Long-term oxygen therapy in children with sickle cell disease and hypoxaemia.

OBJECTIVE: To evaluate the acceptability and safety profile of nocturnal long-term oxygen therapy (LTOT) in children with sickle cell disease (SCD) and chronic hypoxaemia. DESIGN: Retrospective cohort study. PATIENTS, SETTING AND INTERVENTION: Children with SCD who started LTOT from 2014 to early 2019 in two tertiary hospitals in London, UK were retrospectively enrolled. Patients who started disease-modifying therapies <12 months before LTOT or while on LTOT were excluded. MAIN OUTCOME MEASURES: Minor and major adverse events during LTOT were reported. Laboratory and clinical data, transcranial Doppler (TCD) scans and overnight oximetry studies performed at steady state within 12 months before and after starting LTOT were compared. RESULTS: Nineteen children (10 males; median age 12 years, range 6-15) were included. Nearly half of them (9/19; 47%) were on hydroxyurea at baseline. No child discontinued LTOT because of intolerance or poor adherence. No major adverse events were reported. Laboratory data did not show significant changes in haemoglobin and reticulocyte count after 1 year of follow-up. No statistically significant change in the incidence of vaso-occlusive pain events was noted (median annual rate from 0.5 to 0 episode per patient/year; p=0.062). Overnight oximetry tests performed while on LTOT showed improvements in all oxygen saturation parameters (mean overnight and nadir SpO2, % of time spent with SpO2 <90%) compared with the baseline. CONCLUSION: LTOT is a safe and feasible treatment option for children with SCD and chronic hypoxaemia.

A novel mixed living high training low intervention and the hematological module of the athlete biological passport.

Exposure to either natural or simulated hypoxia induces hematological adaptations that may affect the parameters of the Athlete Biological Passport (ABP). The aim of the present study was to examine the effect of a novel, mixed hypoxic dose protocol on the likelihood of producing an atypical ABP finding. Ten well-trained middle-distance runners participated in a "live high, train low and high" (LHTLH) altitude training camp for 14 days. The participants spent ˜6 hr.d-1 at 3000-5400 m during waking hours and ˜10 h.d-1 overnight at 2400-3000 m simulated altitude. Venous blood samples were collected before (B0), and after 1 (D1), 4 (D4), 7 (D7), and 14 (D14) days of hypoxic exposure, and again 14 days post exposure (P14). Samples were analyzed for key parameters of the ABP including reticulocyte percentage (Ret%), hemoglobin concentration ([Hb]), and the OFF-score. The ABP adaptive model was administered at a specificity of 99% to test for atypical findings. We found significant changes in [Hb] and Ret% during the hypoxic intervention. Consequently, this led to ABP threshold deviations at 99% specificity in three participants. Only one of these was flagged as an "atypical passport finding" (ATPF) due to deviation of the OFF-score. When this sample was evaluated by ABP experts it was considered "normal". In conclusion, it is highly unlikely that the present hypoxic exposure protocol would have led to a citation for a doping violation according to WADA guidelines.

Partial splenectomy for hereditary spherocytosis: a multi-institutional review.

BACKGROUND/PURPOSE: Partial splenectomy has emerged as a surgical option for selected children with hereditary spherocytosis, with the goal of reducing anemia while preserving splenic function. This multi-institutional study is the largest series to date examining outcomes data for partial splenectomy in patients with hereditary spherocytosis. METHODS: Data were collected retrospectively from 5 North American pediatric hospitals. Sixty-two children underwent partial splenectomy for hereditary spherocytosis between 1990 and 2008. RESULTS: At 1 year following partial splenectomy, mean hemoglobin significantly increased by 3.0 ± 1.4 g/dL (n = 52), reticulocyte count decreased by 6.6% ± 6.6% (n = 41), and bilirubin level decreased by 1.3 ± 0.9 mg/dL (n = 25). Patients with poor or transient hematologic response were found to have significantly more splenic regeneration postoperatively compared with patients with a durable clinical response (maximal spleen dimension, 9.0 ± 3.4 vs 6.3 ± 2.2 cm). Clinically significant recurrence of anemia or abdominal pain led to completion splenectomy in 4.84% of patients. No patients developed postsplenectomy sepsis. CONCLUSIONS: Our multi-institutional review indicates that partial splenectomy for hereditary spherocytosis leads to sustained and clinically significant improvement in hematologic profiles and clinical symptoms in most patients. Our data support partial splenectomy as an alternative for selected children with hereditary spherocytosis.

