Differences in red blood cell mass profiles impact intravascular volume and outcome risk in chronic heart failure.

AIMS: To identify different red blood cell mass (RBCM) profiles, separate from haemoglobin concentrations, and their impact on blood volume expansion and clinical outcomes in chronic heart failure. METHODS AND RESULTS: RBCM was measured at hospital discharge using standardized nuclear medicine indicator-dilution methodology in patients following diuretic treatment for clinical congestion. Individual RBCM phenotypes were prospectively identified and analysed for heart failure-related mortality or first rehospitalization over 1 year. Of 132 patients, 42 (32%) demonstrated normal RBCM, 36 (27%) RBCM deficit (true anaemia), and 54 (41%) RBCM excess (erythrocythemia). Dilutional 'anaemia' defined by haemoglobin <12 g/dL with normal or an excess in RBCM with plasma volume expansion was identified in 37 (28%) patients. There were 61 composite outcome events, which included 38 deaths (29% of cohort) occurring over the 1 year follow-up period [14/36 (39%) in RBCM deficit, 12/42 (29%) in normal RBCM, and 12/54 (22%) in RBCM excess subgroups]. By Kaplan-Meier and multivariate analyses, RBCM excess was independently associated with the best event-free survival while RBCM deficit (true anaemia) the poorest outcomes; both compared with normal RBCM (P < 0.001). Dilutional 'anaemia' demonstrated a lower risk compared with true anaemia (P = 0.03). CONCLUSIONS: Markedly different RBCM profiles are identifiable among comparably compensated heart failure patients, and this variability carries significant implications for post-hospital outcomes. Novel to this analysis and in contrast to RBCM deficit is the independent association of RBCM excess with better event-free survival compared with normal RBCM. The distinction of RBCM profiles to guide risk stratification and individualized patient management strategies warrants further study.

Common clonal origin of three distinct hematopoietic neoplasms in a single patient: B-cell lymphoma, T-cell lymphoma, and polycythemia vera.

The potential for more than one distinct hematolymphoid neoplasm to arise from a common mutated stem or precursor cell has been proposed based on findings in primary human malignancies. Particularly, angioimmunoblastic T-cell lymphoma (AITL), which shares a somatic mutation profile in common with other hematopoietic malignancies, has been reported to occur alongside myeloid neoplasms or clonal B-cell proliferations, with identical mutations occurring in more than one cell lineage. Here we report such a case of an elderly woman who was diagnosed over a period of 8 years with diffuse large B-cell lymphoma, polycythemia vera, and AITL, each harboring identical somatic mutations in multiple genes. Overall, at least five identical nucleotide mutations were shared across multiple specimens, with two identical mutations co-occurring at variable variant allele frequencies in all three specimen types. These findings lend credence to the theory that a common mutated stem cell could give rise to multiple neoplasms through parallel hematopoietic differentiation pathways.

Simulated Altitude via Re-Breathing Creates Arterial Hypoxemia but Fails to Improve Elements of Running Performance.

Acclimatization to altitude has been shown to improve elements of performance. Use of simulated altitude is popular among athletes across the sports spectrum. This work was on a handheld, re-breathing device touted to enhance performance. Seven recreationally-trained athletes used the device for 18 hours over the course of the 37-day intervention trial. The elevations simulated were progressively increased from 1,524m to 6,096m. To ascertain potential efficacy, four performance trials were included (familiarization, baseline, and 2 follow-ups). Hematological (hematocrit, hemoglobin, and lactate), physiological (respiratory exchange ratio, heart rate, and oxygen consumption), and perceptual (Borg's RPE) variables were monitored at rest, during two steady state running economy stages, and at maximal effort during each visit. The device is clearly capable of creating arterial hypoxemic conditions equating to high altitude. This fact is exemplified by average pulse oximetry values of approximately 78.5% in the final 6-day block of simulation. At the same time, there were no changes observed in any hematological (p>0.05), physiological (p>0.05), or perceptual (p>0.05) variable at either follow-up performance trial. Relative VO2 data was analyzed with a 15-breath moving average sampling frequency in accordance with our recent findings (Scheadler et al.) reported in Medicine and Science in Sports and Exercise. Effect sizes are reported within, but most were trivial (d=0.0-0.19). Overall, findings align with speculation that a more robust altitude stimulus than can be offered by short-term arterial hypoxemia is required for changes to be evidenced. The device has shown some promise in other work, but our data is not supportive.

Impact of menstruation on select hematology and clinical chemistry variables in cynomolgus macaques.

BACKGROUND: In preclinical studies with cynomolgus macaques, it is common to have one or more females presenting with menses. Published literature indicates that the blood lost during menses causes decreases in red blood cell mass variables (RBC, HGB, and HCT), which would be a confounding factor in the interpretation of drug-related effects on clinical pathology data, but no scientific data have been published to support this claim. OBJECTIVES: This investigation was conducted to determine if the amount of blood lost during menses in cynomolgus macaques has an effect on routine hematology and serum chemistry variables. METHODS: Ten female cynomolgus macaques (Macaca fascicularis), 5 to 6.5 years old, were observed daily during approximately 3 months (97 days) for the presence of menses. Hematology and serum chemistry variables were evaluated twice weekly. RESULTS: The results indicated that menstruation affects the erythrogram including RBC, HGB, HCT, MCHC, MCV, reticulocyte count, RDW, the leukogram including neutrophil, lymphocyte, and monocyte counts, and chemistry variables, including GGT activity, and the concentrations of total proteins, albumin, globulins, and calcium. The magnitude of the effect of menstruation on susceptible variables is dependent on the duration of the menstrual phase. Macaques with menstrual phases lasting ≥ 7 days are more likely to develop changes in variables related to chronic blood loss. CONCLUSIONS: In preclinical toxicology studies with cynomolgus macaques, interpretation of changes in several commonly evaluated hematology and serum chemistry variables requires adequate clinical observation and documentation concerning presence and duration of menses. There is a concern that macaques with long menstrual cycles can develop iron deficiency anemia due to chronic menstrual blood loss.

Peripheral Venous Hemoglobin and Red Blood Cell Mass Mismatch in Volume Overload Systolic Heart Failure: Implications for Patient Management.

Peripheral venous hemoglobin (Hb) measurements are considered to accurately reflect circulating red blood cell mass (RBCM). In volume overload decompensated chronic heart failure (DCHF), reliance on Hb values may be misleading. Using quantitative radiolabel blood volume analysis (BVA), we evaluated the relation of RBCM to volume overload and reliability of Hb measurements to reflect RBC status in patients hospitalized for DCHF. Of 32 patients evaluated (LVEF <50 %), 19 met WHO Hb criteria for anemia. By BVA, however, only 4/19 had true anemia (low Hb and low RBCM) while 15/19 demonstrated plasma volume expansion dilution-related "anemia" (6 low Hb/normal RBCM, 9 low Hb/excess RBCM). The remaining 13/32 had normal range Hb (12 with excess RBCM). Overall, 66 % of cohort demonstrated RBCM excess. RBC profiles are highly variable in DCHF, and peripheral Hb values are often misleading in identifying RBC status. These findings have implications for volume management.