scholarly journals Impact of Hyperfiltration during Early Childhood on the Natural History of Albuminuria in Pediatric Sickle Cell Anemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 8-8
Author(s):  
Jeffrey Lebensburger ◽  
Lee Hilliard ◽  
Thomas H. Howard ◽  
Inmaculada Aban ◽  
Daniel Feig
Keyword(s):  
Early Childhood ◽  
Natural History ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
First Episode ◽  
Event Analysis ◽  
Time To Event ◽  
History Of ◽  
The Mean

Abstract Introduction: Pediatric patients with Sickle Cell Anemia (SCA) are at risk for developing albuminuria. Hyperfiltration precedes the development of albuminuria in patients with diabetes but the natural history of hyperfiltration on the progression to albuminuria has not been studied in children with SCA. Methods: We have enrolled 185 participants with HbSS or SB0 thalassemia in a prospective pediatric cohort study evaluating progression to chronic kidney disease; the mean current age of participants in this cohort is 14 years. We have abstracted 817 urine microalbumin creatinine measurements and 891 estimations of GFR (eGFR) by Cystatin C. Abnormal urine albumin/creatinine is defined as >30mg/g. We defined persistent albuminuria as two abnormal spot urine microalbumin/creatinine measurements over three consecutive measurements and intermittent albuminuria as one abnormal urine measurement with two consecutive repeat measurement as normal. We performed descriptive and univariate statistics to characterize the natural history of the development of albuminuria. Next, as standard of care definitions of hyperfiltration (>140 ml/min/1.87) are not appropriate in SCA during early childhood (4-10 years of age), we a priori defined hyperfiltration as an eGFR ≥180 ml/min/1.87. We categorized patients with hyperfiltration during early childhood if the mean eGFR was >180 ml/min/1.87. We abstracted the mean white blood cell count (WBC), hemoglobin (Hb), and SCA therapy during early childhood and performed estimates of the odds ratio and used chi-squared test to compare the proportion of those who progressed to persistent albuminuria. Finally, we performed time to event analysis to obtain the estimated Kaplan-Meier curves for participants with and without hyperfiltration and used logrank test to compare their survival distributions. Results: Among the 185 participants, 55 participants (30%) were identified with at least one episode of albuminuria and 130 patients (70%) have not yet developed an episode of albuminuria. Among the 55 participants identified with an albuminuria event, 36 participants (66%) are categorized as having persistent albuminuria while 19 patients (34%) demonstrated intermittent or only one episode of albuminuria. The mean age at the identification of a first albuminuria event was 11.0 years (range 2-18 years). Comparing patients that progressed to persistent vs intermittent albuminuria, we identified no significant differences for age at first episode of albuminuria (13.2 vs 11.9 years, p=0.3) or type of SCA modifying therapy at first episode of albuminuria (p=0.4). We identified 90 participants with eGFR obtained between 4-10 years; 39 (43%) participants were categorized with hyperfiltration and 51 participants had a mean eGFR < 180 ml/min/1.87. Nine of the 39 (23%) participants categorized with hyperfiltration have progressed to develop persistent albuminuria as compared to 3 (6%) of the 51 without hyperfiltration progressed to persistent albuminuria; hyperfiltration was associated with a 4.8 higher odds of developing persistent proteinuria. (p=0.02). The mean eGFR during early childhood was also significantly higher among participants that progressed to albuminuria (186 vs 169 ml/min/1.87, p=0.04). We identified no significant impact of mean WBC (p=0.13), mean hemoglobin (p=0.07), or SCA therapy (p=0.22) in this subset of patients on progression to persistent albuminuria. As the current age of participants impacts identifying albuminuria outcomes, we performed a time to event analysis; participants identified with hyperfiltration during early childhood develop persistent albuminuria at an earlier age than participants without persistent albuminuria (logrank p=0.004). Finally, while persistent albuminuria was significantly associated with hyperfiltration during early childhood, we did not identify a difference in eGFR between patients with and without albuminuria during adolescence (Figure 1). Conclusion: Although 30% of patients with SCA will develop an episode of albuminuria during childhood, only 19% of cohort participants developed persistent albuminuria. Early hyperfiltration is predictive for developing albuminuria and therapies should target reducing hyperfiltration in the first decade of life. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Transcranial Doppler in Sickle Cell Anemia Adult Patients: Brazilian Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3736-3736
Author(s):  
Gisele S. Silva ◽  
Maria S. Figueiredo ◽  
Perla Vicari ◽  
Airton R. Massaro ◽  
Adauto Castelo Filho ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Transcranial Doppler ◽  
Stroke Risk ◽  
Arterial Disease ◽  
Neurological Complications ◽  
Adult Patients ◽  
History Of ◽  
The Mean

