Safety of Weekly Primaquine in Glucose 6 Phosphatase Dehydrogenase (G6PD) Deficient Children

Aim: To assess the Safety of weekly Primaquine in Glucose 6 Phosphatase Dehydrogenase (G6PD) deficient children, for radical treatment of Plasmodium vivax malaria Study Design: cross sectional study Place and Duration: Pediatrics Out Patient Department, Liaquat University of Medical and Health Sciences Hyderabad from 11 January 2018 to 31st August 2019 (total 20 months’ duration) Methodology: A sample of 40 patients was studied during study period. Male children between 4 years to 12 years of age having confirmed vivax malaria were included in the study. If G6PD result showed decreased level of G6PD level then, they were enrolled for study. MP was checked by thick and thin slide method. 5 ml blood was taken in anticoagulant bottle for G6PD, liver function test, creatinine, complete blood count, and reticulocyte count tests. Haemoglobin < 7 g/dL, reticulocyte count > 4, SGPT > 80, G6PD Level < 60% of normal and creatinine > 1.2 was considered significant. Treatment was given with Artemether and Lumefantrine for 3 days while Primaquine, 0 .75 mg base/kg body weights once a week was given for 8 weeks. Patients were followed at OPD initially on 3rd day of therapy then every week for 8 weeks for any hemolysis. Results: There was no hemolysis during the first week and 8 weeks after therapy. Most common side effect was abdominal pain 4 (10%). Mean hemoglobin was 11.8mg/dl. Plasmodium vivax was negative on 3rd day of therapy, it was also negative on 8 week of therapy. Reticulocyte count, Liver function test, creatinine were also normal on 8 weeks of therapy. Conclusion: Primaquine 0.75mg//kg/week for total eight weeks is highly effective for the radical cure of Plasmodium vivax in G6PD deficient children. There is no recurrence of Plasmodium vivax after 8 weeks of therapy. We found this regimen safe as there was no hemolysis demonstrated in children.

Large Hemoglobin Differences at Birth in Monochorionic Twins with a Placental Chorangioma and Delayed Cord Clamping

We report a case of a monochorionic diamniotic twin with an uncomplicated pregnancy, but with an unexpected large intertwin hemoglobin (Hb) difference at birth. Twin 1 was delivered vaginally and had an uneventful neonatal course. The umbilical cord of Twin 1 was clamped approximately 5 min after birth. After the birth of Twin 1, Twin 2 developed severe bradycardia and showed limited cardiac output on ultrasound, for which an emergency cesarean section was performed. A full blood count revealed an Hb of 20.1 g/dL for Twin 1 and 10.2 g/dL for Twin 2 (intertwin difference 9.9 g/dL). Reticulocyte counts were similar, 40‰ and 38‰, respectively. Placental examination revealed 10 vascular anastomoses, including one arterio-arterial anastomosis with a diameter of 1.4 mm. Additionally, a large chorangioma was present on the placental surface of Twin 2. There was no color difference on the maternal side of the placenta. Based on the reticulocyte count ratio and the placental characteristics, twin anemia polycythemia sequence was ruled out as the cause of the large intertwin Hb difference. In this report, we discuss the various potential causes that could explain the large intertwin Hb difference including the role of delayed cord clamping in Twin 1, and the role of a large chorangioma, which may have attracted blood from the fetal circulation of Twin 2.

Efficacy and Safety of Eltrombopag with or without Immunosuppressant in Patients with Relapsed/Refractory Acquired Aplastic Anemia: A Real-World Experience

