Serum Levels of Substance P Are Elevated in Patients With Sickle Cell Disease and Increase Further During Vaso-Occlusive Crisis

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3148-3151 ◽  
Author(s):  
Lisa A. Michaels ◽  
Kwaku Ohene-Frempong ◽  
Huaqing Zhao ◽  
Steven D. Douglas
Keyword(s):  
Sickle Cell Disease ◽  
Substance P ◽  
Sickle Cell ◽  
Therapeutic Potential ◽  
Serum Levels ◽  
Control Group ◽  
Cell Disease ◽  
Neurokinin Receptor ◽  
Pain Crisis ◽  
American Society

As a mediator of neurogenic inflammation and pain, we hypothesized that levels of the neuropeptide Substance P (SP) would be elevated in patients with sickle cell disease (SCD) with vaso-occlusive pain crisis. SP is a known stimulator of tumor necrosis factor- (TNF-) release and a promoter of interleukin-8 (IL-8), which are reported to be increased in SCD. These cytokines enhance adhesion of leukocytes to endothelium and may play a role in vaso-occlusive events. Serum levels of IL-8, TNF, and SP were studied in three groups of children aged 2 to 18 years: 30 well children with SCD, 21 with SCD in pain crisis, and 20 healthy age-matched controls. Serum levels of SP were elevated in all SCD patients and were highest in patients in pain crisis. The percentage of sera with detectable levels of IL-8 (>5.0 pmol/L) was increased in SCD patients as compared with the control group. IL-8 levels were similar for well SCD patients and those with pain. TNF levels were not significantly different among the three groups. In three children with SCD, SP was measured at baseline and again during pain crisis. In each case, serum levels during pain crisis were higher than they were when the patient was well. We conclude that levels of SP are high in patients with SCD and increase during pain crisis. These results imply that SP plays a prominent role in the pain and inflammation of SCD and may be a measurable laboratory marker of vaso-occlusive crisis. We speculate that neurokinin receptor antagonists may have a therapeutic potential in the treatment of crisis pain. © 1998 by The American Society of Hematology.

Serum Levels of Substance P Are Elevated in Patients With Sickle Cell Disease and Increase Further During Vaso-Occlusive Crisis

Blood ◽  
1998 ◽  
Vol 92 (9) ◽  
pp. 3148-3151 ◽  
Author(s):  
Lisa A. Michaels ◽  
Kwaku Ohene-Frempong ◽  
Huaqing Zhao ◽  
Steven D. Douglas
Keyword(s):  
Sickle Cell Disease ◽  
Substance P ◽  
Sickle Cell ◽  
Therapeutic Potential ◽  
Serum Levels ◽  
Control Group ◽  
Cell Disease ◽  
Neurokinin Receptor ◽  
Pain Crisis ◽  
American Society

Abstract As a mediator of neurogenic inflammation and pain, we hypothesized that levels of the neuropeptide Substance P (SP) would be elevated in patients with sickle cell disease (SCD) with vaso-occlusive pain crisis. SP is a known stimulator of tumor necrosis factor- (TNF-) release and a promoter of interleukin-8 (IL-8), which are reported to be increased in SCD. These cytokines enhance adhesion of leukocytes to endothelium and may play a role in vaso-occlusive events. Serum levels of IL-8, TNF, and SP were studied in three groups of children aged 2 to 18 years: 30 well children with SCD, 21 with SCD in pain crisis, and 20 healthy age-matched controls. Serum levels of SP were elevated in all SCD patients and were highest in patients in pain crisis. The percentage of sera with detectable levels of IL-8 (>5.0 pmol/L) was increased in SCD patients as compared with the control group. IL-8 levels were similar for well SCD patients and those with pain. TNF levels were not significantly different among the three groups. In three children with SCD, SP was measured at baseline and again during pain crisis. In each case, serum levels during pain crisis were higher than they were when the patient was well. We conclude that levels of SP are high in patients with SCD and increase during pain crisis. These results imply that SP plays a prominent role in the pain and inflammation of SCD and may be a measurable laboratory marker of vaso-occlusive crisis. We speculate that neurokinin receptor antagonists may have a therapeutic potential in the treatment of crisis pain. © 1998 by The American Society of Hematology.