Abstract Sickle cell anemia (SCA) may cause a variety of neurological complications, including stroke and headaches. Stroke occurs in up to 9% of children with SCA, and transcranial Doppler (TCD) studies have demonstrated that increased velocities are related to higher stroke risk. Throbbing headache occurs in SCA but its cause, frequency, and relationship to TCD velocities have received little attention. On the other hand, there are few TCD studies in adult patients. Our aims were: 1) to describe the main features of TCD in adult SCA patients, and 2) to investigate if there were correlation between TCD features and presence of headache. TCD was performed in 56 adult SCA patients (≥ 16 years old) and in 56 healthy individuals (HI), matched by age and race. There were 6 patients with a remote history of stroke but none were on chronic transfusion. The SCA group was submitted to a neurological evaluation and specifically asked about the occurrence of headache and its characteristics. The highest flow velocity (maxFV) recorded for each artery was considered the most representative. We analyzed the frequency of FV asymmetry (side-to-side difference > 20%) and focal FV changes. The mean maxFV was significantly higher in patients (117.7 ± 21.6 cm/s) than in HI (72.45 ± 11.48 cm/s) (p<0.005). Only one patient had maxFV higher than 170 cm/s. The frequencies of asymmetry and of focal FV changes were significantly higher in SCA. Forty-one patients (73.2%) reported having headaches. Twenty-eight patients (50%) had severe (= 5 for pain intensity at a 1–10 scale) and frequent headaches (at least once a month). This group of patients presented TCD velocities significantly higher than patients without or with milder headaches (p=0.035). In conclusion, TCD maxFV was significantly higher in adult patients with SCA than HI, however, only one patient was considered at risk of stroke according to TCD criteria described in children. FV asymmetry and focal FV changes may be markers for arterial disease in adult SCA patients, and need to be further confirmed by neuroimaging and clinical follow up studies. The patients with severe headaches presented TCD velocities significantly higher than patients without or with milder headaches, but this finding needs to be confirmed by more and larger studies.

scholarly journals Association of MBL2 polymorphism with Leg Ulcers Development in Sickle Cell Anemia Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4912-4912
Author(s):  
Marcos André Cavalcanti Bezerra ◽  
Isabela Cristina Farias ◽  
Diego Arruda Falcão ◽  
Igor de Farias Domingos ◽  
Luana Laranjeira Prado ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
Clinical Manifestations ◽  
Monogenic Disease ◽  
Prior History ◽  
Leg Ulcers ◽  
Immune Disorder ◽  
History Of ◽  
Mbl Deficiency

Abstract Leg ulcers are the most common clinical manifestations of sickle cell anemia (SCA), a monogenic disease with huge clinical diversity among patients. They affect 8% to 10% of SCA patients, reaching a percentage greater than 50% in patients residing in tropical areas. These ulcers occur due to vascular occlusion, tissue hypoxia, hemolysis and genetic factors, presenting a slow healing, high recurrence rate and huge susceptibility to infection. Recently, some studies have shown a positive relationship between the complement system and the development of some vascular diseases and injuries such as leg ulcers in non-SCA patients. Mannan-binding lectin (MBL) is an important component of the humoral innate immune system, and MBL possesses several characteristics indicating that it may play an essential role in wound healing; modulating inflammation and contributing to the clearance of microorganisms and apoptotic cells. In a recent study of chronic leg and foot ulcer patients, serum MBL levels were significantly different between wounds of different etiologies, with chronic venous leg ulcers patients having a higher frequency of MBL deficiency. Polymorphisms in the MBL2 are associated with a reduction in the MBL protein serum levels, increasing risk of developing leg ulcers and also the maintenance of these wounds, compromising the integrity of the immune defence and its response to potential invading pathogens. Here, we aimed to determine the frequency of polymorphisms in the promoter region -221 (Y / X) and -550 (H / L) and exon 1 of the MBL2 and assess the clinical impact of these variants in a northeastern Brazilian SCA population who presented leg ulcers. Two-hundred seventy-five unrelated SCA patients were included. According the leg ulcers presence, the total cohort was classified in patients presenting current or prior history of leg ulcers (n=100) and SCA patients above 18 years with no history of leg ulcers (n=175). Molecular analysis was performed by qPCR. Our population was in Hardy-Weinberg equilibrium. The allelic frequency of haplotypes associated with high MBL production (HYA, LYA) was 54.5% for cases and 62.9% in controls. The genotypes related to low MBL production (HYO, LYO) in cases and controls was 27.5% and 18.6%, respectively. The frequency of genotype related to intermediate MBL production (LXA) was 18% in cases and 18.5% in controls. We had no statistically significant results when we analyzed only the polymorphisms (P>0.05). However, the phenotypic analysis between high and low MBL production revealed that patients with leg ulcers have lower MBL protein levels (P=0.019). We focused specifically on a possible role of MBL deficiency on healing complications, based on the facts that MBL deficiency is the most common immune disorder, and that a common causality for prolonged healing of these ulcers is infection or colonization by bacteria. In our study, MBL deficiency appears to increase the risk of developing leg ulcers in SCA patients. Disclosures No relevant conflicts of interest to declare.

