Low-Dose Ketamine Infusion In Adult Patients With Sickle Cell Disease – Impact On Management Of Acute Painful Episodes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2249-2249
Author(s):  
Michel Gowhari ◽  
Aileen Chu ◽  
Julie Golembiewski ◽  
Robert E. Molokie
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Pain Control ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Adult Patients ◽  
Cell Disease ◽  
Ketamine Infusion ◽  
The Past ◽  
Painful Episode

Abstract Introduction Acute painful (vaso-occlusive) episode is the clinical hallmark of sickle cell disease (SCD). Individuals with SCD may experience acute episodes of severe debilitating pain that requires an acute care/emergency room visit and/or hospitalization. While parenteral opioids are the mainstay of treatment, the use of these agents may be complicated by toxicity, tolerance, and opioid-induced hyperalgesia. Additionally, using one medication/mode of treatment may be inadequate to achieve optimal safe pain control. Ketamine as an adjuvant treatment (administered in low sub-anesthetic doses) has been recognized for its utility in the management of a variety of painful conditions, ranging from oncologic to post-operative pain. However, there is limited literature supporting its use in treating acute sickle painful episodes. Here we have undertaken a retrospective analysis of adult patients with SCD who were treated with low-dose ketamine infusion during an acute painful episode in order to determine its effects of lowering opioid requirements. Methods A retrospective chart and database review was conducted on all patients with SCD who received low-dose ketamine infusion during an acute painful episode in the past three years at a single institution. After a review of inpatient pharmacy records, thirty unique subjects with SCD were identified to have received low-dose ketamine infusion during an acute painful episode in the past three years. For each of these subjects, total and daily (24hr) opioid requirements were determined for the admissions of a vaso-occlusive episode where ketamine infusion was used as an adjuvant for pain control and compared to the prior admission. For the ketamine admission, opioid requirements before, during, and after infusion were also compared. The opioid requirement was converted to intravenous morphine equivalents for standardized comparison. Total opioid and daily (24hr) requirements were determined for each admission. Results Full analysis of all thirty subjects (uncomplicated and complicated pain crises, ketamine infusion of any duration) revealed that the opioid requirement was significantly lower after ketamine compared to before ketamine was started (Wilcoxon signed-rank test P=0.029). The total opioid requirement during the entire ketamine admission, however, was not significantly different from the total opioid requirement during the non-ketamine admission (P=0.088). When a sub-analysis was performed on subjects receiving a ketamine infusion for greater than 24 hours (N=22), the 24hr opioid requirement was significantly lower after ketamine compared to before ketamine was started (P=0.0397). The total opioid requirement during the entire ketamine admission was not significantly different from the total opioid requirement during the non-ketamine admission (P=0.194). When a sub-analysis was performed on subjects with an uncomplicated vaso-occlusive episode (N=17), 24hr opioid requirement was significantly lower after ketamine compared to before ketamine was started (P=0.036). Additionally, the average daily opioid requirement throughout the entire ketamine admission was significantly lower than the average daily opioid requirement during the non-ketamine admission (P=0.001). The total opioid requirement during the entire ketamine admission was not significantly different from the total opioid requirement during the non-ketamine admission (P=1). For the full and subgroup analyses of opioid requirements during the ketamine admission, there was a significantly greater amount of opioid required before the ketamine was started compared to during and after ketamine infusion. Conclusion The use of low-dose infusion of ketamine as an adjuvant for pain control in patients with SCD during vaso-occlusive episode resulted in a significant decrease in opioid requirements. Hence it appears that a low-dose ketamine infusion has utility in the treatment of acute pain crises in adult patients with sickle cell disease. Disclosures: No relevant conflicts of interest to declare.

