Correlation of Iron Levels with Asthma and Lung Function in Pediatric Patients with Sickle Cell Anemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-12
Author(s):  
Yusra D Shaikh ◽  
Nataly Apollonsky ◽  
Bruce Bernstein
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Serum Iron ◽  
Pediatric Patients ◽  
Pulmonary Complications ◽  
Acute Chest Syndrome ◽  
Iron Level ◽  
Obstructive Sleep ◽  
History Of ◽  
Hb S

Introduction:Significant morbidity and mortality in patients with sickle cell disease (SCD) is attributed to the pulmonary sequalae of the disease. Patients with SCD often suffer airway hyper-reactivity, acute chest syndrome (ACS), chronic lung disease, pulmonary hypertension (PHTN), and obstructive sleep apnea (OSA). Recent literature has provided evidence supporting the strong association between asthma and airway hyper-reactivity in SCD. One of the factors linked to chronic inflammation and asthma is iron status. The present study examined whether iron levels are associated with pulmonary complications in pediatric patients with SCD. Method:Through retrospective review of electronic medical records (EMR) we evaluated patients with diagnosis of asthma and SCD. All patients with available PFT (3/21/2013-3/11/2020) and iron studies were included in the analysis. Chi square and ANOVA tests were used to explore relationships of respiratory conditions with lab data and relevant medical history. Results:The analysis reviewed information of 100 patients with SCD -- 56 males and 44 females The sample population had the following genotypes: 63% Hemoglobin (Hb) SS, 23% Hb SC, 2% Hb S Beta Zero Thalassemia, and 12% Hb S Beta Thalassemia. 38% of these patients were receiving treatment via hydroxyurea. The results generated found that patients with a large airway obstruction (LAO) had a marginally statistically significantly higher serum iron level than those with no LAO (p=0.067.) Patients with homozygous Hb S disease were four times as likely to have a history of ACS (p=0.004) than those without and were marginally significantly more likely to be SS and SB0Thal (p=0.052). Patients with history of ACS had a significantly higher mean iron saturation and lower total iron binding capacity (TIBC.) Patients with PHTN had significantly higher serum iron levels (p=0.029). Conclusion:Our findings reveal that while iron might play a more significant role in the development of PHTN and ACS in patients with SCD, the role in asthma is borderline in our sample. These findings, although of borderline statistical significance p=0.067, are clinically noteworthy. These results may open a new window for therapy targeted at maintaining iron in normal physiologic ranges to decrease pulmonary complications in patients with sickle cell anemia. Further studies with larger samples are necessary to clarify the meaning of our marginally significant findings. Disclosures No relevant conflicts of interest to declare.

Pulmonary Function in Children with Sickle Cell Anemia Following Treatment with Hydroxyurea.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1435-1435 ◽  
Author(s):  
Elizabeth Record ◽  
Tamara New ◽  
Randall Brown ◽  
LeRoy Graham ◽  
R. Clark Brown
Keyword(s):  
Pulmonary Function ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Pulmonary Function Tests ◽  
Pulmonary Complications ◽  
Acute Chest Syndrome ◽  
P Value ◽  
Chronic Injury ◽  
History Of ◽  
Abnormal Pulmonary Function

