Predictors of Adverse Outcomes in Hospitalized Adult Patients with Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3197-3197
Author(s):  
Fahd Rahman ◽  
Roy N. Gay ◽  
Samir K. Ballas ◽  
Juan C. Zubieta ◽  
Zekarias Berhane ◽  
...  
Keyword(s):  
At Risk ◽  
Logistic Regression ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Acute Pain ◽  
Reticulocyte Count ◽  
Laboratory Data ◽  
Adverse Outcomes ◽  
Acute Chest Syndrome ◽  
Cell Disease

Abstract The identification of patients with sickle cell disease at risk of serious complications at the time of hospital admission can help stratify patients who will need aggressive management. We identified predictors associated with adverse outcomes such as frequent hospitalizations, acute pain crises and acute chest syndromes. To that end, we retrospectively reviewed medical records of 265 adult sickle cell disease patients, hospitalized between 1/1/98 and 2/3/05 at Mercy Catholic Medical Center, with complete clinical and laboratory data. 195/73.6% had HbSS and the rest had HbSC, HbSβ-thal0,HbS-βthal+or HbSOarab disease. 59 variables were considered including demographic, hematological, biochemical, clinical and treatment data. Logistic regression models were used to obtain associations between variables, and to adjust for confounding effects. Analysis showed that adverse events during admission included acute pain crises in 249/94%, acute chest syndromes in 25/9.4% and strokes in 5/1.9% patients. Other outcomes were a greater than 2 hospitalizations per year 82/31.9%, more than 2 pain crises per year 145/54.7%, transfusion required during admission 72/27.2%, length of hospital stay more than 5 days 105/39.6% and death during hospitalization 13/4.9%. Multivariate logistic regression analysis revealed 21 factors with statistically significant associations. A reticulocyte count greater than 1.5 (OR 3.98, CI 1.48–10.69, P.006) and employment status (OR .31, CI .13-.75, P.009) were associated with more admissions per year. History of acute chest syndrome (OR 5.33, CI 1.7–16.77, P.004), reticulocyte count greater than 1.5 (OR 3.46, CI .91–13.11, P.067) and care provided by a nonhematologist (OR 5.04, CI 1.7–14.95, P.0035) were linked with more pain crises per year. Pain crises during admission were associated with HbSS disease (OR 9.31, CI 2.17–39.9, P.01) and out patient folate therapy(OR 6.23, CI 1.45–26.84, P.003). Patients with leukocytosis (OR 3.41, CI 1.2–9.67, P.02) and a higher serum glucose level (OR 7.54, CI 2.6–21.86, P.0002) were linked to more acute chest syndromes. Females (OR .1, CI .03–.37, P.0004) were at lower risk of having acute chest syndromes. Outpatient folate therapy (OR .07, CI .007–.69, P.02) was associated with lower numbers of acute neurological events. Patients with initial hemoglobin levels less than 7 g/dL (OR 1.99, CI 1–4, P.0007) and prolonged hospitalization (OR 7.06, CI 3.63–13.74, P.0001) frequently required transfusions. Variant diseases (OR .28, CI .13–.58, P.05) required fewer transfusions. Deaths during hospitalization were lower with folate therapy (OR .18, CI .05–.63, P.007) and a transfusion requirement during admission (OR 5.07, CI 1.45–17.64, P.01) predicted more deaths. HbSS patients (OR 2.52, CI 1.1–5.8, P.03), substance abusers (OR 2.93, CI 1.21–7.08, P.01), those requiring antihistamines during admission (OR 3.33, CI 1.38–8.03, P.007), or requiring more than 2 hospitalizations per year (OR 2.62, CI 1.26–5.43, P.009) had hospital stays longer than 5 days while in females odds were low for this outcome (OR .30, CI .15–.59, P.0005). In conclusion, simple tools like a complete history, physical examination, demographic and laboratory data can help clinicians and health care providers to gauge severity of the illness and deliver tailored management protocols targeting these “at risk” sickle cell disease patients.

scholarly journals Hematological Changes from Baseline in Children with Sickle Cell Disease Admitted for Acute Chest Syndrome Compared to Acute Pain Crisis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4909-4909
Author(s):  
Timothy Klouda ◽  
Nataly Apollonsky ◽  
Deepti Raybagkar ◽  
Bruce Bernstein
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Acute Pain ◽  
Neutrophil Count ◽  
Laboratory Data ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
History Of ◽  
Pain Crisis ◽  
Hematological Changes

