurrences, (median follow up = 7.9 years; 2-18 years), providing a basis for discussion on the indications of long-term transfusion therapy for sickle cell patients presenting with their first CVA.

EXPLORING PARENT-SIBLING COMMUNICATION IN FAMILIES OF CHILDREN WITH SICKLE CELL DISEASE

PubMed Central

Graff, J. Carolyn; Hankins, Jane S.; Hardy, Belinda T.; Hall, Heather R.; Roberts, Ruth J.; Neely-Barnes, Susan L.

2011-01-01

Focus group interviews were conducted with parents of children with sickle cell disease to explore parent-sibling communication about sickle cell disease. Communication was influenced by attributes and behaviors of the parent, the child with sickle cell disease, and the sibling; extended family, neighbors, friends, and church members or social networks; and available, accessible resources related to the child’s health, child’s school, and parent employment. Outcomes that influenced and were influenced by factors within and outside the parent-sibling dyad and nuclear family included parent satisfaction, parent roles, family intactness, and status attainment. These findings support previous research with African American families and expand our views of the importance of educating parents, family members, and others about sickle cell disease. The findings suggest a need to explore sibling perception of this communication, parent and sibling perception of the impact of frequent hospitalizations and clinic visits on the sibling and family, and variations within families of children with sickle cell disease. PMID:20384476

Dietary ω-3 fatty acids protect against vasculopathy in a transgenic mouse model of sickle cell disease.

PubMed

Kalish, Brian T; Matte, Alessandro; Andolfo, Immacolata; Iolascon, Achille; Weinberg, Olga; Ghigo, Alessandra; Cimino, James; Siciliano, Angela; Hirsch, Emilio; Federti, Enrica; Puder, Mark; Brugnara, Carlo; De Franceschi, Lucia

2015-07-01

The anemia of sickle cell disease is associated with a severe inflammatory vasculopathy and endothelial dysfunction, which leads to painful and life-threatening clinical complications. Growing evidence supports the anti-inflammatory properties of ω-3 fatty acids in clinical models of endothelial dysfunction. Promising but limited studies show potential therapeutic effects of ω-3 fatty acid supplementation in sickle cell disease. Here, we treated humanized healthy and sickle cell mice for 6 weeks with ω-3 fatty acid diet (fish-oil diet). We found that a ω-3 fatty acid diet: (i) normalizes red cell membrane ω-6/ω-3 ratio; (ii) reduces neutrophil count; (iii) decreases endothelial activation by targeting endothelin-1 and (iv) improves left ventricular outflow tract dimensions. In a hypoxia-reoxygenation model of acute vaso-occlusive crisis, a ω-3 fatty acid diet reduced systemic and local inflammation and protected against sickle cell-related end-organ injury. Using isolated aortas from sickle cell mice exposed to hypoxia-reoxygenation, we demonstrated a direct impact of a ω-3 fatty acid diet on vascular activation, inflammation, and anti-oxidant systems. Our data provide the rationale for ω-3 dietary supplementation as a therapeutic intervention to reduce vascular dysfunction in sickle cell disease. Copyright© Ferrata Storti Foundation.

The management of painful crisis in sickle cell disease.

PubMed

Wright, Josh; Ahmedzai, Sam H

2010-06-01

Until recently management of sickle pain was the province of haematologists. However, a recent National Confidential Enquiry into Patient Outcome and Death report highlighted problems with the management of pain and opioid analgesia in this group and suggested a multiagency approach similar to that used in palliative care. Pain is the most frequent complication of this haemoglobin disorder. Sickle cell disease is very variable with many patients leading full lives with long periods with little or no pain. At the other end of the spectrum there are those who exist in a sea of pain. The mechanisms of sickle pain are poorly understood and evidence for the best treatment modalities sparse. Historically there has been a dearth of clinical trials in sickle cell; however, this is starting to be addressed. In this review we will give a brief overview of the disease and its pathogenesis before examining the epidemiology, management of pain in sickle cell disease. We will also review recent evidence regarding quality of life and discuss the role of opioid hyperalgesia in sickle cell disease.

Staged Single Ventricle Palliation and Homozygous Sickle Cell Disease.

PubMed

Maddali, Madan Mohan; Junghare, Minakshi Sandip; Nishant, Arora Ram; Kandachar, Pranav Subbaraya; Valliattu, Johan

2016-04-01

Hypoxemia is a well-known trigger for precipitating a sickling crisis in patients with sickle cell disease. Patients undergoing staged single ventricle palliation have hypoxemia during the initial stages of the Fontan pathway. The successful completion of staged single ventricle palliation in a child with a combination of homozygous sickle cell disease and a single ventricle physiology that tolerate prolonged hypoxemia during earlier stages of Fontan pathway is described. © 2016 Wiley Periodicals, Inc.

Numerical Simulation of Sickle Cell Blood Flow in the Microcirculation

NASA Astrophysics Data System (ADS)

Berger, Stanley A.; Carlson, Brian E.

2001-11-01

A numerical simulation of normal and sickle cell blood flow through the transverse arteriole-capillary microcirculation is carried out to model the dominant mechanisms involved in the onset of vascular stasis in sickle cell disease. The transverse arteriole-capillary network is described by Strahler's network branching method, and the oxygen and blood transport in the capillaries is modeled by a Krogh cylinder analysis utilizing Lighthill's lubrication theory, as developed by Berger and King. Poiseuille's law is used to represent blood flow in the arterioles. Applying this flow and transport model and utilizing volumetric flow continuity at each network bifurcation, a nonlinear system of equations is obtained, which is solved iteratively using a steepest descent algorithm coupled with a Newton solver. Ten different networks are generated and flow results are calculated for normal blood and sickle cell blood without and with precapillary oxygen loss. We find that total volumetric blood flow through the network is greater in the two sickle cell blood simulations than for normal blood owing to the anemia associated with sickle cell disease. The percentage of capillary blockage in the network increases dramatically with decreasing pressure drop across the network in the sickle cell cases while there is no blockage when normal blood flows through simulated networks. It is concluded that, in sickle cell disease, without any vasomotor dilation response to decreasing oxygen concentrations in the blood, capillary blockage will occur in the microvasculature even at average pressure drops across the transverse arteriole-capillary networks.

Validity of simple clinical and biological parameters as screening tool for sickle cell anemia for referral to tertiary center in highly resource constraints.

PubMed

Kadima, Bertin Tshimanga; Gini-Ehungu, Jean Lambert; Mbutiwi, Fiston Ikwa Ndol; Bahati, John Tunda; Aloni, Michel Ntetani

2017-11-01

In the Democratic Republic of Congo, the incidence of sickle cell anemia (SCA) is estimated around 40 000 neonates per year. However, it is notoriously difficult to perform conventional electrophoresis in all hospitals and laboratories, especially at peripheral levels and rural area. A panel of multiple clinical and laboratory features that would enhance sickle cell disease were assessed for the detection of the disease in highly resource-scarce settings. A prospective study was conducted in Kinshasa. Venous blood samples were drawn from each study participant in order to determine the hematologic parameters, the peripheral smears, and the hemoglobin electrophoresis. We used Cohen's κ statistic to examine the agreement of each variable and diagnosis of sickle cell disease. A total of 807 patients were screened for sickle cell disease. Among these 807 children, 36 (4.5%) were homozygous for Hb S disease. The presence of at least 8% erythroblasts (PPV: 91%, NPV: 99%, sensitivity: 83.3%, specificity: 99.6%, κ value: .86) and sickle cells (PPV:100%, NPV: 98%, sensitivity: 50%, specificity: 100%, κ value: .66) in the peripheral blood smear had an acceptable agreement for sickle cell disease. These two biological markers may guide the clinician in the decision-making to initiate the management of the children as a sickle cell patient, pending confirmation of the disease by electrophoresis techniques. © 2017 Wiley Periodicals, Inc.

Perinatal Maternal Mortality in Sickle Cell Anemia: Two Case Reports and Review of the Literature.

PubMed

Rizk, Sanaa; Pulte, Elizabeth D; Axelrod, David; Ballas, Samir K

As outcomes of patients with sickle cell anemia improve and survival into adulthood with good quality of life and expectation of long-term survival becomes more common, challenges have developed, including issues related to reproduction. Pregnancy is frequently complicated in patients with sickle cell anemia with mortality up to 4.0%. Here we report maternal perinatal mortality in two women with sickle cell anemia who died post-partum due to acute chest syndrome (ACS), caused by bone marrow fat embolism and review the literature pertinent to this subject. Patient A was a 28-year-old woman with sickle cell anemia with multiple complications. At 30 weeks' gestation she developed hemolysis associated with poor placental function necessitating delivery by C-section. The fetus was delivered successfully but she died due to multi organ failure after delivery. Autopsy showed pulmonary and amniotic fluid embolization. Patient B was a 37-year-old woman with uncomplicated sickle cell anemia who presented with pre term labor and crisis, then ACS and fetal distress. The infant was delivered successfully but the patient died after cardiovascular collapse. Autopsy results showed fat and bone marrow embolization as the cause of death. Pregnancy continues to be high risk for patients with sickle cell anemia including those with mild disease. Maternal perinatal mortality could be unpredictable due to serious complications of sickle cell disease. More studies to assess maternal perinatal mortality are needed.

Sexuality and sickle cell anemia

PubMed Central

Côbo, Viviane de Almeida; Chapadeiro, Cibele Alves; Ribeiro, João Batista; Moraes-Souza, Helio; Martins, Paulo Roberto Juliano

2013-01-01

Background Sickle cell disease, the most common hereditary blood disease in the world, is the result of an atypical hemoglobin called S (Hb S) which, when homozygous (Hb SS) is the cause of sickle cell anemia. Changes of puberty, correlated with a delayed growth spurt, begin late in both male and female sickle cell anemia individuals with repercussions on sexuality and reproduction. The objectives of this exploratory and descriptive study were to characterize the development of sexuality in adults with sickle cell anemia by investigating the patient's perception of their sex life, as well as the information they had and needed on this subject. Methods Twenty male and female sickle cell anemia patients treated at the Hemocentro Regional de Uberaba (UFTM) with ages between 19 and 47 years old were enrolled. A socioeconomic questionnaire and a semi-structured interview on sexuality, reproduction and genetic counseling were applied. Results This study shows that the sickle cell anemia patients lacked information on sexuality especially about the risks of pregnancy and the possible inheritance of the disease by their children. Moreover, the sexual life of the patients was impaired due to pain as well as discrimination and negative feelings experienced in close relationships. Conclusion The health care of sickle cell anemia patients should take into account not only the clinical aspects of the disease, but also psychosocial aspects by providing counseling on sexuality, reproduction and genetics, in order to give this population the possibility of a better quality of life. PMID:23741184

A Comprehensive Fluid Dynamic-Diffusion Model of Blood Microcirculation with Focus on Sickle Cell Disease

NASA Astrophysics Data System (ADS)

Le Floch, Francois; Harris, Wesley L.

2009-11-01

A novel methodology has been developed to address sickle cell disease, based on highly descriptive mathematical models for blood flow in the capillaries. Our investigations focus on the coupling between oxygen delivery and red blood cell dynamics, which is crucial to understanding sickle cell crises and is unique to this blood disease. The main part of our work is an extensive study of blood dynamics through simulations of red cells deforming within the capillary vessels, and relies on the use of a large mathematical system of equations describing oxygen transfer, blood plasma dynamics and red cell membrane mechanics. This model is expected to lead to the development of new research strategies for sickle cell disease. Our simulation model could be used not only to assess current researched remedies, but also to spur innovative research initiatives, based on our study of the physical properties coupled in sickle cell disease.

Myonecrosis in Sickle Cell Anemia: Case Study.

PubMed

Turaga, Lalita Prabha; Boddu, Prajwal; Kipferl, Steve; Basu, Anupam; Yorath, Martin

2017-01-30

BACKGROUND Myonecrosis is one of the more poorly studied, painful manifestations of sickle cell crisis. Medical literature is sparse detailing the manifestations and management of such symptoms. In myonecrosis, red cells containing sickle hemoglobin become rigid, resulting in reduced blood flow and myonecrosis. CASE REPORT We present a case study of a patient in sickle cell crisis with an episode of acute pain and swelling to the intrinsic muscles of the foot as a prominent feature of the crises. Although muscle biopsy is considered the gold standard for the diagnosis of myositis or myonecrosis, a low intensity signal on T1 and high intensity signal on T2 at the affected muscle belly can be as conclusive as imaging studies. In an actively sickling patient any invasive intervention should be avoided as it can result in ischemic necrosis of the tissues, due to interruption of capillary flow in end-arteries. CONCLUSIONS Early recognition is critical in sickle cell disease management, allowing for prompt and aggressive fluid resuscitation which remains a cornerstone in the management of most sickle cell vaso-occlusive crises. In this instance, off loading the extremity and early fluid resuscitation resolved the pain and swelling and prevented myonecrosis.

Hematopoietic Progenitor Cell Mobilization is More Robust in Healthy African American Compared to Caucasian Donors and is not Affected by the Presence of Sickle Cell Trait

PubMed Central

Panch, Sandhya R.; Yau, Yu Ying; Fitzhugh, Courtney D.; Hsieh, Matthew M.; Tisdale, John F.; Leitman, Susan F.

2016-01-01

Background G-CSF-stimulated hematopoietic progenitor cells (HPCs) collected by apheresis have become the predominant graft source for HPC transplantation in adults. Among healthy allogeneic donors, demographic characteristics (age, sex, BMI) and baseline hematologic counts affect HPC mobilization, leading to variability in CD34+ apheresis yields. Racial differences in HPC mobilization are less well characterized. Methods We retrospectively analyzed data from 1,096 consecutive G-CSF-stimulated leukapheresis procedures in healthy allogeneic African American (AA) or Caucasian donors. Results In a multivariate analysis, after adjusting for age, sex, BMI, baseline platelet and MNC counts, and daily G-CSF dose, peak CD34+ cell mobilization was significantly higher among AAs (n=215) than Caucasians (n=881) (123 ± 87 vs 75 ± 47 cells/uL; p<0.0001). A ceiling effect was observed with increasing G-CSF dose (10 vs 16 mcg/kg/day) in AAs (123 ± 88 vs 123 ± 87) but not in Caucasians (74 ± 46 vs 93 ± 53, p<0.001). In AA donors, presence of sickle cell trait (SCT, n=41) did not affect CD34+ mobilization (peak CD34+ 123 ± 91 vs 107 ±72 cells/uL, HbAS vs HbAA, p=0.34). Adverse events were minimal and similar across race. Conclusions AAs demonstrated significantly better CD34 mobilization responses to G-CSF than Caucasians. This was independent of other demographic and hematologic parameters. Studying race-associated pharmacogenomics in relation to G-CSF may improve dosing strategies. Adverse event profile and CD34 mobilization were similar in AA donors with and without SCT. Our findings suggest that it would be safe to include healthy AA donors with SCT in unrelated donor registries. PMID:27167356

Hematopoietic Stem Cell Transplantation in Thalassemia and Sickle Cell Disease. Unicenter Experience in a Multi-Ethnic Population.

PubMed Central

Marziali, Marco; Isgrò, Antonella; Gaziev, Javid; Lucarelli, Guido

2009-01-01

Hematopoietic stem cell transplantation (HSCT) still remains the only definitive cure currently available for patients with thalassemia and sickle cell anemia. Results of transplant in thalassemia and in sickle cell anemia have steadily improved over the last two decades due to improvements in preventive strategies, and effective control of transplant-related complications. From 2004 through 2009, 145 consecutive patients with thalassemia and sickle cell anemia, ethnically heterogeneous from Mediterranean and Middle East countries, were given HSCT in the International Center for Transplantation in Thalassemia and Sickle Cella Anemia in Rome. This experience is characterized by two peculiarities: patients were ethnically very heterogeneous and the vast majority of these patients were not regularly transfesed/chelated and therefore were highly sensitized due to RBC transfusions without leukodepletion filters. Consequently, they could have a high risk of graft rejection as a result of sensitization to HLA antigens. The Rome experience of SCT in patients with thalassemia and sickle cell anemia confirmed the results obtained in Pesaro, and most importantly showed the reproducibility of these results in other centers. PMID:21415995

Peripheral Vasoconstriction and Abnormal Parasympathetic Response to Sighs and Transient Hypoxia in Sickle Cell Disease

PubMed Central

Sangkatumvong, Suvimol; Khoo, Michael C. K.; Kato, Roberta; Detterich, Jon A.; Bush, Adam; Keens, Thomas G.; Meiselman, Herbert J.; Wood, John C.

2011-01-01

Rationale: Sickle cell disease is an inherited blood disorder characterized by vasoocclusive crises. Although hypoxia and pulmonary disease are known risk factors for these crises, the mechanisms that initiate vasoocclusive events are not well known. Objectives: To study the relationship between transient hypoxia, respiration, and microvascular blood flow in patients with sickle cell. Methods: We established a protocol that mimics nighttime hypoxic episodes and measured microvascular blood flow to determine if transient hypoxia causes a decrease in microvascular blood flow. Significant desaturations were induced safely by five breaths of 100% nitrogen. Measurements and Main Results: Desaturation did not induce change in microvascular perfusion; however, it induced substantial transient parasympathetic activity withdrawal in patients with sickle cell disease, but not controls subjects. Marked periodic drops in peripheral microvascular perfusion, unrelated to hypoxia, were triggered by sighs in 11 of 11 patients with sickle cell and 8 of 11 control subjects. Although the sigh frequency was the same in both groups, the probability of a sigh inducing a perfusion drop was 78% in patients with sickle cell and 17% in control subjects (P < 0.001). Evidence for sigh-induced sympathetic nervous system dominance was seen in patients with sickle cell (P < 0.05), but was not significant in control subjects. Conclusions: These data demonstrate significant disruption of autonomic nervous system balance, with marked parasympathetic withdrawal in response to transient hypoxia. They draw attention to an enhanced autonomic nervous system–mediated sigh–vasoconstrictor response in patients with sickle cell that could increase red cell retention in the microvasculature, promoting vasoocclusion. PMID:21616995

Genetic resistance to malaria, oxidative stress and hemoglobin oxidation.

PubMed

Destro Bisol, G

1999-09-01

I describe a model which posits the molecular basis of some malaria-resistance genes in the interaction between oxidized hemoglobin and membrane components. The model is supported by a considerable body of evidence which indicates that erythrocytes of genetically protected individuals (carriers of sickle cell trait, alpha- and beta-thalassemia, and G6PD deficiency) are susceptible to the increase of oxidation of hemoglobin following H2O2 release in the host cell by Plasmodium falciparum. I suggest that the irreversible interaction between oxidized hemoglobin and the red cell membrane could trigger mechanisms that: (i) reduce invasion of erythrocytes by the falciparum parasite; (ii) impair parasite survival and development within the cell; (iii) accelerate infected erythrocyte clearance by phagocytosis.

Resolution of Misconceptions of Latency and Adolescent Sicklers.

ERIC Educational Resources Information Center

Christy-Levine, Diane

Misconceptions regarding sickle cell disease are qualitatively different among latency age patients as compared to adolescents. The evolution and resolution of these misconceptions determine the effectiveness of self-help programs for sickle cell patients. The Mount Sinai Hospital Sickle Cell Counseling Service is a coordinated center for sickle…

African American Students' Awareness of Sickle Cell Disease.

ERIC Educational Resources Information Center

Ogamdi, Simon O.

1994-01-01

Reports a study that investigated knowledge level about sickle cell disease among students at a predominantly black university. Survey results indicated the students most directly concerned did not well understand the basic facts about sickle cell disease. Most students could not recall whether they had ever been tested. (SM)

76 FR 74067 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-30

... Project Formative Research to Support the Development of Sickle Cell Disease Educational Messages and... seeks to improve the quality of life of people living with sickle cell disease (SCD). To accomplish this... associated with sickle cell disease. To develop valuable messages and materials, CDC will conduct formative...

The Student with Sickle Cell Anemia.

ERIC Educational Resources Information Center

Tetrault, Sylvia M.

1981-01-01

Sickle cell anemia is the most common and severe of inherited chronic blood disorders. In the United States, sickle cell anemia is most common among the Black population. Among the most commonly occurring symptoms are: an enlarged spleen, episodes of severe pain, easily contracted infections, skin ulcers, and frequent urination. (JN)

Newborn Sickle Cell Screening: Benefits and Burdens Realized.

ERIC Educational Resources Information Center

Rowley, Peter T.; Huntzinger, Donna J.

1983-01-01

Follow-up data on a program that screened 17 newborns for sickle cell anemia suggests that in order to derive maximum benefit from such screening physicians need to better understand the differential diagnosis, treatment, and inheritance of sickle cell disease, and individual guidance must be provided to families. (GC)

Children with Sickle-Cell Anemia: Parental Relations, Parent-Child Relations, and Child Behavior.

ERIC Educational Resources Information Center

Evans, Robert C.; And Others

1988-01-01

Investigated the influence of a child with sickle-cell anemia on parental affiliation, parent-child relationships, and parents' perception of their child's behavior. In the sickle-cell group, parents' interpersonal relationship suffered; parent-child relationship and child behavior correlated significantly; and single-parent families estimated…

38 CFR 1.303 - Policy.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Immunodeficiency Virus (HIV), or Sickle Cell Anemia Note: Sections 1.460 through 1.499 of this part concern the... immunodeficiency virus, or sickle cell anemia in VA records and are applicable in combination with other... immunodeficiency virus, or sickle cell anemia. The statutory authority for the drug abuse provisions and alcoholism...

38 CFR 1.303 - Policy.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Immunodeficiency Virus (HIV), or Sickle Cell Anemia Note: Sections 1.460 through 1.499 of this part concern the... immunodeficiency virus, or sickle cell anemia in VA records and are applicable in combination with other... immunodeficiency virus, or sickle cell anemia. The statutory authority for the drug abuse provisions and alcoholism...

38 CFR 1.303 - Policy.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Immunodeficiency Virus (HIV), or Sickle Cell Anemia Note: Sections 1.460 through 1.499 of this part concern the... immunodeficiency virus, or sickle cell anemia in VA records and are applicable in combination with other... immunodeficiency virus, or sickle cell anemia. The statutory authority for the drug abuse provisions and alcoholism...

38 CFR 1.303 - Policy.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Immunodeficiency Virus (HIV), or Sickle Cell Anemia Note: Sections 1.460 through 1.499 of this part concern the... immunodeficiency virus, or sickle cell anemia in VA records and are applicable in combination with other... immunodeficiency virus, or sickle cell anemia. The statutory authority for the drug abuse provisions and alcoholism...

38 CFR 1.303 - Policy.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Immunodeficiency Virus (HIV), or Sickle Cell Anemia Note: Sections 1.460 through 1.499 of this part concern the... immunodeficiency virus, or sickle cell anemia in VA records and are applicable in combination with other... immunodeficiency virus, or sickle cell anemia. The statutory authority for the drug abuse provisions and alcoholism...

Protrusio acetabuli in sickle-cell anemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martinez, S.; Apple, J.S.; Baber, C.

1984-04-01

Of 155 adults with sickle-cell anemia (SS, SC), radiographs of the pelvis or hip demonstrated protrusio acetabuli on at least one side in 14 (3 men and 11 women), as indicated by projection of the acetabular line medial to the ilio-ischial line. All 14 patients had bone changes attributable to sickle-cell anemia, including marrow hyperplasia and osteonecrosis; however, the severity of femoral or acetabular osteonecrosis did not appear directly related to the protrusion. The authors conclude that sickle-cell anemia can predispose to development of protrusio acetabuli.

Acute colonic pseudoobstruction in a child with sickle cell disease treated with neostigmine.

PubMed

Khosla, Arjun; Ponsky, Todd A

2008-12-01

Sickle cell disease is a disorder that produces significant morbidity and mortality. Vaso-occlusive pain crises are the most common presenting symptom associated with sickle cell patients. A rare, yet important to recognize, complication of sickle cell disease is acute colonic pseudoobstruction, also known as Ogilvie's syndrome. These patients may present with symptoms that are difficult to distinguish from other etiologies of abdominal pain, but a thorough diagnostic workup can provide important clues. Furthermore, there is no agreement on optimal treatment of pseudoobstruction. We report the first pediatric case of acute pseudoobstruction secondary to sickle cell disease that was treated successfully with neostigmine. Early recognition of this phenomenon is important as it alters patient management, can be treated medically, and may avoid unnecessary surgical intervention.

A massive intestinal vaso-occlusive crisis or "girdle syndrome" in a 6-year-old boy observed as a first manifestation of sickle cell disease.

PubMed

Knorr, M; Bienemann, K; Walde, G; Kaufhold, A; Schündeln, M M

2014-11-01

Sickle cell disease is a chronic hematologic disease with variable but often severe systemic symptoms. In this report, we describe a 6-year-old boy presenting with acute bowel pseudo-obstruction. During this episode, previously undiagnosed sickle cell disease was discovered upon peripheral blood smear analysis. The condition was therefore interpreted as a massive intestinal vaso-occlusive crisis or "girdle syndrome". Conservative treatment with hydration therapy, analgesia and a manual partial exchange transfusion was initiated. The patient fully recovered within 5 days. Girdle syndrome is a rare but severe adverse event associated with sickle cell disease that must be considered as differential diagnosis in patients with sickle cell disease. © Georg Thieme Verlag KG Stuttgart · New York.

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice.

PubMed

Cahill, Lindsay S; Gazdzinski, Lisa M; Tsui, Albert Ky; Zhou, Yu-Qing; Portnoy, Sharon; Liu, Elaine; Mazer, C David; Hare, Gregory Mt; Kassner, Andrea; Sled, John G

2017-03-01

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO 2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia.

Functional and anatomical evidence of cerebral tissue hypoxia in young sickle cell anemia mice

PubMed Central

Gazdzinski, Lisa M; Tsui, Albert KY; Zhou, Yu-Qing; Portnoy, Sharon; Liu, Elaine; Mazer, C David; Hare, Gregory MT; Kassner, Andrea; Sled, John G

2016-01-01

Cerebral ischemia is a significant source of morbidity in children with sickle cell anemia; however, the mechanism of injury is poorly understood. Increased cerebral blood flow and low hemoglobin levels in children with sickle cell anemia are associated with increased stroke risk, suggesting that anemia-induced tissue hypoxia may be an important factor contributing to subsequent morbidity. To better understand the pathophysiology of brain injury, brain physiology and morphology were characterized in a transgenic mouse model, the Townes sickle cell model. Relative to age-matched controls, sickle cell anemia mice demonstrated: (1) decreased brain tissue pO2 and increased expression of hypoxia signaling protein in the perivascular regions of the cerebral cortex; (2) elevated basal cerebral blood flow , consistent with adaptation to anemia-induced tissue hypoxia; (3) significant reduction in cerebrovascular blood flow reactivity to a hypercapnic challenge; (4) increased diameter of the carotid artery; and (5) significant volume changes in white and gray matter regions in the brain, as assessed by ex vivo magnetic resonance imaging. Collectively, these findings support the hypothesis that brain tissue hypoxia contributes to adaptive physiological and anatomic changes in Townes sickle cell mice. These findings may help define the pathophysiology for stroke in children with sickle cell anemia. PMID:27165012

Events of hospitalization among children with sickle cell disease.

PubMed

Fosdal, Marian B; Wojner-Alexandrov, Anne W

2007-08-01

Previous research has identified vaso-occlusive pain crisis as the most common reason for hospitalization among pediatric patients with sickle cell disease. We sought to identify contributors to hospitalization and length of stay (LOS) for this patient population. A descriptive design was used to determine factors associated with hospitalization and LOS for patients with sickle cell disease at an urban tertiary care pediatric hospital in the Midwest. Sickle cell disease as a principal or secondary diagnosis during calendar year 2003 was used to identify patients for study inclusion. Data were collected from subjects' medical records and the hospital accounting system. 72 African American subjects, ranging in age from infant to 24 years (mean = 10.3) met study inclusion criteria, and accounted for 186 hospitalizations. Sickle cell pain crisis was the most common diagnosis associated with hospitalization (n = 122). Adolescent age was significantly associated with longer LOS (r = .451; p<.001), and females stayed on average 2.1 days longer than male subjects (p = .001). Age and gender appear to be associated with LOS in pediatric patients with sickle cell disease, although specific factors underlying these findings remain unclear. Further research is necessary to determine how the complex interplay of social, cultural, developmental, and physiologic factors may contribute to the hospitalization experience of children and adolescents with sickle cell disease.

Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

PubMed Central

Joiner, C H; Platt, O S; Lux, S E

1986-01-01

The mechanism by which sickle cells and xerocytic red cells become depleted of cations in vivo has not been identified previously. Both types of cells exhibit elevated permeabilities to sodium and potassium, in the case of sickle cells, when deoxygenated. The ouabain-insensitive fluxes of sodium and potassium were equivalent, however, in both cell types under these conditions. When incubated 18 hours in vitro, sickle cells lost cations but only when deoxygenated. This cation depletion was blocked by ouabain, removal of external potassium, or pretreatment with 4,4'-diisothiocyanostilbene-2,2'-disulfonate, which blocks the increase in cation permeability induced by deoxygenation. The loss of cation exhibited by oxygenated xerocytes similarly incubated was also blocked by ouabain. These data support the hypothesis that the elevated "passive" cation fluxes of xerocytes and deoxygenated sickle cells are not directly responsible for cation depletion of these cells; rather, these pathologic leaks interact with the sodium pump to produce a net loss of cellular cation. PMID:2430999

Cation depletion by the sodium pump in red cells with pathologic cation leaks. Sickle cells and xerocytes.

PubMed

Joiner, C H; Platt, O S; Lux, S E

1986-12-01

The mechanism by which sickle cells and xerocytic red cells become depleted of cations in vivo has not been identified previously. Both types of cells exhibit elevated permeabilities to sodium and potassium, in the case of sickle cells, when deoxygenated. The ouabain-insensitive fluxes of sodium and potassium were equivalent, however, in both cell types under these conditions. When incubated 18 hours in vitro, sickle cells lost cations but only when deoxygenated. This cation depletion was blocked by ouabain, removal of external potassium, or pretreatment with 4,4'-diisothiocyanostilbene-2,2'-disulfonate, which blocks the increase in cation permeability induced by deoxygenation. The loss of cation exhibited by oxygenated xerocytes similarly incubated was also blocked by ouabain. These data support the hypothesis that the elevated "passive" cation fluxes of xerocytes and deoxygenated sickle cells are not directly responsible for cation depletion of these cells; rather, these pathologic leaks interact with the sodium pump to produce a net loss of cellular cation.

Ischemic duodenal ulcer, an unusual presentation of sickle cell disease.

PubMed

Julka, Rahul N; Aduli, Farshad; Lamps, Laura W; Olden, Kevin W

2008-03-01

Sickle cell disease is caused by molecular abnormalities in the formation of hemoglobin, leading to pain crisis from recurrent vascular occlusion by sickled hemoglobin. Impaired flow in the microvasculature can lead to ischemia, tissue infarction and ulceration. Abdominal pain, a common complaint in sickle cell disease, can be due to an uncommon etiology, ischemic duodenal ulceration. This is due to primary mucosal infarction caused by sickling, leading to poor healing of infarcted areas. Prompt endoscopic and/or urgent surgical intervention should be considered, particularly if anticoagulation is an issue, as proton pump inhibitor use is ineffective in healing this type of ulcer.

Multiscale modeling of sickle anemia blood blow by Dissipative Partice Dynamics

NASA Astrophysics Data System (ADS)

Lei, Huan; Caswell, Bruce; Karniadakis, George

2011-11-01

A multi-scale model for sickle red blood cell is developed based on Dissipative Particle Dynamics (DPD). Different cell morphologies (sickle, granular, elongated shapes) typically observed in in vitro and in vivo are constructed and the deviations from the biconcave shape is quantified by the Asphericity and Elliptical shape factors. The rheology of sickle blood is studied in both shear and pipe flow systems. The flow resistance obtained from both systems exhibits a larger value than the healthy blood flow due to the abnormal cell properties. However, the vaso-occulusion phenomenon, reported in a recent microfluid experiment, is not observed in the pipe flow system unless the adhesive interactions between sickle blood cells and endothelium properly introduced into the model.