scholarly journals The impact of proteinuria on serum levels of trace elements in sickle cell disease patients

2015 ◽  
Vol 3 (3) ◽  
pp. 16-20
Author(s):  
MA Emokpae ◽  
AD Tijani
Keyword(s):  
Trace Metals ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Levels ◽  
Control Group ◽  
Cell Disease ◽  
Urine Protein ◽  
Iron And Zinc ◽  
The Impact ◽  
Sulphosalicylic Acid

Micronutrient deficiency has been recognized as a serious complication in sickle cell disease (SCD) patients and the impact of proteinuria on the levels of trace metals has not been evaluated in our setting. This study evaluates the impact of proteinuria on serum levels of copper, iron, zinc and magnesium in SCD patients. Serum Iron, Zinc, copper and magnesium were assayed by colorimet-ric methods. Urine protein was initially assayed using urinalysis dipstick method while those that were positive for macro-albuminuria were re-evaluated using sulphosalicylic acid colorimetric tech-nique. Out of the 100 SCD patients, 29 had macro-albuminuria while 71were negative for macro-albuminuria. Serum levels of copper in SCD patients was higher (p˂0.001) than that in controls, while serum levels of zinc, iron and magnesium were lower (p˂0.001) in SCD patients compared to that of the control group. The levels of copper (p<0.02), iron (p<0.05) and magnesium (p<0.05) were significantly lower in SCD patients with proteinuria while Zinc (p<0.02) was significantly higher in SCD patients with proteinuria compared to those without proteinuria. Proteinuria corre-lated negatively (p<0.001) with copper while magnesium, iron and zinc correlated positively with proteinuria in SCD patients. Proteinuria in SCD patients impacted on the levels of measured trace metals and magnesium. The levels of these metals may be routinely determined in this group of patients.Keywords: Proteinuria, sickle cell disease, trace metals, magnesium, copper

Impact of Intravenous Opioid Shortage on Managing Pain Crisis in Sickle Cell Disease

2021 ◽  
pp. 106002802110245
Author(s):  
Jin Han ◽  
Santosh L. Saraf ◽  
Michel Gowhari ◽  
Faiz Ahmed Hussain ◽  
Shivi Jain ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Pain Crisis

scholarly journals Is there a role for selective vasodilation in the management of sickle cell disease?

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 597-602 ◽  
Author(s):  
GP Rodgers ◽  
MS Roy ◽  
CT Noguchi ◽  
AN Schechter
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Microvascular Obstruction ◽  
Controlled Study ◽  
Control Group ◽  
Cell Disease ◽  
Retinal Arteriolar

Abstract To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.

scholarly journals End points for sickle cell disease clinical trials: renal and cardiopulmonary, cure, and low-resource settings

2019 ◽  
Vol 3 (23) ◽  
pp. 4002-4020 ◽  
Author(s):  
Ann T. Farrell ◽  
Julie Panepinto ◽  
Ankit A. Desai ◽  
Adetola A. Kassim ◽  
Jeffrey Lebensburger ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Patient Reported Outcome ◽  
Cell Disease ◽  
End Points ◽  
Low Resource Settings ◽  
Low Resource ◽  
Patient Reported ◽  
The Us ◽  
American Society

Abstract To address the global burden of sickle cell disease and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to patient-reported outcome, pain (non–patient-reported outcomes), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the end-organ considerations, measurement of cure, and low-resource settings panels as well as relevant findings and recommendations from the biomarkers panel.

scholarly journals American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support

2020 ◽  
Vol 4 (2) ◽  
pp. 327-355 ◽  
Author(s):  
Stella T. Chou ◽  
Mouaz Alsawas ◽  
Ross M. Fasano ◽  
Joshua J. Field ◽  
Jeanne E. Hendrickson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Guideline Development ◽  
Practice Research ◽  
Evidence Based ◽  
Red Cell ◽  
Cell Disease ◽  
American Society

