Impact of Hydroxyurea On Peri-Operative Management and Outcomes in Children with Sickle Cell Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2567-2567
Author(s):  
Masanori Hayashi ◽  
Agustin Calatroni ◽  
Brittany Herzberg ◽  
Courtney Thornburg
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Operative Management ◽  
Wilcoxon Test ◽  
Categorical Variables ◽  
Acute Chest Syndrome ◽  
Transfusion Therapy ◽  
Significant Difference ◽  
Operative Complications ◽  
Post Operative Complications

Abstract Abstract 2567 Poster Board II-544 Surgical procedures in children with sickle cell anemia (SCA) can be complicated by vasoocclusive events (VOE) such as acute chest syndrome (ACS) and pain. Peri-operative management requires a multidisciplinary approach to provide appropriate pre-operative intravenous hydration and intra- and post-operative monitoring. Transfusion therapy has been controversial. Our institution previously described a low incidence of complications in children who received serial transfusions over 3-4 weeks prior to surgery. Subsequently, an increasing number of children have been prescribed hydroxyurea (HU) to prevent SCA complications. In general, children on HU at our institution only receive a single top-off transfusion the day prior to surgery if their hemoglobin is less than 10 g/dL. We hypothesized that children in the HU group would have a lower number of serial transfusion compared to the non-HU group and that there would be no difference in complications or days to discharge between the two groups. We conducted a single-institution retrospective cohort study of children with SCA, who were age less than 18 years and underwent at least one surgical procedure at Duke University Medical Center between January 1, 2003 and April 30, 2008. Data were abstracted from electronic and written medical records. Descriptive statistics were used to characterize the cohort. Wilcoxon test was used to compare continuous variables and Pearson test was used to compare categorical variables between the non-HU and HU groups. Fifty-three subjects were included (Table 1). The non-HU group was significantly younger than the HU group, but children in the non-HU group were significantly more likely to be transfused pre-operatively, primarily with serial transfusions or erythrocytopheresis, compared to the HU group. One subject in the non-HU group developed a pre-operative delayed hyperhemolytic transfusion reaction. Post-operative complications are detailed in Table 1; the overall rate was low. Two subjects in the HU group developed acute chest syndrome despite pre-operative transfusion; one episode was likely related to underlying asthma and poor response to hydroxyurea; the second was likely related to pain and hypoventilation after laparoscopic splenectomy and tonsillectomy/adenoidectomy. Overall, there were no significant differences in complications and no significant difference in days to discharge between the two groups. In summary, children with SCA on HU may safely undergo surgery without significantly reducing their percent HbS. Nonetheless, attention should still be made towards multidisciplinary effort to reduce intra- and post-operative complications, and clinicians should consider response to HU, pulmonary status and type of surgery when planning peri-operative management in children with SCA on HU. Disclosures: Off Label Use: hydroxyurea in young children.

Clinical Complications in Adult Patients with Sickle Cell Anemia and β-Thalassemia-Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4767-4767
Author(s):  
Giovanna Graziadei ◽  
Alessia Marcon ◽  
Martina Soldarini ◽  
Ilaria Gandolfi ◽  
Luisa Ronzoni ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Acute Chest Syndrome ◽  
P Value ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Clinical Complications ◽  
Significant Difference ◽  
The Mean