Pulmonary artery segmentation and quantification in sickle cell associated pulmonary hypertension

NASA Astrophysics Data System (ADS)

Linguraru, Marius George; Mukherjee, Nisha; Van Uitert, Robert L.; Summers, Ronald M.; Gladwin, Mark T.; Machado, Roberto F.; Wood, Bradford J.

2008-03-01

Pulmonary arterial hypertension is a known complication associated with sickle-cell disease; roughly 75% of sickle cell disease-afflicted patients have pulmonary arterial hypertension at the time of death. This prospective study investigates the potential of image analysis to act as a surrogate for presence and extent of disease, and whether the size change of the pulmonary arteries of sickle cell patients could be linked to sickle-cell associated pulmonary hypertension. Pulmonary CT-Angiography scans from sickle-cell patients were obtained and retrospectively analyzed. Randomly selected pulmonary CT-Angiography studies from patients without sickle-cell anemia were used as negative controls. First, images were smoothed using anisotropic diffusion. Then, a combination of fast marching and geodesic active contours level sets were employed to segment the pulmonary artery. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries. From the centerline, the diameters at the pulmonary trunk and first branch of the pulmonary arteries were measured automatically. Arterial diameters were normalized to the width of the thoracic cavity, patient weight and body surface. Results show that the pulmonary trunk and first right and left pulmonary arterial branches at the pulmonary trunk junction are significantly larger in diameter with increased blood flow in sickle-cell anemia patients as compared to controls (p values of 0.0278 for trunk and 0.0007 for branches). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance.

Erythropoiesis and myocardial energy requirements contribute to the hypermetabolism of childhood sickle cell anemia.

PubMed

Hibbert, Jacqueline M; Creary, Melissa S; Gee, Beatrice E; Buchanan, Iris D; Quarshie, Alexander; Hsu, Lewis L

2006-11-01

We hypothesized that an elevated hemoglobin synthesis rate (SynHb) and myocardial oxygen consumption (MVO2) contribute to the excess protein and energy metabolism reported in children with sickle cell anemia. Twelve children (6-12 years old) with asymptomatic sickle cell and 9 healthy children matched for age and sex were studied. Measurements were whole-body protein turnover by [1-C]leucine, SynHb by [N]glycine, resting energy expenditure by indirect calorimetry and the systolic blood pressure-heart rate product used as an index of MVO2. Protein energy cost was calculated from protein turnover. Statistical analysis included Spearman correlations and partial correlation analyses. Although body mass index was significantly lower for sickle cell versus controls (P < 0.02), children with asymptomatic sickle cell had 52% higher protein turnover (P < 0.0005). Proportional reticulocyte count, SynHb, MVO2 and resting energy expenditure were also significantly higher in children with sickle cell (P < 0.01). Protein turnover correlated significantly with both SynHb (r = 0.63, P < 0.01) and reticulocyte percentage (r = 0.83, P < 0.0001). Partial correlation of these 3 variables showed reticulocyte percentage as the only variable to be significantly associated with protein turnover, even after adjusting for sickle cell anemia (P = 0.03). Partial correlation of log resting energy expenditure on MVO2 was significant, controlling for protein energy cost, sex and age (P = 0.03). These results indicate that metabolic demands of increased erythropoiesis and cardiac energy consumption account for much of the excess protein and energy metabolism in children with sickle cell anemia.

Sickle cell crisis and endothelin antagonists.

PubMed

Angerio, Allan D; Lee, Nicole D

2003-01-01

Sickle cell crisis may be more complex than a vaso-occlusive event in response to hypoxia. Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogen secreted in response to hypoxia. ET-1 contributes to the vaso-occlusion and inflammation in sickle cell crisis. ET-1 antagonists may be useful in the prevention and treatment of crisis.

Etiology of Strokes in Children with Sickle Cell Anemia

ERIC Educational Resources Information Center

DeBaun, Michael R.; Derdeyn, Colin P.; McKinstry, Robert C., III

2006-01-01

The most devastating complication of sickle cell anemia is cerebral infarction, affecting [approximately]30% of all individuals with sickle cell anemia. Despite being one of the most common causes of stroke in infants and children, the mechanism of cerebral infarction in this population has not been extensively studied and is poorly understood.…

Students with Sickle Cell Anemia Participating in Recess

ERIC Educational Resources Information Center

Lucas, Matthew D.; Devlin, Katharine M.

2011-01-01

The participation of a student with Sickle Cell Anemia in recess can often be both challenging and rewarding for the student and teacher. This paper will address common characteristics of students with Sickle Cell Anemia and present basic solutions to improve the experience of these students in the recess setting. Initially the definition,…

Management of sickle cell disease in patients undergoing cardiac surgery.

PubMed

Crawford, Todd C; Carter, Michael V; Patel, Rina K; Suarez-Pierre, Alejandro; Lin, Sophie Z; Magruder, Jonathan Trent; Grimm, Joshua C; Cameron, Duke E; Baumgartner, William A; Mandal, Kaushik

2017-02-01

Sickle cell disease is a life-limiting inherited hemoglobinopathy that poses inherent risk for surgical complications following cardiac operations. In this review, we discuss preoperative considerations, intraoperative decision-making, and postoperative strategies to optimize the care of a patient with sickle cell disease undergoing cardiac surgery. © 2017 Wiley Periodicals, Inc.

38 CFR 1.467 - Restrictions on the use of identification cards and public signs.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Immunodeficiency Virus (hiv), Or Sickle Cell Anemia § 1.467 Restrictions on the use of identification cards and... abuse, alcoholism or alcohol abuse, HIV infection, or sickle cell anemia treatment program. A facility... alcohol abuse, HIV infection, or sickle cell anemia. (b) Treatment locations should not be identified by...

38 CFR 1.467 - Restrictions on the use of identification cards and public signs.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Immunodeficiency Virus (hiv), Or Sickle Cell Anemia § 1.467 Restrictions on the use of identification cards and... abuse, alcoholism or alcohol abuse, HIV infection, or sickle cell anemia treatment program. A facility... alcohol abuse, HIV infection, or sickle cell anemia. (b) Treatment locations should not be identified by...

38 CFR 1.467 - Restrictions on the use of identification cards and public signs.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Immunodeficiency Virus (hiv), Or Sickle Cell Anemia § 1.467 Restrictions on the use of identification cards and... abuse, alcoholism or alcohol abuse, HIV infection, or sickle cell anemia treatment program. A facility... alcohol abuse, HIV infection, or sickle cell anemia. (b) Treatment locations should not be identified by...

38 CFR 1.467 - Restrictions on the use of identification cards and public signs.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Immunodeficiency Virus (hiv), Or Sickle Cell Anemia § 1.467 Restrictions on the use of identification cards and... abuse, alcoholism or alcohol abuse, HIV infection, or sickle cell anemia treatment program. A facility... alcohol abuse, HIV infection, or sickle cell anemia. (b) Treatment locations should not be identified by...

38 CFR 1.467 - Restrictions on the use of identification cards and public signs.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Immunodeficiency Virus (hiv), Or Sickle Cell Anemia § 1.467 Restrictions on the use of identification cards and... abuse, alcoholism or alcohol abuse, HIV infection, or sickle cell anemia treatment program. A facility... alcohol abuse, HIV infection, or sickle cell anemia. (b) Treatment locations should not be identified by...

"Untangling Sickle-Cell Anemia and the Teaching of Heterozygote Protection"

ERIC Educational Resources Information Center

Howe, Eric Michael

2007-01-01

Introductory biology textbooks often use the example of sickle-cell anemia to illustrate the concept of heterozygote protection. Ordinarily scientists expect the frequency of a gene associated with a debilitating illness would be low owing to its continual elimination by natural selection. The gene that causes sickle-cell anemia, however, has a…

Unusual causes of abdominal pain: sickle cell anemia.

PubMed

Ahmed, Shahid; Shahid, Rabia K; Russo, Linda A

2005-04-01

Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crises. The vascular occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestation of the disease. Abdominal pain is an important component of vaso-occlusive painful crises. It often represents a substantial diagnostic challenge in this population of patients. These episodes are often attributed to micro-vessel occlusion and infarcts of mesentery and abdominal viscera. Abdominal pain due to sickle cell vaso-occlusive crisis is often indistinguishable from an acute intra-abdominal disease process such as acute cholecystitis, acute pancreatitis, hepatic infarction, ischemic colitis and acute appendicitis. In the majority of cases, however, no specific cause is identified and spontaneous resolution occurs. This chapter will focus on etiologies, pathophysiology and management of abdominal pain in patients with sickle cell disease.

Tissue factor expression by endothelial cells in sickle cell anemia.

PubMed

Solovey, A; Gui, L; Key, N S; Hebbel, R P

1998-05-01

The role of the vascular endothelium in activation of the coagulation system, a fundamental homeostatic mechanism of mammalian biology, is uncertain because there is little evidence indicating that endothelial cells in vivo express tissue factor (TF), the system's triggering mechanism. As a surrogate for vessel wall endothelium, we examined circulating endothelial cells (CEC) from normals and patients with sickle cell anemia, a disease associated with activation of coagulation. We find that sickle CEC abnormally express TF antigen (expressed as percent CEC that are TF-positive), with 66+/-13% positive in sickle patients in steady-state, 83+/-19% positive in sickle patients presenting with acute vasoocclusive episodes, and only 10+/-13% positive in normal controls. Repeated samplings confirmed this impression that TF expression is greater when sickle patients develop acute vasoocclusive episodes. Sickle CEC are also positive for TF mRNA, with excellent concurrence between antigen and mRNA expression. The TF expressed on the antigen-positive CEC is functional, as demonstrated by a binding assay for Factor VIIa and a chromogenic assay sensitive to generation of Factor Xa. By establishing that endothelial cells in vivo can express TF, these data imply that the vast endothelial surface area does provide an important pathophysiologic trigger for coagulation activation.

Nutritional status, hospitalization and mortality among patients with sickle cell anemia in Tanzania

PubMed Central

Cox, Sharon E.; Makani, Julie; Fulford, Anthony J.; Komba, Albert N.; Soka, Deogratius; Williams, Thomas N.; Newton, Charles R.; Marsh, Kevin; Prentice, Andrew M.

2011-01-01

Background Reduced growth is common in children with sickle cell anemia, but few data exist on associations with long-term clinical course. Our objective was to determine the prevalence of malnutrition at enrolment into a hospital-based cohort and whether poor nutritional status predicted morbidity and mortality within an urban cohort of Tanzanian sickle cell anemia patients. Design and Methods Anthropometry was conducted at enrolment into the sickle cell anemia cohort (n=1,618; ages 0.5–48 years) and in controls who attended screening (siblings, walk-ins and referrals) but who were found not to have sickle cell anemia (n=717; ages 0.5–64 years). Prospective surveillance recorded hospitalization at Muhimbili National Hospital and mortality between March 2004 and September 2009. Results Sickle cell anemia was associated with stunting (OR=1.92, P<0.001, 36.2%) and wasting (OR=1.66, P=0.002, 18.4%). The greatest growth deficits were observed in adolescents and in boys. Independent of age and sex, lower hemoglobin concentration was associated with increased odds of malnutrition in sickle cell patients. Of the 1,041 sickle cell anemia patients with a body mass index z-score at enrolment, 92% were followed up until September 2009 (n=908) or death (n=50). Body mass index and weight-for-age z-score predicted hospitalization (hazard ratio [HZR]=0.90, P=0.04 and HZR=0.88, P=0.02) but height-for-age z-score did not (HZR=0.93, NS). The mortality rate of 2.5 per 100 person-years was not associated with any of the anthropometric measures. Conclusions In this non-birth-cohort of sickle cell anemia with significant associated undernutrition, wasting predicted an increased risk of hospital admission. Targeted nutritional interventions should prioritize treatment and prevention of wasting. PMID:21459787

Birth control necessary to limit family size in tribal couples with aberrant heterosis of G-6-PD deficiency and sickle cell disorders in India: an urgency of creating awareness and imparting genetic counseling.

PubMed

Balgir, R S

2010-06-01

(i) To study the outcome of ignorance and lack of awareness about sickle cell disease and G-6-PD deficiency among Dhelki Kharia tribal families of Orissa, and (ii) to study the reproductive output in relation to clinical genetics and patho-physiological implications. A random genetic study of screening for hemoglobinopathies and G-6-PD deficiency among Dhelki Kharia tribal community in Sundargarh district of Orissa was carried out for intervention during the year 2000-2004. A total of 81 Dhelki Kharia families were screened and six families with double heterozygosity for above genetic anomalies were encountered. About 2-3 ml. intravenous blood samples were collected in EDTA by disposable syringes and needles after taking informed consent from each individual in the presence of a doctor and community leaders and sent to laboratory at Bhubaneswar for hematological investigations. Analysis was carried out following the standard procedures after cross checking for quality control. There were 12 (about 52%) children out of 23 who were either suffering from sickle cell trait or disease in concurrence with G-6-PD deficiency in hemizygous/heterozygous/homozygous condition in Dhelki Kharia tribal community of Orissa. There were on an average 3.83 number of surviving (range 2-6) children per mother in families of G-6-PD deficiency and sickle cell disorders. The average number of children (3.83) born (range 2-6 children) per mother to carrier/affected mother was much higher than the average for India (2.73). It is very difficult to maintain the normal health of an affected child with aberrant anomalies due to exorbitant cost of treatment, frequent transfusions and huge involvement of economy. One of the implications of aberrant heterosis is its adverse affects on routine individual physiology and hard activities. It is suggested to limit the family size in carrier couples to avoid aberrant heterosis of hereditary hemolytic disorders in their offsprings.

The Epidemiology and Management of Lung Diseases in Sickle Cell Disease: Lessons Learned from Acute and Chronic Lung Disease in Cystic Fibrosis.

PubMed

Willen, Shaina M; DeBaun, Michael R

2018-06-01

Although sickle cell disease and cystic fibrosis are two of the most common monogenic diseases presenting in childhood worldwide, cystic fibrosis and sickle cell disease enjoy vastly different funding and collaborative research efforts. Pulmonary complications in cystic fibrosis have well established guidelines and multidisciplinary involvement focusing on comorbidities, routine monitoring, infectious complications, nutrition, and treatment recommendations. These guidelines can provide a framework on which to build knowledge of lung disease in sickle cell disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Sickle Mice Are Sensitive to Hypoxia/Ischemia-Induced Stroke but Respond to Tissue-Type Plasminogen Activator Treatment.

PubMed

Sun, Yu-Yo; Lee, Jolly; Huang, Henry; Wagner, Mary B; Joiner, Clinton H; Archer, David R; Kuan, Chia-Yi

2017-12-01

The effects of lytic stroke therapy in patients with sickle cell anemia are unknown, although a recent study suggested that coexistent sickle cell anemia does not increase the risk of cerebral hemorrhage. This finding calls for systemic analysis of the effects of thrombolytic stroke therapy, first in humanized sickle mice, and then in patients. There is also a need for additional predictive markers of sickle cell anemia-associated vasculopathy. We used Doppler ultrasound to examine the carotid artery of Townes sickle mice tested their responses to repetitive mild hypoxia-ischemia- and transient hypoxia-ischemia-induced stroke at 3 or 6 months of age, respectively. We also examined the effects of tPA (tissue-type plasminogen activator) treatment in transient hypoxia-ischemia-injured sickle mice. Three-month-old sickle cell (SS) mice showed elevated resistive index in the carotid artery and higher sensitivity to repetitive mild hypoxia-ischemia-induced cerebral infarct. Six-month-old SS mice showed greater resistive index and increased flow velocity without obstructive vasculopathy in the carotid artery. Instead, the cerebral vascular wall in SS mice showed ectopic expression of PAI-1 (plasminogen activator inhibitor-1) and P-selectin, suggesting a proadhesive and prothrombotic propensity. Indeed, SS mice showed enhanced leukocyte and platelet adherence to the cerebral vascular wall, broader fibrin deposition, and higher mortality after transient hypoxia-ischemia. Yet, post-transient hypoxia-ischemia treatment with tPA reduced thrombosis and mortality in SS mice. Sickle mice are sensitive to hypoxia/ischemia-induced cerebral infarct but benefit from thrombolytic treatment. An increased resistive index in carotid arteries may be an early marker of sickle cell vasculopathy. © 2017 American Heart Association, Inc.

Left ventricular function by echocardiogram in children with sickle cell anaemia in Mumbai, Western India.

PubMed

Tidake, Abhay; Gangurde, Pranil; Taksande, Anup; Mahajan, Ajay; Nathani, Pratap

2015-10-01

Cardiovascular events and complications are the leading cause of mortality and morbidity in patients with sickle cell disease. Cardiac abnormalities occur frequently and at an early stage in sickle cell anaemia patients, despite being more evident in adulthood. Sickle cell anaemia patients are increasingly able to reach adulthood owing to improved healthcare, and may, therefore, suffer the consequences of chronic cardiac injury. Thus, the study of cardiac abnormalities is essential in children The aim of this study was to determine the echocardiographic changes in left ventricular function in children suffering from sickle cell disease in Mumbai, Western India. The study comprised of 48 cases of sickle cell anaemia and 30 non-anaemic controls with normal haemoglobin and electrophoresis pattern. M-mode, two-dimensional, and Doppler echocardiographic measurements of patients and controls were performed according to the criteria of the American Echocardiography Society. On Doppler study, the A wave height was increased and the E/A ratio was decreased, whereas the deceleration and isovolumetric relaxation times were prolonged, which is typically seen in slowed or impaired myocardial relaxation (p<0.001). Although chamber dilatations were present, echocardiographic parameters showed no statistically significant correlation with severity of anaemia and age among the sickle cell patients. We conclude that the increased left ventricular stiffness, compared with controls, might be due to fibrosis related to ischaemia caused by SS disease in addition to wall hypertrophy.

Characterizing emergency admissions of patients with sickle cell crisis in NHS brent: observational study

PubMed Central

Green, Stuart A; AlJuburi, Ghida; Majeed, Azeem; Okoye, Ogo; Amobi, Carole; Banarsee, Ricky; Phekoo, Karen J

2012-01-01

Objectives To characterize emergency admissions for patients with sickle cell crisis in NHS Brent and to determine which patients and practices may benefit most from primary care intervention. Design Observational study Setting Emergency departments attended by residents of the London borough of Brent Participants Patients with sickle cell disease registered with a general practitioner (GP) in the borough of Brent Main outcome measures Analysis of admissions between January 2008 and July 2010 that included length of stay (average and <2 days versus ≥2 days) by age group and registered GP practice. Results Thirty six percent of sickle cell disease admission spells resulted in a length of stay of less than two days. Seventy four percent of total bed days are associated with patients with more than one admission during the period of analysis, i.e. multiple admissions. Two general practices in Brent were identified as having the highest number of patients admitted to the emergency department for sickle cell crisis and may benefit most from primary care intervention. Discussion Patients with short length of stay and multiple admissions may be potentially amenable to primary care intervention. The practices which have the highest numbers of sickle cell disease patients who frequently seek emergency care will be earmarked for an education intervention designed to help further engage general practitioners in the care and management of their sickle cell patients. PMID:22768371

Characterizing emergency admissions of patients with sickle cell crisis in NHS brent: observational study.

PubMed

Green, Stuart A; Aljuburi, Ghida; Majeed, Azeem; Okoye, Ogo; Amobi, Carole; Banarsee, Ricky; Phekoo, Karen J

2012-06-01

To characterize emergency admissions for patients with sickle cell crisis in NHS Brent and to determine which patients and practices may benefit most from primary care intervention. Observational study Emergency departments attended by residents of the London borough of Brent Patients with sickle cell disease registered with a general practitioner (GP) in the borough of Brent Analysis of admissions between January 2008 and July 2010 that included length of stay (average and <2 days versus ≥2 days) by age group and registered GP practice. Thirty six percent of sickle cell disease admission spells resulted in a length of stay of less than two days. Seventy four percent of total bed days are associated with patients with more than one admission during the period of analysis, i.e. multiple admissions. Two general practices in Brent were identified as having the highest number of patients admitted to the emergency department for sickle cell crisis and may benefit most from primary care intervention. Patients with short length of stay and multiple admissions may be potentially amenable to primary care intervention. The practices which have the highest numbers of sickle cell disease patients who frequently seek emergency care will be earmarked for an education intervention designed to help further engage general practitioners in the care and management of their sickle cell patients.

[Perioperative management of laparoscopic cholecystectomy in children with homozygous sickle cell disease].

PubMed

Ndoye, M Diop; Bah, M Diao; Pape, I Ndiaye; Diouf, E; Kane, O; Bèye, M; Fall, B; Ka-Sall, B

2008-09-01

Sickle cell disease is a public health problem in Africa. The aim of this prospective study was to evaluate per and post-operative complications of laparoscopic cholecystectomy in sickle cell children in Senegal. from January 1999 to December 2006, an anesthetic protocol was applied to 39 sickle cell children undergoing a cholecystectomy. Among them, 20 experienced laparoscopic cholecystectomy. All these 20 patients had previously suffered from sickle cell visceral complications and were classified as ASA II (11 cases) and as ASA III (9 cases). Blood transfusion program aimed at sustaining haemoglobin level between 10 and 12 g/dl was implemented. The preoperative monitoring and anesthesia management were the same for these patients. During perioperative period, the prevention of pain, hypovolemia, hypothermia and acidosis was achieved. The mean insufflation duration of laparoscopy was 23 min (17-60 min), the mean surgery duration was 55 min (40-110 min), and the mean anesthesia duration was 78 min (88-135 min). Postoperative complications occurred in 9 patients: acute chest syndrome (n=2), postoperative hemolysis (n=5), vaso-occlusive crisis (n=2). Laparoscopic cholecystectomy can be carried out in sickle cell children affected with gallstones, provided that general anaesthetic rules were respected. An appropriate pre-, per- and postoperative anaesthesia is mandatory to reduce postoperative complications in children with sickle cell disease. Searching for early diagnosis of gallstones before occurrence of visceral complications should allow further optimal laparoscopic surgery.

Brazilian Guidelines for transcranial doppler in children and adolescents with sickle cell disease

PubMed Central

Lobo, Clarisse Lopes de Castro; Cançado, Rodolfo Delfini; Leite, Ana Claudia Celestino Bezerra; dos Anjos, Ana Claudia Mendonça; Pinto, Ana Cristina Silva; Matta, Andre Palma da Cunha; Silva, Célia Maria; Silva, Gisele Sampaio; Friedrisch, João Ricardo; Braga, Josefina Aparecida Pellegrini; Lange, Marcos Christiano; Figueiredo, Maria Stella; Rugani, Marília Álvares; Veloso, Orlando; Moura, Patrícia Gomes; Cortez, Paulo Ivo; Adams, Robert; Gualandro, Sandra Fátima Menosi; de Castilho, Shirley Lopes; Thomé, Ursula; Zetola, Viviane Flumignan

2011-01-01

Background Sickle cell disease is the most common monogenic hereditary disease in Brazil. Although strokes are one of the main causes of morbidity and mortality in these patients, the use of transcranial Doppler to identify children at risk is not universally used. Objective To develop Brazilian guidelines for the use of transcranial Doppler in sickle cell disease children and adolescents, so that related health policies can be expanded, and thus contribute to reduce morbidity and mortality. Methods The guidelines were formulated in a consensus meeting of experts in transcranial Doppler and sickle cell disease. The issues discussed were previously formulated and scientific articles in databases (MEDLINE, SciELO and Cochrane) were carefully analyzed. The consensus for each question was obtained by a vote of experts on the specific theme. Results Recommendations were made, including indications for the use of transcranial Doppler according to the sickle cell disease genotype and patients age; the necessary conditions to perform the exam and its periodicity depending on exam results; the criteria for the indication of blood transfusions and iron chelation therapy; the indication of hydroxyurea; and the therapeutic approach in cases of conditional transcranial Doppler. Conclusion The Brazilian guidelines on the use of transcranial doppler in sickle cell disease patients may reduce the risk of strokes, and thus reduce the morbidity and mortality and improve the quality of life of sickle cell disease patients. PMID:23284243

Depression in sickle cell disease.

PubMed Central

Hasan, Syed Parwez; Hashmi, Shahzad; Alhassen, Mohammed; Lawson, William; Castro, Oswaldo

2003-01-01

PURPOSE: To assess the prevalence of depressive symptoms and examine the contribution of demographics, disease severity, and health care use variables to depressive symptoms in sickle cell patients who had been in stable health for at least one month. PATIENTS AND METHODS: Subjects were a convenience sample of 27 men and 23 women selected during a routine visit to the sickle cell clinic at Howard University Hospital. Depression was assessed using a cut-off score from the Beck Depression Inventory (BDI) and related to a variety of health outcomes. RESULTS: The results of the analyses indicate that 44% (n=22) of the sample scored within the mild to severe (>20) range of depression on the BDI. Depressed sickle cell patients were more frequently treated in emergency rooms and more likely to be hospitalized with vaso-occlusive crises. Patients more likely to be depressed were: those with low family income (<$10,000); less than high school education; female; those who had multiple blood transfusions; poor pain control; inadequate social support; hydroxyurea use; and had histories of frequent vaso-occlusive crises. CONCLUSION: The prevalence of depressive symptoms in sickle cell patients is high compared to the general African American population. Our findings confirmed previous studies examining the occurrence of depression in adults with sickle cell disease. Treatment of depression should be strongly considered to improve the quality of life and probably disease course in sickle cell patients. PMID:12911250

38 CFR 1.511 - Disclosure of claimant records in connection with judicial proceedings generally.

Code of Federal Regulations, 2010 CFR

2010-07-01

... sickle cell anemia treatment records, which are protected under 38 U.S.C. 7332, where the records sought... and sickle cell anemia treatment records, which are protected under 38 U.S.C. 7332, where the records... virus and sickle cell anemia treatment, a subpoena is insufficient for such disclosure. Specific...

A Group Counseling Approach for Persons Who Work With Sickle Cell Anemia Clients.

ERIC Educational Resources Information Center

Calvin, Richmond

Although many workshops on sickle cell anemia have been held, it is still difficult to implement a comprehensive training program for sickle cell anemia clients in many communities. Research data on the topic are somewhat nebulous and insufficient political and social pressure have been exerted to change attitudes and take action towards the…

Current Sickle Cell Screening Program for Newborns in New York City, 1979-1980.

ERIC Educational Resources Information Center

Grover, Ranjeet; And Others

1983-01-01

Screening tests indicated that 141 out of 106,565 infants examined in New York City during 1979-80, had various forms of sickle cell anemia. Follow-up of 131 patients confirmed the original diagnoses, suggesting that the New York City Follow-up Program for Sickle Cell Screening of newborns was successful. (Author/MJL)

Thrombotic thrombocytopenic purpura in a patient with sickle cell crisis.

PubMed

Bolaños-Meade, J; Keung, Y K; López-Arvizu, C; Florendo, R; Cobos, E

1999-12-01

The combination of sickle cell disease crisis and thrombotic thrombocytopenic purpura has been described only a few times. Here we present the case of a patient with a hemolytic crisis due to sickle cell disease complicated by thrombotic thrombocytopenic purpura. We also review the cases previously reported and compare and contrast them, highlighting diagnostic challenges.

Sickle cell hepatopathy.

PubMed

Bandyopadhyay, Ranjana; Bandyopadhyay, Sanjay K; Dutta, Anita

2008-01-01

Sickle cell hepatopathy is a well-documented entity that ranges from the self-limiting hepatic right upper quadrant syndrome to the potentially lethal intrahepatic cholestasis and acute hepatic sequestration syndromes. We describe a 26-year-male with homozygous sickle cell disease who had this unique hepatic presentation and was documented to have characteristic findings of cholestasis, portal inflammation and sinusoidal dilatation on histopathology.

38 CFR 1.511 - Disclosure of claimant records in connection with judicial proceedings generally.

Code of Federal Regulations, 2014 CFR

2014-07-01

... sickle cell anemia treatment records, which are protected under 38 U.S.C. 7332, where the records sought... and sickle cell anemia treatment records, which are protected under 38 U.S.C. 7332, where the records... virus and sickle cell anemia treatment, a subpoena is insufficient for such disclosure. Specific...

38 CFR 1.511 - Disclosure of claimant records in connection with judicial proceedings generally.

Code of Federal Regulations, 2011 CFR

2011-07-01

... sickle cell anemia treatment records, which are protected under 38 U.S.C. 7332, where the records sought... and sickle cell anemia treatment records, which are protected under 38 U.S.C. 7332, where the records... virus and sickle cell anemia treatment, a subpoena is insufficient for such disclosure. Specific...

38 CFR 1.511 - Disclosure of claimant records in connection with judicial proceedings generally.

Code of Federal Regulations, 2012 CFR

2012-07-01

... sickle cell anemia treatment records, which are protected under 38 U.S.C. 7332, where the records sought... and sickle cell anemia treatment records, which are protected under 38 U.S.C. 7332, where the records... virus and sickle cell anemia treatment, a subpoena is insufficient for such disclosure. Specific...

38 CFR 1.511 - Disclosure of claimant records in connection with judicial proceedings generally.

Code of Federal Regulations, 2013 CFR

2013-07-01

... sickle cell anemia treatment records, which are protected under 38 U.S.C. 7332, where the records sought... and sickle cell anemia treatment records, which are protected under 38 U.S.C. 7332, where the records... virus and sickle cell anemia treatment, a subpoena is insufficient for such disclosure. Specific...

A Review of the Literature: Use of the Health Belief Model in Sickle Cell Research

ERIC Educational Resources Information Center

Mayo-Gamble, Tilicia L.

2014-01-01

Individuals with sickle cell disease experience a life-time of morbidity as well as a decreased lifespan. Since African Americans are disproportionately affected by the disease, sickle cell contributes to growing health disparities within this population. Thus, addressing issues related to the disease presents an increased need for health…

Association between sickle cell anemia and alpha thalassemia reveals a high prevalence of the α3.7 triplication in congolese patients than in worldwide series.

PubMed

Mikobi, Tite Minga; Lukusa, Prosper Tshilobo; Aloni, Michel Ntetani; Lumaka, Aimé; Akilimali, Pierre Zalagile; Devriendt, Koenraad; Matthijs, Gert; Mbuyi Muamba, Jean-Marie; Race, Valerie

2018-01-01

Information about the association with alpha thalassemia in sickle cell patients is unknown in the Democratic Republic of Congo. There is very little data on the alpha thalassemia in patients suffering from sickle cell anemia in Central Africa, and their consequences on the clinical expression of the disease. A cross-sectional study was conducted in 106 sickle cell patients living in the country's capital Kinshasa. The diagnosis of sickle cell anemia was confirmed with a molecular test using PCR-RFLP (restriction fragment length polymorphism) technique. The diagnosis of thalassemia was performed by the technique of multiplex ligation dependent probe amplification. The mean age of our patients was 22.4±13.6 years. The α 3.7 heterozygous deletion, the α 3.7 homozygous deletion and the α 3.7 triplication were respectively encountered in 23.6%, 25.5% , and 11.3% of patients. Patients with normal αα/αα genotype represented 39.6% of the study population. The average of severe vaso-occlusive crises, the rates of blood transfusions per year, the rate of osteonecrosis, cholelithiasis and leg ulcers were significantly lower in the group of patients with α 3.7 homozygous deletion and α 3.7 triplication. The prevalence of α 3.7 triplication was higher in sickle cell patients in the Democratic Republic of Congo than in worldwide series. The α 3.7 triplication and α 3.7 homozygous deletion were associated with less severe forms of the Sickle cell anemia in Congolese patients. These results showed the need to investigate systematically the alpha-globin gene mutations in sickle cell population in Central Africa. © 2017 Wiley Periodicals, Inc.