Abstract Background: Pulmonary function is particularly susceptible to acute and chronic injury occurring in patients with sickle cell anemia (SCA). Acute Chest Syndrome (ACS), a common and potentially fatal complication of SCA, can be the cause or the consequence of abnormal pulmonary function (Siddiqui & Ahmed, 2003). Use of hydroxyurea therapy (HU) is increasing for children with recurrent pulmonary complications, following the findings that HU reduces risk of ACS in adults (Charache et al, 1995). How HU may improve pulmonary function in children with SCA is still ill-defined. The purpose of this study was to assess the change observed on serial pulmonary function tests (PFT) for children prescribed HU for abnormal pulmonary function. Methods: Over 240 children with pulmonary complications, such as acute chest syndrome, reactive airway disease, and chronic hypoxia, have been evaluated in the Sickle Cell Pulmonary Clinic at Children’s Healthcare of Atlanta since beginning in July 2000. As part of the Clinic’s standard of care, PFT were routinely attempted on children over the age of 5. A retrospective review of PFT results was done for the children with SCA and prior abnormal PFT. Children were included in the HU cohort (+HU) if repeat PFTs were available following > 3 months on HU therapy and if time on HU did not include frequent RBC transfusions. Children without history of HU therapy (−HU) were selected for comparison. PFTs were performed on a standard plethysmograph. Paired t-test was used to evaluate observed differences. Results: Thirty-one children with prior abnormal PFT had test before and following prescription of HU. Their mean age was 12.6 (range 6–20) years and mean duration of HU was 21 (range 4–47) months at the time of the repeat PFT. Hematologic changes expected on HU occurred for all 31 children. Twenty-four children followed for abnormal PFT had no history of HU (−HU) and matched the +HU group by gender, age (mean 12.3, range 7–19 years), duration followed at time of repeat PFT (mean 19, range 3–66 months; p=0.36), and initial hematologic parameters. Spirometry findings changed for +HU group, and remained stable for −HU group. Mean FVC and FEV1 values improved significantly on HU, when compared to initial (PreHU) PFT and to −HU controls. Conversion to a normal PFT, as interpreted by a pediatric pulmonologist masked to treatment status, occurred in 18 (58%) and 2 (8%) children in the +HU and −HU groups, respectively. Table 1: Serial PFT and hematologic parameters according to HU exposure −HU (n=24) +HU (n=31) Initial Repeat # PreHU Repeat 1 % predicted value for age, sex and height of subject. 2Mean (SD) #No significant changes compared to Initial, p > 0.05. *P value < 0.001 compared to PreHU; ++P value < 0.001 compared to −HU repeat. PFT parameter 1 TLC 88 (13.6)2 85 (11.7) 85 (13.4) 90 (13.5) FVC 78 (9.8) 79 (9.9) 75 (12.6) 90 (13.2)*,++ FEV1 75 (9.6) 74 (12.2) 72 (11.4) 86 (10.2)*,++ FEF 25-75 75 (22) 72 (28.0) 77 (23.4) 79 (26.8) FEV1/FVC (%) 85(6.7) 82 (9.8) 87 (11.8) 86 (11.1) Pulse oximetry (%) 95 (3.1) 96 (2.4) 94 (4.4) 97 (2.8)* WBC (x103/ul) 14 (3.8) 13 (2.9) 13.02 (2.9) 9.0 (2.1) *,++ Hb (g/dl) 8.0 (0.1) 8.0 (0.9) 7.8 (1.1) 9.1 (1.3) *,++ MCV (fl) 84 (9.2) 85 (10.0) 87.3 (8.1) 101.2 (10.1) *,++ HbF (%) 4.3 (1.5) 5.2 (5.2) 6.0 (3.8) 14.0 (7.3) *,++ Conclusions: Serial PFTs showed improved pulmonary function, following initiation of HU therapy in children with prior abnormal PFT. Routine PFT assessments of children prescribed HU may serve as an objective measure of clinical response in children with SCA and pulmonary complications. These results will help in the design of future prospective studies examining the clinical benefits of HU therapy for children at risk for long-term pulmonary complications.

Prevalence of Pulmonary Hypertension (PHTN) in Sickle Cell Disease (SCD) Adolescents with Pulmonary Complications.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3759-3759
Author(s):  
Onyinye C. Onyekwere ◽  
Andrew Campbell ◽  
James Williams ◽  
Peter Gaskin ◽  
Sohail Rana ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Sickle Cell ◽  
Pulmonary Complications ◽  
Acute Chest Syndrome ◽  
University Of Michigan ◽  
Cell Disease ◽  
Hemoglobin F ◽  
Howard University ◽  
History Of

