scholarly journals Safe Use of Hydroxyurea in Sickle Cell Disease Patients Hospitalized for Painful Vaso-Occlusive Episodes: Results of the Randomized, Open-Label Helps Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2303-2303
Author(s):  
Nicola Conran ◽  
Kleber Yotsumoto Fertrin ◽  
Claudia de Alvarenga Maximo ◽  
Thais Oliveira ◽  
Clarisse Lobo ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Adverse Events ◽  
Sickle Cell ◽  
Acute Phase ◽  
Standard Of Care ◽  
Cell Disease ◽  
Open Label ◽  
Pain Scores ◽  
To Receive

Painful vaso-occlusive episodes (VOE) constitute the most frequent acute complication of sickle cell disease (SCD). However, despite the high economic and personal burden of hospitalization for VOE, there exists no therapeutic approach for VOE other than pain management and hydration. Hydroxyurea (HU) is frequently used continuously to augment levels of fetal hemoglobin (HbF) in patients with SCD, in association with clinical amelioration. However, in addition to its cytostatic effects, HU has immediate anti-inflammatory effects that inhibit vaso-occlusive processes in the microcirculation of mice with SCD, mediated by stimulation of cyclic guanosine monophosphate (cGMP) signaling (Almeida et al., Blood 120(14):2879, 2012). The Hydroxyurea in the Emergency Room to Lessen Pain in Sickle Cell Crisis (HELPS) study (NCT03062501) was a phase II, single-center, randomized, open-label interventional Study (Phase II) designed to evaluate, primarily, the safety of moderate-to-high daily doses of HU in SCD patients in the acute phase of VOE management. Thirty HbSS patients were included in the study within 24h of VOE onset at the Hemorio, Rio de Janeiro, Brazil. Inclusion criteria were: Arrival at the ER within 8h previous to inclusion, confirmed VOE associated with a pain scale score of > 6 within the last 24h, and a pain score of >4 at the time of inclusion. Patients with baseline neutrophil counts < 3.0 (103mm-3) and platelet (PLT) counts < 90 (103mm-3) were excluded from the study due to concerns regarding myelosuppression. Females not in use of contraception, patients hospitalized for VOE within the last 4 weeks and those that had received transfusions in the last 8 weeks were also excluded. Fifteen patients were randomized to the non-intervention arm to receive the center's standard of care, while 15 were randomized to the intervention arm to receive 30-45 mg/kg HU immediately upon study inclusion, and up to two more daily HU doses (if still hospitalized), plus standard of care. During hospitalization, pain scores were recorded every 6 hours, blood counts, and transaminases were determined at 24 h. Adverse events (CTCAE version 4.03), pain medication administered, and length of stay were recorded. Patients were recalled for a post-VOE visit at 7 days after the last HU dose for evaluation for physical exam, late adverse events, blood counts, and transaminases. Twenty-nine patients concluded the study, with 14 patients in the non-intervention arm and 15 in the intervention arm (aged 31.3±10.1 yrs). Four and three patients in each group (respectively) were on continuous HU therapy upon inclusion, and one patient in the non-intervention arm continued taking HU (20 mg/kg/day) throughout the study. Patients in the intervention arm each received up to three daily administrations of HU (mean dose, 31±5 mg/Kg/day; mean number of doses administered, 1.6 per patient). One patient experienced emesis within 2 h of first dose and did not receive a top-up dose. With regard to preliminary safety data, adverse events did not differ significantly between the arms; 4 grade 1-2 events occurred in each of the groups within 24 h of inclusion (all nausea/emesis) and nausea and/or pain were reported in 5 and 3 patients in the non-intervention and intervention arms, respectively, throughout the study. One serious adverse event (death due to sepsis) occurred in the non-intervention arm. Transaminases, red blood cell count, Hb and hematocrit did not differ significantly between the two arms at 24h after inclusion and at the post VOE consultation (number returning; 13 and 12, respectively). No myelosuppression was seen, but the intervention group had a significant decrease in leukocyte count and an increase in PLT count at 7 days post HU, compared to baseline (WBC; 11.9±4.8, 16.4 ±7.0 x 103mm-3: PLT; 570±275, 428±139 x 103mm-3, P<0.05, respectively). Sample numbers were too small to detect any statistically significant decrease in length of stay, pain scores, or opioid usage. However, data indicate that the use of up to three consecutive daily doses of approximately 30 mg/kg HU in the acute phase of the management of SCD patients with VOE is feasible and safe, independently of whether patients already take HU on a continuous basis. Results will aid in the design of larger multicenter trials to evaluate the potential efficacy of the use of oral or intravenous HU during hospitalization for SCD VOE. Financial Support: FAPESP, Brazil. Disclosures Fertrin: Agios Pharmaceuticals, Inc.: Research Funding. OffLabel Disclosure: Use of up to 3 doses of hydroxyurea (30-45 mg/kg/day) in patients with sickle cell disease hospitalized for acute painful vaso-occlusive episodes.

