Acute Chest Syndrome in Children with Sickle Cell Disease

PubMed Central

Bakshi, Nitya; Krishnamurti, Lakshmanan

2017-01-01

Acute chest syndrome (ACS) is a frequent cause of acute lung disease in children with sickle cell disease (SCD). Patients may present with ACS or may develop this complication during the course of a hospitalization for acute vaso-occlusive crises (VOC). ACS is associated with prolonged hospitalization, increased risk of respiratory failure, and the potential for developing chronic lung disease. ACS in SCD is defined as the presence of fever and/or new respiratory symptoms accompanied by the presence of a new pulmonary infiltrate on chest X-ray. The spectrum of clinical manifestations can range from mild respiratory illness to acute respiratory distress syndrome. The presence of severe hypoxemia is a useful predictor of severity and outcome. The etiology of ACS is often multifactorial. One of the proposed mechanisms involves increased adhesion of sickle red cells to pulmonary microvasculature in the presence of hypoxia. Other commonly associated etiologies include infection, pulmonary fat embolism, and infarction. Infection is a common cause in children, whereas adults usually present with pain crises. Several risk factors have been identified in children to be associated with increased incidence of ACS. These include younger age, severe SCD genotypes (SS or Sβ0 thalassemia), lower fetal hemoglobin concentrations, higher steady-state hemoglobin levels, higher steady-state white blood cell counts, history of asthma, and tobacco smoke exposure. Opiate overdose and resulting hypoventilation can also trigger ACS. Prompt diagnosis and management with intravenous fluids, analgesics, aggressive incentive spirometry, supplemental oxygen or respiratory support, antibiotics, and transfusion therapy, are key to the prevention of clinical deterioration. Bronchodilators should be considered if there is history of asthma or in the presence of acute bronchospasm. Treatment with hydroxyurea should be considered for prevention of recurrent episodes. This review evaluates the

Acute Chest Syndrome in Children with Sickle Cell Disease.

PubMed

Jain, Shilpa; Bakshi, Nitya; Krishnamurti, Lakshmanan

2017-12-01

Acute chest syndrome (ACS) is a frequent cause of acute lung disease in children with sickle cell disease (SCD). Patients may present with ACS or may develop this complication during the course of a hospitalization for acute vaso-occlusive crises (VOC). ACS is associated with prolonged hospitalization, increased risk of respiratory failure, and the potential for developing chronic lung disease. ACS in SCD is defined as the presence of fever and/or new respiratory symptoms accompanied by the presence of a new pulmonary infiltrate on chest X-ray. The spectrum of clinical manifestations can range from mild respiratory illness to acute respiratory distress syndrome. The presence of severe hypoxemia is a useful predictor of severity and outcome. The etiology of ACS is often multifactorial. One of the proposed mechanisms involves increased adhesion of sickle red cells to pulmonary microvasculature in the presence of hypoxia. Other commonly associated etiologies include infection, pulmonary fat embolism, and infarction. Infection is a common cause in children, whereas adults usually present with pain crises. Several risk factors have been identified in children to be associated with increased incidence of ACS. These include younger age, severe SCD genotypes (SS or Sβ 0 thalassemia), lower fetal hemoglobin concentrations, higher steady-state hemoglobin levels, higher steady-state white blood cell counts, history of asthma, and tobacco smoke exposure. Opiate overdose and resulting hypoventilation can also trigger ACS. Prompt diagnosis and management with intravenous fluids, analgesics, aggressive incentive spirometry, supplemental oxygen or respiratory support, antibiotics, and transfusion therapy, are key to the prevention of clinical deterioration. Bronchodilators should be considered if there is history of asthma or in the presence of acute bronchospasm. Treatment with hydroxyurea should be considered for prevention of recurrent episodes. This review evaluates the

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 ...

Sickle cell disease

PubMed Central

2011-01-01

Introduction Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to a third of adults are carriers of the defective sickle cell gene, and 1% to 2% of babies are born with the disease. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: what are the effects of pharmaceutical and non-pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? What are the effects of pharmaceutical and non-pharmaceutical interventions to treat pain in people with sickle cell crisis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 38 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, antibiotic prophylaxis in children <5 years of age, antibiotic prophylaxis in children >5 years of age, aspirin, avoidance of cold environment, blood transfusion, codeine, corticosteroid (with narcotic analgesics), diflunisal, hydration, hydroxyurea, ibuprofen, ketorolac, limiting physical exercise, malaria chemoprophylaxis, morphine (controlled-release oral after initial intravenous bolus, repeated intravenous doses), oxygen, paracetamol, patient-controlled analgesia, pneumococcal vaccines

Sickle cell disease

PubMed Central

2009-01-01

Introduction Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises, and increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to a third of adults are carriers of the defective sickle cell gene, and 1-2% of babies are born with the disease. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmaceutical and non-pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? What are the effects of pharmaceutical and non-pharmaceutical interventions to treat pain in people with sickle cell crisis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 38 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, antibiotic prophylaxis in children under 5 years of age, aspirin, avoidance of cold environment, blood transfusion, codeine, corticosteroid (with narcotic analgesics), diflunisal, hydration, hydroxyurea, ibuprofen, ketorolac, limiting physical exercise, malaria chemoprophylaxis, morphine (controlled-release oral after initial intravenous bolus, repeated intravenous doses), oxygen, paracetamol, patient-controlled analgesia, penicillin prophylaxis in children over 5 years of age, piracetam

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.

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

Acute gastrointestinal vaso-occlusive ischemia in sickle cell disease: CT imaging features and clinical outcome.

PubMed

Gardner, Carly S; Jaffe, Tracy A

2016-03-01

The purpose of this study was to determine the incidence, specific imaging features, and outcome of gastrointestinal vaso-occlusive ischemia (GVOI) in sickle cell patients undergoing CT for acute abdominal pain. This HIPAA-compliant, IRB-approved retrospective study evaluated sickle cell patients with an abdominal pain crisis and acute gastrointestinal abnormalities on CT from 1/2006 to 1/2014. CT findings were divided into those compatible and incompatible with bowel ischemia or clinical diagnosis of GVOI. Two abdominal radiologists (1, 13 years' experience) reviewed the CTs for specific imaging features of ischemia. Clinical laboratory values (lactate, WBC) and outcome were recorded. Descriptive statistics and Wilcoxon-Mann-Whitney two-sample rank-sum test were performed. Of 217 CTs, 33 had acute gastrointestinal abnormalities: 75% (25/33) consistent with ischemia and clinical GVOI. Complications of ischemia occurred in 16% (4/25): ileus (50%), perforation (25%), and pneumatosis (25%). In uncomplicated cases, all had bowel wall thickening: segmental 52% (11/21) or diffuse 48% (10/21). The colon was commonly involved (76%, 16/21), particularly the ascending (57%, 12/21). Most abnormalities (52%, 11/21) were in the superior mesenteric artery distribution. Average lactate (4.3 ± 4.0 mmol/L, p = 0.02) and WBC count (20.1 ± 10.4, ×1000 cells/μL, p = 0.01) were significantly higher in GVOI. Overall mortality in patients with GVOI was 17% (3/18). GVOI is an important feature of the acute abdominal crisis in patients with sickle cell disease and can be seen in up to 75% of patients with abnormal bowel findings on CT. The diagnosis should be strongly considered in sickle cell patients with CT findings of diffuse or segmental bowel wall thickening, particularly involving the colon.

Bacteriuria in pregnant women with sickle cell trait.

PubMed

Thurman, Andrea Ries; Steed, Lisa L; Hulsey, Thomas; Soper, David E

2006-05-01

The purpose of this study was to compare the following outcome variables in pregnant patients with sickle cell trait and matched pregnant control patients: asymptomatic bacteriuria, acute cystitis, urinary pathogens that were present, and pyelonephritis. This was a retrospective cohort study that was conducted at a university clinic. Pregnant patients with sickle cell trait (n = 455) were matched with control patients (n = 448) for race, age, gestational age at entry into prenatal care, and number of prenatal visits. Women with sickle cell trait received urine testing significantly more often. There was no difference in the incidence of positive urine cultures, urinary pathogens, or asymptomatic bacteriuria among the comparison groups. Sickle cell trait carriers had significantly higher rates of pyelonephritis, but many affected patients had risk factors, such as previous pyelonephritis or noncompliance with therapy. Sickle cell trait carriers were no more susceptible to acute cystitis and asymptomatic bacteriuria than were the control patients. On the basis of these data, we outline recommendations for urinary screening and pyelonephritis prevention in pregnant patients with sickle cell trait.

Acute splenic sequestration in a pregnant woman with homozygous sickle-cell anemia.

PubMed

Maia, Carolina Bastos; Nomura, Roseli Mieko Yamamoto; Igai, Ana Maria Kondo; Fonseca, Guilherme Hencklain; Gualandro, Sandra Menosi; Zugaib, Marcelo

2013-01-01

Homozygous (SS) sickle-cell anemia complicated by acute splenic sequestration in adults is a rare event, and it has never been reported during pregnancy. A 25-year-old woman with homozygous (SS) sickle-cell disease was hospitalized at 32 weeks' of gestation presenting weakness, abdominal pain, fever and hemoglobin of 2.4 g/dl. Abnormal fetal heart rate was detected by means of cardiotocography, and 5 units of packed red cells were transfused. Cesarean was performed at 37 weeks. Both mother and baby were discharged in a good general condition. This case report demonstrates the importance of immediate blood transfusion for treatment of fetal distress in cases of splenic sequestration during pregnancy. This treatment is essential for avoiding maternal and fetal complications.

Sickle cell disease

PubMed Central

2016-01-01

Introduction Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to one third of adults are carriers of the defective sickle cell gene, and 1% to 2% of babies are born with the disease. Methods and outcomes We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2015 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). Results At this update, searching of electronic databases retrieved 369 studies. After deduplication and removal of conference abstracts, 136 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 99 studies and the further review of 37 full publications. Of the 37 full articles evaluated, three already included systematic reviews were updated, two systematic reviews, two RCTs, and one subsequent RCT were added at this update. We performed a GRADE evaluation for 12 PICO combinations. Conclusions In this systematic overview, we categorised the efficacy for five interventions based on information about the effectiveness and safety of antibiotic prophylaxis in children aged under 5 years, antibiotic prophylaxis in children aged 5 years or older, hydroxyurea, malaria chemoprophylaxis, and pneumococcal vaccines. PMID:26808098

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.

Gastrointestinal and hepatic complications of sickle cell disease.

PubMed

Ebert, Ellen C; Nagar, Michael; Hagspiel, Klaus D

2010-06-01

Sickle cell disease (SCD) is an autosomal recessive abnormality of the beta-globin chain of hemoglobin (Hb), resulting in poorly deformable sickled cells that cause microvascular occlusion and hemolytic anemia. The spleen is almost always affected by SCD, with microinfarcts within the first 36 months of life resulting in splenic atrophy. Acute liver disorders causing right-sided abdominal pain include acute vaso-occlusive crisis, liver infarction, and acute hepatic crisis. Chronic liver disease might be due to hemosiderosis and hepatitis and possibly to SCD itself if small, clinically silent microvascular occlusions occur chronically. Black pigment gallstones caused by elevated bilirubin excretion are common. Their small size permits them to travel into the common bile duct but cause only low-grade obstruction, so hyperbilirubinemia rather than bile duct dilatation is typical. Whether cholecystectomy should be done in asymptomatic individuals is controversial. The most common laboratory abnormality is an elevation of unconjugated bilirubin level. Bilirubin and lactate dehydrogenase levels correlate with one another, suggesting that chronic hemolysis and ineffective erythropoiesis, rather than liver disease, are the sources of hyperbilirubinemia. Abdominal pain is very common in SCD and is usually due to sickling, which resolves with supportive care. Computed tomography scans might be ordered for severe or unremitting pain. The liver typically shows sickled erythrocytes and Kupffer cell enlargement acutely and hemosiderosis chronically. The safety of liver biopsies has been questioned, particularly during acute sickling crisis. Treatments include blood transfusions, exchange transfusions, iron-chelating agents, hydroxyurea, and allogeneic stem-cell transplantation. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

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

Raised D-dimer levels in acute sickle cell crisis and their correlation with chest X-ray abnormalities

PubMed Central

Dar, Javeed; Mughal, Inam; Hassan, Hilali; Al Mekki, Taj E.; Chapunduka, Zivani; Hassan, Imad S. A.

2010-01-01

Objective: Quantitation of D-dimer level during a sickling crisis and its correlation with other clinical abnormalities. Design: Prospective longitudinal study. Setting: Armed Forces Hospital, Southern Region, Kingdom of Saudi Arabia. Patients: Adult patients (12 years and older) admitted acutely with a sickle cell crisis who consent to taking part in the study. Candidates may re-participate if they are readmitted with a further acute painful crisis. Results: 36 patients with homozygous sickle cell disease consented to take part in the study. D-dimer levels were raised in 31 (68.9%) of 45 episodes of painful crisis of whom 13 had an abnormal chest X-ray. Of those with a normal chest X-ray only one patient had a raised D-dimer level: sensitivity of 92.3%, specificity 40.6%, positive predictive value 38.7% and negative predictive value of 92.9% for an abnormal chest X-ray. Conclusion: D-dimer levels are frequently raised during an acute painful crisis. A normal level has a high negative predictive value for an abnormal chest X-ray. PMID:21063468

Raised D-dimer levels in acute sickle cell crisis and their correlation with chest X-ray abnormalities.

PubMed

Dar, Javeed; Mughal, Inam; Hassan, Hilali; Al Mekki, Taj E; Chapunduka, Zivani; Hassan, Imad S A

2010-10-08

Quantitation of D-dimer level during a sickling crisis and its correlation with other clinical abnormalities. Prospective longitudinal study. Armed Forces Hospital, Southern Region, Kingdom of Saudi Arabia. Adult patients (12 years and older) admitted acutely with a sickle cell crisis who consent to taking part in the study. Candidates may re-participate if they are readmitted with a further acute painful crisis. 36 patients with homozygous sickle cell disease consented to take part in the study. D-dimer levels were raised in 31 (68.9%) of 45 episodes of painful crisis of whom 13 had an abnormal chest X-ray. Of those with a normal chest X-ray only one patient had a raised D-dimer level: sensitivity of 92.3%, specificity 40.6%, positive predictive value 38.7% and negative predictive value of 92.9% for an abnormal chest X-ray. D-dimer levels are frequently raised during an acute painful crisis. A normal level has a high negative predictive value for an abnormal chest X-ray.

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.

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.

Acute on chronic liver failure in a patient with sickle cell anaemia (HbSS)

PubMed Central

Im, Dana DaEun; Essien, Utibe; DePasse, Jacqueline W; Chiappa, Victor

2015-01-01

A man in his late 40s with sickle cell anaemia (HbSS) presented to the emergency department with 2 weeks of diffuse oedema, increased abdominal girth and dyspnoea. His anasarca was thought to be indicative of an acute decompensation of his known liver cirrhosis with transfusion-induced haemosiderosis. While his anasarca improved with diuresis, his direct hyperbilirubinaemia suddenly worsened without any signs of haemolysis, biliary disease or obstruction. He also developed an acute worsening in serum creatinine (1.17–7.0 mg/dL in 7 days) despite subsequent treatment for presumed hepatorenal syndrome (HRS). Given his clinical decline, the patient's goals of care were transitioned to comfort measures only. His clinical presentation and rapid liver and renal deterioration were most typical of sickle cell intrahepatic cholestasis (SCIC). SCIC can lead to rapid deterioration in renal function and can be mistaken for HRS. When SCIC is suspected, consideration of exchange transfusions should be made early. PMID:26135492

[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.

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

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

CT abdominal imaging findings in patients with sickle cell disease: acute vaso-occlusive crisis, complications, and chronic sequelae.

PubMed

Gardner, Carly S; Boll, Daniel T; Bhosale, Priya; Jaffe, Tracy A

2016-12-01

Sickle cell disease (SCD) is the most prevalent hemoglobinopathy. Survival in patients with SCD has improved over the past few decades. These patients experience a lifetime of repeated acute pain crises, which are thought to result from sickling and microvascular occlusions; acute abdominal pain is common. Moreover, repeated crises often lead to organ dysfunction, such as asplenia, hepatic failure, and renal failure. The spleen, liver, biliary system, kidneys, and gastrointestinal tract can all be affected. Patients may undergo CT to further direct clinical management. We review the spectrum of CT imaging findings of abdominal manifestations in patients with SCD, from the acute microvascular occlusive pain crisis to the potential complications and chronic sequelae.

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.

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 ...

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.

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.

[Susceptibility of induced sickle in samples of heterozygous hemoglobin S patients (sickle cell trait) suffering diabetes mellitus type 2].

PubMed

Díaz-Piedra, Pablo; Cervantes-Villagrana, Alberto Rafael; Ramos-Jiménez, Raúl; Presno-Bernal, José Miguel; Cervantes-Villagrana, Rodolfo Daniel

2015-01-01

Hemoglobin S is an abnormal protein that induces morphological changes in erythrocyte in low-oxygen conditions. In Mexico, it is reported that up to 13.7% of the population with mutation in one allele are considered asymptomatic (sickle cell trait). The sickle cell trait and diabetes mellitus are conditions that occur together in more than one million patients worldwide. Both diseases possibly produce microvascular changes in retinopathy and acute chest syndrome. The aim of this study was to evaluate the induction of sickle cells in samples of diabetic patients with sickle cell trait to identify altered red cell parameters. We obtained samples of diabetic patients to determine hemoglobin A1c and S; furthermore, red blood cell biometrics data were analyzed. We found that older men with diabetes were susceptible to generate sickle cells and this correlated with reduced red blood cell count and an increase in media cell volume. In samples of women diabetes, there were no differences. We conclude that samples from patients with sickle cell trait and diabetes can cause sickle cells with high frequency in men, with lower red blood cells count and increased mean corpuscular volume as susceptibility parameters.

Acute pain in children and adults with sickle cell disease: management in the absence of evidence-based guidelines.

PubMed

Field, Joshua J; Knight-Perry, Jessica E; Debaun, Michael R

2009-05-01

Acute, vaso-occlusive pain is the most characteristic complication of sickle cell disease (SCD). Although there has been rigorous work examining the pathogenesis of vaso-occlusion, fewer studies have focused on approaches to the clinical management of acute pain. In this review, we will examine the epidemiology and management strategies of acute pain events and we will identify limitations in the best available studies. Most acute pain events in adults with SCD are managed at home without physician contact. Prior descriptions of the natural history of pain episodes from the Cooperative Study of Sickle Cell Disease relied on physician contact, limiting the generalizability of these findings to current practice. Patient-controlled analgesia has replaced on-demand therapy to become the standard for management of severe pain events in children and adults with SCD requiring hospital admission. Unfortunately, most clinical practice guidelines for the management of acute pain are not based on randomized clinical trials. As a result, our practice of pain management is primarily limited to expert opinion and inferences from observational studies. Additional clinical trials in management of acute pain in children and adults with SCD are critical for the development of evidence-based guidelines.

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.

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

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

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.

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

Nitric oxide metabolite levels in acute vaso-occlusive sickle-cell crisis.

PubMed

Lopez, B L; Barnett, J; Ballas, S K; Christopher, T A; Davis-Moon, L; Ma, X

1996-12-01

1) To measure nitric oxide (NO) metabolite levels in patients presenting to the ED in acute vaso-occlusive sickle-cell crisis (SCC), and 2) to determine whether a relationship exists between NO metabolite levels and pain. A prospective, observational study of patients with documented sickle-cell anemia (SCA), aged > or = 18 years, presenting in typical, acute SCC was conducted in an urban, university teaching hospital. Excluded were those with atypical pain or acute, coexistent disease (as evidenced by fever, tachycardia, tachypnea, or hypotension). Pain scores were measured by a 10-cm visual analog scale (VAS). Blood NO metabolite levels for SCC patients and control subjects (healthy volunteers, n = 9; SCA control subjects not in SCC, n = 10) were determined using an NO-specific chemiluminescence technique that measured plasma nitrite and nitrate, the stable end-products of NO. The acute SCC patients were divided into 3 groups, with the range for the SCC-normal (n = 5) group defined as within 2 SD of the healthy volunteer control patients. The SCC-low patients (n = 21) had NO metabolite levels below this range and the SCC-high (n = 21) patients had levels above this range. The SCA and healthy volunteer control groups had similar NO metabolite levels (25.3 vs 22.6 mumol; p = 0.10). The 3 acute SCC groups had the following mean NO levels: 1) SCC-normal = 21.3 +/- 1.6 mumol; 2) SCC-low = 7.2 +/- 1.1 mumol; and 3) SCC-high = 43.7 +/- 3.5 mumol. The SCC-high NO-level group had significantly lower VAS pain scores when compared with the SCC-low and SCC-normal NO-level groups (6.52 +/- 1.85 cm vs 8.76 +/- 0.83 cm, and 8.62 +/- 1.29 cm, p = 0.02). NO metabolite levels vary in SCC patients. Elevated levels are associated with lower pain scores, while lower levels are associated with higher pain scores, indicating that NO metabolites may potentially represent a marker for compensatory mechanisms in SCC tissue ischemia. Further work is needed to delineate the usefulness of NO

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.