Abstract Despite the high prevalence of PHTN in adults with SCD, the prevalence in the pediatric population with SCD is not known. We hypothesized that elevated pulmonary artery pressures may be found in SCD adolescents with history of pulmonary complications, such as acute chest syndrome (ACS), obstructive sleep apnea (OSA), asthma, and reactive airway disease. Thirty such sickle cell disease adolescents were screened at Howard University or University of Michigan for PHTN with Doppler echocardiography. We defined PHTN as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/sec (corresponding to a pulmonary artery systolic pressure greater than 35 mm Hg). PHTN was found in 16 SCD patients (53.3%) and 5 (16.7%) had TRV > 3.0 m/sec. Clinical findings according to the presences or absence of PHTN are shown in the table. Potential factors contributing to PHTN in patients with SCD include chronic hemolysis and chronic hypoxia. Our results suggest that PHTN is common among SCD adolescents with a history of pulmonary complications. Consideration should be given to screening such patients for PHTN and exploring treatment options. Further studies are urgently needed to clarify the prevalence and mechanisms of PHTN in adolescents with SCD. Clinical and demographic data of 30 SCD adolescents with pulmonary findings who underwent echocardiography at Howard University Hospital or University of Michigan PHTN (N = 16) No PHTN (N = 14) P Age in years (mean +/− SD) 15.9 +/− 3.2 17.4 +/− 2.3 0.17 Females (no. and %) 5 (31.3) 7 (50) 0.5 Hemoglobin SS Phenotype (no and %) 14 (87.5 11 (78.6) 0.5 Hemoglobin concentration (mean +/− SD) 8.0 +/− 2.1 9.3 +/−1.9 0.11 White blood cells (mean +/− SD) 10.9 +/− 2.9 9.7 +/− 3.7 0.4 Platelet (mean +/− SD) 475 +/− 172 364 +/− 240 0.17 Hemoglobin F percent (mean +/− SD) 5.1 +/− 3.5 6.4 +/− 5.5 0.6 Lactate dehydrogenase (mean +/− SD) 505 +/− 162 264 +/− 50 0.002 Total bilirubin (mean +/− SD) 4.1 +/− 2.6 3.4 +/− 2.6 0.5 Creatinine concentration (mean +/− SD) 0.6 +/− 0.2 0.7 +/− 0.2 0.18 Aspartate transaminase (mean +/− SD) 48 +/− 27 36 +/− 16 0.18 Alanine transaminase (mean +/− SD) 51 +/− 37 39 +/− 20 0.3

scholarly journals Targeted Education after an Emergency Department Visit Increases Hydroxyurea Initiation in Children with Sickle Cell Anemia

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 868-868
Author(s):  
Sarah Kappa ◽  
Lydia Pecker ◽  
Deepika S. Darbari ◽  
Robert Nickel
Keyword(s):  
Emergency Department ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
National Health System ◽  
Clinic Visit ◽  
Acute Chest Syndrome ◽  
Hemoglobin F ◽  
History Of ◽  
One Year

Abstract Introduction: Hydroxyurea decreases many complications of sickle cell anemia (SCA) but is underused in treatment-eligible patients. Barriers to hydroxyurea initiation occur on the health care system, provider, and patient level. Novel strategies to increase hydroxyurea use in patients with SCA are needed. To address this challenge at our center, we implemented the Quick Start Hydroxyurea Initiation Project (Q-SHIP). Methods: Patients with SCA were eligible to participate in Q-SHIP if they presented to the Children's National Health System (CNHS) emergency department (ED) for pain or acute chest syndrome and were not taking hydroxyurea. Patients <9 months old, on chronic transfusions, pregnant, or not followed by CNHS hematology were excluded. Eligible patients were referred to a weekly Q-SHIP clinic visit focused on hydroxyurea education and were offered initiating treatment at the visit's conclusion. Participants completed a pre-session questionnaire, discussed hydroxyurea with a hematologist using a handbook developed by CNHS, and watched videos featuring patients and parents of children with SCA sharing their experience with hydroxyurea. Subjects were classified as starting hydroxyurea if they had a clinic visit for hydroxyurea monitoring within 3 months of participation in a Q-SHIP session. Results: Over 13 months (2/1/2016 - 3/31/2017) 65 eligible patients participated in Q-SHIP a median of 5 days (IQR 2, 20 days) after ED or hospital discharge. Although 44% (28/64) of participants reported no previous hydroxyurea offer, provider clinic documentation indicated that 61% (17/28) of these families had declined a previous hydroxyurea offer. After Q-SHIP, 55% (36/65) of participants started hydroxyurea. Subjects who started hydroxyurea after Q-SHIP were similar to those who did not, except subjects who started were more likely have a history of an intensive care unit admission (Table 1). After a median follow-up of 11 months, 81% (29/36) of participants who started hydroxyurea after Q-SHIP continued on therapy. Among Q-SHIP participants continuing treatment, mean corpuscular volume increased by a median of 8.6 fL (IQR +5.4, +17.7, p<0.0001) and hemoglobin F increased by a median of 5.8% (IQR +3.0, +11.3, p<0.001). One year after implementation of Q-SHIP, the proportion of treatment-eligible patients with SCA who presented to the ED with pain or ACS who were receiving hydroxyurea increased; February 2016: 56% (32/57) vs. February 2017: 73% (43/59), p=0.059. Conclusion: Addressing indications for hydroxyurea therapy in a clinic encounter exclusively for this purpose soon after a SCA complication is a meaningful time to meet with families of children with SCA to initiate treatment. Disclosures No relevant conflicts of interest to declare.