Management of iron deficiency anaemia in gynaecological patients at Jinnah Postgraduate Medical Centre, Karachi.

OBJECTIVE: To determine the efficacy and safety of subcutaneously administered recombinant human erythropoietin in combination with intravenous iron sucrose for the management of iron deficiency anaemia in gynaecological patients in Jinnah Postgraduate Medical Centre Karachi. METHODS: It was an interventional quasi experimental study carried out in the Department of Obstetrics /Gynaecology, at JPMC from 1st Nov 2007 to May 2008. All patients with indications for major Gynaecological surgery with iron deficiency anaemia having a mean haemoglobin level of 7 gm/dl were selected and the target haemoglobin was 11 gm/dl. Patients who were symptomatic, had chronic bleeding, renal failure or had signs of anaemia other than iron deficiency were excluded from the study. All investigations were done on day one before the start of therapy, and then treatment was initiated with recombinant human erythropoietin in a dose of 5000 IU subcutaneously and injection Iron Sucrose 200 mg in 100cc NaCI intravenously on 3 alternate days. The parameters checked in succession on day 4 and day 10 included increase in haemoglobin level, haematocrit, reticulocyte count, and time required to reach the target haemoglobin. RESULTS: Twenty three patients fulfilled the inclusion criteria and were selected for the study. At the end of 10 days of starting therapy increase in haemoglobin was on an average of 2.8 gm/dl, increase in mean corpuscular volume was 4fl, Serum Iron increased by 99.86 ug%, total iron binding capacity decreased by 30.86%, transferrin saturation increased by 15.5% .There were no serious reactions to Erythropoietin or Iron sucrose CONCLUSION: It is concluded that recombinant erythropoietin along with iron sucrose safely increased the haemoglobin level in 10 days to the target level thus rendering the patients fit for surgery and, none of the selected patients needed blood transfusion.

The effect of common hematologic abnormalities on the ability of blood models to detect erythropoietin abuse by athletes.

BACKGROUND AND OBJECTIVES: Algorithms that combine scores from multiple blood parameters are demonstrably effective in highlighting recombinant human erythropoietin (rHuEPO) administration, and have been used to deter rHuEPO use by athletes. These models are sensitive to atypical levels of blood parameters encountered during altered states of red cell production. Because hematologic abnormalities can also result in unusual blood profiles, the aim of this study was to document the incidence and magnitude of such abnormalities in an elite athlete population. DESIGN AND METHODS: We screened blood samples obtained from 413 female and 739 male elite athletes from 12 countries for known hematologic abnormalities, and compared the algorithm scores for these athletes with those of their healthy counterparts. We also established the magnitude of blood parameters required for model scores to exceed cut-offs associated with rHuEPO use. RESULTS: We found that 0.7% of male and 2.4% of female athletes were iron deficient either with our without anemia. An additional 1.4% of males and 1.0% of females had hemoglobinopathies. On average these athletes' model scores were at or below the score of their healthy counterparts. The greatest influence on our models was hemoglobin concentration. Values of other parameters must exceed normal ranges by a substantial margin in order for model scores to approach levels associated with rHuEPO use. INTERPRETATION AND CONCLUSIONS: The hematologic disorders we encountered in elite athletes were not associated with model scores that exceeded the nominal cut-offs that we have previously recommended to delineate rHuEPO use. We did not find any abnormalities among elite endurance athletes that were associated with high model scores.