Abstract Abstract 4767 Background. Sickle-Cell Disease (SCD) is one of the most common severe monogenic inherited disorders worldwide, due to hemoglobin S (HbS), with reduced affinity for the oxygen. HbS polymerization, leading to erythrocyte rigidity, vaso-occlusion and hemolytic anemia, is central in the pathophysiology and crucial for the clinical outcome. The term SCD refers to Sickle Cell Anemia (SCA) due to homozygosis for βS allele, HbS/β-thalassemia (T-SCD) due to compound of β-thal and βS allele, and HbSC disease, owing to the coinheritance of βS and βcalleles. SCD is a multiorgan disease characterized by recurrent acute events and progressive organ damage, worsening during the life. Aims. This is a retrospective monocentric study aimed to assess and compare the clinical complications among 59 adult SCD patients, followed at the Hereditary Anemia Centre of the Foundation IRCCS “Ca Granda” Ospedale Maggiore Policlinico, in Milan, Italy. Methods. Mutation analysis of the b globin gene was established by direct DNA sequencing on the ABI Prism 310 genetic analyzer. Clinical and hematological features were evaluated by routine tests and physical examination, with special attention to the erythropoiesis stress parameters as LDH values and extramedullary erythropoietic (EE) masses. Results. Fifty-nine adult SCD patients, 16 SCA and 43 T-SCD, were evaluated. In T-SCD patients detected b-mutations were severe (b°) in 69.8%, and moderate or mild (b+-b++) in 30.2%. The mean age of SCA patients was 36±9 and 41±11 years for T-SCD patients. For both groups the mean follow-up was 20±6 years, while the mean age at the presentation in our Centre was 32±8 years in SCA patients and 31±10 years in T-SCD ones. Five out of 16 (31.2%) SCA patients and 16/43 (37.2%) T-SCD patients were male. HbF mean levels were 6.9±5.1% and 10.1±7.2%, respectively in SCA and T-SCD group; surprisingly Hb mean levels were lower in SCA (9.3±1.3 g/dl) than in T-SCD (9.9±1.4 g/dl) patients. Comparing SCA and T-SCD, there was statistically significant difference in splenic features: splenectomy was performed in 2/16 (12.5%) SCA patients vs 21/43 (48.8%) T-SCD patients (p-value < 0.01). Splenomegaly was absent in SCA, while was detected in 11/22 (50%) T-SCD (p-value < 0.0001); all SCA patients had functional asplenia, not observed in T-SCD patients; splenic infarctions were absent in SCA patients and were detected in 7/22 (31.8%) T-SCD patients, of whom 5 had splenomegaly and 2 had normal spleen size (pvalue <0.001). On the other side, there was not statistically significant difference in the prevalence of stroke, acute chest syndrome (ACS), bone pain crisis, sepsis, leg ulcers and priapism. However, we observed some clinical differences, even if not statistically significant. Cholecistectomy was performed in 4/16 (25%) SCA patients vs 17/43 (39.5%) T-SCD patients, and gallstones were detected respectively in 5/12 (41.7%) and in 14/26 (53.8%) of SCA and T-SCD patients. Thrombotic events were absent in SCA patients, compared to 4/43 (9.3%) T-SCD patients. Furthermore, we detected EE in 3/16 (18.6%) SCA and in 3/43 (7%) T-SCD, all carrying b° thal mutations. We underlie that Hb levels and LDH values were higher in SCA than in T-SCD patients (823±295 vs 689±209 U/L). About the treatment, 14/16 (87.5%) SCA and 31/43 (72%) T-SCD underwent to top-up transfusion; 5/43 (11.6%) T-SCD were regularly transfused. Seven out of 16 (43.8%) SCA and 18/43 (41.8%) T-SCD patients were treated with Hydroxycarbamide (HU). Criteria for transfusion therapy were: painful crisis not responsive to HU, major clinical complications, such as stroke or ACS, extramedullary erythropoietic masses associated with high LDH levels and low Hb values. Conclusions. These data suggest that SCA and T-SCD patients have similar clinical course. Splenomegaly is present only in T-SCD patients, probably due to the increased amount of extravascular hemolysis. Surprisingly, SCA patients showed EE and lower Hb levels with higher LDH values compared to T-SCD ones. This could be related to the prevalence of intravascular hemolysis, that can lead to erythropoietic stress in SCA, even if tissues are better oxygenated in these patients because of biochemical characteristic of HbS in terms of decreased oxygen affinity. These observations could be important to evaluate transfusion and HU treatment. Disclosures: Cappellini: Novartis: Research Funding.