Safety and Efficacy of Adjuvant Low-Dose Ketamine Therapy for Patients with Sickle Cell Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3226-3226 ◽  
Author(s):  
Caitlin M. Neri ◽  
Sophie Pestieau ◽  
Heather Young ◽  
Angelo Elmi ◽  
Deepika S. Darbari
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Pain Control ◽  
Low Dose ◽  
Red Blood Cell Transfusion ◽  
Bivariate Analysis ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Ketamine Infusion ◽  
Pain Scores

Abstract Abstract 3226 Background/Objectives: Opioids are the mainstay of therapy for painful vasoocclusive crises (VOCs) in sickle cell disease (SCD). For some patients, opioid-induced hyperalgesia caused by activation of N-methyl-D-aspartate (NMDA) receptors has been considered to contribute to poor analgesia. Ketamine, an NMDA receptor antagonist, could be a useful adjunct therapy; however safety concerns remain with its use. We examined records of SCD patients at our institution who received ketamine as an adjuvant to opioids at the discretion of anesthesia pain services over the past 4 years. We sought to explore the safety of ketamine and determine its effect on daily opioid requirement in SCD patients hospitalized for VOCs. Methods: The Institutional Review Board at Children's National Medical Center approved this study. A retrospective case-crossover study was conducted through review of the electronic medical record. For each patient we selected 2-paired hospitalizations occurring within 2 years of each other. One hospitalization where the patient received low-dose ketamine infusion in addition to opioid patient controlled analgesia (PCA), and a second hospitalization where the same patient received opioid PCA alone. We compared clinical characteristics of hospitalizations where patients did or did not receive ketamine. Exploratory bivariate analysis (paired t-test and McNemar's test) was used to compare variables between the pairs. Results: Thirty-three patients were identified to have at least 2 hospitalizations for VOC within 20 months of each other where they received adjuvant ketamine infusion during one, while not during the other. Average age was 15.6 ± 3.4 years, 67 % were females, and 36 % were on hydroxyurea therapy. SCD genotypes included homozygous SS 70%, SC 24 %, S-beta-zero thalassemia 3%, and S-beta-plus thalassemia 3%. Mean number of admissions in the 6 months prior to the ketamine hospitalization was 2 (range 0–5) and 64 % had ≥ 2 prior admissions within 6 months. Ketamine dose was 0.1 mg/kg/h for all patients except one who briefly received 0.15 mg/kg/hr. During the ketamine and opioid PCA hospitalization patients reported overall higher pain scores (6.53 vs. 5.94 out of 10; p = 0.0356), required higher doses of opioid (0.0395 mg/kg/hr vs. 0.0323 mg/kg/hr; p = 0.0038), and had a longer length of stay (LOS) (5.6 vs. 4.4 days; p =0.0148) as compared to the PCA alone hospitalization. Patients were more likely to have a diagnosis of acute chest syndrome (ACS) at some point during the ketamine and opioid PCA hospitalization (42% vs. 15 %; p = 0.0126) as compared to the opioid PCA alone hospitalization. Patients were more likely to be treated with additional adjuvant pain control agents (diazepam, lorazepam, gabapentin, pregabalin, amitripyline, or duloxetine) during the ketamine and opioid PCA admission as compared with opioid PCA alone admissions (45% vs. 9% p = 0.0013). Rates of red blood cell transfusion and ICU transfer were not different between the hospitalizations. In 3 patients ketamine was discontinued due to vivid dreams delusions, or dizziness. Nausea, pruritis, sedation, and use of complementary therapies were similar between hospitalizations. Conclusions: We did not observe an opioid sparing effect of ketamine infusion as hypothesized in this group of frequently hospitalized patients. Low-dose ketamine is a safe adjuvant medication for SCD patients hospitalized for VOCs. Higher opioid use during ketamine and opioid PCA admissions is likely due to patients experiencing more severe VOCs as indicated by higher pain scores involving multiple sites, higher rates of ACS, and longer LOS. These severity measures may have contributed to the decision of the pain medicine service to add low-dose ketamine infusion to standard opioid PCA in this retrospective sample. Finally, VOCs in this group of frequently admitted individuals may represent chronic pain which is known to be minimally responsive to most pharmacologic therapies. Patients receiving ketamine appear to be using additional adjuvant pain agents and may be underutilizing hydroxyurea. Prospective randomized studies of adjuvant ketamine therapy in patients with SCD are warranted to determine true efficacy. Disclosures: Off Label Use: Ketamine is a non-barbiturate phencyclidine derivative that is approved for use as a surgical anesthetic. It is not approved for use in pain management, however is commonly used in low-doses as an adjunct to traditional pain control therapies.