Background: Eltrombopag (EPAG) with or without immunosuppressant (IST) has been applied in acquired aplastic anemia (AA), yet data of EPAG+IST in relapsed/refractory AA was limited, and no study has compared efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients. Aims: To evaluate and compare the efficacy and safety between EPAG+IST and EPAG monotherapy in relapsed/refractory AA patients in a real-world setting. Methods: Data from patients diagnosed as acquired AA in our center were retrospectively collected. All the enrolled patients were refractory/relapsed to the standard IST for at least 6 months before EPAG. All patients had been treated with EPAG, which was started at 25 mg/day and increased every 2 weeks to a maximum of 150 mg/day until a best response was achieved. Meanwhile, some patients were treated with cyclosporin A (CsA) or tacrolimus (FK506) at the same time. EPAG had to be prescribed for at least 6 months before evaluation. Complete response (CR), overall response (OR) and relapse rate, as well as adverse events and factors which could affect efficacy were analyzed. Results: Totally 99 patients (83 non-severe AA (NSAA) and 16 SAA) were included in the study. The median age at EPAG initiation was 46 (13-88) years old, the median time of EPAG treatment was 11 (6-41) months and the median time of follow-up was 18 (6-41) months. 72 patients were treated with EPAG+IST, including 41 (56.9%) treated with EPAG+FK506 and 31 (43.1%) treated with EPAG+CsA. 27 patients were treated with EPAG alone. No significant difference was found between EPAG+IST group and EPAG group in patient baseline characteristics like age, male proportion, NSAA proportion, presence of PNH clone, proportion of previous ATG+CsA / CsA treatment, previous IST duration and dosage. With compatible follow-up time, EPAG exposure duration and dosage, there was no significant difference in OR/CR rate at 3 rd/6 th/12 th month between patients who was treated with EPAG+FK506 and EPAG+CsA. Under similar compatible baseline conditions, the OR rate was 33.3% vs 22.2% (P=0.284) at 3 rd month, 61.1% vs 37.0% (P=0.032) at 6 th month, and 67.2% vs 42.1% (P=0.051) at 12 th month for patients treated with EPAG+IST and EPAG alone, respectively, but no significant difference was found in time to response (3 (1-12) vs 3 (1-7) months, P=0.679) or CR rate at 3 rd/6 th/12 th month (6.9%/12.5%/20.7% vs 3.7%/7.4%/5.3%, P&gt;0.05) between the two groups. Relapse occurred at 6 th to 12 th month of EPAG treatment, and the relapse rate at 12 th month was 9.8% and 27.3% (P=0.154) for patients treated with EPAG+IST and EPAG alone, respectively. For patients treated with EPAG+IST, responders had a significantly higher baseline reticulocyte count (60.25 (11.5-230.5)×10 9/L vs 16.7 (6.6-56.6)×10 9/L, P=0.040) compared with non-responders. No predictive factors for the overall response were found for patients treated with EPAG alone. Adverse events which led to dosage regulation were gastrointestinal disorders (2.8% vs 3.7%, P=1.000), elevated creatinine (2.8% vs 0, P=0.599), elevated ALT (1.4% vs 0, P=1.000) and arthralgia (0 vs 3.7%, P=0.280) for patients with EPAG+IST and EPAG, respectively. No deaths were found in either group, while the clone evolution rate was 2.8% and 3.7% (P=1.000) in EPAG+IST and EPAG monotherapy group, respectively. Conclusion: EPAG+IST had higher OR rate than EPAG monotherapy with similar side effects for patients with relapsed/refractory acquired AA. Those with higher baseline reticulocyte count were more likely to respond to EPAG+IST. Key words: relapsed/refractory, aplastic anemia, eltrombopag, immunosuppressant, efficacy Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: In the presented study, eltrombopag was prescribed in relapsed/refractory aplastic anemia patients.

