First report of coexistence of sickle cell disease and neurofibromatosis Type 1 in a Saudi patient with family history of neurofibromatosis Type 1

Background Breast cancer is the leading cancer in women leading to over 400,000 deaths per year worldwide. It begins in the breast tissue and can metastasize to other organs if early diagnosis and treatment is not instituted. Women with sickle cell disease are usually spared from breast cancer and other solid tumours due to the tumoricidal effect of sickled erythrocytes. Breast cancers are rare among these group of patients. Despite its rare occurrence, this paper was to emphasize the need for breast cancer screening among female sickle cell disease patients who have positive family history of breast cancer. Case description OO was a 30-year old woman with sickle cell disease who presented to the hospital one and half years ago with a seven months history of right breast swelling and pains. She had lost her mother to breast cancer about 15 years ago. Mammography and histology of breast biopsy confirmed diagnosis of invasive ductal carcinoma of the right breast. Financial constraint was a major challenge in managing this patient as she was unable to buy her chemotherapy. She developed features suggestive of metastasis such as seizures and hepatomegaly. She was stabilized and discharged home but we lost her to follow up. She died at home. Conclusion Breast cancer is rare among females with sickle cell disease; any of them with a family history should be routinely screened for early diagnosis and treatment.

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Prenatal Hemoglobinopathy Screening Practices: Areas for Improvement

Blood ◽

10.1182/blood-2019-126084 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2298-2298

Author(s):

Scott Moerdler ◽

Ellen Fraint ◽

Ellen Silver ◽

Siobhan M Dolan ◽

Kafui A Demasio ◽

...

Keyword(s):

African American ◽

Family History ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Prenatal Screening ◽

Sickle Cell Trait ◽

Cell Disease ◽

Black African ◽

Screening Practices ◽

History Of

Background: Sickle cell disease is one of the most common inherited red blood cell disorders, yet many are not aware of their carrier status (Treadwell, J Nat Med Assoc, 2006), which can lead to confusion around pregnancy and newborn diagnosis. Furthermore, data is emerging about the severe and life-threatening risks of sickle cell trait (Kark, NEJM, 1987 and Olaniran, Am J Nephro, 2019). The American College of Obstetricians and Gynecologists' guidelines recommend that pregnant women of African, Mediterranean and Southeast Asian descent be screened for hemoglobinopathies with a complete blood count (CBC) and hemoglobin electrophoresis (ACOG, Opinion #691, 2017). However, adherence to this practice and frequency of improper screening with Sickledex is unknown. Proper screening and counseling can impact families' knowledge and allow them to establish relationships with hematology providers earlier. Objectives: We sought to assess prenatal hemoglobinopathy screening practice patterns and methods of Obstetrics & Gynecology (OBGYN) and Family Medicine (FM) providers in the Tri-State regional area. Methods: A cross-sectional electronic survey was administered to OBGYN and FM practitioners from six tri-state area institutions using publicly available information and contacts at each institution. Questions focused on prenatal hemoglobinopathy screening practices using case scenarios with variations on parental trait status and ethnicities. Chi-square analyses were used to compare the two provider groups on categorical variables. Results: There were 167 total responses; 120 surveys were complete, of which 87 were OBGYN and 33 FM providers. Respondents were mainly faculty (69/120, 58%) and from academic medical centers (n=107). 42% of providers reported that they ask "76-100%" of their patients about a personal history of sickle cell disease or trait. When asked about the proportion of pregnant patients with a positive family history of a hemoglobinopathy, there was a significant difference between OBGYN and FM providers, with 95% of OBGYN providers responding that they screen "76-100%" of those patients as opposed to only 75% of FM providers screening with the same frequency (p=0.0034). When asked about screening practices for patients without a personal/family history of a hemoglobinopathy, OBGYN providers consistently screen more frequently (Figure 1). When analyzed by ethnic background, screening practices were significantly different only between the subspecialty providers who "always" or "often" screened for hemoglobinopathies in mothers of Asian descent (p=0.03). Over 73% of providers report that they "always" screen patients of Mediterranean, Asian, and Middle Eastern descent and 84% always screen patients of Black descent. Over 30% of all respondents said they would use Sickledex for screening in case scenarios for a Black/African American mother, even when it was already known that she is a sickle cell carrier. In cases where the mother's hemoglobinopathy status was unknown, over 80% of providers responded that they would "always" evaluate with a hemoglobin electrophoresis regardless of Black/African American or Mediterranean descent. In terms of referrals to Hematology, in a case where both parents have sickle cell trait 46% of providers would "never" refer that family to Hematology. Conclusion: This pilot survey highlights differences in the methods and likelihood of prenatal hemoglobinopathy screening based on the type of prenatal care provider. Screening differences can lead to variations in prenatal guidance, diagnostic procedures, informed decision-making and knowledge of families referred to pediatric hematology clinics. This is the first study analyzing prenatal screening for hemoglobinopathies in OBGYN and FM. This study demonstrates that not all prenatal providers adhere to existing ACOG recommendations regarding which patients to screen for hemoglobinopathies and suggests an actionable area in which to enhance education for prenatal providers. Specifically, providers need to be educated that the use of Sickledex is an inappropriate laboratory screening test, since it will not detect other hemoglobinopathies. Improving prenatal screening practices by collaborating with hematologists may increase adherence to guidelines and allow for earlier relationship building with hematology. Figure 1 Disclosures Manwani: GBT: Consultancy, Research Funding; Novartis: Consultancy; Pfizer: Consultancy.