Acute phase proteins and interleukins in steady state sickle cell disease

2009 ◽  
Vol 61 (1) ◽  
pp. 49-54 ◽  
Author(s):  
Konstantinos L. Bourantas ◽  
Georgios N. Dalekos ◽  
Alexandres Makis ◽  
Aristidis Chaidos ◽  
Stavroula Tsiara ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Cell Disease

scholarly journals Vitamin D and Nonskeletal Complications among Egyptian Sickle Cell Disease Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Mona Hamdy ◽  
Niveen Salama ◽  
Ghada Maher ◽  
Amira Elrefaee
Keyword(s):  
Vitamin D ◽  
Sickle Cell Disease ◽  
Vitamin D Deficiency ◽  
Sickle Cell ◽  
Standard Of Care ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Disease ◽  
P Values ◽  
Indirect Bilirubin ◽  
Deficient Group

Lower levels of vitamin D have been documented in many patients with sickle cell disease (SCD), but data are still inconclusive regarding the association between vitamin D deficiency (VDD) and the occurrence or the severity of various SCD complications. Our study aimed to detect the prevalence of vitamin D deficiency among Egyptian patients with SCD and to associate it with the clinical course of the disease. We measured the level of 25-hydroxy vitamin D in 140 children (age from 4.3 to 15.5years), 80 patients with SCD and 60 controls using enzyme-linked immunosorbent assay. Vitamin D was deficient in 60% of SCD compared to 26.7% of controls. Severe VDD was significantly higher in SCD patients than controls. Patients were divided into 2 groups; Normal group (32 patients) and Deficient group (48 patients). There were statistically significant differences between the 2 groups regarding their age, height percentile, the presence of clinical jaundice, and osseous changes (P values 0.043, 0.024, 0.001, and 0.015, respectively). Hemoglobin and hematocrit values were significantly lower in Deficient group (P values 0.022 and 0.004, respectively) while the levels of aspartate aminotransferase, lactate dehydrogenase, and total and indirect bilirubin were significantly higher in the same group (P values 0.006, 0.001, 0.038, and 0.016, respectively). The frequency of blood transfusions, hospitalization, and vasoocclusive crisis previous year as well as the history of bone fracture and recurrent infections proved to be significantly higher in Deficient group. These findings suggest that VDD may play a role in the pathogenesis of hemolysis and other complication of SCD. Vitamin D monitoring and supplementation in patients with SCD should be implemented as a standard of care to potentially improve health outcomes in these affected patients.

scholarly journals Implementing a standard-of-care clinic for stroke prevention in children with sickle cell disease in Nigeria: a feasible strategy outside a clinical trial setting

2017 ◽  
Vol 1 (Suppl) ◽  
pp. 23-25
Author(s):  
Najibah A. Galadanci ◽  
Shehu U. Abdullahi ◽  
Leah D. Vance ◽  
Musa A. Tabari ◽  
Shehi Abubakar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Stroke Prevention ◽  
Standard Of Care ◽  
Cell Disease ◽  
Care Clinic ◽  
Clinical Trial Setting ◽  
Trial Setting

scholarly journals Featured Article: Depletion of HDL3 high density lipoprotein and altered functionality of HDL2 in blood from sickle cell patients