Serum Transferrin: An Independent Predictor of Mortality in Sickle Cell Anemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2126-2126
Author(s):  
Zahra Pakbaz ◽  
Mariana E Hildesheim ◽  
Shoaib Alam ◽  
Darlene Allen ◽  
Caterina Minniti ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
Independent Predictor ◽  
Stable Condition ◽  
Acute Chest Syndrome ◽  
Serum Transferrin ◽  
Significant Difference

Abstract Abstract 2126 Introduction: Serum ferritin (SF), the most convenient marker of iron burden in sickle cell anemia (SCA), is potentially confounded by effects of inflammation in SCA. Serum transferrin (STF) has been described as one of the independent predictors of elevated tricuspid regurgitant velocity (TRV) in SCA. Therefore in this report we investigate the potential predictive role of STF in morbidity and mortality of individuals with SCA. Methods: Patients with sickle cell disease documented by high-pressure liquid chromatography were eligible for the study. Four hundred and sixty SCA patients were recruited in this study from the community through multimedia advertisements, community outreach, and regional clinics. All evaluated patients were screened by history taking, physical examination, laboratory studies, and transthoracic echocardiography. All patients provided written informed consent. The advertisements and protocol were approved by the institutional review boards of the National Heart, Lung, and Blood Institute and Howard University. Only outpatients in stable condition were included; patients who had had a vaso-occlusive crisis within the previous two weeks or an episode of acute chest syndrome within the previous four weeks were excluded. Results: Two hundred and sixty two participants with HbSS were included in the data analysis. Forty-seven percent were male. Median age was 32 years old. Median TRV in this cohort was 2.4 m/s. Forty nine percent of participants had TRV≥2.5 m/s and 19% had TRV≥3 m/s. Patients with lower STF (<164 mg/dl) were older (p=0.01), had more blood transfusions in the past (p<0.0001) and did not have more complications of sickle disease (priapism, acute chest syndrome, leg ulcers or emergency room visits, all p>0.05), but all-cause death rate was higher (22% vs. 6%, p=0.0001). Hemoglobin, CRP, alkaline phosphatase, uric acid, placenta growth factor (<0.001), SF and iron saturation were found to be higher and kidney function was worse. Patients with lower STF level were also more likely to have TRV≥3.0 m/s (32% vs. 13%, p<0. 001) but there was no significant difference in BNP and ejection fraction. Patients with lower STF had endothelial dysfunction, as indicated by a blunted forearm blood flow (FBF) response to infusion of acetylcholine into the brachial artery (p<0.01). Among age, gender, BNP, TRV,GFR,WBC, STF, systolic blood pressure and fetal hemoglobin, the Cox proportional analysis of mortality found TRV, GFR and STF the independent significant predictors of mortality in this cohort. Kaplan-Meier survival curve showed that patients with transferrin <164 mg/dl had significantly lower survival (p<0.001). Conclusion: In this cohort of adults with sickle cells anemia, STF is found to be an independent predictor of endothelial dysfunction, high TRV and mortality. It may be a more sensitive predictor than serum ferritin. We propose that iron overload may induce a state of endothelial dysfunction that is a risk factor for clinical vasculopathy and death. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical and Hematological Evaluation of Patients with Sickle Cell Anemia Before and After Four Years of Using Hydroxyurea

10.3823/2469 ◽  
2017 ◽  
Vol 10 ◽  
Author(s):  
Ieda Maria Gonçalves Pacce Bispo ◽  
Maria Lúcia Ivo ◽  
Valter Aragão do Nascimento ◽  
Alexandra Maria Almeida Carvalho de Pinto ◽  
Olinda Maria Rodrigues de Araújo ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Hematological Parameters ◽  
Fetal Hemoglobin ◽  
Hemoglobin Concentration ◽  
Teaching Hospitals ◽  
Acute Chest Syndrome ◽  
Mean Values ◽  
Significant Difference ◽  
Before And After

