Ferritin Levels Do Not Reflect the Severity of Iron Overload in Diamond Blackfan Anemia

Introduction: Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome (IBMFS) characterized by hypoplastic anemia, congenital malformations and an increased risk to develop malignancies.Until now, treatment of DBA consists of red blood cell (RBC) transfusions, glucocorticoids (GC) and allogeneic hematopoietic stem cell transplantation in a selection of patients. Whereas RBC transfusions are the main cause of IO, elevated iron parameters have also been reported in non-transfusion-dependent DBA patients. Here we investigated the incidence and severity of IO in a well-described cohort of transfusion-dependent and non-transfusion-dependent DBA patients in order to gain more insight in the regulation of iron metabolism in DBA, and to provide clinical guiding to improve the diagnosis and management of IO in DBA. Methods: In this retrospective, observational study we have included twenty-nine pediatric and adult DBA patients for whom at least one serum ferritin level and/or MRI result was available. Ten patients (34%) were classified as transfusion-dependent (TD) (ten or more transfusions during the twelve months prior to evaluation). Non-transfusion-dependent (NTD) patients (66%) were treated with either GC, incidental transfusions or received no treatment. Transfusion burden (transfusion history) was assessed via medical records. Serum ferritin levels ≥250 ng/mL in males and ≥150 ng/mL in females were considered to be elevated. Results of MRI were expressed as liver iron content (LIC) and as cardiac T2* in milliseconds (ms). LIC ≥3 mg/g indicates significant hepatic IO, and LIC ≥7 mg/g is associated with clinical morbidity. Cardiac T2* ≤20 ms indicates significant cardiac IO. Results: In 15/29 (52%) MRI analysis of IO was performed. Hepatic IO (LIC >3 mg/g) was present in 9/29 (31%) of DBA patients, of which 8/9 (89%) had moderate to severe IO (LIC>7mg/g), despite the fact that all but one were treated with chelation therapy. Overall serum ferritin levels and LIC correlated significantly (r=0.7907, p<0.001), and all TD patients with LIC ≥7 mg/g had serum ferritin levels ³400 ng/mL, however, none of the patients had a serum ferritin >1000 ng/mL (Figure 1A). Interestingly, in the NTD group, hepatic IO was present in 2/7 patients (29%), who both only had mildly elevated serum ferritin levels (263 ng/mL and 277 ng/mL) and were not treated with iron chelation therapy. Based on total transfusion burden since birth, patients were classified in distinct groups: nine patients who received ³10 transfusions during life (9/10) were diagnosed with hepatic IO, whilst none of the patients who received <10 transfusions were diagnosed with hepatic IO. Both mean serum ferritin levels and mean LIC values were significantly higher in patients with ³10 transfusions compared to all with <10 transfusions (Figure 1B-C). Discussion: We demonstrate that IO is common in DBA yet can be easily overlooked in NTD patients that were treated with transfusions in the past. While serum ferritin levels significantly correlated with LIC values, this parameter cannot be used exclusively to screen for IO or titrate iron chelation therapy. We conclude that in clinical practice, biochemical parameters in combination with transfusion history justify a low-threshold to perform an MRI-based evaluation of IO, and to start adequate chelation therapy. Figure 1 Figure 1. Disclosures Van Beers: Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Novartis: Research Funding; RR Mechatronics: Research Funding. Wijk: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Axcella health: Research Funding; Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding.

605 Group and Save Sampling in Total Knee and Hip Arthroplasty: Is It Necessary?

Aim To induce a change in practice with regard to pre-op G&S sampling. This is common practice in elective orthopaedics. Transfusion rates are negligible. Therefore, omitting this practice can reduce the financial burden on the Trust. Method Patient's undergoing elective primary total knee or hip arthroplasty over a 1-year period were retrieved from a database. Data regarding pre/post-op haemoglobin levels and transfusion status was obtained from patient case notes and Trust ICE pathology reporting system. Results There were a total of 454 patient's (251 undergoing TKR, 203 undergoing THR). Four patient's (1.6%) in the TKR group and 11 patient's (5.4%) in the THR group required transfusion. Of these patient's, 5 had cardiac problems and 6 had pre-operative anaemia. Conclusions Routine G&S sampling is unnecessary in the majority of cases and should only be reserved for certain cases (patient's with significant cardiac problems and those with a transfusion history). Patient's with pre-operative anaemia should have optimisation of haemoglobin level prior to the procedure.