2017 ◽  
Vol 242 (12) ◽  
pp. 1244-1253 ◽  
Author(s):  
Eric Soupene ◽  
Sandra K Larkin ◽  
Frans A Kuypers
Keyword(s):  
Sickle Cell Disease ◽  
High Density Lipoprotein ◽  
Sickle Cell ◽  
Acute Phase ◽  
Whole Blood ◽  
Density Lipoprotein ◽  
High Density ◽  
High Density Lipoproteins ◽  
Mrna Levels ◽  
Cell Disease

In sickle cell disease (SCD), alterations of cholesterol metabolism is in part related to abnormal levels and activity of plasma proteins such as lecithin cholesterol acyltransferase (LCAT), and apolipoprotein A-I (ApoA-I). In addition, the size distribution of ApoA-I high density lipoproteins (HDL) differs from normal blood. The ratio of the amount of HDL2 particle relative to the smaller higher density pre-β HDL (HDL3) particle was shifted toward HDL2. This lipoprotein imbalance is exacerbated during acute vaso-occlusive episodes (VOE) as the relative levels of HDL3 decrease. HDL3 deficiency in SCD plasma was found to relate to a slower ApoA-I exchange rate, which suggests an impaired ABCA1-mediated cholesterol efflux in SCD. HDL2 isolated from SCD plasma displayed an antioxidant capacity normally associated with HDL3, providing evidence for a change in function of HDL2 in SCD as compared to HDL2 in normal plasma. Although SCD plasma is depleted in HDL3, this altered capacity of HDL2 could account for the lack of difference in pro-inflammatory HDL levels in SCD as compared to normal. Exposure of human umbilical vein endothelial cells to HDL2 isolated from SCD plasma resulted in higher mRNA levels of the acute phase protein long pentraxin 3 (PTX3) as compared to incubation with HDL2 from control plasma. Addition of the heme-scavenger hemopexin protein prevented increased expression of PTX3 in sickle HDL2-treated cells. These findings suggest that ApoA-I lipoprotein composition and functions are altered in SCD plasma, and that whole blood transfusion may be considered as a blood replacement therapy in SCD. Impact statement Our study adds to the growing evidence that the dysfunctional red blood cell (RBC) in sickle cell disease (SCD) affects the plasma environment, which contributes significantly in the vasculopathy that defines the disease. Remodeling of anti-inflammatory high density lipoprotein (HDL) to pro-inflammatory entities can occur during the acute phase response. SCD plasma is depleted of the pre-β particle (HDL3), which is essential for stimulation of reverse cholesterol from macrophages, and the function of the larger HDL2 particle is altered. These dysfunctions are exacerbated during vaso-occlusive episodes. Interaction of lipoproteins with endothelium increases formation of inflammatory mediators, a process counteracted by the heme-scavenger hemopexin. This links hemolysis to lipoprotein-mediated inflammation in SCD, and hemopexin treatment could be considered. The use of RBC concentrates in transfusion therapy of SCD patients underestimates the importance of the dysfunctional plasma compartment, and transfusion of whole blood or plasma may be warranted.

Evaluation of Intravenous Diphenhydramine Use in Patients with Sickle Cell Vaso-Occlusive Crisis

2020 ◽  
pp. 001857872095417
Author(s):  
Katherine Rector ◽  
Shelby Merchant ◽  
Rachel Crawford ◽  
Justin R. Arnall ◽  
James Symanowski ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Cell Disease ◽  
Median Length ◽  
Significant Difference ◽  
Oral Group ◽  
Icd 10 ◽  
Secondary Endpoints ◽  
Group 2

