The prevalence and demographic determinants of blood donors receiving testosterone replacement therapy at a large USA blood service organization.

BACKGROUND: Blood donors receiving testosterone replacement therapy (TRT) often require therapeutic phlebotomy due to erythrocytosis. Red blood cells (RBCs) donated by eligible TRT donors are approved for collection and transfusion. This study was aimed at defining the prevalence and demographic determinants of TRT donors at a large USA blood service organization. STUDY DESIGN: Donation data from TRT donors and matched controls was collected from a de-identified electronic donor database across 16 blood centers in 2017-2018. Demographic determinants included race, sex, age, hemoglobin (Hb), body mass index (BMI), mean arterial pressure (MAP), and the frequency of donations in the 2-year period. RESULTS: TRT donors comprised 1.6% of the donor population and produced 2.2% of RBC units during 2018. TRT donors were likely to be middle-aged white or Hispanic men, with high prevalence of obesity (50.8% of TRT donors had BMI ≥30 kg/m2 compared with 36.2% in controls) and intensive donation frequency (1 to 29 donations in 2 years vs. 1 to 12 in controls). TRT donors had significantly (p < 0.0001) higher MAP and Hb compared with controls (MAP 99.9 ± 9.81 vs. 96.5 ± 10.1 mmHg; Hb 17.8 ± 1.44 vs. 15.6 ± 1.37 g/dL). One year of donations was associated with significant decreases in MAP and Hb for TRT donors. CONCLUSIONS: TRT is associated with high prevalence of erythrocytosis and obesity that may explain the intensive donation frequency, high MAP, and Hb. Frequent phlebotomies had a moderately positive effect on blood pressure and Hb levels. Potential implications of TRT on the quality of the RBC products require further evaluation.

Noninvasive Assessment of Excessive Erythrocytosis as a Screening Method for Chronic Mountain Sickness at High Altitude.

Vyas, Kaetan J., David Danz, Robert H. Gilman, Robert A. Wise, Fabiola León-Velarde, J. Jaime Miranda, and William Checkley. Noninvasive assessment of excessive erythrocytosis as a screening method for chronic mountain sickness at high altitude. High Alt Med Biol 16:162-168, 2015.--Globally, over 140 million people are at risk of developing chronic mountain sickness, a common maladaptation to life at high altitude (>2500 meters above sea level). The diagnosis is contingent upon the identification of excessive erythrocytosis (EE). Current best practices to identify EE require a venous blood draw, which is cumbersome for large-scale surveillance. We evaluated two point-of-care biomarkers to screen for EE: noninvasive spot-check tests of total hemoglobin and oxyhemoglobin saturation (Pronto-7, Masimo Corporation). We conducted paired evaluations of total serum hemoglobin from a venous blood draw and noninvasive, spot-check testing of total hemoglobin and oxyhemoglobin saturation with the Pronto-7 in 382 adults aged ≥35 years living in Puno, Peru (3825 meters above sea level). We used the Bland-Altman method to measure agreement between the noninvasive hemoglobin assessment and the gold standard lab hemoglobin analyzer. Mean age was 58.8 years and 47% were male. The Pronto-7 test was unsuccessful in 21 (5%) participants. Limits of agreement between total hemoglobin measured via venous blood draw and the noninvasive, spot-check test ranged from -2.8 g/dL (95% CI -3.0 to -2.5) to 2.5 g/dL (95% CI 2.2 to 2.7), with a bias of -0.2 g/dL (95% CI -0.3 to -0.02) for the difference between total hemoglobin and noninvasive hemoglobin concentrations. Overall, the noninvasive spot-check test of total hemoglobin had a better area under the receiver operating characteristic curve compared to oxyhemoglobin saturation for the identification of EE as measured by a gold standard laboratory hemoglobin analyzer (0.96 vs. 0.82; p<0.001). Best cut-off values to screen for EE with the Pronto 7 were ≥19.9 g/dL in males and ≥17.5 g/dL in females. At these cut-points, sensitivity and specificity were both 92% and 89% for males and females, respectively. A noninvasive, spot-check test of total hemoglobin had low bias and high discrimination for the detection of EE in high altitude Peru, and may be a useful point-of-care tool for large-scale surveillance in high-altitude settings.

Polycythemia as rare secondary direct manifestation of acromegaly: management and single-centre epidemiological data.

