Unusually High Prevalence of Stroke and Cerebral Vasculopathy in Hemoglobin SC Disease: A Retrospective Single Institution Study.

INTRODUCTION: Unlike homozygous hemoglobin SS (HbSS) disease, stroke is a rare complication in hemoglobin SC (HbSC) disease. However, recent studies have demonstrated a high prevalence of silent stroke in HbSC disease. The factors associated with stroke and cerebral vasculopathy in the HbSC population are unknown. METHODS: We conducted a retrospective study of all patients with sickle cell disease treated at the University of Missouri, Columbia, over an 18-year period (2000-2018). The goal of the study was to characterize the silent, overt stroke, and cerebral vasculopathy in HbSC patients and compare them to patients with HbSS and HbS/ß thalassemia1 (thal) in this cohort. We also analyzed the laboratory and clinical factors associated with stroke and cerebral vasculopathy in the HbSC population. RESULTS: Of the 34 HbSC individuals, we found that the overall prevalence of stroke and cerebral vasculopathy was 17.7%. Only females had evidence of stroke or cerebral vasculopathy in our HbSC cohort (33.3%, p = 0.019). Time-averaged means of maximum velocities were lower in the HbSC group than the HbSS group and did not correlate with stroke outcome. Among HbSC individuals, those with stroke and cerebral vasculopathy had a marginally higher serum creatinine than those without these complications (0.77 mg/dL vs. 0.88 mg/dL, p = 0.08). Stroke outcome was associated with recurrent vaso-occlusive pain crises (Rec VOCs) (75 vs. 25%, p = 0.003) in HbSC patients. The predominant cerebrovascular lesions in HbSC included microhemorrhages and leukoencephalopathy. CONCLUSION: There is a distinct subset of individuals with HbSC who developed overt, silent stroke, and cerebral vasculopathy. A female predominance and association with Rec VOCs were identified in our cohort; however, larger clinical trials are needed to identify and confirm specific clinical and laboratory markers associated with stroke and vasculopathy in HbSC disease.

Epstein-Barr virus-induced sickle hepatopathy.

Sickle hepatopathy comprises a spectrum of disorders that vary in severity. Intravascular sickling and sinusoidal occlusion are the principal drivers of sickle hepatopathy, but infection or autoimmunity can act as triggers. We describe two cases of acute sickle hepatopathy initiated by primary Epstein-Barr virus (EBV) infection, a previously unreported association. The first case entailed a 14-year-old girl with hemoglobin SC (HbSC) disease who developed hepatic sequestration crisis that responded to a simple transfusion of erythrocytes. The second case was that of a 16-year-old boy with HbSC disease who experienced life-threatening intrahepatic cholestasis with multiorgan failure.

Polymorphisms in genes that affect the variation of lipid levels in a Brazilian pediatric population with sickle cell disease: rs662799 APOA5 and rs964184 ZPR1.

This cross-sectional study investigated associations between SNPs in metabolizing lipid genes, alpha-thalassemia and laboratory parameters in two forms of sickle cell disease (SCD), sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in a pediatric population. Among the groups SCA and HbSC was found a higher proportion of increased triglycerides (TG) in SCA. High levels of TG were significantly associated with lower hemoglobin (p = 0.006) and HDL-C (p = 0.037), higher white blood cell count (p = 0.027), LDH (p = 0.004) and bilirubins (p < 0.05) in SCD. Patients with HDL-C ≤40 mg/dL had higher markers hemolytic levels. Therapy of HU significantly influenced several hematological and biochemical parameters but not lipid fractions. Genotypes of the APOA5 rs662799 were not associated with lipid levels. The G-risk allele rs964184/ZPRI ZNF259/ZPR1 gene (GC + GG genotypes) was associated with increased levels of TG in children ≥10 years old (p = 0.045) and the atherogenic ratio TG/HDL-C (p = 0.032) in SCD. The use of HU improves levels of hemolysis and inflammation markers in SCD with high TG and, while not interfering with lipid levels, seems to overlap the effect of the G-risk allele in on them. This study reported for the first time that rs964184 SNP could be a genetic modifier of TG in SCD.