Purpose: To compare the incidence of oversedation between oral and parenteral diphenhydramine therapy for treatment of opioid-induced pruritus in patients with sickle cell disease vaso-occlusive crisis (SCD VOC). Methods: This retrospective, single-center, cohort study included patients greater than or equal to 18 years old with sickle cell disease admitted for vaso-occlusive crisis who received either intravenous or oral diphenhydramine for opioid-induced pruritus. Patients were identified through ICD-9 and ICD-10 codes from June 1, 2016 through July 1, 2017. Rates of oversedation were compared between the 2 formulations. Secondary endpoints included length of stay, amount and duration of diphenhydramine, rate of acute chest and indication for IV therapy. Results: Fifty unique patients were included in the analysis representing 121 admissions. Seven patients received both formulations on separate admissions and were included in both groups. Twenty-nine percent of patients in the IV diphenhydramine group experienced oversedation (12/42) versus 13% in the oral diphenhydramine group (2/15, P = .312). The average number of admissions was significantly higher in the IV versus oral group (2.45 vs 1.20; P = .005) with average and median length of stay also significantly higher in the IV versus oral group (30.57, 16.0 vs 10.67, 10.0; P = .003). Conclusion: While there was no statistically significant difference in the rates of oversedation with use of IV versus oral diphenhydramine formulations, patients with SCD VOC who received IV diphenhydramine had more frequent admissions and a longer length of stay. Clinicians may consider oral diphenhydramine preferentially in appropriate patients over IV administration.

Variation in hospitalizations and hospital length of stay in children with vaso-occlusive crises in sickle cell disease

2005 ◽  
Vol 44 (2) ◽  
pp. 182-186 ◽  
Author(s):  
Julie A. Panepinto ◽  
David C. Brousseau ◽  
Cheryl A. Hillery ◽  
J. Paul Scott
Keyword(s):  
Sickle Cell Disease ◽  
Length Of Stay ◽  
Sickle Cell ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Cell Disease

Adjuvant interventions with opioids for vaso-occlusive crisis in sickle cell disease: A mixed treatment network meta-analysis of randomized controlled clinical trials

2020 ◽  
Vol 16 (4) ◽  
pp. 267-275
Author(s):  
Kannan Sridharan, MD, DM ◽  
Gowri Sivaramakrishnan, MDS
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell Disease ◽  
Adverse Events ◽  
Magnesium Sulfate ◽  
Sickle Cell ◽  
Meta Analysis ◽  
Favorable Effect ◽  
Secondary Outcome ◽  
Cell Disease ◽  
Number Of Patients

Objective: Vaso-occlusive crisis is the most common clinical feature requiring opioid analgesics in patients with sickle cell disease. We conducted a network meta-analysis to compare the drugs that can be used as add-on with opioids for vaso-occlusive crisis.Design: Network meta-analysis of randomized clinical trials.Patients: Sickle cell disease patients with vaso-occlusive crisis receiving adjuvants to opioids for pain management.Main outcome measures: A number of patients with complete pain relief and pain scores assessed either by visual analog or by a numerical rating scale were the primary outcomes. Adverse events and dose of opioids (in morphine equivalents) for pain alleviation between the treatment arms were the secondary outcome measures.Results: Eleven studies evaluating the addition of ketorolac, magnesium sulfate, ketoprofen, ibuprofen, methadone, inhalational nitric oxide, methylprednisolone, and arginine with morphine were obtained. The pooled analysis showed a favorable effect in the pain reduction for the additions of arginine {–2 [–3.39, –0.61]} and ibuprofen {–1.7 [–3.26, –0.14]} with morphine. Arginine has high probability of being the “best” in the pool followed by ibuprofen. No significant differences were observed in the risk of adverse events {ketoprofen—0.84 [0.42, 1.65]; magnesium sulfate—1.81 [0.64, 5.81]; and arginine—2.08 [0.18, 24.31]}. A significant lower dose of opioid was required when given adjunctive to arginine, inhalational nitric oxide, and methylprednisolone.Conclusion: We observed that arginine and ibuprofen could produce additional analgesic effects when combined with morphine in vaso-occlusive crisis.