Background: Red cell transfusions remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. Guidance for specific indications and administration of transfusion, as well as screening, prevention, and management of alloimmunization, delayed hemolytic transfusion reactions (DHTRs), and iron overload may improve outcomes. Objective: Our objective was to develop evidence-based guidelines to support patients, clinicians, and other healthcare professionals in their decisions about transfusion support for SCD and the management of transfusion-related complications. Methods: The American Society of Hematology formed a multidisciplinary panel that was balanced to minimize bias from conflicts of interest and that included a patient representative. The panel prioritized clinical questions and outcomes. The Mayo Clinic Evidence-Based Practice Research Program supported the guideline development process. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to form recommendations, which were subject to public comment. Results: The panel developed 10 recommendations focused on red cell antigen typing and matching, indications, and mode of administration (simple vs red cell exchange), as well as screening, prevention, and management of alloimmunization, DHTRs, and iron overload. Conclusions: The majority of panel recommendations were conditional due to the paucity of direct, high-certainty evidence for outcomes of interest. Research priorities were identified, including prospective studies to understand the role of serologic vs genotypic red cell matching, the mechanism of HTRs resulting from specific alloantigens to inform therapy, the role and timing of regular transfusions during pregnancy for women, and the optimal treatment of transfusional iron overload in SCD.

scholarly journals Serum Iron Levels and Copper-to-Zinc Ratio in Sickle Cell Disease

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 180
Author(s):  
Charles Antwi-Boasiako ◽  
Gifty Dankwah ◽  
Robert Aryee ◽  
Charles Hayfron-Benjamin ◽  
Alfred Doku ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Serum Levels ◽  
Zinc Homeostasis ◽  
Healthy Controls ◽  
Cell Disease ◽  
Flame Atomic Absorption ◽  
Iron Copper ◽  
Copper And Zinc

Background and Objectives: Altered copper and zinc homeostasis may influence the antioxidant defense system and consequently lead to oxidative stress and associated complications in sickle cell disease (SCD) patients. Iron levels have been reported to increase in sickle cell patients due to frequent blood transfusion, chronic intravenous haemolysis and increased absorption of iron from the gastrointestinal tract. These elevated levels of iron may also lead to extensive oxidative damage. The current study evaluated serum levels of iron, copper and zinc in SCD patients and “healthy” controls. Materials and Methods: The study was a cross-sectional one, comprising 90 SCD patients with Haemoglobin SS and Haemoglobin SC genotypes and 50 HbAA “healthy” controls. Serum levels of iron, copper and zinc were measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd, VIC, Australia). Copper and zinc ratios were calculated and analyzed. Results: Serum levels of iron and copper were significantly elevated in the SCD patients, compared to their “healthy” counterparts (p < 0.001). These levels were further increased in patients with haemoglobin SS in vaso-occlusive crises (HbSS VOCs). Serum zinc levels were, however, significantly lower in the SCD patients, particularly during vaso-occlusion. The copper-to-zinc ratio was also found to be significantly higher in the SCD patients. Conclusion: Elevated copper-to-zinc ratio may be a biomarker of sickle cell oxidative stress and associated complications. The ratio may also be informative for the management of sickle cell oxidative burden. The significantly lower levels of zinc in the SCD patients may warrant zinc supplementation.

scholarly journals 2019 sickle cell disease guidelines by the American Society of Hematology: methodology, challenges, and innovations

2019 ◽  
Vol 3 (23) ◽  
pp. 3945-3950 ◽  
Author(s):  
M. Hassan Murad ◽  
Robert I. Liem ◽  
Eddy S. Lang ◽  
Elie A. Akl ◽  
Joerg J. Meerpohl ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Guideline Development ◽  
A Priori ◽  
Cell Transplant ◽  
Cell Disease ◽  
Hematopoietic Stem ◽  
Assessment Development ◽  
Cerebrovascular Complications ◽  
American Society