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. ...

Management of the acute painful crisis in sickle cell disease- a re-evaluation of the use of opioids in adult patients.

PubMed

Telfer, Paul; Bahal, Nawal; Lo, Alice; Challands, Joanne

2014-07-01

Management of the acute painful crisis (APC) of sickle cell disease (SCD) remains unsatisfactory despite advances in the understanding and management of acute pain in other clinical settings. One reason for this is an unsophisticated approach to the use of opioid analgesics for pain management. This applies to haematologists who are responsible for developing acute sickle pain management protocols for their patients, and to health care staff in the acute care setting. The objective of this article is to evaluate the evidence for use of opioids in APC management. We have highlighted the possibilities for improving management by using alternatives to morphine, and intranasal (IN) or transmucosal routes of administration for rapid onset of analgesia in the emergency department (ED). We suggest how experience gained in managing acute sickle pain in children could be extrapolated to adolescents and young adults. We have also questioned whether patients given strong opioids in the acute setting are being safely monitored and what resources are required to ensure efficacy, safety and patient satisfaction. We also identify aspects of care where there are significant differences of opinion, which require further study by randomized controlled trial. © 2014 John Wiley & Sons Ltd.

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.

Sickle cell disease pain management in adolescents: a literature review.

PubMed

Wilson, Bridget H; Nelson, Jessica

2015-04-01

Sickle cell disease (SCD) pain continues to emerge in adolescents. More than 98,000 individuals are believed to have SCD in the United States. In fact, 1 in 500 Black infants will be affected by SCD. Identifying standards of care for this unique population can improve pain management and treatment. A significant effect of vaso-occlusive crisis is a decrease in the quality of life in children. Therefore, pain management is multidimensional and includes pharmacologic, physical, and psychological strategies. A review of the literature was conducted to identify best practices regarding pain management in adolescents with sickle cell anemia. Key words such as pain, pain management, adolescent sickle cell anemia, and acute sickle cell pain were entered into databases to reveal qualitative and quantitative studies from 2009 to the present. Many of the research articles identified poor SCD pain management. Studies showed that acute SCD pain management is essential and should be evaluated and robustly managed to achieve optimum pain relief for patients. Acute SCD pain usually occurs as a result of vaso-occlusive crisis. Untreated acute SCD pain can result in morbidity and mortality in adolescents. Nursing knowledge is critical to reducing the stigma and improving management of SCD pain. Nurses play a vital role in the introduction of evidence-based practice within the clinical setting. In an effort to educate nurses and other health care professionals about SCD, this article is a literature review of studies concerning SCD and pain management in emergency rooms. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

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 ...

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.

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 ...

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

Splenic syndrome in patients at high altitude with unrecognized sickle cell trait: splenectomy is often unnecessary.

PubMed

Sheikha, Anwar

2005-10-01

The health risks associated with sickle cell trait are minimal in this sizable sector of the world's population, and many of these patients have no information about their sickle cell status. Splenic syndrome at high altitude is well known to be associated with sickle cell trait, and unless this complication is kept in mind these patients may be subjected to unnecessary surgery when they present with altitude-induced acute abdomen. Four patients were admitted to the surgical ward with a similar complaint of acute severe left upper abdominal pain after arrival to the mountainous resort city of Abha, Saudi Arabia. All were subjected to splenectomy because of lack of suspicion regarding sickle cell status. Histologic examination of the spleen showed all patients had sickle cells in the red pulp. On further assessment all were found to have sickle cell trait with splenic infarction. In a similar study of 6 patients with known sickle cell disease who had comparable problems when they travelled to the Colorado mountains, all made an uncomplicated recovery with conservative management. In ethnically vulnerable patients with splenic syndrome, sickle cell trait should be ruled out before considering splenectomy. These patients could respond well to supportive management, and splenectomy would be avoided.

Sickle cell disease: acute clinical manifestations in early childhood and molecular characteristics in a group of children in Rio de Janeiro

PubMed Central

da Silva Filho, Isaac Lima; Ribeiro, Georgina Severo; Moura, Patrícia Gomes; Vechi, Monica Longo; Cavalcante, Andréa Cony; de Andrada-Serpa, Maria José

2012-01-01

Objectives To describe clinical events of sickle cell disease and the correlation with β-globin haplotypes and α-thalassemia in under 6-year-old children. Methods A retrospective study was conducted of under 6-year-old children from the neonatal screening program in Rio de Janeiro. Forty-eight male and 48 female children were enrolled in this study, 79 with sickle cell anemia and 17 with hemoglobin SC. The mean age was 29.9 (standard deviation = 20.9) months, 62 (16.2 ± 8.6) were aged between 0-3 years old and 34 (54.9 ± 11.3) were from 3-6 years old. Painful events, acute splenic sequestration, hemolytic crises, hand-foot and acute chest syndromes and infections were evaluated. Results The events were more frequent in under 3-year-old children, 94% of children had at least one episode. Infection was the most common event affecting 88.5% of children. Acute splenic sequestration took place earlier, while painful crises and acute chest syndromes in under 6-year-old children. Thal-α 3.7 was observed in 20.9% of cases. Bantu was the most frequent haplotype found, followed by Benin. No correlation was observed between clinical events and β-globin haplotypes. Children with sickle cell anemia and α-thalassemia have less infectious events. No correlation was found among these polymorphisms and clinical events, however, the majority of children with Bantu/Bantu and without α-thalassemia had more clinical events. PMID:23049419

[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.

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.

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.

[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.

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.

MEK1/2 inhibitors reverse acute vascular occlusion in mouse models of sickle cell disease.

PubMed

Zhao, Yulin; Schwartz, Evan A; Palmer, Gregory M; Zennadi, Rahima

2016-03-01

In sickle cell disease (SCD), treatment of recurrent vasoocclusive episodes, leading to pain crises and organ damage, is still a therapeutic challenge. Vasoocclusion is caused primarily by adherence of homozygous for hemoglobin S (SS) red blood cells (SSRBCs) and leukocytes to the endothelium. We tested the therapeutic benefits of MEK1/2 inhibitors in reversing vasoocclusion in nude and humanized SCD mouse models of acute vasoocclusive episodes using intravital microscopy. Administration of 0.2, 0.3, 1, or 2 mg/kg MEK1/2 inhibitor to TNF-α-pretreated nude mice before human SSRBC infusion inhibited SSRBC adhesion in inflamed vessels, prevented the progression of vasoocclusion, and reduced SSRBC organ sequestration. By use of a more clinically relevant protocol, 0.3 or 1 mg/kg MEK1/2 inhibitor given to TNF-α-pretreated nude mice after human SSRBC infusion and onset of vasoocclusion reversed SSRBC adhesion and vasoocclusion and restored blood flow. In SCD mice, 0.025, 0.05, or 0.1 mg/kg MEK1/2 inhibitor also reversed leukocyte and erythrocyte adhesion after the inflammatory trigger of vasoocclusion and improved microcirculatory blood flow. Cell adhesion was reversed by shedding of endothelial E-selectin, P-selectin, and αvβ3 integrin, and leukocyte CD44 and β2 integrin. Thus, MEK1/2 inhibitors, by targeting the adhesive function of SSRBCs and leukocytes, could represent a valuable therapeutic intervention for acute sickle cell vasoocclusive crises. © FASEB.

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.

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.

Sickle cell crisis in the adult: chest radiographic findings and comparison with pediatric sickle cell disease.

PubMed

Miller, J A; Hinrichs, C R

2001-02-01

With the advent of improved therapy, an increasing proportion of individuals suffering from sickle cell disease (SCD) are surviving into adulthood. In contrast to children, little has been documented concerning the typical radiographic findings in adults presenting with sickle cell crises (SCC). We describe the chest radiographic (CXR) manifestations of adults with SCD presenting in SSC, correlated to hemoglobin (Hb) values, and compare them to those of the pediatric sickle cell population. The chest radiographs of 66 consecutive adults presenting to our emergency department complaining of symptoms consistent with acute SCC were retrospectively reviewed over a 12-month period. The radiographic findings were correlated with admission Hb values and compared with those of 50 children with known SCD presenting with SCC. Chi square analysis revealed no significant difference between the cardiovascular and bony findings in the adults and in those of the pediatric controls (p > 0.08-p > 1.0). However, one important difference in the two cohorts was that upper lobe infiltrates occurred exclusively in the pediatric group (p = 0.06). There was a statistically significant (p < 0.05) difference in cardiovascular and skeletal abnormalities between adults with Hb above and below the mean (8.2 g/dL). The radiographic features of adults presenting in acute SCCs are similar to those of children. Although the chest radiograph is often normal, in decreasing frequency, cardiovascular abnormalities, pneumonia sparing the upper lobes, and aseptic osteonecrosis of the shoulders and spine are not uncommon. There is a significant relationship, however, between cardiovascular abnormalities and Hb levels.

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: ...

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

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.

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.

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.

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. ...

The obstetric management of sickle cell disease.

PubMed

Howard, Jo; Oteng-Ntim, Eugene

2012-02-01

Sickle cell disease (SCD) is the most common inherited disease worldwide and is associated with anaemia and intermittent severe pain. Pregnant women who are affected have increased maternal and fetal mortality and morbidity. In view of this obstetricians should have an awareness of this condition and its complications, and pregnancies in women with SCD should be managed by a multidisciplinary team with experience of high risk pregnancies. Ideally women should be seen preconceptually for optimisation of their SCD and partner screening. Antenatal care should include regular outpatient visits with regular monitoring for pre-eclampsia and of fetal growth. Blood transfusion should be used for the treatment of acute anaemia, acute chest syndrome or acute stroke but there is not sufficient evidence currently to recommend its use prophylactically. There is an increased prevalence of sickle crisis during pregnancy and patients should be monitored carefully throughout this time. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

Effectiveness, safety, and cost of partial exchange transfusions in patients with sickle-cell anemia at a sickle cell disease center in sub-Saharan Africa.

PubMed

Boma Muteb, P; Kaluila Mamba, J F J; Muhau Pfutila, P; Bilo, V; Panda Mulefu, J D; Diallo, D A

2017-11-01

The partial exchange transfusions necessary for management of some sickle-cell complications raise the issue of effectiveness in the context of limited resources and inadequate blood safety. This study evaluated the effectiveness, safety, and cost of partial exchange transfusions in 39 patients with sickle-cell anemia in Lubumbashi, looking at the patients' age and gender and the tolerability and direct cost of the transfusions. Excel and SPSS 18 were used for data entry and analysis. Chi2 and Fisher exact tests were used for comparisons. A P-value ≤ 5% was considered statistically significant. The average age of patients was 8.6 ± 6.4 years, and the majority were girls. The most frequent indications were stroke, severe infections, severe vasooclusive crises, and acute chest syndrome. Partial exchange transfusions were effective in improving hemoglobin and hematocrit as well as the percentage of HbS. No acute accident was observed during any partial exchange transfusion; one anti-Kell alloimmunization and 2 cases of iron overload were observed. The annual cost of partial exchange transfusions per patient requiring (and able to afford) regular treatment was US $ 3,345 without iron chelation and more than US $ 5000 with chelation. Partial exchange transfusions are effective and tolerated, but financially inaccessible to the majority of our sickle cell patients. Thus, an assessment is needed of the economic burden of sickle cell complications that require partial exchange transfusions in the context of countries with limited financial resources.

Toward understanding family-related characteristics of young adults with sickle-cell disease or sickle-cell trait in the USA.

PubMed

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

2016-06-01

To describe the family-related characteristics of young adults with sickle-cell disease or sickle-cell trait prior to taking part in a randomised controlled trial on sickle-cell reproductive health education. There is a critical need for educational programmes that target the reproductive needs of young adults with sickle-cell disease or trait. However, little is known about the family-related characteristics (i.e., demographic attributes and reproductive health behaviours) in which these young adults live. A descriptive cross-sectional analysis. At study enrolment, 234 young adults (mean age = 25·9 years, 65% female) completed the SCKnowIQ questionnaire. Descriptive statistics depict the demographic attributes and reproductive health behaviours of young adults with sickle-cell disease (n = 138) or trait (n = 96). For group comparisons, independent t tests or Fisher's tests were used, as appropriate. Young adults with sickle-cell trait had significantly higher education, income and health insurance than those with sickle-cell disease. Both groups believed that sickle-cell disease was a severe condition. A majority of young adults with sickle-cell disease (65%) had no children compared to 42% of those with sickle-cell trait. Most young adults (85% sickle-cell disease, 82% sickle-cell trait) were not planning a pregnancy in the next six months, and many used condoms, withdrawal or oral contraceptives. Socioeconomic disparities exist between young adults with sickle-cell disease and sickle-cell trait. Future research that advances education about how and when to communicate appropriate genetic risk information to partners and children especially for young adults with sickle-cell trait would be beneficial. Awareness of the similarities and differences in the family-related characteristics among young adults with sickle-cell disease or trait can allow for more tailored reproductive education. © 2016 John Wiley & Sons Ltd.

Toward Understanding Family-Related Characteristics of Young Adults with Sickle Cell Disease or Sickle Cell Trait in the USA

PubMed Central

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

2016-01-01

Aims and objectives To describe the family-related characteristics of young adults with sickle cell disease or sickle cell trait prior to taking part in a randomized controlled trial on sickle cell reproductive health education. Background There is a critical need for educational programs that target the reproductive needs of young adults with sickle cell disease or trait. However, little is known about the family-related characteristics (i.e., demographic attributes and reproductive health behaviors) in which these young adults live. Design A descriptive cross-sectional analysis. Method At study enrollment, 234 young adults (mean age = 25.9 years, 65% female) completed the SCKnowIQ questionnaire. Descriptive statistics depict the demographic attributes and reproductive health behaviors of young adults with sickle cell disease (n = 138) or trait (n = 96). For group comparisons, independent t tests or Fisher’s tests were used, as appropriate. Results Young adults with sickle cell trait had significantly higher education, income, and health insurance than those with sickle cell disease. Both groups believed that sickle cell disease was a severe condition. A majority of young adults with sickle cell disease (65%) had no children compared to 42% of those with sickle cell trait. Most young adults (85% sickle cell disease, 82% sickle cell trait) were not planning a pregnancy in the next six months and many used condoms, withdrawal, or oral contraceptives. Conclusions Socioeconomic disparities exist between young adults with sickle cell disease and sickle cell trait. Future research that advances education about how and when to communicate appropriate genetic risk information to partners and children especially for young adults with sickle cell trait would be beneficial. Relevance to clinical practice Awareness of the similarities and differences in the family-related characteristics among young adults with sickle cell disease or trait can allow for more tailored

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

Tapered oral dexamethasone for the acute chest syndrome of sickle cell disease.

PubMed

Quinn, Charles T; Stuart, Marie J; Kesler, Karen; Ataga, Kenneth I; Wang, Winfred C; Styles, Lori; Smith-Whitley, Kim; Wun, Ted; Raj, Ashok; Hsu, Lewis L; Krishnan, Suba; Kuypers, Frans A; Setty, Yamaja; Rhee, Seungshin; Key, Nigel S; Buchanan, George R

2011-10-01

Tapered oral dexamethasone for acute chest syndrome (ACS) in sickle cell anaemia was studied using a novel ACS assessment tool and investigational biomarkers. Twelve participants were randomized (mean age 17·3 years) before early study termination. Dexamethasone decreased duration of hospitalization for ACS by 20·8 h compared to placebo (P = 0·024). Rebound pain occurred in both groups (3 dexamethasone versus 1 placebo). Overall, dexamethasone decreased the leucocyte activation biomarker, sL-selectin; however, participants with rebound pain had higher sL-selectin within 24 h of treatment (dexamethasone or placebo). This ACS assessment tool was feasibly applied, and sL-selectin is a promising biomarker of ACS therapy. © 2011 Blackwell Publishing Ltd.

Tapered oral dexamethasone for the acute chest syndrome of sickle cell disease

PubMed Central

Quinn, Charles T.; Stuart, Marie J.; Kesler, Karen; Ataga, Kenneth I.; Wang, Winfred C.; Styles, Lori; Smith-Whitley, Kim; Wun, Ted; Raj, Ahsok; Hsu, Lewis L.; Krishnan, Suba; Kuypers, Frans A; Setty, B. N. Yamaja; Rhee, Seungshin; Key, Nigel S.; Buchanan, George R.

2011-01-01

Summary Tapered oral dexamethasone for acute chest syndrome (ACS) in sickle cell anaemia was studied using a novel ACS assessment tool and investigational biomarkers. Twelve participants were randomized (mean age 17.3 years) before early study termination. Dexamethasone decreased duration of hospitalization for ACS by 20.8 h compared to placebo (P=0.024). Rebound pain occurred in both groups (3 dexamethasone vs. 1 placebo). Overall, dexamethasone decreased the leucocyte activation biomarker, sL-selectin; however, participants with rebound pain had higher sL-selectin within 24 h of treatment (dexamethasone or placebo). This ACS assessment tool was feasibly applied, and sL-selectin is a promising biomarker of ACS therapy. PMID:21848879

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.

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

Nucleosomes and neutrophil activation in sickle cell disease painful crisis

PubMed Central

Schimmel, Marein; Nur, Erfan; Biemond, Bart J.; van Mierlo, Gerard J.; Solati, Shabnam; Brandjes, Dees P.; Otten, Hans-Martin; Schnog, John-John; Zeerleder, Sacha

2013-01-01

Activated polymorphonuclear neutrophils play an important role in the pathogenesis of vaso-occlusive painful sickle cell crisis. Upon activation, polymorphonuclear neutrophils can form neutrophil extracellular traps. Neutrophil extracellular traps consist of a meshwork of extracellular DNA, nucleosomes, histones and neutrophil proteases. Neutrophil extracellular traps have been demonstrated to be toxic to endothelial and parenchymal cells. This prospective cohort study was conducted to determine neutrophil extracellular trap formation in sickle cell patients during steady state and painful crisis. As a measure of neutrophil extracellular traps, plasma nucleosomes levels were determined and polymorphonuclear neutrophil activation was assessed measuring plasma levels of elastase-α1-antitrypsin complexes in 74 patients in steady state, 70 patients during painful crisis, and 24 race-matched controls using Enzyme Linked Immunosorbent Assay. Nucleosome levels in steady state sickle cell patients were significantly higher than levels in controls. During painful crisis levels of both nucleosomes and elastase-α1-antitrypsin complexes increased significantly. Levels of nucleosomes correlated significantly to elastase-α1-antitrypsin complex levels during painful crisis, (Sr = 0.654, P<0.001). This was seen in both HbSS/HbSβ0-thalassemia (Sr=0.55, P<0.001) and HbSC/HbSβ+-thalassemia patients (Sr=0.90, P<0.001) during painful crisis. Levels of nucleosomes showed a correlation with length of hospital stay and were highest in patients with acute chest syndrome. These data support the concept that neutrophil extracellular trap formation and neutrophil activation may play a role in the pathogenesis of painful sickle cell crisis and acute chest syndrome. PMID:23911704

Targeting novel mechanisms of pain in sickle cell disease.

PubMed

Tran, Huy; Gupta, Mihir; Gupta, Kalpna

2017-11-30

Patients with sickle cell disease (SCD) suffer from intense pain that can start during infancy and increase in severity throughout life, leading to hospitalization and poor quality of life. A unique feature of SCD is vaso-occlusive crises (VOCs) characterized by episodic, recurrent, and unpredictable episodes of acute pain. Microvascular obstruction during a VOC leads to impaired oxygen supply to the periphery and ischemia reperfusion injury, inflammation, oxidative stress, and endothelial dysfunction, all of which may perpetuate a noxious microenvironment leading to pain. In addition to episodic acute pain, patients with SCD also report chronic pain. Current treatment of moderate to severe pain in SCD is mostly reliant upon opioids; however, long-term use of opioids is associated with multiple side effects. This review presents up-to-date developments in our understanding of the pathobiology of pain in SCD. To help focus future research efforts, major gaps in knowledge are identified regarding how sickle pathobiology evokes pain, pathways specific to chronic and acute sickle pain, perception-based targets of "top-down" mechanisms originating from the brain and neuromodulation, and how pain affects the sickle microenvironment and pathophysiology. This review also describes mechanism-based targets that may help develop novel therapeutic and/or preventive strategies to ameliorate pain in SCD. © 2017 by The American Society of Hematology.

[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.

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.

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.