Intermittent Transfusions for Treatment of Thalassemia in the State of Georgia, 2007-2016

Background: Individuals with Non-Transfusion Dependent Thalassemia (NTDT) may require infrequent transfusions. Knowing transfusion history, while important, can be challenging in this subgroup. Study Design: Hospital discharge data in Georgia (2007-2016) was reviewed. Thalassemia patients were defined as ≥3 encounters with a thalassemia diagnosis code. Transfusion was defined by the presence of a diagnosis, CPT, revenue, or HCPCS code for red cell transfusion. Results: There were 428 patients identified; 57 received multi-site transfusions. Conclusion: Georgia hospitals provide intermittent transfusions to low volumes of probable NTDT patients. Patient and provider education may help assure adherence to best practices, avoiding serious transfusion complications.

A follow-up audit of the completion of bone marrow specimen request forms at an academic laboratory

Background: In order to ensure that patients receive individualised treatment following bone marrow biopsy, it is necessary for clinicians to provide complete clinical information on bone marrow request forms (BMRFs). An audit of BMRFs six years previously showed poor completion, especially with regard to filling in full blood count results, transfusion history, medication history, information about the clinical examination and HIV status. This lead the laboratory to design a new bone marrow specimen request form. We did a follow-up audit to see if the new form had helped to improve the completion rates. Methods: We compared 400 forms to the 357 that were audited in 2013. The following details were recorded: date and time of collection, patient demographics, requesting doctor’s details, clinical information, current medication, transfusion history and HIV status, and details of the procedure completed by technologists, registrars and pathologists. Results: The 2019 follow-up audit showed significant improvements in the completion of the transfusion history, as well as the clinical examination and HIV status. Registrars and pathologists signed off forms regularly. The completion of patient demographic details, and requesting doctors’ names and telephone numbers worsened. Discussion and conclusion: We recommend that the form be simplified so the requesting doctors only need to tick yes or no, in a tick-box format, if a full blood count has been done in the preceding 24 hours. There needs to be a dedicated space for the hospital and laboratory stickers. Only the name and telephone number of one doctor should be requested. This doctor should preferably be the most senior doctor involved with patient care. All referring laboratories and hospitals will be consulted before updating the form. Unfortunately, it seems that the only way to force the completion of request forms is to introduce an electronic order entry system that does not accept incomplete forms.

Postoperative fever workup in pediatric neurosurgery patients

OBJECTIVEFevers are common in the postoperative period, and adult data indicate that workup for an isolated fever is not warranted in the first 4 postoperative days (PODs). Pediatric literature on the subject similarly questions the value of further investigation during the first 2 PODs. The purpose of this study was to determine the incidence of acute fever in the postoperative pediatric neurosurgical population, as well as to assess the utility of performing further workup on these patients.METHODSA single-institution retrospective study was performed to assess pediatric neurosurgery patients following surgical intervention for the diagnoses of craniosynostosis, Chiari malformation, and brain tumors from 2009 to 2018. Fevers were identified during the first 4 PODs and were defined as a temperature ≥ 38.0°C. The patient charts were queried for urinalysis and urine culture (UA/Ucx), chest radiographs, blood cultures, CSF culture, respiratory viral panel, white blood cell (WBC) count, transfusion history, development of wound infection, and placement of external ventricular drains (EVDs) or lumbar drains. Thirty-day postoperative microbiology results and readmissions were reviewed. Descriptive statistics were performed using logistic regression analysis.RESULTSTwo hundred thirty-five patients were evaluated, and 61% had developed fevers within the first 4 PODs. Thirty-eight (26.6%) of the 143 febrile patients underwent further workup, and those with high fevers (> 39.0°C) were more likely to undergo further evaluation, which most commonly included UA/Ucx (21.7%). Approximately 1% (2/235) of the patients were found to have an infection during the first 4 days, and 8 additional patients developed a complication following the initial 4 days and within the first 30 PODs. The development of infectious complications within the first 4 PODs did not correlate with acute postoperative fevers (p = 0.997), nor did the development of complications within the 30 days following surgery (p = 0.776); however, multiple days of acute postoperative fevers (p = 0.034) and the presence of an EVD (p = 0.001) were associated with the development of infectious complications within 30 days. Acute postoperative fevers were associated with EVD placement (p = 0.038), as well as blood product transfusions and an increased WBC count (p < 0.001).CONCLUSIONSIsolated fevers manifesting within the first 4 PODs are rarely associated with an infectious etiology. Additional factors should be taken into consideration when deciding to pursue further investigation.