Abstract Title: Hematological Changes from Baseline in Children with Sickle Cell Disease Admitted for Acute Chest Syndrome Compared to Acute Pain Crisis Authors: Timothy Klouda1, Deepti. Raybagkar2, Bruce Bernstein1, Nataly Apollonsky2, Institutes:1Pediatrics, St Christopher's Hospital for Children, Philadelphia, PA, United States, 2Hematology, St Christopher's Hospital for Children, Philadelphia, PA, United States, Introduction: Children with Sickle Cell Disease suffer from multiple complications including acute pain crisis (VOC) and acute chest syndrome (ACS). Nearly 30% of children with SCD have had one episode of ACS, with the incidence higher in early childhood. The proposed pathophysiology of ACS is thought to be multi-factorial, with pulmonary fat embolism or infectious etiology being identified in a large number of patients. Increased sickling due to hypoxemia or pain has been shown to place patients at risk for ACS development., Studies have shown an increase in inflammatory markers including leukocytes and neutrophils, along with a decreased hemoglobin in SCD children who developed ACS, but no studies to date have compared laboratory changes during the acute illness to their baseline values. We hypothesized that children with SCD who are admitted for ACS will have a larger decrease in hemoglobin from baseline and a higher increase in white blood cell count from baseline when compared to those admitted for an acute pain crisis. Methods: Through retrospective chart review of patients with SCD admitted to St.Christopher's Hospital for Children we identified 45 patients with ACS. Laboratory data collected on admission from chart review included SCD genotype, age, BMI, hemoglobin, white blood cell count, absolute neutrophil count, absolute eosinophil count, platelets, reticulocyte count, hemoglobin F, vital signs and medication history. All 45 children had laboratory data collected from an acute pain crisis that occurred during a different admission for comparison. Collected data was compared to baseline laboratory data, collected during routine visit at sickle cell clinic within 1 year of admission. Changes in laboratory data from baseline during admission for ACS were compared to changes during admission for uncomplicated VOC. Results: Children with SCD who were admitted or developed ACS during admission had a larger increase in leukocyte count (6.99 vs 4.18, p=0.027) and neutrophil count (6.3 vs 3.74, p=0.04) from baseline compared to those admitted for VOC alone. Patients with ACS development also had a larger decrease in platelets (-124.74 vs -56.21, p=.047) from baseline when compared to VOC admissions. There was no statistically significant change from baseline labs when comparing hemoglobin (p=0.10), eosinophil count (p=.382), reticulocyte count (p=0.754), AST (p=0.061) and ALT (p=0.082) in the ACS and VOC groups. Children with a history of 2 or more lifetime ACS were more likely to have OSA (p=0.021), 3 or more VOCs in the past year (p=0.002), and a history of splenectomy, but it was not found to be statistically significant (p=0.155) Conclusion: Children with SCD who developed or were admitted with ACS had a significant increase in leukocyte and neutrophil count from baseline, and a decrease in platelets when compared to VOC admissions. There was no significant change from baseline in hemoglobin, reticulocyte and eosinophils detected. Future larger and multi-center prospective studies need to be performed to confirm the various changes identified in hematological markers seen in ACS vs VOC. Disclosures No relevant conflicts of interest to declare.

Alloimmunization Does Not Modify the Clinical Profile of Sickle Cell Disease Patients from Salvador-Brazil

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4799-4799
Author(s):  
Angela Zanette ◽  
Karla O. Mota ◽  
Marilda Souza Goncalves ◽  
Laise Vilasboas Schettini ◽  
Lais Magalhaes Aguiar ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Clinical Outcomes ◽  
Sickle Cell ◽  
Laboratory Data ◽  
Clinical Profile ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Hemoglobin S ◽  
Hemoglobin C ◽  
Significant Difference