Objective: Evaluating clinical and hematological-clinical parameters of patients with sickle cell anemia (SCA) before and after four years of using hydroxyurea (HU).  Method: A retrospective cohort study implementing a quantitative, descriptive and analytical approach developed in two public teaching hospitals located in the Central-West region of Brazil, from November 2010 to October 2011. Data collection was performed through medical records of 32 patients with SCA to assess clinical and hematological parameters before and after HU treatment. The study was approved by the UFMS Ethics Committee under protocol number 1890/2010. Results: All of the 32 patients were homozygous with a mean age in the prescription of hydroxyurea of 19.72±7.58 years, an initial dose of 15.59±4.27 mg/kg/day, and 22.48±5.35 mg/kg/day in the fourth year of treatment. Regarding the use of HU, average values of some hematological parameters presented a significant difference in the fourth year compared to the mean values prior to HU use, such as fetal hemoglobin (14.49±7.52%), red blood cells (2.54±0.38x1012/L), hematocrit (25.30±4.03%) and hemoglobin (9.22±3.34g/dL).  Conclusion: Treatment with hydroxyurea showed a significant increase in fetal hemoglobin levels, increased hemoglobin, hematocrit and average corpuscular hemoglobin concentration, with reduced episodes of pain, infection and acute chest syndrome in such a way as to reaffirm its efficiency in treating these patients. Keywords: Hemoglobin; Sickle Cell Anemia; Hydroxyurea.

scholarly journals Transfusion Therapy in a Multi-Ethnic Sickle Cell Population Real-World Practice. a Preliminary Data Analysis of Multicentre Survey

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2389-2389 ◽  
Author(s):  
Giovanna Graziadei ◽  
Laura Sainati ◽  
Pietro Bonomo ◽  
Donatella Venturelli ◽  
Nicoletta Masera ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Research Funding ◽  
Acute Chest Syndrome ◽  
Therapeutic Approaches ◽  
Transfusion Therapy ◽  
Acute Anemia ◽  
Italian Regions ◽  
Number Of Patients ◽  
Significant Difference ◽  
Caucasian Patients

Abstract Introduction. Despite the increasing of number of patients with Sickle Cell Disease (SCD) in Italy, due to multi-ethnic migratory phenomena, a large percentage of Caucasian sickle population is already present in Italy mainly with b-thal/HbS genotype. Red cell transfusion is one effective treatment for both acute and chronic complications of SCD, while hydroxycarbamide (HC) is used to reduce the frequency of painful vaso-occlusive crises (VOCs) and decrease the need for blood transfusion. Through the National Comprehensive Reference Centers for SCD, the Italian Society of Thalassemia and Hemoglobinopathies (SITE), in collaboration with the Society Italian Transfusion Medicine and Immunohematology (SIMTI) and the Italian Association of Hematology and Pediatric Oncology (AIEOP) conducted a national survey to collect information on different therapeutic approaches used for SCD patients. Aim. To assess therapeutic approaches used a large Italian cohort of patients with SCD, accounting for age, genotype and ethnicity. Patients and Methods. Observational Longitudinal Systemic Multicentre Study (https://clinicaltrials.gov/ct2/show/NCT03397017). Data were collected from 2015 to 2018 through a standard web-based application (www.SITE-italia.org) encrypted by the Central Server. All the SCD patients, treated or not treated, were included in order to identify the overall number and all gave written informed consent. The study was approved by Ethics Committee of Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico of Milan, Italy. Results. Thirty-four centers were involved from 14 Italian regions and 1,579 patients were enrolled (802 male and 777 female; median age 23 years - IQR, 25th-75th 10-41 yrs). Genotype, age and ethnicity distribution are shown in Table 1A. As expected, the median age of non-Caucasian patients, mainly HbSS, is significantly lower than Caucasian ones (p<0.001). Out of 1,579, 365 SCD patients (23%) did not receive any therapy. Acute transfusion regimen (ATR), Chronic transfusion regimen (CTR) and HC were given in monotherapy, respectively in 160, 226 and 197 patients, or in succession/combination in 631 (Table 1B), distributed throughout genotypes. The main reasons for ATR were acute anemia (384 events) and VOCs (352), followed by acute chest syndrome (ACS; 170), surgery (82), pregnancy (64), splenic sequestration (26), stroke (9); multi-organ failure (MOFs 6) and priapism (5). For CRT, it was acute anemia (306 events) and prevention of VOCs (371), ACS (107), primary stroke prevention (78) and secondary prevention stroke (55), pain HC-resistent (39) and leg ulcers (12). For 275 patients out of 631 it was possible to follow the timing of therapy switching (Table 1C). Of 275 patients, 67.6% switched from ATR/CRT to HC, 2.9% from HC to CRT and 6.5% stopped every therapy. Out of 275 patients, 104 were treated with overlapping therapeutic regimen. Discussion. The significant difference of age in Caucasian and non-Caucasian patients is probably due to the efficacy of the national prevention program of hemoglobinopathies, because the non-Caucasian patients are prevalently born out of Italy. The transfusional approach is similar in HbSS and b°-thal/HbS and b+-thal/HbS patients regarding both ATR and CTR. HbSC genotype needed less therapies(p <0.001), confirming a less severe clinical pattern. About the combo or sequential therapy, HC was the more frequent chronic therapy used lifelong, mainly in patients with HbSS, because of wide spread of age and transfusional match problems due to different ethnicity. Summary/Conclusion. The transfusional approach is similar in HbSS, b°-thal/HbS and b+-thal/HbS patients with similar indications, prevalently VOCs and anemia. The significant higher age in Caucasian cohort and the consequent long term follow up could be the cause of variable therapeutic approach observed, however Hydroxycarbamide seemed to be the therapy more frequently used and finally suggested to manage chronic manifestations. Figure. Figure. Disclosures Origa: Apopharma: Honoraria; Novartis: Honoraria; Bluebird Bio: Consultancy; Cerus Corporation: Research Funding. Forni:Apopharma: Other: DSM Board; Celgene: Research Funding; Novartis: Other: travel expenses, Research Funding; Shire: Research Funding; Roche: Consultancy.