Hemolytic Disease of the Fetus and Newborn Caused by Maternal Autoantibody with Mimicking Anti-E Specificity

Objective There are few reports of hemolytic disease of the fetus and newborn (HDFN) caused by maternal autoantibodies. Methods We describe the case of a pregnant patient aged 26 years with systemic lupus erythematosus without any transfusion history who developed autoantibody with mimicking anti-E specificity. Her newborn developed HDFN caused by the maternal autoantibody. Results The clinical symptoms of the newborn were not serious. After bilirubin light phototherapy and other symptomatic supportive treatment, the baby was discharged with a good prognosis. Conclusion This is the first reported case of HDFN caused by maternal autoantibody with mimicking anti-E specificity. However, the real antigenic target of the autoantibody was not clear.

Hepatitis B Virus Infection and Its Determinants among Pregnant Women in Ethiopia: A Systematic Review and Meta-Analysis

Background. Hepatitis B virus (HBV) is an infectious and a global public health problem. The prevalence of HBV infection among pregnant women is between 2.3% and 7.9%. HBV infection during pregnancy is associated with prenatal transmission to the fetus. HBV has an effective vaccine which reduces up to 96% of the transmission. Although different studies were conducted in Ethiopia, none of them showed the national prevalence of HBV infection among pregnant women. Therefore, this study was conducted to determine the pooled prevalence of HBV and its associated factors in Ethiopia. Methods. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for articles. All observational published studies were retrieved using relevant search terms in Google Scholar, African Online Journal, CINAHL, and PubMed databases. Newcastle-Ottawa assessment checklist for observational studies was used for critical appraisal of the included articles. The meta-analysis was done with STATA version 14 software. The I2 statistics were used to test heterogeneity whereas Begg’s and Egger’s tests were used to assess publication bias. Odds ratio (OR) with a 95% confidence interval (CI) was presented using the forest plot. Results. A total of twenty-three studies were included in this systematic review and meta-analysis. The pooled prevalence of HBV in Ethiopia was 4.75% (95% CI: 4.06, 5.44). The subgroup analysis showed a higher prevalence of HBV infection among pregnant women in Gambella (7.9%) and the lowest in Southern Nations, Nationalities, and Peoples’ Region (SNNPR) (2.3%). Associated factors with HBV infection include history of multiple sexual partner (OR=6.02 (95%CI=3.86, 9.36)), blood transfusion history (OR=5.71 (95%CI=3.25, 10.04)), abortion history (OR=3.58 (95%CI=2.10, 6.09)), and history of body tattoo (OR=2.83 (95%CI=1.55, 5.17)). Conclusions. HBV infection among pregnant women is a common public health problem in Ethiopia. Multiple sexual partners, abortion history, blood transfusion history, and body tattoo were significantly associated with HBV infection. Policies and strategies should focus on factors identified in this study to improve the prevention of HBV among pregnant women.

