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Introduction Numerous clinical studies related the plasma level of C-reactive protein ( CRP) to the erythrocyte sedimentation rate ( ESR) independent of the kind of disease. The molecular regulation of the process is unknown. Methods We performed a meta-analysis of 10 previous studies and experimentally probed for a direct action of CRP on red blood cells ( RBCs) by different methods including determination of a microscopic aggregation index, Ca2+ imaging and analysis of sedimentation experiments. Results The meta-analysis revealed a statistically significant correlation (Pearson coefficient of 0.37; P < 0.0001), but we could not find any experimental evidence for a direct CRP- RBC interaction. Instead, we could confirm a correlation between fibrinogen level and ESR. Conclusion Therefore, we concluded that CRP and ESR cannot account for nor replace each other as a diagnostic measure. The correlation between CRP level and ESR is most probably caused by fibrinogen, because its increase coincides with elevated CRP levels. [ABSTRACT FROM AUTHOR]

. Burri E, Hochholzer K, Arenja N, Martin-Braschler H, Kaestner L, Gekeler H, Hatziisaak T, Büttiker M, Fräulin A, Potocki M, Breidthardt T, Reichlin T, Socrates T, Twerenbold R, Mueller C (University Hospital Basel, Basel; University Hospital, Basel, Switzerland). B-type natriuretic peptide in the evaluation and management of dyspnoea in primary care. J Intern Med 2012; 272: 504-513. Objectives. The rapid and accurate diagnosis of heart failure in primary care is a major unmet clinical need. We evaluated the additional use of B-type natriuretic peptide (BNP) levels. Design. A randomized controlled trial. Setting. Twenty-nine primary care physicians in Switzerland and Germany coordinated by the University Hospital Basel, Switzerland. Subjects. A total of 323 consecutive patients presenting with dyspnoea. Interventions. Assignment in a 1 : 1 ratio to a diagnostic strategy including point-of-care measurement of BNP ( n = 163) or standard assessment without BNP ( n = 160). The total medical cost at 3 months was the primary end-point. Secondary end-points were diagnostic certainty, time to appropriate therapy, functional capacity, hospitalization and mortality. The final diagnosis was adjudicated by a physician blinded to the BNP levels. Results. Heart failure was the final diagnosis in 34% of patients. The number of hospitalizations, functional status and total medical cost at 3 months [median $1655, interquartile range (IQR), 850-3331 vs. $1541, IQR 859-2827; P = 0.68] were similar in both groups. BNP increased diagnostic certainty as defined by the need for further diagnostic work-up (33% vs. 45%; P = 0.02) and accelerated the initiation of the appropriate treatment (13 days vs. 25 days; P = 0.01). The area under the receiver-operating characteristics curve for BNP to identify heart failure was 0.87 (95% confidence interval, 0.81-0.93). Conclusions. The use of BNP levels in primary care did not reduce total medical cost, but improved some of the secondary end-points including diagnostic certainty and time to initiation of appropriate treatment. [ABSTRACT FROM AUTHOR]

Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE-). Blood samples were collected from 30 EE+ and 15 EE- in La Rinconada (Peru, 5100-5300 m a.s.l.), with special attention given to the sampling pre-analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet-poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE- and LL (all P < 0.01). At normalized haematocrit, clotting times were normalized in most individuals. Conversely, maximal clot firmness was normalized only in FIBTEM and not in EXTEM/INTEM assays, suggesting abnormal platelet activity. Thrombin generation, levels of plasma clotting factors and inhibitors, and standard coagulation assays were mostly normal in all groups. No highlanders reported a history of venous thromboembolism based on the dedicated survey. Collectively, these results indicate that EE+ do not present a hypercoagulable profile potentially favouring thrombosis., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Adenosine Triphosphatase (ATPase) Phospholipid Transporting 11C gene (ATP11C) encodes the major phosphatidylserine (PS) flippase in human red blood cells (RBCs). Flippases actively transport phospholipids (e.g., PS) from the outer to the inner leaflet to establish and maintain phospholipid asymmetry of the lipid bilayer of cell membranes. This asymmetry is crucial for survival since externalized PS triggers phagocytosis by splenic macrophages. Here we report on pathophysiological consequences of decreased flippase activity, prompted by a patient with hemolytic anemia and hemizygosity for a novel c.2365C > T p.(Leu789Phe) missense variant in ATP11C. ATP11C protein expression was strongly reduced by 58% in patient-derived RBC ghosts. Furthermore, functional characterization showed only 26% PS flippase activity. These results were confirmed by recombinant mutant ATP11C protein expression in HEK293T cells, which was decreased to 27% compared to wild type, whereas PS-stimulated ATPase activity was decreased by 57%. Patient RBCs showed a mild increase in PS surface exposure when compared to control RBCs, which further increased in the most dense RBCs after RBC storage stress. The increase in PS was not due to higher global membrane content of PS or other phospholipids. In contrast, membrane lipid lateral distribution showed increased abundance of cholesterol-enriched domains in RBC low curvature areas. Finally, more dense RBCs and subtle changes in RBC morphology under flow hint toward alterations in flow behavior of ATP11C-deficient RBCs. Altogether, ATP11C deficiency is the likely cause of hemolytic anemia in our patient, thereby underlining the physiological role and relevance of this flippase in human RBCs., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Including artificial intelligence in haematological education is compulsory but should not be limited to students. Experienced haematologist and decision-makers in the clinical environment have at least similar needs. This is because of the tremendous potential, opportunities and benefits the timely inclusion of artificial intelligence offers in diagnosis, prediction and personalised therapy. Commentary on: Chai et al. Integrating artificial intelligence into haematology training and practice: opportunities, threats and proposed solutions. Br J Hematol 2022;198:807-811., (© 2022 The Author. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Aims: Total haemoglobin mass (tot-Hb) increases during high-altitude acclimatization. Normalization of tot-Hb upon descent is thought to occur via neocytolysis, the selective destruction of newly formed erythrocytes. Because convincing experimental proof of neocytolysis is lacking, we performed a prospective study on erythrocyte survival after a stay at the Jungfraujoch Research Station (JFJRS; 3450 m)., Methods: Newly formed erythrocytes of 12 male subjects (mean age 23.3 years) were age cohort labelled in normoxia (110 m) and during a 19-day high-altitude sojourn by ingestion of 13 C2- and 15 N-labelled glycine respectively. Elimination dynamics for erythrocytes produced in normoxia and at high altitude were measured by isotope ratio mass spectrometry of haem, by determining tot-Hb, reticulocyte counts, erythrocyte membrane protein 4.1a/4.1b ratio and by mathematical modelling., Results: Tot-Hb increased by 4.7% ± 2.7% at high altitude and returned to pre-altitude values within 11 days after descent. Elimination of 13 C- (normoxia) and 15 N- (high altitude) labelled erythrocytes was not different. Erythropoietin levels and counts of CD71-positive reticulocytes decreased rapidly after descent. The band 4.1a/4.1b ratio decreased at altitude and remained low for 3-4 days after descent and normalized slowly. There was no indication of haemolysis., Conclusion: We confirm a rapid normalization of tot-Hb upon descent. Based on the lack of accelerated removal of age cohorts of erythrocytes labelled at high altitude, on patterns of changes in reticulocyte counts and of the band 4.1a/4.1b ratio and on modelling, this decrease did not occur via neocytolysis, but by a reduced rate of erythropoiesis along with normal clearance of senescent erythrocytes., (© 2021 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)