Abstract Introduction: The hemoglobinopathies are the most common monogenic disorders known. A mutation in the gene for β globin gave origin to hemoglobin S, an abnormal hemoglobin originated in Africa. Sickle cell disease (SCD) is characterized by the presence of hemoglobin S, which results in vasoocclusion episodes and hemolytic anemia throughout patients life. Vascular occlusion leads to acute events and progressive disabling organ damage. Sickle cell anemia is the homozygous state SS, while hemoglobinopathy SC is a doubly heterozygous state, where hemoglobin S occurs in combination with hemoglobin C. Brazil has a prominent African ancestry and SCD is highly prevalent in some regions of the country. In Bahia State, for example, neonatal screening data have shown that, from every 650 children born alive, one has SCD, mostly homozygous SS. Among other therapeutic measures, packed red blood cells (RBC) play a prominent role in SCD management. In situations such as acute chest syndrome (ACS), primary and secondary prevention of stroke, splenic or hepatic sequestration crisis, severe anemia, complicated pregnancy, isquemic organ damages and others, the transfusions may save lives. Although RBC may contribute to reduce morbidity and improve quality of life in SCD patients, there still are risks. Among other risk categories, alloimmunization may result from transfusions and occurs in 5 % to 50 % of SCD patients. It is still not known whether allosensibilization significantly affects the clinical outcomes in SCD. Objecive: The purpose of this study was to compare the clinical profile of multitransfused adult SCD patients who developed alloantibodies (ALO) to patients with the same disease, coming from the same population who did not become alloimmunized (non-ALO). Methods: This is a cross sectional study where medical records of SCD patients, referred to a reference center of Salvador, the capital of Bahia State, Brazil, were reviewed. Only SCD patients 18 years of age or older were included. They had received at least 3 RBC transfusions from 2004 to 2007, or had any alloantibody identified during this period. Patient characteristics, clinical findings, number of transfusions, frequency and specificity of alloantibodies, laboratory data, and the main clinical outcomes were reviewed. Results: a hundred and eight patients were included: 105 SS and 3 SC. The pre-transfusional RBC matching was done to ABH, D,C,c,E,e and Kell antigens. 56 patients developed alloantibodies (53 SS and 3 SC). Anti-E, anti-K, and anti-C were the most prevalent alloantibodies identified (39,3 %, 21,4 % and 16,1 %, respectively). Among the variables addressed in this study, age (higher in non-ALO, .041) and antiglobulin test positivity, more prevalente in ALO (.0001), depicted statistically significant difference. A few patients developed immune hemolysis, controlled successfully with corticosteroids. Alloimmunization was more prevalent among women, although no statistically significant difference was reached between ALO and non-ALO Other variables such as number of transfusions, hematological profile, biochemical data and complications such as stroke, leg ulcers, osteonecrosis, renal disease, abnormal cardiac features, and pulmonary hypertension did not show significant difference between both groups. Conclusion: his study shows that, although alloimmunization is a potential dangerous consequence of RBC transfusions, it did not modify the clinical profile of SCD alloimmunized patients. The concomitance of allosensibilization and autoantibodies in SCD leads to additional difficulties in the RBC matching for transfusion and may exacerbate hemolysis. In order to address autoimmunity in SCD, prospective studies with larger samples are needed.

Refining Th Predictive Value of Secretory Phospholipase A2 In Sickle Cell Disease Patients with Acute Chest Syndrome

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 846-846 ◽  
Author(s):  
Lori Styles ◽  
Carrie Greene Wager ◽  
Richard J. Labotka ◽  
Kim Smith-Whitley ◽  
Alexis A. Thompson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Phospholipase A2 ◽  
Sickle Cell ◽  
Predictive Value ◽  
Laboratory Data ◽  
Research Network ◽  
Acute Chest Syndrome ◽  
Secretory Phospholipase A2 ◽  
Cell Disease ◽  
Secretory Phospholipase

Abstract Abstract 846 Elevation of the serum level of secretory phospholipase A2 (sPLA2) has previously been reported to predict impending acute chest syndrome (ACS) in sickle cell disease (SCD) patients admitted with pain. The Sickle Cell Disease Clinical Research Network initiated the PROACTIVE Feasibility Study to 1) assess the feasibility of screening, randomizing and treating with simple transfusion eligible patients and 2) assess the predictive utility of sPLA2 in screening for imminent ACS, characterize the distribution of sPLA2 values in sickle cell patients hospitalized with pain, and define a cut-off point for predicting ACS to optimize its reliability, sensitivity and specificity in predicting ACS. All SCD patients (hemoglobin SS, SC and SBeta-thalassemia) admitted for pain at a participating center were to be screened for eligibility; patients with a diagnosis of ACS at entry were not eligible. sPLA2 levels were drawn daily on consenting patients for up to three days during the admission. All patients had at least one CXR (mandated at 72 hr if not done for clinical indications) during the course of their hospital stay to determine if they had developed a new infiltrate, considered diagnostic for ACS. Patients who developed T>38°C, a sPLA2 level > 100ng/ml and had a normal CXR were eligible for randomization to observation or simple transfusion; the remaining patients were followed in an Observation arm. Of 421 patients potentially eligible for screening, 238 were enrolled in the study with 10 of these patients randomized (4 to transfusion 6 to standard care). Of these, 203 patients had from one to three sPLA2 levels drawn prior to an ACS diagnosis or did not develop ACS; if transfused, they received blood only after a diagnosis of ACS was made. Twenty-two of these patients (11%) developed ACS. Analysis of the maximum sPLA2 levels prior to ACS diagnosis revealed that a threshold of 45 ng/ml was the most accurate level to predict ACS (accuracy: 73%, sensitivity: 73%, specificity: 73%). The positive predictive value (PPV: 25%) was low due to the relative infrequency of ACS events. When sPLA2 levels were analyzed in children versus adults, sPLA2 was more accurate for adults in predicting ACS with a level of 65ng/ml having accuracy: 88%, sensitivity: 44%, specificity: 95%, PPV: 57%. The addition of a requirement for fever did not improve the accuracy of sPLA2 in either adults or children. Further analysis of sPLA2 levels with various clinical and laboratory data is ongoing to improve the PPV of sPLA2. These results indicate that sPLA2 can predict ACS with good sensitivity, but may require additional parameters to be useful in clinical management of SCD patients admitted with pain and at risk for ACS. Supported by the NHLBI. Disclosures: Labotka: HemaQuest Pharmaceuticals, Inc: Research Funding.

Five years of experience with hydroxyurea in children and young adults with sickle cell disease

Blood ◽  
2001 ◽  
Vol 97 (11) ◽  
pp. 3628-3632 ◽  
Author(s):  
Alina Ferster ◽  
Parvine Tahriri ◽  
Christiane Vermylen ◽  
Geneviève Sturbois ◽  
Francis Corazza ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Laboratory Data ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Significant Difference ◽  
History Of ◽  
Ischemic Attack

The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; clinical and laboratory data have been obtained for 82 patients at 1 year, 61 at 2 years, 44 at 3 years, 33 at 4 years, and 22 after 5 years. On HU, the number of hospitalizations and days hospitalized dropped significantly. Analysis of the 22 patients with a minimum of 5 years of follow-up confirm a significant difference in the number of hospitalizations (P = .0002) and days in the hospital (P < .01), throughout the treatment when compared to prior to HU therapy. The probabilities of not experiencing any event or any vaso-occlusive crisis requiring hospitalization during the 5 years of treatment were, respectively, 47% and 55%. On HU, the rate per 100 patient-years of severe events was estimated to be 3.5% for acute chest syndrome, 1.2% for aplastic crisis, 0.4% for splenic sequestration; it was 0% for the 9 patients with a history of stroke or transient ischemic attack followed for an average of 4 years. No important adverse effect occurred. Long-term chronic treatment with HU for patients with SCD appears feasible, effective, and devoid of any major toxicity; in patients with a history of stroke, HU may be a valid alternative to chronic transfusion support.

scholarly journals Procalcitonin to Reduce Antibiotic Exposure during Acute Chest Syndrome in Adult Patients with Sickle-Cell Disease

2020 ◽  
Vol 9 (11) ◽  
pp. 3718
Author(s):  
Keyvan Razazi ◽  
Ségolène Gendreau ◽  
Elise Cuquemelle ◽  
Mehdi Khellaf ◽  
Constance Guillaud ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Bacterial Infection ◽  
Sickle Cell ◽  
Major Complication ◽  
Adverse Outcomes ◽  
Acute Chest Syndrome ◽  
Antibiotic Exposure ◽  
Cell Disease ◽  
Intervention Phase ◽  
Entire Cohort

Acute chest syndrome (ACS) is a major complication of sickle-cell disease. Bacterial infection is one cause of ACS, so current guidelines recommend the routine use of antibiotics. We performed a prospective before–after study in medical wards and an intensive-care unit (ICU). During the control phase, clinicians were blinded to procalcitonin concentration results. We built an algorithm using the obtained measurements to hasten antibiotic cessation after three days of treatment if bacterial infection was not documented, and procalcitonin concentrations were all <0.5 μg/L. During the intervention period, the procalcitonin algorithm was suggested to physicians as a guide for antibiotic therapy. The primary endpoint was the number of days alive without antibiotics at Day 21. One-hundred patients were analyzed (103 ACS episodes, 60 in intervention phase). Possible or proven lung infection was diagnosed during 13% of all ACS episodes. The number of days alive without antibiotics at Day 21 was higher during the intervention phase: 15 [14–18] vs. 13 [13,14] days (p = 0.001). More patients had a short (≤3 days) antibiotic course during intervention phase: 31% vs 9% (p = 0.01). There was neither infection relapse nor pulmonary superinfection in the entire cohort. A procalcitonin-guided strategy to prescribe antibiotics in patients with ACS may reduce antibiotic exposure with no apparent adverse outcomes.

Clinical and Laboratory Predictors for Renal Damage in Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3252-3252
Author(s):  
Santosh L Saraf ◽  
Robert Molokie ◽  
Johara Hassan ◽  
Michel Gowhari ◽  
James Lash ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Reticulocyte Count ◽  
Female Gender ◽  
P Value ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Indirect Bilirubin ◽  
Laboratory Variables