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 &lt;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&lt;0.0001) and hemoglobin F increased by a median of 5.8% (IQR +3.0, +11.3, p&lt;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.

Therapeutic Phlebotomy in Children with Sickle Cell Anemia, Stroke, and Iron Overload: The SWiTCH Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1044-1044 ◽  
Author(s):  
Banu Aygun ◽  
Nicole A Mortier ◽  
Karen Kesler ◽  
Willliam H Schultz ◽  
Ofelia A. Alvarez ◽  
...  
Keyword(s):  
Adverse Events ◽  
Iron Overload ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Recurrent Stroke ◽  
Venous Access ◽  
Study Entry ◽  
Liver Iron ◽  
History Of ◽  
The Mean

Abstract Abstract 1044 Background: Stroke With Transfusions Changing to Hydroxyurea (SWiTCH Clinical Trials.gov NCT00122980), an NHLBI-sponsored Phase III multicenter trial, compared chronic blood transfusions/chelation to hydroxyurea/phlebotomy for the reduction of recurrent stroke and improvement in iron overload management in children with sickle cell anemia (SCA) and history of overt stroke. To date, however, phlebotomy to manage iron overload has not been commonly performed in children, especially those with SCA. Objective: To describe the experience with SWiTCH phlebotomy procedures, including success rate, associated adverse events, and effect on liver iron stores. Methods: Quantitative liver iron concentration (LIC) was measured by liver biopsy at study entry. Only subjects with LIC > 5 mg Fe/gram dry weight liver (DWL) were eligible for randomization. Those randomized to hydroxyurea/phlebotomy received decreasing volumes of monthly transfusion during hydroxyurea dose escalation, which lasted 4–9 months. Phlebotomy was performed every 4±1 weeks after discontinuation of transfusions. The prescribed phlebotomy volume was 10 mL/kg (maximum 500 mL) for Hb ≥ 8.0 gm/dL, and 5 mL/kg for Hb 7.0–7.9 gm/dL. Phlebotomy was held if Hb was <7.0 gm/dL. Phlebotomy was performed over 30 minutes with immediate normal saline replacement, typically using peripheral venous access. Exit LIC by liver biopsy was obtained in those completing 30 months of therapy. Ferritin was monitored monthly in all subjects using a centralized laboratory. Results: Sixty-seven children (mean age 13.0 ± 4.0 years; range 5.2–19.0 years) with history of previous stroke and transfusion therapy for an average of 7.4 ± 3.8 years (range 1.5–15.5 years) were randomized to the hydroxyurea/phlebotomy arm. Most of them had also received chelation therapy: 47 (71%) with deferoxamine for an average of 4.8 ± 3.2 years, and 57 (86%) with deferasirox for 1.5 ± 0.8 years prior to study entry. Their average entry LIC was 16.5 ± 9.4 mg/gram DWL. Sixty of 67 children (90%) successfully transitioned to hydroxyurea after 7.2 ± 2.4 months of transfusion overlap; one subject had a stroke during overlap and six failed to demonstrate adequate response/compliance to hydroxyurea to safely discontinue transfusions. These 60 subjects received an average of 8 ± 3 transfusions providing 63 ± 44 mL/kg PRBCs before completing transition and commencing phlebotomy, and 3 ± 3 transfusions providing 19 ± 20 mL/kg PRBCs after starting phlebotomy, for various clinical indications. During the course of the study, a total of 935 phlebotomies were performed (mean 16 per subject) removing an average total volume of 127 ± 74 mL/kg per subject. The mean pre-phlebotomy Hb level on hydroxyurea (9.1 gm/dL) was not significantly different than the mean pre-transfusion Hb during the transfusion overlap period (9.0 gm/dL). Mean ferritin for these 60 subjects on the hydroxyurea/phlebotomy arm decreased from 3523 ± 2150 ng/mL at study entry to 2227 ± 1646 ng/mL (p<0.0001) at exit; and decreased in 50 of 60 subjects. For the 23 patients on the hydroxyurea/phlebotomy arm who completed 30 months of study treatment, the average LIC was unchanged (18.5 mg Fe/gram DWL at entry compared to 18.1 mg Fe/gram at exit, p=0.817). However, average ferritin level for these subjects was significantly lower at exit (4216 ± 2799 ng/mL vs 2356 ± 2032 ng/mL, respectively, p=0.0003). Of 968 protocol-directed phlebotomy procedures, 935 (97%) were performed; 94% of which were at full prescribed volume. Of the 33 phlebotomy procedures that were not performed, 11 were held due to Hb < 7.0 gm/dL and 9 due to poor venous access. There were only 33 grade 2 adverse events (3.5% prevalence) reported in 12 subjects and no serious adverse events. The most common complication was hypotension (9 events; 5 subjects) followed by dizziness, syncope, headache and weakness. Six subjects had a recurrent stroke but there was no temporal relationship to the phlebotomy procedures. Conclusions: Therapeutic phlebotomies were well-tolerated and did not result in worsening anemia or stroke recurrence in this cohort of children with SCA and previous stroke switched to hydroxyurea. Although ferritin levels decreased significantly, we did not demonstrate an overall decrease in LIC in this heavily iron overloaded cohort, most likely due to continued iron loading with transfusions in the overlap period and subsequent short duration of phlebotomy. Disclosures: Off Label Use: Use of hydroxyurea in children with sickle cell anemia.