Pulmonary Complications of Sickle Cell Anemia

Chest Imaging ◽  
2019 ◽  
pp. 141-145
Author(s):  
Constantine Raptis
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Community Acquired Pneumonia ◽  
Pulmonary Complications ◽  
Acute Chest Syndrome ◽  
Globin Chain ◽  
Cell Disease ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
History Of

“Sickle cell disease” describes the spectrum of pathology in patients with at least one HbS chain and one other abnormal β‎ globin chain. Although patients with sickle cell disease often present with a simple community acquired pneumonia, acute chest syndrome must be considered in patients presenting with chest pain and fever, as it carries an increased risk of mortality, especially in adults. A few other entities, including rib infarction and subdiaphragmatic pathologies, can mimic the symptoms of acute chest syndrome. Finally, the findings of sickle cell disease on chest radiography will be discussed. Radiologists must be familiar with these findings in order to accurately interpret imaging studies, especially when the history of sickle cell is not provided.

Does high serum iron level induce low bone mass in sickle cell anemia ?

BioMetals ◽  
2010 ◽  
Vol 24 (1) ◽  
pp. 19-22 ◽  
Author(s):  
Mir Sadat-Ali ◽  
Osama Sultan ◽  
Haifa Al-Turki ◽  
Abdulmohsen AlElq
Keyword(s):  
Bone Mass ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Serum Iron ◽  
High Serum ◽  
Iron Level ◽  
Low Bone Mass ◽  
Serum Iron Level

Sickle Cell Disease

2018 ◽  
Author(s):  
Ann Ng ◽  
Erin S. Williams
Keyword(s):  
African American ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Sickle Cell Trait ◽  
Organ Damage ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Systemic Involvement ◽  
History Of

Sickle cell anemia (sickle cell disease) is a common hemoglobinopathy with anywhere from 90,000 to 100,000 Americans affected. This chronic condition has a predominance in populations of African descent, occurring in approximately 1 out of 365 African American births, compared to 1 out of 16,300 Hispanic births. The sickle cell trait can be detected in 1 of 13 African American births. One of the most common complications associated with sickle cell anemia, vaso-occlusive crises by sickled cells, results in severe pain. Other issues associated with this condition include acute chest syndrome, lung infections, end organ damage, and stroke. With improvements in the management and prevention of pain crises, infection, and other systemic involvement, these patients are living longer, thus increasing the potential for surgical needs. Whether it is for routine surgeries or surgeries that are due to the natural history of the disease; the pediatric anesthesiologist must be knowledgeable of the management of these patients in order to prevent morbidity and mortality.

Predicting Hydroxyurea Responses in Children with Sickle Cell Anemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2131-2131 ◽  
Author(s):  
Russell E. Ware ◽  
Nicole A Mortier ◽  
Matthew P Smeltzer ◽  
Thad A Howard ◽  
Amy C Kimble ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Dose Escalation ◽  
Half Life ◽  
Pediatric Patients ◽  
Dose Titration ◽  
Serum Lactate Dehydrogenase ◽  
Acute Chest Syndrome ◽  
Baseline Creatinine ◽  
Baseline Bmi