Microparticles As Biomarkers Of Osteonecrosis Of The Hip In Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2226-2226
Author(s):  
Anne M Marsh ◽  
Raymond Schiffelers ◽  
Ginny Gildengorin ◽  
Frans A Kuypers ◽  
Carolyn Hoppe
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Vascular Occlusion ◽  
Predictive Biomarker ◽  
Acute Chest Syndrome ◽  
Mobility Limitations ◽  
Cell Disease ◽  
The Past ◽  
D Dimer

Abstract Introduction Sickle cell disease (SCD) is the most common cause of osteonecrosis of the femoral head (ONFH) in children. ONFH is a debilitating condition that is associated with mobility limitations, chronic pain, and an impaired quality of life. While the mechanisms that cause ONFH remain unknown, ischemia from recurrent microvascular occlusion is likely to play a role. Vascular occlusion may result directly from obstruction by sickled cells, or indirectly via complex interdependent pathways characterized by sustained endothelial activation, chronic inflammation, and coagulation. Microparticles (MP) are small, cell membrane-derived vesicles generated in response to cellular activation, injury or apoptosis. MPs have emerged as potential modulators of inflammation and thrombosis and have been found to be elevated in patients with ONFH in the general population. Objective This pilot study examined whether microparticle levels in patients with SCD who have ONFH differ from SCD patients without ONFH, as well as healthy African American (AA) controls. Methods Subjects were recruited at their baseline status and were excluded if they had been transfused within the past 30 days, hospitalized for a vaso-occlusive pain episode, acute chest syndrome, fever or surgery within the past 30 days, or had bony lesions of the femur or hip due to causes unrelated to SCD. For MP analysis, whole blood was collected in sodium citrate tubes and centrifuged for 15 minutes at 1500 x g at 20° C to generate platelet poor plasma. Aliquots of the plasma were immediately frozen and stored at -80° C until the time of MP analysis. 300 μl samples were diluted in PBS and centrifuged at 10000 x g for 1hr and the supernatant was centrifuged at 100,000 x g for 2 hr. The pellet was re-suspended in 1 mL of PBS and subjected to nanoparticle-tracking analysis to determine concentration and size. Additional laboratory biomarkers of inflammation and coagulation, including highly-sensitive C-reactive protein (hs-CRP), von Willebrand factor antigen (vWF Ag), tissue factor (TF), and D-dimer were analyzed for differences between groups. Analysis of variance was used to compare MP and biomarker levels between the three groups. The institutional review board at Children's Hospital & Research Center Oakland approved the study protocol and written informed consent was obtained from all participants. Results Characteristics of the 30 subjects enrolled are shown in Table I. Total microparticle levels in ONFH(+) patients were 2.3-fold higher than in ONFH(-) patients, and 2.5-fold higher than in AA controls (Figure 1). Mean MP levels for ONFH(+) patients, ONFH(-) patients, and AA controls were 4.55 x 1010, 1.99 x 1010, and 1.85 x 1010, respectively. Microparticle levels in ONFH(-) SCD patients did not differ from AA controls. There were no statistically significant differences in hsCRP, vWF Ag, TF, or D-dimer levels between the ONFH(-) and ONFH(+) groups. Conclusions The results of this study demonstrate significantly elevated MP levels in individuals with SCD who have ONFH. Additional studies are needed to better understand the mechanistic effects of MPs on the development of ONFH and to determine whether MP levels may be useful as a predictive biomarker for early disease detection. This publication was supported by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131. Disclosures: No relevant conflicts of interest to declare.