Polycythemia associated with acromegaly is usually caused by the systemic manifestations of the disease, such as sleep-apnea or concomitant erythropoietin-secreting kidney tumors. The recognition of underlying pathologies requires a thorough diagnostic process. We report a unique case of acromegaly with polycythemia, not caused by commonly described manifestations of the disease, and receding with octreotide therapy. The medical history of 141 acromegalic patients followed by the Endocrinology Unit of the San Martino University Hospital in Genoa has been also reviewed, together with the literature evidence for similar cases. The diagnostic workflow and 2-years follow-up of a 43-years old acromegalic, polycythemic man with a history of past smoking, moderate hypertension, and mental retardation are described. The hematological parameters of our cohort was retrospectively compared with those of a healthy, age/gender-related control group as well. Therapy with octreotide LAR, 20 mg i.m. q28d was begun soon after diagnosis of acromegaly in the polycythemic patient. Haematocrit level, hormonal setting, as well as pituitary tumor size and visual perimetry during treatment were recorded. Octreotide LAR treatment normalized hormonal alterations, as well as hematological parameters. Polycythemia has not recurred after 2 years of therapy. The median hemoglobin and hematocrit levels of the retrospectively analyzed cohort of acromegalic were significantly lower than normal ranges of a healthy, age/sex- related control population. In conclusions, polycythemia can be a direct, albeit rare, secondary manifestation of acromegaly, that must be considered during the diagnostic work-up of acromegalic patients presenting with such disorder.

Normal ranges for packed cell volume and hemoglobin concentration in adults: relevance to 'apparent polycythemia'.

Published data from Europe and North America indicate that for non-iron-deficient adult Caucasian males, the normal mean packed cell volume (PCV) is 0.46 and the 2.5-97.5 percentile interval is 04.0-0.53. Corresponding values for adult Caucasian females are: mean PCV 0.42; 2.5-97.5 percentile interval 0.36-0.48. It is not usually appropriate to undertake studies of polycythemia in adult Caucasian males with PCV < 0.55 (Hb Conc. < 180 g/L) or in adult Caucasian females with PCV < 0.50 (Hb Conc. < 16.5 g/L). Application of this principle will reduce the number of inappropriate and costly studies that would otherwise be performed in patients whose PCV values are only in the upper percentiles of the normal range, and will help to avoid misdiagnoses and therapeutic misadventures.

Performance characteristics of Hemox-Analyzer for assessment of the hemoglobin dissociation curve.

The Hemox-Analyzer (TCS, Medical Products Division, Southampton, PA) is an automatic system for determining the oxyhemoglobin dissociation curve (ODC) and P50 values. The ODC is recorded during deoxygenation with nitrogen gas and plotted on graph paper; the oxygen tension is detected by a Clark electrode, while the oxyhemoglobin fraction (%HbO2) is evaluated by a dual-wavelength spectrophotometer. Even though this instrument has been commercially available for more than 20 years, its performance characteristics have been assessed. We evaluated the performance characteristics of the Hemox-Analyzer. P50 was tested in 28 healthy volunteers, in 16 anemic and in 9 polycythemic patients. To test its precision we evaluated both inter- and intra-assay variability. The system shows good precision: standard deviation was 0.39 for assays in duplicate, CV = 1.9% for intra-assay and CV = 3.0% for inter-assay measurements. The mean P50 values were 25.2 +/- 1.5 mmHg in normal volunteers and 27.3 +/- 1.4 mmHg in anemic patients. The Hemox-Analyzer is a simple, quick and reliable instrument for recording the oxyhemoglobin dissociation curve. Both the P50 value and observation of the fine structure of the curve can furnish information about the delivery of oxygen to tissues.

Randomized controlled trial of Ringer solution versus serum for partial exchange transfusion in neonatal polycythaemia.

UNLABELLED: We tested whether crystalliod solutions could be used instead of colloid solutions for partial exchange transfusions (PET) in polycythaemic neonates because crystalloid solutions are cheap, carry no risk of anaphylactic reactions and can be sterilized. We randomly assigned 20 term neonates with venous haematocrit (Hct) > 0.65 l/l to PET with either a serum preparation (BISEKO) or Ringer solution. Plasma volume (PV) was measured with Evans blue dilution. Blood volume (BV) and red cell mass were calculated from PV and venous Hct. Before PET both serum and Ringer groups had the same Hct (0.69 (0.66-0.76) vs 0.69 (0.66-0.71) l/l; median (range)) and BV (108 (81-116) versus 96 (68-121) ml/kg. During PET an equivalent amount of blood was withdrawn stepwise (19 (14-26) versus 17 (13-25) ml/kg and replaced by either serum or Ringer solution. More of the Ringer solution (median 77%) than of the serum (median 36%) given left the intravascular space within 4 h after PET (P = 0.016); but there was no significant difference in Hct after Ringer-PET compared to serum-PET (median 0.58 vs 0.56 l/l). No infant required repeat PET. Ringer-PET reduced BV from high to normal values (from median 96 to 83 ml/kg; P = 0.005), whereas after serum-PET BV remained high (from median 108 to 98 ml/kg; not significant). CONCLUSION: PET with Ringer solution resulted in a haemodilution comparable to PET with serum and a correction of hypervolaemia.

Quantitative assessment of erythropoiesis and functional classification of anemia based on measurements of serum transferrin receptor and erythropoietin.