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To Give or Not to Give: RhD Immunoglobulin for an RHD*39 Pregnant Woman with Sickle Cell Disease

Transfusion Medicine and Hemotherapy ◽

10.1159/000512644 ◽

2021 ◽

pp. 1-5

Author(s):

Justin E. Juskewitch ◽

Craig D. Tauscher ◽

Sheila K. Moldenhauer ◽

Jennifer E. Schieber ◽

Eapen K. Jacob ◽

...

Keyword(s):

Pregnant Woman ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Pregnancy Termination ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Childbearing Age ◽

Procedural Complications ◽

History Of ◽

Chronic Hemolysis

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.

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Concurrent Bilateral Central Retinal Artery Occlusion Secondary to Sickle Cell Crisis

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/23247096211028392 ◽

2021 ◽

Vol 9 ◽

pp. 232470962110283

Author(s):

Gowri Renganathan ◽

Piruthiviraj Natarajan ◽

Lela Ruck ◽

Roberto Prieto ◽

Bharat Ved Prakash ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Vision Loss ◽

Central Retinal Artery Occlusion ◽

Retinal Artery Occlusion ◽

Artery Occlusion ◽

Cell Disease ◽

Sickle Cell Crisis ◽

History Of ◽

Retinal Artery

Vascular occlusive crisis with a concurrent vision loss on both eyes is one of the most devastating disability for sickle cell disease patients. Reportedly occlusive crisis in the eyes is usually temporary whereas if not appropriately managed can result in permanent vision loss. A carefully managed sickle cell crisis could prevent multiple disabilities including blindness and stroke. We report a case of a 24-year-old female with a history of sickle cell disease who had acute bilateral vision loss during a sickle crisis and recovered significantly with a timely emergent erythrocytapheresis.

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History of Pain is Associated with Hospitalization and Severe Course of COVID-19 in Children with Sickle Cell Disease

Journal of Pain ◽

10.1016/j.jpain.2021.03.118 ◽

2021 ◽

Vol 22 (5) ◽

pp. 607-608

Author(s):

Lana Mucalo ◽

Amanda Brandow ◽

Mahua Dasgupta ◽

Sadie Mason ◽

Pippa Simpson ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Cell Disease ◽

History Of ◽

History Of Pain

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The natural history of sickle cell disease

Current Opinion in Pediatrics ◽

10.1097/00008480-199802000-00010 ◽

1998 ◽

Vol 10 (1) ◽

pp. 49-52 ◽

Cited By ~ 17

Author(s):

Carolyn Hoppe ◽

Lori Styles ◽

Elliott Vichinsky

Keyword(s):

Sickle Cell Disease ◽

Natural History ◽

Sickle Cell ◽

Cell Disease ◽

History Of

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Prevalence and Predisposing Factors of Atrial Fibrillation in a Multi-Ethnic Society: The Impact of Racial Differences in Bahrain

Open Journal of Cardiovascular Surgery ◽

10.4137/ojcs.s8032 ◽

2011 ◽

Vol 4 ◽

pp. OJCS.S8032 ◽

Cited By ~ 1

Author(s):

Taysir Garadah ◽

Saleh Gabani ◽

Mohamed Al Alawi ◽

Ahmed Abu-Taleb

Keyword(s):

Atrial Fibrillation ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Middle Eastern ◽