Sickle Cell Hemoglobin C Disease Patient Undergoing Coronary Artery Bypass Grafting with Complete Exchange Blood Transfusion during Cardiopulmonary Bypass.

Sickle cell disorders are associated with increased risk of sickling and vaso-occlusive complications when undergoing cardiopulmonary bypass (CPB) surgery. Monitoring of certain parameters such as venous and arterial oxygen content, hematocrit, acid base homeostasis, and body temperature are required for a superior outcome. Furthermore, perioperative exchange transfusion has a positive effect on the outcome of surgery and on the survival of patients undergoing heart surgery. Avoiding intraoperative hypoxia and hypothermia, and minimizing hemoglobin S (HbS) and hemoglobin C (HbC) levels with exchange transfusion make bypass surgery relatively safe with enhanced outcomes in these cases. The exact HbS level for conducting cardiac surgery with CPB is not known, however, a HbS level <30% is considered safe for conducting CPB. By using a "discard" cardiotomy reservoir and priming the oxygenator reservoir with donor blood, we were able to reduce the intraoperative circulating HbS and HbC levels to less than 15% and sequester the plasma and clotting factors from the discarded blood using intraoperative plasmapheresis.

Red cell exchange transfusion halts progressive proliferative sickle cell retinopathy in a teenaged patient with hemoglobin SC disease.

A male with sickle SC disease presented at age 8 years with proliferative sickle cell retinopathy (PSCR) and bilateral vitreous hemorrhage which spontaneously resolved, then recurred at 13 years of age. Despite conventional therapy with repeated pan-retinal photocoagulation and pars plana vitrectomy, he developed progressive PSCR and recurrent vitreous hemorrhage over the next 30 months. We describe the successful use of chronic red cell exchange transfusion (RCE) to preserve his vision and stabilize the retinopathy.

Compound heterozygosity for Hb C/Hb S (HBB: c.19G>A/HBB: c.20A>T) diseases observed in a Syrian family: a case report.

Hemoglobin S and Hemoglobin C disease is a type of sickle cell disease caused by two mutations at codon 6 of ß-globin gene. These mutations cause changes in the shape of the red blood cells. Little is known about its presence in our region. Case Presentation: The authors describe a case of a Syrian family consisting of father, mother, two daughters, and son. The mother presented with anemia, episodes of fatigue, and extreme pain (vaso-occlusive crisis). Beta and alpha-globin gene mutations have been analyzed using molecular detection methods. The results revealed that, the mother, second daughter, and son were all double heterozygous for hemoglobin C and S associated with the -α3.7 deletion mutation. The husband and the first daughter were found to have the hemoglobin C trait. Discussion: Hemoglobin (Hb) SC has been known to have a higher frequency in black populations and is restricted to persons of West African descent. In our case, all family members had dark brown skin color, and they were all diagnosed with Hb C or Hb SC. The mother, second daughter, and son had the clinical manifestations associated with Hb SC disease, and their values of mean cell volume and mean cell hemoglobin were low due to the presence of the -α3.7 deletion mutation. The husband and the first daughter do not have any serious health problems. Conclusions: To the best of the knowledge, this is the first case of compound heterozygous for hemoglobin C and S to be reported from a Syrian family.

A Patient With Hemoglobin SC Disease and Acute Ischemic Stroke Presenting With Altered Mental Status.

A 57-year-old woman with a history of hypertension, diabetes mellitus, obesity, asthma, and hemoglobin SC disease presented to the emergency department by her home health aide after she was found having altered mental status. According to her home health aide, the patient was responding with "Ok" to her questions for more than a day. The hemoglobin on admission was 8.5 g/dL. A magnetic resonance imaging (MRI) without contrast of the brain showed acute cortical infarcts superimposed on the old infarct zone. The patient received 1 unit of packed red blood cells and a session of exchange transfusion, in addition to aspirin, clopidogrel, and atorvastatin during the hospital stay. When a patient known to have sickle cell disease presents with acute neurological deficits, the first consideration is usually acute ischemic stroke due to vaso-occlusion in the cerebral vessels. However, it is essential to not overlook other potential causes of acute neurological deficits.

Acute Splenic Sequestration Crisis in Hemoglobin SC Disease: Efficiency of Red Cell Exchange.