2015 Clinical trials update in sickle cell anemia

PubMed Central

Archer, Natasha; Galacteros, Frédéric; Brugnara, Carlo

2017-01-01

Polymerization of HbS and cell sickling are the prime pathophysiological events in sickle cell disease (SCD). Over the last 30 years, a substantial understanding at the molecular level has been acquired on how a single amino acid change in the structure of the beta chain of hemoglobin leads to the explosive growth of the HbS polymer and the associated changes in red cell morphology. O2 tension and intracellular HbS concentration are the primary molecular drivers of this process, and are obvious targets for developing new therapies. However, polymerization and sickling are driving a complex network of associated cellular changes inside and outside of the erythrocyte, which become essential components of the inflammatory vasculopathy and result in a large range of potential acute and chronic organ damages. In these areas, a multitude of new targets for therapeutic developments have emerged, with several ongoing or planned new therapeutic interventions. This review outlines the key points of SCD pathophysiology as they relate to the development of new therapies, both at the pre-clinical and clinical levels. PMID:26178236

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.

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.

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.

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.

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.

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.

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

State of the Art Management of Acute Vaso-occlusive Pain in Sickle Cell Disease.

PubMed

Puri, Latika; Nottage, Kerri A; Hankins, Jane S; Anghelescu, Doralina L

2018-02-01

Acute vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD). Multiple complex pathophysiological processes can result in pain during a VOC. Despite significant improvements in the understanding and management of SCD, little progress has been made in the management of pain in SCD, although new treatments are being explored. Opioids and non-steroidal anti-inflammatory drugs (NSAIDs) remain the mainstay of treatment of VOC pain, but new classes of drugs are being tested to prevent and treat acute pain. Advancements in the understanding of the pathophysiology of SCD and pain and the pharmacogenomics of opioids have yet to be effectively utilized in the management of VOC. Opioid tolerance and opioid-induced hyperalgesia are significant problems associated with the long-term use of opioids, and better strategies for chronic pain therapy are needed. This report reviews the mechanisms of pain associated with acute VOC, describes the current management of VOC, and describes some of the new therapies under evaluation for the management of acute VOC in SCD.

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

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...

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...

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

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

Prenatal Sickle Cell Screening Education Effect on the Follow-up Rates of Infants with Sickle Cell Trait.

ERIC Educational Resources Information Center

Yang, Yih-Ming; Andrews, Susan; Peterson, Rose; Shah, Arvind; Cepeda, Manuel

2000-01-01

Assesses the effect of prenatal education about newborn sickle cell screening on parents' compliance with the follow-up for infants with sickle cell trait. Results show that parents whose prenatal education included sickle cell hemoglobinopathy information retained significantly more of the information given during the post-natal education than…

Renal amyloidosis in a child with sickle cell anemia.

PubMed

Simşek, Behçet; Bayazit, Aysun K; Ergin, Melek; Soran, Mustafa; Dursun, Hasan; Kilinc, Yurdanur

2006-06-01

The kidney is frequently affected in patients with sickle cell syndrome, i.e., homozygous and heterozygous patients, with a consequently large spectrum of renal abnormalities that may range from minimal functional changes to chronic renal failure. Here, we present a 13-year-old boy with sickle cell anemia (SCA) (HbSS) who was referred to our unit with nephrotic syndrome. Renal biopsy revealed AA type amyloidosis on the basis of light microscopic findings, indicating Congo red staining and immunohistochemistry. He had neither a family history of familial Mediterranean fever (FMF) nor any complaint of recurrent abdominal pain, arthritis, and fever, but frequent painful vaso-occlusive crises. The patient was found to have no MEFV gene (Mediterranean feVer) mutations either. Painful episodic attacks might provoke recurrent acute inflammation, leading to repeated stimulation of acute phase responses and cause secondary amyloidosis. To our knowledge, this boy is the first case of SCA complicated by renal amyloidosis observed in childhood.

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 ...

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

Differentiating osteomyelitis from bone infarction in sickle cell disease.

PubMed

Wong, A L; Sakamoto, K M; Johnson, E E

2001-02-01

This brief review discusses one possible approach to evaluating the sickle cell patient with bone pain. The major differential diagnoses include osteomyelitis and bone infarction. Based on previous studies, we provide an approach to assessing and treating patients with the possible diagnosis of osteomyelitis. An algorithm has been provided, which emphasizes the importance of the initial history and physical examination. Specific radiographic studies are recommended to aid in making the initial assessment and to determine whether the patient has an infarct or osteomyelitis. Differentiating osteomyelitis from infarction in sickle cell patients remains a challenge for the pediatrician. This algorithm can be used as a guide for physicians who evaluate such patients in the acute care setting.

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.

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.

[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.

Emergency Medicine Management of Sickle Cell Disease Complications: An Evidence-Based Update.

PubMed

Simon, Erica; Long, Brit; Koyfman, Alex

2016-10-01

Sickle cell disease (SCD) affects approximately 100,000 individuals in the United States. Due to alterations in the structural conformation of hemoglobin molecules under deoxygenated conditions, patients with SCD are predisposed to numerous sequelae, many of which require acute intervention. Our aim was to provide emergency physicians with an evidence-based update regarding the diagnosis and management of SCD complications. SCD patients experience significant morbidity and mortality secondary to cerebrovascular accident, acute chest syndrome, acute vaso-occlusive pain crises, SCD-related multi-organ failure, cholecystitis, acute intrahepatic cholestasis, acute sickle hepatic crisis, acute hepatic sequestration, priapism, and renal disease. Emergency physicians must recognize acute manifestations of SCD in order to deliver timely management and determine patient disposition. A comprehensive review of the emergency department management of acute SCD complications is provided. Comprehensive understanding of these aspects of SCD can assist physicians in expediting patient evaluation and treatment, thus decreasing the morbidity and mortality associated with this hemoglobinopathy. Copyright © 2016 Elsevier Inc. All rights reserved.

Associations between environmental factors and hospital admissions for sickle cell disease

PubMed Central

Piel, Frédéric B.; Tewari, Sanjay; Brousse, Valentine; Analitis, Antonis; Font, Anna; Menzel, Stephan; Chakravorty, Subarna; Thein, Swee Lay; Inusa, Baba; Telfer, Paul; de Montalembert, Mariane; Fuller, Gary W.; Katsouyanni, Klea; Rees, David C.

2017-01-01

Sickle cell disease is an increasing global health burden. This inherited disease is characterized by a remarkable phenotypic heterogeneity, which can only partly be explained by genetic factors. Environmental factors are likely to play an important role but studies of their impact on disease severity are limited and their results are often inconsistent. This study investigated associations between a range of environmental factors and hospital admissions of young patients with sickle cell disease in London and in Paris between 2008 and 2012. Specific analyses were conducted for subgroups of patients with different genotypes and for the main reasons for admissions. Generalized additive models and distributed lag non-linear models were used to assess the magnitude of the associations and to calculate relative risks. Some environmental factors significantly influence the numbers of hospital admissions of children with sickle cell disease, although the associations identified are complicated. Our study suggests that meteorological factors are more likely to be associated with hospital admissions for sickle cell disease than air pollutants. It confirms previous reports of risks associated with wind speed (risk ratio: 1.06/standard deviation; 95% confidence interval: 1.00–1.12) and also with rainfall (1.06/standard deviation; 95% confidence interval: 1.01–1.12). Maximum atmospheric pressure was found to be a protective factor (0.93/standard deviation; 95% confidence interval: 0.88–0.99). Weak or no associations were found with temperature. Divergent associations were identified for different genotypes or reasons for admissions, which could partly explain the lack of consistency in earlier studies. Advice to patients with sickle cell disease usually includes avoiding a range of environmental conditions that are believed to trigger acute complications, including extreme temperatures and high altitudes. Scientific evidence to support such advice is limited and

Associations between environmental factors and hospital admissions for sickle cell disease.

PubMed

Piel, Frédéric B; Tewari, Sanjay; Brousse, Valentine; Analitis, Antonis; Font, Anna; Menzel, Stephan; Chakravorty, Subarna; Thein, Swee Lay; Inusa, Baba; Telfer, Paul; de Montalembert, Mariane; Fuller, Gary W; Katsouyanni, Klea; Rees, David C

2017-04-01

Sickle cell disease is an increasing global health burden. This inherited disease is characterized by a remarkable phenotypic heterogeneity, which can only partly be explained by genetic factors. Environmental factors are likely to play an important role but studies of their impact on disease severity are limited and their results are often inconsistent. This study investigated associations between a range of environmental factors and hospital admissions of young patients with sickle cell disease in London and in Paris between 2008 and 2012. Specific analyses were conducted for subgroups of patients with different genotypes and for the main reasons for admissions. Generalized additive models and distributed lag non-linear models were used to assess the magnitude of the associations and to calculate relative risks. Some environmental factors significantly influence the numbers of hospital admissions of children with sickle cell disease, although the associations identified are complicated. Our study suggests that meteorological factors are more likely to be associated with hospital admissions for sickle cell disease than air pollutants. It confirms previous reports of risks associated with wind speed (risk ratio: 1.06/standard deviation; 95% confidence interval: 1.00-1.12) and also with rainfall (1.06/standard deviation; 95% confidence interval: 1.01-1.12). Maximum atmospheric pressure was found to be a protective factor (0.93/standard deviation; 95% confidence interval: 0.88-0.99). Weak or no associations were found with temperature. Divergent associations were identified for different genotypes or reasons for admissions, which could partly explain the lack of consistency in earlier studies. Advice to patients with sickle cell disease usually includes avoiding a range of environmental conditions that are believed to trigger acute complications, including extreme temperatures and high altitudes. Scientific evidence to support such advice is limited and sometimes

Spontaneous uterine artery rupture during pregnancy in a woman with sickle cell disease: a case report.

PubMed

Fiori, Olivia; Prugnolles, Hervé; Darai, Emile; Uzan, Serge; Berkane, Nadia

2007-07-01

Spontaneous rupture of uterine vessels during pregnancy is rare and usually involves uteroovarian veins. Presenting symptoms include acute-onset abdominal pain and maternal hypovolemic collapse due to hemoperitoneum. An atypical case of subacute uterine artery rupture at 27 weeks of gestation occurred in a woman with sickle cell disease. A 28-year-old, nulliparous woman with sickle cell disease was admitted at 27 weeks of gestation for sharp abdominal pain radiating to the right flank. The first diagnosis included acute renal colic and a sickling vasoocclusive crisis. One week after admission the patient experienced paroxysmal, diffuse abdominal pain associated with acute fetal distress requiring an emergency cesarean section. Laparotomy revealed an 800-mL hemoperitoneum. Active bleeding from a ruptured uterine artery was observed and successfully treated by selective suture. Spontaneous rupture of the uterine artery during pregnancy may present as a 2-step process.

[Infection and sickle cell anemia].

PubMed

Bégué, P

1999-01-01

Sickle cell disease is associated with frequent and often severe infections as a result of immune function impairment and functional asplenia. Also, infection can trigger a vasoocclusive crisis. Pneumococcal bacteremia and meningitis are so severe as to warrant prophylactic penicillin therapy, which has provided a dramatic decrease in early mortality. Bacterial pneumonia is common in patients younger than four years, with most cases being due to S. pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae. Acute chest syndrome is both a difficult differential diagnosis and a common concomitant of bacterial pneumonia. Osteomyelitis is generally due to a salmonella, most often S. enteritidis; multiple foci are common and treatment is difficult, with some patients developing chronic osteomyelitis with sequestration. Parvovirus B 19 infection causes acute bone marrow failure. Malaria does not result in cerebral malaria but can lead to severe anemia or vasoocclusive crisis, and should therefore be effectively prevented. Antimicrobials are generally selected for efficacy against pneumococci (septicemia, meningitis), Salmonella (septicemia, meningitis, osteomyelitis), and mycoplasmas (pneumonia). Prophylactic therapy is of paramount importance and relies on long-term or lifelong penicillin therapy started at four months of age and on closely-spaced immunizations, most notably against pneumococci, the hepatitis B virus, S. typhi, and H. influenzae. Resistant pneumococcal strains have not been reported to cause prophylactic treatment failures. Conjugated pneumococcal vaccines are effective in protecting infants and should therefore be used in sickle cell patients.

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.

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

Use of a clinical pathway to improve the acute management of vaso-occlusive crisis pain in pediatric sickle cell disease.

PubMed

Ender, Katherine L; Krajewski, Jennifer A; Babineau, John; Tresgallo, Mary; Schechter, William; Saroyan, John M; Kharbanda, Anupam

2014-04-01

The most common, debilitating morbidity of sickle cell disease (SCD) is vaso-occlusive crisis (VOC) pain. Although guidelines exist for its management, they are generally not well-followed, and research in other pediatric diseases has shown that clinical pathways improve care. The purpose of our study was to determine whether a clinical pathway improves the acute management of sickle cell vaso-occlusive crisis (VOC) pain in the pediatric emergency department (PED). Pain management practices were prospectively investigated before and after the initiation of a clinical pathway in the PED of an urban, tertiary care center with 50,000 ED visits per year and approximately 200 active sickle cell patients. The pathway included instructions for triage, monitoring, medication administration, and timing of assessments and interventions. Data were eligible from 35 pre-pathway and 33 post-pathway visits. Primary outcome was time interval to administration of first analgesic medication. Statistical analysis was by Student's t-test, using natural-log-transformed data for outcomes with skewed distribution curves. Time interval to first analgesic improved from 74 to 42 minutes (P = 0.012) and to first opioid from 94 to 46 minutes (P = 0.013). The percentage of patients who received ketorolac increased from 57% to 82% (P = 0.03). Decrease in time interval to subsequent pain score assessment was not statistically significant (110 to 72 minutes (P = 0.07)), and change in pain score was not different (P = 0.25). The use of a clinical pathway for sickle cell VOC in the PED can improve important aspects of pain management and merits further investigation and implementation. © 2013 Wiley Periodicals, Inc.

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,…

Sickle cell disease in tribal populations in India

PubMed Central

Colah, Roshan B.; Mukherjee, Malay B.; Martin, Snehal; Ghosh, Kanjaksha

2015-01-01

The sickle gene is widespread among many tribal population groups in India with prevalence of heterozygotes varying from 1-40 per cent. Co-inheritance of the sickle gene with β-thalassaemia, HbD Punjab and glucose-6-phosphate dehydrogenase (G6PD) deficiency has also been reported. Most of the screening programmes in India now use high performance liquid chromatography (HPLC) analysis although the solubility test is also sensitive and cheap. Sickle cell disease (SCD) among tribal populations is generally milder than among non-tribal groups with fewer episodes of painful crises, infections, acute chest syndrome and need for hospitalization. This has partly been attributed to the very high prevalence of α-thalassaemia among these tribes as well as higher foetal haemoglobin levels. However, the clinical presentation is variable with many cases having a severe presentation. There is not much information available on maternal and perinatal outcome in tribal women with sickle cell disease. Newborn screening programmes for SCD have recently been initiated in Maharashtra, Gujarat, Odisha and Chattisgarh and monitoring these birth cohorts will help to understand the natural history of SCD in India. Prenatal diagnosis is acceptable by tribal families in India. The Indian Council of Medical Research and the National Rural Health Mission in different States are undertaking outreach programmes for better management and control of the disease. PMID:26139766

Clinical correlates of acute pulmonary events in children and adolescents with sickle cell disease*

PubMed Central

Paul, Rabindra; Minniti, Caterina P.; Nouraie, Mehdi; Luchtman-Jones, Lori; Campbell, Andrew; Rana, Sohail; Onyekwere, Onyinye; Darbari, Deepika S.; Ajayi, Olaid; Arteta, Manuel; Ensing, Gregory; Sable, Craig; Dham, Niti; Kato, Gregory J.; Gladwin, Mark T.; Castro, Oswaldo L.; Gordeuk, Victor R.

2013-01-01

Objectives We aimed to identify risk factors for acute pulmonary events in children and adolescents in the Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH) study. Methods Patients with hemoglobin SS (n=376) and other sickle cell genotypes (n=127) aged 3-20 years were studied at four centers in a cross-sectional manner. A sub-group (n=293) was followed for a median of 21 months (range 9-35). Results A patient-reported history of one or more acute pulmonary events, either acute chest syndrome (ACS) or pneumonia, was obtained in 195 hemoglobin SS patients (52%) and 51 patients with other genotypes (40%). By logistic regression, history of acute pulmonary events was independently associated with patient-reported history of asthma (p<0.0001), older age (p=0.001), >3 severe pain episodes in the preceding 12 months (p=0.002), higher tricuspid regurgitation velocity (TRV) (p=0.028), and higher white blood cell (WBC) count (p=0.043) among hemoglobin SS patients. History of acute pulmonary events was associated with >3 severe pain episodes (p=0.009) among patients with other genotypes. During follow-up, 43 patients (15%) had at least one new ACS episode including 11 without a baseline history of acute pulmonary events. History of acute pulmonary events (odds ratio 5.4; p<0.0001) and younger age (odds ratio 0.9; p=0.010) were independently associated with developing a new episode during follow-up. Conclusions Asthma history, frequent pain and higher values for TRV and WBC count were independently associated with history of acute pulmonary events in hemoglobin SS patients and frequent pain was associated in those with other genotypes. Measures to reduce pain episodes and control asthma may help to decrease the incidence of acute pulmonary events in SCD. PMID:23560516

'It means everyone should know their status': exploring lay conceptions of sickle cell trait and sickle cell trait screening among African Americans within middle reproductive age.

PubMed

Mayo-Gamble, Tilicia L; Barnes, Priscilla A; Cunningham Erves, Jennifer; Middlestadt, Susan E; Lin, Hsien-Chang

2017-02-21

This study examined the meaning of sickle cell trait and sickle cell trait screening from the lay perspective of African Americans. African Americans (N = 300), ages 18-35 and unaware of their sickle cell trait status, completed two open-ended questions from a larger survey. One question asked for their understanding of sickle cell trait; the other asked for their understanding of sickle cell trait screening. Content analysis occurred in two phases: (1) In vivo and holistic coding; and (2) focused coding. Four categories emerged illustrating lay conceptions of sickle cell trait; (1) Perceived as an illness; (2) Perceived recognition of the inheritance pattern of sickle cell trait; (3) Perceived lack of knowledge of sickle cell trait; and (4) Perceived importance of sickle cell trait. Five categories emerged illustrating lay conceptions for sickle cell trait screening: (1) Perceived recognition that screening means getting tested for sickle cell trait; (2) Perceived lack of knowledge of sickle cell trait screening; (3) Perceived health benefit of sickle cell trait screening; (4) Perceived importance of sickle cell trait screening; and (5) Perceived barriers to sickle cell trait screening. Sickle cell trait and sickle cell trait screening are concepts that are both regarded as important among this high-risk population. However, there is still misunderstanding concerning the hereditary nature and reproductive implications of sickle cell trait. Interventions seeking to improve communication on the need for sickle cell trait screening should begin by identifying what the population at large understands, knows and/or believes to improve their ability to make informed health decisions.

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

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 ...

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.

Psychological therapies for sickle cell disease and pain.

PubMed

Anie, Kofi A; Green, John

2015-05-08

not the sensory component (pain intensity), mean difference 0.00 (95% confidence interval -9.39 to 9.39). One study of family psycho-education was not associated with a reduction in depression. Another study evaluating cognitive behavioural therapy had inconclusive results for the assessment of coping strategies, and showed no difference between groups assessed on health service utilisation. In addition, family home-based cognitive behavioural therapy did not show any difference compared to disease education. One study of patient education on health beliefs showed a significant improvement in attitudes towards health workers, mean difference -4.39 (95% CI -6.45 to -2.33) and medication, mean difference -1.74 (95% CI -2.98 to -0.50). Nonetheless, these results may not apply across all ages, severity of sickle cell disease, types of pain (acute or chronic), or setting. Evidence for the efficacy of psychological therapies in sickle cell disease is currently limited. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions in sickle cell disease.

Efficacy of tramadol vs meperidine in vasoocclusive sickle cell crisis.

PubMed

Uzun, Belkan; Kekec, Zeynep; Gurkan, Emel

2010-05-01

Despite progress in management, patients with sickle cell disease who are experiencing acute painful episode are often incompletely treated. We compared meperidine and tramadol with respect to their effects on the hemodynamics and pain relief in patients with sickle cell disease who were admitted to the emergency department with painful crisis. A total of 68 patients with sickle cell disease were randomly assigned to receive either tramadol 1.5 mg/kg (n = 34) or meperidine 1 mg/kg (n = 34). Hemodynamic parameters were recorded at regular intervals after analgesic infusions. Pain intensity and relief were documented by visual analog and pain relief scale, respectively. Sedation level was defined according to Ramsay sedation scale. Both meperidine and tramadol administration resulted in a significant reduction in systolic and diastolic blood pressure after 2 hours (P < .05). Efficacy in pain relief between the analgesics was more rapid and better in the meperidine group, although the degree of relief were significantly improved compared to baseline levels in both groups (P < .05). Sedation was more commonly seen in the meperidine arm. None of the patients had experienced neurotoxicity. In summary, both agents had proven safe and effective for emergent use in patients with sickle cell disease. Avoiding meperidine injections as recommended with previous guidelines needs to be carefully reconsidered especially when low doses are mentioned. (c) 2010. Published by Elsevier Inc.

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.