Predictors of Length of Stay and Time to Readmission in Adult Patients with Sickle Cell Disease: A Single Institution Experience in the UK

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2130-2130
Author(s):  
Emma Drasar ◽  
Sarah A Bennett ◽  
Nisha Vasavda ◽  
Swee Lay Thein
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Severe Disease ◽  
Adult Patients ◽  
Rank Test ◽  
Continuous Variables ◽  
Cell Disease ◽  
The Uk

Abstract Abstract 2130 Background: Sickle cell disease (SCD) is characterised by chronic hemolytic anemia and recurrent acute clinical events. The most common cause of hospital attendance is acute pain and in our patient population it accounts for 84% of all admissions. Financial pressure has led to an interest in the factors affecting length of stay (LOS) and readmission rate (RAR). The 30 day RAR has been highlighted by the UK government as a care standard. In the UK general hospital population the 30 day RAR is 6.5% of all admissions with an estimated cost to the NHS of £1.6 billion/year. A study in the US showed RAR to be 33.4% in the sickle cell population, with a lower rate in children (23%). In SCD multiple factors have been postulated to influence RAR and LOS including patient demographics (e.g. sex and socio-economic status), and hospital variables (hospital status). This retrospective study aims to assess the clinical factors which affect LOS and RAR in the SCD population at a busy London teaching hospital. Methods: The study group consisted of 505 adult patients who were recorded on the King's College Hospital Sickle Cell Database between 1st of January 2009 and 31st of December 2010. The Electronic Patient Record was examined for patient ward, dates of admission and discharge, time to hematology review and time to readmission (TTR) were calculated. Patients with SCD are primarily cared for by hematology however, out of hours, patients may be initially admitted under another medical team and then have their care transferred to the hematology team. Red blood cell units transfused and time to first transfusion were recorded for each event. Data were analyzed statistically using t-tests or Mann-Whitney-U for binary variables (e.g. sex), and Spearman's rank test for continuous variables (e.g. age). TTR was analysed as a binary (≤30 days or >30 days) and continuous variable. Results: The cohort of 505 patients included 299 (60%) female and 206 (40%) male. Mean age was 35 years (range 18–80). 315 patients (63%) had HbSS and 9 (2%) had HbSβ0, 160 (32%) HbSC and 21 (4%) HbSβ+. 207 of the 505 patients had a total of 586 admissions over the study period (mean 3 admissions/ patient, range 1–19). 156 (75%) of the admitted patients had HbSS or HbSβ0 (SCA), 47 (23%) HbSC and 4 (2%) HbSB+. Age of the admission group ranged from 18–80 years (mean 33). LOS ranged from 0 – 116 (mean 7, median 5) days. 45% (264/586) of all admissions could be accounted for by 7% of patients and 83% (489/586) of admissions were patients with SCA. There were 279 readmissions during the study period, (100 [36%] within 30 days) by 83 patients. 72/83 (87%) of readmitted patients had SCA compared to 10/83 (4%) HbSC. Of readmissions within 30 days 95% were by patients with SCA. Further analysis was limited to the SCA group. Female patients had a significantly longer LOS (median 5 days) than male patients (4 days) p = 0.002. There was significant correlation between LOS and TTR (R = 0.11 p=0.03). Patients admitted directly under the hematology team or who were transferred to their care had a significantly longer LOS (5 days) than those who were never admitted under hematology (2 days) p <0.0001. Patients admitted to the hematology wards also had a significantly longer LOS (5 days) compared with those on wards belonging to other specialities (4 days) p = 0.008. Delay to review by the hematology team correlated significantly with increased LOS (R = 0.12 p = 0.02) as does delay to transfusion (R = 0.45 p <0.0001). Interestingly delay to review by the hematology team appears to delay transfusion (R = 0.23 p = 0.011). The number of transfused units also correlated significantly with both LOS (R=0.39 p <0.0001) and an increase in time to readmission (R=0.136 p=0.008). Conclusion: There are a disproportionate number of admissions by patients with SCA who also had a greater proportion of readmissions, reflecting the relative severity of this condition compared to HbSC. These results also highlight that there is a small cohort of patients with relatively more severe disease who have an increased LOS and increased requirement for intervention in the form of transfusion. Delay to review and therefore the decision to transfuse also appears to increase LOS, although involvement of the hematology team does not reduce it. Increased LOS and receiving transfusion treatment do appear to be associated with a delay in time to readmission. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Autoimmune Disease and Its Treatment on Adults with Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4182-4182
Author(s):  
Jennel Zeppieri ◽  
Desmond Aroke ◽  
Alice J. Cohen
Keyword(s):  
Autoimmune Disease ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Low Dose ◽  
Adult Patients ◽  
High Dose ◽  
Complement Pathway ◽  
Cell Disease ◽  
Pain Crisis ◽  
Ed Visits