Abstract Abstract 3252 Renal failure is an independent marker for developing other forms of chronic organ damage and for early mortality in sickle cell disease (SCD). We conducted a retrospective, cross-sectional chart review of 292 adults with SCD (type SS or S-beta thal) treated at the University of Illinois Medical Center to assess the prevalence and factors related to kidney damage. Data was recorded from a clinic visit at least four weeks from a vaso-occlusive pain episode or red blood cell transfusion. The glomerular filtration rate (GFR) was calculated using the modification of diet in renal disease formula. Hemoglobinuria was defined by dipstick urinalysis showing trace, small, or moderate blood and <2 RBC/high power field. Urine albumin to creatinine ratios of 30 to 300 mg/g and >300 mg/g were categorized as microalbuminuria and macroalbuminuria, respectively. The median age was 33 years and 46% of patients were on hydroxyurea. We observed microalbuminuria in 41%, macroalbuminuria in 20%, hemoglobinuria in 41% and GFR <90 mL/min in 20% of adults with SCD. Univariate associations with GFR <90 mL/min are summarized in Table 1. By logistic regression, macroalbuminuria (OR 7.5, 95% CI: 2.5–22.2; p<0.0001) and age (OR 1.11, 95% CI: 1.06–1.16; p <0.0001) were independent predictors of GFR <90 mL/min (r2 = 0.23). Given the strong correlation of macroalbuminuria with GFR <90 mL/min, we explored factors related to degree of albuminuria. Univariate associations with degree of albuminuria are shown in Table 2. Logistic regression showed that independent predictors for macroalbuminuria were the presence of hemoglobinuria (OR 93.7, 95% CI: 15.2–576.5; p<0.0001) and age (OR 1.07, 95% CI: 1.01–1.14; p=0.03) (r2=0.28, p<0.0001). We further explored predictors of hemoglobinuria given its independent association with macroalbuminuria. By logistic regression, the strongest predictor of hemoglobinuria was the natural log LDH (OR 32.4; 95% CI: 8.4–124.9; p<0.0001) (r2=0.22), but other markers of hemolysis including higher absolute reticulocyte count, greater indirect bilirubin concentration and lower hemoglobin concentration were also associated with hemoglobinuria in univariate analyses. In summary, increasing age and macroalbuminuria were independent factors associated with GFR < 90mL/min in this cohort of adults with SCD, and intravascular hemolysis as reflected in hemoglobin-positive urine dipstick with negative microscopy was associated with macroalbuminuria. Further research is needed to determine if measures to decrease intravascular hemolysis and to prevent the development of macroalbuminuria can preserve renal function in patients with SCD. Investigation is also needed to identify genomic and genetic markers that put patients at risk for kidney disease and might serve as targets for preventive and therapeutic interventions. Table 1: Correlation of GFR to clinical and laboratory variables. Variable N >90 N <90 p-value Age (years) 234 30 (25–39) 58 45 (37–54) <0.0001 Female gender 234 141 (60%) 58 38 (65%) 0.63 MAP 231 86 (90–93) 58 91 (86–98) <0.0001 HU therapy 110 48 (44%) 30 16 (53%) 0.35 Hemoglobin (g/dL) 234 8.9 (7.9–10) 58 8.1 (7.4–8.9) <0.0001 LDH (u/L) 146 309 (235–425) 41 375 (251–481) 0.11 Absolute Reticulocyte Count (×103/μL) 111 332 (234–444) 29 302 (197–368) 0.001 Hgb F (%) 218 5.5 (2.9–9.8) 52 5.5 (2.5–9.8) 0.98 Albuminuria: Microalbuminuria Macroalbuminuria 112 46 (41%) 30 11 (36.7%) 0.001 15 (13%) 13 (43.4%) Table 2: Correlation of Albuminuria to clinical and laboratory variables. Variable N Normal N Micro-albuminuria N Macro-albuminuria p-value Age (years) 57 32 (26–42) 58 38 (28–48) 28 35 (27–45) 0.20 Female gender 57 43 (75%) 58 34 (59%) 28 18 (64%) 0.16 MAP (mmHg) 56 86 (80–97) 58 88 (84–92) 28 91 (84–98) 0.24 HU therapy 56 24 (42.9%) 57 24 (42.1%) 28 17 (60.7%) 0.22 Hemoglobin (g/dL) 57 8.9 (8.1–10.3) 58 8.1 (7.5–9.4) 28 8.5 (6.9–9.4) 0.008 LDH (u/L) 54 270 (212–358) 49 363 (251–434) 27 377 (355–488) <0.0001 Indirect bilirubin (mg/dL) 56 1.7 (1.2–2.5) 57 2.4 (1.4–3.3) 28 2.0 (1.3–4.3) 0.03 Absolute reticulocyte count (×103/μL) 57 256 (213–399) 56 332 (243–448) 28 369 (276–466) 0.06 Hgb F (%) 52 6.6 (2.7–9.7) 56 5.1 (2.8–11.7) 26 7.8 (3.7–13) 0.54 Hemoglobinuria 53 3 (5.7%) 54 29 (53.7%) 26 22 (84.6%) <0.0001 Disclosures: No relevant conflicts of interest to declare.

scholarly journals Heme oxygenase-1 gene promoter polymorphism is associated with reduced incidence of acute chest syndrome among children with sickle cell disease

Blood ◽  
2012 ◽  
Vol 120 (18) ◽  
pp. 3822-3828 ◽  
Author(s):  
Christopher J. Bean ◽  
Sheree L. Boulet ◽  
Dorothy Ellingsen ◽  
Meredith E. Pyle ◽  
Emily A. Barron-Casella ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Heme Oxygenase ◽  
Sickle Cell ◽  
Globin Gene ◽  
Fetal Hemoglobin ◽  
Promoter Polymorphism ◽  
Adverse Outcomes ◽  
Acute Chest Syndrome ◽  
Heme Oxygenase 1 ◽  
Cell Disease

Abstract Sickle cell disease is a common hemolytic disorder with a broad range of complications, including vaso-occlusive episodes, acute chest syndrome (ACS), pain, and stroke. Heme oxygenase-1 (gene HMOX1; protein HO-1) is the inducible, rate-limiting enzyme in the catabolism of heme and might attenuate the severity of outcomes from vaso-occlusive and hemolytic crises. A (GT)n dinucleotide repeat located in the promoter region of the HMOX1 gene is highly polymorphic, with long repeat lengths linked to decreased activity and inducibility. We examined this polymorphism to test the hypothesis that short alleles are associated with a decreased risk of adverse outcomes (hospitalization for pain or ACS) among a cohort of 942 children with sickle cell disease. Allele lengths varied from 13 to 45 repeats and showed a trimodal distribution. Compared with children with longer allele lengths, children with 2 shorter alleles (4%; ≤ 25 repeats) had lower rates of hospitalization for ACS (incidence rate ratio 0.28, 95% confidence interval, 0.10-0.81), after adjusting for sex, age, asthma, percentage of fetal hemoglobin, and α-globin gene deletion. No relationship was identified between allele lengths and pain rate. We provide evidence that genetic variation in HMOX1 is associated with decreased rates of hospitalization for ACS, but not pain. This study is registered at www.clinicaltrials.gov as #NCT00072761.

scholarly journals A Pilot Study of Eptifibatide for Treatment of Acute Pain Episodes in Sickle Cell Disease.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2102-2102
Author(s):  
Payal C Desai ◽  
Julia Brittain ◽  
Susan Jones ◽  
Adam McDonald ◽  
Douglas R Wilson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Board Of Directors ◽  
Sickle Cell ◽  
Acute Pain ◽  
Research Funding ◽  
Point Estimate ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Opioid Use ◽  
Advisory Committees

Abstract Abstract 2102 Background: Despite the abundant laboratory evidence of platelet activation and inflammation in sickle cell disease (SCD), the contribution of these changes to the pathogenesis of SCD remains uncertain. Patients with SCD exhibit increased platelet activation in the non-crisis, “steady state,” and further increases with acute pain episodes. In addition, levels of the inflammatory mediator, CD40 ligand (CD40L) are increased in the plasma and significantly reduced in the platelets of SCD patients compared to healthy individuals. CD40L may contribute to the pathogenesis of acute pain episodes. Despite an improved understanding of the pathophysiology of SCD, the treatment of acute pain episodes is supportive. We performed a randomized, placebo-controlled study to evaluate the safety and efficacy of eptifibatide, a synthetic peptide inhibitor of the glycoprotein (GP) IIb/IIIa receptor, in patients with SCD during acute painful episodes. Methods: In this single site placebo-controlled trial, eligible patients admitted for acute painful episodes received eptifibatide (two 180 mg/kg boluses 10 minutes apart, followed by a continuous infusion at 2 mg/kg/min for 6 hours) or placebo at a ratio of 2:1. The Post-Treatment Phase lasted for up to 7 days or until resolution of the crisis, whichever was shorter, but no less than 24 hours after discontinuation of infusion. The Follow-up Phase included safety evaluations obtained 14 to 17 days and 28 to 35 days after discontinuation of infusion. The primary outcomes were major bleeding episodes and the largest observed decrease in platelet count during the study. We also evaluated the effect of eptifibatide on the duration of acute pain episodes, pain intensity, duration of hospitalization, total opioid use and acute chest syndrome. Results: Thirteen patients (SS - 10, Sb0 - 2, SC - 1) were randomized to receive either eptifibatide (N=9; 6 females; median age - 25 years) or placebo (N=4; 3 females; median age - 31 years). One patient in the eptifibatide arm withdrew consent following completion of study drug infusion and 1 patient in the placebo arm was withdrawn early because she did not meet eligibility criteria. In the intent-to-treat analysis, there were no major bleeding episodes in either group (point estimate of difference in eptifibatide vs. placebo proportion: 0.0, 95% CI; −0.60, 0.37).There was one minor bleeding episode in a patient on the eptifibatide arm (point estimate of difference in eptifibatide vs. placebo proportion: 0.11, 95% CI: −0.502, 0.494). There was a trend for the largest decrease in platelet count to be greater in the eptifibatide arm compared to the placebo arm, although the difference was not statistically significant (Hodges-Lehman estimate of location shift for eptifibatide vs. placebo: −82, 95% CI; −281, 54). There was no significant difference in the proportion of patients with thrombocytopenia between the treatment groups (point estimate of difference in eptifibatide vs. placebo proportion: 0.11, 95% CI: −0.587, 0.495). The median time to discharge and the median time to crisis resolution were 3.0 days for both treatment arms. The median total opioid use was 400.2 morphine equivalents (ME) for the eptifibatide group and 1471 ME for the placebo group (Hodges-Lehman estimate of location shift for eptifibatide vs. placebo: −65.8, 95% CI: −2519, 1700). There was one episode of acute chest syndrome in each treatment arm. Conclusions: In this small study of SCD patients hospitalized with acute painful episodes, eptifibatide appeared to be safe, but did not improve the times to crisis resolution or hospital discharge. Eptifibatide was associated with a reduced requirement for opioid analgesics, although the difference was not statistically significant. Clinicaltrials.gov Identifier: NCT00834899. Disclosures: Parise: BD: Consultancy; Biogen-Idec: Consultancy; NIH: Research Funding; AHA: Research Funding; SCDAC-NIH: Membership on an entity's Board of Directors or advisory committees; BRI Milwaukee: Membership on an entity's Board of Directors or advisory committees. Ataga:Pfizer: Consultancy; HemaQuest Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adventrx Pharmaceuticals: Consultancy. Off Label Use: Eptifibatide, a glycoprotein IIb/IIIa inhibitor, was evaluated as treatment for acute pain episodes in patients with sickle cell disease.