Abstract The American Society of Hematology (ASH) convened 5 guideline panels to develop clinical practice recommendations addressing 5 management areas of highest importance to individuals living with sickle cell disease: pain, cerebrovascular complications, pulmonary and kidney complications, transfusion, and hematopoietic stem cell transplant. Panels were multidisciplinary and consisted of patient representatives, content experts, and methodologists. The Mayo Clinic Evidence-Based Practice Center conducted systematic reviews based on a priori selected questions. In this exposition, we describe the process used by ASH, including the GRADE approach (Grades of Recommendations, Assessment, Development and Evaluation) for rating certainty of the evidence and the GRADE Evidence to Decision Framework. We also describe several unique challenges faced by the guideline panels and the specific innovations and solutions used to address them, including a curriculum to train patients to engage in guideline development, dealing with the opioid crisis, and working with indirect and noncomparative evidence.

scholarly journals P10 An audit to assess the prescribing of analgesia in children who present with pain crisis due to Sickle Cell Disease (SCD)

2020 ◽  
Vol 105 (9) ◽  
pp. e11.1-e11
Author(s):  
Masuma Dhanji
Keyword(s):  
Sickle Cell Disease ◽  
Integrated Care ◽  
Sickle Cell ◽  
Care Pathway ◽  
Electronic Prescribing ◽  
List Type ◽  
Cell Disease ◽  
Paediatric Patients ◽  
Pain Crisis ◽  
Integrated Care Pathway

AimTo assess the prescribing of analgesia to manage pain crises in children with SCD. This was to establish whether the Trust was meeting national and local standards. Prompt pain control is essential to reduce length of stay and further complications.1Standards100% of admissions will be prescribed regular paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) at the recommended frequency unless contraindicated in accordance with national guidance.2 3100% of admissions will be prescribed appropriate doses of analgesia with consideration to weight and age in accordance with local policy.4MethodThe audit was registered with the Trust’s audit committee. A list of paediatric patients with the diagnosis of SCD was sought from paediatricians with an interest in haematology. A data collection form was created. Data was collected retrospectively over a one-year period. A total of 60 admissions were reviewed to check whether analgesia was prescribed regularly at the recommended frequency, and at the correct dose. Results were analysed using descriptive statistical analysis. Exclusion criteria included patients with hospital admissions under 24 hours.ResultsA total of 55 admissions were included in the final sample. The audit showed the Trust was non-adherent to both standards assessed. A total of 45% (95% CI [31.9%, 58.1%]) of admissions were prescribed regular analgesia. A total of 78% (95% CI [67.9%, 88.9%] of admissions were prescribed appropriate doses of analgesia. Two main reasons were found as to why analgesia was prescribed at the incorrect dose. This was due to incorrect weights recorded on the electronic system (n=4) and doses based on age only (n=8).ConclusionThe results show prescribers are familiar with the correct doses of analgesia but fail to prescribe analgesia regularly. This highlights an opportunity for education and training in the management of pain crisis in SCD. One recommendation includes development of an integrated care pathway booklet for paediatric patients presenting with pain crisis due to SCD. Integrated care pathway booklets have been implemented for other conditions such as cystic fibrosis yielding positive outcomes. The results have highlighted key issues surrounding the electronic prescribing system such as out-of-date weights remaining on the system unless updated, and default treatment protocols. The electronic prescribing system requires refinement for use within paediatrics. One suggestion includes compulsory weight field on admission. Limitations of this audit included small sample size. There was a lack of data to make suggestions based on different ages.ReferencesRees D, Olujohungbe A, Parker N, et al. Guidelines for the management of the acute painful crises in sickle cell disease. Br J Haemato 2003;120:744–752.National Institute for Health and Care Excellence (2012) Sickle cell disease: managing acute painful episodes in hospital. NICE Guideline (CG143).Paediatric Formulary Committee. BNF for Children (2018–2019). London: BMJ Group, Pharmaceutical Press, and RCPCH Publications; (2018).General Hospital (2015) Management of sickle cell disease in paediatric patients (CG377).

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