Association of anti-HCV sero-prevalence with blood transfusion and practice of haemodialysis from multiple centres in patients on maintenance haemodialysis

Objectives: To determine the frequency of anti-HCV in patients on maintenance haemodialysis (HD) and its association with history of blood transfusion and with the practice of HD from more than one center. Methods: All the patients on maintenance HD at Bahria International hospital (BIH) Rawalpindi from March 2019 to May 2019 were included. Demographic details, history of blood transfusions and history of HD from any other center in addition to BIH, were recorded. Anti-HCV was done by chemiluminescent assay. Chi-square was used to compare the categorical variables. Odds ratio (OR) and relative risk (RR) for the groups exposed to risk were calculated. Results: Of 96 patients, 40 (41.6%) were anti-HCV positive. Sixty–two (64.6%) had transfusion history. Thirty-one (50%) of these 62 were anti–HCV positive as compared to 9 (26.5%) of 34 with no history of transfusion (p=0.025); OR=2.78 (p=0.0278), RR=1.89 (p=0.0420). Among 66(68.7%) of 96 who had HD from other centres in addition to ours, 33(50%) were anti-HCV positive as compared to 7(23.3%) of 23 who had HD from BIH only (p=0.014); OR=3.29 (p=0.0167), RR=2.14 (p=0.0309). Conclusion: There was a high prevalence (41.6%) of anti-HCV in our HD patients and anti-HCV positivity had significant association with history of blood transfusion as well as with history of HD from multiple centres. doi: https://doi.org/10.12669/pjms.36.2.1343 How to cite this:Amjad U, Ahmad SQ, Mir S, Ayub M. Association of anti-HCV sero-prevalence with blood transfusion and practice of haemodialysis from multiple centres in patients on maintenance haemodialysis. Pak J Med Sci. 2020;36(2):---------. doi: https://doi.org/10.12669/pjms.36.2.1343 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Comorbidities and Complications in Adults with Pyruvate Kinase Deficiency