scholarly journals Hemolytic, Vaso-Occlusive and Renal Complications of SCD: Report from the Central Missouri Cohort

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1091-1091
Author(s):  
Lila Wahidi Nolan ◽  
Yilin Yoshida ◽  
Emily Coberly ◽  
Bindu Kanathezhath Sathi
Keyword(s):  
African American ◽  
Sickle Cell Disease ◽  
Renal Insufficiency ◽  
Sickle Cell ◽  
Laboratory Data ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
University Of Missouri ◽  
Persistent Proteinuria ◽  
Renal Complications

Abstract Background The clinical phenotype and complications of sickle cell disease (SCD) are heterogeneous and disease outcomes are influenced by both genetic and non-genetic factors, including geography, socioeconomic and educational status and access to health care. These factors serve a role in the quality of life and overall survival in the SCD population. Prior studies have sought to characterize the genotype-phenotype relationship and geographic clustering of SCD with distinct clinical differences found between the African and Asian SCD subtypes. The Central Missouri SCD Cohort (MU-SCD Cohort) has a heterogeneous population of SCD patients who seek medical care from University of Missouri. The clinical characteristics and frequency of SCD-related complications in this group have not yet been defined. This is a retrospective cohort analysis of patients HbSS, HbSC, and HbS/b-thalassemia in central Missouri, ranging in age from the first through the sixth decade of life. We hypothesize that SCD patients from central Missouri, with its mix of African American, Congolese, Nigerian, Kenyan, Southeast Asian and other refugee populations, will have clinical complications distinct from the previously described North American Sickle Cell Disease series and needs further characterization. Objective To survey the SCD phenotype by evaluating complications of patients in the MU-Sickle Cell Disease Cohort. Methods We retrospectively reviewed clinical and laboratory data for pediatric and adult SCD patients who were treated at the University of Missouri between 2002 to 2018. Prevalence of major vaso-occlusive, hemolytic and renal complications by decade was estimated. Results A total of 81 patients were reviewed, with five excluded due to insufficient clinical data. The sample size for prevalence estimation was 76, 61, 30, 14 and 8 for first to fifth decade, respectively. In this cohort, 60.5% were male with average age of 21.2 years. Genotypes represented included 52.6% HbSS, 38.2% HbSC, and 7.9% HbS/b-thalassemia. A total of 94.7% of patients identified as African American. Clinical features of vaso-occlusive complications predominated in the first two decades of life. The frequency of acute chest syndrome for patients ages ≤10 years and 11-20 years of age were 23.7% and 21.3%, respectively (Table 1). Seven children (9.2%) developed overt stroke by age 10 years. Greater than one vaso-occlusive pain crisis occurred in 46% of patients in the first decade of life and thereafter declined with age (Figure 1). In contrast, the MU-SCD Cohort exhibited increasing frequency of hemolytic complications with advancing age. The peak prevalence of pulmonary hypertension occurred between the ages of 21-30 years (13.3%). In congruence, only 4% of patients aged ≤10 years were diagnosed with gallstones requiring cholecystectomy, which increased to 57.1% at age 31-40 years. Reticulocytopenia was noted in the fourth decade with further decline in the fifth decade of life (Figure 2). Renal evaluation revealed an average estimated glomerular filtration rate (eGFR) of 149.9 ± 43 in patients ≤10 years, with progressive decline to 117.3 ± 25 in SCD patients aged 41-50 years (Figure 3). The average serum creatinine demonstrated an increasing trend with advancing age. There was a prevalence of persistent proteinuria in patients older than 11 years. Disease modifying agents were assessed, in which only 21% of patients ≤10 years, 25% of patients aged 11-20 years, and 15.8% of patients aged 21-30 years received therapy with hydroxyurea (Table 1). The use of exchange transfusion or packed red blood cell (pRBC) transfusion for anemia was predominant in SCD patients aged ≤20 years. Conclusions This is the first report describing prevalence of SCD-related complications in the MU-SCD Cohort. We identified this population to have an increasing frequency of hemolytic complications and sickle cell nephropathy with advancing age. Onset of persistent proteinuria occurred in the second decade of life, followed by renal insufficiency or end stage renal disease in subsequent decades. As previously demonstrated in the Cooperative Study of Sickle Cell Disease and the Jamaican SCD Cohort study, renal insufficiency was a significant risk factor for early mortality. Further studies are required for identification of biomarkers and institution of early intervention strategies to prevent end-organ damage and decrease mortality in SCD. Disclosures No relevant conflicts of interest to declare.