Interleukin 8 Level, Reticulocyte Counting and aPTT Ratio in Brazilian Sickle Cell Anemia Patients with Leg Ulcers

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4835-4835
Author(s):  
Magnun N N Santos ◽  
Eliel Wagner Faber ◽  
Dulcinéia Martins Albuquerque ◽  
Romulo Tadeu Dias Oliveira ◽  
Marcos André Cavalcanti Bezerra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Plasma Levels ◽  
Conflicts Of Interest ◽  
Organ Damage ◽  
Northeastern Brazil ◽  
Leg Ulcers ◽  
Increased Risk ◽  
History Of

Abstract Abstract 4835 Background: Sickle cell anemia (SCA) is characterized by a chronic inflammatory state in which oxidative stress, particularly in the endothelium, exerts a strong influence on the pathogenesis of vaso-occlusion and may be implicated in patients' clinical heterogeneity and survival. It has been suggested that the cytokine production profile of cells involved in the immune response may vary among patients with SCA. Leg ulcers (LU) represent a severe complication in these patients, and this condition has been associated with specific end-organ damage and an increase in morbidity and mortality. Recent studies have shown that venous obstruction, endothelial dysfunction, coagulopathy and infections are implicated in the complex pathogenesis of LU. Aims: To determine IL-1β, IL-6 and IL-8 plasma levels and gene expression rates as well as hematological and coagulation parameters and correlate these with the history of LU in adult SCA patients followed up at HEMOPE, in the state of Pernambuco, northeastern Brazil. Methods: Peripheral blood samples from 92 patients (median age 27 years; 42 female; 52 male; all Afro-descendants) in the steady state who had been diagnosed with SCA (HbSS), had not received a transfusion and were not using hydroxyurea were analyzed. Plasma levels of cytokines were determined by ELISA, and the gene expression rates by qRT-PCR. The patients' clinical and laboratorial characteristics were obtained from their medical charts. Statistical analysis was performed using the SAS System for Windows version 9.2. Results: Median age was higher in patients with a history of LU than in those without a history (33.1 vs. 28.4; p = 0.04). Although no statistically significant (p = 0.5) differences in IL-8 gene expression rates were observed, IL-8 plasma levels were significantly higher in patients with a history of LU than in patients without a history (23.8 vs. 7.7; p = 0.01) (Figure 1). Thus, patients with high levels of IL-8 had an increased risk for the occurrence of leg ulcers (OR = 1.01; 95% CI = 1.00–1.02). The ROC curve showed that IL-8 levels higher than 8.55 pg/mL could indicate the presence of LU (accuracy = 71.6%; sensitivity = 73.7%; specificity = 68.5%). The laboratory tests revealed reticulocyte counts and activated partial thromboplastin time (aPTT) ratios (R) that were significantly higher in patients with a history of LU than in those without a history (11.8 vs. 8.4, p = 0.01; 1.1 vs. 0.9, p = 0.04, respectively). Both the higher reticulocyte counts and R values were associated with increased risk for the occurrence of leg ulcers in these patients (OR = 1.12, 95% CI = 1.02 – 1.20; OR = 24.28, 95% CI = 1.20 – 486.09, respectively). Conclusion: In this study, patients who had had LU at some time in their lives showed significantly higher IL-8 levels, reticulocyte counts and R values than patients who had never had LU. Our results therefore suggest a relationship between the parameters described above and LU in patients with SCA. These parameters could perhaps be used, in association with different genetic modulators that may contribute to different clinical phenotypes observed in this disease, as markers of this clinical manifestation of SCA or of a propensity to develop it. Financial Support: CAPES (Brazil)/FAPESP/CNPq/INCTS Disclosures: No relevant conflicts of interest to declare.