Abstract Background: Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. Within the United States, it affects 1 in 100,000 people and 1 in 365 African American births. Management requires a comprehensive team dedicated to improving quality of life by minimizing the frequency of pain crisis, hospitalizations and infections that ultimately can reduce mortality. Susceptibility to infections among SCD patients is partly attributed to impaired host defense from chronic activation of the alternative complement pathway. This complement pathway dysregulation has also been suggested to predispose SCD patients to an array of autoimmune diseases (AID). It has been reported that the prevalence of AID in SCD teens and adults is 1.8%. The overlapping clinical manifestations and hematological abnormalities represent a challenge in diagnosing a coexisting AID among SCD patients and likely contribute to an under-reporting of its prevalence in the literature. Once coexistence is established, optimizing the management of each disease is challenging as the therapeutic treatment particularly the use of high dose steroids may exacerbate complications of SCD. The aim of this study was to assess the impact of AID and its treatment on SCD outcomes. Methods: In our retrospective review of 300 adult patients cared for in the adult SCD center from 2016-2021 we identified four patients (1.3%) who met the criteria of SCD and a confirmed diagnosis of an AID. Data that was reviewed included: age, type of SCD, type of AID, treatments of both, number of hospitalizations and ED visits and complications. Results: Four patients, all women between the ages of 38-42 years at the time of AID diagnosis, were identified. The coexisting SCD type and AID were as follows: HbSS with hereditary persistent of HbF(HPFH) and systemic lupus erythematous (SLE), HbSC and SLE with Sjogren's disease, S beta thalessemia+ and SLE with Raynaud's phenomena and HbSS with rheumatoid arthritis (RA). None of the patients were on hydroxyurea. None of the patients were treated with high dose steroids for their AID. Patient 1: HbSS/HPFH with infrequent hospitalizations for vasoocclusive pain crisis (VOC) A rash noted during her second pregnancy prompted a skin biopsy, revealing cutaneous SLE for which treatment with hydroxychloroquine (HC) was initiated. She had one admission for VOC pain crisis at 34 weeks of gestation. Her HC was discontinued prior to delivery. She had an elective C-section at 39 weeks and delivered a healthy 7 lb. baby. 6 weeks post partum she developed severe joint pains and fatigue. She experienced symptom relief with resumption of HC and a low dose prednisone (P) 10 mg. No additional immunosuppressive therapy was started as she continues to breast-feed. Patient 2: HbSC, with SLE and Sjogrens disease with frequent ED visits and admissions for VOC prior to her AID diagnosis. At AID diagnosis she was started on HC and pilocarpine resulting in a prompt reduction in ED visits for pain. She then began to experience worsening arthropathy presumed to be secondary to SLE and was started on methotrexate (MTX). She was hospitalized for community-acquired pneumonia /acute chest syndrome with pleural effusion and pulmonary infiltrates. After no response to antibiotics, she was started on P 30 mg with relief. Because of SLE flare with steroid taper and concern for high dose steroids she was started on rituximab 375 mg/m2 weekly x4. Her pulmonary infiltrates resolved. She continues to have frequent ED/admissions for pain events for VOC. Patient 3: HbSS with frequent ED/admissions for VOC prior to her diagnosis of RA, AVN and pulmonary hypertension. Her AID was treated with MTX and low dose P. Because of RA progression she started etanercept. She had 1 episode of sepsis and septic arthritis and continues to have frequent VOC. Patient 4: Sb+thalassemia with infrequent VOC diagnosed with SLE with Raynaud phenomena. She has been treated with HC without VOC but frequent urinary tract infections. Conclusion: Optimal treatment of adult patients with coexisting SCD and an AID is challenging. In this small group of patients, treatment with a variety of immunosuppressive agents other than high dose steroids, has led to control of the autoimmune disease but no clear improvement of sickle cell pain events and some atypical infections have occurred. Continued tracking of cases of SCD with AID should be done to better understand management and long term outcomes. Disclosures No relevant conflicts of interest to declare.