scholarly journals P-EGS27 Outcomes of disorders of the gallbladder, biliary tract, and pancreas during COVID pandemic

2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Christophe Thomas ◽  
Freddie Dowker ◽  
Hettie O'Connor ◽  
Liam Horgan
Keyword(s):  
Conservative Management ◽  
Significant Proportion ◽  
Operative Management ◽  
Definitive Treatment ◽  
Categorical Variables ◽  
Gallstone Pancreatitis ◽  
Retrospective Audit ◽  
Increased Risk ◽  
Operative Complications ◽  
Post Operative Complications

Abstract Background Biliary disorders make up a significant proportion of the acute general surgical workload. Effective management allows definitive treatment with relief of symptoms and reduced impact to patients due to recurrent admissions and complications. During the first COVID-19 wave and lockdown there were reduced surgical presentations to hospital and patients presented later. Surgical services were forced to implement different practices including more conservative/non operative management potentially increasing the possibility of recurrent presentations and greater complications in biliary-pancreatic presentations. Methods We performed a retrospective audit of patients presenting to our unit with ICD 10 codes: K80;Cholelithiasis, K81;Cholecystitis and K85;Acute pancreatitis. We used the period of the first wave of the COVID pandemic March – August 2020(COVID) and compared this to the same period in 2019(pre-COVID). On note review those with inaccurate coding were excluded. Patient demographics, admission details, investigations, surgical management, operative details, and post-operative complications were recorded. The primary outcomes were change in operative management, representation, and post-operative complications. χ2 test was used to test for significance of categorical variables. Results Conclusions The two groups were demographically similar with equal spread of primary diagnoses however there were significant differences in outcomes. Patients presenting with cholecystitis and gallstone pancreatitis had significantly reduced rates of definitive management. The increase in adverse operative findings is likely secondary to patients presenting later and initial conservative management. The increase in complications for the COVID cohort correlates with the increase in adverse findings/operative complexity. Conservative management with the aim of reducing COVID exposure inadvertently resulted in increased risk to patients with increased presentations/admissions. Despite this risk there were no COVID cases in our cohort.

Extended, Flexible Program Matching Red Cell Antigens for Patients with Sickle Cell Anemia Provides for Both Chronic and Intermittent Transfusions.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2899-2899
Author(s):  
Daniel R. Ambruso ◽  
Michele LaSalle-Williams ◽  
Tuan Le ◽  
Laura Cole ◽  
Kathy Hassell ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Perfect Match ◽  
Clinical Situation ◽  
Red Cells ◽  
Acute Chest Syndrome ◽  
Blood Group Antigens ◽  
Red Cell ◽  
Transfusion Therapy ◽  
Antibody Screen

Abstract Introduction: Transfusion of packed red cells (PRBCs) remains the major treatment of severe complications in sickle cell anemia. Patients may require acute, intermittent transfusions for some problems while other, more severe complications are treated with chronic transfusion (≥ 6 months) regimens to replace and suppress production of sickle cells. One of the main complications of transfusion therapy is production of red cell alloantibodies which significantly increases the risk of subsequent transfusions and limits the timely provision of appropriate blood products. Since 1978, we have provided sickle cell patients with extended matching of PRBCs to reduce the rate of alloimmunization. The flexibility of the program is adapted to meet both acute and chronic needs of the patient population. Methods: Records of patients with sickle hemoglobinopathies enrolled in the Colorado Sickle Cell Treatment and Research Center between December 31, 1993 and January 1, 2006 were reviewed under a protocol approved by the COMIRB at UCDHSC. At enrollment, serologic testing was completed on patients for the following blood group antigens: ABO; Rhesus (C,c,D,E,e); Kell (K,k); Duffy (Fya,Fyb); Kidd (Jka,Jkb); Lewis (Lea,Leb); and MNS (M,N,S,s). Donors were typed for the same antigens. For all transfusions, a perfect match was sought. When exact matches at all loci could not be found, mismatches were allowed when necessary for Fyb and MNS because of lower risk of sensitization and for Le because of infrequent hemolytic transfusion reactions. Antibody screens were completed as part of crossmatch technique at the time of each transfusion by standard methods. When an antibody screen was positive, standard antiglobulin and enzyme techniques and cell panels were used to identify the antibody. For the purposes of this study, information about patients with sickle cell anemia, complications, numbers and types of transfusions were reviewed. Results: Over the past 13 years, a total of 6,978 transfusions were provided to 104 patients (mean 68, range 1–519). In this group, 90 patients (86.5%) had HbSS, 11 (10.6%) had HbSC, and 3 (2.9%) had HbS β-thalassemia. Indications for transfusions included vaso-occlusive crisis, aplastic crises, splenic sequestration, and preparation for surgery, acute chest syndrome, stroke and priapism. Fifty-two patients (50%) received simple transfusions only while 33 (32%) had only PRBC exchange and 19 (18%) required both modalities. Of the total group, 42 (40%) were on chronic transfusions and 11 (10%) had both intermittent and chronic transfusions. The protocol and system for delivering matched PRBCs was flexible enough that even when red cells were needed for intermittent transfusions in 62 (60%) patients, delivery of the products was easily accomplished. In only 8 patients receiving 13 units of PRBCs was the clinical situation so urgent that non-antigen matched units was required. Conclusion: PRBCs with extended antigen matching were provided to our population of patients with sickle cell anemia. The program provided blood components for both intermittent and chronic transfusion schemes with very few patients having such urgent conditions that they required products without extended matching.

Asthma Is Associated with Acute Chest Syndrome, but Not an Increase Rate of Hospitalization for Pain among Children with Sickle Cell Anemia: A Retrospective Cohort Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3406-3406
Author(s):  
Francoise Bernaudin ◽  
Robert C. Strunk ◽  
Annie Kamdem ◽  
Cecile Arnaud ◽  
Ping An ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Therapeutic Intervention ◽  
Retrospective Cohort ◽  
Inhaled Corticosteroids ◽  
Medical Center ◽  
Acute Chest Syndrome ◽  
Thoracic Pain ◽  
Transfusion Therapy

Abstract Introduction In this study, we sought to validate the previous findings that asthma increases the incidence of acute chest syndrome (ACS) and pain in children with sickle cell anemia (SCA). Methods A retrospective cohort was comprised of children with SCA evaluated for at least six months from a single medical center. Asthma was defined as being present when the first wheezing episode was heard by a physician after the age of 2 years or after 3 episodes of bronchiolitis before the age of 2 years. ACS was defined as a recent abnormal X-ray of the lungs associated with fever, respiratory signs or thoracic pain. A painful episode was defined as pain that resulted in hospitalization. Therapeutic intervention (hydroxyurea, blood transfusion therapy or transplant) was uniformly applied to all children with three or more episodes of pain that required hospitalization within a 12 month period. Patient years were accumulated from birth until death, lost to follow up, last visit to the center or a therapeutic intervention, whichever came first. Results A total of 297 children with SCA were evaluable for a doctor diagnosis of asthma for a total of 1,805 patient-years. The mean length of follow-up was 6.1 patient-years. A doctor diagnosis of asthma was present in 8.4% (25 of 297). Among the children with asthma 75% (19 of 25) were consistently prescribed a beta 2 agonist or inhaled corticosteroids. After adjustment for the effect of age, asthma was significantly associated with ACS event (p = 0.03) but pain was not (>0.05). Conclusion Among children with SCA, asthma is associated with an increased incidence of ACS, but not pain that required hositalization. The absence of an association between asthma and pain may be related to uniform therapeutic intervention for children with repetitive painful episodes that require hospitalizations coupled with active treatment for asthma in most of the children.

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.

Predicting Acute Chest Syndrome in Sickle Cell Disease Patients Hospitalized for Acute Vasoocclusive Events.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3390-3390
Author(s):  
Daniel A. Dworkis ◽  
Vikki G. Nolan ◽  
Lillian C. McMahon ◽  
Elizabeth S. Klings ◽  
Martin H. Steinberg
Keyword(s):  
High Risk ◽  
Sickle Cell Disease ◽  
Hospital Admission ◽  
Clinical Outcomes ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Alpha Thalassemia ◽  
Significant Difference

Abstract Acute painful vasoocclusive events (VOE) and acute chest syndrome (ACS) are the leading causes of hospitalization among patients with sickle cell disease (SCD). Although most patients with ACS are hospitalized explicitly for that reason, up to 36% of patients who were admitted for VOEs subsequently developed ACS, usually within several days of admission. Since ACS can be associated with hypoxemia and respiratory failure, leading to a need for blood transfusion and ventilatory support, the ability to predict which patients are at high risk for this serious complication might lead to better clinical outcomes. Using the results of standard-of-care blood testing obtained upon hospital admission, we present a novel model to predict the risk of developing ACS following hospitalization for a VOE. To generate this model, we retrospectively evaluated the records of 1,263 participants in the Cooperative Study of Sickle Cell Disease (CSSCD), with either sickle cell anemia (with or without co-incident alpha thalassemia) or HbSC disease, who were hospitalized for an acute VOE. During their hospitalization, 148 of these patients developed ACS, defined in the CSSCD as a new pulmonary infiltrate on a chest x-ray or evidence of pleuritic chest pain, with or without dyspnea; the remaining patients, who did not develop ACS, served as controls. Case patients were aged 7 to 55 years, with a mean age of 23 years; control patients were aged 5 to 72 years with a mean age of 24.5 years. Males were slightly more likely to develop ACS; 56% of case patients were male, compared with 46% of control patients (OR 1.5, 1.05–2.10). There was a significant difference in the distribution of SCD genotype, with fewer patients with HbSC disease and sickle cell anemia-alpha thalassemia in the control group (p=0.002). For each patient, we included in the model the hematocrit, hemoglobin concentration, mean corpuscular volume, reticulocyte count, white blood cell count with differential, and platelet count at hospital admission, along with their age, gender, and SCD genotype. Random Forest (RF) software, implemented in the R language, was used to create a set of 500 classification and regression trees using 80% of the subjects, and was then tested on the remaining 20%. For each test patient, each randomly generated decision tree classified the patient as high or low risk, and the consensus of the 500 tree forest was used to predict if the patient would develop ACS. This data driven approach produced a robust predictive model, while reducing analyst input and eliminating the need to identify important confounders a priori, as would be the case if attempting these analyses using stepwise logistic regression. The RF model correctly classified 95% of the patients for the development of ACS, with 67% sensitivity and 99% specificity. Neutrophil bands and platelet counts were identified by RF as the two most important predictors for the development of ACS, concordant with the potential roles of infection and infarction in its pathogenesis. With future validation, perhaps including prospective studies, this simple model, along with other predictors such as serum phospholipase A2 and studies of genetic modulators of this phenotype, could aid in identifying individuals who are at high risk for developing ACS. Ultimately, for patients hospitalized with VOEs, better identification of the risk of developing ACS might lead to more appropriate treatment with better clinical outcomes.

Cognitive Dysfunction Occurs In Children with Sickle Cell Anemia without Cerebral Ischemic Insult or Vasculopathy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1076-1076
Author(s):  
Clarisse Lobo ◽  
Patricia Moura ◽  
Patricia Rio ◽  
Heber Maia ◽  
Juliana Fernandes ◽  
...  
Keyword(s):  
Academic Achievement ◽  
Cognitive Function ◽  
Cognitive Dysfunction ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Brain Mri ◽  
Neurocognitive Deficits ◽  
Ischemic Insult ◽  
Transfusion Therapy ◽  
Significant Difference

Abstract Abstract 1076 Background: Sickle cell anemia (SCA) has been associated with impairments in general cognitive functioning as measured by IQ scores and other neurocognitive measures. Children with SCA and overt stroke are the most affected, but those with silent infarcts (SI) on brain magnetic resonance imaging (MRI) also have cognitive impairment. Transcranial doppler ultrasonography (TCD) screening has allowed identification of individuals at high risk for stroke, in whom institution of prophylactic transfusion therapy produces a dramatic reduction in the incidence of primary stroke. Elevated TCD velocities have been reported to predict neurocognitive impairment in patients with SCA. We hypothesize that children with SCA with normal TCD velocities and no overt stroke or SI on brain MRI will have normal cognitive performance when compared with normal-matched controls. We investigated the academic achievement and cognitive function among children with SCA with normal brain MRI and normal TCD velocities, and compared their results with normal age and race matched controls. Methods: School age children with SCA who had normal MRI and TCD exams were evaluated. Controls (classmates and siblings) were matched for race, age, and social-economic status. SCA patients receiving chronic transfusion therapy or with a history of prior overt stroke were not eligible. All participants were followed at Instituto Estadual de Hematologia Arthur de Siqueira Cavalcanti (HEMORIO). All patients and controls underwent MRI examination (to document the absence of stroke and SI) and cognitive testing. In addition, SCA subjects underwent TCD testing and had hematologic laboratory testing. SCA subjects were not experiencing pain or any other complication during study evaluations. The WISC-III was obtained as a measure of intellectual function, and achievement scores in reading, writing, and arithmetic were used to evaluate school performance. Comparisons among patients and controls were made using the Mann-Whitney test. This study was approved by the HEMORIO Ethics committee and all participants signed informed consent. Results: SCA patients had significantly lower total IQ and academic achievement than healthy controls (Table). Discussion: This is the first report showing cognitive dysfunction in children with SCA with both normal MRI and TCD examination. Early neurocognitive deficits are known to occur in children with SCA. In general, a patient with SCA in Brazil has a low socioeconomic status, low educational level, and poor access to health services, placing these children at higher risk of neurocognitive complications from the disease. Our study shows that children with SCA perform worse on measures of key cognitive function when compared with healthy matched controls, even without evidence of elevated velocities in the main cerebral arterial vessels or radiological insult to the brain. There was a significant difference in total IQ and school achievement among SCA patients and controls; however this was not true for verbal or executive IQ, suggesting that the cognitive compromise in this population is global. Cognitive dysfunction may occur long before lesions are observed on the MRI (ischemic insult) or on the TCD (vasculopathy), underscoring the need for preemptive screening and treatment of cognitive dysfunction in children with SCA. Disclosures: Off Label Use: Hydroxyurea for prevention of neuropsychological changes in SCD.

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