Abstract Abstract 2131 Background: Over the past 15 years, numerous prospective and cross-sectional clinical trials have demonstrated that hydroxyurea has both laboratory and clinical efficacy for pediatric patients with sickle cell anemia (SCA). In infants, toddlers, children, and adolescents, hydroxyurea administered at maximum tolerated dose (MTD) leads to significant increases in hemoglobin (Hb) concentration, MCV, and %HbF along with simultaneous decreases in neutrophils, reticulocytes, total bilirubin, and serum lactate dehydrogenase. Clinical benefits include reduction in acute vaso-occlusive events (pain and acute chest syndrome), and emerging data suggest protection against chronic organ damage with a low risk of genotoxicity. For individual patients, however, the %HbF response to hydroxyurea and the MTD dose itself are highly variable. Currently there are no accurate predictors of the final %HbF or the MTD dose. Methods: To address the phenotypic variability, the Hydroxyurea Study of Long-Term Effects (HUSTLE, NCT00305175) was designed to capture prospectively first-dose (20 mg/kg) pharmacokinetics (PK) of hydroxyurea including maximum serum concentration (Cmax), area under the concentration curve (AUC), apparent oral clearance (CL/F), half-life (t1/2), and apparent volume of distribution (V/F). A consistent dose escalation schedule was then used to achieve a stable MTD, at which time PK studies were repeated and hydroxyurea responses (%HbF and MTD dose) were recorded along with other pharmacodynamics parameters. Results: After written informed consent, a total of 98 pediatric patients commenced hydroxyurea, 65 of whom reached MTD with complete paired PK information. In the majority of patients (39 of 65), a ‘fast/slow’ absorption phenotype identified at first-dose PK analysis was retained at MTD, supporting the concept of a genetic basis for this variation. Inter-individual PK variability was substantially greater than intra-individual variability; for example, the coefficient of variation (%CV) for CL/F was 44.4% on day 1 and 42.3% at MTD among all subjects, but averaged only 12.8% within the same subject. The CL/F was partly dependent on the rate of absorption but was most strongly influenced by subject weight and serum creatinine. At MTD, the average AUC was 114 ± 22.3 mg·h/mL, and the %CV of AUC was reduced from 24.8% on first-dose PK to 19.5% at MTD, likely reflecting dose titration toward a common degree of myelosuppression. In an attempt to predict the MTD dose toward this target AUC using data available at baseline, ‘best-fit’ equations were developed such as the following with or without PK data: Predicted MTD (mg/kg/day) = 31.9 - [17.1*Baseline Creatinine] - [0.14*Baseline BMI] + [0.0036*Baseline ARC] Predicted MTD (mg/kg/day) = 32.6 - [15.1*Baseline Creatinine] - [0.16*Baseline BMI] - [0.56*First-dose half-life] + [0.0034*Baseline ARC] - [0.48*PK phenotype (fast=0, slow=1)] A simpler equation for predicting MTD dose using only baseline creatinine and weight was then developed: Predicted MTD (mg) = 400 - [1000*Baseline Creatinine] + [21*weight] Conclusions: The relatively small intra-individual PK variability at hydroxyurea MTD compared to baseline PK studies, coupled with a similar degree of drug exposure when patients achieve a stable MTD, supports future investigation to predict the optimal hydroxyurea dose prior to the first dosing. Prediction equations of the MTD should be tested prospectively against standard dose-escalation schedules. Disclosures: Off Label Use: Hydroxyurea for children with sickle cell disease.

scholarly journals Physiological properties and characteristic reactions of hydroxyurea

2020 ◽  
Vol 22 (100) ◽  
pp. 94-102
Author(s):  
O. G. Demchuk ◽  
M. R. Hrytsyna ◽  
L. O. Kobryn ◽  
M. B. Kalytovska ◽  
B. V. Gutyj
Keyword(s):  
Sickle Cell Disease ◽  
Life Expectancy ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Genetic Disorder ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Erythroid Precursors ◽  
Hb S

As it was mentioned in the previous paper, we observed the mechanism of action the interesting drug, first synthesized back in 1869 for the first time, called Hydroxyurea. A century later, phase I and II trials began to test its safety in humans with solid tumors. It was first approved by the FDA in 1967 for the treatment of neoplastic diseases and is presently approved for the treatment of melanoma, resistant chronic myelocytic leukemia (CML), and recurrent, metastatic testicular and ovarian cancer. Sickle cell disease is a genetic disorder that decreases life expectancy by 25 to 30 years. Individuals are diagnosed with sickle cell disease if they have one of several genotypes that result in at least half of their hemoglobin being hemoglobin S (HbS). Sickle cell anemia refers specifically to the condition associated with homozygosity for the Hb S mutation (Hb SS). Several other hemoglobin mutations, when occurring with an Hb S mutation, cause a similar but often milder disease than sickle cell anemia. In addition to reduced life expectancy, patients with sickle cell disease experience chronic pain and reduced quality of life. Painful crises, also known as vaso-occlusive crises, are the most common reason for emergency department use and hospitalization, and acute chest syndrome is the most common cause of death. Prior to the approval of hydroxyurea for use in sickle cell disease, patients with this condition were treated only with supportive therapies. These measures included penicillin in children to prevent pneumococcal disease, routine immunizations, and hydration and narcotic therapy to treat painful events. Red blood cell transfusions increase the blood’s oxygen carrying capacity and decrease the concentration of cells with abnormal hemoglobin, but chronic transfusion therapy predictably leads to iron overload and alloimmunization. Therapies such as hydroxyurea that raise fetal hemoglobin (Hb F, α2γ2) levels are promising because they effectively lower the concentration of Hb S within a cell, resulting in less polymerization of the abnormal hemoglobin.Hydroxyurea’s efficacy in sickle cell disease is generally attributed to its ability to raise the levels of Hb F in the blood; however, the mechanisms by which it does so are unclear. Early studies suggested that hydroxyurea is cytotoxic to the more rapidly dividing late erythroid precursors, resulting in the recruitment of early erythroid precursors with an increased capacity to produce HbF.