Use of Low-dose Ketamine Infusion for Pediatric Patients With Sickle Cell Disease-related Pain

2010 ◽  
Vol 26 (2) ◽  
pp. 163-167 ◽  
Author(s):  
William T. Zempsky ◽  
Kristin A. Loiselle ◽  
John M. Corsi ◽  
J. Nathan Hagstrom
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Low Dose ◽  
Pediatric Patients ◽  
Cell Disease ◽  
Ketamine Infusion

Fever In Hospitalized Adult Patients with Sickle Cell Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2652-2652
Author(s):  
Deepa Jeyakumar ◽  
Matthew Zibelman ◽  
Ryan Hurth ◽  
Lani Krauz ◽  
Santosh Saraf ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Hospital Setting ◽  
Adult Patients ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Indwelling Catheters ◽  
Upper Limit ◽  
Pain Crisis

Abstract Abstract 2652 Background: Sickle cell disease is complicated by veno-occlusive crises leading to pain crises, chronic end-organ damage and early mortality. With recent advances in the management of sickle cell disease in childhood, sickle cell patients are living longer. However, our understanding of the clinical course of adult sickle cell disease remains limited and is based largely on extrapolation of knowledge from children with sickle cell disease. Unfortunately, adult patients remain at an elevated risk of infections due to encapsulated organisms in the setting of functional asplenia. This risk is exacerbated by possible indwelling catheters and exposure to the health care environment. Fever in these patients can herald a serious infection. Alternatively, brisk hemolysis can be associated with fever. Wierenga, et. al. (2001) described that fevers to 39F in children were associated with acute chest syndrome (21%), painful vaso-occlusive crisis (27%), and bacteremia in 6%. To our knowledge, no such review of fever in hospitalized adult sickle cell patients has been published in the medical literature. Therefore, the clinician is placed in a diagnostic dilemma regarding the management of fever in adult patients with sickle cell disease. Objective: To determine the etiologies of fevers in hospitalized adult patients with sickle cell disease in an urban tertiary hospital setting. Methods: We performed an IRB-approved retrospective analysis of 143 admissions between 1995–2008 with sickle cell pain crisis and had a fever greater than 38.5C during the admission. The aim was to determine the prevalence of fevers due to infectious versus hemolysis-related causes in the population of interest. Elevated white blood cell count (defined as greater than 1.5x upper limit of normal), radiologic and/or culture data were used to classify a fever as due to infection. Elevated LDH and total bilirubin (defined as greater than 2x upper limit of normal) were used to classify a fever as due to hemolysis. The risks of infection in patients on hydroxyurea as well as indwelling catheters (including central lines and foley catheters) were assessed. We also evaluated the risk of hemolysis in patients on hydroxyurea. Finally, the use of antibiotics and duration of the fever in patients with hemolysis and infection were also evaluated. Results: Among patients admitted with sickle cell pain crisis and had a fever during their hospitalization, we found evidence of infection in 65% and hemolysis in 58%. Interestingly, 35% had evidence of both infection and hemolysis. Approximately, 11.8% had no significant evidence of infection or hemolysis. Antibiotics were used in 66% of all patients with pain crisis and fever. Among the patients who received antibiotics, 81% had evidence of infection and 19% had no evidence of infection. Approximately 1/5 patients with fevers received antibiotics despite the absence of evidence of infection. Infections were not increased among hydroxyurea users (61.5% with fever) over non-hydroxyurea users (67.9% with fever), p = 0.4. Fevers due to documented infections were found in 78% of patients with indwelling catheters compared with 62% of patients without catheters, p≤0.05. The risk of fever due to hemolysis was not significantly different between hydroxyurea and non-hydroxyurea users at 58% versus 57% respectively, p=0.9. Of patients with fevers for more than one day, infection was found in 69% of patients compared with 31% of patients who had no evidence of infection p=0.5. Whereas, of patients with fevers for more than one day, hemolysis was found in 57% of patients compared with 42% of patients who did not have evidence of hemolysis with p=0.9. Conclusions: Among adult sickle cell patients hospitalized with pain crisis and fever, hemolysis accounted for 58% of cases while infections accounted for 65% with 35% evidence of both. Infections were not increased among hydroxyurea users. Indwelling catheters did increase the risk of fevers due to infection. The risk of fever due to hemolysis was not significantly increased among patients on hydroxyurea. Finally, in patients with fevers for more than one day, hemolysis accounted for 57% of cases and infection accounted for 45%. These findings provide initial investigation of the etiologies of fevers in adult hospitalized sickle cell patients and further studies are necessary to confirm these findings. Disclosures: No relevant conflicts of interest to declare. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Average Monthly Cost of Iron Chelator Treatment in Adult Patients with Sickle Cell Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4858-4858
Author(s):  
Samip Master ◽  
Richard Preston Mansour
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Retrospective Analysis ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Private Insurance ◽  
Iron Chelator ◽  
Adult Patients ◽  
Cell Disease ◽  
Monthly Cost