scholarly journals Effect of Sickle Cell Anemia Therapies on the Natural History of Growth and Puberty Patterns

2019 ◽  
Vol 41 (8) ◽  
pp. 606-611
Author(s):  
Vishnu Nagalapuram ◽  
Varsha Kulkarni ◽  
Justin Leach ◽  
Inmaculada Aban ◽  
Krishnaveni Sirigaddi ◽  
...  
Keyword(s):  
Natural History ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
History Of

Effect of the Erythrocyte Apheresis On Immunological Parameters in Sickle Cell Anemia Patients in Crisis Period.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4191-4191
Author(s):  
Yurdanur Kilinc ◽  
Ferda Tekinturhan ◽  
Birol Guvenc ◽  
Refik Burgut ◽  
Ilgen Sasmaz ◽  
...  
Keyword(s):  
Blood Cell ◽  
Nk Cells ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
Blood Perfusion ◽  
Body Volume ◽  
Surface Markers ◽  
Immunological Parameters ◽  
The Mean

Abstract Abstract 4191 PURPOSE: Erythrocyte apheresis is an effective therapy in the acute and chronic treatment of sickle cell anemia (SCA). The main goal of erythrocyte apheresis is to improve blood perfusion through reducing Hemoglobin S (HbS) to < %30 and keeping hemoglobin (Hb) at desired level. The aim of this study was to evaluate the effect of the erythrocyte apheresis on immunological parameters in SCA patients with crisis. METHODS Between February 2009 and June 2009, 37 patients (20 female / 17 male) received 44 apheresis treatments at Hemapheresis Unit of Cukurova University School of Medicine, Adana, Turkey. The median age was 22 (Range, 4-56) years and the mean body weight was 51.9±18.6 kilograms. The apheresis procedures were carried out using a Cobe Spectra Cell Separator. A mean of 1.77 body volume calculated red blood cell volumes were exchanged with a mean duration of 125.9±34.9 minutes (Table 1). Sickling negative and leukoreduced packed red cells were used for apheresis treatments. Hemoglobin electrophoreses, complete blood counts, immunoglobins, specific surface markers for T, B and natural killer (NK) cells were performed before and after each procedure. While three patients had a SCA-induced functional asplenia, none of the patients was HIV-seropositive. RESULTS The erythrocyte apheresis resulted in a decrease on white blood cell (WBC) counts as expected. Average pre and post apheresis WBC counts were 12883±5775/mm3 and 8506±3331/mm3 (p<0.001) respectively. Accordingly, a decrease in post procedure lymphocyte, monocyte and granulocyte counts was observed. Because small amounts of patient's plasma were removed with red blood cells during apheresis procedures, serum levels of immuglobulins were also decreased. CD3, CD4 and CD8 for T cells, CD11b for monocytes, CD20 for B cells, CD56 as a NK marker and CD45 for leukocytes were analyzed and all of surface markers showed an increase after erythrocyte apheresis. The average pre apheresis HbS level was 78.90±19.20%, whereas the mean post apheresis HbS level was found to be 23.85±13.27% (p<0.001) (Table 2). CONCLUSIONS The erythrocyte apheresis is an effective and rapid procedure to reduce HbS concentration without increasing blood viscosity. Apheresis treatments have also been found to be beneficial in decreasing the leukocyte counts and serum immunoglobulins levels in the blood. Flow cytometric analyses revealed that T, B and NK cells were increased after apheresis treatment. Interestingly, the change in CD4/CD8 ratio was not statistically significant (p>0.05). This shows that vascular wall integrity is maintained and apheresis can be safely performed in SCA patients. In our study, blood perfusion was restored and blood chemistry was improved to optimal levels after erythrocyte apheresis. As a result, crisis periods were shortened. Disclosures: No relevant conflicts of interest to declare.

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&gt;C), rs1748033(T&gt;C), rs11203366(G&gt;A), rs11203367 (T &gt;C), rs2240340 (T&gt;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 &gt; 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 &gt; 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.

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