Predisposing Factors ◽

Cell Disease ◽

Clinical Events ◽

History Of ◽

The Mean ◽

One Year

Background The prevalence and epidemiological data of atrial fibrillation (AF) among multi-ethnic populations is less well studied worldwide. Aim Evaluation of the prevalence and predisposing factors of AF in patients who were admitted to acute medical emergencies (ER) in Bahrain over the period of one year. Methods Two hundred and fifty three patients with onset of AF were studied. The mean difference of biochemical data and clinical characteristics between Middle Eastern (ME) and sub continental (SC) patients was evaluated. The odds ratio of different predisposing factors for the development of clinical events in AF patients was assessed using multiple logistic regression analysis. Results Out of 7,450 patients that were admitted to ER over one year, 253 had AF based on twelve leads Electrocardiogram (ECG), with prevalence of 3.4%. In the whole study, the mean age was 59.45 ± 18.27 years, with 164 (65%) male. There were 150 ME patients (59%), and 107 (41%) SC, 55 (22%) were Indian (IND) and 48 (19%) were South Asian (SA). In the whole study clinical presentation was of 48% for palpitation, pulmonary edema was of 14%, angina pectoris on rest of 12%, 10% had embolic phenomena, 6% had dizziness, and 7% were asymptomatic. The odds ratio of different variables for occurrence of clinical events in the study was positive of 2.2 for history of hypertension, 1.8 for sickle cell disease, 1.2 for high body mass index (BMI) >30, 1.1 for mitral valve disease. The ME patients, compared with SC, were older, had significantly higher body mass index, higher history of rheumatic valve disease, sickle cell disease with high level of uric acid and lower hemoglobin. The history of hypertension, DM and smoking was higher among the SC patients. The rate of thyroid disease was equal in both groups. Conclusion The prevalence of atrial fibrillation was 3.4% with male predominance of 65%. Patients of sub continental origin were younger with a significantly high history of hypertension and ischemic heart disease. The patients of Middle Eastern origin had significantly high rate of rheumatic heart disease, and sickle cell disease. The history of hypertension was the most important independent clinical predictor of adverse events in patients presented with AF.

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Attention Deficits in Children with Sickle Cell Disease

Perceptual and Motor Skills ◽

10.2466/pms.2002.95.1.57 ◽

2002 ◽

Vol 95 (1) ◽

pp. 57-67 ◽

Cited By ~ 8

Author(s):

Nina A. Nabors ◽

Angela K. Freymuth

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Adaptive Functioning ◽

Prior History ◽

Cell Disease ◽

Attentional Deficits ◽

Wide Range Achievement Test ◽

Wide Range ◽

History Of ◽

Timed Test

Previous research has suggested that children with sickle cell disease may exhibit cognitive deficits even in the absence of direct cerebrovascular involvement (stroke). This study was designed to assess specific attentional deficits in children with sickle cell disease. 12 children with sickle cell disease (Hb SS) with a prior history of stroke, 14 children with sickle cell disease (Hb SS) without evidence of stroke, and 13 similar aged siblings (Hb AA or Hb AS) were compared on measures of attention, intellectual functioning, achievement, and adaptive Functioning, Significant differences were found between children with sickle cell disease (with or without stroke) and healthy controls on a timed test of visual scanning, the Coding subtest of the Wechsler Intelligence Scale for Children—Revised, and subtests of Reading, Arithmetic, and Spelling from the Wide Range Achievement Test-Revised. The differences between children with sickle cell disease and their healthy siblings appear to be the result of strokes rather than sickle cell disease itself as children with sickle cell disease without strokes did not significantly differ from controls. Implications for the effects of sickle cell disease and stroke on academic performance are discussed.

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Alkaline Phosphatase Is Associated with Red Cell Alloimmunization in the Pulmonary Hypertension and Hypoxic Response (PUSH) Sickle Cell Disease Cohort

Blood ◽

10.1182/blood-2020-143036 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 20-20

Author(s):

Victoria Brooks ◽

Oluwalonimi Adebowale ◽

Victor R. Gordeuk ◽

Sergei Nekhai ◽

James G. Taylor

Keyword(s):

Risk Factors ◽

Alkaline Phosphatase ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Research Funding ◽

Severe Disease ◽

Case Control ◽

Red Cell ◽

Cell Disease ◽

History Of

Background: Blood transfusion is a common therapy for sickle cell disease (SCD). Although, highly effective, a major limitation is development of alloantibodies to minor blood group antigens on donor red cells. Alloimmunization has a prevalence of 2-5% for transfusions in the general population, but it is significantly higher in SCD. Risk factors for alloimmunization have been poorly characterized, although number of lifetime transfusions is an important risk factor. Alloimmunization has been clinically observed in children with a prevalence of about 7%. With development of each antibody, blood donor matching becomes increasingly difficult and expensive with an increased risk for transfusion reactions and diminished availability of compatible red cell units for treatment of SCD. The ability to identify risk factors for developing alloantibodies would be beneficial for clinicians. To identify markers for alloimmunization in SCD, we have analyzed children and adults who developed this complication. Methods: We analyzed The Pulmonary Hypertension and Hypoxic Response in Sickle Cell Disease (PUSH) study, which enrolled n=468 pediatric and n=59 adult SCD subjects. In both children and adults, alloimmunization cases were defined as a history of at least 1 alloantibody. Controls in both cohorts were defined as subjects with no history of alloantibodies and receipt of more than 10 lifetime red cell transfusions. All others within the study who did not meet these criteria were assigned to a third comparison group. To identify differences between cases, controls and all others, we performed univariate analyses (using ANOVA or Kruskal Wallace where appropriate) for clinical parameters and laboratories. Case control comparisons were also performed for selected variables and plasma levels for 11 cytokines. Results were further analyzed using regression modeling. Results: The overall prevalence of alloimmunization was 7.3% among children (34/468 subjects; median age 12, range 3-20 years) compared to 28.8% in adults (17/59 subjects; median age 37, range 18-73 years). When only considering those with >10 lifetime transfusions, the prevalence was considerably higher at 29.3% and 54.8% in children and adults, respectively. At the same time, 8 pediatric (23.5%) and 5 adult (29.4%) alloimmunization cases had received fewer than 10 transfusions. In a 3-way pediatric cohort comparison (cases, controls and all others), risk factors associated with alloimmunization included SS genotype, older age and markers of more severe disease (higher ferritin, WBCs, platelets and total bilirubin). Comparison of cases to controls showed alkaline phosphatase (P=0.05) was significantly lower in cases, whereas AST (P=0.02) was significantly higher even with adjustment for age. Levels of plasma cytokines MCP-1 (P=0.01) and IFNgamma (P=0.08) were lower in cases from a subset of the pediatric cohort. In adults, only 4/59 (6.8%) subjects had never received a lifetime transfusion (all non-SS). In the adult 3-way comparisons, only SS genotype and higher ferritin were associated with alloimmunization. The adult case control analysis showed higher absolute monocyte count (P=0.02), absolute eosinophil count (P=0.04) and absolute basophil count (P=0.008) in association with alloimmunization cases. In addition, alkaline phosphatase was again significantly lower among cases (P=0.02) as seen in the pediatric cohort. There were no significant differences in cytokine levels among adults. Conclusions: When considering only transfused SCD patients, the prevalence of alloimmunization is higher than 30%. As seen in prior studies, higher lifetime red cell transfusions are an important risk factor especially among adults where most patients have received transfusions. Children who develop alloantibodies appear to have laboratory markers of more severe disease, but this is not observed in adults. A novel association observed across both pediatric and adult subjects is a significantly lower serum alkaline phosphatase in those with alloantibodies. The results of this study suggest a need for improved tracking of red cell transfusion therapy in the US for SCD patients due to a high prevalence of alloimmunization. Further study is also needed to elucidate the significance of the alkaline phosphatase association. Disclosures Gordeuk: CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; Ironwood: Research Funding; Imara: Research Funding.

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Sickle Cell Anemia

10.1093/med/9780199937837.003.0079 ◽

2017 ◽

Author(s):

Eboni I Lance ◽

Andrew W. Zimmerman

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Blood Cells ◽

Marrow Transplant ◽

Neurologic Complications ◽

Cell Disease ◽

Transfusion Therapy ◽

Hematological Disorder ◽

History Of ◽

Underlying Mechanisms

Sickle cell disease is a genetic hematological disorder involving red blood cells that become deformed when stressed. Patients with homozygous hemoglobin SS disease often have multiple systemic and neurologic complications, particularly stroke. Intellectual disability is commonly seen in the population, in patients with and without a history of stroke, attributed to different underlying mechanisms of brain injury. Autism is rare and not described in sickle cell disease in the literature to date. Many treatments (chronic transfusion therapy, hydroxyurea, bone marrow transplant) are in trials at this time to see if risk of stroke and other neurologic complications can be reduced (ClinicalTrials.gov identifiers: NCT01425307, NCT01389024, NCT00152113).

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