Introduction: Iron overload in adult patients with sickle cell disease (SCD) can lead to variety of complications like liver dysfunction/cirrhosis, cardiac enlargement, diabetes mellitus, hypogonadism and arthropathy. These complication can be prevented by iron chelation therapy .We did retrospective analysis to find incidence of iron over load in this population and also did a survey to find the insurance status in this population. Methods: We take care of approximately 300 adult patients with SCD at out hematology clinic. We did retrospective analysis to investigate the prevalence of iron overload in this population. We also did survey on 100 adult patients with SCD to find out about the insurance converge for them. Web search was done to find out the average monthly cost of iron chelators. Results: On retrospective analysis of 458 adult patients with SCD, we found that 117/458(25.58%) had iron over load. Majority of them, 93/117 were SS type of SCD. Results of survey done on 100 adult patients with SCD showed that 61 had Medicaid, 2 were free care, 25 had Medicare and 12 had private insurance. The average monthly cost of Deferiprone is $ 18762, while that of Deferasirox is $ 13,082. Conclusions: Iron over load is a common complication affecting a quarter of the adult patients with SCD. The treatment of iron overload is expensive, as just the iron-chelator therapy costs approximately 160 to 220 K per year. In an attempt to minimize additional iron accumulation in our chronically transfused patient population we encourage the schedule of exchange of 1 unit phlebotomy and 1 unit of red cell infusion every two weeks. Disclosures No relevant conflicts of interest to declare.

scholarly journals HMGB1 As a Novel Platelet Agonist That Acts Synergistically with ADP to Activate Platelets in Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1073-1073
Author(s):  
Deirdre Nolfi-Donegan ◽  
Sruti Shiva ◽  
Cheryl A Hillery
Keyword(s):  
Sickle Cell Disease ◽  
Synergistic Effect ◽  
Platelet Activation ◽  
Sickle Cell ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Statistical Tests ◽  
Cell Disease

Abstract Background: Sickle cell disease (SCD) is a proinflammatory and prothrombotic disorder that exhibits increased platelet activation. High mobility group box 1 (HMGB1) is a nuclear protein that can mediate inflammation when released from inflammatory or ischemic cells. HMGB1 is increased in many inflammatory disease states including SCD. Recent data suggests HMGB1 activates platelets and may work synergistically with potent platelet agonists such as collagen and thrombin, but little is known regarding HMGB1-platelet interactions in combination with weaker agonists like ADP, or in isolated platelets. Moreover, the effect of HMGB1 on platelet activation has not been evaluated in SCD. We hypothesized that the in vitro addition of low-dose recombinant HMGBI (rHMBG1) to isolated platelets will lower the threshold dose of physiologic agonists required to achieve platelet activation, and that this effect is exaggerated in SCD. Methods: Platelets were isolated from healthy controls (n=4) and patients with hemoglobin SS disease (SCD; n=5). The level of platelet activation was assessed after treatment with ADP at concentrations of 0 μM, 0.5 μM, 2 μM, and 5 μM with the addition of either low-dose rHMGB1 (10 μg/mL) or the same volume of vehicle. Percent platelet activation was measured via flow cytometry using PE antibody to GPIIb (CD41) to select for platelets, and PAC1 to detect the activation-dependent conformational change in integrin αIIbβ3 (GP IIb-IIIa). Platelet activation was interpreted as percent of platelets that bound PAC1. Data was analyzed using FlowJo software and nonparametric statistical tests. Results: Mean baseline platelet activation was 1.5% (range 0.4-3.3%) for control platelets and 7.3% (1.4-17.7%) for SCD platelets (p=0.19). In the SCD group, the addition of low-dose rHMGB1 (10 μg/mL) increased the mean percent of activated platelets from 7.3% to 26.5% (10.9-43%) (p=0.01). In comparison, mean activation of control platelets increased from only 1.5% to 19.5% (8.3-42.7%) after addition of rHMGB1 (p=0.12). Having illustrated that rHMGB1 can activate washed SCD platelets, we then compared the synergistic effect of rHMGB1 with ADP. There was increased platelet activation observed when ADP was added to rHMGB1 in SCD platelets: ADP 0.5 μM increased mean platelet activation from 13.8% (range 0.3-25.3%) to 54.4% (6.7-84.9%) with the addition of rHMGB1 (p=0.02); ADP 2 μM increased platelet activation from 14.1% (2.8-23.8%) to 56.2% (22.2-88.6%) with rHMGB1 (p=0.006); and ADP 5 μM increased platelet activation from 21.4% (2.5-30.1%) to 65.3% (31.7-85.9%) after adding rHMGB1 (p=0.004) (Fig 1; * and **, diamonds vs stars). We did not find a similar statistically significant synergistic effect in the control samples treated with ADP compared to combined HMGB1 + ADP, except at ADP dose 2 μM where platelet activation increased from 14.94% (4.6-28.6%) to 39.1% (19.5-56.0%) after the addition of rHMGB1 (p=0.04; Fig 1; #, square vs circle). Activation of platelets with just ADP was not different comparing control with SCD platelets (Fig 1; circles vs stars). Similarly, activation of platelets with both ADP and rHMGB1 was not significantly different comparing control with SCD platelets except for a trend at 0.5 μM ADP + rHMGB1 10 μg/mL with 19.29% (6.6-38.7) in controls vs 54.44% (6.7-84.9) in the SCD group (p=0.07) (Fig 1; diamonds vs squares). Summary: We found that rHMGB1 acts both independently and synergistically with ADP to increase platelet activation in SCD platelets. In our small cohort, SCD platelets had increased responsiveness to low dose-rHMGB1 compared to control platelets. Moreover, combining rHMGB1 with ADP greatly enhanced platelet activation in SCD but not control platelets. Our data suggest that SCD platelets are sensitized to HMGB1 in the presence of weaker agonists such as ADP. This heightened responsiveness of SCD platelets to HMGB1 may explain the enhanced platelet activation and inflammation associated with SCD in vivo. With further study, HMGB1 could be a target of clinical drug-directed therapy in SCD patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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