Adverse Events in Sickle Cell Patients with Nocturnal Hypoxia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3793-3793
Author(s):  
Andrew D. Campbell ◽  
Megumi Okumura ◽  
Ndidi Unaka ◽  
Sally Hutchinson ◽  
Onyinye Onyekwere
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Sickle Cell Disease ◽  
Adverse Events ◽  
Sickle Cell ◽  
Case Series ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Obstructive Sleep ◽  
The Relationship

Abstract The relationship between hemoglobin dexoygenation and sickling is well known. However, the relationship between hypoxia and severity of disease in sickle cell patients has not been well established. Recently, nocturnal hypoxemia has been associated with higher incidence of CNS events including strokes, and elevated TCDs. We present our case series on 13 patients(12 SS, 1 SC) with sickle cell disease (SCD) who have nocturnal hypoxia. Approximately 75 patients were screened at the University of Michigan Sickle Cell clinic for nocturnal hypoxia either by symptoms of obstructive sleep apnea or by longitudinal baseline clinic 02 saturations (02 Sat &lt;92%). Of the 13 hypoxic pts, median baseline O2 Sat 90%(n=13, mean 90) and the median nocturnal O2sat (Nctnl 02 sat) 84%(n=13, mean 80%) with 10/13 with moderate-severe nocturnal hypoxia (O2sats&lt;85%)based on sleep studies. Multiple adverse events noted in the cohort were pulmonary hypertension (PHTN TRJV&gt;2.5, n=9, median 2.74/mean 2.74,) frequent pain episodes(&gt;3visits to ER or hospitalizations/year, n=7, with 5 pts &gt;5/year ), recurrent acute chest syndrome( ≥ 3 episodes, n= 10), CNS events (n=3 silent infarcts, vascular stenosis), priapism( (n=4, among 6 males ). Also reported were possible causes of the underlying hypoxia including obstructive sleep apnea(OSA)(n=7 of 11 pts), asthma(n= 10 of 13 pts), and chronic lung disease( n=8). In conclusion, the persistence of nocturnal hypoxia in pediatric sickle cell disease could possibly contribute to the development of severe complications of sickle cell disease. Treatment of underlying hypoxia (ie nighttime oxygen, maximize asthma treatment, T&A for OSA)may help prevent complications and lead to the improvement clinical symptoms. Further, chronic nocturnal hypoxia may complicate pulmonary disease and accelerated the development of PHTN. More studies are needed to clarify the mechanism of hypoxia in SCD. Table I. Clinical &Demographic Data of 13 SCD Patients with Nocturnal Hypoxia. Age:(6–22y/o, mean 15) Sex: M=6 F=7 Clinical: Total Mild Mod Sev. Genotype: SS=12, SC=1 Mean Range Nctnl Hypoxia(&lt;%) 13 3 5(&lt;85) 5(&lt;80) Baseline O2 Sat(%) 90 +3.0 86–97 Obstr Sleep Apnea 7 3 3 1 Nctnl 02 sat (%) 80+8.4 59–87 Pulm HTN 9 4 4 1 Total #Apneic Events(11) 65.6+80 6–256 Rest. Lung Ds. 8 2 5 1 Obstr. Apneic Events(7) 27+68.5 0–221 # of Episodes &lt;3 3–4 &gt;4 Hypopneic Events(9) 32.5+38 0–132 ACS 2 5 5 TRJet Velocity 2.74+.42 2–3.5 Severe Pain Crises/yr 1 2 5

Safety and Efficacy of Sildenafil Therapy for Doppler-Defined Pulmonary Hypertension in Patients with Sickle Cell Disease: Preliminary Results of the Walk-PHaSST Clinical Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 571-571 ◽  
Author(s):  
Roberto F Machado ◽  
Robyn J Barst ◽  
Nancy A Yovetich ◽  
Kathryn L Hassell ◽  
Jonathan C. Goldsmith ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Adverse Events ◽  
Arterial Pressure ◽  
Sickle Cell ◽  
Research Funding ◽  
Cell Disease ◽  
Safety And Efficacy ◽  
Preliminary Results ◽  
Significant Difference

Abstract Abstract 571 Background: Pulmonary hypertension (PH) is associated with increased mortality in patients with sickle cell disease (SCD). Methods: Walk-PHaSST (treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy) is a multi-center (10 United States and United Kingdom Centers), placebo-controlled, double-blind 16-week trial evaluating the safety and efficacy of oral sildenafil for the treatment of Doppler-defined PH (tricuspid regurgitant jet velocity [TRV] ≥2.7m/s) in adults and children (aged >12 years) with SCD. The primary endpoint was the six-minute walk distance (6MWD). The study was designed with a planned screening of approximately 1000 subjects, to enroll 132 subjects for inclusion in the nested Main Interventional Trial (MIT). In the screening trial, subjects were evaluated by history and physical examination, laboratory screening, transthoracic Doppler echocardiography and 6MWD. Randomized subjects were stratified by TRV (2.7-2.9 m/s and ≥3.0 m/s), and those in upper strata underwent a right heart catheterization (RHC). Preliminary Results: Of the 722 screened subjects, 150 (26%) had both a TRV ≥2.7 m/s AND 6MWD of 150-500 meters (m), qualifying for MIT enrollment. A total of 74 subjects (13%) were randomized into the MIT. The study was prematurely stopped due to a statistically significant increase in serious adverse events (SAEs) in the sildenafil arm after 33 subjects had completed the 16 week assessments and 74 subjects (37 sildenafil: 23 female, 47 ± 12 years, TRV 3.0 ± 0.4 m/s, 6MWD 378 ± 93 m; 37 placebo: 23 female, 44 ± 14 years, TRV 2.9 ± 0.3 m/s, 6MWD 381 ± 75 m) had been randomized in the MIT. To evaluate safety and efficacy, all 74 subjects were evaluated, with pre-defined primary and secondary endpoint analysis and imputation rules for missing data. Baseline gender, hemoglobin phenotype, TRV and 6MWD were similar between sildenafil and placebo (all p>0.05). There was a significant increase in SAEs in the sildenafil arm (46% vs. 22% of randomized subjects; p=0.048) but no significant difference in adverse events (AEs; 76% vs. 68%; p=0.607). Sickle cell anemia with crisis (hospitalization defining the SAE) accounted for the significant difference in SAEs (35% vs. 11%; p=0.025). In reference to AEs, patients on sildenafil tended to have more headache (27% vs. 14%; p=0.247) and more blurred vision (11% vs. 3%; p=0.358). No other SAEs or AEs by organ system or preferred term were significantly different (all p > 0.43). There were no AEs classified as life-threatening and there was one death in the placebo arm. To assess potential efficacy, all 33 subjects with TRV of ≥3.0 m/s underwent RHC and received a single test dose of 60 mg of sildenafil; data are currently availabel for 22 of those subjects. Although this dose of sildenafil acutely decreased mean pulmonary arterial pressure (p=0.01), and mean systemic arterial pressure (p<0.01), the change in pulmonary vascular resistance was not significant. There were no apparent safety issues with the acute sildenafil dosing (e.g. priapism). After 16 weeks of sildenafil, there was no difference in the change in TRV (adjusted mean change from baseline: sildenafil -0.10 ± 0.08 m/s, placebo -0.13 ± 0.8 m/s; p=0.7) or in 6MWD (adjusted mean change from baseline: sildenafil -17 ± 20.9 m, placebo +1.4 ± 21.8 m; p=0.47). On the Brief Pain Inventory (BPI), sildenafil subjects reported worsening pain during walking (p=0.07; p=0.17) and less enjoyment of life (p=0.09; p=0.04) vs. placebo at the interim visits (6 and 10 week, respectively). For subjects in the sildenafil group, no difference was detected in 6MWD for those experiencing a VOC vs. those without a VOC (adjusted mean 386 ± 15.9 m; 372 ± 11.7 m; p=0.39). Preliminary Conclusions: In conclusion, sildenafil significantly increased rates of VOCs requiring hospitalization vs. placebo. The premature study termination for safety concerns limited the sample size for efficacy assessments; however, further investigation may be warranted in a more select group of patients with optimized hydroxyurea and transfusion therapy. Based on the completed analyses, no relationship has been established between experiencing pain (via serious VOC) and 6MWD. Additional analyses will focus on determining whether pain (as measured by BPI) is correlated with change in 6MWD. Finally, these data suggest a potential role for the cyclic cGMP axis in the pathobiology of VOC and sickle cell disease related pain. Disclosures: Barst: Pfizer: Consultancy, Research Funding. Gibbs:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Girgis:Pfizer: Research Funding. Badesch:Pfizer: Consultancy, Research Funding.

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