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

Preoperative blood transfusions for sickle cell disease

PubMed Central

Estcourt, Lise J; Fortin, Patricia M; Trivella, Marialena; Hopewell, Sally

2016-01-01

ongoing trials identified. These trials were conducted between 1988 and 2011. The majority of people included had haemoglobin (Hb) SS SCD. The majority of surgical procedures were considered low or intermediate risk for developing sickle cell-related complications. Aggressive versus simple red blood cell transfusions One trial (551 participants) compared an aggressive transfusion regimen (decreasing sickle haemoglobin to less than 30%) to a simple transfusion regimen (increasing haemoglobin to 100 g/l). This trial re-randomised participants and therefore quantitative analysis was only possible on two subsets of data: participants undergoing cholecystectomy (230 participants); and participants undergoing tonsillectomy or adenoidectomy surgeries (107 participants). Data were not combined as we do not know if any participant received both surgeries. Overall, the quality of the evidence was very low across different outcomes according to GRADE methodology. This was due to the trial being at high risk of bias primarily due to lack of blinding, indirectness and the outcome estimates being imprecise. Cholecystectomy subgroup results are reported in the abstract. Results for both subgroups were similar. There was no difference in all-cause mortality between people receiving aggressive transfusions and those receiving conservative transfusions. No deaths occurred in either subgroup. There were no differences between the aggressive transfusion group and conservative transfusion group in the number of people developing: an acute chest syndrome, risk ratio 0.84 (95% confidence interval 0.38 to 1.84) (one trial, 230 participants, very low quality evidence);vaso-occlusive crisis, risk ratio 0.30 (95% confidence interval 0.09 to 1.04) (one trial, 230 participants, very low quality evidence);serious infection, risk ratio 1.75 (95% confidence interval 0.59 to 5.18) (one trial, 230 participants, very low quality evidence);any perioperative complications, risk ratio 0.75 (95% confidence

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.

[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.

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)

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

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.

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.

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.

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.

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

The use of incentive spirometry in pediatric patients with sickle cell disease to reduce the incidence of acute chest syndrome.

PubMed

Ahmad, Fahd A; Macias, Charles G; Allen, Joseph Y

2011-08-01

To determine if incentive spirometry (IS) in pediatric patients admitted with sickle cell disease for nonrespiratory complaints will decrease acute chest syndrome (ACS). This was an Institutional Review Board-approved before-after 2-year retrospective cohort study evaluating an evidence-based guideline (EBG) initiating mandatory IS in admitted pediatric sickle cell patients from a tertiary children's emergency center. Student t testing and χ² analysis were performed. There were 1551 patient visits. About 258 visits were enrolled in the pre-EBG year, and 230 in the EBG year. Between year characteristics were similar. The EBG year reported higher use of hydroxyurea (P<0.01), analgesics (P=0.02), and chest pain (P=0.03). Sixty-seven patients (25.9%) in the pre-EBG year received transfusions versus 51 (22.5%) in the EBG year (NS). Twenty-five (9.6%) of the pre-EBG patients received blood for ACS versus 14 (6.1%) in the EBG group (absolute risk reduction: 3.5%, 95% confidence interval: -1-8.4%). Subgroup analysis revealed that patients who presented with back pain experienced a significant decrease in the development of ACS in the EBG year (P=0.04, absolute risk reduction: 14%, 95% confidence interval: 1-28%, number needed to treat: 8). Mandatory IS for sickle cell disease patients admitted without respiratory complaints reduces transfusions and ACS, particularly for those presenting with back pain.

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.

Optimizing the care model for an uncomplicated acute pain episode in sickle cell disease.

PubMed

Telfer, Paul; Kaya, Banu

2017-12-08

The pathophysiology, clinical presentation, and natural history of acute pain in sickle cell disease are unique and require a disease-centered approach that also applies general principles of acute and chronic pain management. The majority of acute pain episodes are managed at home without the need to access health care. The long-term consequences of poorly treated acute pain include chronic pain, adverse effects of chronic opioid usage, psychological maladjustment, poor quality of life, and excessive health care utilization. There is no standard protocol for management of an acute pain crisis in either the hospital or the community. The assumptions that severe acute pain must be managed in the hospital with parenteral opioids and that strong opioids are needed for home management of pain need to be questioned. Pain management in the emergency department often does not meet acceptable standards, while chronic use of strong opioids is likely to result in opioid-induced hyperalgesia, exacerbation of chronic pain symptoms, and opioid dependency. We suggest that an integrated approach is needed to control the underlying condition, modify psychological responses, optimize social support, and ensure that health care services provide safe, effective, and prompt treatment of acute pain and appropriate management of chronic pain. This integrated approach should begin at an early age and continue through the adolescent, transition, and adult phases of the care model. © 2016 by The American Society of Hematology. All rights reserved.

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

Circulating DNA: a potential marker of sickle cell crisis.

PubMed

Vasavda, Nisha; Ulug, Pinar; Kondaveeti, Sheila; Ramasamy, Karthik; Sugai, Taku; Cheung, Gordon; Rees, David C; Awogbade, Moji; Bannister, Sybil; Cunningham, Juliette; Menzel, Stephan; Thein, Swee Lay

2007-10-01

Free circulating DNA is present in the plasma of healthy subjects, and is elevated in conditions characterized by increased cell death, such as cancer and physical trauma. Analysis of circulating DNA in plasma could provide a useful biomarker in sickle cell disease (SCD) in view of the increased cell turnover through chronic ongoing haemolysis, recurrent vaso-occlusion and inflammation. Plasma DNA was determined by real-time quantitative polymerase chain reaction (PCR) amplification of the beta-globin gene (HBB) in 154 patients with SCD [105 haemoglobin (Hb)SS, 46 HbSC and three HbS/beta(0) thalassaemia] and 53 ethnically matched controls. Blood samples were obtained from all patients in steady state; 21 of the 154 patients were also sampled during admission to hospital for acute pain. Median concentration of circulating plasma DNA in acute pain was more than 10-fold that in steady state and in controls - 10070 vs. 841 and 10070 vs. 933 genome equivalents/ml respectively (P < 0.0001, in both cases). During steady state, patients had plasma DNA levels similar to controls. Plasma DNA levels in SCD correlated with C-reactive protein levels (P < 0.005) and total white cell counts (P < 0.05) in steady state. The study shows that plasma DNA concentration may have potential as a biomarker in sickle cell patients.

Drugs for preventing red blood cell dehydration in people with sickle cell disease.

PubMed

Nagalla, Srikanth; Ballas, Samir K

2016-03-04

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. This is an updated version of a previously published review. 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: 28 November 2015. 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

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.

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.

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.

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.

Perioperative Management of Sickle Cell Disease.

PubMed

Adjepong, Kwame Ofori; Otegbeye, Folashade; Adjepong, Yaw Amoateng

2018-01-01

Over 30 million people worldwide have sickle cell disease (SCD). Emergent and non-emergent surgical procedures in SCD have been associated with relatively increased risks of peri-operative mortality, vaso-occlusive (painful) crisis, acute chest syndrome, post-operative infections, congestive heart failure, cerebrovascular accident and acute kidney injury. Pre-operative assessment must include a careful review of the patient's known crisis triggers, baseline hematologic profile, usual transfusion requirements, pre-existing organ dysfunction and opioid use. Use of preoperative blood transfusions should be selective and decisions individualized based on the baseline hemoglobin, surgical procedure and anticipated volume of blood loss. Intra- and post-operative management should focus on minimizing hypoxia, hypothermia, acidosis, and intravascular volume depletion. Pre- and post-operative incentive spirometry use should be encouraged.

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.

How I treat and manage strokes in sickle cell disease

PubMed Central

Kassim, Adetola A.; Galadanci, Najibah A.; Pruthi, Sumit

2015-01-01

Neurologic complications are a major cause of morbidity and mortality in sickle cell disease (SCD). In children with sickle cell anemia, routine use of transcranial Doppler screening, coupled with regular blood transfusion therapy, has decreased the prevalence of overt stroke from ∼11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurologic deficit includes evaluation by a multidisciplinary team (a hematologist, neurologist, neuroradiologist, and transfusion medicine specialist); prompt neuro-imaging and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion) is recommended if the hemoglobin is >4 gm/dL and <10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and long-term management of strokes in SCD. PMID:25824688

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

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.

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.

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.

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.

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.

Marked Direct Hyperbilirubinemia due to Ceftriaxone in an Adult with Sickle Cell Disease

PubMed Central

Khurram, Daniyeh; Shamban, Leonid; Kornas, Robert; Paul, Maryann

2015-01-01

Drugs are a significant cause of liver injury. Drug-induced liver injury (DILI) can cause acute hepatitis, cholestasis, or a mixed pattern. Ceftriaxone is a commonly used antibiotic and has been associated with reversible biliary sludge, pseudolithiasis, and cholestasis. A 32-year-old male with sickle cell disease was admitted to the hospital for acute sickle cell crisis. On the second day of hospitalization, he developed cough and rhonchi with chest X-ray revealing right middle lobe infiltrates. Ceftriaxone and azithromycin were initiated. Subsequently, he developed conjugated hyperbilirubinemia and mild transaminitis. His total bilirubin trended upwards from 3.3 mg/dL on admission to 17 mg/dL. It was predominantly conjugated bilirubin, with preadmission bilirubin levels of 3-4 mg/dL. His transaminases were mildly elevated as well compared to previous levels. Extensive workup for bilirubin elevation was unremarkable. Ceftriaxone was switched to levofloxacin and the hyperbilirubinemia improved. On ambulatory follow-up, his bilirubin remained below 4 mg/dL. Ceftriaxone may be associated with marked direct hyperbilirubinemia particularly in sickle cell patients with chronic liver chemistry abnormalities. In the case of elevated bilirubin with concomitant ceftriaxone use, elimination of the offending agent should be considered. PMID:26101675

Prevalence of human parvovirus B19 in sickle cell disease and healthy controls.

PubMed

Teuscher, T; Baillod, B; Holzer, B R

1991-01-01

The serological HPV status of 35 patients with SCA (Hb SS), randomly chosen from a sickle cell clinic in rural south-west Togo and of 13 household members with normal haemoglobin type (Hb AA) was assessed. No difference in HPV-IgG seropositivity rate was found. In 30 urban hospital patients from Abidjan, Ivory Coast, who were in acute painful sickle cell crisis HPV-IgG seropositivity rate increased with age. In only one (HIV positive) patient HPV-IgM antibodies were detected. It is concluded that HPV-infection exists in West Africa (1) and that there is no evidence for increased seroprevalence in SCA (2). HPV does not seem to trigger acute painful crises in SCA (3). The age-specific HPV seropositivity increase in urban patients may be due to differing transmission rates in urban and rural areas.

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

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.

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 Cell Trait, Exercise, and Altitude.

ERIC Educational Resources Information Center

Eichner, Edward R.

1986-01-01

Sickle cell trait is generally benign and does not shorten life, but it may confer some small risk with extremes of exercise or altitude. Research concerning these risks is presented, and it is concluded sickle cell trait is no barrier to outstanding athletic performance. (Author/MT)

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.

Inflammation in sickle cell disease.

PubMed

Conran, Nicola; Belcher, John D

2018-01-01

The primary β-globin gene mutation that causes sickle cell disease (SCD) has significant pathophysiological consequences that result in hemolytic events and the induction of the inflammatory processes that ultimately lead to vaso-occlusion. In addition to their role in the initiation of the acute painful vaso-occlusive episodes that are characteristic of SCD, inflammatory processes are also key components of many of the complications of the disease including autosplenectomy, acute chest syndrome, pulmonary hypertension, leg ulcers, nephropathy and stroke. We, herein, discuss the events that trigger inflammation in the disease, as well as the mechanisms, inflammatory molecules and cells that propagate these inflammatory processes. Given the central role that inflammation plays in SCD pathophysiology, many of the therapeutic approaches currently under pre-clinical and clinical development for the treatment of SCD endeavor to counter aspects or specific molecules of these inflammatory processes and it is possible that, in the future, we will see anti-inflammatory drugs being used either together with, or in place of, hydroxyurea in those SCD patients for whom hematopoietic stem cell transplants and evolving gene therapies are not a viable option.

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.

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.

Perioperative Management of Sickle Cell Disease

PubMed Central

Adjepong, Kwame Ofori; Otegbeye, Folashade

2018-01-01

Over 30 million people worldwide have sickle cell disease (SCD). Emergent and non-emergent surgical procedures in SCD have been associated with relatively increased risks of peri-operative mortality, vaso-occlusive (painful) crisis, acute chest syndrome, post-operative infections, congestive heart failure, cerebrovascular accident and acute kidney injury. Pre-operative assessment must include a careful review of the patient’s known crisis triggers, baseline hematologic profile, usual transfusion requirements, pre-existing organ dysfunction and opioid use. Use of preoperative blood transfusions should be selective and decisions individualized based on the baseline hemoglobin, surgical procedure and anticipated volume of blood loss. Intra- and post-operative management should focus on minimizing hypoxia, hypothermia, acidosis, and intravascular volume depletion. Pre- and post-operative incentive spirometry use should be encouraged. PMID:29755709

[Hydrocholecystis, a rare etiology of painful abdominal crisis in sickle cell disease. About two cases].

PubMed

Tsiba, J B; Mpemba-Loufoua, A B; Makosso, E; Nzingoula, S

2007-02-01

The authors report two cases of hydocholecystis causing abdominal pains in the sickle cell child. The patients were two girls aged respectively 4 and 12. Hydrocholecystis is defined by acute distension of the gallbladder The diagnosis was made by scan which allowed to follow the evolution in the two sickle cell children. After two crises, no more recurrence was noted in the first patient, on the other hand in the second child recurrences became more frequent. Some authors indicate surgery systematically while others recommend it only after several recurrences.

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)

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...

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 ...

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

Asthma Management in Sickle Cell Disease

PubMed Central

Morris, Claudia R.

2013-01-01

Asthma is a common comorbid factor in sickle cell disease (SCD). However, the incidence of asthma in SCD is much higher than expected compared to rates in the general population. Whether “asthma” in SCD is purely related to genetic and environmental factors or rather is the consequence of the underlying hemolytic and inflammatory state is a topic of recent debate. Regardless of the etiology, hypoxemia induced by bronchoconstriction and inflammation associated with asthma exacerbations will contribute to a cycle of sickling and subsequent complications of SCD. Recent studies confirm that asthma predisposes to complications of SCD such as pain crises, acute chest syndrome, and stroke and is associated with increased mortality. Early recognition and aggressive standard of care management of asthma may prevent serious pulmonary complications and reduce mortality. However, data regarding the management of asthma in SCD is very limited. Clinical trials are needed to evaluate the effectiveness of current asthma therapy in patients with SCD and coincident asthma, while mechanistic studies are needed to delineate the underlying pathophysiology. PMID:24324967

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

Addressing challenges of clinical trials in acute pain: The Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study.

PubMed

Nottage, Kerri A; Hankins, Jane S; Faughnan, Lane G; James, Dustin M; Richardson, Julie; Christensen, Robbin; Kang, Guolian; Smeltzer, Matthew; Cancio, Maria I; Wang, Winfred C; Anghelescu, Doralina L

2016-08-01

Neuropathic pain is a known component of vaso-occlusive pain in sickle cell disease; however, drugs targeting neuropathic pain have not been studied in this population. Trials of acute pain are complicated by the need to obtain consent, to randomize participants expeditiously while optimally treating pain. We describe the challenges in designing and implementing the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study (NCT01954927), a phase II, randomized, double-blind, placebo-controlled trial to determine the effect of gabapentin for vaso-occlusive crisis. In the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study, we aim to assess the analgesic effect of gabapentin during vaso-occlusive crisis. Difficulties we identified included avoiding delay of notification of study staff of potential participants which we resolved by automated notification. Concern for rapid randomization and drug dispensation was addressed through careful planning with an investigational pharmacy and a single liquid formulation. We considered obtaining consent during well-visits to avoid the time constraints with acute presentations, but the large number of patients and limited duration that consent is valid made this impractical. In all, 79% of caregivers/children approached have agreed to participate. The trial is currently active, and enrollment is at 45.8% of that targeted (76 of 166) and expected to continue for two more years. Maintaining staff availability after-hours remains problematic, with 8% of screened patients missed for lack of available staff. Lessons learned in designing a trial to expedite procedures in the acute pain setting include (1) building study evaluations upon a standard-of-care backbone; (2) implementing a simple study design to facilitate consent and data capture; (3) assuring ample, well-trained study staff; and (4) utilizing technology to automate procedures

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.

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

Oral ketamine for sickle cell crisis pain refractory to opioids.

PubMed

Jennings, Cara A; Bobb, Barton T; Noreika, Danielle M; Coyne, Patrick J

2013-06-01

There is literature demonstrating that the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has analgesic properties that can be used as an adjuvant to opiates for pain relief in multiple various conditions and pain states. However, there is a lack of published information on ketamine used in persons with sickle cell disease in acute pain crises. The Virginia Commonwealth University Palliative Care team was consulted on a 38-year-old African American female with sickle cell thalassemia in severe acute pain crisis overlying chronic pain related to her disease. Pain control was unable to be achieved with escalating doses of opiates and other adjuvant medications. The patient responded well to an intravenous test dose of ketamine and was subsequently placed on an oral regimen of ketamine in addition to opiates. In the 24-hour period following ketamine initiation, the patient's pain was able to be controlled on decreased amounts of opiates. She was eventually transitioned to an oral opiate and ketamine regimen, which allowed her to be discharged home with pain levels close to her baseline and the ability to function and perform all activities of daily living.

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 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.

Non-traumatic spontaneous acute epidural hematoma in a patient with sickle cell disease.

PubMed

Serarslan, Yurdal; Aras, Mustafa; Altaş, Murat; Kaya, Hasan; Urfalı, Boran

2014-01-01

A 19-year-old female with sickle cell anemia (SCD) was referred to our hospital after two days of hospitalization at another hospital for a headache crisis. This headache crisis was due to a raised intracranial pressure; these symptoms were noted and included in her comprehensive list of symptoms. There was an acute drop in the hemoglobin and hematocrit levels. The cranial CT scan demonstrated a left fronto-parietal acute epidural hematoma (AEH) and a calvarial bone expansion, which was suggestive of medullary hematopoiesis. The patient underwent emergent craniotomy and evacuation of the hematoma. There were no abnormal findings intra-operatively apart from the AEH, except skull thickening and active petechial bleeding from the dural arteries. Repeated CT scan showed a complete evacuation of the hematoma. The possible underlying pathophysiological mechanisms were discussed. In addition to the factors mentioned in the relevant literature, any active petechial bleeding from the dural arteries on the separated surface of the dura from the skull could have contributed to the expanding of the AEH in our patient. Neurosurgeons and other health care providers should be aware of spontaneous AEH in patients with SCD. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

[Blood transfusion assessment to 112 homozygous sickle-cell disease patients in university hospital of Brazzaville].

PubMed

Dokekias, A Elira; Ossini, L Ngolet; Tsiba, F O Atipo; Malanda, F; Koko, I; De Montalembert, M

2009-01-01

Homozygous, sickle-cell disease (SCD) is responsible for acute complication, especially anaemic crisis and special situation such as acute chest syndrome, stroke and acute priapism. Pregnancy sickle-cell disease presents high risk for the mother and the fetus. In these indications, blood transfusion is the main therapy aiming to reduce anaemia in order to restore hemoglobin's rate or to increase normal Hb proportion. This study aims to assess the short-term efficiency of the red cell transfusion in SCD homozygous form. One hundred and twelve homozygous sickle-cell patients were enrolled in this prospective study: 59 females and 53 males, median age is 21,8 years (extremes: 2 and 45 years). These patients are mostly with very low income. Two groups of patients are included in this study. In the first group, patients present acute anemia crisis caused by infections disease (malaria, bacterial infections). In the second group (20 cases), SCD patients have particularly situations: pregnancy (10 cases); stroke (six cases); cardiac failure (two cases) and priapism (two cases). Transfusion treatment in first group is simple regimen. Transfusion of EC increased median Hb level at 2,9 g/dl (extremes: 1,1 and 4,7). In the second group of patients, 16 cases were transfused by manual partial exchange (1-3) and four patients received simple regimen of transfusion. Median Hb level was 3,1g/dl (extremes: 2,4-4,9 g/dl). HbS percentage reduction was after PTE between -30 and -66,8% (median: -52,6%). According to our diagnostic possibilities (blood serologic test), we have not found any contamination by HIV, HBV and HCV (virus).

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.

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)

Sickle Cell Disease: An Opportunity for Palliative Care across the Life Span

PubMed Central

Johnson, Bonnye; Mack, A. Kyle; Labotka, Richard; Molokie, Robert E.

2010-01-01

Sickle cell disease is a chronic illness that impacts patients physically and emotionally and can do so at an early age. An ecological model of palliative care that involves improved communication among the health care team, patients, and their families can be beneficial. Open and honest communication regarding advance care planning, disease management, relief of pain and other symptoms, and bereavement and grief are all important for the patient, family, and health care team. Given the multiple acute and chronic complications of sickle cell disease, an approach to care that is holistic and comprehensive may help to improve a patient’s biological function and the perceived health, functional status, and quality of life of the patient and family. PMID:20804884

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.

Severe Vaso-Occlusive Episodes Associated with Use of Systemic Corticosteroids in Patients with Sickle Cell Disease

PubMed Central

Darbari, Deepika S.; Castro, Oswaldo; Taylor, James G.; Fasano, Ross; Rehm, Jeffrey; Gordeuk, Victor R.; Minniti, Caterina P.

2017-01-01

Patients with sickle cell disease (SCD) are occasionally prescribed systemic corticosteroids to treat steroid-responsive conditions. Additionally, use of systemic corticosteroids for sickle cell pain episodes and acute chest syndrome is under investigation. We report 4 patients with SCD who developed severe vaso-occlusive events following the administration of systemic steroids. We also review similar cases from the literature and suggest measures for reducing the potential risk associated with use of systemic corticosteroids in this group of patients. We conclude that corticosteroids should be used with caution in patients with SCD. PMID:28643632

Sickle cell 'girdle syndrome' progressing to ischaemic colitis and colonic perforation.

PubMed

Qureshi, A; Lang, N; Bevan, D H

2006-02-01

Abdominal pain of presumed vasocclusive origin, often termed 'girdle syndrome' because of the circumferential distribution of the pain, is common in sickle cell anaemia (SCA). Evidence of progression to bowel infarction is rare. A 27-year-old man with SCA developed chest and abdominal pain unresponsive to opiate analgesia. Abdominal X-ray showed dilated bowel loops because of partial obstruction. Despite reduction of HbS to 23% by automated red cell exchange, abdominal pain worsened. A CT scan was the most informative investigation and showed free peritoneal air. He underwent emergency hemicolectomy and reversible ileostomy formation. Histology of the resected colon was consistent with acute ischaemic colitis. Early surgical intervention remains essential in SCA when abdominal pain does not respond to maximal therapy including red cell exchange: as this case illustrates, sickle girdle syndrome has the capacity to progress to irreversible ischaemic colitis and necrotic perforation of the bowel wall.

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

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

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

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.

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)

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 ...

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

Sickle cell disease in children.

PubMed

Meier, Emily Riehm; Miller, Jeffery L

2012-05-07

Early identification of infants with sickle cell disease (SCD) by newborn screening, now universal in all 50 states in the US, has improved survival, mainly by preventing overwhelming sepsis with the early use of prophylactic penicillin. Routine transcranial Doppler screening with the institution of chronic transfusion decreases the risk of stroke from 10% to 1% in paediatric SCD patients. Hydroxyurea decreases the number and frequency of painful crises, acute chest syndromes and number of blood transfusions in children with SCD. Genetic research continues to be driven toward the prevention and ultimate cure of SCD before adulthood. This review focuses on clinical manifestations and therapeutic strategies for paediatric SCD as well as the evolving topic of gene-focused prevention and therapy.

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.

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

Non-pharmacologic management of sickle cell pain.

PubMed

Bodhise, Paul Brown; Dejoie, Marjorie; Brandon, Zemoria; Simpkins, Stanley; Ballas, Samir K

2004-06-01

Patients with sickle cell disease (SCD) suffer from both acute and chronic pain. The latter includes avascular necrosis of the hip joints mostly in the adult population. It has a negative impact on the quality of life of affected individuals and is often associated with depression, disability, unemployment and dependence on opioid analgesics. In this study, we show that a non-pharmacologic approach to management with deep tissue/deep pressure massage therapy technique, including neuromuscular trigger point treatment with acupressure, in patients with SCD has a salutary effect on pain relief and quality of life. Copyright 2004 Taylor and Francis Ltd

Blood transfusion and 30-day readmission rate in adult patients hospitalized with sickle cell disease crisis

PubMed Central

Nouraie, Mehdi; Gordeuk, Victor R.

2015-01-01

Background Sickle cell disease (SCD) patients hospitalized with vaso-occlusive pain crisis tend to have prolonged length of stay (LOS) and high 30-day readmission rates. We investigated the associations of demographic characteristics, comorbidities and blood transfusion during hospitalization with these outcomes. Study Design Repeated regression analysis was used to analyze 39,324 admissions of 4,348 adults with sickle cell crisis from 2007–2012 in the Truven Health MarketScan® Medicaid Databases. Results The mean (95% range) LOS was 5.9 (1.0–19.0) days and the 30-day readmission rate was 39.6% (95% confidence interval [CI]: 39.1%–40.0%). Older age, chronic cardiopulmonary, renal or liver disease and sepsis were associated with both longer LOS and greater 30-day readmission rate. Female gender, iron overload, acute chest syndrome, acute renal failure and stroke were additional predictors of longer LOS. Simple red blood cell transfusion was administered in 31.3% of the admissions, and these patients tended to have more severe disease (chronic cardiopulmonary or kidney disease, acute chest syndrome, acute kidney or liver failure, sepsis). Nevertheless, transfusion was associated with a reduced estimated odds ratio of inpatient mortality of 0.75 (95% CI: 0.57–0.99) and a decreased odds ratio of 30-day readmission of 0.78 (95% CI: 0.73–0.83). Conclusion Our findings point to blood transfusion as a potential means to reduce the 30-day readmission rate among Medicaid patients hospitalized with sickle cell crisis. There is a need for a prospective study to examine the potential benefit and safety of simple blood transfusion for this purpose. PMID:26126756

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.

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

[Issues and difficulties in the relationship between patients and caregivers in painful sickle cell vaso-occlusive crisis].

PubMed

Dzierzynski, N; Stankovic Stojanovic, K; Georgin-Lavialle, S; Lionnet, F

2016-02-01

Sickle cell patients in acute pain situation experiment cognitive, behavioral and emotional changes that can accentuate their pain and disrupt communication with caregivers. On the other hand, caregivers have to face pain assessment difficulties and their own psychological reactions to their patient's pain. The gap between the patient's experience and caregiver's evaluation can lead to conflict and non-adherence treatment, and have a direct impact on the sickle cell disease prognosis. There is nothing inevitable about these phenomena, whose knowledge allows the action and opens up prospects for improving the management of sickle cell disease pain. This article is a narrative review updating the interactions between acute pain and some configurations, such as the inability to discern emotions, catastrophizing, post-traumatic stress or feeling ostracized. The overestimation of patient's addiction by caregivers also influences the pain itself. Open communication, as well as some treatments, medicated or not, a consistent institutional organization and a multidisciplinary approach altogether have an analgesic role by acting on pain cognitive and emotional components. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

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.

Impact of a dedicated infusion clinic for acute management of adults with sickle cell pain crisis.

PubMed

Lanzkron, Sophie; Carroll, C Patrick; Hill, Peter; David, Mandy; Paul, Nicklaine; Haywood, Carlton

2015-05-01

Most adults with sickle cell disease (SCD) receive care for their acute painful episodes in an emergency department (ED) setting. The purpose of this article is to describe the impact of opening a dedicated treatment center for adults with SCD [Sickle Cell Infusion Clinic (SCIC)] on patient outcomes and on hospital discharges for SCD. Descriptive data including demographics, time to first dose of narcotic, and pain scores were collected on patients presenting to the SCIC and ED. Maryland hospital discharge data were obtained from the Maryland Health Services Cost Review Commission. Analyses were conducted using T tests, χ(2) tests, and simple generalized estimating equation regression models accounting for the clustered nature of observations, as appropriate. There were 3,874 visits to the SCIC by 361 unique patients; 85% of those visits resulted in the patient being sent home. During the same time period, there were 3,408 visits to the ED by 558 unique patients with SCD. The overall admission rate from the ED for these patients was 35.9% but decreased significantly over the time period with a rate of 20% in December 2011. There was a significant decrease in readmissions over time for the entire Baltimore Metro area with the likelihood of readmission decreasing by 7% over time. The SCIC model provides adults with SCD access to high quality care that decreases the need for hospital admission. Further research needs to be done to evaluate the cost effectiveness of this model. © 2015 Wiley Periodicals, Inc.

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.

Hepatitis C virus in sickle cell disease.

PubMed Central

Hassan, Mohamed; Hasan, Syed; Giday, Samuel; Alamgir, Laila; Banks, Alpha; Frederick, Winston; Smoot, Duane; Castro, Oswaldo

2003-01-01

PURPOSE: To determine the prevalence of hepatitis C virus antibodies (anti-HCV) in patients with sickle cell disease. PATIENTS AND METHODS: Between 1983 and 2001, 150 patients from the Howard University Hospital Center for Sickle Cell Disease were screened for HCV antibody (52% women, 48% men, mean age 34 years). Frozen serum samples from 56 adult sickle cell patients who had participated in previous surveys (1983-92) of HIV and HTLV-1 serology and who were tested in 1992 for anti-HCV antibody--when commercial ELISA test (Ortho) became available--were included in this paper. Of the 150 patients in the study, 132 had sickle cell anemia genotype (SS), 15 had sickle cell hemoglobin-C disease (SC) and three had sickle beta thalassemia. Clinical charts were reviewed for history of blood transfusion, IV drug abuse, homosexuality, tattooing, iron overload, and alcohol abuse. RESULTS: Antibodies to HCV were detected in 53 patients (35.3%). Of the 55 patients who had frozen serum samples tested in 1992, 32 (58%) were reactive for anti-HCV, while only 21 of the 95 patients (22%) tested after 1992 were positive for HCV antibodies (P<0.001). Thirty-nine of 77 patients (51%) who received more than 10 units of packed red blood cells were positive for HCV antibody, and only 14 of 61 patients (23%) who received less than 10 units of packed red blood cells transfusion were positive for HCV antibodies (P<0.001). None of the 12 patients who never received transfusion were positive for HCV antibody. In the 53 anti-HCV positive patients, the mean alanine amino-transferase (ALT) value was 98- and 81 U/L, respectively, for males and females. These values were normal for the HCV-antibody negative patients. The aspartate amino-transferase (AST) and the total bilirubin were also higher in the anti-HCV positive patients compared to patients in the anti-HCV negative group. Forty-four patients (57.1%) who were transfused more than 10 units developed iron overload defined by a serum ferritin

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

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.

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

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.

Safety of Pegfilgrastim (Neulasta) in Patients with Sickle Cell Trait/Anemia

PubMed Central

Patnaik, Mrinal M.; Peethambaram, Prema P.

2013-01-01

Pegfilgrastim (Neulasta) is a recombinant filgrastim (human granulocyte colony-stimulating factor (G-CSF)) attached to a polyethylene glycol (PEG) molecule and is given as part of chemotherapy regimens that are associated with significant myelosuppression and risk for febrile neutropenia. Prescribing information available on manufacturer's website for the drug warns us about possible severe sickle cell crises related to the medication but does not report the actual incidence or the use in patients with sickle cell trait. Caution is advised when using it in patients with sickle cell disease. Here we present a case of a Caucasian female with known sickle cell trait (SCT) with no prior complications who developed a presumed sickle cell crisis after getting Neulasta, as a part of the chemotherapy regimen used to treat her breast cancer. Based on our literature review, this appears to be the first case report of a patient with SCT developing a sickle cell crisis with the pegylated form of recombinant filgrastim. Given the dearth of literature regarding the use of G-CSF and its related pegylated forms in patients with sickle cell anemia and sickle cell trait, a discussion of potential mechanisms and review of current literature and guidelines is also presented. PMID:24396616

[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.

A Survey of the Pain Management of Acute Painful Crisis among Patients with Sickle Cell Disease at Two Centres in Jamaica.

PubMed

Augier, R; Jenkins, S; Bortolusso Ali, S; Tennant, I; Williams-Johnson, J; Reid, M

2014-06-01

The aim of this survey was to establish the pain management approaches to acute painful crisis (APC) in sickle cell patients at two healthcare facilities and to compare with available guidelines. A multi-centre observational survey of the management of APC in sickle cell patients was conducted. Data were collected at the Sickle Cell Unit (SCU), Tropical Medicine Research Institute (TMRI) and Accident and Emergency Department (A&E), University Hospital of the West Indies. One hundred episodes of uncomplicated APC involving 81 patients managed at the SCU clinic and 64 episodes at the A&E in a total of 28 patients were included in the data set. Drugs used at the SCU included oral morphine, codeine and paracetamol and intramuscular diclofenac. At the A&E, parenteral morphine and pethidine were most commonly used. At the SCU, the mean time to initiation of analgesics was 38 minutes (IQR 25 to 50 minutes); at the A&E, this was 111 minutes (IQR 50 to 150 minutes). At the SCU, the mean duration of stay (DOS) was 2.9 hours (IQR 1.9 to 3.8 hours) with 94% of the patients being discharged home. At the A&E, the mean DOS was 13.0 hours (IQR 8.3 to 16.9 hours) with 93% of the patients being discharged home. The A&E patient group contained multiple high frequency presenters. Documentation of pain severity scores was inconsistent. The findings of the survey indicate that the management of APC at the two centres is substantially different. Further study is required to investigate patient satisfaction, centre preference and analgesic therapy efficacy.

Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease

PubMed Central

Laurin, Louis-Philippe; Nachman, Patrick H.; Desai, Payal C.; Ataga, Kenneth I.; Derebail, Vimal K.

2014-01-01

Background Albuminuria is an early manifestation of sickle cell nephropathy. Prior small case series suggests benefit of hydroxyurea in reducing albuminuria, with a similar trend noted in pediatric studies. We aimed to comprehensively evaluate hydroxyurea use and prevalence of albuminuria in adult sickle cell patients. Methods We performed a cross-sectional study of 149 adult patients followed between 2000 and 2011 in a comprehensive sickle cell clinic. All patients were assessed for albuminuria either by direct measurement or by urinary chemical strip (dipstick) testing. Urinary albumin-to-creatinine ratios (UACRs) were available for 112 patients. Hydroxyurea exposure was defined as ≥3 months of therapy before the assessment of albuminuria. Albuminuria was defined as either UACR ≥30 mg/g or ≥1+ proteinuria on two separate dipsticks. We constructed a multivariate logistic regression model to assess the association between hydroxyurea and albuminuria. Results The prevalence of albuminuria was lower among patients on hydroxyurea (34.7 versus 55.4%; P = 0.01) as was median albumin excretion (17.9 versus 40.5 mg/g; P = 0.04). In multivariate analysis, hydroxyurea was associated with a lower likelihood of albuminuria (odds ratio 0.28, 95% CI: 0.11–0.75, P = 0.01), adjusting for age, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, tricuspid regurgitant jet velocity, hypertension and acute chest syndrome. Conclusions In our population of sickle cell patients, those using hydroxyurea were less than one-third as likely to exhibit albuminuria. Hydroxyurea use may prevent development of overt nephropathy or the progression of sickle cell disease nephropathy to end-stage renal disease, and its use for this indication merits further investigation. PMID:24084325

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.

Microfluidic approach of Sickled Cell Anemia

NASA Astrophysics Data System (ADS)

Abkarian, Manouk; Loiseau, Etienne; Massiera, Gladys

2012-11-01

Sickle Cell Anemia is a disorder of the microcirculation caused by a genetic point mutation that produces an altered hemoglobin protein called HbS. HbS self-assembles reversibly into long rope like fibers inside the red blood cells. The resulting distorded sickled red blood cells are believed to block the smallest capillaries of the tissues producing anemia. Despite the large amount of work that provided a thorough understanding of HbS polymerization in bulk as well as in intact red blood cells at rest, no consequent cellular scale approaches of the study of polymerization and its link to the capillary obstruction have been proposed in microflow, although the problem of obstruction is in essence a circulatory problem. Here, we use microfluidic channels, designed to mimic physiological conditions (flow velocity, oxygen concentration, hematocrit...) of the microcirculation to carry out a biomimetic study at the cellular scale of sickled cell vaso-occlusion. We show that flow geometry, oxygen concentration, white blood cells and free hemoglobin S are essential in the formation of original cell aggregates which could play a role in the vaso-occlusion events.

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.

Abdominal pain in children with sickle cell disease.

PubMed

Rhodes, Melissa M; Bates, David Gregory; Andrews, Tina; Adkins, Laura; Thornton, Jennifer; Denham, Jolanda M

2014-02-01

The differential diagnosis of abdominal pain is broad in any child, and further complicated in children with sickle cell disease (SCD). Acute causes of abdominal pain may require emergent surgery, such as for appendicitis or obstruction caused by a bezoar. Rapid intervention is necessary and life-saving in children with SCD and acute splenic or hepatic sequestration. The majority of children with SCD presenting to the physician's office or emergency department will have subacute reasons for their abdominal pain, including but not limited to constipation, urinary tract infection, peptic ulcer disease, and cholecystitis. Vaso-occlusive pain often presents in children as abdominal pain, but is a diagnosis of exclusion. The case of a 10-year-old girl with intermittent abdominal pain is used as a starting point to review the pathophysiology, diagnosis, and treatment of the most acute and common causes of abdominal pain in children with SCD.

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.

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.

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.

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.

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.

Sickle Cell Disease

MedlinePlus

... message, please visit this page: About CDC.gov . Learn Tips for Receiving Better Care in the Emergency Department in Our Fact ... related care in the United States. Read Supplement » VIDEO Sickle Cell Disease: When to Transfuse Learn about indications for blood transfusion in patients with ...

Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype.

PubMed

Hsieh, Matthew M; Fitzhugh, Courtney D; Weitzel, R Patrick; Link, Mary E; Coles, Wynona A; Zhao, Xiongce; Rodgers, Griffin P; Powell, Jonathan D; Tisdale, John F

2014-07-02

Myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) is curative for children with severe sickle cell disease, but toxicity may be prohibitive for adults. Nonmyeloablative transplantation has been attempted with degrees of preparative regimen intensity, but graft rejection and graft-vs-host disease remain significant. To determine the efficacy, safety, and outcome on end-organ function with this low-intensity regimen for sickle cell phenotype with or without thalassemia. From July 16, 2004, to October 25, 2013, 30 patients aged 16-65 years with severe disease enrolled in this nonmyeloablative transplant study, consisting of alemtuzumab (1 mg/kg in divided doses), total-body irradiation (300 cGy), sirolimus, and infusion of unmanipulated filgrastim mobilized peripheral blood stem cells (5.5-31.7 × 10(6) cells/kg) from human leukocyte antigen-matched siblings. The primary end point was treatment success at 1 year after the transplant, defined as a full donor-type hemoglobin for patients with sickle cell disease and transfusion independence for patients with thalassemia. The secondary end points were the level of donor leukocyte chimerism; incidence of acute and chronic graft-vs-host disease; and sickle cell-thalassemia disease-free survival, immunologic recovery, and changes in organ function, assessed by annual brain imaging, pulmonary function, echocardiographic image, and laboratory testing. Twenty-nine patients survived a median 3.4 years (range, 1-8.6), with no nonrelapse mortality. One patient died from intracranial bleeding after relapse. As of October 25, 2013, 26 patients (87%) had long-term stable donor engraftment without acute or chronic graft-vs-host disease. The mean donor T-cell level was 48% (95% CI, 34%-62%); the myeloid chimerism levels, 86% (95% CI, 70%-100%). Fifteen engrafted patients discontinued immunosuppression medication with continued stable donor chimerism and no graft-vs-host disease. The normalized hemoglobin and

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

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)

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)

Clinically significant differences in the visual analog pain scale in acute vasoocclusive sickle cell crisis.

PubMed

Lopez, Bernard L; Flenders, Pamela; Davis-Moon, Linda; Corbin, Theodore; Ballas, Samir K

2007-01-01

This study sought to determine the minimum clinically significant change in the visual analog scale (VAS) during the Emergency Department (ED) treatment of adult vasoocclusive sickle cell crisis (VOC). Sickle cell anemia patients presenting to the ED with their typical VOC pain had a 100 mm VAS administered prior to each of up to three standard analgesic injections administered as part of a treatment protocol. At each assessment, subjects were asked to describe their pain as "much better," a "little better," "the same," "a little worse," or "much worse." The change in the VAS (DeltaVAS) between assessments was measured. The main outcome of the measurement was change in the VAS associated with a description of a change in pain of "a little less" or "a little more." Seventy four subjects presented with initially high pain scores [VAS = 79.47 mm, 95% confidence interval (CI) = 75.99 to 82.95 mm]. In the "little better/little worse" combined group, the DeltaVAS was 13.5 mm (95% CI = 11.25 cm to 15.74 cm). A change in the 100 mm VAS of 13.5 mm is the minimum clinically significant change during ED treatment of VOC. A DeltaVAS <13.5 mm may not be clinically important. This finding may assist the clinician in the assessment of pain improvement for adult sickle cell patients with VOC.

Alternative donor hematopoietic stem cell transplantation for sickle cell disease

PubMed Central

Eckrich, Michael J.; Epstein, Stacy; Barnhart, Carrie; Cannon, Mark; Fukes, Tracy; Hyland, Michelle; Shah, Krishna; Grochowski, Darci; Champion, Elizabeth; Ivanova, Anastasia

2017-01-01

Most patients who could be cured of sickle cell disease (SCD) with stem cell transplantation do not have a matched sibling donor. Successful use of alternative donors, including mismatched family members, could provide a donor for almost all patients with SCD. The use of a reduced-intensity conditioning regimen may decrease late adverse effects. Ten patients with symptomatic SCD underwent CD34+ cell-selected, T-cell–depleted peripheral blood stem cell transplantation from a mismatched family member or unrelated donor. A reduced-intensity conditioning regimen including melphalan, thiotepa, fludarabine, and rabbit anti-thymocyte globulin was used. Patients were screened for a companion study for immune reconstitution that included a donor lymphocyte infusion given 30-42 days after transplant with intravenous methotrexate as graft-versus-host disease (GVHD) prophylaxis. Seven eligible patients were treated on the companion study. Nine of 10 patients are alive with a median follow-up of 49 months (range, 14-60 months). Surviving patients have stable donor hematopoietic engraftment (mean donor chimerism, 99.1% ± 0.7%). There were no sickle cell complications after transplant. Two patients had grade II-IV acute GVHD. One patient had chronic GVHD. Epstein-Barr virus–related posttransplant lymphoproliferative disorder (PTLD) occurred in 3 patients, and 1 patient died as a consequence of treatment of PTLD. Two-year overall survival was 90%, and event-free survival was 80%. A reduced-intensity conditioning regimen followed by CD34+ cell-selected, T-cell–depleted alternative donor peripheral blood stem cell transplantation achieved primary engraftment in all patients with a low incidence of GVHD, although PTLD was problematic. This trial was registered at clinicaltrials.gov as #NCT00968864. PMID:29296761

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.

Prevalence of Sickle Cell Trait in the Southern Suburb of Beirut, Lebanon.

PubMed

El Ariss, Abdel Badih; Younes, Mohamad; Matar, Jad; Berjaoui, Zeina

2016-01-01

The objective of this study was to assess the prevalence, gender differences, and time trends of Sickle Cell Trait in the Southern Suburb of Beirut, Lebanon, as well as to highlight the importance of screening for Sickle Cell Trait carriers in this population. Another objective was to describe a new screening technique for Sickle Cell Trait carriers. This was a retrospective cohort study carried out at a private laboratory in the Southern Suburb of Beirut, Lebanon between 2002 and 2014. The sickling test was carried out for each patient using two methods: the classical "sodium metabisulfite sickling test", and the new "sickling test method" used in the private lab. As a confirmatory test, hemoglobin electrophoresis was run on a random sample of 223 cases which were found to be positive using the two sickling tests. A total of 899 cases were found to be positive for the sickle cell trait out of 184,105 subjects screened during the 12-year period, prevalence = 0.49% (95% CI: 0.46 - 0.52). Among the total sample, females were found to have higher prevalence, where no time trend over the studied period was noted. The haemoglobin electrophoresis method confirmed the results of this new sickling test technique among the random sample of the 223 cases. We found that the prevalence of sickle cell trait is lower as compared to other Arab countries, higher in females, with no significant time trend. The sickle cell test was found to be an accurate, simple and cheap test that could be easily added as a requirement for the pre-marital testing to screen for Sickle Cell Trait carriers.

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

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.

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…

[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.

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.

Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease.

PubMed

Laurin, Louis-Philippe; Nachman, Patrick H; Desai, Payal C; Ataga, Kenneth I; Derebail, Vimal K

2014-06-01

Albuminuria is an early manifestation of sickle cell nephropathy. Prior small case series suggests benefit of hydroxyurea in reducing albuminuria, with a similar trend noted in pediatric studies. We aimed to comprehensively evaluate hydroxyurea use and prevalence of albuminuria in adult sickle cell patients. We performed a cross-sectional study of 149 adult patients followed between 2000 and 2011 in a comprehensive sickle cell clinic. All patients were assessed for albuminuria either by direct measurement or by urinary chemical strip (dipstick) testing. Urinary albumin-to-creatinine ratios (UACRs) were available for 112 patients. Hydroxyurea exposure was defined as ≥3 months of therapy before the assessment of albuminuria. Albuminuria was defined as either UACR ≥30 mg/g or ≥1+ proteinuria on two separate dipsticks. We constructed a multivariate logistic regression model to assess the association between hydroxyurea and albuminuria. The prevalence of albuminuria was lower among patients on hydroxyurea (34.7 versus 55.4%; P = 0.01) as was median albumin excretion (17.9 versus 40.5 mg/g; P = 0.04). In multivariate analysis, hydroxyurea was associated with a lower likelihood of albuminuria (odds ratio 0.28, 95% CI: 0.11-0.75, P = 0.01), adjusting for age, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, tricuspid regurgitant jet velocity, hypertension and acute chest syndrome. In our population of sickle cell patients, those using hydroxyurea were less than one-third as likely to exhibit albuminuria. Hydroxyurea use may prevent development of overt nephropathy or the progression of sickle cell disease nephropathy to end-stage renal disease, and its use for this indication merits further investigation. © The Author 2013. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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.

Determining the longitudinal validity and meaningful differences in HRQL of the PedsQL™ Sickle Cell Disease Module.

PubMed

Panepinto, Julie A; Paul Scott, J; Badaki-Makun, Oluwakemi; Darbari, Deepika S; Chumpitazi, Corrie E; Airewele, Gladstone E; Ellison, Angela M; Smith-Whitley, Kim; Mahajan, Prashant; Sarnaik, Sharada A; Charles Casper, T; Cook, Larry J; Leonard, Julie; Hulbert, Monica L; Powell, Elizabeth C; Liem, Robert I; Hickey, Robert; Krishnamurti, Lakshmanan; Hillery, Cheryl A; Brousseau, David C

2017-06-12

Detecting change in health status over time and ascertaining meaningful changes are critical elements when using health-related quality of life (HRQL) instruments to measure patient-centered outcomes. The PedsQL™ Sickle Cell Disease module, a disease specific HRQL instrument, has previously been shown to be valid and reliable. Our objectives were to determine the longitudinal validity of the PedsQL™ Sickle Cell Disease module and the change in HRQL that is meaningful to patients. An ancillary study was conducted utilizing a multi-center prospective trial design. Children ages 4-21 years with sickle cell disease admitted to the hospital for an acute painful vaso-oclusive crisis were eligible. Children completed HRQL assessments at three time points (in the Emergency Department, one week post-discharge, and at return to baseline (One to three months post-discharge). The primary outcome was change in HRQL score. Both distribution (effect size, standard error of measurement (SEM)) and anchor (global change assessment) based methods were used to determine the longitudinal validity and meaningful change in HRQL. Changes in HRQL meaningful to patients were identified by anchoring the change scores to the patient's perception of global improvement in pain. Moderate effect sizes (0.20-0.80) were determined for all domains except the Communication I and Cognitive Fatigue domains. The value of 1 SEM varied from 3.8-14.6 across all domains. Over 50% of patients improved by at least 1 SEM in Total HRQL score. A HRQL change score of 7-10 in the pain domains represented minimal perceived improvement in HRQL and a HRQL change score of 18 or greater represented moderate to large improvement. The PedsQL™ Sickle Cell Disease Module is responsive to changes in HRQL in patients experiencing acute painful vaso-occlusive crises. The study data establish longitudinal validity and meaningful change parameters for the PedsQL™ Sickle Cell Disease Module. ClinicalTrials.gov (study

Sickle Cell Unit.

ERIC Educational Resources Information Center

Canipe, Stephen L.

Included in this high school biology unit on sickle cell anemia are the following materials: a synopsis of the history of the discovery and the genetic qualities of the disease; electrophoresis diagrams comparing normal, homozygous and heterozygous conditions of the disease; and biochemical characteristics and population genetics of the disease. A…

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.

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.

Prevalence of Sickle Cell Trait in the Southern Suburb of Beirut, Lebanon

PubMed Central

El Ariss, Abdel Badih; Younes, Mohamad; Matar, Jad; Berjaoui, Zeina

2016-01-01

Objective The objective of this study was to assess the prevalence, gender differences, and time trends of Sickle Cell Trait in the Southern Suburb of Beirut, Lebanon, as well as to highlight the importance of screening for Sickle Cell Trait carriers in this population. Another objective was to describe a new screening technique for Sickle Cell Trait carriers. Methods This was a retrospective cohort study carried out at a private laboratory in the Southern Suburb of Beirut, Lebanon between 2002 and 2014. The sickling test was carried out for each patient using two methods: the classical “sodium metabisulfite sickling test”, and the new “sickling test method” used in the private lab. As a confirmatory test, hemoglobin electrophoresis was run on a random sample of 223 cases which were found to be positive using the two sickling tests. Results A total of 899 cases were found to be positive for the sickle cell trait out of 184,105 subjects screened during the 12-year period, prevalence = 0.49% (95% CI: 0.46 – 0.52). Among the total sample, females were found to have higher prevalence, where no time trend over the studied period was noted. The haemoglobin electrophoresis method confirmed the results of this new sickling test technique among the random sample of the 223 cases. Conclusion We found that the prevalence of sickle cell trait is lower as compared to other Arab countries, higher in females, with no significant time trend. The sickle cell test was found to be an accurate, simple and cheap test that could be easily added as a requirement for the pre-marital testing to screen for Sickle Cell Trait carriers. PMID:26977274

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.

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,…

Effects of Poloxamer 188 on red blood cell membrane properties in sickle cell anaemia.

PubMed

Sandor, Barbara; Marin, Mickaël; Lapoumeroulie, Claudine; Rabaï, Miklos; Lefevre, Sophie D; Lemonne, Nathalie; El Nemer, Wassim; Mozar, Anaïs; Français, Olivier; Le Pioufle, Bruno; Connes, Philippe; Le Van Kim, Caroline

2016-04-01

Vaso-occlusive crisis (VOC) is the main acute complication in sickle cell anaemia (SS) and several clinical trials are investigating different drugs to improve the clinical severity of SS patients. A phase III study is currently exploring the profit of Velopoloxamer in SS during VOCs. We analysed, in-vitro, the effect of poloxamer (P188) on red blood cell (RBC) properties by investigating haemorheology, mechanical and adhesion functions using ektacytometry, microfluidics and dynamic adhesion approaches, respectively. We show that poloxamer significantly reduces blood viscosity, RBC aggregation and adhesion to endothelial cells, supporting the beneficial use of this molecule in SS therapy. © 2016 John Wiley & Sons Ltd.

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.

Folate supplementation in people with sickle cell disease

PubMed Central

Dixit, Ruchita; Nettem, Sowmya; Madan, Simerjit S; Soe, Htoo Htoo Kyaw; Abas, Adinegara BL; Vance, Leah D; Stover, Patrick J

2017-01-01

-blind placebo-controlled quasi-randomised triaI of supplementation of folic acid in people with sickle cell disease. A total of 117 children with homozygous sickle cell (SS) disease aged six months to four years of age participated over a one-year period (analysis was restricted to 115 children). Serum folate measures, obtained after trial entry at six and 12 months, were available in 80 of 115 (70%) participants. There were significant differences between the folic acid and placebo groups with regards to serum folate values above 18 μg/l and values below 5 μg/l. In the folic acid group, values above 18 μg/l were observed in 33 of 41 (81 %) compared to six of 39 (15%) participants in the placebo (calcium lactate) group. Additionally, there were no participants in the folic acid group with serum folate levels below 5 μg/l, whereas in the placebo group, 15 of 39 (39%) participants had levels below this threshold. Haematological indices were measured in 100 of 115 (87%) participants at baseline and at one year. After adjusting for sex and age group, the investigators reported no significant differences between the trial groups with regards to total haemoglobin concentrations, either at baseline or at one year. It is important to note that none of the raw data for the outcomes listed above were available for analysis. The proportions of participants who experienced certain clinical events were analysed in all 115 participants, for which raw data were available. There were no statistically significant differences noted; however, the trial was not powered to investigate differences between the folic acid and placebo groups with regards to: minor infections, risk ratio 0.99 (95% confidence interval 0.85 to 1.15); major infections, risk ratio 0.89 (95% confidence interval 0.47 to 1.66); dactylitis, risk ratio 0.67 (95% confidence interval 0.35 to 1.27); acute splenic sequestration, risk ratio 1.07 (95% confidence interval 0.44 to 2.57); or episodes of pain, risk ratio 1.16 (95

A Unique Cause of Intestinal and Splenic Infarction in a Sickle Cell Trait Patient

PubMed Central

Asfaw, Sofya H.; Falk, Gavin A.; Morris-Stiff, Gareth; Tuthill, Ralph J.; Moorman, Matthew L.; Samotowka, Michael A.

2013-01-01

Sickle-cell trait is a common genetic abnormality in the African American population. A sickle-cell crisis in a patient with sickle-cell trait is uncommon at best. Abdominal painful crises are typical of patients with sickle cell anemia. The treatment for an abdominal painful crisis is usually medical and rarely surgical. We present the case of a cocaine-induced sickle-cell crisis in a sickle-cell trait patient that resulted in splenic, intestinal, and cerebral infarctions and multisystem organ failure necessitating a splenectomy, subtotal colectomy, and small bowel resection. This case highlights the diagnostic dilemma that abdominal pain can present in the sickle-cell population and illustrates the importance of recognizing the potential for traditionally medically managed illnesses to become surgical emergencies. PMID:23738181

A unique cause of intestinal and splenic infarction in a sickle cell trait patient.

PubMed

Asfaw, Sofya H; Falk, Gavin A; Morris-Stiff, Gareth; Tuthill, Ralph J; Moorman, Matthew L; Samotowka, Michael A

2013-01-01

Sickle-cell trait is a common genetic abnormality in the African American population. A sickle-cell crisis in a patient with sickle-cell trait is uncommon at best. Abdominal painful crises are typical of patients with sickle cell anemia. The treatment for an abdominal painful crisis is usually medical and rarely surgical. We present the case of a cocaine-induced sickle-cell crisis in a sickle-cell trait patient that resulted in splenic, intestinal, and cerebral infarctions and multisystem organ failure necessitating a splenectomy, subtotal colectomy, and small bowel resection. This case highlights the diagnostic dilemma that abdominal pain can present in the sickle-cell population and illustrates the importance of recognizing the potential for traditionally medically managed illnesses to become surgical emergencies.

[Aplastic crisis in sickle cell anemia induced by parvovírus B19

PubMed

Borsato, M L; Bruniera, P; Cusato, M P; Spewien, K E; Durigon, E L; Toporovski, J

2000-01-01

PURPOSE: Transient aplastic crisis is reported in an eight-month old child with sickle cell anemia and acute B19 parvovirus infection. This fact is uncommon in this age. PATIENT AND METHODS: The authors review the literature and describe a clinical case of an eight-month old child with sickle cell anemia presented with profound anemia and reticulocytopenia. His peripheral blood was analyzed for parvovirus B19 using the polymerase chain reaction (PCR), and for anti B19 immunoglobulin Ig M, and Ig G by enzyme-linked immunosorbent assay (ELISA). RESULTS: An eight-month old child with sickle cell anemia was admitted to the hospital with fever and profound anemia (HB = 3.8g/ dl) and reticulocytopenia (2%). A diagnosis of aplastic crisis was established. The results indicate that Ig M and PCR were positive and Ig G negative. The patient needed erytrocyte transfusion, and was discharged on hospital day 4. CONCLUSIONS: The clinical and laboratory features indicate that human parvovirus B19 was the etiologic agent of an aplastic crisis in an eight-month old child. According to the international literature this event is uncommon for this age; in addition, this is the first time it appears in the Brazilian literature.

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. .

Magnesium for treating sickle cell disease.

PubMed

Than, Nan Nitra; Soe, Htoo Htoo Kyaw; Palaniappan, Senthil K; Abas, Adinegara Bl; De Franceschi, Lucia

2017-04-14

Sickle cell disease is an autosomal recessive inherited haemoglobinopathy which causes painful vaso-occlusive crises due to sickle red blood cell dehydration. Vaso-occlusive crises are common painful events responsible for a variety of clinical complications; overall mortality is increased and life expectancy decreased compared to the general population. Experimental studies suggest that intravenous magnesium has proven to be well-tolerated in individuals hospitalised for the immediate relief of acute (sudden onset) painful crisis and has the potential to decrease the length of hospital stay. Some in vitro studies and open studies of long-term oral magnesium showed promising effect on pain relief but failed to show its efficacy. The studies show that oral magnesium therapy may prevent sickle red blood cell dehydration and prevent recurrent painful episodes. There is a need to access evidence for the impact of oral and intravenous magnesium effect on frequency of pain, length of hospital stay and quality of life. To evaluate the effects of short-term intravenous magnesium on the length of hospital stay and quality of life in children and adults with sickle cell disease. To determine the effects of long-term oral magnesium therapy on the frequency of painful crises and the quality of life in children and adults with sickle cell disease. We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register: 01 December 2016.Date of last search of other resources (clinical trials registries): 29 March 2017. We searched for published and unpublished randomized controlled studies of oral or intravenous magnesium compared to placebo or no magnesium. Authors independently assessed the study quality and extracted the data using standard Cochrane methodologies. We

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.

Pancreatitis in the Setting of Vaso-occlusive Sickle Cell Crisis: A Rare Encounter.

PubMed

Hasan, Badar; Asif, Talal; Braun, Cody; Bahaj, Waled; Dosokey, Eslam; Pauly, Rebecca R

2017-04-25

Acute pancreatitis is a common cause of acute abdominal pain. Gallstones and alcohol abuse account for the majority of the cases. Pancreatic ischemia is an uncommon but established cause of pancreatitis associated with connective tissue diseases, vasculitis, and shock. Our case highlights a rare case of vaso-occlusive crisis (VOC) in a patient with sickle cell (SC) disease leading to pancreatitis. Treatment remains largely conservative but exchange transfusion may be the therapy of choice in severely hypoxic patients or in patients with high pre-treatment hemoglobin S levels.

Acute chest syndrome is associated with single nucleotide polymorphism-defined beta globin cluster haplotype in children with sickle cell anaemia

PubMed Central

Bean, Christopher J.; Boulet, Sheree L.; Yang, Genyan; Payne, Amanda B.; Ghaji, Nafisa; Pyle, Meredith E.; Hooper, W. Craig; Bhatnagar, Pallav; Keefer, Jeffrey; Barron-Casella, Emily A.; Casella, James F.; DeBaun, Michael R.

2013-01-01

Summary Genetic diversity at the human β-globin locus has been implicated as a modifier of sickle cell anaemia (SCA) severity. However, haplotypes defined by restriction fragment length polymorphism sites across the β-globin locus have not been consistently associated with clinical phenotypes. To define the genetic structure at the β-globin locus more thoroughly, we performed high-density single nucleotide polymorphism (SNP) mapping in 820 children who were homozygous for the sickle cell mutation (HbSS). Genotyping results revealed very high linkage disequilibrium across a large region spanning the locus control region and the HBB (β-globin gene) cluster. We identified three predominant haplotypes accounting for 96% of the βS-carrying chromosomes in this population that could be distinguished using a minimal set of common SNPs. Consistent with previous studies, fetal haemoglobin level was significantly associated with βS-haplotypes. After controlling for covariates, an association was detected between haplotype and rate of hospitalization for acute chest syndrome (ACS) (incidence rate ratio 0.51, 95% confidence interval 0.29–0.89) but not incidence rate of vaso-occlusive pain or presence of silent cerebral infarct (SCI). Our results suggest that these SNP-defined βS-haplotypes may be associated with ACS, but not pain or SCI in a study population of children with SCA. PMID:23952145

Erythropoietin in sickle cell disease: relation of erythropoietin levels to crisis and other complications.

PubMed

Haddy, T B

1982-01-01

Erythropoietin responsible for the hormonal regulation of red blood cell production. Its formation is largely controlled by the kidneys. A number of assay methods for erythropoietin are available. Asymptomatic patients with sickle cell disease have elevated erythropoietin levels, as expected with chronic hemolysis. When complicated by chronic renal failure, erythropoietin levels do not rise appropriately. Chronic infection has not been studied, but the erythropoietin response in acute infection does not seem to conform to a pattern. Aplastic crises are characterized by very high levels of erythropoietin, suggesting bone marrow suppression, but events that trigger the crises remain obscure. In vaso-occlusive crises, there is also some suggestion of mild and transient lack of bone marrow response. Patients with sickle cell disease, with their chronic high erythropoietin anemia and susceptibility to altered states, are uniquely suited for investigating the physiology of erythropoietin, especially under the constraints of present assay methods.

Clinical findings associated with cardiovascular autonomic dysfunction in adult sickle cell anaemia patients.

PubMed

Oguanobi, Nelson I; Onwubere, Basden J C; Anisiuba, Benedict C; Ike, Samuel O; Ejim, Emmanuel C; Ibegbulam, Obike G

2012-04-01

Involvement of the cardiovascular autonomic nervous system in various diseases is often associated with increased morbidity and mortality. The objective of this study was to examine the clinical features associated with cardiovascular autonomic neuropathy (CAN) in adult Nigerians with sickle cell anaemia. A cross-sectional study was carried out on 62 steady state sickle cell anaemia patients recruited from the adult out-patient clinic. Cardiovascular autonomic dysfunction was determined based on abnormal values in at least two of five non-invasive tests: Valsalva manoeuvre, heart rate variation during deep breathing, heart rate response to standing, blood pressure response to sustained handgrip, and blood pressure response to standing. All the subjects were initially evaluated in the clinic for symptoms of cardiovascular disease and peripheral vascular disease, and then clinically examined to assess their cardiovascular and neurological status at rest. Out of the 44 patients with cardiovascular autonomic neuropathy 23 were males, while 21 were females. The mean ages were 28.3 +/- 5.8 y for patients with CAN and 28.0 +/- 5.0 y for patients without CAN (P = 0.817). Sickle cell anaemia patients with CAN had significantly lower ankle systolic blood pressure, reduced ankle brachial blood pressure index, mean arterial blood pressure and haematocrit than patients without CAN. Of all the variables evaluated leg ulcers, postural dizziness, erectile dysfunction in men, and history of recurrent acute chest syndromes were found significantly more in patients with CAN than without. Clinical abnormalities tend to worsen with increasing degree of cardiovascular autonomic dysfunction. Significant cardiac morbidity is associated with abnormal cardiovascular autonomic function in sickle cell anaemia.

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

Positive expiratory pressure device acceptance by hospitalized children with sickle cell disease is comparable to incentive spirometry.

PubMed

Hsu, Lewis L; Batts, Brenda K; Rau, Joseph L

2005-05-01

The pulmonary complication in sickle cell disease known as acute chest syndrome (ACS) has potential for high morbidity and mortality. A randomized trial demonstrated that incentive spirometry (IS) reduces the rate of ACS, leading to a role for respiratory therapy in hospital management of sickle cell pain. However, use of IS can be limited by chest wall pain, or by difficulty with the coordinated inspiration in a young child. Intermittent positive expiratory pressure (PEP) therapy may be easier for a child's coordination and more comfortable than IS for a child with chest wall pain. To compare PEP therapy with conventional IS for children hospitalized for sickle cell pain with respect to patient satisfaction, length of hospital stay, and progression to ACS. This pilot study enrolled 20 children upon hospitalization for sickle cell pain in the thorax, randomly assigning them to either PEP (n = 11) or IS (n = 9) therapy, administered by a therapist hourly while awake. The randomization assigned an older distribution to PEP than IS (12.3 vs 8.8 y). Patient satisfaction was high for both respiratory care devices, and there was no difference between the PEP and IS groups (4.5 vs 4.4, p = 0.81). Length of hospital stay was similar (5 vs 4.3 d, p = 0.56). No children in either group progressed to ACS. These preliminary results show no difference in the primary outcomes in the 2 groups. Intermittent PEP therapy warrants further study as an alternative to IS for sickle cell patients at high risk for ACS, as effective preventive respiratory therapy.

Organ damage in sickle cell disease study (ORDISS): protocol for a longitudinal cohort study based in Ghana.

PubMed

Anie, Kofi A; Paintsil, Vivian; Owusu-Dabo, Ellis; Ansong, Daniel; Osei-Akoto, Alex; Ohene-Frempong, Kwaku; Amissah, Kofi Aikins; Addofoh, Nicholas; Ackah, Ezekiel Bonwin; Owusu-Ansah, Amma Twumwa; Ofori-Acquah, Solomon Fiifi

2017-08-28

Sickle cell disease is highly prevalent in Africa with a significant public health burden. Nonetheless, morbidity and mortality in sickle cell disease that result from the progression of organ damage is not well understood. The Organ Damage in Sickle Cell Disease Study (ORDISS) is designed as a longitudinal cohort study to provide critical insight into cellular and molecular pathogenesis of chronic organ damage for the development of future innovative treatment. ORDISS aims to recruit children aged 0-15 years who attend the Kumasi Centre for Sickle Cell Disease based at the Komfo Anokye Teaching Hospital in Kumasi, Ghana. Consent is obtained to collect blood and urine samples from the children during specified clinic visits and hospitalisations for acute events, to identify candidate and genetic markers of specific organ dysfunction and end-organ damage, over a 3 year period. In addition, data concerning clinical history and complications associated with sickle cell disease are collected. Samples are stored in biorepositories and analysed at the Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana and the Centre for Translational and International Haematology, University of Pittsburgh, USA. Appropriate statistical analyses will be performed on the data acquired. Research ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals, and the key findings presented at national and international conferences. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

Characterization of mortality in children with sickle cell disease diagnosed through the Newborn Screening Program.

PubMed

Sabarense, Alessandra P; Lima, Gabriella O; Silva, Lívia M L; Viana, Marcos Borato

2015-01-01

To characterize the deaths of 193 children with sickle cell disease screened by a neonatal program from 1998 to 2012 and contrast the initial years with the final years. Deaths were identified by active surveillance of children absent to scheduled appointments in Blood Bank Clinical Centers (Hemominas). Clinical and epidemiological data came from death certificates, neonatal screening database, medical records, and family interviews. Between 1998 and 2012, 3,617,919 children were screened and 2,591 had sickle cell disease (1:1,400). There were 193 deaths (7.4%): 153 with SS/Sβ(0)-thalassemia, 34 SC and 6 Sβ(+)thalassemia; 76.7% were younger than five years; 78% died in the hospital and 21% at home or in transit. The main causes of death were infection (45%), indeterminate (28%), and acute splenic sequestration (14%). In 46% of death certificates, the term "sickle cell" was not recorded. Seven-year death rate for children born between 1998 and 2005 was 5.43% versus 5.12% for those born between 2005 and 2012 (p = 0.72). Medical care was provided to 75% of children; 24% were unassisted. Medical care was provided within 6 hours of symptom onset in only half of the interviewed cases. In 40.5% of cases, death occurred within the first 24 hours. Low family income was recorded in 90% of cases, and illiteracy in 5%. Although comprehensive and effective, neonatal screening for sickle cell disease was not sufficient to significantly reduce mortality in a newborn screening program. Economic and social development and increase of the knowledge on sickle cell disease among health professionals and family are needed to overcome excessive mortality. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

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.

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.

Prophylactic versus selective blood transfusion for sickle cell disease in pregnancy.

PubMed

Okusanya, Babasola O; Oladapo, Olufemi T

2016-12-22

% confidence interval (CI) 0.61 to 13.22; very low-quality evidence) or markers of severe maternal morbidity (pulmonary embolism (no events); congestive cardiac failure (RR 1.00, 95% CI 0.07 to 15.38; very low-quality evidence); acute chest syndrome (RR 0.67, 95% CI 0.12 to 3.75)) between the treatment groups (prophylactic blood transfusion versus selective blood transfusion). Low-quality evidence indicated that prophylactic blood transfusion reduced the risk of pain crisis compared with selective blood transfusion (RR 0.28, 95% CI 0.12 to 0.67, one trial, 72 women; low-quality evidence), and no differences in the occurrence of acute splenic sequestration (RR 0.33, 95% CI 0.01 to 7.92; low-quality evidence), haemolytic crises (RR 0.33, 95% CI 0.04 to 3.06) or delayed blood transfusion reaction (RR 2.00, 95% CI 0.54 to 7.39; very low-quality evidence) between the comparison groups.Other relevant maternal outcomes pre-specified for this review such as cumulative duration of hospital stay, postpartum haemorrhage and iron overload, and infant outcomes, admission to neonatal intensive care unit (NICU) and haemolytic disease of the newborn, were not reported by the trial. Evidence from one small trial of very low quality suggests that prophylactic blood transfusion to pregnant women with sickle cell anaemia (HbSS) confers no clear clinical benefits when compared with selective transfusion. Currently, there is no evidence from randomised or quasi-randomised trials to provide reliable advice on the optimal blood transfusion policy for women with other variants of sickle cell disease (i.e. HbSC and HbSβThal). The available data and quality of evidence on this subject are insufficient to advocate for a change in existing clinical practice and policy.

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.

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.

Buccal Micronucleus Cytome Assay in Sickle Cell Disease.

PubMed

Naga, Mallika Bokka Sri Satya; Gour, Shreya; Nallagutta, Nalini; Ealla, Kranti Kiran Reddy; Velidandla, Surekha; Manikya, Sangameshwar

2016-06-01

Sickle Cell Anaemia (SCA) is a commonly inherited blood disorder preceded by episodes of pain, chronic haemolytic anaemia and severe infections. The underlying phenomenon which causes this disease is the point mutation in the haemoglobin beta gene (Hbβ) found on chromosome 11 p. Increased oxidative stress leads to DNA damage. DNA damage occurring in such conditions can be studied by the buccal micronucleus cytome assay, which is a minimally invasive method for studying chromosomal instability, cell death and regenerative potential of human buccal tissue. To evaluate genomic instability in patients with sickle cell disease by buccal micronucleus cytome assay. The study included 40 sickle cell anemia patients (Group A) and 40 age and sex matched controls (Group B). Buccal swabs were collected and stained with Papanicolaou (PAP). Number of cells with micronucleus, binuclei, nuclear bud, pyknosis and karyolysis were counted in two groups as parameters for the evaluation of genome stability. All the analysis was done using t-test. A p-value of <0.001 was considered statistically significant. There was a statistically significant increase in micronuclei number in SCA patients when compared with controls. Karyolytic (un-nucleated) cell number in Group A was more than to those of the controls. The results might suggest that patients with sickle cell anaemia have genome instability which is represented by the presence of micronuclei in the somatic cells. Presence of apoptotic cells might only indicate the bodily damage to the tissue as a result of the disease.

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 ...

Treatment of dental complications in sickle cell disease.

PubMed

Mulimani, Priti; Ballas, Samir K; Abas, Adinegara B L; Karanth, Laxminarayan

2016-04-22

Sickle cell disease is the most common single gene disorder and the commonest haemoglobinopathy found with high prevalence in many populations across the world. Management of dental complications in people with sickle cell disease requires special consideration for three main reasons. Firstly, dental and oral tissues are affected by the blood disorder resulting in several oro-facial abnormalities. Secondly, living with a haemoglobinopathy and coping with its associated serious consequences may result in individuals neglecting their oral health care. Finally, the treatment of these oral complications must be adapted to the systemic condition and special needs of these individuals, in order not to exacerbate or deteriorate their general health.Guidelines for the treatment of dental complications in this population who require special care are unclear and even unavailable in many aspects. Hence this review was undertaken to provide a basis for clinical care by investigating and analysing the existing evidence in the literature for the treatment of dental complications in people with sickle cell disease. To assess methods of treating dental complications in people with sickle cell disease. We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books.Date of last search: 11 April 2016.Additionally, we searched nine online databases (PubMed, Google Scholar, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Literature in the Health Sciences in Latin America and the Caribbean database, African Index Medicus, Index Medicus for South East Asia Region, Index Medicus for the Eastern Mediterranean Region, Indexing of Indian Medical Journals). We also searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organizations, pharmaceutical companies and researchers working in this field

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.

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

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.

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.…

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.

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.

Epidural analgesia in a child with sickle cell disease complicated by acute abdominal pain and priapism.

PubMed

Labat, F; Dubousset, A M; Baujard, C; Wasier, A P; Benhamou, D; Cucchiaro, G

2001-12-01

We describe a case of a 9-yr-old child with sickle cell disease complicated by abdominal vaso-occlusive crisis and priapism. Both complications were successfully treated with a combination of epidural local anesthetics and morphine.

Sickle Cell Anemia Bibliography.

ERIC Educational Resources Information Center

Christy, Steven C.

Presents sources for the acquisition of medical, social, psychological, educational, and practical knowledge of sickle cell anemia. The materials listed are designed to help parents, educators, and public service workers. Materials include journal articles, films, brochures, slides, and fact sheets. The usual bibliographic information is given.…

Aeroallergen sensitization predicts acute chest syndrome in children with sickle cell anaemia.

PubMed

Willen, Shaina M; Rodeghier, Mark; Strunk, Robert C; Bacharier, Leonard B; Rosen, Carol L; Kirkham, Fenella J; DeBaun, Michael R; Cohen, Robyn T

2018-02-01

Asthma is associated with higher rates of acute chest syndrome (ACS) and vaso-occlusive pain episodes among children with sickle cell anaemia (SCA). Aeroallergen sensitization is a risk factor for asthma. We hypothesized that aeroallergen sensitization is associated with an increased incidence of hospitalizations for ACS and pain. Participants in a multicentre, longitudinal cohort study, aged 4-18 years with SCA, underwent skin prick testing to ten aeroallergens. ACS and pain episodes were collected from birth until the end of the follow-up period. The number of positive skin tests were tested for associations with prospective rates of ACS and pain. Multivariable models demonstrated additive effects of having positive skin tests on future rates of ACS (incidence rate ratio (IRR) for each positive test 1·23, 95% confidence interval [CI] 1·11-1·36, P < 0·001). Aeroallergen sensitization was not associated with future pain (IRR 1·14, 95%CI 0·97-1·33, P = 0·11). Our study demonstrated that children with SCA and aeroallergen sensitization are at increased risk for future ACS. Future research is needed to determine whether identification of specific sensitizations and allergen avoidance and treatment reduce the risk of ACS for children with SCA. © 2018 John Wiley & Sons Ltd.

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

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.

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

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

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...

Buccal Micronucleus Cytome Assay in Sickle Cell Disease

PubMed Central

Naga, Mallika Bokka Sri Satya; Gour, Shreya; Nallagutta, Nalini; Velidandla, Surekha; Manikya, Sangameshwar

2016-01-01

Introduction Sickle Cell Anaemia (SCA) is a commonly inherited blood disorder preceded by episodes of pain, chronic haemolytic anaemia and severe infections. The underlying phenomenon which causes this disease is the point mutation in the haemoglobin beta gene (Hbβ) found on chromosome 11 p. Increased oxidative stress leads to DNA damage. DNA damage occurring in such conditions can be studied by the buccal micronucleus cytome assay, which is a minimally invasive method for studying chromosomal instability, cell death and regenerative potential of human buccal tissue. Aim To evaluate genomic instability in patients with sickle cell disease by buccal micronucleus cytome assay. Materials and Methods The study included 40 sickle cell anemia patients (Group A) and 40 age and sex matched controls (Group B). Buccal swabs were collected and stained with Papanicolaou (PAP). Number of cells with micronucleus, binuclei, nuclear bud, pyknosis and karyolysis were counted in two groups as parameters for the evaluation of genome stability. Results All the analysis was done using t-test. A p-value of <0.001 was considered statistically significant. There was a statistically significant increase in micronuclei number in SCA patients when compared with controls. Karyolytic (un-nucleated) cell number in Group A was more than to those of the controls. Conclusion The results might suggest that patients with sickle cell anaemia have genome instability which is represented by the presence of micronuclei in the somatic cells. Presence of apoptotic cells might only indicate the bodily damage to the tissue as a result of the disease. PMID:27504413

Current Management of Sickle Cell Anemia

PubMed Central

McGann, Patrick T.; Nero, Alecia C.; Ware, Russell E.

2013-01-01

Proper management of sickle cell anemia (SCA) begins with establishing the correct diagnosis early in life, ideally during the newborn period. The identification of affected infants by neonatal screening programs allows early initiation of prophylactic penicillin and pneumococcal immunizations, which help prevent overwhelming sepsis. Ongoing education of families promotes the early recognition of disease-released complications, which allows prompt and appropriate medical evaluation and therapeutic intervention. Periodic evaluation by trained specialists helps provide comprehensive care, including transcranial Doppler examinations to identify children at risk for primary stroke, plus assessments for other parenchymal organ damage as patients become teens and adults. Treatment approaches that previously highlighted acute vaso-occlusive events are now evolving to the concept of preventive therapy. Liberalized use of blood transfusions and early consideration of hydroxyurea treatment represent a new treatment paradigm for SCA management. PMID:23709685

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.

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.

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.

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.

The aeromedical significance of sickle-cell trait : a review.

DOT National Transportation Integrated Search

1976-01-01

This report present some of the technical background necessary for understanding the aeromedical importance of sickle-cell disease and the sickle-trait carrier, whose erythrocytes contain mixtures of hemoglobin S and normal hemoglobin A. This carrier...

Cold hypersensitivity increases with age in mice with sickle cell disease.

PubMed

Zappia, Katherine J; Garrison, Sheldon R; Hillery, Cheryl A; Stucky, Cheryl L

2014-12-01

Sickle cell disease (SCD) is associated with acute vaso-occlusive crises that trigger painful episodes and frequently involves ongoing, chronic pain. In addition, both humans and mice with SCD experience heightened cold sensitivity. However, studies have not addressed the mechanism(s) underlying the cold sensitization or its progression with age. Here we measured thermotaxis behavior in young and aged mice with severe SCD. Sickle mice had a marked increase in cold sensitivity measured by a cold preference test. Furthermore, cold hypersensitivity worsened with advanced age. We assessed whether enhanced peripheral input contributes to the chronic cold pain behavior by recording from C fibers, many of which are cold sensitive, in skin-nerve preparations. We observed that C fibers from sickle mice displayed a shift to warmer (more sensitive) cold detection thresholds. To address mechanisms underlying the cold sensitization in primary afferent neurons, we quantified mRNA expression levels for ion channels thought to be involved in cold detection. These included the transient receptor potential melastatin 8 (Trpm8) and transient receptor potential ankyrin 1 (Trpa1) channels, as well as the 2-pore domain potassium channels, TREK-1 (Kcnk2), TREK-2 (Kcnk10), and TRAAK (Kcnk4). Surprisingly, transcript expression levels of all of these channels were comparable between sickle and control mice. We further examined transcript expression of 83 additional pain-related genes, and found increased mRNA levels for endothelin 1 and tachykinin receptor 1. These factors may contribute to hypersensitivity in sickle mice at both the afferent and behavioral levels. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Mortality in children, adolescents and adults with sickle cell anemia in Rio de Janeiro, Brazil.

PubMed

Lobo, Clarisse Lopes de Castro; Nascimento, Emilia Matos do; Jesus, Leonardo José Carvalho de; Freitas, Thiago Gotelip de; Lugon, Jocemir Ronaldo; Ballas, Samir K

To determine the mortality rate of children, adolescents and adults with sickle cell anemia in Rio de Janeiro, Brazil. The number of deaths, the mortality rate and the causes of deaths in patients with sickle cell anemia who were treated and followed up at our institution for 15 years were determined and compared to data available for the Brazilian population. The overall number of deaths was 281 patients with a mortality rate of 16.77%. Survival probability was significantly higher in females. The number of deaths and the mortality rate were age-specific with a significant increase in the 19- to 29-year-old age group. The remaining life expectancy of the patients with sickle cell anemia was less than that of Brazilians at large. The gap between the two was about 20 years for ages between one and five years with this gap decreasing to ten years after the age of 65 years. The most common causes of death were infection, acute chest syndrome, overt stroke, organ damage and sudden death during painful crises. To the best of our knowledge, this is the first Brazilian study in a single institution in Rio de Janeiro; the mortality rate was 18.87% among adult patients with sickle cell anemia. The mortality rates in children and adults are higher than those reported in developed countries of the northern hemisphere. Copyright © 2017 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

Hydroxyurea is associated with lower costs of care of young children with sickle cell anemia.

PubMed

Wang, Winfred C; Oyeku, Suzette O; Luo, Zhaoyu; Boulet, Sheree L; Miller, Scott T; Casella, James F; Fish, Billie; Thompson, Bruce W; Grosse, Scott D

2013-10-01

In the BABY HUG trial, young children with sickle cell anemia randomized to receive hydroxyurea had fewer episodes of pain, hospitalization, and transfusions. With anticipated broader use of hydroxyurea in this population, we sought to estimate medical costs of care in treated versus untreated children. The BABY HUG database was used to compare inpatient events in subjects receiving hydroxyurea with those receiving placebo. Unit costs were estimated from the 2009 MarketScan Multi-state Medicaid Database for children with sickle cell disease, aged 1 to 3 years. Inpatient costs were based on length of hospital stay, modified by the occurrence of acute chest syndrome, splenic sequestration, or transfusion. Outpatient expenses were based on the schedule required for BABY HUG and a "standard" schedule for 1- to 3-year-olds with sickle cell anemia. There were 232 hospitalizations in the subjects receiving hydroxyurea and 324 in those on placebo; length of hospital stay was similar in the 2 groups. Estimated outpatient expenses were greater in those receiving hydroxyurea, but these were overshadowed by inpatient costs. The total estimated annual cost for those on hydroxyurea ($11 072) was 21% less than the cost of those on placebo ($13 962; P = .038). Savings on inpatient care resulted in a significantly lower overall estimated medical care cost for young children with sickle cell anemia who were receiving hydroxyurea compared with those receiving placebo. Because cost savings are likely to increase with age, these data provide additional support for broad use of hydroxyurea treatment in this population.

Hydroxyurea Is Associated With Lower Costs of Care of Young Children With Sickle Cell Anemia

PubMed Central

Oyeku, Suzette O.; Luo, Zhaoyu; Boulet, Sheree L.; Miller, Scott T.; Casella, James F.; Fish, Billie; Thompson, Bruce W.; Grosse, Scott D.

2013-01-01

BACKGROUND AND OBJECTIVE: In the BABY HUG trial, young children with sickle cell anemia randomized to receive hydroxyurea had fewer episodes of pain, hospitalization, and transfusions. With anticipated broader use of hydroxyurea in this population, we sought to estimate medical costs of care in treated versus untreated children. METHODS: The BABY HUG database was used to compare inpatient events in subjects receiving hydroxyurea with those receiving placebo. Unit costs were estimated from the 2009 MarketScan Multi-state Medicaid Database for children with sickle cell disease, aged 1 to 3 years. Inpatient costs were based on length of hospital stay, modified by the occurrence of acute chest syndrome, splenic sequestration, or transfusion. Outpatient expenses were based on the schedule required for BABY HUG and a “standard” schedule for 1- to 3-year-olds with sickle cell anemia. RESULTS: There were 232 hospitalizations in the subjects receiving hydroxyurea and 324 in those on placebo; length of hospital stay was similar in the 2 groups. Estimated outpatient expenses were greater in those receiving hydroxyurea, but these were overshadowed by inpatient costs. The total estimated annual cost for those on hydroxyurea ($11 072) was 21% less than the cost of those on placebo ($13 962; P = .038). CONCLUSIONS: Savings on inpatient care resulted in a significantly lower overall estimated medical care cost for young children with sickle cell anemia who were receiving hydroxyurea compared with those receiving placebo. Because cost savings are likely to increase with age, these data provide additional support for broad use of hydroxyurea treatment in this population. PMID:23999955

Proceedings of a Sickle Cell Disease Ontology workshop - Towards the first comprehensive ontology for Sickle Cell Disease.

PubMed

Mulder, Nicola; Nembaware, Victoria; Adekile, Adekunle; Anie, Kofi A; Inusa, Baba; Brown, Biobele; Campbell, Andrew; Chinenere, Furahini; Chunda-Liyoka, Catherine; Derebail, Vimal K; Geard, Amy; Ghedira, Kais; Hamilton, Carol M; Hanchard, Neil A; Haendel, Melissa; Huggins, Wayne; Ibrahim, Muntaser; Jupp, Simon; Kamga, Karen Kengne; Knight-Madden, Jennifer; Lopez-Sall, Philomène; Mbiyavanga, Mamana; Munube, Deogratias; Nirenberg, Damian; Nnodu, Obiageli; Ofori-Acquah, Solomon Fiifi; Ohene-Frempong, Kwaku; Opap, Kenneth Babu; Panji, Sumir; Park, Miriam; Pule, Gift; Royal, Charmaine; Sangeda, Raphael; Tayo, Bamidele; Treadwell, Marsha; Tshilolo, Léon; Wonkam, Ambroise

2016-06-01

Sickle cell disease (SCD) is a debilitating single gene disorder caused by a single point mutation that results in physical deformation (i.e. sickling) of erythrocytes at reduced oxygen tensions. Up to 75% of SCD in newborns world-wide occurs in sub-Saharan Africa, where neonatal and childhood mortality from sickle cell related complications is high. While SCD research across the globe is tackling the disease on multiple fronts, advances have yet to significantly impact on the health and quality of life of SCD patients, due to lack of coordination of these disparate efforts. Ensuring data across studies is directly comparable through standardization is a necessary step towards realizing this goal. Such a standardization requires the development and implementation of a disease-specific ontology for SCD that is applicable globally. Ontology development is best achieved by bringing together experts in the domain to contribute their knowledge. The SCD community and H3ABioNet members joined forces at a recent SCD Ontology workshop to develop an ontology covering aspects of SCD under the classes: phenotype, diagnostics, therapeutics, quality of life, disease modifiers and disease stage. The aim of the workshop was for participants to contribute their expertise to development of the structure and contents of the SCD ontology. Here we describe the proceedings of the Sickle Cell Disease Ontology Workshop held in Cape Town South Africa in February 2016 and its outcomes. The objective of the workshop was to bring together experts in SCD from around the world to contribute their expertise to the development of various aspects of the SCD ontology.

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.

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

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.

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.

Infectious complications after surgical splenectomy in children with sickle cell disease

PubMed Central

Monaco, Cypriano Petrus; Fonseca, Patricia Belintani Blum; Braga, Josefina Aparecida Pellegrini

2015-01-01

OBJECTIVE: To evaluate the frequency of infectious complications in children with sickle cell disease (SCD) after surgical splenectomy for acute splenic sequestration crisis. METHODS: Retrospective cohort of children with SCD who were born after 2002 and were regularly monitored until July 2013. Patients were divided into two groups: cases (children with SCD who underwent surgical splenectomy after an episode of splenic sequestration) and controls (children with SCD who did not have splenic sequestration and surgical procedures), in order to compare the frequency of invasive infections (sepsis, meningitis, bacteremia with positive blood cultures, acute chest syndrome and/or pneumonia) by data collected from medical records. Data were analyzed by descriptive statistical analysis. RESULTS: 44 patients were included in the case group. The mean age at the time of splenectomy was 2.6 years (1-6.9 years) and the mean postoperative length of follow-up was 6.1 years (3.8-9.9 years). The control group consisted of 69 patients with a mean age at the initial follow-up visit of 5.6 months (1-49 months) and a mean length of follow-up of 7.2 years (4-10.3 years).All children received pneumococcal conjugate vaccine. No significant difference was observed between groups in relation to infections during the follow-up. CONCLUSIONS: Surgical splenectomy in children with sickle cell disease that had splenic sequestration did not affect the frequency of infectious complications during 6 years of clinical follow-up. PMID:25913493

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

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.

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.

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.

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.

Pathophysiological insights in sickle cell disease.

PubMed

Odièvre, Marie-Hélène; Verger, Emmanuelle; Silva-Pinto, Ana Cristina; Elion, Jacques

2011-10-01

The first coherent pathophysiological scheme for sickle cell disease (SCD) emerged in the sixties-seventies based on an extremely detailed description of the molecular mechanism by which HbS in its deoxy-form polymerises and forms long fibres within the red blood cell that deform it and make it fragile. This scheme explains the haemolytic anaemia, and the mechanistic aspects of the vaso-occlusive crises (VOCs), but, even though it constitutes the basic mechanism of the disease, it does not account for the processes that actually trigger VOCs. This paper reviews recent data which imply: red blood cell dehydration, its abnormal adhesion properties to the endothelium, the participation of inflammatory phenomenon and of a global activation of all the cells present in the vessel, and finally, abnormalities of the vascular tone and of nitric oxide metabolism. These data altogether have shed a new light on the pathophysiology of the first molecular disease i.e. sickle cell disease.

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

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.

Community Health Workers as Support for Sickle Cell Care

PubMed Central

Hsu, Lewis L.; Green, Nancy S.; Ivy, E. Donnell; Neunert, Cindy; Smaldone, Arlene; Johnson, Shirley; Castillo, Sheila; Castillo, Amparo; Thompson, Trevor; Hampton, Kisha; Strouse, John J.; Stewart, Rosalyn; Hughes, TaLana; Banks, Sonja; Smith-Whitley, Kim; King, Allison; Brown, Mary; Ohene-Frempong, Kwaku; Smith, Wally R.; Martin, Molly

2016-01-01

Community health workers are increasingly recognized as useful for improving health care and health outcomes for a variety of chronic conditions. Community health workers can provide social support, navigation of health systems and resources, and lay counseling. Social and cultural alignment of community health workers with the population they serve is an important aspect of community health worker intervention. Although community health worker interventions have been shown to improve patient-centered outcomes in underserved communities, these interventions have not been evaluated with sickle cell disease. Evidence from other disease areas suggests that community health worker intervention also would be effective for these patients. Sickle cell disease is complex, with a range of barriers to multifaceted care needs at the individual, family/friend, clinical organization, and community levels. Care delivery is complicated by disparities in health care: access, delivery, services, and cultural mismatches between providers and families. Current practices inadequately address or provide incomplete control of symptoms, especially pain, resulting in decreased quality of life and high medical expense. The authors propose that care and care outcomes for people with sickle cell disease could be improved through community health worker case management, social support, and health system navigation. This report outlines implementation strategies in current use to test community health workers for sickle cell disease management in a variety of settings. National medical and advocacy efforts to develop the community health workforce for sickle cell disease management may enhance the progress and development of “best practices” for this area of community-based care. PMID:27320471

Community Health Workers as Support for Sickle Cell Care.

PubMed

Hsu, Lewis L; Green, Nancy S; Donnell Ivy, E; Neunert, Cindy E; Smaldone, Arlene; Johnson, Shirley; Castillo, Sheila; Castillo, Amparo; Thompson, Trevor; Hampton, Kisha; Strouse, John J; Stewart, Rosalyn; Hughes, TaLana; Banks, Sonja; Smith-Whitley, Kim; King, Allison; Brown, Mary; Ohene-Frempong, Kwaku; Smith, Wally R; Martin, Molly

2016-07-01

Community health workers are increasingly recognized as useful for improving health care and health outcomes for a variety of chronic conditions. Community health workers can provide social support, navigation of health systems and resources, and lay counseling. Social and cultural alignment of community health workers with the population they serve is an important aspect of community health worker intervention. Although community health worker interventions have been shown to improve patient-centered outcomes in underserved communities, these interventions have not been evaluated with sickle cell disease. Evidence from other disease areas suggests that community health worker intervention also would be effective for these patients. Sickle cell disease is complex, with a range of barriers to multifaceted care needs at the individual, family/friend, clinical organization, and community levels. Care delivery is complicated by disparities in health care: access, delivery, services, and cultural mismatches between providers and families. Current practices inadequately address or provide incomplete control of symptoms, especially pain, resulting in decreased quality of life and high medical expense. The authors propose that care and care outcomes for people with sickle cell disease could be improved through community health worker case management, social support, and health system navigation. This paper outlines implementation strategies in current use to test community health workers for sickle cell disease management in a variety of settings. National medical and advocacy efforts to develop the community health workforce for sickle cell disease management may enhance the progress and development of "best practices" for this area of community-based care. Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.

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.

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.

Sickle cell disease biochip: a functional red blood cell adhesion assay for monitoring sickle cell disease

PubMed Central

ALAPAN, YUNUS; KIM, CEONNE; ADHIKARI, ANIMA; GRAY, KAYLA E.; GURKAN-CAVUSOGLU, EVREN; LITTLE, JANE A.; GURKAN, UMUT A.

2016-01-01

Sickle cell disease (SCD) afflicts millions of people worldwide and is associated with considerable morbidity and mortality. Chronic and acute vaso-occlusion are the clinical hallmarks of SCD and can result in pain crisis, widespread organ damage, and early movtality. Even though the molecular underpinnings of SCD were identified more than 60 years ago, there are no molecular or biophysical markers of disease severity that are feasibly measured in the clinic. Abnormal cellular adhesion to vascular endothelium is at the root of vaso-occlusion. However, cellular adhesion is not currently evaluated clinically. Here, we present a clinically applicable microfluidic device (SCD biochip) that allows serial quantitative evaluation of red blood cell (RBC) adhesion to endothelium-associated protein-immobilized microchannels, in a closed and preprocessing-free system. With the SCD biochip, we have analyzed blood samples from more than 100 subjects and have shown associations between the measured RBC adhesion to endothelium-associated proteins (fibronectin and laminin) and individual RBC characteristics, including hemoglobin content, fetal hemoglobin concentration, plasma lactate dehydrogenase level, and reticulocyte count. The SCD biochip is a functional adhesion assay, reflecting quantitative evaluation of RBC adhesion, which could be used at baseline, during crises, relative to various long-term complications, and before and after therapeutic interventions. PMID:27063958

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

"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…

Sickle cell retinopathy: A literature review.

PubMed

Ribeiro, Marina Viegas Moura Rezende; Jucá, João Vitor de Omena; Alves, Anna Luyza Correia Dos Santos; Ferreira, Caio Victor Oliveira; Barbosa, Fabiano Timbó; Ribeiro, Êurica Adélia Nogueira

2017-12-01

Hemoglobinopathies are a group of hereditary diseases that cause quantitative or qualitative changes in the shape, function or synthesis of hemoglobin. One of the most common is sickle cell anemia, which, due to sickling of erythrocytes, causes vaso-occlusive phenomena. Among the possible ocular manifestations, the most representative is retinopathy, which can lead to blindness if left untreated. Therefore, periodic ophthalmologic monitoring of these patients is important for early diagnosis and adequate therapeutic management, which can be done localy by treating the lesions in the eyes, or systemically.

Inpatient management of sickle cell pain: a 'snapshot' of current practice.

PubMed

Miller, Scott T; Kim, Hae-Young; Weiner, Debra; Wager, Carrie G; Gallagher, Dianne; Styles, Lori; Dampier, Carlton D

2012-03-01

The Sickle Cell Disease Clinical Research Network (SCDCRN) designed the PROACTIVE Feasibility Study (ClinicalTrials.gov NCT00951808) to determine whether elevated serum levels of secretory phospholipase A2 (sPLA2) during hospitalization for pain would permit preemptive therapy of sickle cell acute chest syndrome (ACS) by blood transfusion. While PROACTIVE was not designed to assess pain management and was terminated early due to inadequate patient accrual, collection of clinical data allowed a "snapshot" of current care by expert providers. Nearly half the patients admitted for pain were taking hydroxyurea; hydroxyurea did not affect length of stay. Providers commonly administered parenteral opioid analgesia, usually morphine or hydromorphone, to adults and children, generally by patient-controlled analgesia (PCA). Adult providers were more likely to prescribe hydromorphone and did so at substantially higher morphine equivalent doses than were given to adults receiving morphine; the latter received doses similar to children who received either medication. All subjects treated with PCA received higher daily doses of opioids than those treated by time-contingent dosing. Physicians often restricted intravenous fluids to less than a maintenance rate and underutilized incentive spirometry, which reduces ACS in patients hospitalized for pain.

Inpatient Management of Sickle Cell Pain: a Snapshot of Current Practice

PubMed Central

Miller, Scott T.; Kim, Hae-Young; Weiner, Debra; Wager, Carrie G.; Gallagher, Dianne; Styles, Lori; Dampier, Carlton D.

2012-01-01

The Sickle Cell Disease Clinical Research Network (SCDCRN) designed the PROACTIVE Feasibility Study (ClinicalTrials.gov NCT00951808) to determine whether elevated serum levels of secretory phospholipase A2 (sPLA2) during hospitalization for pain would permit preemptive therapy of sickle cell acute chest syndrome (ACS) by blood transfusion. [1, 2] While PROACTIVE was not designed to assess pain management and terminated early due to inadequate patient accrual, collection of clinical data allowed a “snapshot” of current care by expert providers. Nearly half the patients admitted for pain were taking hydroxyurea; hydroxyurea did not affect length of stay. Providers commonly administered parenteral opioid analgesia, usually morphine or hydromorphone, to adults and children, generally by patient-controlled analgesia (PCA). Adult providers were more likely to prescribe hydromorphone and did so at substantially higher morphine equivalent doses than were given to adults receiving morphine; the latter received doses similar to children who received either medication. All subjects treated with PCA received higher daily doses of opioids than those treated by time-contingent dosing. Physicians often restricted intravenous fluids to less than a maintenance rate and underutilized incentive spirometry, which reduces ACS in patients hospitalized for pain. [3] PMID:22231150

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

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.

Fatal overdose due to prescription fentanyl patches in a patient with sickle cell/beta-thalassemia and acute chest syndrome: A case report and review of the literature.

PubMed

Biedrzycki, Olaf J; Bevan, David; Lucas, Sebastian

2009-06-01

Introduced into clinical practice in the 1960s, the analgesic fentanyl is 100 times more potent than morphine. Various methods of administration exist including the transdermal Duragesic patch system, widely used in chronic pain and palliative care settings. Numerous, often imaginative methods of abuse of fentanyl patches have been reported; the majority of fatal fentanyl overdose cases resulting from deliberate abuse or suicide. We describe the accidental overdose of a young black male with sickle cell/beta-thalassemia who had been using the Duragesic system for almost 2 years.At autopsy the macroscopic findings were of nonspecific opiate overdose with congested heavy lungs. Histopathological examination revealed severe sickling of red blood cells in the lungs (acute chest syndrome). Toxicological examination revealed blood and urine fentanyl levels of 40 microg/L and 400 microg/L (10 fold and 100 fold higher than therapeutic levels). The mast cell tryptase was also significantly elevated at 76 microg/L, (Normal 2-14 microg/L). We discuss the relevance of these findings with regard to the cause of death, and stress the need to consider fentanyl when confronted with nonspecific signs of opiate overdose as it is not detected in routine toxicological drug screens.

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.

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.

Sickle cell disease in adults: developing an appropriate care plan.

PubMed

Matthie, Nadine; Jenerette, Coretta

2015-10-01

Sickle cell disease (SCD) is primarily characterized by pain. This chronic pain with acute exacerbations is the most common reason for hospital visits, admissions, and readmissions, particularly in young adults (aged 18–39 years). People who present to the hospital for pain crises often report that nurses lack knowledge of SCD and, consequently, they do not provide appropriate, timely care. Because pain episodes often result in hospital admissions, this article highlights prominent issues that staff nurses need to know. Using a review of the literature and case studies, the authors provide recommendations to improve care of adults with SCD. No objective signs of a sickle cell pain crisis exist. Patients react to pain in different ways and use various coping mechanisms in response. Suspected opioid addiction should not affect the provision of nursing care. Pain must be treated appropriately to decrease the potential for prolonged admissions and/or readmissions. Patients are to be acknowledged as experts and collaborated with in developing an appropriate plan of care. Advocacy on behalf of the patient is important for better communication with providers. With this knowledge, nurses will be better equipped to provide the appropriate and timely care required to manage pain crises experienced by individuals living with SCD.

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.

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.

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.

Awareness of Sickle Cell Trait Status: A Cross-Sectional Survey of Antenatal Women in Ghana.

PubMed

Obed, Samuel Amenyi; Asah-Opoku, Kwaku; Aboagye, Serwah; Torto, Magdalene; Oppong, Samuel Antwi; Nuamah, Mercy Anna

2017-03-01

AbstractThis study was conducted to evaluate pregnant women's awareness of sickle cell disease and sickle cell trait and the factors that contribute to it. Two hundred and six pregnant women with at least 20 weeks gestation answered a questionnaire regarding awareness of their trait status and questions to test their knowledge of sickle cell disease. Although the majority of patients were aware of their trait status (87.4%), only 29% of knowledge questions were answered correctly; patients who self-identified as having sickle cell trait did not do better. Patients who responded that they knew a good deal about sickle cell disease scored an average of 3.5 points (number of correct responses to nine questions) more than individuals who responded that they knew nothing ( P < 0.001). Individuals who knew they had been tested for the sickle cell trait scored approximately 2 points higher than those who did not know whether they had been tested ( P = 0.004). Respondents with at least secondary education scored on average 1 point higher on the knowledge test than those with less education ( P = 0.004). Knowing someone with sickle cell disease was associated with a mean score of 1.25 points higher than individuals who did not know any affected individual ( P = 0.000).There is a deficit in the knowledge of sickle cell disease among Ghanaian pregnant women. Therefore, there is the need for public education on sickle cell disease.

Sickle cell children traveling abroad: primary risk is infection.

PubMed

Runel-Belliard, Camille; Lesprit, Emmanuelle; Quinet, Béatrice; Grimprel, Emmanuel

2009-01-01

Pediatricians taking care of sickle cell children in France are concerned about giving travel advice. Very few articles are published and no study has been done about it. A lot of pediatricians are using their own experience to decide if sickle cell children can travel abroad. Studying the consequences of such travel for sickle cell children is important to discuss common recommendations. We conducted a prospective study from June 2006 to December 2007 on desires to travel expressed during our consultations with sickle cell children. We studied notable events that occurred during travel and at least 2 months after return. Of 52 desires to travel, 10 were cancelled. All of the 42 trips were to Africa. Median duration of travel was 1.29 months (0.5-3). Median age at travel was 7.6 years (0.2-17.7). Events during travel were two hospitalizations (4.8%), a transfusion (2.4%), and four paramedical or medical examinations (9.6%). After return, four events occurred: two SS children had Plasmodium falciparum malaria (4.8%) and two had digestive bacteremia (4.8%) in SC and Sbeta+ children. No event occurred during plane travel. None of our patients died. The primary risk for sickle cell children traveling to Africa is infection: malaria first and digestive septicemia second. These risks are increased by long travel and poor sanitary conditions. Each travel should be prepared a long time before departure, and each pediatrician should insist on malaria prophylaxis and sanitary conditions, especially for young children. Trips should be shorter than 1 month when possible. A longer prospective study will be done to confirm these results.

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.

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.