The Effect of Voxelotor on Exercise Capacity of Youths with Sickle Cell Anemia

Background/Hypothesis: Children and adults with sickle cell anemia (SCA) exhibit decreased cardiopulmonary fitness. Anemia is directly related to oxygen carrying capacity and is one factor that affects cardiopulmonary fitness. The new sickle cell drug voxelotor raises hemoglobin in patients with SCA treated or untreated with hydroxyurea. We hypothesized that voxelotor improves exercise capacity in youths with SCA. Methods: A single-center, open-label, single-arm longitudinal interventional pilot study was conducted for patients with SCA age &gt; 12. Participants performed baseline Cardiopulmonary Exercise Testing (CPET#1), took 1500mg voxelotor for 2 months, then CPET was repeated (CPET#2). A modified Bruce Protocol using 2-minute stages was performed on a motorized treadmill, for a goal of 8-12 minutes of exercise. Breath by breath gas exchange data were collected and analyzed using a VMax Encore 29C metabolic cart. The metabolic test included standard monitoring of heart rate, EKG ST changes, arrhythmias, and O2 saturation. A respiratory quotient &gt;1.1 was used as evidence of participant effort. Peak oxygen consumption (peak VO2), anaerobic threshold (AT), O2 pulse, VE/VCO2 slope, and time exercised in CPET#1 and CPET#2 were compared for each participant. The primary endpoint was peak VO2. Hemoglobin (Hgb), reticulocyte count, and bilirubin were measured before CPET#1 and CPET#2. Pill count was used to monitor medication adherence and left shift of the P50 oxygen dissociation curve was used to document biochemical effect of voxelotor. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected at the end of the study. Statistical analysis was performed using Student's paired T-test. Results: Nine SCA patients ages 12-20, including 4 males and 5 females, completed the study. All had Hgb SS and were stably maintained on hydroxyurea, which was continued without dose change during the study. After 2 months of voxelotor, all participants demonstrated expected hematologic changes, including mean rise in Hgb +1.3 g/dL (95% C.I.= 0.8, 1.7), mean decrease in reticulocyte count -2.4% (95% C.I.= -4.1, -0.8), and mean decrease in bilirubin -0.4 mg/dL (95% C.I.= -0.8, -0.1). All participants demonstrated voxelotor adherence and leftward shift of p50 (Table 1). Oxygen consumption, measured as percent predicted peak VO2 (ml/kg/min), ranged from 52% to 80% in CPET#1 and from 55% to 71% in CPET#2. The changes in peak VO2 for individual participants ranged from -10% to +10% of predicted peak VO2, with a mean difference of -2.2% (95% CI = -7.1, 2.7), which is insignificant (p=0.3). Using +/- 6% as variability in peak VO2 measurement, 5 participants exhibited no change, 3 participants had decrease in peak VO2 of -7%, -9%, and -10%, while peak VO2 increased by +10% for a single participant, who started to exercise on his own after starting voxelotor. Changes in individuals' anaerobic threshold, O2 pulse, VE/VCO2 slope, and time exercised were not significant and did not correlate with changes in peak VO2. All participants achieved respiratory quotient &gt;1.1, assuring participant effort during CPET (Table 2). On the 7-point PGIC questionnaire evaluating activity limitations, symptoms, emotions, and overall quality of life, 7 out of 9 participants reported positive change, including "a great deal better," "definite," and "moderate" improvements. Two participants reported minimal to no change, and no participants reported worsening. In comparison, clinicians reported "minimal" to "much" improvement on CGIC for all participants. Overall, patient impression of improvement was higher than clinician impression of improvement. Conclusion: This pilot study demonstrated the feasibility of using CPET to evaluate exercise capacity longitudinally in youths with SCA. After addition of voxelotor to hydroxyurea for 2 months, all patients perceived global improvement. Peak VO2 did not change in 8 out of 9 participants and improved for 1 participant who exercised between the 2 CPETs. To increase peak VO2, higher Hgb increase, concurrent regular exercise, and longer exposure to voxelotor may be necessary. This study was funded by Global Blood Therapeutics Figure 1 Figure 1. Disclosures Larkin: Forma Therapeutics, Inc.: Research Funding. Dulman: Pfizer: Other: own stock. Kuypers: Forma Therapeutics, Inc.: Research Funding.

Hyperhemolysis Syndrome in SCD Patient: Reminder of a Rare but Life-Threatening Complication of Blood Transfusion

Background: Sickle cell disease (SCD) patients are at risk of developing multiple complications from transfusions, including alloimmunization to red blood cell (RBC) antigens, delayed hemolytic transfusion reactions, and hyperhemolysis syndrome (HS). HS is a serious complication of transfusion characterized by the destruction of both transfused and autologous RBCs with resulting severe anemia and post transfusion hemoglobin lower than pretransfusion levels. We report the case of a middle age female patient with known SCD who developed severe HS following a blood transfusion. We aim to remind physicians of the importance of conservative blood transfusions in SCD patients in order to avoid serious transfusion-related complications. Case report: A 57-year-old African American patient, with known history of SCD who was doing well with a baseline hemoglobin (Hgb) of 6-7 g/dl. Transfusion history included 4 units of Packed Red Blood Cell (PRBC) during the 5 years prior to this presentation, all of which for mild, non-resolving vaso-occlusive pain crisis. Her most recent transfusion was 7 days prior to her presentation, she received 1 unit of PRBC for a Hgb level of 6.3 g/dl, associated with mild musculoskeletal pain and fatigue. She presented to the Emergency Department 4 days later with worsening fatigue, decreased oral intake and dark urine. On presentation, she was normotensive, afebrile and mildly tachycardic. She had increasing oxygen requirements to maintain O2 saturation above 94%. Her blood work showed a Hgb of 2.8 g/dl (12-15 g/dL), hematocrit 8.3 % (36-46 %), RBC count 0.87 M/uL (4.15-5.55 M/uL), Mean Corpuscular Volume 95.5 fl (80-100 fl), elevated White Cell Count at 28.4 K/uL (3.8-10.6 K/uL), and platelet count 125 K/uL (150-450 K/uL). Hemolysis labs showed low haptoglobin of &lt; 30 mg/dl (30-200 mg/dl), elevated Lactate Dehydrogenase at 3420 IU/L (&lt; 250 IU/L), total bilirubin 2.7 mg/dl (&lt; 1.2 mg/dl), direct bilirubin 0.6 mg/dl (0-0.3 mg/dl), and reticulocyte count 3.5% (0.5-1.5 %; reticulocytopenia relative to degree of anemia). A disseminated intravascular coagulation (DIC) panel showed fibrinogen of 263 mg/dL (200-450 mg/dL), D-dimer greater than 20 ug/mL (&lt; 0.50 ug/ml), prothrombin time of 19.8 seconds (s) (11.5-14.5 s), and partial thromboplastin time of 32 s (22-36 s). High sensitivity troponin was elevated at 650 ng/L (&lt; 19 ng/L). Antibody screen and direct antiglobulin test (DAT) were negative. Peripheral blood smear showed severe anemia with marked anisopoikilocytosis including numerous blister cells, occasional sickle cells and numerous nucleated red blood cells. The recent history of blood transfusion and the current laboratory workup were consistent with HS. Patient was admitted to the intensive care unit (ICU) for management; she initially received 1g intravenous iron dextran and intravenous immunoglobulin (IVIG) 0.4 g/kg for 5 days. She was also started on erythropoietin, folic acid, and vitamin B12. Her reticulocyte count improved to 19%. Given no improvement in Hgb levels, systemic steroids were started after ruling out infectious etiologies. She initially received methylprednisolone 125mg daily for 2 days, followed by oral prednisone 60mg daily for 7 days. Patient had increased oxygen requirements during admission, had an elevated lactate to 4 mmol/L, and had a drop in Hgb to 2.1 g/dL. She was still managed conservatively with oxygen supplementation and intravenous crystalloid fluids. The decision was to avoid transfusions unless they were life-saving. Patient remained in the ICU unit for 5 days, then was transferred to the hematology floor where she remained hospitalized for 7 days. Oxygen requirements and patient's symptoms steadily improved, hemolysis labs trended down, and reticulocyte count improved. Hgb levels improved gradually to highest of 5.7 g/dl prior to discharge. Patient was then discharged to follow up with her hematologist in the outpatient setting. Conclusion: This case aims to highlight the importance of early recognition of HS to avoid wrong management with RBC transfusion. Our patient had severe anemia and was managed with transfusion-free approach with good outcome. This case is also meant to remind physicians of the importance of conservative blood transfusions in SCD patients in order to avoid serious and life-threatening transfusion-related complications. Disclosures No relevant conflicts of interest to declare.

Clinical Profile and Long-Term Outcomes of Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with Eculizumab in a Real-World Setting: High Frequency of Anemia Despite Decreased Intravascular Hemolysis

Background: Eculizumab, an anti-C5 antibody, was approved for the treatment of patients (pts) with symptomatic paroxysmal nocturnal hemoglobinuria (PNH) in 2007 and has been the standard of care for over a decade. However, published data on real-world outcomes of eculizumab-treated pts with PNH are limited. The aim of this study was to describe the clinical profile of pts with PNH treated with eculizumab by characterizing their short- and long-term laboratory and clinical outcomes. Methods: This retrospective study (Versmold et al, Blood 2020) used preexisting medical records of eculizumab-treated pts with PNH (treatment duration ≥24 weeks [wks]) treated at the University Hospital Essen, Germany prior to April 2018. Anonymized data were collected via electronic case report forms. Laboratory data were extracted from the hospital computer system. Lactate dehydrogenase (LDH), hemoglobin, absolute reticulocyte count (ARC), and bilirubin profiles were assessed at baseline (12 months before treatment) and during the treatment phase (up to 13.2 years [yrs] follow-up). Breakthrough hemolysis (BTH) was defined as ≥1 new symptom or sign of intravascular hemolysis (including fatigue, hemoglobinuria, abdominal pain, dyspnea, anemia [hemoglobin &lt;10 g/dL], major adverse vascular event [including thrombosis], dysphagia, or erectile dysfunction in the presence of elevated LDH [≥2 × the upper limit of normal (ULN)] after reduction of LDH to ≤1.5 × ULN). Extravascular hemolysis was defined as persistence of reticulocytes &gt;100 × 10 9/L with bilirubin &gt;1 × ULN and positive direct Coombs test or reticulocytes &gt;100 × 10 9/L with bilirubin &gt;1 × ULN and ≥1 positive C3c or C3d test. Complete hematologic response was zero blood transfusions with hemoglobin ≥12 g/dL and LDH ≤1.5 × ULN and major hematologic response was zero blood transfusions with hemoglobin ≥12 g/dL and LDH &gt;1.5 × ULN within any 24-wk window (Risitano et al, Front Immunol 2019). Transfusion-dependence was ≥2 blood transfusions within any 24-wk period. Pts transferred from other centers or within 24 wks of treatment were excluded due to missing baseline data. Results: The study included 56 pts with PNH (mean age: 42.9 yrs [± 17.6]; 46.4% female) treated with eculizumab for ≥24 wks (mean follow-up: 5.24 yrs [± 3.25]) during the study period. The median duration from diagnosis to starting eculizumab was 1.57 yrs. Overall, 18 pts (32.1%) had aplastic anemia at diagnosis, 10 (17.9%) had symptoms of high disease activity, and 34 (60.7%) had a blood transfusion in the prior 12 months. The most reported disease-related symptoms at baseline were anemia (28.6%), fatigue (26.8%), thrombosis (21.4%), dyspnea (17.9%), dysphagia (10.7%), erectile dysfunction (10.0%), kidney complications (8.9%), abdominal pain (8.9%), and hemoglobinuria (7.1%). Mean hemoglobin (n=44) was 9.67 g/dL [± 2.06] and LDH in the past 12 months (n=47) was 1480 U/L [± 1010]. During the first 24-wk treatment phase, 37% (20/54) of pts had LDH &gt;1.5 × ULN, 31% (14/45) had ARC &gt;1.5 × ULN, and 17% (8/47) had hemoglobin ≥12 g/dL (Figure). Among pts with response data, 15% (7/47) had complete hematologic response and 2% (1/47) had major hematologic response within 24 wks. Documented BTH with symptoms occurred in 11% (6/56). Moreover, 23% (13/56) of pts were transfusion-dependent, increasing to 39% (22/56) when including pts who had ≥1 transfusion during the first 24 wks of treatment. Six pts (11%) received a higher-than-labeled dose (600 mg intravenous [IV] weekly for 4 wks, 900 mg IV 1 wk later, then 900 mg IV every 2 wks thereafter) of eculizumab. Over the long term (ie, between 25 and 246 wks), 11.1-34.7% of pts received blood transfusions and 7.0-21.7% had LDH &gt;1.5 × ULN in any 24-wk window; whereas 36.1-72.7% had ARC &gt;1.5 × ULN (Figure). Moreover, 65.8-77.3% of pts had hemoglobin &lt;12 g/dL within any 24-wk period and 69.0-77.2% did not meet the criteria for major or complete hematologic response during any 24-wk period from wks 25 to 246. During the treatment phase, no meningococcal infections were reported. Conclusions: In this long-term real-world study, a considerable proportion of pts with PNH treated with eculizumab did not achieve optimal clinical outcomes with an ongoing burden of disease (ie, low hemoglobin level with high reticulocyte count due to extravascular hemolysis, BTH, etc.). Future exploration of other therapies that improve pt outcomes could help to address remaining unmet medical needs. Figure 1 Figure 1. Disclosures Alashkar: Alexion: Honoraria; Novartis: Honoraria; BMS/Celgene: Honoraria; Bluebird Bio: Honoraria. Ofori-Asenso: F. Hoffmann-La Roche Ltd: Current Employment. Xu: F. Hoffmann-La Roche AG: Current Employment. Liu: Genesis Research: Current Employment. Katz: F. Hoffman-La Roche Ltd: Current Employment. Shang: F. Hoffman-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Roeth: Apellis Pharmaceuticals: Consultancy, Honoraria; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Bioverativ, a Sanofi company: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Kira: Consultancy, Honoraria.

Reticulocyte Count: The Forgotten Factor in Transfusion Decisions for Extremely Low Birth Weight Infants

Objective Extremely low birth weight (ELBW) infants often receive transfusions of packed red blood cells (PRBCs). Long-term outcomes of infants treated with liberal versus restricted transfusion criteria have been evaluated with conflicting results. Clinicians incorporate a reticulocyte count (RC) in their transfusion decisions. There is a lack of information on reference ranges for RCs in growing ELBW infants and whether infant's chronologic age or corrected gestational age (GA) generates a specific trend in the RCs. Our aim was to evaluate the levels of RCs obtained from ELBW infants over the course of the initial hospitalization. Study Design A retrospective chart review of ELBW infants treated in the neonatal intensive care unit (NICU) and had RCs performed. We analyzed the RCs to observe trends based on the chronologic age and corrected GA. Results A total of 738 RCs were analyzed. A positive trend in RCs that reached a peak at 32 to 34 weeks' corrected GA and then experienced a downward trend was observed. Conclusion Our report examines a very common hematologic test that is theoretically helpful but is in need of guidelines concerning the appropriate frequency of testing and its utility in making transfusion decisions in ELBW infants. Key Points

Investigation of the correlation between immature reticulocyte fraction and reticulocyte hemoglobin content with common tests for iron deficiency anemia

Reticulocyte hemoglobin content (Ret-He, the hemoglobin within reticulocytes or immature red blood cells) and immature reticulocyte fraction (IRF, the immature fraction of the absolute-reticulocyte-count) are tests that provide insight into erythropoiesis and iron status earlier than conventional iron studies offering the added benefit of not being acute-phase-reactants. Studies have shown that Ret-He is a diagnostic marker for iron-deficiency-anemia (IDA), but fewer studies have investigated IRF. Our laboratory is currently planning to report these parameters when reticulocyte is ordered. Since these are new parameters, we wanted to investigate their overall correlation with complete blood count (CBC) and other iron studies to gain a better appreciation of their utility in our patient population. The aim of this study was to compare the overall correlation of Ret-He and IRF with seven tests used in the evaluation of IDA. To our knowledge these parameters have not all been directly correlated within a single study. CBC and reticulocytes were quantified using XN 9000 hematology analyzers (Sysmex Corporation), ferritin (DXI 800, Beckman Coulter Inc.), and % iron-saturation (measured using total iron-binding-capacity (TIBC)=transferrin*1.18 on Cobas 6000, Roche Diagnostics). Two de-identified cohorts of patients undergoing physician-ordered reticulocyte testing were used for this analysis. Dataset 1 (DS1): (N=2026 from Mayo Clinic Florida) had Ret-He and IRF compared to absolute-reticulocyte-count (Ret), ferritin and % iron saturation. Dataset 2 (DS2): (N=3990 from Mayo Clinic Rochester) had Ret-He and IRF compared to the red-cell-indices of the CBC including hemoglobin (Hgb), mean-corpuscular-volume (MCV), mean-corpuscular-hemoglobin (MCH), and mean-corpuscular-hemoglobin-concentration (MCHC). Correlation coefficients were calculated using Spearman rank-order (ρ) wherein values below +/-0.39 are weak, between +/-0.40-0.59 are considered moderate, and values above +/-0.60 are considered strong. For DS1, Ret-He demonstrated the following correlations: Ret (ρ=0.01), ferritin (ρ=0.33), % iron saturation (ρ=0.63). IRF demonstrated: Ret (ρ=0.46), ferritin (ρ=-0.05), % iron saturation (ρ=-0.22). For DS2, Ret-He demonstrated the following correlations: Hgb (ρ=0.17), MCV (ρ=0.64), MCH (ρ=0.74), MCHC (ρ=0.56). IRF demonstrated Hgb (ρ=-0.41), MCV (ρ=0.10), MCH (ρ=0.04), MCHC (ρ=-0.11). Ret-He and IRF demonstrated different correlative profiles suggesting they may have differing uses. Ret-He was strongly positively-correlated with % iron saturation, MCV, MCH and moderately positively-correlated with MCHC. These positive-correlations are consistent with relationships established in the literature. Interestingly, Ret-He was only weakly correlated with ferritin, possibly owing to ferritin being an acute-phase-reactant. IRF had a moderate positive correlation with Ret and moderate inverse correlation with Hgb. Both of these IRF relationships are consistent with other reports, but both relationships have not been shown in the same study before, preventing direct comparison until now. The literature suggests IRF may have more potential in monitoring treatment than in diagnosis. One limitation of these datasets is their lack of clinical correlation such as established iron-deficiency, anemia status, or treatment information.

Physiological and Clinical Impact of Repeated Inhaled Oxygen Variation on Erythropoietin Levels in Patients After Surgery

The “Normobaric Oxygen Paradox” (NOP) is a physiologic mechanism that induces an increase of endogenous erythropoietin (EPO) production by creating a state of relative hypoxia in subjects previously exposed to hyperoxia, followed by a rapid return to normoxia. Oxygen exposure duration and inspired oxygen fraction required to observe a significant increase in EPO or hemoglobin are not clearly defined. Consequently, we here study the effect of one model of relative hypoxia on EPO, reticulocytes and hemoglobin stimulation in patients after surgery. Patients were prospectively randomized in two groups. The O2 group (n = 10) received 100% oxygen for 1 h per day for eight consecutive days, via a non-rebreathing mask. The control group (n = 12) received no oxygen variation. Serum EPO, hemoglobin and reticulocyte count were measured on admission and postoperatively on days seven and nine. Percentage EPO at day nine with respect to the baseline value was significantly elevated within the groups [O2 group: 323.7 (SD ± 139.0); control group: 365.6 (SD± 162.0)] but not between them. No significant difference was found between the groups in terms of reticulocytes count and hemoglobin. Our NOP model showed no difference on EPO increase between the two groups. However, both groups expressed separately significant EPO elevation.