Introduction: Pyruvate kinase (PK) deficiency causes a defect in the glycolytic pathway, leading to a hereditary hemolytic anemia. Management is supportive and consists of splenectomy, transfusions, and chelation therapy. Aim: To better understand the comorbidity and complication profile of adults with PK deficiency, and the extent to which transfusion frequency contributes, the objectives of this study were to (1) quantify the prevalence of comorbidities and complications according to transfusion history and (2) compare the types and rates of select comorbidities and complications with the general population. Methods: Data were obtained from the enrollment survey of the PK Deficiency Natural History Study (NHS), a longitudinal, retrospective and prospective cohort study in which clinical, laboratory, transfusion, and radiologic data were collected; all participants were confirmed to have 2 mutations in the PKLR gene. Patients (n=122) were eligible for this analysis if they were ≥18 years of age and had sufficient data on transfusion history to enable classification into 1 of 3 cohorts: "Ever Regularly Transfused" (ERT, defined as ≥6 transfusions in any 12-month period), "Never Regularly Transfused" (NRT, defined as having ≥1 lifetime transfusion but never having >4 transfusions in any 12-month period), or "Never Transfused" (NT). To contextualize the findings, the frequencies of select conditions were compared with an age- and gender-matched cohort of individuals from the insured, general US population who did not have any hemolytic anemia diagnoses and had ≥5 years of continuous enrollment in the Truven MarketScan administrative claims database. The NHS reported lifetime prevalence rates, whereas rates obtained from the MarketScan data were based on diagnosis and procedure codes over varying look-back periods; therefore, to minimize bias, we limited PK deficiency vs. general population comparisons to (1) chronic conditions that require lifetime management and would thus still be recorded in claims data years after initial diagnosis, and/or (2) conditions for which a diagnosis/procedure date was available in the NHS and could be matched in time to the average 8-year look-back period for the general population. Frequencies were compared across mutually exclusive cohorts using Fisher's exact 2-tailed tests of significance. Results: ERT (n=65), NRT (n=30), and NT patients (n=27) had a mean age of 34.2, 39.5, and 37.2 years at enrollment, respectively (not significant [ns]), with 46.2%, 56.7%, and 59.3%, respectively, being male (ns). ERT patients trended toward being more likely than NT patients to be Amish and have the homozygous R479H splice variant (30.8% vs 11.1% [p=0.064]) but were significantly less likely to have a missense/missense PKLR genotype (32.3% vs 70.4% [p=0.001]). Compared with the general population, patients with PK deficiency had significantly higher rates of splenectomy, cholecystectomy, osteoporosis, liver cirrhosis, pulmonary hypertension, and current prophylactic antibiotic and anticoagulant use (Table). Rates of splenectomy, cholecystectomy, and osteoporosis were significantly higher in patients with PK deficiency, regardless of transfusion cohort, and both ERT and NRT patients had significantly higher rates of liver cirrhosis than individuals from the general population. A gradient was seen across transfusion cohorts for other conditions. Notably, 83.1% of ERT patients, 50.0% of NRT patients, and 25.9% of NT patients had a history of liver iron overload. ERT patients were also significantly more likely than NRT and NT patients to have had a splenectomy, cholecystectomy, and/or thrombosis, and to currently use prophylactic antibiotics. Findings were consistent when the analysis was restricted to non-Amish patients with PK deficiency. Conclusions: Patients with PK deficiency have higher rates of select comorbidities and complications than age- and gender-matched individuals who do not have PK deficiency. Even patients with PK deficiency who have never been transfused are at increased risk of complications of the disease and its treatment. Disclosures Boscoe: Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Yan:Agios Pharmaceuticals, Inc.: Consultancy. Hedgeman:IBM Watson Health: Employment. van Beers:Agios Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Research Funding; RR Mechatronics: Research Funding. Al-Samkari:Agios: Consultancy, Research Funding; Dova: Consultancy, Research Funding; Moderna: Consultancy. Barcellini:Incyte: Consultancy; Alexion: Consultancy, Speakers Bureau; Agios Pharmaceuticals, Inc.: Consultancy; Novartis: Speakers Bureau; Apellis: Consultancy; bioverativ: Consultancy. Eber:Agios Pharmaceuticals, Inc.: Consultancy. Glader:Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Chonat:Alexion: Other: advisory board; Agios Pharmaceuticals, Inc.: Other: advisory board. Rothman:Agios: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Kuo:Agios: Consultancy; Alexion: Consultancy, Honoraria; Apellis: Consultancy; Bioverativ: Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy; Celgene: Consultancy; Novartis: Consultancy, Honoraria; Pfizer: Consultancy. Kwiatkowski:Agios: Consultancy; bluebird bio, Inc.: Consultancy, Research Funding; Imara: Consultancy; Apopharma: Research Funding; Novartis: Research Funding; Celgene: Consultancy; Terumo: Research Funding. Ravindranath:Agios Pharmaceuticals, Inc.: Other: I am site PI on several Agios-sponsored studies, Research Funding. Neufeld:Octapharma, Shire Pharmaceuticals (Baxalta), Novo Nordisk, Celgene, NHLBI/NIH: Research Funding; Octapharma, Agios, Acceleron, Grifols, Pfizer, CSL Behring, Shire Pharmaceuticals (Baxalta), Novo Nordisk, ApoPharma, Genentech, Novartis, Bayer Healthcare: Consultancy; Octapharma: Other: study investigator, NuProtect study (Octapharma-sponsored). Holzhauer:Agios Pharmaceuticals, Inc.: Consultancy. Verhovsek:Sickle Cell Disease Association of Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding; Canadian Haemoglobinopathy Association: Membership on an entity's Board of Directors or advisory committees; Vertex: Consultancy; Sickle Cell Awareness Group of Ontario: Membership on an entity's Board of Directors or advisory committees. Kunz:Novartis: Membership on an entity's Board of Directors or advisory committees. Sheth:Apopharma: Other: Clinical trial DSMB; Celgene: Consultancy; CRSPR/Vertex: Other: Clinical Trial Steering committee. Despotovic:Novartis: Research Funding; Dova: Honoraria. Grace:Agios Pharmaceuticals, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding.