Background: Sickle cell disease (SCD) is the most common inherited blood disorder in the United States (US), affecting approximately 100,000 individuals in the country who are primarily of African descent. One of the most prevalent complications of SCD is pain as a result of episodic vaso-occlusive crises. Over time, many individuals with SCD develop chronic pain and opioid dependence for pain management. L-glutamine (EndariTM) was approved by the US Food and Drug Administration in 2017 for patients 5 years-old and older to reduce complications from SCD after reviewing a phase-III placebo-controlled trial. In this study, L-glutamine led to a reduction in median number of pain crises and increased time to first pain crisis when compared to placebo (Niihara et al, NEJM, 2018). However, the impact of L-glutamine on opioid use over time remains unknown. In this study, we evaluated the effect on opioid use in individuals who were started on L-glutamine for worsening SCD related pain. Methods: After institutional review board approval, we retrospectively reviewed the electronic medical record (EMR) of individuals with SCD followed at the University of North Carolina Pediatric and Adult Sickle Cell clinics prescribed L-glutamine in 2018-2019 for worsening acute and chronic SCD-related pain. The North Carolina state controlled substance reporting system, an online clinical tool which collects information on dispensed controlled substance prescriptions to patients that is freely available to prescribers, was also reviewed for filled opioid prescriptions (and milligram morphine equivalents - MME) for each patient. Data, including health care utilization (e.g. hospitalizations and emergence room (ER) visits) and hemoglobin levels for each patient were also evaluated in the EMR for the four months preceding and the four months after L-glutamine was started to determine if changes were sustained. Results: We identified four female patients (ages ranging from 9 to 24 years-old) with SS genotype and chronic pain with acute exacerbations who had significant opioid prescription reduction after starting L-glutamine. Three individuals were taking the maximum tolerated dosing of hydroxyurea and experiencing escalating pain crises prior to initiation of L-glutamine. One patient was intolerant of hydroxyurea and was on a chronic transfusion program for chronic pain management when she was started on L-glutamine for worsening chronic pain. All patients, or caregivers, reported a reduction in acute on chronic pain after initiating L-glutamine. Each patient had a reduction in 4-month total opioid prescription use (in MME) after starting L-glutamine, ranging from a 21% reduction to 100% reduction (Figure 1). Heath care utilization significantly decreased in 1 patient after starting L-glutamine, with 3 ER visits and 2 hospitalizations in the pre-treatment period and no ER visits or hospitalizations in the post-treatment period. There was no difference in the average hemoglobin levels pre-and-post L-glutamine initiation among the patients (9.8g/dL vs. 9.7g/dL). Discussion: L-glutamine appears to have some benefit in reducing pain and opioid use, as well as healthcare utilization, in a subset of patients with SCD and chronic pain. Although we evaluated a small number of patients, all individuals (or caregivers) reported decreased pain very soon after starting L-glutamine. One patient stopped opioid use altogether in the time period evaluated. Future studies should investigate if effectiveness of L-glutamine may be based on unique red cell metabolic profiles, SCD genotype, or timing of drug initiation in these and similar patients. Future investigations will also determine long-term tolerability of L-glutamine and if the reduction in opioid use is sustained for longer periods among these patients and other responders. Disclosures Carden: GBT: Honoraria; NIH: Research Funding.
Hb D-Ibadan [beta87(F3)Thr-->Lys] is a common variant in the Nigerian population, which has been reported in association with Hb S [beta6(A3)Glu-->Val] and with beta-thalassemia. Unlike the Hb S/Hb D-Los Angeles [beta121(GH4)Glu-->Gln] combination, compound heterozygosity for Hb D-Ibadan and Hb S does not result in a sickling disorder. We report the first case of a combination of Hb D-Ibadan with beta+-thalassemia, and the first observation of Hb S/Hb D-Ibadan in the African-American population. In both cases, the characterization of Hb D-Ibadan was achieved by sequencing of the genomic DNA. Although protein based methods such as isoelec-trofocusing and high performance liquid chromatography may suggest that the "D-like" variant is different from Hb D-Los Angeles, the definitive identification of the variant by structural analysis or molecular genetic methods should be undertaken, particularly in newborn screening programs when the variant is found in combination with Hb S.
In patients with sickle cell disease (SCD) and diabetes mellitus (DM), hemoglobin A1c (HbA1c) is unreliable and the American Diabetes Association recommends monitoring long‐term glycemia by measuring serum glucose, but use of serum fructosamine (SF), a measurement independent of red cell lifespan, has been reported. SF as a screen for DM in SCD, however, is not standardized and its relationship to serum glucose has not been validated. Further, screening for DM was not adequately addressed in the 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines for SCD management. Blood transfusions, an important treatment for some patients with SCD, can also impact HbA1c. We present a case of a patient with SCD and cystic fibrosis‐related diabetes on monthly chronic transfusions therapy (CTT) who had well‐correlated “steady state” HbA1c and SF levels over time, suggesting for the first time these markers may actually be useful when following long‐term glycemic control in patients with SCD on CTT programs.
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