Acute splenic sequestration crisis (ASSC) is recognized as a serious complication of sickle cell disease in children. ASSC presents with progressive splenic enlargement, transfusion-dependent anemia, and, eventually, circulatory compromise. ASSC is rare in adult patients, thus making its management and outcome in adults not well-defined. The purpose of this article is to describe our experience in managing ASSC in an adult female with hemoglobin (Hb) SC disease. The patient underwent an automated red blood cell (RBC) exchange, thus avoiding a planned splenectomy. To the best of our knowledge, our case is the third report in the literature on the use of RBC exchange in adults with HbSC disease and ASSC. RBC exchange should be considered in adults with HbSC disease with ASSC not responding to simple transfusion; a treatment that could alleviate patients' symptoms and avoid splenectomy complications, especially in young patients.

Cerebral fat embolism syndrome in sickle cell disease without evidence of shunt.

Fat embolism syndrome (FES) is a known complication of sickle cell disease (SCD) that occurs secondary to vaso-occlusive crises, bone marrow infarction, and the subsequent release of fat globules into the venous circulation. Although neurologic involvement is common, the pathophysiology of cerebral fat emboli remains controversial. While fat microemboli can enter the arterial circulation through right-to-left shunts, the systemic release of free fatty acids may also cause indirect endothelial damage and disruption of the blood-brain-barrier. We present an unusual case of cerebral fat emboli in SCD that occurred in the absence of acute chest syndrome or right-to-left shunt, favoring a biochemical etiology. Treatment of FES includes supportive care and emergent red cell exchange transfusions.

Bilateral tractional retinal detachment in hemoglobin SC disease patient / Descolamento tracional de retina bilateral em hemoglobinopatia S-C

ABSTRACT A 36-year-old black male presented with a progressive loss of visual acuity in both eyes for 7 years. He had a history of tractional retinal detachment in the right eye and vitreous hemorrhage followed by retinal detachment in the left eye. He denied any systemic illness, trauma, or drug abuse. After clinical investigation, he was diagnosed with SC hemoglobinopathy and proliferative sickle cell retinopathy stage V in both eyes.

RESUMO Paciente do sexo masculino, 36 anos, negro, apresentou baixa acuidade visual progressiva em ambos os olhos por 7 anos. Possuía antecedentes de descolamento tracional de retina no olho direito e hemorragia vítrea, seguida de descolamento de retina no olho esquerdo. Negava doenças sistêmicas, trauma ou abuso de drogas. Após investigação clínica, foi diagnosticado com hemoglobinopatia S-C e retinopatia falciforme proliferativa estágio V em ambos os olhos.

Sequential development of human herpes virus 8-positive diffuse large B-cell lymphoma and chronic myelomonocytic leukemia in a 59 year old female patient with hemoglobin SC disease.

Hematolymphoid neoplasms, including lymphoma and myeloid neoplasms, can occur in patients with sickle cell disease (SCD) or equivalent hemoglobinopathy, but an underlying connection between the two conditions has yet to be fully determined. Herein, we report a unique case of sequential development of two separate hematolymphoid neoplasms, human herpes virus 8 (HHV8)-positive diffuse large B-cell lymphoma (DLBCL) and chronic myelomonocytic leukemia, in a 59 year-old African American female with hemoglobin SC disease. While etiology of immunodeficiency is unknown, the potential causes include hydroxyurea therapy, disease related immunomodulation, chronic inflammation, and relatively old age. The leukemia cells demonstrated profound trilineage dysplasia and harbored complex cytogenetic abnormalities with loss of chromosome 5q and 7q, which are often observed in therapy-related myeloid neoplasms. Besides the potential causes listed above, we propose that myeloid leukemia in this setting may result from genomic changes due to excessive hematopoietic replication triggered by a hemolysis-induced cytokine storm. While myeloid neoplasms in the setting of SCD seems to herald a dismal clinical outcome per the literature, the HHV8-positive DLBCL in our case was apparently indolent, opposing the current perception of its clinical outcome.

Staged single-ventricle palliation in an infant with hemoglobin SC disease.