scholarly journals PADI4 Gene Polymorphism As a Risk Factor for Acute Chest Syndrome in Sickle Cell Anemia Patients

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 954-954 ◽  
Author(s):  
Francine Chenou ◽  
Bidossessi Wilfried Hounkpe ◽  
Dulcinéia Martins de Albuquerque ◽  
Igor de Farias Domingos ◽  
Aderson da Silva Araujo ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Gene Polymorphisms ◽  
Conflicts Of Interest ◽  
Inflammatory Diseases ◽  
Clinical Manifestations ◽  
Chronic Inflammatory Disease ◽  
Acute Chest Syndrome ◽  
Cycle Sequencing ◽  
History Of

Abstract Introduction: Sickle cell anemia (SCA) is a chronic inflammatory disease with heterogeneous clinical features and the reasons for the heterogeneity of the clinical manifestations has not been fully elucidated. New mediators of the pathogenesis of SCA described recently include the formation of Neutrophil Extracellular Traps (NETs), which may contribute to the amplification of inflammation via the production of pro-inflammatory mediators. Peptidylarginine Deiminase 4 (PADI4) is a critical regulator of NETosis by mediating histone citrullination, an essential step for the generation of NETs. There appears to be a relationship between PADI4 gene polymorphisms and the pathophysiology of other inflammatory diseases in which NETosis seems to be relevant. Our aim was to investigate the association of PADI4 gene polymorphisms [rs874881(G>C), rs1748033(T>C), rs11203366(G>A), rs11203367 (T >C), rs2240340 (T>C)], which have been previously associated with increased PADI4 mRNA stability and with some clinical manifestations in cohorts of SCA patients. Methods: The study included 194 SCA patients (93 males and 101 females with mean age 33.29 ± 9.54 years) being followed up at the Hematology and Hemotherapy Foundation of Pernambuco (HEMOPE), Recife, Brazil. PADI4 gene polymorphisms were performed by Polymerase Chain Reaction (PCR) and their products were sequenced using the Big Dye Terminator Cycle Sequencing Ready Reaction Kit v3.1 (Applied Biosystems, CA, USA). These results obtained were compared with the clinical data obtained from the patients' records. Ethical approval was obtained from Ethics Committee of HEMOPE and all patients gave informed consent. Results: The frequencies of the genotypes found were as follows: rs874881 (22.2% GG, 50.5% GC, 27.3% CC); rs1748033 (17% TT, 42.3% TC, 40.7% CC); rs11203366 (21.1% GG, 50% GA, 28.9% AA); rs11203367 (20.6% TT, 49.5% TC, 29.9% CC); rs2240340 (24.7% TT, 46.4% TC, 28.9% CC). The distribution of the genotypes was in accordance with the Hardy-Weinberg equilibrium (p > 0.05). Twenty-four patients (12.4%) presented with a history of acute chest syndrome (ACS), 27 (13.9%) with stroke, 168 (86.6%) with vaso-occlusive crisis (VOC), and 81 (47.8%) with leg ulcers (LU). No association was observed between the polymorphisms studied and the history of LU, VOC and stroke in the patients (p > 0.05). However, for rs 874881 and 1748033 with the G and T alleles, respectively, were associated with a higher risk of ACS (OR: 2.96, p = 0.02 and OR: 4.75, p = 0.01, respectively). Conclusion: In the present study, we found an association between the wild type alleles (rs874881G and rs1748033T) and a history of ACS in our cohort of SCA patients. There is need for future studies on these polymorphisms in larger cohorts of SCA patients to affirm this association. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document