We evaluated the quantitative value of a simple model of erythropoiesis, based on the basic assumptions that the red blood cell (RBC) mass determines erythropoietin (Epo) production, which in turn stimulates erythropoietic activity. The RBC mass was quantitated by direct isotopic measurement (RCM), Epo production by serum Epo levels, and erythropoiesis by the ferrokinetic measurement of the erythron transferrin uptake (ETU), the serum transferrin receptor (TfR) level, and the reticulocyte (retic) index, and was completed by an evaluation of overall marrow erythron cellularity. We studied a total of 195 subjects, including 31 normal individuals, 38 patients with polycythemia, and 126 patients with various forms of anemia. Instead of only quantitating Epo and erythropoiesis in absolute terms, we also evaluated them in relation to the degree of anemia or polycythemia, and expressed the results as a ratio of observed values to values predicted from the regression equations between hematocrit (Hct) on the one hand, and Epo, TfR, and ETU on the other, obtained in a carefully selected subpopulation. The slope of the regression of TfR (as well as ETU) versus Hct was very similar to the slope of the regression of Epo versus Hct. Average EPO and TfR (as well as ETU) values predicted from the regression equations were quite comparable to observed values in most groups of subjects, with exceptions predictable from knowledge of the pathophysiology of these hematologic disorders. We identified four major patterns of erythropoiesis, ie, normal, hyperdestruction (with variants of hemolysis or ineffective erythropoiesis), intrinsic marrow hypoproliferation, and defective Epo production. Dissecting out groups of patients showed much greater heterogeneity than when patients were analyzed by group. This was particularly true in the case of a hypoproliferative component being combined with hyperdestruction, giving what we called a "mixed disorder of erythropoiesis." We conclude that the pathophysiology of anemia can be assessed by a simple measurement of Hct, retic index, Epo, and TfR levels, with Epo and TfR being more informative when expressed in relation to the degree of anemia. The model is particularly useful for detecting the presence of multiple mechanisms of anemia in the same patient. However, it has limitations inherent to the relative invalidity of TfR in iron deficiency, the imprecision of a retic count, and the difficulty in distinguishing hemolysis from ineffective erythropoiesis in some patients and in recognizing a component of hyperdestruction in hypoproliferative anemia.

Assessment of an EIA for measuring human serum erythropoietin as compared with RIA and an in-vitro bioassay.

A recently developed enzyme-linked immunosorbent assay (EIAZ, ELISA) using two murine monoclonal anti-erythropoietin antibodies was compared with a radioimmunoassay (RIA) and a commercial in-vitro bioassay, EPOS, for measuring serum erythropoietin (Epo) in humans. Specificity and validity for Epo-EIA and the other two assays were examined. The serum Epo in normal subjects was 18 +/- 12 mU/ml (mean +/- SD, n = 80) for EIA compared with 22.5 +/- 18.5 mU/ml (n = 20) for RIA and 136 +/- 132 mU/ml (n = 14) for the bioassay. The serum Epo concentrations in normals and patients were highly comparable between EIA and RIA for Epo (P less than 0.01, r = 0.95). Epo concentrations by the EIA for normal female and male subjects were 20.5 +/- 13 and 16.5 +/- 10 mU/ml, respectively. Epo levels in patients with secondary polycythaemia or autoimmune haemolytic anaemia were significantly higher than normal subjects by the three methods. Epo levels in patients with chronic renal failure were within the normal range. By the EPOS bioassay, the Epo concentrations of normals and patients with renal failure were significantly higher than expected (136 +/- 132 and 447 +/- 273, respectively). Due to its inherent design, the EPOS bioassay possibly measures bone marrow proliferative activity in response to other serum growth regulators besides erythropoietin and was found to be unsuitable for clinical assessment of Epo. We concluded that the new EIA and RIA were similarly sensitive, reliable and accurate for measurement of serum Epo. The EIA method has the advantage of being less time consuming, more convenient and avoids the use of a radioisotope.

Use of serum from patients with polycythaemia or haemochromatosis for laboratory external quality assurance exercises.

Some External Quality Assessment Schemes (EQAS) require large volumes of human serum. During a one year period, 595 units of blood were obtained from 87 patients with haemochromatosis and polycythaemia, who underwent therapeutic venesection at the Edinburgh and South East Scotland Blood Transfusion Service. Serum from 59% of these donations was used in the EQAS for peptide hormones and related substances. The cost of the serum collection was 109 pounds/litre, but was only 33 pounds/litre of serum if the cost of the actual venesection was excluded. Results from tests on the sera were satisfactory in a variety of immunoassays for several different hormones. EQA schemes with requirements for large volumes of serum should consider therapeutic venesection as a cost effective means of obtaining serum.

[Assessment of the erythropoietin-producing function of the kidney and liver under controlled perfusion]. / Otsenka éritropoétinprodutsiruiushchei funktsii pochki i pecheni v usloviiakh upravliaemoi perfuzii.

The balance of erythropoietin production by the dog kidney and liver was studied during controlled normoxic perfusion. The hormone production was stimulated by acute posthemorrhagic anemia (bloodletting of 25% total blood volume) combined with subcutaneous injection of cobaltous chloride (250 microM/kg body weight). The increase in erythropoietin level was revealed in posthypoxic animal perfusate after 6 hours of perfusion. The amount of hepatic erythropoietin was shown to be 2.5 times higher than that excreted by kidneys.