Staged single-ventricle palliation is used to treat many cyanotic congenital heart diseases. Hemoglobin sickle cell disease is associated with anemia and significant vascular sickling sequelae, which increase the risk associated with single-ventricle palliation. To our knowledge, there are no reports in the English-language medical literature of single-ventricle palliation having been performed on a patient who had either sickle cell anemia or sickle cell-hemoglobin C disease. Herein, we discuss our clinical and surgical management of an infant with tricuspid atresia type IA and hemoglobin sickle cell disease who survived single-ventricle palliative procedures through the 2nd stage of a bidirectional Glenn anastomosis.

Bone marrow necrosis and fat embolism syndrome: a dreadful complication of hemoglobin sickle cell disease.

Sickle cell disease encompasses a wide range of genotypic presentation with particular clinical features. The entity affects millions of people, particularly those whose ancestors came from sub-Saharan Africa and other countries in the Western Hemisphere, Saudi Arabia, and India. Currently, the high frequency of S and C genes reflects natural selection through the protection of heterozygotes against severe malaria, the high frequency of consanguineous marriages, improvement of some public health policies and the nutritional standards in the poorer countries where newborns are now living long enough to present for diagnosis and management. Although there is a high burden of the disease, in many countries, the new-born sickle cell screening test is being performed and is rendering an early diagnosis; however, it is still difficult for sickle cell patients to find proper treatment and adequate follow-up. Moreover, in many countries, patients are neither aware of their diagnosis nor the care they should receive to prevent complications; also, they do not receive adequate genetic counseling. Hemoglobin SC (HbSC) disease is the most frequent double sickle cell heterozygosis found in Brazil. The clinical course tends to be more benign with fewer hospitalizations compared with double homozygotic SS patients. However, HbSC patients may present severe complications with a fatal outcome. We report the case of a 36-year-old man who presented to the emergency care facility with symptoms consistent with the diagnosis of sickling crisis. The outcome was unfavorable and death occurred just hours after admission. The autopsy revealed a generalized vaso-occlusive crisis by sickled red cells, bone marrow necrosis, and fat embolism syndrome.

Comparative study of sickle cell anemia and hemoglobin SC disease: clinical characterization, laboratory biomarkers and genetic profiles.

BACKGROUND: In this study, we evaluate the association of different clinical profiles, laboratory and genetic biomarkers in patients with sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in attempt to characterize the sickle cell disease (SCD) genotypes. METHODS: We conducted a cross-sectional study from 2013 to 2014 in 200 SCD individuals (141 with SCA; 59 with HbSC) and analyzed demographic data to characterize the study population. In addition, we determined the association of hematological, biochemical and genetic markers including the ßS-globin gene haplotypes and the 3.7 Kb deletion of α-thalassemia (-α3.7Kb-thal), as well as the occurrence of clinical events in both SCD genotypes. RESULTS: Laboratory parameters showed a hemolytic profile associated with endothelial dysfunction in SCA individuals; however, the HbSC genotype was more associated with increased blood viscosity and inflammatory conditions. The BEN haplotype was the most frequently observed and was associated with elevated fetal hemoglobin (HbF) and low S hemoglobin (HbS). The -α3.7Kb-thal prevalence was 0.09 (9%), and it was associated with elevated hemoglobin and hematocrit concentrations. Clinical events were more frequent in SCA patients. CONCLUSIONS: Our data emphasize the differences between SCA and HbSC patients based on laboratory parameters and the clinical and genetic profile of both genotypes.

Stroke in a Child with Hemoglobin SC Disease: A Case Report Describing use of Hydroxyurea after Transfusion Therapy.

Children with hemoglobin SC (HbSC) disease suffer a significant incidence of silent cerebral infarcts but stroke is rare. A 2-year-old African American boy with HbSC disease presented with focal neurologic deficits associated with magnetic resonance imaging evidence of cerebral infarction with vascular abnormalities. After the acute episode he was treated with monthly transfusions and subsequently transitioned to hydroxyurea therapy. The benefits of hydroxyurea as a fetal hemoglobin inducer in HbSC disease, to ameliorate clinical symptoms are supported by retrospective studies. This case highlights the rare occurrence of stroke in a child with HbSC disease and the use of hydroxyurea therapy.