Echocardiography in sickle cell anaemia patients under 20 years of age: a descriptive study in the Brazilian Western Amazon.

PubMed

Ribera, Melissa C V; Ribera, Ricardo B; Koifman, Rosalina J; Koifman, Sérgio

2015-01-01

Cardiac abnormalities in sickle cell anaemia are frequent and early, despite being more evident in adulthood. The study on cardiac abnormalities is essential in the current context, as, owing to improved health, children are increasingly able to reach adulthood and suffering the consequences of chronic cardiac injury. The aim of this study was to determine the prevalence of echocardiographic changes in patients under 20, suffering from sickle cell disease in Rio Branco, Brazilian Western Amazon. The descriptive epidemiological study compare two sets of children and adolescents, one including sickle cell anaemia patients (n=45), and other one (n=109) without sickle cell anaemia or heart disease. The echocardiographic measurements were indexed according to body surface using z-scores, and the prevalence of echocardiographic changes in both groups, with their respective 95% confidence intervals, ascertained and compared. Compared with the non-sickle cell anaemia series, the sickle cell anaemia group showed z-scores 13.1-fold higher for the diastolic diameter of the left ventricle, 5.2 times higher for the thickness of the posterior wall, 4.9 higher for the left atrium, 2.5 times higher for the right ventricle and 2.0 times higher for the septum thickness. Also the rate of left ventricular mass, systolic pressure of the right ventricle and the relative wall thickness were significantly higher in sickle cell anaemia set. Cardiac abnormalities were observed in 93.5% of patients. Early detection of cardiac abnormalities and quantifying them using the indexation of echocardiographic measurements according to body surface will allow proper identification and attendance of these children.

[Severe upper abdominal pain during a long distance flight].

PubMed

Bestehorn, D; Schmidt, C; Lock, G

2014-10-01

A 43-year-old woman of Ghanaian origin presented with severe upper abdominal pain starting on a long distance flight. Physical examination revealed tenderness on palpation in the left upper abdomen and flank. There was no report of pre-existing conditions or permanent medication in the medical history. Laboratory tests showed signs of haemolytic anemia and elevated inflammatory parameters. The "thick blood smear" was normal. Ultrasonography revealed an enlarged spleen (14×5 cm) with inhomogeneous parenchyma and vast, diffusely spread hypoechoic lesions in perihilar location, interpreted as extended splenic infarction. Symptom onset on a long distance flight, haemolytic anemia and extended splenic infarction led to the assumption of a vasoocclusive crisis with haemolysis. Moleculargenetic tests proved the presence of HbSC-sickle cell disease and heterozygous alpha-thalassemia. After infusion of crystalloid solution the patient was asymptomatic further on. Due to splenic infarction she received prophylactic treatment with Cefuroxim. A vaccination against pneumococci, meningococci and Haemophilus influenza B was recommended. Mild hypoxia and dehydration on a long distance flight can trigger a sickle cell crisis and may contribute to late clinical manifestation and diagnosis of sickle cell disease in some cases. Patients suffering from HbSC-sickle cell disease are at risk for the same life-threatening complications as patients with HbSS-sickle cell disease. HbSC-sickle cell disease should not be considered as a mild form of HbSS-sickle cell disease but as a separate disease with specific clinical manifestations. In contrast-enhanced ultrasonography, splenic infarction due to sickle cell crisis may markedly differ from "typical" arterial thromboembolic infarction. © Georg Thieme Verlag KG Stuttgart · New York.

[Management of sickle cells disease by households in Bamako].

PubMed

Sangho, Hamadoun; Keïta, Haoua Dembélé; Keïta, Assan Sidibé; Diarra, Fatoumata Y; Belemou, Boureyma; Dia, Amadou; Traoré, Mahamadou; Keïta, Fatoumata Danfaga; Diarra, Assa; Diakité, Baye; Diallo, Dapa; Sidibé, Toumani

2009-01-01

The sickle cell disease constitutes a major problem of public health. We find 5% to 20% of carriers of this disease in West Africa and 40% among some populations in central Africa (Congo, Zaire) and Nigeria (Beguè). In Mali prevalence is estimated to 12% with 3% for the homozygote form. It is a known disease and well documented on the scientific plan and its management is better and better codified nowadays, which contributes to the improvement of life quality. For this reason, Centre for Research and Documentation on Child Survival (CREDOS) lead this study. The aim was to assess the knowledge of the mothers for a best management of sickle cell disease in the households. We conducted a cross-sectional study with single passage realized in the households in 6 communes of Bamako district. We inquired 360 parents of children less than 5 years, according to the method of cluster sampling. The study found that 95.8% of mothers know the sickle cell disease. In addition 63.9% of the mothers didn't know the complications of the sickle cell disease and 58% the causes. In the event of discovered sickle cell disease, 58.3% of the mothers stated to want to resort to a medical structure in first intention, 18.3% with self medication and 13.9% with the traditional practitioner. In front of a sickle cell disease crisis, 56% stated to have recourse to modern medicine against 15.2% with the traditional practitioner. Household's implication in the management of the child sickle cell disease suffers a low knowledge of cause, clinical signs, and complications of this disease by the parents. For a better knowledge of this pathology by the families, information and education of the populations through messages BCC are necessary.

A Comprehensive, Ethnically Diverse Library of Sickle Cell Disease-Specific Induced Pluripotent Stem Cells.

PubMed

Park, Seonmi; Gianotti-Sommer, Andreia; Molina-Estevez, Francisco Javier; Vanuytsel, Kim; Skvir, Nick; Leung, Amy; Rozelle, Sarah S; Shaikho, Elmutaz Mohammed; Weir, Isabelle; Jiang, Zhihua; Luo, Hong-Yuan; Chui, David H K; Figueiredo, Maria Stella; Alsultan, Abdulraham; Al-Ali, Amein; Sebastiani, Paola; Steinberg, Martin H; Mostoslavsky, Gustavo; Murphy, George J

2017-04-11

Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, β-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS) mutation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Psychological therapies for sickle cell disease and pain.

PubMed

Anie, K A; Green, J

2002-01-01

Sickle cell disease comprises a group of genetic blood disorders, and occurs when the sickle haemoglobin gene is inherited from both parents. The effects of the condition are: varying degrees of anaemia which if severe reduce the capacity for mobility; predisposition to obstruction of small blood capillaries causing pain in muscle and bone known as "crises"; damage to major organs such as the spleen, liver, kidneys, and lungs; and increased vulnerability to severe infections. There are both medical and non-medical complications, and treatment is usually symptomatic and palliative in nature. Psychological intervention for individuals with sickle cell disease seems viable in complementing current medical treatment, and studies examining their efficacy appear to have also yielded encouraging results. To examine the evidence that in patients with sickle cell disease, psychological treatment improves the ability to cope with the condition. The Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references from comprehensive electronic database searches. Also, hand searching relevant journals, hand searching abstract books of conference proceedings, and searches on the Internet were performed. Date of the most recent search of the Group's specialised register: January 2001. All randomised or quasi-randomised controlled trials comparing the use of psychological intervention to no (psychological) intervention in patients with sickle cell disease. Both reviewers independently extracted data and assessed trial quality. Five studies were identified in the initial search, of which three studies, with a total of 158 patients were eligible for inclusion in the review. Published data reveal that family education and cognitive behavioural therapy can help patients cope with sickle cell disease. Patient education programmes improve knowledge and attitudes of patients with sickle cell disease. There is as yet however, insufficient evidence to demonstrate the role of other psychological therapies. This systematic review has clearly identified the need for well-designed, adequately powered, multicentre randomised controlled trials assessing the effectiveness of specific intervention in sickle cell disease.

Left ventricular myocardial performance assessed by 2-dimensional speckle tracking echocardiography in patients with sickle cell crisis.

PubMed

Sengupta, Shantanu P; Jaju, Rahul; Nugurwar, Abhijeet; Caracciolo, Giuseppe; Sengupta, Partho P

2012-01-01

The status of left ventricle in sickle cell anemia presenting in sickle crisis and follow up has been minimally studied in past. To determine the left ventricular (LV) myocardial performance in these patients, we performed the study to assess two dimensional strains imaging which allowed a rapid and an accurate analysis of global and regional LV myocardial performance in longitudinal, radial, and circumferential directions. In this prospective study, 2-dimensional echocardiography (2DE) images of the LV were obtained in 52 subjects which included 32 patients (23 ± 8yrs, 16 male) with homozygous sickle cell anemia (SCA) in sickle cell crisis and 20 healthy controls (23 ± 5 yrs, 11 male) using apical 4-chamber and parasternal short-axis at the basal, mid, and apical levels. Of these 32 patients, 2DE was performed again in 18 patients in follow up (8 months ± 5 days). Longitudinal, circumferential and radial strains (LS, CS and RS respectively) were quantified and compared in an 18-segment model using a novel speckle tracking system (2D Cardiac Performance Analysis, TomTec Imaging System, Munich, Germany). There was no significant difference in LV ejection fraction between both the groups (59.32 ± 12.6 vs. 52.3 ± 7.9; p-value > 0.05). In comparison with normal controls and follow up of sickle cell patients, peak LS was significantly attenuated in the subendocardial and subepicardial regions during sickle cell crisis (p < 0.05). However, a significant reduction in circumferential strain was evident only in subepicardial region (p < 0.001). Also patients in sickle cell crisis showed significantly higher radial strain parameters than controls (p < 0.001). Patients with SCA presenting in sickle cell crisis have reduced longitudinal shortening. LV myocardial performance remains unaltered due to relatively preserved circumferential shortening and increased radial thickening. Copyright © 2012 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

Therapeutic strategies in Sickle Cell Anemia: The past present and future.

PubMed

Fernandes, Queenie

2017-06-01

Sickle Cell Anemia (SCA) was one of the first hemoglobinopathies to be discovered. It is distinguished by the mutation-induced expression of a sickle cell variant of hemoglobin (HbS) that triggers erythrocytes to take a characteristic sickled conformation. The complex physiopathology of the disease and its associated clinical complications has initiated multi-disciplinary research within its field. This review attempts to lay emphasis on the evolution, current standpoint and future scope of therapeutic strategies in SCA. Copyright © 2017 Elsevier Inc. All rights reserved.

The lived experiences of adolescents with sickle cell disease in Kingston, Jamaica.

PubMed

Forrester, Andrea Brown; Barton-Gooden, Antoinette; Pitter, Cynthia; Lindo, Jascinth L M

2015-01-01

To explore the lived experiences of adolescents with sickle cell disease, in Kingston, Jamaica. A descriptive qualitative design was used for this research. In-depth interviews were conducted with six adolescents with sickle cell disease at a Sickle Cell Unit operated by the University of the West Indies. Interviews were audiotaped, transcribed, and thematically analyzed. The majority of the adolescents demonstrated a positive self-concept. They reported strong family, school, and peer support which made them feel accepted. All were actively engaged in social activities such as parties, but had challenges participating in sporting activities. Various coping strategies were utilized to address challenges of the disease including praying, watching television, and surfing the Internet. Sickle cell disease can be very challenging for the adolescent, but with positive self-concept and increased social support, especially from family and peers, these adolescents were able to effectively cope with their condition and live productive lives.

[Pathophysiology of sickle cell disease].

PubMed

Elion, J; Laurance, S; Lapouméroulie, C

2010-12-01

It has been 100 years since Herrick published the first medical case report of sickle cell disease. In 1949, Pauling discovered hemoglobin S (HbS). As early as the 1960-70s, emerged a coherent detailed molecular-level description of pathophysiology of sickle disease. It involved polymerization of deoxyhemoglobin S with formation of long fibers inside red blood cells (RBC) causing a distorted sickle shape and shortened lifespan. These changes constitute the basic disease process and account for hemolytic anemia and for obstructive events underlying vasoocclusive crises (VOC). However, they do not explain the mechanisms that trigger VOC. The purpose of this review is to present recent data on dehydration of sickle cell RBC, abnormalities in RBC adhesion to the vascular endothelium, the role of inflammatory events and of activation of all cells in the vessel, and abnormalities of vascular tone and carbon monoxide metabolism. These data provide new insight into the pathophysiology of the first molecular disease.

Duodenal perforation: an unusual complication of sickle cell anemia.

PubMed

Acıpayam, Can; Aldıç, Güliz; Akçora, Bülent; Çelikkaya, Mehmet Emin; Aşkar, Hasan; Dorum, Bayram Ali

2014-01-01

Duodenal perforation in childhood is a rare condition with a high mortality rate if not treated surgically. Primary gastroduodenal perforation is frequently associated with peptic ulcer and exhibits a positive family history. Helicobacter pylorus is the most significant agent. Secondary gastroduodenal perforation may be a finding of specific diseases, such as Crohn disease, or more rarely may be associated with diseases such as cystic fibrosis or sickle cell anemia. A 14-year-old boy presented with abdominal and back pain. The patient was operated on for acute abdomen and diagnosed with duodenal perforation. Helicobacter pylorus was negative. There was no risk factor to account for duodenal perforation other than sickle cell anemia. Surgical intervention was successful and without significant sequelae. Duodenal perforation is a rare entity described in patients with sickle cell anemia. To our knowledge, this is the first report of duodenal perforation in a patient sickle cell anemia.

Duodenal perforation: an unusual complication of sickle cell anemia

PubMed Central

Acıpayam, Can; Aldıç, Güliz; Akçora, Bülent; Çelikkaya, Mehmet Emin; Aşkar, Hasan; Dorum, Bayram Ali

2014-01-01

Duodenal perforation in childhood is a rare condition with a high mortality rate if not treated surgically. Primary gastroduodenal perforation is frequently associated with peptic ulcer and exhibits a positive family history. Helicobacter pylorus is the most significant agent. Secondary gastroduodenal perforation may be a finding of specific diseases, such as Crohn disease, or more rarely may be associated with diseases such as cystic fibrosis or sickle cell anemia. A 14-year-old boy presented with abdominal and back pain. The patient was operated on for acute abdomen and diagnosed with duodenal perforation. Helicobacter pylorus was negative. There was no risk factor to account for duodenal perforation other than sickle cell anemia. Surgical intervention was successful and without significant sequelae. Duodenal perforation is a rare entity described in patients with sickle cell anemia. To our knowledge, this is the first report of duodenal perforation in a patient sickle cell anemia. PMID:25422692

Microvascular oxygen consumption during sickle cell pain crisis.

PubMed

Rowley, Carol A; Ikeda, Allison K; Seidel, Miles; Anaebere, Tiffany C; Antalek, Matthew D; Seamon, Catherine; Conrey, Anna K; Mendelsohn, Laurel; Nichols, James; Gorbach, Alexander M; Kato, Gregory J; Ackerman, Hans

2014-05-15

Sickle cell disease is an inherited blood disorder characterized by chronic hemolytic anemia and episodic vaso-occlusive pain crises. Vaso-occlusion occurs when deoxygenated hemoglobin S polymerizes and erythrocytes sickle and adhere in the microvasculature, a process dependent on the concentration of hemoglobin S and the rate of deoxygenation, among other factors. We measured oxygen consumption in the thenar eminence during brachial artery occlusion in sickle cell patients and healthy individuals. Microvascular oxygen consumption was greater in sickle cell patients than in healthy individuals (median [interquartile range]; sickle cell: 0.91 [0.75-1.07] vs healthy: 0.75 [0.62-0.94] -ΔHbO2/min, P < .05) and was elevated further during acute pain crisis (crisis: 1.10 [0.78-1.30] vs recovered: 0.88 [0.76-1.03] -ΔHbO2/min, P < .05). Increased microvascular oxygen consumption during pain crisis could affect the local oxygen saturation of hemoglobin when oxygen delivery is limiting. Identifying the mechanisms of elevated oxygen consumption during pain crisis might lead to the development of new therapeutic interventions. This trial was registered at www.clinicaltrials.gov as #NCT01568710.

Imaging of musculoskeletal manifestations in sickle cell disease patients.

PubMed

Kosaraju, Vijaya; Harwani, Alok; Partovi, Sasan; Bhojwani, Nicholas; Garg, Vasant; Ayyappan, Sabarish; Kosmas, Christos; Robbin, Mark

2017-05-01

Sickle cell disease (SCD) is a hereditary red cell disorder with clinical manifestations secondary to sickling or crescent-shaped distortion of the red blood cells. Major clinical manifestations of SCD include haemolytic anaemia and vaso-occlusive phenomena resulting in ischaemic tissue injury and organ damage. Chronic sequelae of the anaemia and vaso-occlusive processes involving the musculoskeletal system include complications related to extramedullary haematopoiesis, osteonecrosis, myonecrosis and osteomyelitis. Sickle cell bone disease is one of the commonest clinical presentations. Awareness and knowledge of the imaging features related to these complications are essential for early diagnosis and prompt management. In this article, the pathophysiology and key imaging findings related to these complications are reviewed.

Beyond the Definitions of the Phenotypic Complications of Sickle Cell Disease: An Update on Management

PubMed Central

Ballas, Samir K.; Kesen, Muge R.; Goldberg, Morton F.; Lutty, Gerard A.; Dampier, Carlton; Osunkwo, Ifeyinwa; Wang, Winfred C.; Hoppe, Carolyn; Hagar, Ward; Darbari, Deepika S.; Malik, Punam

2012-01-01

The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the β globin gene resulting in the substitution of glutamic acid by valine at position 6 of the β globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes. PMID:22924029

Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management.

PubMed

Ballas, Samir K; Kesen, Muge R; Goldberg, Morton F; Lutty, Gerard A; Dampier, Carlton; Osunkwo, Ifeyinwa; Wang, Winfred C; Hoppe, Carolyn; Hagar, Ward; Darbari, Deepika S; Malik, Punam

2012-01-01

The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the β globin gene resulting in the substitution of glutamic acid by valine at position 6 of the β globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.

The effect of xanthine oxidase and hypoxanthine on the permeability of red cells from patients with sickle cell anemia.

PubMed

Al Balushi, Halima W M; Rees, David C; Brewin, John N; Hannemann, Anke; Gibson, John S

2018-03-01

Red cells from patients with sickle cell anemia (SCA) are under greater oxidative challenge than those from normal individuals. We postulated that oxidants generated by xanthine oxidase (XO) and hypoxanthine (HO) contribute to the pathogenesis of SCA through altering solute permeability. Sickling, activities of the main red cell dehydration pathways (P sickle , Gardos channel, and KCl cotransporter [KCC]), and cell volume were measured at 100, 30, and 0 mmHg O 2 , together with deoxygenation-induced nonelectrolyte hemolysis. Unexpectedly, XO/HO mixtures had mainly inhibitory effects on sickling, P sickle , and Gardos channel activities, while KCC activity and nonelectrolyte hemolysis were increased. Gardos channel activity was significantly elevated in red cells pharmacologically loaded with Ca 2+ using the ionophore A23187, consistent with an effect on the transport system per se as well as via Ca 2+ entry likely via the P sickle pathway. KCC activity is controlled by several pairs of conjugate protein kinases and phosphatases. Its activity, however, was also stimulated by XO/HO mixtures in red cells pretreated with N-ethylmaleimide (NEM), which is thought to prevent regulation via changes in protein phosphorylation, suggesting that the oxidants formed could also have direct effects on this transporter. In the presence of XO/HO, red cell volume was better maintained in deoxygenated red cells. Overall, the most notable effect of XO/HO mixtures was an increase in red cell fragility. These findings increase our understanding of the effects of oxidative challenge in SCA patients and are relevant to the behavior of red cells in vivo. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Let's Talk about the Needs of African American Children with Sickle Cell Disease: A Recognized "Other Health Impairment."

ERIC Educational Resources Information Center

Dooley, Elizabeth A.; Perkins, Nechelle

Children who inherit sickle cell disease, primarily African Americans and Hispanics, are at risk for serious medical conditions and require special care both at home and in school. Sickle cell disease is recognized as an "Other Health Impairment" and identified students may be eligible for special education services under the Individuals…

76 FR 6694 - Disclosure of Medical Information to the Surrogate of a Patient Who Lacks Decision-Making Capacity

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-08

... virus, or sickle cell anemia, without first obtaining the written consent of the patient. 38 U.S.C. 7332... virus, or sickle cell anemia in VA records and are applicable in combination with other regulations..., infection with the human immunodeficiency virus, or sickle cell anemia to a surrogate of the patient who is...

[Hydrocholecystis, unrecognized cause of painful abdominal crises in patients with sickle cell anemia].

PubMed

Cabrol, S; Desjardin, F; Baruchel, S; Bégué, P; Cordier, M D; Lasfargues, G

1985-12-01

The first case of painful abdominal crisis caused by hydrops of the gallbladder during sickle cell disease is reported. The cholecystosonography allowed diagnosis and supervision in a 4 year-old black boy with sickle cell anemia. The persistence of hydrops led to cholecystectomy. Pathophysiology is discussed according to the other etiologies reported in the literature.

Evaluating the Use of Ketamine for Pain Control With Sickle Cell Crisis in Pregnancy: A Report of 2 Cases.

PubMed

Gimovsky, Alexis C; Fritton, Kate; Viscusi, Eugene; Roman, Amanda

2018-01-01

Sickle cell crises occur frequently during pregnancy and are difficult to treat, even with high-dose opioids. Analgesia with ketamine has been suggested as an alternative, but its use during pregnancy is underreported. Two pregnant patients with uncontrolled sickle cell pain were treated with ketamine. Patient A reported no decrease in her pain, but her opioid requirements decreased. Patient B's pain resolved during ketamine administration. No serious maternal or neonatal adverse effects occurred. Ketamine may be considered as an adjunct analgesic in pregnant patients with sickle cell pain, although prospective clinical data are needed to fully assess its efficacy.

Coexistence of sickle cell disease and severe congenital neutropenia: first impressions can be deceiving.

PubMed

Wali, Yasser; Beshlawi, Ismail; Fawaz, Naglaa; Alkhayat, Aisha; Zalabany, Mahmoud; Elshinawy, Mohamed; Al-Kindi, Salam; Al-Rawas, Abdul Hakim A; Klein, Christoph

2012-09-01

We report an Omani family in whom the propositus had a rare coexistence of sickle cell disease and severe congenital neutropenia associated with a mutation in ELANE. In contrast to his siblings with sickle cell disease, the severity of HbSS-associated complications such as painful crises and acute chest syndrome was significantly reduced. His course of the disease had markedly worsened after initiating G-CSF therapy. These clinical observations suggest that neutropenia may ameliorate inflammatory responses and thus display a modulating factor with respect to the clinical course of sickle cell disease. © 2012 John Wiley & Sons A/S.

Use of Social Support during Communication about Sickle Cell Carrier Status

PubMed Central

Bradford, Lisa; Roedl, Sara J.; Christopher, Stephanie A.; Farrell, Michael H.

2012-01-01

Objective To examine the use of social support behaviors by primary care providers during delivery of positive newborn screening results for Sickle Cell Anemia carrier status. Methods Transcripts from 125 primary care providers who conveyed Sickle Cell Anemia carrier status to standardized parents were content analyzed using categories derived from Cutrona and Suhr’s social support taxonomy. Frequencies and cross-tabulation matrices were calculated to study providers’ social support utilization. Results Results showed most primary care providers (80%) incorporate social support behaviors into delivery of Sickle Cell Anemia carrier results and most frequently employed social network (61.6%) and informational support (38.4%) behaviors. Providers used tangible aid (8%), esteem (1.6%), and emotional support (9.6%) behaviors less frequently. Conclusion Cutrona and Suhr’s taxonomy may be a useful tool for assessing supportive communication during the delivery of Sickle Cell Anemia carrier status and could be incorporated into population scale assessments of communication quality assurance. Practice Implications Primary care providers may need training in how to adapt supportive behaviors to parents’ needs during communication of Sickle Cell Anemia carrier status. They also may benefit from specific training about how to use esteem and emotional support. PMID:22658247

Spontaneous extradural and subgaleal hematoma: A rare neurosurgical crisis of sickle cell disease

PubMed Central

Mishra, Sudhansu S.; Senapati, Satya B.; Gouda, Amiya K.; Behera, Sanjay K.; Patnaik, Ashis

2017-01-01

Extradural hematoma (EDH) in absence of trauma is a rare entity with only few cases reported in literature. The various causes reported include: Vascular malformation of dura, coagulopathies, sinus infection, middle ear or orbital infection, and tumor. Occurrence of spontaneous EDH as a complication of sickle cell disease is even much rarer. We report a case with sickle cell disease who presented with spontaneous extradural and subgaleal hematomas following an episode of vaso-oclusive crisis. He was managed successfully with surgery. The association of epidural hematomas in sickling hemoglobinopathies is reviewed. In all cases, we noticed one episode of sickle cell crisis just before the occurrence of spontaneous EDH. Perhaps this crisis puts an extra demand over the hematopoietic skull tissue disrupting inner and outer skull margins leading to spontaneous EDH and subgaleal hematoma. PMID:28413532

The endothelin B receptor plays a crucial role in the adhesion of neutrophils to the endothelium in sickle cell disease

PubMed Central

Koehl, Bérengère; Nivoit, Pierre; El Nemer, Wassim; Lenoir, Olivia; Hermand, Patricia; Pereira, Catia; Brousse, Valentine; Guyonnet, Léa; Ghinatti, Giulia; Benkerrou, Malika; Colin, Yves; Le Van Kim, Caroline; Tharaux, Pierre-Louis

2017-01-01

Although the primary origin of sickle cell disease is a hemoglobin disorder, many types of cells contribute considerably to the pathophysiology of the disease. The adhesion of neutrophils to activated endothelium is critical in the pathophysiology of sickle cell disease and targeting neutrophils and their interactions with endothelium represents an important opportunity for the development of new therapeutics. We focused on endothelin-1, a mediator involved in neutrophil activation and recruitment in tissues, and investigated the involvement of the endothelin receptors in the interaction of neutrophils with endothelial cells. We used fluorescence intravital microscopy analyses of the microcirculation in sickle mice and quantitative microfluidic fluorescence microscopy of human blood. Both experiments on the mouse model and patients indicate that blocking endothelin receptors, particularly ETB receptor, strongly influences neutrophil recruitment under inflammatory conditions in sickle cell disease. We show that human neutrophils have functional ETB receptors with calcium signaling capability, leading to increased adhesion to the endothelium through effects on both endothelial cells and neutrophils. Intact ETB function was found to be required for tumor necrosis factor α-dependent upregulation of CD11b on neutrophils. Furthermore, we confirmed that human neutrophils synthesize endothelin-1, which may be involved in autocrine and paracrine pathophysiological actions. Thus, the endothelin-ETB axis should be considered as a cytokine-like potent pro-inflammatory pathway in sickle cell disease. Blockade of endothelin receptors, including ETB, may provide major benefits for preventing or treating vaso-occlusive crises in sickle cell patients. PMID:28385784

Attitudes and beliefs of sports medicine providers to sickle cell trait screening of student athletes.

PubMed

Acharya, Kruti; Benjamin, Holly J; Clayton, Ellen W; Ross, Lainie F

2011-11-01

To describe the attitudes of members of the American Medical Society for Sports Medicine (AMSSM) toward the new National Collegiate Athletic Association (NCAA) policy to require all Division I student athletes be screened for sickle cell trait (SCT), have prior evidence of testing, or sign a waiver. Cross-sectional survey of members of the AMSSM electronic mailing list was conducted. Descriptive, McNemar, and χ2 statistics were performed. Internet survey. Of the 1765 AMSSM e-mail list members, 370 returned partial or completed surveys. Dependent variables included familiarity with the NCAA policy, support of universal or targeted screening programs, preferences regarding screening methodologies, and athletic restrictions or modifications for student athletes identified with SCT. Respondents' gender, race/ethnicity, and involvement as an NCAA team physician were independent variables. Of the respondents, 76% were men, 85% were whites, and 53% served as NCAA Division I team physicians. Ninety percent were aware of the policy. There was greater support for targeted (76%, 267 of 353) compared with universal (39%, 137 of 353; P < 0.01) screening, with targeting based on race/ethnicity and sport. Respondents supported targeted screening of varsity and freshman athletes in all NCAA divisions, but most (88%) also supported waivers. Respondents favored using existing medical records (73%) or Sickledex screening (71%) methodologies despite concerns about inaccuracies (16% for each methodology). Most respondents agreed that there is discrimination in athletic participation and obtaining insurance. There is lack of consensus within the AMSSM regarding the current NCAA SCT screening policy. Implementation must take into consideration potential discrimination.

Relationships between sickle cell trait, malaria, and educational outcomes in Tanzania.

PubMed

Croke, Kevin; Ishengoma, Deus S; Francis, Filbert; Makani, Julie; Kamugisha, Mathias L; Lusingu, John; Lemnge, Martha; Larreguy, Horacio; Fink, Günther; Mmbando, Bruno P

2017-08-15

Sickle Cell Trait (SCT) has been shown to be protective against malaria. A growing literature suggests that malaria exposure can reduce educational attainment. This study assessed the relationship and interactions between malaria, SCT and educational attainment in north-eastern Tanzania. Seven hundred sixty seven children were selected from a list of individuals screened for SCT. Febrile illness and malaria incidence were monitored from January 2006 to December 2013 by community health workers. Education outcomes were extracted from the Korogwe Health and Demographic Surveillance system in 2015. The primary independent variables were malaria and SCT. The association between SCT and the number of fever and malaria episodes from 2006 to 2013 was analyzed. Main outcomes of interest were school enrolment and educational attainment in 2015. SCT was not associated with school enrolment (adjusted OR 1.42, 95% CI [0.593,3.412]) or highest grade attained (adjusted grade difference 0.0597, 95% CI [-0.567, 0.686]). SCT was associated with a 29% reduction in malaria incidence (adjusted IRR 0.71, 95% CI [0.526, 0.959]) but not with fever incidence (adjusted IRR 0.905, 95% CI [0.709-1.154]). In subgroup analysis of individuals with SCT, malaria exposure was associated with reduced school enrollment (adjusted OR 0.431, 95% CI [0.212, 0.877]). SCT appears to reduce incidence of malaria. Overall, children with SCT do not appear to attend more years of school; however children who get malaria despite SCT appear to have lower levels of enrolment in education than their peers.

Basal cell adhesion molecule/lutheran protein. The receptor critical for sickle cell adhesion to laminin.

PubMed Central

Udani, M; Zen, Q; Cottman, M; Leonard, N; Jefferson, S; Daymont, C; Truskey, G; Telen, M J

1998-01-01

Sickle red cells bind significant amounts of soluble laminin, whereas normal red cells do not. Solid phase assays demonstrate that B-CAM/LU binds laminin on intact sickle red cells and that red cell B-CAM/LU binds immobilized laminin, whereas another putative laminin binding protein, CD44, does not. Ligand blots also identify B-CAM/LU as the only erythrocyte membrane protein(s) that binds laminin. Finally, transfection of murine erythroleukemia cells with human B-CAM cDNA induces binding of both soluble and immobilized laminin. Thus, B-CAM/LU appears to be the major laminin-binding protein of sickle red cells. Previously reported overexpression of B-CAM/LU by epithelial cancer cells suggests that this protein may also serve as a laminin receptor in malignant tumors. PMID:9616226

Implementation of Indigenous Electronic Medical Record System to Facilitate Care of Sickle Cell Disease Patients in Chhattisgarh.

PubMed

Choubey, Mona; Mishra, Hrishikesh; Soni, Khushboo; Patra, Pradeep Kumar

2016-02-01

Sickle cell disease (SCD) is prevalent in central India including Chhattisgarh. Screening for SCD is being carried out by Government of Chhattisgarh. Electronic Medical Record (EMR) system was developed and implemented in two phases. Aim was to use informatics techniques and indigenously develop EMR system to improve the care of SCD patients in Chhattisgarh. EMR systems had to be developed to store and manage: i) huge data generated through state wide screening for SCD; ii) clinical data for SCD patients attending the outpatient department (OPD) of institute. 'State Wide Screening Data Interface' (SWSDI) was designed and implemented for storing and managing data generated through screening program. Further, 'Sickle Cell Patients Temporal Data Management System' (SCPTDMS) was developed and implemented for storing, managing and analysing sickle cell disease patients' data at OPD. Both systems were developed using VB.Net and MS SQL Server 2012. Till April 2015, SWSDI has data of 1294558 persons, out of which 121819 and 4087 persons are carriers and patients of sickle cell disease respectively. Similarly till June 2015, SCPTDMS has data of 3760 persons, of which 923 are sickle cell disease patients (SS) and 1355 are sickle cell carriers (AS). Both systems are proving to be useful in efficient storage, management and analysis of data for clinical and research purposes. The systems are an example of beneficial usage of medical informatics solutions for managing large data at community level.

Haptoglobin gene polymorphisms and interleukin-6 and -8 levels in patients with sickle cell anemia

PubMed Central

Pierrot-Gallo, Bruna Spinella; Vicari, Perla; Matsuda, Sandra Satiko; Adegoke, Samuel Ademola; Mecabo, Grazielle; Figueiredo, Maria Stella

2015-01-01

Background Haptoglobin genotypes, and interleukin-6 and -8 participate in the pathophysiology of sickle cell anemia. The expression of cytokines is regulated by genetic mechanisms however the effect of haptoglobin polymorphisms on these cytokines is not fully understood. This study aimed to compare the frequency of haptoglobin genotypes and the interleukin-6 and -8 concentrations in sickle cell anemia patients and controls to investigate the association between haptoglobin genotypes and cytokine levels. Methods Sixty sickle cell anemia patients and 74 healthy individuals were analyzed. Haptoglobin genotypes were determined by multiplex polymerase chain reaction, and the interleukin-6 and -8 levels by enzyme linked immunosorbent assay. The association between haptoglobin genotypes and cytokines was investigated by statistical tests. Results Hp2-1 was the most common genotype in both the cases and controls while Hp1-1 was less frequent among sickle cell anemia patients. Interleukin-6 and -8 levels were higher in patients than controls (p-value <0.0001). There was no significant difference in interleukin-6 and -8 concentrations between the genotypes (p-value >0.05). A similar trend was observed among the controls. Conclusion Although, levels of interleukin-6 and -8 were higher in the sickle cell anemia patients, they appeared not to be related to the haptoglobin genotypes. Further investigations are necessary to identify factors responsible for increased secretion of the interleukin-6 and -8 pro-inflammatory cytokines in patients with sickle cell anemia. PMID:26408368

CDC Grand Rounds: Improving the Lives of Persons with Sickle Cell Disease.

PubMed

Hulihan, Mary; Hassell, Kathryn L; Raphael, Jean L; Smith-Whitley, Kim; Thorpe, Phoebe

2017-11-24

Approximately 100,000 Americans have sickle cell disease (SCD), a group of recessively inherited red blood cell disorders characterized by abnormal hemoglobin, called hemoglobin S or sickle hemoglobin, in the red blood cells. Persons with hemoglobin SS or hemoglobin Sß 0 thalassemia, also known as sickle cell anemia (SCA), have the most severe form of SCD. Hemoglobin SC disease and hemoglobin Sß + thalassemia are other common forms of SCD. Red blood cells that contain sickle hemoglobin are inflexible and can stick to vessel walls, causing a blockage that slows or stops blood flow. When this happens, oxygen cannot reach nearby tissues, leading to attacks of sudden, severe pain, called pain crises, which are the clinical hallmark of SCD. The red cell sickling and poor oxygen delivery can also cause damage to the brain, spleen, eyes, lungs, liver, and multiple other organs and organ systems. These chronic complications can lead to increased morbidity, early mortality, or both. Tremendous strides in treating and preventing the complications of SCD have extended life expectancy. Now, nearly 95% of persons born with SCD in the United States reach age 18 years (1); however, adults with the most severe forms of SCD have a life span that is 20-30 years shorter than that of persons without SCD (2).

USP38, FREM3, SDC1, DDC, and LOC727982 Gene Polymorphisms and Differential Susceptibility to Severe Malaria in Tanzania.

PubMed

Manjurano, Alphaxard; Sepúlveda, Nuno; Nadjm, Behzad; Mtove, George; Wangai, Hannah; Maxwell, Caroline; Olomi, Raimos; Reyburn, Hugh; Drakeley, Christopher J; Riley, Eleanor M; Clark, Taane G

2015-10-01

Populations exposed to Plasmodium falciparum infection develop genetic mechanisms of protection against severe malarial disease. Despite decades of genetic epidemiological research, the sickle cell trait (HbAS) sickle cell polymorphism, ABO blood group, and other hemoglobinopathies remain the few major determinants in severe malaria to be replicated across different African populations and study designs. Within a case-control study in a region of high transmission in Tanzania (n = 983), we investigated the role of 40 new loci identified in recent genome-wide studies. In 32 loci passing quality control procedures, we found polymorphisms in USP38, FREM3, SDC1, DDC, and LOC727982 genes to be putatively associated with differential susceptibility to severe malaria. Established candidates explained 7.4% of variation in severe malaria risk (HbAS polymorphism, 6.3%; α-thalassemia, 0.3%; ABO group, 0.3%; and glucose-6-phosphate dehydrogenase deficiency, 0.5%) and the new polymorphisms, another 4.3%. The regions encompassing the loci identified are promising targets for the design of future treatment and control interventions. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Exchange and simple transfusion in sickle-cell diseases in pregnancy

PubMed Central

Buckle, A. E. R.; Price, T. M. L.; Whitmore, D. N.

1969-01-01

The management of sickle-cell crisis in a pregnant patient by exchange transfusion is described, the procedure leading to immediate and dramatic improvement in the condition. Partial exchange transfusion in three other patients with sickle-cell anaemia, judged by episodes of crisis in previous pregnancies to be at particular risk, is also reported and the value of this method of management discussed. PMID:5359314

Early Detection of Breast Cancer via Multiplane Correlation Breast Imaging

DTIC Science & Technology

2007-04-01

thalassemia and sickle cell anemia) and Wilson’s disease (liver copper overload), are characterized by increased iron and copper concentration respectively...iron overload associated with thalassemia and sickle cell anemia) and Wilson’s disease (liver copper overload) are both characterized by increased...element concentration in the liver [4]. Patients suffering from thalassemia and sickle cell anemia often require weekly blood transfusions. With each

Predictors of osteoclast activity in patients with sickle cell disease

PubMed Central

Nouraie, Mehdi; Cheng, Kevin; Niu, Xiaomei; Moore-King, Evadne; Fadojutimi-Akinsi, Margaret F.; Minniti, Caterina P.; Sable, Craig; Rana, Sohail; Dham, Niti; Campbell, Andrew; Ensing, Gregory; Kato, Gregory J.; Gladwin, Mark T.; Castro, Oswaldo L.; Gordeuk, Victor R.

2011-01-01

Background Bone changes are common in sickle cell disease, but the pathogenesis is not fully understood. Tartrate-resistant acid phosphatase (TRACP) type 5b is produced by bone-resorbing osteoclasts. In other forms of hemolytic anemia, increased iron stores are associated with osteoporosis. We hypothesized that transfusional iron overload would be associated with increased osteoclast activity in patients with sickle cell disease. Design and Methods We examined tartrate-resistant acid phosphatase 5b concentrations in patients with sickle cell disease and normal controls of similar age and sex distribution at steady state. Serum tartrate-resistant acid phosphatase 5b concentration was measured using an immunocapture enzyme assay and plasma concentrations of other cytokines were assayed using the Bio-Plex suspension array system. Tricuspid regurgitation velocity, an indirect measure of systolic pulmonary artery pressure, was determined by echocardiography. Results Tartrate-resistant acid phosphatase 5b concentrations were higher in 58 adults with sickle cell disease than in 22 controls (medians of 4.4 versus 2.4 U/L, respectively; P=0.0001). Among the patients with sickle cell disease, tartrate-resistant acid phosphatase 5b independently correlated with blood urea nitrogen (standardized beta=0.40, P=0.003), interleukin-8 (standardized beta=0.30, P=0.020), and chemokine C-C motif ligand 5 (standardized beta=−0.28, P=0.031) concentrations, but not with serum ferritin concentration. Frequent blood transfusions (>10 units in life time) were not associated with higher tartrate-resistant acid phosphatase 5b levels in multivariate analysis. There were strong correlations among tartrate-resistant acid phosphatase 5b, alkaline phosphatase and tricuspid regurgitation velocity (r>0.35, P<0.001). Conclusions Patients with sickle cell disease have increased osteoclast activity as reflected by serum tartrate-resistant acid phosphatase 5b concentrations. Our results may support a potential role of inflammation rather than increased iron stores in stimulating osteoclast activity in sickle cell disease. The positive relationships among tartrate-resistant acid phosphatase 5b, alkaline phosphatase and tricuspid regurgitation velocity raise the possibility of a common pathway in the pulmonary and bone complications of sickle cell disease. PMID:21546502

Hydroxycarbamine: from an Old Drug Used in Malignant Hemopathies to a Current Standard in Sickle Cell Disease

PubMed Central

Cannas, Giovanna; Poutrel, Solène; Thomas, Xavier

2017-01-01

While hydroxycarbamide (hydroxyurea, HU) has less and fewer indications in malignant hemopathies, it represents the only widely used drug which modifies sickle cell disease pathogenesis. Clinical experience with HU for patients with sickle cell disease has been accumulated over the past 25 years in Western countries. The review of the literature provides increasing support for safety and efficacy in both children and adults for reducing acute vaso-occlusive events including pain episodes and acute chest syndrome. No increased incidence of leukemia and teratogenicity was demonstrated. HU has become the standard-of-care for sickle cell anemia but remains underused. Barriers to its use should be identified and overcome. PMID:28293403

Idiopathic intracranial hypertension and sickle cell disease: two case reports.

PubMed

Segal, Laura; Discepola, Marino

2005-12-01

Two patients with sickle cell disease presented with headaches and visual disturbances, typical complaints of this disorder. However, prompt diagnosis of idiopathic intracranial hypertension and initiation of medical therapy lead to improved symptoms and restored vision. Ophthalmologists should consider sickle cell disease to be an independent risk factor for idiopathic intracranial hypertension when a patient is being assessed for visual disturbances. Although a rare condition, idiopathic intracranial hypertension has several key signs useful in establishing a diagnosis. It is critical to recognize the warning signs and symptoms to prevent devastating ophthalmologic complications. We report the first cases of idiopathic intracranial hypertension in patients with the novel Quebec-Chori beta-chain variant of sickle cell disease.

Bilateral orbital bone infarction in sickle-cell disease.

PubMed

Ghafouri, Roya H; Lee, Irene; Freitag, Suzanne K; Pira, Tony N

2011-01-01

This is a case of a 2-year-old boy with sickle cell disease who presented with bilateral eyelid swelling, limited extraocular motility, and lateral subperiosteal fluid collection associated with bilateral lateral orbital wall infarctions on MRI. The patient was managed medically with intravenous fluids, analgesics, broad-spectrum antibiotics, systemic steroids, and clinically improved. Patients with sickle cell disease are susceptible to infarction of the orbital bones during vaso-occlusive crises. Orbital wall infarction can lead to acute proptosis and restricted extraocular motility. Orbital wall infarction should be considered in sickle cell patients with orbital diseases so that appropriate treatment can be instituted promptly to prevent the serious sequelae of orbital compression syndrome.

Cerebral vasculopathy in children with sickle cell anemia.

PubMed

Fasano, Ross M; Meier, Emily R; Hulbert, Monica L

2015-01-01

Sickle cell anemia (SCA)-associated cerebral vasculopathy and moyamoya is a unique entity reflecting the abnormal interactions between sickled red blood cells (RBCs) and the cerebral arterial endothelium. Endothelial injury, coagulation activation, and the inflammatory response generated by sickled RBCs are implicated in the development of cerebral vasculopathy, but the pathophysiology remains incompletely understood. SCA-specific screening and treatment guidelines have successfully reduced the incidence of overt strokes in this high-risk population. However, despite aggressive hematological management, many children with cerebral vasculopathy due to SCA have progressive vasculopathy and recurrent strokes; therefore, more effective therapies, such as revascularization surgery and curative hematopoietic stem cell transplant, are urgently needed. Copyright © 2014 Elsevier Inc. All rights reserved.

Fetal hemoglobin in sickle cell anemia: The Arab-Indian haplotype and new therapeutic agents.

PubMed

Habara, Alawi H; Shaikho, Elmutaz M; Steinberg, Martin H

2017-11-01

Fetal hemoglobin (HbF) has well-known tempering effects on the symptoms of sickle cell disease and its levels vary among patients with different haplotypes of the sickle hemoglobin gene. Compared with sickle cell anemia haplotypes found in patients of African descent, HbF levels in Saudi and Indian patients with the Arab-Indian (AI) haplotype exceed that in any other haplotype by nearly twofold. Genetic association studies have identified some loci associated with high HbF in the AI haplotype but these observations require functional confirmation. Saudi patients with the Benin haplotype have HbF levels almost twice as high as African patients with this haplotype but this difference is unexplained. Hydroxyurea is still the only FDA approved drug for HbF induction in sickle cell disease. While most patients treated with hydroxyurea have an increase in HbF and some clinical improvement, 10 to 20% of adults show little response to this agent. We review the genetic basis of HbF regulation focusing on sickle cell anemia in Saudi Arabia and discuss new drugs that can induce increased levels of HbF. © 2017 Wiley Periodicals, Inc.

Effects of Cyanate and 2,3-Diphosphoglycerate on Sickling RELATIONSHIP TO OXYGENATION

PubMed Central

Jensen, Michael; Bunn, H. Franklin; Halikas, George; Kan, Yuet Wai; Nathan, David G.

1973-01-01

Cyanate and 2,3-diphosphoglycerate (2,3-DPG) both influence the oxygen affinity of hemoglobin. The studies presented here concern the effects of these compounds on the sickling phenomenon. The inhibitory effect of cyanate on sickling is largely due to the fact that it increases the percentage of oxyhemoglobin S at a given oxygen tension. In addition, cyanate inhibits sickling by a mechanism that is independent of oxygenation. In this paper, we have demonstrated that the viscosity of carbamylated sickle blood was lower than that of non-carbamylated controls at the same oxygen saturation. Furthermore, carbamylation resulted in an increase in the minimum concentration of deoxy-sickle hemoglobin required for gelation. Like cyanate, 2,3-DPG affected sickling of intact erythrocytes by two mechanisms. Since 2,3-DPG decreases the percentage of oxyhemoglobin S at a given oxygen tension, sickling is enhanced. In addition, 2,3-DPG had a direct effect. When the intracellular 2,3-DPG concentration was increased in vitro, a greater percentage of cells were sickled at a given oxygen saturation. Conversely, sickling was inhibited in cells in which 2,3-DPG was artificially lowered. These data indicate that the enhancement of sickling by 2,3-DPG is in part independent of its influence on oxygen affinity. PMID:4729047

Effects of nitric oxide and its congeners on sickle red blood cell deformability.

PubMed

Belanger, Andrea M; Keggi, Christian; Kanias, Tamir; Gladwin, Mark T; Kim-Shapiro, Daniel B

2015-10-01

Sickle cell disease (SCD) is characterized by hemoglobin polymerization upon deoxygenation. Polymerization causes the sickle cells to become rigid and misshapen (sickling). Red blood cell (RBC) dehydration greatly increases polymerization. Cycles of sickling and unsickling cause an influx of calcium that leads to loss of potassium via the calcium-activated Gardos channel, which dehydrates the cells leading to increased polymerization. In this study the effects of nitric oxide (NO) and its congeners on RBC deformability were examined, focusing on sickle RBCs (sRBCs). RBCs from patients with SCD and from nonpatients were exposed to various compounds that release NO or its congeners. Intracellular calcium was increased using a calcium ionophore or cycling of oxygen tension for sRBCs. Deformability was measured by laser-assisted osmotic gradient ektacytometry. Consistent with a previous report, sodium nitroprusside (SNP) was found to protect against calcium-induced loss of deformability in normal RBCs, but (contrary to some previous reports) no effect of any NO donors was observed when calcium influx was not induced. Importantly, in studies of deoxygenation-induced dehydration of sRBCs, SNP resulted in substantial improvements in deformability (p = 0.036) and hydration (p = 0.024). Sodium nitrite showed similar trends. SNP was shown to have no effect on calcium influx, but reduced potassium efflux. These data suggest that SNP and perhaps certain nitrogen oxides (like nitrite) inhibit the Gardos channel and may be able to protect sickle cells from dehydration and thereby improve outcome in the disease. © 2015 AABB.

Day case management of sickle pain: 3 years experience in a UK sickle cell unit.

PubMed

Wright, J; Bareford, D; Wright, C; Augustine, G; Olley, K; Musamadi, L; Dhanda, C; Knight, C

2004-09-01

A day centre was established to determine whether an alternative approach to the management of uncomplicated sickle pain would improve the quality of care and reduce hospital admissions in patients with sickle cell disease. Since the centre opened there has been a 43% decrease in hospital admissions and 49% decrease in occupied bed days. In the third year, 84% of patients treated for severe sickle pain were managed without the need for hospital admission. A centre offering day case management of painful crisis reduced unnecessary hospital admissions for uncomplicated pain. This approach is safe and cost-effective.

Quantifying the abnormal hemodynamics of sickle cell anemia

NASA Astrophysics Data System (ADS)

Lei, Huan; Karniadakis, George

2012-02-01

Sickle red blood cells (SS-RBC) exhibit heterogeneous morphologies and abnormal hemodynamics in deoxygenated states. A multi-scale model for SS-RBC is developed based on the Dissipative Particle Dynamics (DPD) method. Different cell morphologies (sickle, granular, elongated shapes) typically observed in deoxygenated states are constructed and quantified by the Asphericity and Elliptical shape factors. The hemodynamics of SS-RBC suspensions is studied in both shear and pipe flow systems. The flow resistance obtained from both systems exhibits a larger value than the healthy blood flow due to the abnormal cell properties. Moreover, SS-RBCs exhibit abnormal adhesive interactions with both the vessel endothelium cells and the leukocytes. The effect of the abnormal adhesive interactions on the hemodynamics of sickle blood is investigated using the current model. It is found that both the SS-RBC - endothelium and the SS-RBC - leukocytes interactions, can potentially trigger the vicious ``sickling and entrapment'' cycles, resulting in vaso-occlusion phenomena widely observed in micro-circulation experiments.

Salmonella pyomyositis complicating sickle cell anemia: a case report

PubMed Central

2010-01-01

Introduction Pyomyositis is a bacterial infection of skeletal muscle and a rare complication of sickle cell anemia. It may present a difficult problem in diagnosis, leading to delay in appropriate treatment and development of complications including abscess formation and osteomyelitis. Case presentation We report the case of a 44-year-old Afro-Caribbean woman with homozygous sickle cell disease who presented with chest crisis and later developed pyomyositis of her hip and pelvic muscles. Salmonella agbeni was isolated from blood cultures and magnetic resonance imaging confirmed the diagnosis in this case. It is noteworthy of this case that there were no antecedent signs of gastroenteritis. Drainage was not appropriate and she was treated with intravenous antibiotics for six weeks. Conclusions Focal Salmonella infections are uncommon in soft tissue. Pyomyositis should be considered in patients with sickle cell anemia that continue to have muscle pain and high fevers, despite initial management of their sickle cell crisis. Radiological imaging, particularly magnetic resonance imaging, is a crucial tool in establishing the diagnosis. PMID:20591146

Craniofacial bone abnormalities and malocclusion in individuals with sickle cell anemia: a critical review of the literature

PubMed Central

Costa, Cyrene Piazera Silva; de Carvalho, Halinna Larissa Cruz Correia; Thomaz, Erika Bárbara Abreu Fonseca; Sousa, Soraia de Fátima Carvalho

2012-01-01

This study aims to critically review the literature in respect to craniofacial bone abnormalities and malocclusion in sickle cell anemia individuals. The Bireme and Pubmed electronic databases were searched using the following keywords: malocclusion, maxillofacial abnormalities, and Angle Class I, Class II and lass III malocclusions combined with sickle cell anemia. The search was limited to publications in English, Spanish or Portuguese with review articles and clinical cases being excluded from this study. Ten scientific publications were identified, of which three were not included as they were review articles. There was a consistent observation of orthodontic and orthopedic variations associated with sickle cell anemia, especially maxillary protrusions. However, convenience sampling, sometimes without any control group, and the lack of estimates of association and hypotheses testing undermined the possibility of causal inferences. It was concluded that despite the high frequency of craniofacial bone abnormalities and malocclusion among patients with sickle cell anemia, there is insufficient scientific proof that this disease causes malocclusion PMID:23049386

Hydroxyurea therapy of a murine model of sickle cell anemia inhibits the progression of pneumococcal disease by down-modulating E-selectin

PubMed Central

Lebensburger, Jeffrey D.; Howard, Thad; Hu, Yunming; Pestina, Tamara I.; Gao, Geli; Johnson, Melissa; Zakharenko, Stanislav S.; Ware, Russell E.; Tuomanen, Elaine I.; Persons, Derek A.

2012-01-01

Sickle cell anemia is characterized by chronic hemolysis coupled with extensive vascular inflammation. This inflammatory state also mechanistically promotes a high risk of lethal, invasive pneumococcal infection. Current treatments to reduce vaso-occlusive complications include chronic hydroxyurea therapy to induce fetal hemoglobin. Because hydroxyurea also reduces leukocytosis, an understanding of the impact of this treatment on pneumococcal pathogenesis is needed. Using a sickle cell mouse model of pneumococcal pneumonia and sepsis, administration of hydroxyurea was found to significantly improve survival. Hydroxyurea treatment decreased neutrophil extravasation into the infected lung coincident with significantly reduced levels of E-selectin in serum and on pulmonary epithelia. The protective effect of hydroxyurea was abrogated in mice deficient in E-selectin. The decrease in E-selectin levels was also evident in human sickle cell patients receiving hydroxyurea therapy. These data indicate that in addition to induction of fetal hemoglobin, hydroxyurea attenuates leukocyte–endothelial interactions in sickle cell anemia, resulting in protection against lethal pneumococcal sepsis. PMID:22130804

Sickle cell crisis and pregnancy.

PubMed

Parrish, Marc R; Morrison, John C

2013-08-01

Pregnant women with sickle cell disease appear to be more likely to experience antepartum, intrapartum, and postpartum complications when compared with unaffected women. Access to high-risk obstetric care, patient education, and close follow-up is important to minimize maternal morbidity and mortality. A high index of suspicion and good diagnostic acumen is necessary to obtain optimal results in the pregnant patient affected by sickle cell crisis. Copyright © 2013. Published by Elsevier Inc.

Solenostemon monostachyus, Ipomoea involucrata and Carica papaya seed oil versus Glutathione, or Vernonia amygdalina: Methanolic extracts of novel plants for the management of sickle cell anemia disease

PubMed Central

2012-01-01

Background Sickle cell disease (SCD) is a genetic disease caused by an individual inheriting an allele for sickle cell hemoglobin from both parents and is associated with unusually large numbers of immature blood cells, containing many long, thin, crescent-shaped erythrocytes. It is a disease prevalent throughout many populations. The use of medicinal plants and nutrition in managing SCD is gaining increasing attention. Methods The antisickling effects of Solenostemon monostachyus (SolMon), Carica papaya seed oil (Cari-oil) and Ipomoea involucrata (Ipocrata) in male (HbSSM) and female (HbSSF) human sickle cell blood was examined in vitro and compared with controls, or cells treated with glutathione or an antisickling plant (Vernonia amygdalina; VerMyg). Results Levels of sickle blood cells were significantly reduced (P < 0.05) in all the plant-extract treated SCD patients’ blood compared with that of untreated SCD patients. RBCs in SolMon, Ipocrata, and Cari-oil treated samples were significantly higher (P < 0.05) compared with VerMyg-treated samples. The Fe2+/Fe3+ ratio was significantly reduced (P < 0.05) in all plant extract-treated HbSSM samples compared with controls. Hemoglobin concentration was significantly increased (P < 0.05) by SolMon treatment in HbSSF compared with VerMyg. Sickle cell polymerization inhibition exhibited by SolMon was significantly higher (P < 0.05) compared with that of VerMyg in HbSSF blood. Sickle cell polymerization inhibition in SolMon and Ipocrata were significantly higher (P < 0.05) compared with VerMyg in HbSSM blood. All plant extracts significantly reduced (P < 0.05) lactate dehydrogenase activity in both HbSSM and HbSSF-treated blood. Catalase activity was significantly increased (P < 0.05) in HbSSF blood treated with Ipocrata compared with glutathione. Cari-oil treated HbSSM and HbSSF blood had significantly increased (P < 0.05) peroxidase activity compared with controls. Conclusions Methanolic extracts from S. monostachyus, C. papaya seed oil and I. involucrata exhibited particular antisickling properties coupled with the potential to reduce stress in sickle cell patients. Each plant individually or in combination may be useful for the management of sickle cell disease. PMID:23259718

Body mass index and other anthropometric variables in children with sickle cell anaemia.

PubMed

Odetunde, Odutola Israel; Chinawa, Josephat Maduabuchi; Achigbu, Kingsley Ihedioha; Achigbu, Eberechukwu O

2016-01-01

The objectives of this study were to determine the anthropometric variables of children with sickle cell anaemia and comparing it with those with normal haemoglobin genotype. A cross sectional study of anthropometric measurements was conducted over a period of six months. Children with sickle cell anaemia in steady state aged between 6-20 years were recruited. Nutritional assessment was done using anthropometrical variables. Data were analyzed using the Statistical Package for Social Sciences program (SPSS), version 20. The sickle cell patients comprised of 20 males and 20 females. There were an equal number of controls with an equal male to female ratio of 1:1. Forty eight percent (19) of the children with sickle cell anemia were underweight (< 5th %ile) and this is statistically significant. χ(2)=18.02 and p=0.000. When compared with subjects with normal haemoglobin genotype only five of them (13%) were underweight. χ(2)=10.286 and p=0.001. The controls weighed significantly more than the HbSS patients and also had significantly larger body surface compared to the HbSS population (P<0.05). BMI and other anthropometric variables among children with sickle cell anemia were low when compared with children with normal Haemoglobin genotype.

Left ventricular myocardial performance assessed by 2-dimensional speckle tracking echocardiography in patients with sickle cell crisis

PubMed Central

Sengupta, Shantanu P.; Jaju, Rahul; Nugurwar, Abhijeet; Caracciolo, Giuseppe; Sengupta, Partho P.

2012-01-01

Background The status of left ventricle in sickle cell anemia presenting in sickle crisis and follow up has been minimally studied in past. To determine the left ventricular (LV) myocardial performance in these patients, we performed the study to assess two dimensional strains imaging which allowed a rapid and an accurate analysis of global and regional LV myocardial performance in longitudinal, radial, and circumferential directions. Methods In this prospective study, 2-dimensional echocardiography (2DE) images of the LV were obtained in 52 subjects which included 32 patients (23 ± 8yrs, 16 male) with homozygous sickle cell anemia (SCA) in sickle cell crisis and 20 healthy controls (23 ± 5 yrs, 11 male) using apical 4-chamber and parasternal short-axis at the basal, mid, and apical levels. Of these 32 patients, 2DE was performed again in 18 patients in follow up (8 months ± 5 days). Longitudinal, circumferential and radial strains (LS, CS and RS respectively) were quantified and compared in an 18-segment model using a novel speckle tracking system (2D Cardiac Performance Analysis, TomTec Imaging System, Munich, Germany). Results There was no significant difference in LV ejection fraction between both the groups (59.32 ± 12.6 vs. 52.3 ± 7.9; p-value > 0.05). In comparison with normal controls and follow up of sickle cell patients, peak LS was significantly attenuated in the subendocardial and subepicardial regions during sickle cell crisis (p < 0.05). However, a significant reduction in circumferential strain was evident only in subepicardial region (p < 0.001). Also patients in sickle cell crisis showed significantly higher radial strain parameters than controls (p < 0.001). Conclusion Patients with SCA presenting in sickle cell crisis have reduced longitudinal shortening. LV myocardial performance remains unaltered due to relatively preserved circumferential shortening and increased radial thickening. PMID:23253406

Correlation between dipstick urinalysis and urine sediment microscopy in detecting haematuria among children with sickle cell anaemia in steady state in Ilorin, Nigeria.

PubMed

Anigilaje, Emmanuel Ademola; Adedoyin, Olanrewaju Timothy

2013-01-01

Haematuria is one of the clinical manifestations of sickle cell nephropathy. Although dipstick urinalysis detects haemoglobin and by extension haematuria; it does not confirm haematuria. Urine sediment microscopy confirms haematuria and constitutes a non-invasive "renal biopsy". The need to correlate dipstick urinalysis and urine sediment microscopy findings becomes important because of the cheapness, quickness and simplicity of the former procedure. Dipstick urinalysis and urine sediment microscopy were carried (both on first contact and a month after) among consecutive steady state sickle cell anaemia children attending sickle cell clinic at the University of Ilorin Teaching Hospital between October 2004 and July 2005. A total of 75 sickle cell anemia children aged between 1-17 years met the inclusion criteria. Haematuria was found in 12 children (16.0%) and persistent haematuria in 10 children 13.3%. Age and gender did not have significant relationship with haematuria both at first contact (p values 0.087 and 0.654 respectively) and at follow-up (p values 0.075 and 0.630 respectively). Eumorphic haematuria was confirmed in all the children with persistent haematuria with Pearson correlation +0.623 and significant p value of 0.000. The study has revealed a direct significant correlation for haematuria detected on dipstick urinalysis and at urine sediment microscopy. It may therefore be inferred that dipstick urinalysis is an easy and readily available tool for the screening of haematuria among children with sickle cell anaemia and should therefore be done routinely at the sickle cell clinics.

Interleukin 8 as a vaso-occlusive marker in Brazilian patients with sickle cell disease.

PubMed

Gonçalves, M S; Queiroz, I L; Cardoso, S A; Zanetti, A; Strapazoni, A C; Adorno, E; Albuquerque, A; Sant'Ana, A; dos Reis, M G; Barral, A; Barral Netto, M

2001-10-01

Sickle cell disease has a worldwide distribution and is a public health problem in Brazil. Although vaso-occlusive crisis (VOC) is one of the most important clinical features of the disease, there are still several steps of its pathogenesis which are unknown. The increase of the chemotactic factor interleukin 8 (IL-8) has been reported to be involved in sickle cell disease crisis, but this has not been demonstrated conclusively. In the present study we analyzed serum IL-8 levels by ELISA and hematological parameters and hemoglobin patterns by standard techniques in 23 (21 SS and 2 SC) Brazilian patients with sickle cell syndromes during VOC caused by different inducing factors, 22 (21 SS and 1 SC) sickle cell patients out of crisis, and 11 healthy controls. Increased IL-8 levels were observed in 19 of 23 VOC patients (79.2%), 3 of them with more than 1,000 pg/ml. Seventeen of 22 (77.3%) non-crisis patients showed low IL-8 levels (less than 15 pg/ml). Healthy controls had low IL-8 levels. A significant difference in serum IL-8 levels was observed between crisis and non-crisis sickle cell patients (P<0.0001). There was no correlation between IL-8 levels and hematological data or hemoglobin patterns. High serum IL-8 levels were observed in VOC patients independently of the crisis-inducing factor. We conclude that in the studied population, IL-8 concentration may be a useful VOC marker, although the mechanism of the pathogenic process of sickle cell VOC syndromes remains unclear.

Sleep Disorders in Adult Sickle Cell Patients

PubMed Central

Sharma, Sunil; Efird, Jimmy T.; Knupp, Charles; Kadali, Renuka; Liles, Darla; Shiue, Kristin; Boettger, Peter; Quan, Stuart F.

2015-01-01

Study Objectives: While sleep apnea has been studied in children with sickle cell disease (SCD), little is known about sleep disorders in adult sickle cell patients. The objective of this study was to evaluate sleep disordered breathing and its polysomnographic characteristics in adult patients with sickle cell disease. Methods: The analysis cohort included 32 consecutive adult SCD patients who underwent a comprehensive sleep evaluation and overnight polysomnography in an accredited sleep center after reporting symptoms suggesting disordered sleep or an Epworth Sleepiness Scale score ≥ 10. Epworth score, sleep parameters, comorbid conditions, and narcotic use were reviewed and compared in patients with and without sleep disordered breathing. SCD complication rates in the two groups also were compared. Results: In adult SCD patients who underwent overnight polysomnography, we report a high prevalence (44%) of sleep disordered breathing. Disease severity was mild to moderate (mean apnea-hypopnea index = 17/h (95% CI: 10–24/h). Concomitant sleep disorders, including insomnia complaints (57%) and delayed sleep-phase syndrome (57%), also were common in this population. In this limited cohort, we did not find increased SCD complications associated with sleep disordered breathing in adult patients with sickle cell disease. Conclusions: A high burden of sleep disordered breathing and other sleep-related complaints were identified in the adult sickle cell population. Our results provide important information on this unique population. Citation: Sharma S, Efird JT, Knupp C, Kadali R, Liles D, Shiue K, Boettger P, Quan SF. Sleep disorders in adult sickle cell patients. J Clin Sleep Med 2015;11(3):219–223. PMID:25515282

Rare but Lethal Hepatopathy-Sickle Cell Intrahepatic Cholestasis and Management Strategies.

PubMed

Malik, Aamir; Merchant, Chandni; Rao, Mana; Fiore, Rosemary P

2015-11-28

Sickle cell disease can affect the liver by way of the disease process, including sickling in hepatic sinusoids, as well as its treatment, including repeated blood transfusions leading to hemosiderosis and hepatitis. Sickle cell intrahepatic cholestasis (SCIC) is an extreme variant of sickle cell hepatopathy, and is associated with high fatality. We present the case of a 31-year-old man with past medical history of sickle cell disease and cholecystectomy who was admitted with uncomplicated vaso occlusive crisis and during the hospital stay developed fever, upper abdominal pain, and jaundice. There was an accelerated rise in total bilirubin to 50 mg/dL, direct bilirubin 38 mg/dL, and Cr 3.0 mg/dL. Hb was 6.4 g/dL, reticulocyte count 16%, ALT 40 IU/L, AST 155 IU/L, ALP 320 IU/L, and LDH 475 IU/L. Hepatitis panel was negative and MRCP showed normal caliber of the common bile duct, with no obstruction. Exchange transfusion of 9 units of packed red blood cells led to great improvement in his condition. SCIC, unlike the other sickle cell hepatopathies, requires urgent and vigorous exchange transfusion. Renal impairment in SCIC has not been well studied but usually is reversible with the hepatic impairment, as in this case. Unresolved renal impairment requires dialysis and is associated with poor outcome. There is limited data on use of hydroxyurea to prevent SCIC, and liver transplant is associated with high mortality. A timely diagnosis of SCIC and appropriate management is life-saving.

Comprehensive neuropsychological evaluation of children and adolescents with sickle cell anemia: a hospital-based sample.

PubMed

Nunes, Samantha; Argollo, Nayara; Mota, Marivania; Vieira, Camilo; Sena, Eduardo Pondé de

Individuals with sickle cell anemia may suffer symptomatic or silent cerebral infarcts leading to neurocognitive complications. This study investigated the cognitive and intellectual performance of children and adolescents with sickle cell anemia. The socioeconomic status, clinical aspects and behavioral profile of 15 young individuals with sickle cell anemia were evaluated. The Wechsler Intelligence Scale for Children, the Developmental Neuropsychological Assessment Test, and the Child Behavior Checklist were applied. Participants with a history of stroke had lower intelligence quotient (IQ) scores. Alterations were found in attention and executive functioning, language, verbal and visual memory, visuospatial processing and sensorimotor skills. These alterations were found both in the children and adolescents who had had a cerebral infarction and in those who apparently had not. In the majority of cases, there were learning difficulties, a history of repeating school years and a need for specialist educational support. The most common additional diagnoses in accordance with the Diagnostic and Statistical Manual of Mental Disorders IV were depressive disorder, anxiety disorder and somatic disorder, as well as conditions associated with physical and psychosocial repercussions of sickle cell anemia. As sickle cell anemia is considered a progressive cerebral vasculopathy, it is a potential risk factor for neurocognitive and psychosocial development. Therefore, periodic neuropsychological and behavioral evaluations of children and adolescents with sickle cell anemia may represent a useful measure to reduce long-term biopsychosocial repercussions. Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

Association of Sickle Cell Trait With Chronic Kidney Disease and Albuminuria in African Americans

PubMed Central

Naik, Rakhi P.; Derebail, Vimal K.; Grams, Morgan E.; Franceschini, Nora; Auer, Paul L.; Peloso, Gina M.; Young, Bessie A.; Lettre, Guillaume; Peralta, Carmen A.; Katz, Ronit; Hyacinth, Hyacinth I.; Quarells, Rakale C.; Grove, Megan L.; Bick, Alexander G.; Fontanillas, Pierre; Rich, Stephen S.; Smith, Joshua D.; Boerwinkle, Eric; Rosamond, Wayne D.; Ito, Kaoru; Lanzkron, Sophie; Coresh, Josef; Correa, Adolfo; Sarto, Gloria E.; Key, Nigel S.; Jacobs, David R.; Kathiresan, Sekar; Bibbins-Domingo, Kirsten; Kshirsagar, Abhijit V.; Wilson, James G.; Reiner, Alexander P.

2015-01-01

IMPORTANCE The association between sickle cell trait (SCT) and chronic kidney disease (CKD) is uncertain. OBJECTIVE To describe the relationship between SCT and CKD and albuminuria in self-identified African Americans. DESIGN, SETTING, AND PARTICIPANTS Using 5 large, prospective, US population-based studies (the Atherosclerosis Risk in Communities Study [ARIC, 1987–2013; n = 3402], Jackson Heart Study [JHS, 2000–2012; n = 2105], Coronary Artery Risk Development in Young Adults [CARDIA, 1985–2006; n = 848], Multi-Ethnic Study of Atherosclerosis [MESA, 2000–2012; n = 1620], and Women’s Health Initiative [WHI, 1993–2012; n = 8000]), we evaluated 15 975 self-identified African Americans (1248 participants with SCT [SCT carriers] and 14 727 participants without SCT [noncarriers]). MAIN OUTCOMES AND MEASURES Primary outcomes were CKD (defined as an estimated glomerular filtration rate [eGFR] of <60 mL/min/1.73 m2 at baseline or follow-up), incident CKD, albuminuria (defined as a spot urine albumin:creatinine ratio of >30 mg/g or albumin excretion rate >30 mg/24 hours), and decline in eGFR (defined as a decrease of >3 mL/min/1.73 m2 per year). Effect sizes were calculated separately for each cohort and were subsequently meta-analyzed using a random-effects model. RESULTS A total of 2233 individuals (239 of 1247 SCT carriers [19.2%] vs 1994 of 14 722 noncarriers [13.5%]) had CKD, 1298 (140 of 675 SCT carriers [20.7%] vs 1158 of 8481 noncarriers [13.7%]) experienced incident CKD, 1719 (150 of 665 SCT carriers [22.6%] vs 1569 of 8249 noncarriers [19.0%]) experienced decline in eGFR, and 1322 (154 of 485 SCT carriers [31.8%] vs 1168 of 5947 noncarriers [19.6%]) had albuminuria during the study period. Individuals with SCT had an increased risk of CKD (odds ratio [OR], 1.57 [95% CI, 1.34–1.84]; absolute risk difference [ARD], 7.6% [95% CI, 4.7%–10.8%]), incident CKD (OR, 1.79 [95% CI, 1.45–2.20]; ARD, 8.5% [95% CI, 5.1%–12.3%]), and decline in eGFR (OR, 1.32 [95% CI, 1.07–1.61]; ARD, 6.1% [95% CI, 1.4%–13.0%]) compared with noncarriers. Sickle cell trait was also associated with albuminuria (OR, 1.86 [95% CI, 1.49–2.31]; ARD, 12.6% [95% CI, 7.7%–17.7%]). CONCLUSIONS AND RELEVANCE Among African Americans in these cohorts, the presence of SCT was associated with an increased risk of CKD, decline in eGFR, and albuminuria, compared with noncarriers. These findings suggest that SCT may be associated with the higher risk of kidney disease in African Americans. PMID:25393378

Nontraumatic Exertional Rhabdomyolysis Leading to Acute Kidney Injury in a Sickle Trait Positive Individual on Renal Biopsy.

PubMed

Janga, Kalyana C; Greenberg, Sheldon; Oo, Phone; Sharma, Kavita; Ahmed, Umair

2018-01-01

A 26-year-old African American male with a history of congenital cerebral palsy, sickle cell trait, and intellectual disability presented with abdominal pain that started four hours prior to the hospital visit. The patient denied fever, chills, diarrhea, or any localized trauma. The patient was at a party at his community center last evening and danced for 2 hours, physically exerting himself more than usual. Labs revealed blood urea nitrogen (BUN) level of 41 mg/dL and creatinine (Cr) of 2.8 mg/dL which later increased to 4.2 mg/dL while still in the emergency room. Urinalysis revealed hematuria with RBC > 50 on high power field. Imaging of the abdomen revealed no acute findings for abdominal pain. With fractional excretion of sodium (FeNa) > 3%, findings suggested nonoliguric acute tubular necrosis. Over the next couple of days, symptoms of dyspepsia resolved; however, BUN/Cr continued to rise to a maximum of 122/14 mg/dL. With these findings, along with stable electrolytes, urine output matching the intake, and prior use of proton pump inhibitors, medical decision was altered for the possibility of acute interstitial nephritis. Steroids were subsequently started and biopsy was taken. Biopsy revealed heavy deposits of myoglobin. Creatinine phosphokinase (CPK) levels drawn ten days later after the admission were found to be elevated at 334 U/dl, presuming the levels would have been much higher during admission. This favored a diagnosis of acute kidney injury (AKI) secondary to exertional rhabdomyolysis. We here describe a case of nontraumatic exertional rhabdomyolysis in a sickle cell trait (SCT) individual that was missed due to findings of microscopic hematuria masking underlying myoglobinuria and fractional excretion of sodium > 3%. As opposed to other causes of ATN, rhabdomyolysis often causes FeNa < 1%. The elevated fractional excretion of sodium in this patient was possibly due to the underlying inability of SCT positive individuals to reabsorb sodium/water and concentrate their urine. Additionally, because of their inability to concentrate urine, SCT positive individuals are prone to intravascular depletion leading to renal failure as seen in this patient. Disease was managed with continuing hydration and tapering steroids. Kidney function improved and the patient was discharged with a creatinine of 3 mg/dL. A month later, renal indices were completely normal with persistence of microscopic hematuria from SCT.

Thrombotic thrombocytopenic purpura and sickle cell crisis.

PubMed

Shelat, Suresh G

2010-04-01

Described is a case of acute chest syndrome in a sickle-cell patient (hemoglobin SS) who also developed signs and symptoms of thrombotic thrombocytopenic purpura, including thrombocytopenia and hemolysis (anemia, elevated lactate dehydrogenase, presence of schistocytes, dark-colored plasma, and elevations in nucleated red blood cells). The ADAMTS13 activity level was normal. Discussed are the diagnosis and therapeutic management issues and the challenges of differentiating the vasoocclusive and hemolytic complications of sickling red blood cells from the thrombotic microangiopathy of thrombotic thrombocytopenic purpura.

Genetic Modifiers of Sickle Cell Disease

PubMed Central

Steinberg, Martin H.; Sebastiani, Paola

2015-01-01

Sickle cell anemia is associated with unusual clinical heterogeneity for a Mendelian disorder. Fetal hemoglobin concentration and coincident ∝ thalassemia, both which directly affect the sickle erythrocyte, are the major modulators of the phenotype of disease. Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia would be prognostically useful, could inform personalized therapeutics, and might help the discovery of new “druggable” pathophysiologic targets. Genotype-phenotype association studies have been used to identify novel genetic modifiers. In the future, whole genome sequencing with its promise of discovering hitherto unsuspected variants could add to our understanding of the genetic modifiers of this disease. PMID:22641398

Gardos pathway to sickle cell therapies?

PubMed

Joiner, Clinton H

2008-04-15

In this issue of Blood, Ataga and colleagues report that treatment of sickle cell disease patients with senicapoc, a Gardos channel inhibitor, reduces the number of dehydrated cells, increases hemoglobin levels, and diminishes hemolysis.

Sickle cell detection using a smartphone

PubMed Central

Knowlton, S. M.; Sencan, I.; Aytar, Y.; Khoory, J.; Heeney, M. M.; Ghiran, I. C.; Tasoglu, S.

2015-01-01

Sickle cell disease affects 25% of people living in Central and West Africa and, if left undiagnosed, can cause life threatening “silent” strokes and lifelong damage. However, ubiquitous testing procedures have yet to be implemented in these areas, necessitating a simple, rapid, and accurate testing platform to diagnose sickle cell disease. Here, we present a label-free, sensitive, and specific testing platform using only a small blood sample (<1 μl) based on the higher density of sickle red blood cells under deoxygenated conditions. Testing is performed with a lightweight and compact 3D-printed attachment installed on a commercial smartphone. This attachment includes an LED to illuminate the sample, an optical lens to magnify the image, and two permanent magnets for magnetic levitation of red blood cells. The sample is suspended in a paramagnetic medium with sodium metabisulfite and loaded in a microcapillary tube that is inserted between the magnets. Red blood cells are levitated in the magnetic field based on equilibrium between the magnetic and buoyancy forces acting on the cells. Using this approach, we were able to distinguish between the levitation patterns of sickle versus control red blood cells based on their degree of confinement. PMID:26492382

Sickle cell dehydration: Pathophysiology and therapeutic applications.

PubMed

Brugnara, Carlo

2018-01-01

Cell dehydration is a distinguishing characteristic of sickle cell disease and an important contributor to disease pathophysiology. Due to the unique dependence of Hb S polymerization on cellular Hb S concentration, cell dehydration promotes polymerization and sickling. In double heterozygosis for Hb S and C (SC disease) dehydration is the determining factor in disease pathophysiology. Three major ion transport pathways are involved in sickle cell dehydration: the K-Cl cotransport (KCC), the Gardos channel (KCNN4) and Psickle, the polymerization induced membrane permeability, most likely mediated by the mechano-sensitive ion channel PIEZO1. Each of these pathways exhibit unique characteristics in regulation by oxygen tension, intracellular and extracellular environment, and functional expression in reticulocytes and mature red cells. The unique dependence of K-Cl cotransport on intracellular Mg and the abnormal reduction of erythrocyte Mg content in SS and SC cells had led to clinical studies assessing the effect of oral Mg supplementation. Inhibition of Gardos channel by clotrimazole and senicapoc has led to Phase 1,2,3 trials in patients with sickle cell disease. While none of these studies has resulted in the approval of a novel therapy for SS disease, they have highlighted the key role played by these pathways in disease pathophysiology.

Sickle cell detection using a smartphone.

PubMed

Knowlton, S M; Sencan, I; Aytar, Y; Khoory, J; Heeney, M M; Ghiran, I C; Tasoglu, S

2015-10-22

Sickle cell disease affects 25% of people living in Central and West Africa and, if left undiagnosed, can cause life threatening "silent" strokes and lifelong damage. However, ubiquitous testing procedures have yet to be implemented in these areas, necessitating a simple, rapid, and accurate testing platform to diagnose sickle cell disease. Here, we present a label-free, sensitive, and specific testing platform using only a small blood sample (<1 μl) based on the higher density of sickle red blood cells under deoxygenated conditions. Testing is performed with a lightweight and compact 3D-printed attachment installed on a commercial smartphone. This attachment includes an LED to illuminate the sample, an optical lens to magnify the image, and two permanent magnets for magnetic levitation of red blood cells. The sample is suspended in a paramagnetic medium with sodium metabisulfite and loaded in a microcapillary tube that is inserted between the magnets. Red blood cells are levitated in the magnetic field based on equilibrium between the magnetic and buoyancy forces acting on the cells. Using this approach, we were able to distinguish between the levitation patterns of sickle versus control red blood cells based on their degree of confinement.

Epidural analgesia for treatment of a sickle cell crisis during pregnancy.

PubMed

Winder, Abigail D; Johnson, Stacie; Murphy, Jamie; Ehsanipoor, Robert M

2011-08-01

More than 50% of obstetric patients with sickle cell disease will have a pain crisis during pregnancy, and the management of these cases can be challenging. A 20-year-old African American with sickle cell disease presented at 29 4/7 weeks of gestation with severe, debilitating leg and back pain. Large doses of intravenous narcotics did not result in significant pain relief, so a lumbar epidural was placed. This resulted in complete pain relief within several minutes. The patient's symptoms resolved over several days and after a short course of narcotics she was discharged to home, and the remainder of her pregnancy was uncomplicated. Epidural anesthesia should be considered as a potentially effective treatment for a severe sickle cell crisis in obstetric patients.

Ectodermal dysplasia associated with sickle cell disease.

PubMed

Volpato, Luiz Evaristo Ricci; Volpato, Maria Carmen Palma Faria; de Carvalhosa, Artur Aburad; Palma, Vinicius Canavarros; Borges, Alvaro Henrique

2014-01-01

Ectodermal dysplasia and sickle cell anaemia are inherited disorders that affect, respectively, the tissues derived from the embryonic ectoderm and the production of erythrocytes by the bone marrow. The simultaneous occurrence of both disorders is extremely rare. This is a case of both ectodermal dysplasia and sickle cell anaemia reported in a 6-year-old. The patient had been diagnosed with sickle cell anaemia for only six months when he sought treatment presenting with the following: hypotrichosis, dry skin, periocular hyperpigmentation, protruding lips, hypodontia, and morphologically altered teeth. The clinical features combined with his medical history led to the diagnosis of ectodermal dysplasia. Dentists should be prepared to recognise patterns that escape normality to aid in the diagnosis of systemic changes, even in patients with other previous diagnoses.

A comparison study of children with sickle cell disease and their non-diseased siblings on hopelessness, depression, and perceived competence.

PubMed

Lee, E J; Phoenix, D; Brown, W; Jackson, B S

1997-01-01

The purpose of this comparison study was to explore the extent to which hopelessness and self-perceptions of competence are associated with depression in a community population of children with sickle cell disease compared to their non-diseased siblings. Subjects were African-American children drawn randomly from the case management programme at the L.D. Barksdale Sickle Cell Anemia Foundation. Depression scores were higher for the non-diseased siblings. The children with sickle cell disease scored lower on the perceived physical competence scale. Recommendations for practice include increasing hope, improving relationships, monitoring depression in patients and their siblings, and monitoring perceptions of cognitive, social, physical, and general self-worth.

Search for antisickling agents from plants.

PubMed

Dash, Bisnu Prasad; Archana, Y; Satapathy, Nibarana; Naik, Soumendra Kumar

2013-01-01

The sickle cell disease is fatal in nature. Thousands of children are dying off due to this health problem throughout the globe. Due to the rapid development of diagnosis and clinical managements such patients are living up to a respectable age. But as there is no permanent cure the patients are suffering from bone and joint pain, jaundice, hepato-splenomegaly, chronic infections etc. The main physiological complicacy is due to the polymerization of sickle hemoglobin (HbS), (sickling process) inside the red blood cell (RBC) of these patients during deoxygenating state. The change of RBC from spherical to sickle shape is due to the polymerization of mutant hemoglobin (HbS) inside the RBC and membrane distortion during anoxic condition. The mechanism and the process of sickling are very complex and multifactor in nature. To get rid from such complicacies it is necessary to suitably and accurately stop the sickling of RBC of the patients. The potential anti-sickling agents either from natural sources and/or synthetic molecules may be helpful for reducing the clinical morbidity of the patients. A lot of natural compounds from plant extracts have been tried by several workers in recent past. Most of the studies are based on in vitro red cell sickling studies and their mode of action has not been properly understood. Although, few studies have been in vivo in nature pertaining to transgenic sickle animal model, there is paucity of data on the human studies. The result of such studies although has shown some degree of success, a promising anti-sickling agent is yet to be established.

Search for antisickling agents from plants

PubMed Central

Dash, Bisnu Prasad; Archana, Y.; Satapathy, Nibarana; Naik, Soumendra Kumar

2013-01-01

The sickle cell disease is fatal in nature. Thousands of children are dying off due to this health problem throughout the globe. Due to the rapid development of diagnosis and clinical managements such patients are living up to a respectable age. But as there is no permanent cure the patients are suffering from bone and joint pain, jaundice, hepato-splenomegaly, chronic infections etc. The main physiological complicacy is due to the polymerization of sickle hemoglobin (HbS), (sickling process) inside the red blood cell (RBC) of these patients during deoxygenating state. The change of RBC from spherical to sickle shape is due to the polymerization of mutant hemoglobin (HbS) inside the RBC and membrane distortion during anoxic condition. The mechanism and the process of sickling are very complex and multifactor in nature. To get rid from such complicacies it is necessary to suitably and accurately stop the sickling of RBC of the patients. The potential anti-sickling agents either from natural sources and/or synthetic molecules may be helpful for reducing the clinical morbidity of the patients. A lot of natural compounds from plant extracts have been tried by several workers in recent past. Most of the studies are based on in vitro red cell sickling studies and their mode of action has not been properly understood. Although, few studies have been in vivo in nature pertaining to transgenic sickle animal model, there is paucity of data on the human studies. The result of such studies although has shown some degree of success, a promising anti-sickling agent is yet to be established. PMID:23922457

Beta Thalassemia (For Parents)

MedlinePlus

... July 2015 More on this topic for: Parents Kids Teens Blood Transfusions Iron Iron-Deficiency Anemia Blood Test: Hemoglobin Electrophoresis Sickle Cell Disease Alpha Thalassemia Anemia Word! Anemia About Anemia Stem Cell Transplants Blood Transfusions Anemia Sickle Cell Disease ...

Comparative Analysis of Pain Behaviours in Humanized Mouse Models of Sickle Cell Anemia

PubMed Central

Lei, Jianxun; Benson, Barbara; Tran, Huy; Ofori-Acquah, Solomon F.; Gupta, Kalpna

2016-01-01

Pain is a hallmark feature of sickle cell anemia (SCA) but management of chronic as well as acute pain remains a major challenge. Mouse models of SCA are essential to examine the mechanisms of pain and develop novel therapeutics. To facilitate this effort, we compared humanized homozygous BERK and Townes sickle mice for the effect of gender and age on pain behaviors. Similar to previously characterized BERK sickle mice, Townes sickle mice show more mechanical, thermal, and deep tissue hyperalgesia with increasing age. Female Townes sickle mice demonstrate more hyperalgesia compared to males similar to that reported for BERK mice and patients with SCA. Mechanical, thermal and deep tissue hyperalgesia increased further after hypoxia/reoxygenation (H/R) treatment in Townes sickle mice. Together, these data show BERK sickle mice exhibit a significantly greater degree of hyperalgesia for all behavioral measures as compared to gender- and age-matched Townes sickle mice. However, the genetically distinct “knock-in” strategy of human α and β transgene insertion in Townes mice as compared to BERK mice, may provide relative advantage for further genetic manipulations to examine specific mechanisms of pain. PMID:27494522

The Use of Dried Blood Spots: A Potential Tool for the Introduction of a Neonatal Screening Program for Sickle Cell Anemia in Zambia.

PubMed

Chindima, Nanjela; Nkhoma, Panji; Sinkala, Musalula; Zulu, Mildred; Kafita, Doris; Simakando, Marah; Mwaba, Florence; Mantina, Hamakwa; Mutale, Mubanga

2018-01-01

Sickle cell disease is a group of hemoglobin (Hb) disorders resulting from the inheritance of the sickle β-globin gene. It is the most common pathological Hb mutation worldwide with 75% being born in Sub-Saharan Africa. This study aims to determine if dried blood spots (DBSs) can be used for diagnosis of sickle cell in newborns. In Zambia, there is no neonatal screening program for sickle cell anemia (SCA), yet it has been proved that early diagnosis by newborn screening (NBS) using DBSs and access to comprehensive care results in survival to adulthood of over 96% of sickle cell patients. A cross-sectional study was carried out at the University Teaching Hospital to determine whether DBSs can be used to diagnose sickle cell using Hb electrophoresis. Results from DBSs stored for 2 weeks were then compared to those obtained using freshly collected whole blood. To evaluate performance characteristics, the following values were used: true positive, false positive, true negative, and false negative. Ninety-seven participants were included in this study. DBSs had a sensitivity of 100%, a specificity of 94.7%, positive predictive value of 96.7%, negative predictive value of 100%, overall efficiency of 97.9%, and a Kappa r 2 , P < 0.0001 in comparison to fresh whole blood which we used as the gold standard. The use of DBSs can be recommended for NBS of SCA in Zambia due to its high sensitivity, specificity, and stability of hemoglobin.

Hemopexin therapy reverts heme-induced proinflammatory phenotypic switching of macrophages in a mouse model of sickle cell disease.

PubMed

Vinchi, Francesca; Costa da Silva, Milene; Ingoglia, Giada; Petrillo, Sara; Brinkman, Nathan; Zuercher, Adrian; Cerwenka, Adelheid; Tolosano, Emanuela; Muckenthaler, Martina U

2016-01-28

Hemolytic diseases, such as sickle cell anemia and thalassemia, are characterized by enhanced release of hemoglobin and heme into the circulation, heme-iron loading of reticulo-endothelial system macrophages, and chronic inflammation. Here we show that in addition to activating the vascular endothelium, hemoglobin and heme excess alters the macrophage phenotype in sickle cell disease. We demonstrate that exposure of cultured macrophages to hemolytic aged red blood cells, heme, or iron causes their functional phenotypic change toward a proinflammatory state. In addition, hemolysis and macrophage heme/iron accumulation in a mouse model of sickle disease trigger similar proinflammatory phenotypic alterations in hepatic macrophages. On the mechanistic level, this critically depends on reactive oxygen species production and activation of the Toll-like receptor 4 signaling pathway. We further demonstrate that the heme scavenger hemopexin protects reticulo-endothelial macrophages from heme overload in heme-loaded Hx-null mice and reduces production of cytokines and reactive oxygen species. Importantly, in sickle mice, the administration of human exogenous hemopexin attenuates the inflammatory phenotype of macrophages. Taken together, our data suggest that therapeutic administration of hemopexin is beneficial to counteract heme-driven macrophage-mediated inflammation and its pathophysiologic consequences in sickle cell disease. © 2016 by The American Society of Hematology.

Hemoglobin Aggregation in Single Red Blood Cells of Sickle Cell Anemia

NASA Astrophysics Data System (ADS)

Nishio, Izumi; Tanaka, Toyoichi; Sun, Shao-Tang; Imanishi, Yuri; Tsuyoshi Ohnishi, S.

1983-06-01

A laser light scattering technique was used to observe the extent of hemoglobin aggregation in solitary red blood cells of sickle cell anemia. Hemoglobin aggregation was confirmed in deoxygenated cells. The light scattering technique can also be applied to cytoplasmic studies of any biological cell.

RON kinase inhibition reduces renal endothelial injury in sickle cell disease mice

PubMed Central

Khaibullina, Alfia; Adjei, Elena A.; Afangbedji, Nowah; Ivanov, Andrey; Kumari, Namita; Almeida, Luis E.F.; Quezado, Zenaide M.N.; Nekhai, Sergei; Jerebtsova, Marina

2018-01-01

Sickle cell disease patients are at increased risk of developing a chronic kidney disease. Endothelial dysfunction and inflammation associated with hemolysis lead to vasculopathy and contribute to the development of renal disease. Here we used a Townes sickle cell disease mouse model to examine renal endothelial injury. Renal disease in Townes mice was associated with glomerular hypertrophy, capillary dilation and congestion, and significant endothelial injury. We also detected substantial renal macrophage infiltration, and accumulation of macrophage stimulating protein 1 in glomerular capillary. Treatment of human cultured macrophages with hemin or red blood cell lysates significantly increased expression of macrophage membrane-associated protease that might cleave and activate circulating macrophage stimulating protein 1 precursor. Macrophage stimulating protein 1 binds to and activates RON kinase, a cell surface receptor tyrosine kinase. In cultured human renal glomerular endothelial cells, macrophage stimulating protein 1 induced RON downstream signaling, resulting in increased phosphorylation of ERK and AKT kinases, expression of Von Willebrand factor, increased cell motility, and re-organization of F-actin. Specificity of macrophage stimulating protein 1 function was confirmed by treatment with RON kinase inhibitor BMS-777607 that significantly reduced downstream signaling. Moreover, treatment of sickle cell mice with BMS-777607 significantly reduced glomerular hypertrophy, capillary dilation and congestion, and endothelial injury. Taken together, our findings demonstrated that RON kinase is involved in the induction of renal endothelial injury in sickle cell mice. Inhibition of RON kinase activation may provide a novel approach for prevention of the development of renal disease in sickle cell disease. PMID:29519868

Challenge of managing sickle cell disease in a pediatric population living in kinshasa, democratic republic of congo: a sickle cell center experience.

PubMed

Aloni, Michel Ntetani; Nkee, Leonard

2014-01-01

In the Democratic Republic of Congo (DRC), sickle cell disease is not yet really regarded as a health care priority. The patterns of sickle cell disease in patients living in Kinshasa, DRC are discussed and the difficulties encountered in their management are highlighted. The cross-sectional survey is of sickle cell patients and their families attending the Centre de Médecine Mixte et d'Anémie SS de Yolo (CMMASS), Kinshasa, DRC, between January and April 2009. Completed questionnaires were received from 168 respondents (111 girls; 57 boys). Seventy-one percent of the subjects were diagnosed before the age of 2 years but none in the neonatal period. Sickle cell disease was diagnosed in 54.8% of the patients after they had suffered pain crises. Of the 168 subjects, 74.0% had previously received blood transfusions. Seventy-five (45.0%) had more than three severe pain crises per year. A minority of 35.0% reported that they regularly took an antibioprophylaxis. Seventy-five (45.0%) subjects were eligible for hydroxyurea (HU) therapy but in all cases this drug was taken irregularly. Eighty-two percent of drugs were purchased by the parents. One hundred and sixty-three children (97.0%) were vaccinated according to the Expanded Programme on Immunization (EPI), 61.0% against Streptococcus pneumoniae and 16.0% against the Hepatitis B virus (HBV). No case of immunization against Hemophilus influenzae and Salmonella sp was reported. Neonatal screening programs, early educational detection programs for families, use of current method treatments and an implementation of a health insurance system for sickle cell disease will improve detection and management for these and future patients in our population.

Acute Crises and Complications of Sickle Cell Anemia Among Patients Attending a Pediatric Tertiary Unit in Kinshasa, Democratic Republic Of Congo.

PubMed

Aloni, Michel Ntetani; Kadima, Bertin Tshimanga; Ekulu, Pépé Mfutu; Budiongo, Aléine Nzazi; Ngiyulu, René Makuala; Gini-Ehungu, Jean Lambert

2017-06-01

In the Democratic Republic of Congo, the incidence of sickle cell anemia (SCA) is estimated to affect 30,000 to 40,000 neonates per year. However, there is paucity of data on acute clinical manifestations in sickle cell children. In these circumstances, it is difficult to develop a health care policy for an adequate management of sickle cell patients. This was a seven years' retrospective study of children admitted with acute sickle cell crisis in the Department of Pediatrics in University Hospital of Kinshasa, Kinshasa, the Democratic Republic of Congo. A total of 108 patients were identified as having SCA. There were 56 (51%) girls and 52 (49%) boys. Median age was 10.5 years (range 1-24 years). No child was diagnosed by neonatal screening. The median age of diagnosis of sickle cell anemia was 90 months (range: 8-250 months). The median age at the first transfusion was 36 months (range 4-168). In this series, 61 (56.5%) patients were eligible for hydroxyurea. However, this treatment was only performed in 4 (6.6%) of them. Pain episodes, acute anemic crisis and severe infection represent respectively 38.2%, 34.3% and 21.9% of events. Altered sensorium and focal deficit were encountered occasionally and represented 3.4% of acute events. Acute renal manifestations, cholelithiasis and priapism were rarely reported, in this cohort. In Kinshasa, the care of patients suffering from sickle cell anemia is characterized by the delayed diagnosis and low detection of organ complications compared to reports of Western countries. This situation is due to resources deficiencies.

Evolving locally appropriate models of care for Indian sickle cell disease

PubMed Central

Serjeant, Graham R.

2016-01-01

The sickle cell gene in India represents a separate occurrence of the HbS mutations from those in Africa. Sickle cell disease in India occurs against different genetic and environmental backgrounds from those seen in African patients and there is evidence of clinical differences between the populations. Knowledge of the clinical features of African disease was drawn from the Jamaican Cohort Study, based on prospective follow up of all cases of sickle cell disease detected by the screening of 100,000 consecutive newborns in Kingston, Jamaica, and supplemented by observations from the Cooperative Study of Sickle Cell Disease in the US. Defining the principal causes of early morbidity in African sickle cell disease led to successful interventions including pneumococcal prophylaxis, parental education in the early diagnosis of acute splenic sequestration, and the early detection by trans-cranial Doppler of cerebral vessel stenosis predictive of stroke but their success depended on early diagnosis, ideally at birth. Although reducing mortality among patients with African forms of SS disease, the question remains whether these interventions are appropriate or justified in Indian patients. This dilemma is approached by comparing the available data in African and Indian forms of SS disease seeking to highlight the similarities and differences and to identify the deficiencies in knowledge of Indian disease. These deficiencies could be most readily addressed by cohort studies based on newborn screening and since much of the morbidity of African disease occurs in the first five years of life, these need not be a daunting prospect for Indian health care personnel. Newborn screening programmes for sickle cell disease are already underway in India and appropriate protocols and therapeutic trials could quickly answer many of these questions. Without this knowledge, Indian physicians may continue to use possibly unnecessary and expensive models of care. PMID:27377495

Acute Crises and Complications of Sickle Cell Anemia Among Patients Attending a Pediatric Tertiary Unit in Kinshasa, Democratic Republic Of Congo

PubMed Central

Aloni, Michel Ntetani; Kadima, Bertin Tshimanga; Ekulu, Pépé Mfutu; Budiongo, Aléine Nzazi; Ngiyulu, René Makuala; Gini-Ehungu, Jean Lambert

2017-01-01

In the Democratic Republic of Congo, the incidence of sickle cell anemia (SCA) is estimated to affect 30,000 to 40,000 neonates per year. However, there is paucity of data on acute clinical manifestations in sickle cell children. In these circumstances, it is difficult to develop a health care policy for an adequate management of sickle cell patients. This was a seven years’ retrospective study of children admitted with acute sickle cell crisis in the Department of Pediatrics in University Hospital of Kinshasa, Kinshasa, the Democratic Republic of Congo. A total of 108 patients were identified as having SCA. There were 56 (51%) girls and 52 (49%) boys. Median age was 10.5 years (range 1-24 years). No child was diagnosed by neonatal screening. The median age of diagnosis of sickle cell anemia was 90 months (range: 8-250 months). The median age at the first transfusion was 36 months (range 4-168). In this series, 61 (56.5%) patients were eligible for hydroxyurea. However, this treatment was only performed in 4 (6.6%) of them. Pain episodes, acute anemic crisis and severe infection represent respectively 38.2%, 34.3% and 21.9% of events. Altered sensorium and focal deficit were encountered occasionally and represented 3.4% of acute events. Acute renal manifestations, cholelithiasis and priapism were rarely reported, in this cohort. In Kinshasa, the care of patients suffering from sickle cell anemia is characterized by the delayed diagnosis and low detection of organ complications compared to reports of Western countries. This situation is due to resources deficiencies. PMID:28626540

Genetic variants associated with fetal hemoglobin levels show the diverse ethnic origin in Colombian patients with sickle cell anemia.

PubMed

Fong, Cristian; Menzel, Stephan; Lizarralde, María Alejandra; Barreto, Guillermo

2015-01-01

Fetal hemoglobin is an important factor in modulating the severity of sickle cell anemia. Its level in peripheral blood underlies strong genetic determination. Associated loci with increased levels of fetal hemoglobin display population-specific allele frequencies. We investigated the presence and effect of known common genetic variants promoting fetal hemoglobin persistence (rs11886868, rs9399137, rs4895441, and rs7482144) in 60 Colombian patients with sickle cell anemia. Four single nucleotide polymorphisms (SNP) were genotyped by restriction fragment length polymorphisms (RFLP) and the use of the TaqMan procedure. Fetal hemoglobin (HbF) from these patients was quantified using the oxyhemoglobin alkaline denaturation technique. Genotype frequencies were compared with frequencies reported in global reference populations. We detected genetic variants in the four SNPs, reported to be associated with higher HbF levels for all four SNPs in the Colombian patients. Genetic association between SNPs and HbF levels did not reach statistical significance. The frequency of these variants reflected the specific ethnic make-up of our patient population: A high prevalence of rs7482144-'A' reflects the West-African origin of the sickle cell mutation, while high frequencies of rs4895441-'G' and rs11886868-'C' point to a significant influence of an Amerindian ethnic background in the Colombian sickle cell disease population. These results showed that in the sickle cell disease population in Colombia there is not a unique genetic background, but two (African and Amerindian). This unique genetic situation will provide opportunities for a further study of these loci, such as fine-mapping and molecular-biological investigation. Colombian patients are expected to yield a distinctive insight into the effect of modifier loci in sickle cell disease.

Normal muscle oxygen consumption and fatigability in sickle cell patients despite reduced microvascular oxygenation and hemorheological abnormalities.

PubMed

Waltz, Xavier; Pichon, Aurélien; Lemonne, Nathalie; Mougenel, Danièle; Lalanne-Mistrih, Marie-Laure; Lamarre, Yann; Tarer, Vanessa; Tressières, Benoit; Etienne-Julan, Maryse; Hardy-Dessources, Marie-Dominique; Hue, Olivier; Connes, Philippe

2012-01-01

Although it has been hypothesized that muscle metabolism and fatigability could be impaired in sickle cell patients, no study has addressed this issue. We compared muscle metabolism and function (muscle microvascular oxygenation, microvascular blood flow, muscle oxygen consumption and muscle microvascular oxygenation variability, which reflects vasomotion activity, maximal muscle force and local muscle fatigability) and the hemorheological profile at rest between 16 healthy subjects (AA), 20 sickle cell-hemoglobin C disease (SC) patients and 16 sickle cell anemia (SS) patients. Muscle microvascular oxygenation was reduced in SS patients compared to the SC and AA groups and this reduction was not related to hemorhelogical abnormalities. No difference was observed between the three groups for oxygen consumption and vasomotion activity. Muscle microvascular blood flow was higher in SS patients compared to the AA group, and tended to be higher compared to the SC group. Multivariate analysis revealed that muscle oxygen consumption was independently associated with muscle microvascular blood flow in the two sickle cell groups (SC and SS). Finally, despite reduced muscle force in sickle cell patients, their local muscle fatigability was similar to that of the healthy subjects. Sickle cell patients have normal resting muscle oxygen consumption and fatigability despite hemorheological alterations and, for SS patients only, reduced muscle microvascular oxygenation and increased microvascular blood flow. Two alternative mechanisms can be proposed for SS patients: 1) the increased muscle microvascular blood flow is a way to compensate for the lower muscle microvascular oxygenation to maintain muscle oxygen consumption to normal values or 2) the reduced microvascular oxygenation coupled with a normal resting muscle oxygen consumption could indicate that there is slight hypoxia within the muscle which is not sufficient to limit mitochondrial respiration but increases muscle microvascular blood flow.

Acute and chronic hepatobiliary manifestations of sickle cell disease: A review

PubMed Central

Shah, Rushikesh; Taborda, Cesar; Chawla, Saurabh

2017-01-01

Sickle cell disease (SCD) is a common hemoglobinopathy which can affect multiple organ systems in the body. Within the digestive tract, the hepatobiliary system is most commonly affected in SCD. The manifestations range from benign hyperbilirubinemia to overt liver failure, with the spectrum of acute clinical presentations often referred to as “sickle cell hepatopathy”. This is an umbrella term referring to liver dysfunction and hyperbilirubinemia due to intrahepatic sickling process during SCD crisis leading to ischemia, sequestration and cholestasis. In this review, we detail the pathophysiology, clinical presentation and biochemical features of various acute and chronic hepatobiliary manifestations of SCD and present and evaluate existing evidence with regards to management of this disease process. We also discuss recent advances and controversies such as the role of liver transplantation in sickle cell hepatopathy and highlight important questions in this field which would require further research. Our aim with this review is to help increase the understanding, aid in early diagnosis and improve management of this important disease process. PMID:28868180

Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells.

PubMed

Hoban, Megan D; Cost, Gregory J; Mendel, Matthew C; Romero, Zulema; Kaufman, Michael L; Joglekar, Alok V; Ho, Michelle; Lumaquin, Dianne; Gray, David; Lill, Georgia R; Cooper, Aaron R; Urbinati, Fabrizia; Senadheera, Shantha; Zhu, Allen; Liu, Pei-Qi; Paschon, David E; Zhang, Lei; Rebar, Edward J; Wilber, Andrew; Wang, Xiaoyan; Gregory, Philip D; Holmes, Michael C; Reik, Andreas; Hollis, Roger P; Kohn, Donald B

2015-04-23

Sickle cell disease (SCD) is characterized by a single point mutation in the seventh codon of the β-globin gene. Site-specific correction of the sickle mutation in hematopoietic stem cells would allow for permanent production of normal red blood cells. Using zinc-finger nucleases (ZFNs) designed to flank the sickle mutation, we demonstrate efficient targeted cleavage at the β-globin locus with minimal off-target modification. By co-delivering a homologous donor template (either an integrase-defective lentiviral vector or a DNA oligonucleotide), high levels of gene modification were achieved in CD34(+) hematopoietic stem and progenitor cells. Modified cells maintained their ability to engraft NOD/SCID/IL2rγ(null) mice and to produce cells from multiple lineages, although with a reduction in the modification levels relative to the in vitro samples. Importantly, ZFN-driven gene correction in CD34(+) cells from the bone marrow of patients with SCD resulted in the production of wild-type hemoglobin tetramers. © 2015 by The American Society of Hematology.

Dietary supplementation with docosahexanoic acid (DHA) increases red blood cell membrane flexibility in mice with sickle cell disease.

PubMed

Wandersee, Nancy J; Maciaszek, Jamie L; Giger, Katie M; Hanson, Madelyn S; Zheng, Suilan; Guo, YiHe; Mickelson, Barbara; Hillery, Cheryl A; Lykotrafitis, George; Low, Philip S; Hogg, Neil

2015-02-01

Humans and mice with sickle cell disease (SCD) have rigid red blood cells (RBCs). Omega-3 fatty acids, such as docosahexanoic acid (DHA), may influence RBC deformability via incorporation into the RBC membrane. In this study, sickle cell (SS) mice were fed natural ingredient rodent diets supplemented with 3% DHA (DHA diet) or a control diet matched in total fat (CTRL diet). After 8weeks of feeding, we examined the RBCs for: 1) stiffness, as measured by atomic force microscopy; 2) deformability, as measured by ektacytometry; and 3) percent irreversibly sickled RBCs on peripheral blood smears. Using atomic force microscopy, it is found that stiffness is increased and deformability decreased in RBCs from SS mice fed CTRL diet compared to wild-type mice. In contrast, RBCs from SS mice fed DHA diet had markedly decreased stiffness and increased deformability compared to RBCs from SS mice fed CTRL diet. Furthermore, examination of peripheral blood smears revealed less irreversibly sickled RBCs in SS mice fed DHA diet as compared to CTRL diet. In summary, our findings indicate that DHA supplementation improves RBC flexibility and reduces irreversibly sickled cells by 40% in SS mice. These results point to potential therapeutic benefits of dietary omega-3 fatty acids in SCD. Copyright © 2014 Elsevier Inc. All rights reserved.

Complete hydatidiform mole with a surviving coexistent twin in a woman with sickle cell disease: a case report.

PubMed

Mahmoud, Mohamad S; Merhi, Zaher

2007-06-01

Twin pregnancy with an apparently healthy fetus and complete hydatidiform mole (CHMTF) is a rare condition. We present the first reported case in a woman with sickle cell disease. An 18-year-old woman, para 1, gravida 0, with sickle cell disease was diagnosed at 19 weeks as having a complete molar pregnancy with a coexistent live fetus. The patient presented with abdominal pain, nausea, headaches, body aches, joint pain and chest pain on 2 different occasions. She denied having vaginal bleeding. Whether the patient was having a sickle cell crisis or molar pregnancy symptoms (i.e., thyrotoxicosis) was not clear. She was given intravenous hydration and pain management. All her symptoms resolved, confirming sickle cell crisis as the final diagnosis. The pregnancy was uneventful until 35 weeks, when oligohydramnios prompted induction of labor. Suction curettage was performed after delivery for removal of the molar pregnancy. The patient did not show any evidence of persistent trophoblastic disease 2 months after delivery. CHMTF in sickle cell disease patients is challenging. Adequate intravenous hydration and pain management should be started when one suspects a crisis. If the symptoms resolved, thyrotoxicosis due to the molar pregnancy is unlikely. In addition to proper medical management, proper counseling of the patient and close monitoring of both fetus and mother should be undertaken.

[Major sickle cell syndromes and infections associated with this condition in children in Burkina Faso].

PubMed

Douamba, Sonia; Nagalo, Kisito; Tamini, Laure; Traoré, Ismaël; Kam, Madibèlè; Kouéta, Fla; Yé, Diarra

2017-01-01

This study aims to investigate infections in children with major sickle cell syndrome. We conducted a monocentric descriptive retrospective hospital study in Ouagadougou, Burkina Faso, over a ten-year period. All children with major sickle cell syndrome (homozygous SS and double heterozygous SC, SD Punjab , Sβ thalassemic, SO Arab and SE) hospitalized for microbiologically confirmed infections were enrolled in the study. One hundred and thirty-three patients met our inclusion criteria. The SS phenotype accounted for 63.2% of cases and SC 36.8%. The frequency of infections was 21.8%. In 45.9% of cases, these affected children aged 0-5 years. The most frequent signs were osteoarticular pain (42.1%), cough (25.7%), abdominal pain (23.3%), pallor (43.6%). The major diagnoses were bronchopneumonia (31.6%), malaria (16.5%), osteomyelitis (12.8%) and septicemia (10.5%). The isolated pathogenic organisms were Streptococcus pneumoniae (35.5%) and Salmonella spp (33.3%). Third generation cephalosporins were the most commonly prescribed antibiotics. Gros mortality rate was 7.5%. Bacterial infections and malaria dominate the clinical picture of infections in children with major sickle cell syndrome at the at the Pediatrics University Hospital Center Charles De-Gaulle. This study highlights the importance of establishing a national program for the management of sickle-cell anemia, which could help prevent or reduce the occurrence of infections in children with sickle cell syndrome.

Analysis of oxidative status and biochemical parameters in adult patients with sickle cell anemia treated with hydroxyurea, Ceará, Brazil

PubMed Central

Teixeira Neto, Paulo Florentino; Gonçalves, Romélia Pinheiro; Elias, Darcielle Bruna Dias; de Araújo, Cleiton Pinheiro; Magalhães, Hemerson Iury Ferreira

2011-01-01

Background Sickle cell anemia is a hemoglobinopathy caused by a mutation that results in the production of an abnormal hemoglobin molecule, hemoglobin S (Hb S). This is responsible for profound physiological changes, such as the sickling of red blood cells. Several studies have shown that hydroxyurea protects against vaso-occlusive crises. Objective The aim of this study was to evaluate the oxidative stress associated with biochemical parameters in patients with sickle cell anemia treated with hydroxyurea. Methods The study was conducted with 20 male and 25 female patients at the Hospital Universitário Walter Cantídio. The patients were divided into two groups: a study group (n = 12), patients with sickle cell anemia who were receiving hydroxyurea and a control group (n = 33) of sickle cell anemia patients not submitted to hydroxyurea treatment. The biochemical parameters analyzed were ferritin, transferrin, and serum iron. Glutathione was measured in its reduced form to analyze the oxidative state. Results The results showed insignificant increases in the levels of serum iron, transferrin and ferritin in patients treated with hydroxyurea when compared with those who did not take the medication. However, the glutathione levels were significantly higher in patients taking hydroxyurea than in controls. Conclusions These results indicate that hydroxyurea possibly acts as an antioxidant by increasing glutathione levels. PMID:23049297

Use of piracetam improves sickle cell deformability in vitro and in vivo.

PubMed Central

Gini, E K; Sonnet, J

1987-01-01

Microsieving diluted suspensions of oxygenated sickle cell anaemia (HbSS) cells on polycarbonate filters shows that piracetam improves the red cell deformability in vitro. In vivo an oral intake of 160 mg/kg/day divided in four doses enhances the HbSS cell deformability as actively as it does in in vitro experiments. The drug is also able partially to restore the impaired deformability of physiologically deoxygenated HbSS cells. These findings are consistent with the results of clinical trials, which show that continuous treatment with piracetam reduces the incidence of vaso-occlusive crises in patients with sickle cell disease. PMID:3818978

Interventions for treating painful sickle cell crisis during pregnancy.

PubMed

Martí-Carvajal, Arturo J; Peña-Martí, Guiomar E; Comunián-Carrasco, Gabriella; Martí-Peña, Arturo J

2009-01-21

Sickle cell disease is a group of genetic haemoglobin disorders. All over the world, about 300,000 children with these disorders are born each year. Acute sickle cell pain episodes are the most common cause of hospitalisation. Pregnancy in women with sickle cell disease is associated with an increased incidence of maternal and fetal morbidity and mortality. The painful crisis is a severe complication of this illness, and it requires several interventions: packed red cell transfusion, fluid replacement therapy, analgesic drugs, oxygen therapy and steroids; but the approach is not standardised. To assess the effectiveness and safety of different regimens of packed red cell transfusion, oxygen therapy, fluid replacement therapy, analgesic drugs, and steroids for the treatment of painful sickle cell crisis during pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2007), the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register (October 2007), LILACS database (1982 to December 2007) and the following web sites: ClinicalTrials.gov (http://www.clinicaltrials.gov) (December 5, 2007); Current Controlled Trials (http://controlled-trials.com/) (December 5, 2007), and Sistema de Información Esencial en Terapéutica y Salud (http://www.icf.uab.es/informacion/Papyrus/sietes.asp) (December 1, 2007). We also handsearched the European Haematology Association conference (June 2007), the American Society of Hematology conference (December 2007) and reference lists of all retrieved articles. We intended to include randomised clinical trials. We intended to summarise data by standard Cochrane Collaboration methodologies. We could not find any randomised clinical trials on interventions (packed red cell transfusion, oxygen therapy, fluid replacement therapy, analgesic drugs, and steroids) for the treatment of painful sickle cell crisis during pregnancy. This review found no randomised clinical trials on the safety and efficacy of interventions for treating painful sickle cell crisis during pregnancy. The effects of interventions need to be tested in randomised clinical trials.

[French guidelines for the management of adult sickle cell disease: 2015 update].

PubMed

Habibi, A; Arlet, J-B; Stankovic, K; Gellen-Dautremer, J; Ribeil, J-A; Bartolucci, P; Lionnet, F

2015-05-11

Sickle cell disease is a systemic genetic disorder, causing many functional and tissular modifications. As the prevalence of patients with sickle cell disease increases gradually in France, every physician can be potentially involved in the care of these patients. Complications of sickle cell disease can be acute and chronic. Pain is the main symptom and should be treated quickly and aggressively. In order to reduce the fatality rate associated with acute chest syndrome, it must be detected and treated early. Chronic complications are one of the main concerns in adults and should be identified as early as possible in order to prevent end organ damage. Many organs can be involved, including bones, kidneys, eyes, lungs, etc. The indications for a specific treatment (blood transfusion or hydroxyurea) should be regularly discussed. Coordinated health care should be carefully organized to allow a regular follow-up near the living place and access to specialized departments. We present in this article the French guidelines for the sickle cell disease management in adulthood. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute complications of sickle cell disease in children.

PubMed

2001-05-01

Sickle cell disease is a recessively inherited condition in which synthesis of haemoglobin is abnormal. The disease, which occurs mainly in people of African, African-Caribbean, Indian, Mediterranean and Middle Eastern descent, is characterised by chronic anaemia, susceptibility to infection, bouts of severe pain and organ dysfunction. While the life expectancy for patients has improved, from a median survival age of 14 years in the 1970s among those homozygous for the sickle haemoglobin gene to survival into the mid-40s, childhood remains a period of peak mortality and morbidity. Here, we discuss the acute complications of sickle cell disease in children, concentrating on the management of the acutely unwell child.

Potentially Therapeutic Levels of Anti-Sickling Globin Gene Expression Following Lentivirus-mediated Gene Transfer in Sickle Cell Disease Bone Marrow CD34+ Cells

PubMed Central

Urbinati, Fabrizia; Hargrove, Philip W.; Geiger, Sabine; Romero, Zulema; Wherley, Jennifer; Kaufman, Michael L.; Hollis, Roger P.; Chambers, Christopher B.; Persons, Derek A.; Kohn, Donald B.; Wilber, Andrew

2015-01-01

Sickle cell disease (SCD) can be cured by allogeneic hematopoietic stem cell (HSC) transplant. However, this is only possible when a matched donor is available making the development of gene therapy using autologous HSCs a highly desired alternative. We used a culture model of human erythropoiesis to directly compare two insulated, self-inactivating, and erythroid-specific lentiviral vectors, encoding for γ-globin (V5m3-400) or a modified β-globin (βAS3-FB) for production of anti-sickling hemoglobin (Hb) and correction of red cell deformability after deoxygenation. Bone marrow CD34+ cells from three SCD patients were transduced using V5m3-400 or βAS3-FB and compared to mock transduced SCD or healthy donor CD34+ cells. Lentiviral transduction did not impair cell growth or differentiation, as gauged by proliferation and acquisition of erythroid markers. Vector copy number averaged ~1 copy per cell and corrective globin mRNA levels were increased more than 7-fold over mock-transduced controls. Erythroblasts derived from healthy donor and mock-transduced SCD cells produced a low level of HbF that was increased to 23.6 ± 4.1% per vector copy for cells transduced with V5m3-400. Equivalent levels of modified HbA of 17.6 ± 3.8% per vector copy were detected for SCD cells transduced with βAS3-FB. These levels of anti-sickling Hb production were sufficient to reduce sickling of terminal stage RBCs upon deoxygenation. We conclude that the achieved levels of HbF and modified HbA would likely prove therapeutic to SCD patients who lack matched donors. PMID:25681747

β-Globin chain abnormalities with coexisting α-thalassemia mutations

PubMed Central

Canataroglu, Abdullah; Unsal, Cagatay; Yildiz, Sule Menziletoglu; Turhan, Ferda Tekin; Bozdogan, Sevcan Tug; Dincer, Suleyman; Erkman, Hakan

2012-01-01

Introduction The frequency of hemoglobinopathies is still high in Adana, the biggest city of the Cukurova Region that is located in the southern part of Turkey. Our aim was to identify the concomitant mutations in α- and β-globin genes which lead to complex hemoglobinopathies and to establish an appropriate plan of action for each subject, particularly when prenatal diagnosis is necessary. Material and methods We studied the association between the β-globin gene and α-thalassemia genotypes. The reverse hybridization technique was employed to perform molecular analysis, and the results were confirmed by amplification refractory mutation system (ARMS) or restriction fragment length polymorphism (RFLP) technique. Results We evaluated 36 adult subjects (28 female and 8 male; age range: 18-52 years) with concomitant mutations in their α- and β-globin genes. The –α3.7/αα deletion was the commonest defect in the α-chain as expected, followed by α3.7/–α3.7 deletion. Twenty-five of 36 cases were sickle cell trait with coexisting α-thalassemia, while seven Hb S/S patients had concurrent mutations in their α-genes. The coexistence of αPolyA-2α/αα with Hb A/D and with Hb S/D, which is very uncommon, was also detected. There was a subject with compound heterozygosity for β-globin chain (–α3.7/αα with IVSI.110/S), and also a case who had –α3.7/αα deletion with IVSI.110/A. Conclusions Although limited, our data suggest that it would be valuable to study coexisting α-globin mutations in subjects with sickle cell disease or β-thalassemia trait during the screening programs for premarital couples, especially in populations with a high frequency of hemoglobinopathies. PMID:23056075

Association among sickle cell trait, fitness, and cardiovascular risk factors in CARDIA.

PubMed

Liem, Robert I; Chan, Cheeling; Vu, Thanh-Huyen T; Fornage, Myriam; Thompson, Alexis A; Liu, Kiang; Carnethon, Mercedes R

2017-02-09

The contribution of sickle cell trait (SCT) to racial disparities in cardiopulmonary fitness is not known, despite concerns that SCT is associated with exertion-related sudden death. We evaluated the association of SCT status with cross-sectional and longitudinal changes in fitness and risk for hypertension, diabetes, and metabolic syndrome over the course of 25 years among 1995 African Americans (56% women, 18-30 years old) in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Overall, the prevalence of SCT was 6.8% (136/1995) in CARDIA, and over the course of 25 years, 46% (738/1590), 18% (288/1631), and 40% (645/1,611) of all participants developed hypertension, diabetes, and metabolic syndrome, respectively. Compared with participants without SCT, participants with SCT had similar baseline measures of fitness in cross-section, including exercise duration (535 vs 540 seconds; P = .62), estimated metabolic equivalent of tasks (METs; 11.6 vs 11.7; P = .80), maximum heart rate (174 vs 175 beats/min; P = .41), and heart rate at 2 minutes recovery (44 vs 43 beats/min; P = .28). In our secondary analysis, there was neither an association of SCT status with longitudinal changes in fitness nor an association with development of hypertension, diabetes, or metabolic syndrome after adjustment for sex, baseline age, body mass index, fitness, and physical activity. SCT is not associated with reduced fitness in this longitudinal study of young African American adults, suggesting the increased risk for exertion-related sudden death in SCT carriers is unlikely related to fitness. SCT status also is not an independent risk factor for developing hypertension, diabetes, or metabolic syndrome. © 2017 by The American Society of Hematology.

Plasmodium falciparum infection in febrile Congolese children: prevalence of clinical malaria 10 years after introduction of artemisinin-combination therapies.

PubMed

Etoka-Beka, Mandingha Kosso; Ntoumi, Francine; Kombo, Michael; Deibert, Julia; Poulain, Pierre; Vouvoungui, Christevy; Kobawila, Simon Charles; Koukouikila-Koussounda, Felix

2016-12-01

To investigate the proportion of malaria infection in febrile children consulting a paediatric hospital in Brazzaville, to determine the prevalence of submicroscopic malaria infection, to characterise Plasmodium falciparum infection and compare the prevalence of uncomplicated P. falciparum malaria according to haemoglobin profiles. Blood samples were collected from children aged <10 years with an axillary temperature ≥37.5 °C consulting the paediatric ward of Marien Ngouabi Hospital in Brazzaville. Parasite density was determined and all samples were screened for P. falciparum by nested polymerase chain reaction (PCR) using the P. falciparum msp-2 marker to detect submicroscopic infections and characterise P. falciparum infection. Sickle cell trait was screened by PCR. A total of 229 children with fever were recruited, of whom 10% were diagnosed with uncomplicated malaria and 21% with submicroscopic infection. The mean parasite density in children with uncomplicated malaria was 42 824 parasites/μl of blood. The multiplicity of infection (MOI) was 1.59 in children with uncomplicated malaria and 1.69 in children with submicroscopic infection. The mean haemoglobin level was 10.1 ± 1.7 for children with uncomplicated malaria and 12.0 ± 8.6 for children with submicroscopic infection. About 13% of the children harboured the sickle cell trait (HbAS); the rest had normal haemoglobin (HbAA). No difference in prevalence of uncomplicated malaria and submicroscopic infection, parasite density, haemoglobin level, MOI and P. falciparum genetic diversity was observed according to haemoglobin type. The low prevalence of uncomplicated malaria in febrile Congolese children indicates the necessity to investigate carefully other causes of fever. © 2016 John Wiley & Sons Ltd.

Preventive health care and screening of Latin American immigrants in the United States.

PubMed

Weissman, A M

1994-01-01

The Central and South American immigrant population in the United States is large and growing. A review of the preventive health care needs of this population has not previously been done but would be helpful to clinicians caring for immigrants in this country. Using MEDLINE, the literature related to immigrants and their health status was searched, using the key words "immigrant," "refugee," "South/Central/Latin America," "health status," "screening," "nutrition," "parasites," "stomach/gastric cancer," "children," and "psychological." The American Statistics Index and Index to International Statistics were also resources. The available literature was reviewed and led to the recommendations in this article. Screening strategies for Latin American immigrants are discussed for intestinal parasites, tuberculosis, hepatitis B, schistosomiasis, leprosy, American trypanosomiasis (Chagas disease), malaria, human immunodeficiency virus (HIV) infection, cervical and gastric cancer, sickle cell trait, malnutrition, iron-deficiency anemia, incomplete immunizations, dental problems, psychological problems, impairment in the elderly, alcohol use, smoking, physical inactivity, and hypertension. There are not enough data to evaluate fully the screening strategies for most of these conditions, but recommendations are offered based on current knowledge. Screening is recommended for intestinal parasites and schistosomiasis, tuberculosis, hepatitis B in prenatal patients, leprosy in immigrants from high-risk areas, yearly Papanicolaou smears, malnutrition, iron-deficiency anemia, incomplete immunizations, dental problems, history of violence, and depression. Screening for sickle cell trait in prenatal patients from South America and universal hepatitis B screening are less clearly indicated but could be appropriate. Screening for American trypanosomiasis (Chagas disease), malaria, and gastric cancer is not recommended. Screening for HIV infection, functional impairment in the elderly, alcohol use, cigarette smoking, physical inactivity, and hypertension should be the same as for the general population.

Novel single-cell functional analysis of red blood cells using laser tweezers Raman spectroscopy: application for sickle cell disease.

PubMed

Liu, Rui; Mao, Ziliang; Matthews, Dennis L; Li, Chin-Shang; Chan, James W; Satake, Noriko

2013-07-01

Laser tweezers Raman spectroscopy was used to characterize the oxygenation response of single normal adult, sickle, and cord blood red blood cells (RBCs) to an applied mechanical force. Individual cells were subjected to different forces by varying the laser power of a single-beam optical trap, and the intensities of several oxygenation-specific Raman spectral peaks were monitored to determine the oxygenation state of the cells. For all three cell types, an increase in laser power (or mechanical force) induced a greater deoxygenation of the cell. However, sickle RBCs deoxygenated more readily than normal RBCs when subjected to the same optical forces. Conversely, cord blood RBCs were able to maintain their oxygenation better than normal RBCs. These results suggest that differences in the chemical or mechanical properties of fetal, normal, and sickle cells affect the degree to which applied mechanical forces can deoxygenate the cell. Populations of normal, sickle, and cord RBCs were identified and discriminated based on this mechanochemical phenomenon. This study demonstrates the potential application of laser tweezers Raman spectroscopy as a single-cell, label-free analytical tool to characterize the functional (e.g., mechanical deformability, oxygen binding) properties of normal and diseased RBCs. Copyright © 2013 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

The intersection between asthma and acute chest syndrome in children with sickle-cell anaemia

PubMed Central

DeBaun, Michael R; Strunk, Robert C

2016-01-01

Acute chest syndrome is a frequent cause of acute lung disease in children with sickle-cell disease. Asthma is common in children with sickle-cell disease and is associated with increased incidence of vaso-occlusive pain events, acute chest syndrome episodes, and earlier death. Risk factors for asthma exacerbation and an acute chest syndrome episode are similar, and both can present with shortness of breath, chest pain, cough, and wheezing. Despite overlapping risk factors and symptoms, an acute exacerbation of asthma or an episode of acute chest syndrome are two distinct entities that need disease-specific management strategies. Although understanding has increased about asthma as a comorbidity in sickle-cell disease and its effects on morbidity, substantial gaps remain in knowledge about best management. PMID:27353685

Ectodermal Dysplasia Associated with Sickle Cell Disease

PubMed Central

Volpato, Luiz Evaristo Ricci; Volpato, Maria Carmen Palma Faria; de Carvalhosa, Artur Aburad; Palma, Vinicius Canavarros; Borges, Álvaro Henrique

2014-01-01

Ectodermal dysplasia and sickle cell anaemia are inherited disorders that affect, respectively, the tissues derived from the embryonic ectoderm and the production of erythrocytes by the bone marrow. The simultaneous occurrence of both disorders is extremely rare. This is a case of both ectodermal dysplasia and sickle cell anaemia reported in a 6-year-old. The patient had been diagnosed with sickle cell anaemia for only six months when he sought treatment presenting with the following: hypotrichosis, dry skin, periocular hyperpigmentation, protruding lips, hypodontia, and morphologically altered teeth. The clinical features combined with his medical history led to the diagnosis of ectodermal dysplasia. Dentists should be prepared to recognise patterns that escape normality to aid in the diagnosis of systemic changes, even in patients with other previous diagnoses. PMID:25343049

Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management.

PubMed

Yazdanbakhsh, Karina; Ware, Russell E; Noizat-Pirenne, France

2012-07-19

Red blood cell transfusions have reduced morbidity and mortality for patients with sickle cell disease. Transfusions can lead to erythrocyte alloimmunization, however, with serious complications for the patient including life-threatening delayed hemolytic transfusion reactions and difficulty in finding compatible units, which can cause transfusion delays. In this review, we discuss the risk factors associated with alloimmunization with emphasis on possible mechanisms that can trigger delayed hemolytic transfusion reactions in sickle cell disease, and we describe the challenges in transfusion management of these patients, including opportunities and emerging approaches for minimizing this life-threatening complication.

Abdominal pain in adult sickle cell disease patients: a nigerian experience.

PubMed

Akingbola, T S; Kolude, B; Aneni, E C; Raji, A A; Iwara, K U; Aken'Ova, Y A; Soyannwo, O A

2011-12-01

Abdominal pain is a relatively frequent occurrence in sickle cell disease. The aetiology of abdominal pain in sickle cell disease is often difficult to diagnose clinically. Despite the frequent occurrence, diagnostic dilemma, and the need for an accurate, early diagnosis, abdominal pain in sickle cell disease has not been rigorously studied. We therefore sought to describe the different presentations and patterns of abdominal pain in persons with sickle cell disease. A prospective case series of 20 patients was done in which data was collected on demographic characteristics, hemoglobin electrophoresis patterns, a description of the abdominal pain including sites, severity, and type of pain, packed cell volume and the provisional and final diagnosis. Haemoglobin S patients were 17 in number constituting eightyfive percent (85%) of our study population whilst the rest 3 were Hb S+C. Most patients (70%) had one site of abdominal pain. The pain was mainly colicky or tightening, moderate to severe in nature and, in some cases, associated with vomiting. We did not find any significant difference between the steady state PCV and the PCV during the acute abdominal pain episodes. The final diagnosis showed that only 38.8% of the patients had vasoocclusive crises and the reliability index between the provisional diagnosis and the final diagnosis was 67%. Abdominal pain in sickle cell disease may present in different ways and it is important to recognize that the possible diagnoses are numerous. Not all cases are due to vasoocclusive crises. Early diagnosis and prompt treatment can be life saving.

CD34+ (Non-Malignant) Stem Cell Selection for Patients Receiving Allogeneic Stem Cell Transplantation

ClinicalTrials.gov

2017-07-13

Bone Marrow Failure Syndrome; Severe Aplastic Anemia; Severe Congenital Neutropenia; Amegakaryocytic Thrombocytopenia; Diamond-Blackfan Anemia; Schwachman Diamond Syndrome; Primary Immunodeficiency Syndromes; Acquired Immunodeficiency Syndromes; Histiocytic Syndrome; Familial Hemophagocytic Lymphocytosis; Lymphohistiocytosis; Macrophage Activation Syndrome; Langerhans Cell Histiocytosis (LCH); Hemoglobinopathies; Sickle Cell Disease; Sickle Cell-beta-thalassemia

Zinc supplements for treating thalassaemia and sickle cell disease.

PubMed

Swe, Kye Mon Min; Abas, Adinegara B L; Bhardwaj, Amit; Barua, Ankur; Nair, N S

2013-06-28

Haemoglobinopathies, inherited disorders of haemoglobin synthesis (thalassaemia) or structure (sickle cell disease), are responsible for significant morbidity and mortality throughout the world. The WHO estimates that, globally, 5% of adults are carriers of a haemoglobin condition, 2.9% are carriers of thalassaemia and 2.3% are carriers of sickle cell disease. Carriers are found worldwide as a result of migration of various ethnic groups to different regions of the world. Zinc is an easily available supplement and intervention programs have been carried out to prevent deficiency in people with thalassaemia or sickle cell anaemia. It is important to evaluate the role of zinc supplementation in the treatment of thalassaemia and sickle cell anaemia to reduce deaths due to complications. To assess the effect of zinc supplementation in the treatment of thalassaemia and sickle cell disease. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 01 February 2013. Randomised, placebo-controlled trials of zinc supplements for treating thalassaemia or sickle cell disease administered at least once a week for at least a month. Two review authors assessed the eligibility and risk of bias of the included trials, extracted and analysed data and wrote the review. We summarised results using risk ratios or rate ratios for dichotomous data and mean differences for continuous data. We combined trial results where appropriate. We identified nine trials for inclusion with all nine contributing outcome data. Two trials reported on people with thalassaemia (n = 152) and seven on sickle cell anaemia (n = 307).In people with thalassaemia, in one trial, the serum zinc level value showed no difference between the zinc supplemented group and the control group, mean difference 47.40 (95% confidence interval -12.95 to 107.99). Regarding anthropometry, in one trial, height velocity was significantly increased in patients who received zinc supplementation for one to seven years duration, mean difference 3.37 (95% confidence interval 2.36 to 4.38) (total number of participants = 26). In one trial, however, there was no difference in body mass index between treatment groups.Zinc acetate supplementation for three months (in one trial) and one year (in two trials) (total number of participants = 71) was noted to increase the serum zinc level significantly in patients with sickle cell anaemia, mean difference 14.90 (95% confidence interval 6.94 to 22.86) and 20.25 (95% confidence interval 11.73 to 28.77) respectively. There was no significant difference in haemoglobin level between intervention and control groups, at either three months (one trial) or one year (one trial), mean difference 0.06 (95% confidence interval -0.84 to 0.96) and mean difference -0.07 (95% confidence interval -1.40 to 1.26) respectively. Regarding anthropometry, one trial showed no significant changes in body mass index or weight after one year of zinc acetate supplementation. In patients with sickle cell disease, the total number of sickle cell crises at one year were significantly decreased in the zinc sulphate supplemented group as compared to controls, mean difference -2.83 (95% confidence interval -3.51 to -2.15) (total participants 130), but not in zinc acetate group, mean difference 1.54 (95% confidence interval -2.01 to 5.09) (total participants 22). In one trial at three months and another at one year, the total number of clinical infections were significantly decreased in the zinc supplemented group as compared to controls, mean difference 0.05 (95% confidence interval 0.01 - 0.43) (total number of participants = 36), and mean difference -7.64 (95% confidence interval -10.89 to -4.39) (total number of participants = 21) respectively. According to the results, there is no evidence from randomised controlled trials to indicate any benefit of zinc supplementation with regards to serum zinc level in patients with thalassaemia. However, height velocity was noted to increase among those who received this intervention.There is mixed evidence on the benefit of using zinc supplementation in people with sickle cell disease. For instance, there is evidence that zinc supplementation for one year increased the serum zinc levels in patients with sickle cell disease. However, though serum zinc level was raised in patients receiving zinc supplementation, haemoglobin level and anthropometry measurements were not significantly different between groups. Evidence of benefit is seen with the reduction in the number of sickle cell crises among sickle cell patients who received one year of zinc sulphate supplementation and with the reduction in the total number of clinical infections among sickle cell patients who received zinc supplementation for both three months and for one year.The conclusion is based on the data from a small group of trials,which were generally of good quality, with a low risk of bias. The authors recommend that more trials on zinc supplementation in thalassaemia and sickle cell disease be conducted given that the literature has shown the benefits of zinc in these types of diseases.

Regular long-term red blood cell transfusions for managing chronic chest complications in sickle cell disease

PubMed Central

Estcourt, Lise J; Fortin, Patricia M; Hopewell, Sally; Trivella, Marialena; Hambleton, Ian R; Cho, Gavin

2016-01-01

Background Sickle cell disease is a genetic haemoglobin disorder, which can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Sickle cell disease is one of the most common severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. The two most common chronic chest complications due to sickle cell disease are pulmonary hypertension and chronic sickle lung disease. These complications can lead to morbidity (such as reduced exercise tolerance) and increased mortality. This is an update of a Cochrane review first published in 2011 and updated in 2014. Objectives We wanted to determine whether trials involving people with sickle cell disease that compare regular long-term blood transfusion regimens with standard care, hydroxycarbamide (hydroxyurea) any other drug treatment show differences in the following: mortality associated with chronic chest complications; severity of established chronic chest complications; development and progression of chronic chest complications; serious adverse events. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register. Date of the last search: 25 April 2016. We also searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 26 January 2016), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 26 January 2016. Selection criteria We included randomised controlled trials of people of any age with one of four common sickle cell disease genotypes, i.e. Hb SS, Sß0, SC, or Sß+ that compared regular red blood cell transfusion regimens (either simple or exchange transfusions) to hydroxycarbamide, any other drug treatment, or to standard care that were aimed at reducing the development or progression of chronic chest complications (chronic sickle lung and pulmonary hypertension). Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results No studies matching the selection criteria were found. Authors’ conclusions There is a need for randomised controlled trials looking at the role of long-term transfusion therapy in pulmonary hypertension and chronic sickle lung disease. Due to the chronic nature of the conditions, such trials should aim to use a combination of objective and subjective measures to assess participants repeatedly before and after the intervention. PMID:27198469

Piracetam for reducing the incidence of painful sickle cell disease crises.

PubMed

Al Hajeri, A A; Fedorowicz, Z; Omran, A; Tadmouri, G O

2007-04-18

Sickle cell disease is one of the most common genetic disorders. Sickle cell crises in which irregular and dehydrated cells contribute to blocking of blood vessels are characterised by episodes of pain. Treatment is mainly supportive and symptomatic. In vitro studies with piracetam indicate that it has the potential for inhibition and a reversal of the process of sickling of erythrocytes. To assess the effectiveness of piracetam for reducing the incidence of painful sickle cell disease crises. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register which comprises of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of the last search of the Group's Haemoglobinopathies Trials Register: February 2007. Randomised controlled trials comparing orally administered piracetam to placebo or standard care in people, of all ages and both sexes, with sickle cell disease. Two authors independently assessed trial quality and extracted data. Trial authors were contacted for additional information. Adverse effects data were collected from the trials. Three trials involving 169 participants were included in the review. A limited amount of data addressing some of the primary and some of the secondary outcomes were provided, but data were incomplete and based on unvalidated assumptions used in the evaluation of outcomes. One trial reported a reduction in the number of pain crises and their severity with active intervention than placebo but presented no data to confirm these results. A second trial presented a monthly global pain score based on the number of sickle cell crises and severity of pain but included no separate data for these primary outcomes. Although there was no significant difference between the piracetam and placebo periods for the number of days of hospitalisation (P = 0.87) in one trial, inconsistencies in the criteria necessary for hospitalisation during sickle crises did not permit accurate conclusions to be drawn. Two of the trials reported participant satisfaction with piracetam but provided no details as to how this satisfaction had been assessed. There were no reports of toxicity or adverse effects with piracetam other than one participant who experienced dizziness. The small number of included trials and their poor methodological quality provided insufficient reliable evidence to support the routine use of this medication for preventing the incidence of painful sickle cell disease crises.

Detrimental effects of adenosine signaling in sickle cell disease

PubMed Central

Zhang, Yujin; Dai, Yingbo; Wen, Jiaming; Zhang, Weiru; Grenz, Almut; Sun, Hong; Tao, Lijian; Lu, Guangxiu; Alexander, Danny C; Milburn, Michael V; Carter-Dawson, Louvenia; Lewis, Dorothy E; Zhang, Wenzheng; Eltzschig, Holger K; Kellems, Rodney E; Blackburn, Michael R; Juneja, Harinder S; Xia, Yang

2016-01-01

Hypoxia can act as an initial trigger to induce erythrocyte sickling and eventual end organ damage in sickle cell disease (SCD). Many factors and metabolites are altered in response to hypoxia and may contribute to the pathogenesis of the disease. Using metabolomic profiling, we found that the steady-state concentration of adenosine in the blood was elevated in a transgenic mouse model of SCD. Adenosine concentrations were similarly elevated in the blood of humans with SCD. Increased adenosine levels promoted sickling, hemolysis and damage to multiple tissues in SCD transgenic mice and promoted sickling of human erythrocytes. Using biochemical, genetic and pharmacological approaches, we showed that adenosine A2B receptor (A2BR)-mediated induction of 2,3-diphosphoglycerate, an erythrocyte-specific metabolite that decreases the oxygen binding affinity of hemoglobin, underlies the induction of erythrocyte sickling by excess adenosine both in cultured human red blood cells and in SCD transgenic mice. Thus, excessive adenosine signaling through the A2BR has a pathological role in SCD. These findings may provide new therapeutic possibilities for this disease. PMID:21170046

Detrimental effects of adenosine signaling in sickle cell disease.

PubMed

Zhang, Yujin; Dai, Yingbo; Wen, Jiaming; Zhang, Weiru; Grenz, Almut; Sun, Hong; Tao, Lijian; Lu, Guangxiu; Alexander, Danny C; Milburn, Michael V; Carter-Dawson, Louvenia; Lewis, Dorothy E; Zhang, Wenzheng; Eltzschig, Holger K; Kellems, Rodney E; Blackburn, Michael R; Juneja, Harinder S; Xia, Yang

2011-01-01

Hypoxia can act as an initial trigger to induce erythrocyte sickling and eventual end organ damage in sickle cell disease (SCD). Many factors and metabolites are altered in response to hypoxia and may contribute to the pathogenesis of the disease. Using metabolomic profiling, we found that the steady-state concentration of adenosine in the blood was elevated in a transgenic mouse model of SCD. Adenosine concentrations were similarly elevated in the blood of humans with SCD. Increased adenosine levels promoted sickling, hemolysis and damage to multiple tissues in SCD transgenic mice and promoted sickling of human erythrocytes. Using biochemical, genetic and pharmacological approaches, we showed that adenosine A(2B) receptor (A(2B)R)-mediated induction of 2,3-diphosphoglycerate, an erythrocyte-specific metabolite that decreases the oxygen binding affinity of hemoglobin, underlies the induction of erythrocyte sickling by excess adenosine both in cultured human red blood cells and in SCD transgenic mice. Thus, excessive adenosine signaling through the A(2B)R has a pathological role in SCD. These findings may provide new therapeutic possibilities for this disease.

Mild splenic sequestration crises in sickle-hemoglobin C disease.

PubMed

Andrews, J; Buchanan, G R

1984-06-01

Acute splenic sequestration crisis ( ASSC ), a common complication in homozygous sickle cell anemia, has been described infrequently in sickle-hemoglobin C (SC) disease in the absence of high altitude exposure. In this report, we describe three children with hemoglobin SC disease who developed episodes of ASSC that were milder than those generally described in sickle cell anemia. In one patient, an antecedent triggering event was not recognized. The other two children may have had a predisposing cause for massive intrasplenic sickling in that one had an associated mononucleosis syndrome and the other an episode of hypovolemic shock following severe epistaxis. ASSC may occur in patients with SC disease and does not necessarily require a hypoxic trigger associated with high altitudes.

Splenectomy reduces packed red cell transfusion requirement in children with sickle cell disease.

PubMed

Haricharan, Ramanath N; Roberts, Jared M; Morgan, Traci L; Aprahamian, Charles J; Hardin, William D; Hilliard, Lee M; Georgeson, Keith E; Barnhart, Douglas C

2008-06-01

The purpose of the study was to measure the effect of splenectomy on packed-cell transfusion requirement in children with sickle cell disease. Thirty-seven sickle cell children who underwent splenectomies between January 2000 and May 2006 at a children's hospital were reviewed. Data were collected 6 months preoperatively to 12 months postsplenectomy. Paired t test, analysis of variance, and multivariable regression analyses were performed. Of 37 children with median age 11 years (range, 2-18 years), 34 (21 males) had data that allowed analyses. Twenty-six had Hgb-SS, 5 had Hgb-SC, and 3 had Hgb S-Thal. Laparoscopic splenectomy was attempted in 36 and completed successfully in 34 (94% success). The number of units transfused decreased by 38% for 0 to 6 months and by 45% for 6 to 12 months postsplenectomy. Postoperatively, hematocrit levels increased and reticulocytes concurrently decreased with a reduction in transfusion clinic visits. The decrease in transfusion was not influenced by spleen weight, age, or hemoglobin type. Two children had acute chest syndrome (6%), and 1 had severe pneumonia (3%). Laparoscopic splenectomy can be successfully completed in sickle cell children. Splenectomy significantly reduces the packed red cell transfusion requirement and frequency of clinic visits, in sickle cell children for at least 12 months postoperatively.

Effect of Age on Blood Rheology in Sickle Cell Anaemia and Sickle Cell Haemoglobin C Disease: A Cross-Sectional Study.

PubMed

Renoux, Céline; Romana, Marc; Joly, Philippe; Ferdinand, Séverine; Faes, Camille; Lemonne, Nathalie; Skinner, Sarah; Garnier, Nathalie; Etienne-Julan, Maryse; Bertrand, Yves; Petras, Marie; Cannas, Giovanna; Divialle-Doumdo, Lydia; Nader, Elie; Cuzzubbo, Daniela; Lamarre, Yann; Gauthier, Alexandra; Waltz, Xavier; Kebaili, Kamila; Martin, Cyril; Hot, Arnaud; Hardy-Dessources, Marie-Dominique; Pialoux, Vincent; Connes, Philippe

2016-01-01

Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown. Blood viscosity, red blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients. Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age. The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders.

GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice

PubMed Central

Chang, Jungshan; Patton, John T.; Sarkar, Arun; Ernst, Beat

2010-01-01

Leukocyte adhesion in the microvasculature influences blood rheology and plays a key role in vaso-occlusive manifestations of sickle cell disease. Notably, polymorphonuclear neutrophils (PMNs) can capture circulating sickle red blood cells (sRBCs) in inflamed venules, leading to critical reduction in blood flow and vaso-occlusion. Recent studies have suggested that E-selectin expression by endothelial cells plays a key role by sending activating signals that lead to the activation of Mac-1 at the leading edge of PMNs, thereby allowing RBC capture. Thus, the inhibition of E-selectin may represent a valuable target in this disease. Here, we have tested the biologic properties of a novel synthetic pan-selectin inhibitor, GMI-1070, with in vitro assays and in a humanized model of sickle cell vaso-occlusion analyzed by intravital microscopy. We have found that GMI-1070 predominantly inhibited E-selectin–mediated adhesion and dramatically inhibited sRBC-leukocyte interactions, leading to improved microcirculatory blood flow and improved survival. These results suggest that GMI-1070 may represent a valuable novel therapeutic intervention for acute sickle cell crises that should be further evaluated in a clinical trial. PMID:20508165

Conservative treatment of sickle cell avascular necrosis of the femoral head.

PubMed

Washington, E R; Root, L

1985-01-01

Treatment of avascular necrosis of the femoral head in adolescents with sickle cell anemia has not yet been standardized. In this study we review the literature and report on three patients with the Legg-Perthes-type avascular necrosis associated with sickle cell disease. These patients were successfully treated by partial weight-bearing with crutches and active range-of-motion exercises. We have examined physiologic and anatomic factors in this specific disease syndrome, which suggest that this may be the preferred method of treatment.

Medical Planning Criteria for Implementation of Clinical Hyperbaric Facilities.

DTIC Science & Technology

1984-12-01

Leprosy 2. Mycosis, selected refractory 3. Gas gangrene . . 4. Soft tissue infection 5. Diabetic ulcer 6. Sickle cell crisis /hematuria 7. Anemia due to...ulcer 25060 , 25061 25069 6. Sickle cell crisis /hematuria 28250 _ 28260 43 o •.. . " • 7. Anemia due to exceptional blood loss 28510 8. Meningitis...1 .001 1.33 3 . Scleroderma (21) 1 .033 1.00 40 Sickle cell crisis /hematuria (6) 1 .127 2.00 4 Skin grafts/flaps, compromised (34) 1 .074 1.87 10

Fulminant ischaemic colitis with atypical clinical features complicating sickle cell disease.

PubMed

Karim, Anita; Ahmed, S; Rossoff, Leonard J; Siddiqui, R; Fuchs, A; Multz, A S

2002-06-01

Clinically significant ischaemic bowel injury is an exceedingly rare complication of sickle cell disease. It manifests as acute surgical abdomen and may respond to conservative treatment. An unusual fatal case of ischaemic colitis with minimal abdominal findings in a young male during a sickle cell vaso-occlusive pain crisis is described. This case demonstrates that an acute surgical abdomen should be considered in such patients who fail to respond to conservative management as untreated this condition may be fatal.

Lead toxicity masquerading as sickle cell crisis.

PubMed

Nelson, M S; Chisolm, J J

1986-06-01

We recently saw a 12-year-old black boy with known sickle cell disease who had been seen many times for abdominal pain thought to be secondary to a vasoocclusive crisis. The patient eventually was admitted, after a seizure and the onset of obtundation. The etiology of his acute encephalopathy remained unclear until bone films of his knees fortuitously revealed "lead lines." The patient was treated and did well subsequently. This case emphasizes the importance of considering other diagnoses when a sickle cell patient presents with a crisis.

Frontal and orbital bone infarctions causing periorbital swelling in patients with sickle cell anemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garty, I.; Koren, A.; Garzozi, H.

1984-10-01

Two cases of unilateral and bilateral periorbital hematomas occurred in patients with sickle cell anemia. The cause of periorbital swelling in these cases was found to be orbital and frontal bone infarctions, respectively, diagnosed by technetium Tc 99m medronate bone scintigraphy. To our knowledge, periorbital bone infarction, as a part of the differential diagnosis of periorbital hematoma and as part of the possible ocular manifestations in patients with sickle cell anemia, has not previously been described.

Sickle Cell Disease (SCD)

MedlinePlus

... del paciente Transplant process Diseases treated by transplant Acute myeloid leukemia Adrenoleukodystrophy (ALD) Chronic Lymphocytic Leukemia (CLL) ... SCID) Sickle cell disease (SCD) Wiskott-Aldrich syndrome Acute lymphoblastic leukemia (ALL) Other diseases Treatment decisions Learn ...

Increased adherence of sickled and phosphatidylserine-enriched human erythrocytes to cultured human peripheral blood monocytes.

PubMed

Schwartz, R S; Tanaka, Y; Fidler, I J; Chiu, D T; Lubin, B; Schroit, A J

1985-06-01

The precise mechanism by which sickle erythrocytes (RBC) are removed from the circulation is controversial, although it is possible that enhanced recognition of these cells by circulating mononuclear phagocytes could contribute to this process. We investigated this possibility by interacting sickle cells with cultured human peripheral blood monocytes. Our results show that both irreversibly sickled cells (ISC) and deoxygenated reversibly sickled cells (RSC) had a higher avidity for adherence to monocytes than did oxygenated sickle and normal RBC. ISC were the most adherent cell type. Adherence of RSC to monocytes was found to be reversible; reoxygenation of deoxygenated RSC resulted in a significant decrease in RSC--monocyte adherence. Concomitant with alterations in sickle RBC adherence were alterations in the organization and bilayer distribution of membrane phospholipids in these cells. Specifically, enhanced adherence was associated with increased exposure of RBC membrane outer leaflet phosphatidylserine (PS) and phosphatidylethanolamine, whereas lack of adherence was associated with normal patterns of membrane phospholipid distribution. To investigate the possibility of whether the exposure of PS in the outer membrane leaflet of these cells might be responsible for their recognition by monocytes, the membranes of normal RBC were enriched with the fluorescent PS analogue 1-acyl-2[(N-4-nitro-benzo-2-oxa-1,3-diazole)aminocaproyl]-phosphatidy lse rine (NBD-PS) via transfer of the exogenous lipid from a population of donor phospholipid vesicles (liposomes). RBC enriched with NBD-PS exhibited enhanced adherence to monocytes, whereas adherence of RBC enriched with similar amounts of NBD-phosphatidylcholine (NBD-PC) was not increased. Furthermore, preincubation of monocytes with PS liposomes resulted in a approximately 60% inhibition of ISC adherence to monocytes, whereas no inhibition occurred when monocytes were preincubated with PC liposomes. These findings strongly suggest that erythrocyte surface PS may be a ligand recognized by receptors on human peripheral blood monocytes and that abnormal exposure of PS in the outer leaflet of the RBC membrane, as found in sickle RBC, might serve to trigger their recognition by circulating monocytes. Our results further suggest that abnormalities in the organization of erythrocyte membrane phospholipids may have significant pathophysiologic implications, possibly including shortened cell survival.

P-wave dispersion: relationship to left ventricular function in sickle cell anaemia.

PubMed

Oguanobi, N I; Onwubere, B J; Ike, S O; Anisiuba, B C; Ejim, E C; Ibegbulam, O G

2011-01-01

The prognostic implications of P-wave dispersion in patients with a variety of cardiac disease conditions are increasingly being recognised. The relationship between P-wave dispersion and left ventricular function in sickle cell anaemia is unknown. This study was aimed at evaluating the relationship between P-wave dispersion and left ventricular function in adult Nigerian sickle cell anaemia patients. Between February and August 2007, a total of 62 sickle cell anaemia patients (aged 18-44 years; mean 28.27 ± 5.58) enrolled in the study. These were drawn from patients attending the adult sickle cell clinic of the University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu. An equal number of age- and gender-matched normal subjects served as controls. All the participants were evaluated with electrocardiography and echocardiography. P-wave dispersion was defined as the difference between the maximum and minimum P-wave duration measured in a 12-lead electrocardiogram. P-wave duration and P-wave dispersion were significantly higher in patients than in controls. Significant correlation was demonstrated between P-wave dispersion and age in the patients (r = 0.387; p = 0.031). A comparison of subsets of sickle cell anaemia patients and controls with comparable haematocrit values (30-35%) showed significantly higher P-wave duration and P-wave dispersion in the patients than in the controls. The P-wave duration in patients and controls, respectively, was 111.10 ± 14.53 ms and 89.14 ± 16.45 ms (t = 3.141; p = 0.006). P-wave dispersion was 64.44 ± 15.86 ms in the patients and 36.43 ± 10.35 ms in the controls (t = 2.752; p = 0.013). Significant negative correlation was found between P-wave dispersion and left ventricular transmitral E/A ratio (r = -0.289; p = 0.023). These findings suggest that P-wave dispersion could be useful in the evaluation of sickle cell patients with left ventricular diastolic dysfunction. Further prospective studies are recommended to evaluate its prognostic implication on the long-term disease outcome in sickle cell disease patients.

Cholelithiasis and its complications in sickle cell disease in a university hospital.

PubMed

Martins, Raquel Alves; Soares, Renato Santos; Vito, Fernanda Bernadelli De; Barbosa, Valdirene de Fátima; Silva, Sheila Soares; Moraes-Souza, Helio; Martins, Paulo Roberto Juliano

The clinical manifestations of sickle cell disease are related to the polymerization of hemoglobin S. The chronic hemolysis caused by this condition often causes the formation of gallstones that can migrate and block the common bile duct leading to acute abdomen. This study aimed to evaluate the profile of patients with sickle cell disease and cholelithiasis. Patients with sickle cell disease were separated into groups according to the presence or absence of cholelithiasis. Socioepidemiological and clinical characteristics, such as gender, age, use of hydroxyurea and the presence of other hemoglobinopathies were researched in the medical records of patients. A hundred and seven patients with sickle cell anemia were treated at the institution. Of these, 27 (25.2%) had cholelithiasis. The presence of cholelithiasis was higher in the 11-29 age group than in younger than 11 years and over 29 years. No association was found for the presence of cholelithiasis with gender, use of hydroxyurea or type of hemoglobinopathy (hemoglobin SS, hemoglobin SC or sickle beta-thalassemia). Sixteen of the patients had to be submitted to cholecystectomy with 14 of the surgeries being performed by laparoscopy. Complications were observed in three patients and one patient died for reasons unrelated to the surgery. A quarter of patients with sickle cell disease had gallstones, more commonly in the 11- to 29-year age range. Patients should be monitored from childhood to prevent cholelithiasis with preoperative, intra-operative and postoperative care being crucial to reduce the risk of complications in these patients. Copyright © 2016 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

Mathematical modeling of erythrocyte chimerism informs genetic intervention strategies for sickle cell disease.

PubMed

Altrock, Philipp M; Brendel, Christian; Renella, Raffaele; Orkin, Stuart H; Williams, David A; Michor, Franziska

2016-09-01

Recent advances in gene therapy and genome-engineering technologies offer the opportunity to correct sickle cell disease (SCD), a heritable disorder caused by a point mutation in the β-globin gene. The developmental switch from fetal γ-globin to adult β-globin is governed in part by the transcription factor (TF) BCL11A. This TF has been proposed as a therapeutic target for reactivation of γ-globin and concomitant reduction of β-sickle globin. In this and other approaches, genetic alteration of a portion of the hematopoietic stem cell (HSC) compartment leads to a mixture of sickling and corrected red blood cells (RBCs) in periphery. To reverse the sickling phenotype, a certain proportion of corrected RBCs is necessary; the degree of HSC alteration required to achieve a desired fraction of corrected RBCs remains unknown. To address this issue, we developed a mathematical model describing aging and survival of sickle-susceptible and normal RBCs; the former can have a selective survival advantage leading to their overrepresentation. We identified the level of bone marrow chimerism required for successful stem cell-based gene therapies in SCD. Our findings were further informed using an experimental mouse model, where we transplanted mixtures of Berkeley SCD and normal murine bone marrow cells to establish chimeric grafts in murine hosts. Our integrative theoretical and experimental approach identifies the target frequency of HSC alterations required for effective treatment of sickling syndromes in humans. Our work replaces episodic observations of such target frequencies with a mathematical modeling framework that covers a large and continuous spectrum of chimerism conditions. Am. J. Hematol. 91:931-937, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Phase 1 Study of the E-Selectin Inhibitor GMI 1070 in Patients with Sickle Cell Anemia

PubMed Central

Wun, Ted; Styles, Lori; DeCastro, Laura; Telen, Marilyn J.; Kuypers, Frans; Cheung, Anthony; Kramer, William; Flanner, Henry; Rhee, Seungshin; Magnani, John L.; Thackray, Helen

2014-01-01

Background Sickle cell anemia is an inherited disorder of hemoglobin that leads to a variety of acute and chronic complications. Abnormal cellular adhesion, mediated in part by selectins, has been implicated in the pathophysiology of the vaso-occlusion seen in sickle cell anemia, and selectin inhibition was able to restore blood flow in a mouse model of sickle cell disease. Methods We performed a Phase 1 study of the selectin inhibitor GMI 1070 in patients with sickle cell anemia. Fifteen patients who were clinically stable received GMI 1070 in two infusions. Results The drug was well tolerated without significant adverse events. There was a modest increase in total peripheral white blood cell count without clinical symptoms. Plasma concentrations were well-described by a two-compartment model with an elimination T1/2 of 7.7 hours and CLr of 19.6 mL/hour/kg. Computer-assisted intravital microscopy showed transient increases in red blood cell velocity in 3 of the 4 patients studied. Conclusions GMI 1070 was safe in stable patients with sickle cell anemia, and there was suggestion of increased blood flow in a subset of patients. At some time points between 4 and 48 hours after treatment with GMI 1070, there were significant decreases in biomarkers of endothelial activation (sE-selectin, sP-selectin, sICAM), leukocyte activation (MAC-1, LFA-1, PM aggregates) and the coagulation cascade (tissue factor, thrombin-antithrombin complexes). Development of GMI 1070 for the treatment of acute vaso-occlusive crisis is ongoing. Trial Registration ClinicalTrials.gov NCT00911495 PMID:24988449

Assessing Chaos in Sickle Cell Anemia Crises

NASA Astrophysics Data System (ADS)

Harris, Wesley; Le Floch, Francois

2006-11-01

Recent developments in sickle cell research and blood flow modeling allow for new interpretations of the sickle cell crises. With an appropriate set of theoretical and empirical equations describing the dynamics of the red cells in their environment, and the response of the capillaries to major changes in the rheology, a complete mathematical system has been derived. This system of equations is believed to be of major importance to provide new and significant insight into the causes of the disease and related crises. With simulations, it has been proven that the system transition from a periodic solution to a chaotic one, which illustrates the onset of crises from a regular blood flow synchronized with the heart beat. Moreover, the analysis of the effects of various physiological parameters exposes the potential to control chaotic solutions, which, in turn, could lead to the creation of new and more effective treatments for sickle cell anemia. .

Inhibition of cell adhesion by anti–P-selectin aptamer: a new potential therapeutic agent for sickle cell disease

PubMed Central

Gutsaeva, Diana R.; Parkerson, James B.; Yerigenahally, Shobha D.; Kurz, Jeffrey C.; Schaub, Robert G.; Ikuta, Tohru

2011-01-01

Adhesive interactions between circulating sickle red blood cells (RBCs), leukocytes, and endothelial cells are major pathophysiologic events in sickle cell disease (SCD). To develop new therapeutics that efficiently inhibit adhesive interactions, we generated an anti–P-selectin aptamer and examined its effects on cell adhesion using knockout-transgenic SCD model mice. Aptamers, single-stranded oligonucleotides that bind molecular targets with high affinity and specificity, are emerging as new therapeutics for cardiovascular and hematologic disorders. In vitro studies found that the anti–P-selectin aptamer exhibits high specificity to mouse P-selectin but not other selectins. SCD mice were injected with the anti–P-selectin aptamer, and cell adhesion was observed under hypoxia. The anti–P-selectin aptamer inhibited the adhesion of sickle RBCs and leukocytes to endothelial cells by 90% and 80%, respectively. The anti–P-selectin aptamer also increased microvascular flow velocities and reduced the leukocyte rolling flux. SCD mice treated with the anti–P-selectin aptamer demonstrated a reduced mortality rate associated with the experimental procedures compared with control mice. These results demonstrate that anti–P-selectin aptamer efficiently inhibits the adhesion of both sickle RBCs and leukocytes to endothelial cells in SCD model mice, suggesting a critical role for P-selectin in cell adhesion. Anti–P-selectin aptamer may be useful as a novel therapeutic agent for SCD. PMID:20926770

Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability

PubMed Central

Champion, Hunter C.; Campbell-Lee, Sally A.; Bivalacqua, Trinity J.; Manci, Elizabeth A.; Diwan, Bhalchandra A.; Schimel, Daniel M.; Cochard, Audrey E.; Wang, Xunde; Schechter, Alan N.; Noguchi, Constance T.; Gladwin, Mark T.

2007-01-01

Pulmonary hypertension is a highly prevalent complication of sickle cell disease and is a strong risk factor for early mortality. However, the pathophysiologic mechanisms leading to pulmonary vasculopathy remain unclear. Transgenic mice provide opportunities for mechanistic studies of vascular pathophysiology in an animal model. By microcardiac catheterization, all mice expressing exclusively human sickle hemoglobin had pulmonary hypertension, profound pulmonary and systemic endothelial dysfunction, and vascular instability characterized by diminished responses to authentic nitric oxide (NO), NO donors, and endothelium-dependent vasodilators and enhanced responses to vasoconstrictors. However, endothelium-independent vasodilation in sickle mice was normal. Mechanisms of vasculopathy in sickle mice involve global dysregulation of the NO axis: impaired constitutive nitric oxide synthase activity (NOS) with loss of endothelial NOS (eNOS) dimerization, increased NO scavenging by plasma hemoglobin and superoxide, increased arginase activity, and depleted intravascular nitrite reserves. Light microscopy and computed tomography revealed no plexogenic arterial remodeling or thrombi/emboli. Transplanting sickle marrow into wild-type mice conferred the same phenotype, and similar pathobiology was observed in a nonsickle mouse model of acute alloimmune hemolysis. Although the time course is shorter than typical pulmonary hypertension in human sickle cell disease, these results demonstrate that hemolytic anemia is sufficient to produce endothelial dysfunction and global dysregulation of NO. PMID:17158223

Using Formative Research to Develop a Counselor Training Program for Newborn Screening in Ghana

PubMed Central

Anie, Kofi A.; Grant, Althea M.; Ofori-Acquah, Solomon F.; Ohene-Frempong, Kwaku

2015-01-01

Sickle cell disease (SCD), sickle cell trait (SCT) and related conditions are highly prevalent in sub-Saharan Africa. Despite the public health implications, there is limited understanding of the unique needs regarding establishing and implementing extensive screening for newborns and appropriate family counseling. We sought to gain understanding of community attitudes and beliefs about SCD/SCT from counselors and potential counselors in Ghana; obtain their input about goals for counseling following newborn screening; and obtain guidance about developing effective counselor education. Five focus groups with 32 health care providers and health educators from 9 of 10 regions in Ghana were conducted by trained facilitators according to a structured protocol. Qualitative data were coded and categorized to reflect common themes. Saturation was achieved in themes related to genetics/inheritance; common complications of SCD; potential for stigmatization; marital strain; and emotional stress. Misconceptions about SCT as a form of SCD were prevalent as were cultural and spiritual beliefs about the causes of SCD/SCT. Potential positive aspects included affected children's academic achievement as compensation for physical limitations, and family cohesion. This data informed recommendations for content and structure of a counselor training program that was provided to the Ministry of Health in Ghana. PMID:25193810

Hemoglobin electrophoresis

MedlinePlus

... is an abnormal form of hemoglobin associated with sickle cell anemia . In people with this condition, the red blood ... symptoms are much milder than they are in sickle cell anemia. Other, less common, abnormal Hb molecules cause other ...

Acute pancreatitis in sickle cell crisis.

PubMed Central

Kumar, A.; Posner, G.; Marsh, F.; Bellvue, R.; Dosik, H.

1989-01-01

A case of acute pancreatitis, complicated by pseudocyst formation, is described in a patient with sickle cell crisis. The differential diagnosis is discussed and the literature reviewed. Images Figure 1 Figure 2 PMID:2724361

Megalophallus in sickle cell disease.

PubMed

Datta, N S

1977-05-01

A case of megalophallus in sickle cell disease with repeated episodes of priapism is reported. A possible cause of penile hypertrophy with preservation of potency is discussed. Corpus cavernography was helpful in the diagnostic evaluation.

Sickle Cell Disease and Pulmonary Hypertension

MedlinePlus

... My doctor wants to screen me for pulmonary hypertension. Why is this? Sickle cell disease (SCD), a ... What are some of the symptoms of pulmonary hypertension? Because they are somewhat general symptoms, the characteristics ...

Paramagnetic Europium Salen Complex and Sickle-Cell Anemia

NASA Astrophysics Data System (ADS)

Wynter, Clive I.; Ryan, D. H.; May, Leopold; Oliver, F. W.; Brown, Eugene; Hoffman, Eugene J.; Bernstein, David

2005-04-01

A new europium salen complex, Eu(salen)2NH4, was synthesized, and its composition was confirmed by chemical analysis and infrared spectroscopy. Further characterization was carried out by 151 Eu Mössbauer spectroscopy and magnetic susceptibility measurements. Mössbauer spectroscopic measurements were made at varying temperatures between 9 K and room temperature and a value of Debye temperature of 133 ±5 K was computed. Both Mössbauer and magnetic susceptibility measurements confirmed the paramagnetic behavior of this complex and the trivalent state of the europium ion. In view of the fact that the "odd" paramagnetic molecule NO has been shown to reverse sickling of red blood cells in sickle cell anemia, the interaction between the paramagnetic europium salen complex and sickle cells was examined after incubation with this europium complex and shown to have similar effects.

Enhancing self-management in children with sickle cell disease through playing a CD-ROM educational game: a pilot study.

PubMed

Yoon, Saunjoo L; Godwin, Angela

2007-01-01

To determine whether playing a simple CD-ROM educational game (developed specifically for children with sickle cell disease), improved children's knowledge and confidence in selected symptom management and practice. Twenty-two eligible children completed a pretest to determine knowledge and confidence levels, played the Sickle Cell Slime-O-Rama Game, then completed an identical posttest. Significant increases in knowledge (t = 2.828, p =.010) and confidence (t = 3.759, p =.001) levels between pre- and posttests were identified. It is promising that a simple, interacting CD-ROM game allowed children with sickle cell disease to quickly acquire knowledge about the disease and symptom management, and increased their confidence to apply this new knowledge. Results suggest the high utility of this tailored game to foster active self-management behaviors in this population.

Recovery of autologous sickle cells by hypotonic wash.

PubMed

Wilson, Emily; Kezeor, Kelly; Crosby, Monica

2018-01-01

It is important to isolate autologous red blood cells (RBCs) from transfused RBCs in samples from recently transfused patients to ensure that accurate serologic results are obtained. Typically, this isolation can be performed using methods that separate patient reticulocytes from transfused, older donor RBCs. Patients with sickle cell disease (SCD), however, characteristically have RBCs with altered membrane and morphological features, causing their RBCs to take on a sickle-shape appearance different from the biconcave disc-shape appearance of "normal" RBCs. These characteristics enable the use of hypotonic saline solution to lyse normal RBCs while allowing "sickle cells" to remain intact. Because many patients with SCD undergo frequent transfusions to treat their condition, the use of hypotonic saline solution provides a rapid method to obtain autologous RBCs for serologic testing from this patient population using standard laboratory equipment and supplies.

Prevalence of sickle cell disease among Grenadian newborns.

PubMed

Antoine, Magdalene; Lee, Ketty; Donald, Tyhiesia; Belfon, Yonni; Drigo, Ali; Polson, Sharon; Martin, Francis; Mitchell, George; Etienne-Julan, Maryse; Hardy-Dessources, Marie-Dominique

2018-03-01

Objective To establish the birth prevalence of sickle cell disease in Grenada, with a view to assess the requirement for a population-based neonatal screening programme. Methods A two-year pilot neonatal screening programme, involving the Ministry of Health of Grenada, the Sickle Cell Association of Grenada, and the diagnostic laboratory of hemoglobinopathies of the University Hospital of Guadeloupe, was implemented in 2014-2015 under the auspices of the Caribbean Network of Researchers on Sickle Cell Disease and Thalassemia. Results Analysis of 1914 samples processed identified the following abnormal phenotypes: 10 FS, 2 FSC, 183 FAS, 63 FAC. These data indicate β s and β c allele frequencies of 0.054 and 0.018, respectively. Conclusion Neonatal screening conducted in the framework of this Caribbean cooperation can allow rapid detection and earlier management of affected children.

Environmental determinants of severity in sickle cell disease

PubMed Central

Tewari, Sanjay; Brousse, Valentine; Piel, Frédéric B.; Menzel, Stephan; Rees, David C.

2015-01-01

Sickle cell disease causes acute and chronic illness, and median life expectancy is reduced by at least 30 years in all countries, with greater reductions in low-income countries. There is a wide spectrum of severity, with some patients having no symptoms and others suffering frequent, life-changing complications. Much of this variability is unexplained, despite increasingly sophisticated genetic studies. Environmental factors, including climate, air quality, socio-economics, exercise and infection, are likely to be important, as demonstrated by the stark differences in outcomes between patients in Africa and USA/Europe. The effects of weather vary with geography, although most studies show that exposure to cold or wind increases hospital attendance with acute pain. Most of the different air pollutants are closely intercorrelated, and increasing overall levels seem to correlate with increased hospital attendance, although higher concentrations of atmospheric carbon monoxide may offer some benefit for patients with sickle cell disease. Exercise causes some adverse physiological changes, although this may be off-set by improvements in cardiovascular health. Most sickle cell disease patients live in low-income countries and socioeconomic factors are undoubtedly important, but little studied beyond documenting that sickle cell disease is associated with decreases in some measures of social status. Infections cause many of the differences in outcomes seen across the world, but again these effects are relatively poorly understood. All the above factors are likely to account for much of the pathology and variability of sickle cell disease, and large prospective studies are needed to understand these effects better. PMID:26341524

Prevalence of glutathione S-transferase gene deletions and their effect on sickle cell patients.

PubMed

Sanjay, Pandey; Mani, Mishra Rahasy; Sweta, Pandey; Vineet, Shah; Kumar, Ahuja Rajesh; Renu, Saxena

2012-01-01

Glutathione S-transferase gene deletions are known detoxification agents and cause oxidative damage. Due to the different pathophysiology of anemia in thalassemia and sickle cell disease, there are significant differences in the pathophysiology of iron overload and iron-related complications in these disorders. The aim of this study was to estimate the frequency of the GSTM1 and GSTT1 genotypes in sickle cell disease patients and their effect on iron status. Forty sickle cell anemia and sixty sickle ß-thalassemia patients and 100 controls were evaluated to determine the frequency of GST gene deletions. Complete blood counts were performed by an automated cell analyzer. Hemoglobin F, hemoglobin A, hemoglobin A2 and hemoglobin S were measured and diagnosis of patients was achieved by high performance liquid chromatography with DNA extraction by the phenol-chloroform method. The GST null genotype was determined using multiplex polymerase chain reaction and serum ferritin was measured using an ELISA kit. Statistical analysis was by EpiInfo and GraphPad statistics software. An increased frequency of the GSTT1 null genotype (p-value = 0.05) was seen in the patients. The mean serum ferritin level was higher in patients with the GST genotypes than in controls; this was statistically significant for all genotypes except GSTM1, however the higher levels of serum ferritin were due to blood transfusions in patients. GST deletions do not play a direct role in iron overload of sickle cell patients.

Transcranial Doppler Screening Among Children and Adolescents With Sickle Cell Anemia.

PubMed

Reeves, Sarah L; Madden, Brian; Freed, Gary L; Dombkowski, Kevin J

2016-06-01

With transcranial Doppler (TCD) screening, we can identify children and adolescents with sickle cell anemia who are at the highest risk of stroke. An accurate claims-based method for identifying children and adolescents with sickle cell anemia was recently developed and validated that establishes the necessary groundwork to enable large population-based assessments of health services utilization among children and adolescents with sickle cell anemia using administrative claims data. To assess the feasibility of using administrative claims data to identify and describe the receipt of TCD screening among children and adolescents with sickle cell anemia and to characterize opportunities for intervention. Retrospective cross-sectional study using Medicaid claims data from 2005 to 2010. Medicaid claims data were obtained from the following states: Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. Children and adolescents 2 to 16 years of age with sickle cell anemia were identified by the presence of 3 or more Medicaid claims with a diagnosis of sickle cell anemia within a calendar year (2005-2010). A total of 4775 children and adolescents contributed 10 787 person-years throughout the study period. Data were analyzed in 2015. A subset of children and adolescents enrolled for 2 or more consecutive years was identified to examine potential predictors of TCD screening, which included age, sex, previous receipt of TCD screening, state of residence, and health services utilization (well-child visits, outpatient visits, emergency department visits, and inpatient visits). Receipt of TCD screening was assessed by year and state. Using logistic regression with generalized estimating equations, we included associated predictors in a multivariable model to estimate odds of TCD screening. For a total of 4775 children and adolescents 2 to 16 years of age, TCD screening rates increased over the 6-year study period from 22% to 44% (P < .001); rates varied substantially across states. A subset of 2388 children and adolescents with sickle cell anemia (50%) was enrolled for 2 or more consecutive years. Each year of increasing age was associated with 3% lower odds of TCD screening (odds ratio, 0.97 [95% CI, 0.95-0.98]; P = .002). Previous receipt of TCD screening (odds ratio, 2.44 [95% CI, 2.11-2.81]; P < .001) and well-child visits (odds ratio, 1.10 [95% CI, 1.03-1.18]; P = .007) were associated with higher odds of receiving a TCD screening. Despite national recommendations, TCD screening rates remain low. Successful strategies to improve TCD screening rates may capitalize on the numerous health care interactions among children and adolescents with sickle cell anemia.

Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

PubMed Central

Kobari, Ladan; Yates, Frank; Oudrhiri, Noufissa; Francina, Alain; Kiger, Laurent; Mazurier, Christelle; Rouzbeh, Shaghayegh; El-Nemer, Wassim; Hebert, Nicolas; Giarratana, Marie-Catherine; François, Sabine; Chapel, Alain; Lapillonne, Hélène; Luton, Dominique; Bennaceur-Griscelli, Annelise; Douay, Luc

2012-01-01

Background Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors. Design and Methods We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation. Results We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice. Conclusions These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment. PMID:22733021

ABDOMINAL PAIN IN ADULT SICKLE CELL DISEASE PATIENTS: A NIGERIAN EXPERIENCE

PubMed Central

Akingbola, T.S.; Kolude, B.; Aneni, E.C.; Raji, A.A.; Iwara, K.U.; Aken’Ova, Y.A.; Soyannwo, O.A.

2011-01-01

Background: Abdominal pain is a relatively frequent occurrence in sickle cell disease. The aetiology of abdominal pain in sickle cell disease is often difficult to diagnose clinically. Despite the frequent occurrence, diagnostic dilemma, and the need for an accurate, early diagnosis, abdominal pain in sickle cell disease has not been rigorously studied. Objective: We therefore sought to describe the different presentations and patterns of abdominal pain in persons with sickle cell disease. Methods: A prospective case series of 20 patients was done in which data was collected on demographic characteristics, hemoglobin electrophoresis patterns, a description of the abdominal pain including sites, severity, and type of pain, packed cell volume and the provisional and final diagnosis. Results: Haemoglobin S patients were 17 in number constituting eightyfive percent (85%) of our study population whilst the rest 3 were Hb S+C. Most patients (70%) had one site of abdominal pain. The pain was mainly colicky or tightening, moderate to severe in nature and, in some cases, associated with vomiting. We did not find any significant difference between the steady state PCV and the PCV during the acute abdominal pain episodes. The final diagnosis showed that only 38.8% of the patients had vasoocclusive crises and the reliability index between the provisional diagnosis and the final diagnosis was 67%. Conclusion: Abdominal pain in sickle cell disease may present in different ways and it is important to recognize that the possible diagnoses are numerous. Not all cases are due to vasoocclusive crises. Early diagnosis and prompt treatment can be life saving. PMID:25161492

Histopathology of aseptic necrosis of the femoral head in sickle cell disease.

PubMed

Mukisi-Mukaza, Martin; Gomez-Brouchet, Anne; Donkerwolcke, Monique; Hinsenkamp, Maurice; Burny, Franz

2011-08-01

This study compares the histopathology of bone biopsies from patients suffering from sickle cell anaemia (homozygote SS) to heterozygote patients (SA) and homozygotes with aseptic osteonecrosis (AA). The sensitivity to bacterial infection of sickle cell patients raises the question of the aetiology of sepsis in the onset of the necrosis. To our knowledge this study is the first to analyse the histopathology of osteonecrosis of the femoral head, at its early stages, in sickle cell anaemia. At the University Hospital of Pointe-à-Pitre, from 1994 to 2007, 38 bone biopsies were obtained from adult patients with avascular necrosis of the femoral head at the time of a core decompression procedure (SS, SC: 27; AS: 5; AA: 6). The histology of the biopsies confirmed the necrosis; all bacteriological cultures were negative. Patients displaying one S gene (SS, SC, AS) compared to homozygote subjects (AA) showed a significant increase of a nonspecific inflammatory granulomatosis (p = 0.003). No relationship was observed between the radiological stages and the histology whatever the genotype (p = 0.1). Inflammatory histopathology without sepsis or advanced alteration characterises the early stages of sickle cell necrosis. This inflammatory process is absent in idiopathic avascular necrosis.

Intravascular hemolysis and the pathophysiology of sickle cell disease

PubMed Central

Kato, Gregory J.; Steinberg, Martin H.; Gladwin, Mark T.

2017-01-01

Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. Decompartmentalized hemoglobin, arginase 1, asymmetric dimethylarginine, and adenine nucleotides are all products of hemolysis that promote vasomotor dysfunction, proliferative vasculopathy, and a multitude of clinical complications of pulmonary and systemic vasculopathy, including pulmonary hypertension, leg ulcers, priapism, chronic kidney disease, and large-artery ischemic stroke. Nitric oxide (NO) is inactivated by cell-free hemoglobin in a dioxygenation reaction that also oxidizes hemoglobin to methemoglobin, a non–oxygen-binding form of hemoglobin that readily loses heme. Circulating hemoglobin and heme represent erythrocytic danger-associated molecular pattern (eDAMP) molecules, which activate the innate immune system and endothelium to an inflammatory, proadhesive state that promotes sickle vaso-occlusion and acute lung injury in murine models of sickle cell disease. Intravascular hemolysis can impair NO bioavailability and cause oxidative stress, altering redox balance and amplifying physiological processes that govern blood flow, hemostasis, inflammation, and angiogenesis. These pathological responses promote regional vasoconstriction and subsequent blood vessel remodeling. Thus, intravascular hemolysis represents an intrinsic mechanism for human vascular disease that manifests clinical complications in sickle cell disease and other chronic hereditary or acquired hemolytic anemias. PMID:28248201

Glomerular function in sickle cell disease patients during crisis.

PubMed

Aderibigbe, A; Arije, A; Akinkugbe, O O

1994-06-01

An 8 month prospective study was carried out in 20 adult sickle cell disease (SCD) patients 16 sickle cell anaemia (Hbss) and 4 sickle cell Hbc disease (Hbsc); who had vaso-occlusive crises within the study period to determine the extent of the effect of sickle cell crisis on glomerular function in SCD patients during crisis. The male: female ratio was 1:57 and their mean age was 21.1 +/- 7.9 years. Creatinine clearance (CCr), as an index of glomerular function, was determined at the pre-crisis, crisis, 2 and 4 weeks post-crisis and at the end of the study period. The mean values of their CCr dropped from 113.37 +/- 33.80mls/min at pre-crisis stage to 96.39 +/- 30.13mls/min during crisis (p < 0.001) indicating glomerular dysfunction. It improved significantly to 107.75 +/- 30.20mls/min at 4 weeks post-crisis (p < 0.001). There was no significant differences in the mean values of CCr at the end of the study (116.20 +/- 31.43mls/min) compared to the pre-crisis stage (p > 0.05). It is concluded that glomerular dysfunction in SCD patients during crisis is potentially reversible.

Adenosine signaling in normal and sickle erythrocytes and beyond.

PubMed

Zhang, Yujin; Xia, Yang

2012-08-01

Sickle cell disease (SCD) is a debilitating hemolytic genetic disorder with high morbidity and mortality affecting millions of individuals worldwide. Although SCD was discovered more than a century ago, no effective mechanism-based prevention and treatment are available due to poorly understood molecular basis of sickling, the fundamental pathogenic process of the disease. SCD patients constantly face hypoxia. One of the best-known signaling molecules to be induced under hypoxic conditions is adenosine. Recent studies demonstrate that hypoxia-mediated elevated adenosine signaling plays an important role in normal erythrocyte physiology. In contrast, elevated adenosine signaling contributes to sickling and multiple life threatening complications including tissue damage, pulmonary dysfunction and priapism. Here, we summarize recent research on the role of adenosine signaling in normal and sickle erythrocytes, progression of the disease and therapeutic implications. In normal erythrocytes, both genetic and pharmacological studies demonstrate that adenosine can enhance 2,3-bisphosphoglycerate (2,3-BPG) production via A(2B) receptor (ADORA2B) activation, suggesting that elevated adenosine has an unrecognized role in normal erythrocytes to promote O(2) release and prevent acute ischemic tissue injury. However, in sickle erythrocytes, the beneficial role of excessive adenosine-mediated 2,3-BPG induction becomes detrimental by promoting deoxygenation, polymerization of sickle hemoglobin and subsequent sickling. Additionally, adenosine signaling via the A(2A) receptor (ADORA2A) on invariant natural killer T (iNKT) cells inhibits iNKT cell activation and attenuates pulmonary dysfunction in SCD mice. Finally, elevated adenosine coupled with ADORA2BR activation is responsible for priapism, a dangerous complication seen in SCD. Overall, the research reviewed here reveals a differential role of elevated adenosine in normal erythrocytes, sickle erythrocytes, iNK cells and progression of disease. Thus, adenosine signaling represents a potentially important therapeutic target for the treatment and prevention of disease. Copyright © 2012 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Sickle Cell Disease: What You Should Know

MedlinePlus

... people with sickle cell disease. Gene Therapy and Gene Editing: The National Heart, Lung, and Blood Institute is ... Maryland. Researchers are also exploring the feasibility of gene editing, an approach that aims to edit the blood- ...

Step Inside NIH's Sickle Cell Branch

MedlinePlus

... attack it. This is gene transfer, which requires gene editing. Sickle cell disease is caused by a single ... can reverse that mutation in the DNA using gene editing, we could change that one mutant gene back ...

Nursing Diagnoses and Caring for Patients with Sickle Cell Disease.

ERIC Educational Resources Information Center

London, Fran

1990-01-01

This continuing education article is designed to teach nurses to describe sickle cell anemia, identify complications, specify signs and symptoms, and describe nursing interventions. It concludes with a multiple-choice test. (SK)

Best practices for transfusion for patients with sickle cell disease

PubMed Central

Wun, Ted; Hassell, Kathryn

2010-01-01

The β-globin gene mutation in sickle cell anemia results in anemia and repeated bouts of vascular occlusion. The cumulative effect of these vasocclusive events is progressive damage to many organs including the kidneys, lungs, and brain. The transfusion of red blood cells (RBC) can ameliorate many of these complications, but can be associated with both acute and chronic complications, including iron overload. The objective of the Best Practices in Transfusion Medicine for Patients with Sickle Cell Disease (SCD) Conference was to review the available published evidence and clinical experience surrounding the use of RBC transfusions for sickle cell disease by a panel of experts. The expert panel developed explicit clinical guidelines for the use of RBC in SCD patients. The panel also made recommendations for further research. A set of guidelines were produced for dissemination to pertinent stakeholders. If implemented, these clinical pathways have the potential to optimize the use of red blood cell transfusions in SCD.

Drugs for preventing red blood cell dehydration in people with sickle cell disease.

PubMed

Nagalla, Srikanth; Ballas, Samir K

2012-07-11

Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register.Last search of the Group's Trials Register: 25 October 2011. Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment. Both authors independently selected studies for inclusion, assessed study quality and extracted data. Of the 51 studies identified, three met the inclusion criteria. The first study tested the effectiveness of zinc sulphate to prevent sickle cell-related crises in a total of 145 participants and showed a significant reduction in painful crises over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15). However, analysis was restricted due to limited statistical data. Changes to red cell parameters and blood counts were inconsistent. No serious adverse events were noted in the study.The second study was a Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo. Compared to the placebo group the high dose senicapoc showed significant improvement in change in hemoglobin level, number and proportion of dense red blood cells, red blood cell count and indices and hematocrit. The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups. A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises. While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red cell survival (depending on dose), this did not lead to fewer painful crises.

Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics

PubMed Central

Pakbaz, Zahra; Wun, Ted

2014-01-01

Synopsis Recent studies suggest that sickle cell disease is a hypercoagulable state contributing to the vaso-occlusive events in microcirculation resulting in acute and chronic sickle cell related organ damage. In this article, we will review the existing evidence for contribution of hemostatic system perturbation to sickle cell disease pathophysiology. We will also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of VTE. Finally, the potential role of platelet inhibitors and anticoagulants in SCD will be briefly reviewed. PMID:24589271

Gastric trichobezoar: abdominal mass in a child with sickle cell disease.

PubMed

Sciarretta, Jason D; Bond, Sheldon J

2011-11-01

Abdominal pain is a frequent occurrence among the pediatric population and can be a diagnostic challenge. Trichobezoar is a differential diagnosis that is often neglected. Different from previously reported cases, we present a 3-year-old girl with sickle cell disease with complaints of acute abdominal pain, suspecting sickle cell splenic sequestration. The child presented to the emergency department with sharp epigastric pain and an associated palpable upper abdominal mass. This case illustrates a large obstructing gastric trichobezoar and summarizes both the diagnostic modalities and treatment.

Sciatic (Popliteal Fossa) Catheter for Pediatric Pain Management of Sickle Cell Crisis: A Case Report.

PubMed

Weber, Garret; Liao, Sherry; Burns, Micah Alexander

2017-11-15

Sickle cell crisis, or vaso-occlusive crisis (VOC), is a major cause of hospitalizations for adults and children with sickle cell disease, and is associated with increased morbidity and mortality. Despite prompt pharmacological treatment and multimodal pain management, acute pain during a VOC is often not adequately controlled in the pediatric population. We placed a continuous popliteal sciatic nerve block under ultrasound guidance in a pediatric patient for localized refractory pain during a VOC, resulting in improved pain control with preserved sensorimotor function.

A Theoretical Study of some Rheological Properties of the Aggregation of the Molecules Deoxy- Hemoglobin S

NASA Astrophysics Data System (ADS)

Mensah, Francis; Grant, Julius; Thorpe, Arthur

2010-02-01

Sickle cell disease is a serious public health problem that affects many people worldwide. In this paper, the Langevin equation is used for hemoglobin's aggregation in sickle cell anemia. Several parameters are explored such as the time-dependent deformation of the aggregates whose plot gives a sigmoid, the time-dependent expressions obtained for the coefficient of viscosity and the elastic modulus which characterize the aggregation of the sickle hemoglobin. Other properties such as the viscoelastic and the elasto-thixotropic properties of the sickle hemoglobin polymer are also described. An attempt is made to approach the polymerization process in terms of a dynamical system. )