Blood Cell Transfusion Volume Research Articles

Introduction of a ROTEM-assisted strategy improves patient blood management in children undergoing open craniosynostosis repair

Purpose The surgical correction of craniosynostosis by open cranial vault reconstruction (OCVR) is often associated with significant blood loss and perioperative blood transfusion demand. Because of transfusion risks, several attempts have been made to eliminate the need for perioperative homologous blood transfusion with the implementation of goal-directed transfusion protocols. The aim of this study was to determine whether the introduction of a rotational thromboelastometry (ROTEM)–assisted patient blood management strategy would decrease the intraoperative blood transfusion and blood loss levels. Methods Patients younger than 2 years of age who were diagnosed with nonsyndromic single suture synostosis and underwent primary OCVR were investigated in this retrospectively designed cohort study. The children were equally divided into 2 study groups according to the availability of the ROTEM-assisted protocol. The control group had surgery before introduction of the new protocol, whereas the study group was operated on subsequently. Demographic, blood loss, and transfusion data of the preprotocol cohort were compared with those of the postprotocol cohort. Results In total, 100 children, separated in 2 groups (50 patients each), were analyzed. The mean age at the time of surgery was 8.5 months in the pre-ROTEM-assisted protocol group, and 8.7 months in the postimplementation group. The estimated blood volume loss dropped from 60.8 mL/kg to 49.6 mL/kg after initiation of the current strategy. The intraoperative packed red blood cell (PRBC) transfusion volume decreased from 32.6 mL/kg to 17.1 mL/kg. Administration of PRBCs in the postoperative period also was reduced, compared with the period before implementation of the ROTEM-assisted regimen, from 21.8 mL/kg to 15.9 mL/kg. The average length of hospital stay was reduced from 5.4 days to 4.7 days after use of the ROTEM-assisted protocol. Conclusions As indicated by our results, the use of a ROTEM-assisted protocol is associated with considerable reduction in blood volume loss and perioperative allogeneic transfusion requirements in the surgical management of craniosynostosis with OCVR.

C1 inhibitor in canine intravascular hemolysis (C1INCH): study protocol for a randomized controlled trial

BackgroundImmune-mediated hemolytic anemia (IMHA) is a common disease that affects all breeds of dogs and is associated with significant morbidity and mortality. Intravascular hemolysis of erythrocytes in IMHA is caused by complement activation and is often fatal. No current treatments target complement activation in canine IMHA. Human C1 esterase (C1-INH) reduces canine complement-mediated hemolysis in vitro, and a recent pharmacokinetic analysis of an FDA licensed formulation of C1-INH in dogs confirmed that a 50 IU/kg dose of C1-INH is safe to administer to dogs, and effectively inhibits canine complement mediated hemolysis ex-vivo. The C1INCH randomized controlled trial will evaluate the efficacy of this drug in dogs with intravascular hemolysis.MethodsWe will conduct a multicenter, placebo-controlled double-blind randomized clinical trial of C1-INH in dogs with intravascular hemolysis due to IMHA. We will randomize 18 dogs to receive three doses of intravenous C1-INH or saline in 24 h. Immunosuppressive and antithrombotic therapies will be standardized. Primary outcome measures will be changes in plasma free hemoglobin, serum concentrations of LDH, bilirubin, and haptoglobin. Using patient samples, we will evaluate complement activation in canine IMHA using a novel C5b-9 ELISA assay, flow cytometric detection of C3b on RBC, and by measurement of residual plasma complement activity. Secondary outcome measures will be survival to hospital discharge, duration of hospitalization, number and volume of red blood cell transfusions, and rescue therapy requirements. We will monitor dogs for adverse drug reactions. Sample size was estimated from pilot data on LDH and hemolysis index (HI) in dogs with IMHA. To detect 2-way differences between the upper and lower 50% of the LDH and HI values of equivalent size with 80% power at P < 0.05 will require 9 dogs in each arm.DiscussionWe anticipate that IV administration of C1-INH will significantly inhibit complement mediated hemolysis in dogs with intravascular IMHA, as determined by blood biomarker measurements (decreased plasma hemoglobin, LDH and bilirubin, increased haptoglobin). We expect this will translate into significant reductions in transfusion requirements and duration of hospitalization.Trial registrationThis trial has been prospectively registered with the AVMA registry (AAHSD005025).

Serum Level of Hepcidin and Erythropoietic Activity after Hematopoietic Stem Cell Transplantation.

Hepcidin, first identified in human urine as a bactericidal peptide, is now considered a central molecule that regulates iron metabolism. Synthesis of hepcidin is known to be up-regulated by at least two signals: iron signal and interleukin-6 (IL-6) signal. The existence of a third signal, an erythropoiesis-associated pathway, has recently been suggested by several researchers experimenting with a mouse model treated with either chemotherapy or irradiation. However, the finding has not yet been clarified in human clinical settings partly because of difficulty in quantitatively measuring the serum level of hepcidin. Therefore, we monitored and assessed the association between the serum level of hepcidin and erythropoietic activity before and after stem cell transplantation for hematological malignancies, because the conditioning regimen followed by SCT dramatically changes the status of erythropoiesis in patients. The serum level of hepcidin-25 was quantitatively measured using a liquid chromatography tandem mass spectrometry-based assay system with synthetic isotopic hepcidin as an internal control, which made our quantification much more reliable and reproducible with very small intra- and inter-assay CVs. (Intra-assay and inter-assay CVs were <6.7% and <8.8%, respectively.) We also measured serum levels of various iron-related parameters and IL-6 as well as bone morphogenetic protein (BMP)-2 and BMP-4. The level of serum hepcidin-25 at week -1 was high (mean ± SD; 74.9 ± 93.9 ng/ml), compared to that in control sera from 28 healthy volunteers (mean ± SD; 21.9 ± 12.3 ng/ml), and the level further increased and peaked at week+1 after SCT (mean ± SD; 255.9 ± 99.3 ng/ml), possibly due to the high level of IL-6 and suppression of erythropoiesis. The hepcidin level of patients at week+4 with delayed erythropoiesis (reticulocyte count less than 40,000 /μl) was significantly higher (p<0.02) than that in those with rapid erythropoiesis (reticulocyte count more than 80,000 /μl). The result did not change even if cases were limited to those without elevated IL-6 levels to exclude the influence of IL-6 on hepcidin expression. Transferrin saturation increased to almost 100% after conditioning therapy and slowly decreased concurrent with erythroid recovery. In contrast, the serum ferritin level tended to increase even after erythroid engraftment irrespective of serum IL-6 or hepcidin levels and the volume of blood cell transfusions after SCT. The level of serum BMP-2 was significantly elevated at all of these time points after SCT compared to that in control sera from 6 healthy volunteers. Among these findings, the level of serum hepcidin-25 was inversely and precisely correlated with reticulocyte counts during and after SCT, suggesting that serum hepcidin-25 may be a good indicator of erythropoietic activity as well as iron utilization by erythropoiesis. These findings indicated that hepcidin is regulated by erythropoiesis through a putative erythropoiesis-associated factor. High serum hepcidin levels observed in SCT patients might have contributed to the disturbance of iron homeostasis and increased serum ferritin levels. Further investigation is needed to clarify the clinical significance of hepcidin in SCT settings.