Detection of Pulmonary Platelet Thrombi in Acute Chest Syndrome in Sickle Cell Disease: Novel Findings in an Autopsy Case Series

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4093-4093
Author(s):  
Ciprian Anea ◽  
Amidat Adeyemi ◽  
Itia Lee ◽  
Kavita Natrajan ◽  
Greer Falls ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Medical Record ◽  
Sickle Cell ◽  
Acute Pain ◽  
Case Series ◽  
Acute Chest Syndrome ◽  
Autopsy Case ◽  
Cell Disease ◽  
Autopsy Report ◽  
Platelet Thrombi

Abstract Introduction: Acute chest syndrome (ACS) is one of the leading causes of death in patients with sickle cell disease (SCD). The pulmonary manifestations of ACS often appear suddenly and can progress rapidly to fatality. There are multiple identified etiologies associated with the development of ACS including infection, fat or pulmonary embolism, and opiate intoxication. The cause cannot be attributed to a single agent in most cases and if so, is likely determined authoritatively only at autopsy. One potential commonality, however, is that an acute pain event usually precedes the onset of ACS. Although, clearly there remains much to be learned, acute pain events are one of the better characterized aspects of SCD. In most cases, there is an increase in inflammatory markers and indicators of endothelial dysfunction. Platelet activation increases during pain events, as do platelet-derived markers of inflammation. In fact, platelets are emerging as potentially pivotal contributors to the overall inflammatory state of patients. Although patients at steady state typically have high platelet counts, platelet count decrease during pain events. Overt thrombocytopenia has been noted in ACS and is usually attributed to platelet sequestration in the vasculature. Thus, we considered the platelet to be a potential contributor to pulmonary pathology in cases of ACS. To lend support to our hypothesis, we performed an autopsy study of pulmonary histology in patients with SCD and ACS. Objective: To interrogate whether platelet thrombi were significant findings in lungs of patients who died concurrent with ACS. Methods: We performed an autopsy case series. Ten autopsies and corresponding medical records from patients with SCD were selected from those conducted at Georgia Regents Medical Center from 1997-2013. From the medical record or autopsy report, all cases had ACS listed concurrent with or as the primary cause of death. No pediatric cases were included in the series (age range 18-45 years old). Paraffin-embedded lung samples were obtained from all cases. Standard immunohistochemical techniques were used to detect platelet thrombi. A comprehensive perimortem medical record was available for 8 patients. A genotype of either SS or S/β0-Thalassemia was acceptable. Two cases were recorded with an S/β0-Thalassemia genotype, the rest were listed as SS. Results: Profound arterial platelet thrombi were detected in 3 out of the 10 cases. In these 3 positive cases, arterial vessels of all size (large arterial vessels to arterioles) were completely occluded by platelets. All platelet positive cases had a genotype of SS. In 2 of the 3 platelet thrombi positive cases, none of the established causes of ACS were noted in the medical record or autopsy report. In 1 platelet positive case, lipid-laden macrophages and ascites were noted at autopsy. Extensive pulmonary artery remodeling was noted in all 10 cases regardless of age or medical history. Conclusions: This case series illustrates that platelet- rich arterial thrombi are present in potentially up to 33 percent of fatal cases of ACS. These data are thus suggestive of a novel pathological role for platelets in ACS. Disclosures Kutlar: NIH/NIMHD: Research Funding.

Sign in / Sign up

Export Citation Format

Share Document