Original Research: Use of hydroxyurea and phlebotomy in pediatric patients with hemoglobin SC disease.

Hydroxyurea is an excellent therapeutic agent for the pharmacological induction of HbF in patients with sickle cell disease (SCD). However, all completed clinical trials of hydroxyurea have excluded patients with hemoglobin SC (HbSC) disease. HbSC differs significantly in pathophysiology from HbSS, as HbC does not sickle, but instead causes cellular dehydration which potentiates sickling of HbS. Many severely affected HbSC patients have been placed on hydroxyurea on a case by case basis, but there are no large scale prospective data on safety or efficacy of hydroxyurea in this subset of patients with SCD. Here, we report a case series of 14 pediatric patients with HbSC treated to maximum tolerated dose (MTD) with hydroxyurea. Those who failed to show clinical improvement after at least six months at MTD were offered phlebotomy in addition to hydroxyurea. Five out of 11 patients with HbSC who achieved MTD failed to demonstrate clinical improvement on hydroxyurea. Of the four placed on dual hydroxyurea and phlebotomy therapy, all showed at least partial clinical improvement. Percent dense red blood cells (%DRBC) were measured via an ADVIA hematology analyzer. A marked rise in percent dense cells preceded clinical complications in three patients. Dual therapy with hydroxyurea and phlebotomy may be an effective approach to patients with HbSC that do not experience improvement with hydroxyurea alone. Monitoring of %DRBC may predict adverse events and aid in assessing hydroxyurea compliance. Large scale clinical trials are needed to evaluate the safety and efficacy of hydroxyurea and hydroxyurea with phlebotomy in patients with HbSC disease.

Sickle Cell Disease with Cyanotic Congenital Heart Disease: Long-Term Outcomes in 5 Children.

Sickle cell disease is a risk factor for cerebrovascular accidents in the pediatric population. This risk is compounded by hypoxemia. Cyanotic congenital heart disease can expose patients to prolonged hypoxemia. To our knowledge, the long-term outcome of patients who have combined sickle cell and cyanotic congenital heart disease has not been reported. We retrospectively reviewed patient records at our institution and identified 5 patients (3 girls and 2 boys) who had both conditions. Their outcomes were uniformly poor: 4 died (age range, 12 mo-17 yr); 3 had documented cerebrovascular accidents; and 3 developed ventricular dysfunction. The surviving patient had developmental delays. On the basis of this series, we suggest mitigating hypoxemia, and thus the risk of stroke, in patients who have sickle cell disease and cyanotic congenital heart disease. Potential therapies include chronic blood transfusions, hydroxyurea, earlier surgical correction to reduce the duration of hypoxemia, and heart or bone marrow transplantation.

[Breastfeeding and the anthropometric profile of children with sickle cell anemia receiving follow-up in a newborn screening reference service]. / Aleitamento materno e perfil antropométrico de crianças com doença falciforme acompanhadas em serviço de referência em triagem neonatal.

OBJECTIVE: To study breastfeeding history (BF) and the anthropometric status of children with Sickle Cell Disease (SCD). METHODS: A cross-sectional study of 357 children with SS and SC hemoglobinopathies aged between 2 and 6 years old receiving regular follow-up at a Newborn Screening Reference Service (NSRS) between November 2007 and January 2009. The outcome was anthropometric status and the exposures were: BF pattern, type of hemoglobinopathy and child's age and sex. RESULTS: The average (SD) age was 3.7 (1.1) years, 52.9% were boys and 53.5% had SS hemoglobinopathy. The prevalence of exclusive breastfeeding (EBR) up to six months of age was 31.5%, the median EBR times (p25-p75) was 90.0 (24.0-180.0) days and the median weaning ages (p25-p75) was 360.0 (90.0-20.0) days respectively. Normal W/H children experienced EBR for an average duration almost four times longer than malnourished children (p=0.01), and were weaned later (p<0.05). Height deficit was found in 5.0% of children, while all the children with severe short stature had SS hemoglobinopathy and were over 4 years of age. CONCLUSIONS: EBR time and weaning age were greater than found in the literature, which is a possible effect of the multidisciplinary follow-up. Duration of EBR and later weaning were associated with improved anthropometric indicators.