Prediction of Adverse Outcomes in Children with Sickle Cell Disease

2000 ◽  
Vol 342 (21) ◽  
pp. 1612-1613 ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 3718
Author(s):  
Keyvan Razazi ◽  
Ségolène Gendreau ◽  
Elise Cuquemelle ◽  
Mehdi Khellaf ◽  
Constance Guillaud ◽  
...  

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.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3197-3197
Author(s):  
Fahd Rahman ◽  
Roy N. Gay ◽  
Samir K. Ballas ◽  
Juan C. Zubieta ◽  
Zekarias Berhane ◽  
...  

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.


2014 ◽  
Vol 94 (2) ◽  
pp. 157-161 ◽  
Author(s):  
Inês Vaz Silva ◽  
Ana Filipa Reis ◽  
Maria João Palaré ◽  
Anabela Ferrão ◽  
Teresa Rodrigues ◽  
...  

2000 ◽  
Vol 3 (5) ◽  
pp. 45-46
Author(s):  
R. Sundarum ◽  
D. R. Neuspiel

2000 ◽  
Vol 342 (2) ◽  
pp. 83-89 ◽  
Author(s):  
Scott T. Miller ◽  
Lynn A. Sleeper ◽  
Charles H. Pegelow ◽  
Laura E. Enos ◽  
Winfred C. Wang ◽  
...  

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 ◽  
...  

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.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3247-3247
Author(s):  
Shangari Vijenthira ◽  
Jenny Nguyen ◽  
Donald R. Branch ◽  
Gwen Clarke ◽  
Richard Ward ◽  
...  

Abstract BACKGROUND: RBC transfusions play a role in organ- and life-preservation for patients with sickle cell disease (SCD). These in turn are subject to higher-fidelity matches to offset the particularly high condition-specific odds of seroconversion events. Adverse outcomes may be as severe as hyperhemolysis, and/or undertransfusion from the scarcity of suitable antigen profiles. In a woman with HbSS SCD and multiple alloantibodies (-K, -E, Jkb-, -Fya, -S), correspondingly antigen-negative units had nevertheless become invariably crossmatch-incompatible (iXM) owing to the development of an antibody to -Kna, a high-prevalence (but clinically insignificant) target antigen on CR1/CD35. Genotyping ruled out the absence of other rare antigen-negative states at risk of high-frequency antibodies (hrB, hrS, Joa, U). Due to uncertainties on the in-vivo effects of iXM RBC in this patient, the infeasibility of sourcing of complete antigen matches, and challenges ruling out other emerging (and potentially more harmful) antibodies, a prolonged period of transfusion-avoidance ensued. This deferral correlated with progression of SCD-associated dilated non-ischemic cardiomyopathy and restrictive interstitial pulmonary fibrosis. In order to qualify Kna-unselected iXM that were otherwise target-negative for her clinically significant antibodies, a monocyte monolayer assay (MMA) approach was taken to identify, transfuse, and maintain a personalized roster of RBCs for monthly top-up transfusions. METHODS: Selected donors (group O, ±D, ±C, E- K- Jkb- Fya-) were assessed at least once in the MMA by a 4:1 (patient serum) to (candidate unit RBC) ratio, incubated at 37°C for 1 hour. The total number of RBCs phagocytosed in 100 patient monocytes was reported as a phagocytic index (PI), with a significance cut-off of 5 (or lower, if rosettes were noted, and/or a noticeably more incompatible [≥3+] crossmatch was observed compared with other prepared units). Antibody screens (automated solid phase) and manual serologic crossmatches (by both conventional tube- and gel microtube- technique) were performed at each RBC sitting. Interval/pre-RBC tests incorporated hemolytic markers and hemoglobin electrophoresis (HbS%). RESULTS: Of 26 donors examined in 8 MMA arrays over 3 years, 10 were excluded due to high PI (median 6 [range 3.3-54]) and/or differential iXM. Of the remaining 16 (PI 0.9 [0.2-4.5]), RBCs have been transfused from 13, with 56 units [u] (51 fresh/5 frozen-deglycerolized) given in 27 sittings over 113 weeks. Most have donated &gt;1u (7/13 with ≥1u transfused to this recipient, median 4u [range 1-8]). The HbS% fell from 91% to 45% [39-48] (median [IQR], pre-3rd-to-27th sitting) with improved hemolytic markers and freedom from overt incompatibility reactions. A minor allergic reaction on the 1 st sitting (with 2u from the same donor) led to a default mitigation strategy of supernatant reduction and antihistamine-premedication thereafter. All sittings (including 5u from the index donor) were reaction-free until a 2 nd minor allergic reaction 2 years later (associated with 2 other donors). Improvements occurred in cardiac function, performance status, pain, and quality of life over the 1 st 20 months of transfusions, though an acute pulmonary embolism and progressive iron overload have reversed the initial gains. Of 11 donors re-examined in 3 repeat MMA (29-112 weeks later), 10 were re-qualified; the 1 st donor was excluded due to an unexplained PI surge (2.5 to 5.6). Host tolerance otherwise increased to most re-qualified donors in a PI downtrend over time (in 8/10, median 1 st PI 2.1, vs median 2 nd PI 1.0, P=0.006 [paired, 2-sided t-test]). A new sensitization (anti-Cob) was noted before the 14 th sitting, with donor genotypes imputing and disqualifying donor 9. CONCLUSIONS: An MMA-vetted pipeline of RBCs in a once-prohibitively alloimmunized patient with SCD has re-enabled transfusion care by the coordinated efforts of the national blood collector with its donors, its MMA laboratory, and the supervising hospital transfusion service. An unexpected finding in repeated exposures to a limited number of donors was increased tolerance. When the viability of transfusions is restored in SCD, so too are opportunities in disease control and in transfusion-requiring curative treatment options. The number of similarly constrained patients, and the scalability of this innovation, remain to be determined. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2008 ◽  
Vol 111 (2) ◽  
pp. 479-479
Author(s):  
Ellis J. Neufeld

Quinn and colleagues evaluate 3 early severity predictors defined from the Cooperative Study of Sickle Cell Disease in an independent prospective newborn cohort and find them unrelated to long-term adverse outcomes. Despite methodologic differences between the studies, the result calls into question the use of these markers for identification of transplant candidates.


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