Revisiting the most often used item in the haematological tool box-The extent of haemodilution in bone marrow aspirates.

In this issue, a nationwide retrospective Japanese study finds that, in a second opinion setting, one-third of bone marrow aspirates from patients suspected of myelodysplastic syndromes are heavily haemodiluted. Moreover, in four-fifths of such cases, the failure to obtain the correct material for diagnosis went undetected by the referring institution. These data are intriguing, but given their special set-up, caution should be exerted in transposing them to other countries. Commentary on: Ogata et al. Prevalence of massively diluted bone marrow cell samples aspirated from patients with myelodysplastic syndromes (MDS) or suspected MDS: A retrospective analysis of nationwide samples in Japan. Br J Haematol 2024;204:1856-1861.

A novel haemodilution chip mounted on the total thrombus-formation analysis system, a flow chamber system, enables stable analysis of platelet products under low platelet concentration/high shear conditions.

BACKGROUND AND OBJECTIVES: The total thrombus-formation analysis system (T-TAS) can quantitatively analyse the contribution of platelets to haemostasis using reconstituted blood samples. However, it is unsuitable in cases with low platelet counts. We introduced a haemodilution (HD) chip with a shallow chamber depth, adapted to low platelet counts and high shear conditions (1500 s-1). MATERIALS AND METHODS: Blood samples were prepared by mixing red blood cell products, standard human plasma and platelet products; the final platelet count was 50 × 103/µL. Aggregation tests were performed by using the aggregation inducers collagen, adenosine diphosphate (ADP) and ristocetin. Samples with 2-, 4- and 9-day-old platelet products (N = 10) were evaluated. RESULTS: The HD chip enabled the stable analysis of the haemostatic function of all samples at a platelet count of 50 × 103/µL. Haemostatic function was correlated with ADP aggregation (time to 10 kPa [T10]: r = -0.53; area under the curve for 30 min: r = 0.40) and storage period (T10: r = 0.44). CONCLUSION: The HD chip-mounted T-TAS can stably analyse haemostatic function under low platelet counts and high shear conditions; this approach is expected to serve as a bridge to in vivo haemostatic tests with experimental animals.

Fluid distribution during surgery in the flat recumbent, Trendelenburg, and the reverse Trendelenburg body positions.

BACKGROUND: The distribution and elimination of infused crystalloid fluid is known to be affected by general anesthesia, but it is unclear whether changes differ depending on whether the patient is operated in the flat recumbent position, the Trendelenburg ("legs up") position, or the reverse Trendelenburg ("head up") position. METHODS: Retrospective data on hemodilution and urine output obtained during and after infusion of 1-2 L of Ringer's solution over 30-60 min were collected from 61 patients undergoing surgery under general anesthesia and 106 volunteers matched with respect to the infusion volume and infusion time. Parameters describing fluid distribution in the anesthetized and awake subjects were compared by population volume kinetic analysis. RESULTS: General anesthesia decreased the rate constant for urine output by 79% (flat recumbent), 91% (legs up) and 91% (head up), suggesting that laparoscopic surgery per se intensified the already strong anesthesia-induced fluid retention. General anesthesia also decreased the rate constant governing the return of the distributed fluid to the plasma by 32%, 15%, and 70%, respectively. These results agree with laboratory data showing a depressive effect of anesthetic drugs on lymphatic pumping, and further suggest that the "legs up" position facilitates lymphatic flow, whereas the "head up" position slows this flow. Both Trendelenburg positions increased swelling of the "third fluid space". CONCLUSIONS: General anesthesia caused retention of infused fluid with preferential distribution to the extravascular space. Both Trendelenburg positions had a modifying influence on the kinetic adaptations that agreed with the gravitational forces inflicted by tilting to body.

Exploration of the Clinical Effect of Different Autotransfusion Methods on Patients With Femoral Shaft Fracture Surgery.

OBJECTIVE: To explore the clinical effect of predeposit, salvage, and hemodilution autotransfusion on patients with femoral shaft fracture (FSF) surgery. METHODS: Selected patients with FSF were randomly divided into three groups: intraoperative blood salvage autotransfusion, preoperative hemodilution autohemotransfusion, and predeposit autotransfusion. Five days after the operation, the body temperature, heart rate, blood platelet (PLT), and hemoglobin (Hb) of patients were determined. The concentrations of EPO and GM-CSF in the three groups were calculated by ELISA. The content of CD14+ monocytes was calculated by FCM assay. The growth time and condition of the patient's callus were determined at the 30th, 45th, and 60th day after operation. Cox regression analysis was used to analyze the correlation between EPO, GM-CSF, CD14+ mononuclear content, callus growth, and autotransfusion methods. RESULTS: There were no statistically significant differences in body temperature and heart rate between the three groups (p > 0.05). PLT and Hb in the Predeposit group were markedly increased compared with that in the Salvage and Hemodilution groups. The concentrations of EPO and GM-CSF in the Predeposit group were markedly increased compared with that in the Salvage and Hemodilution groups. The content of CD14+ monocytes in the Predeposit group was significantly higher than that in the Salvage and Hemodilution groups. Predeposit autotransfusion promotes callus growth more quickly. CONCLUSION: Predeposit autotransfusion promoted the recovery of patients with FSF after the operation more quickly than salvage autotransfusion and hemodilution autotransfusion.

Low-Volume Acute Normovolemic Hemodilution Does Not Reduce Allogeneic Red Blood Cell Transfusion in Cardiac Surgery in the Modern Era of Patient Blood Management: A Propensity Score-Matched Cohort Study.

OBJECTIVES: Patients undergoing cardiac surgery often require blood transfusions, which are associated with increased morbidity and mortality. Patient blood management (PBM) strategies, including acute normovolemic hemodilution (ANH), have been implemented to minimize allogeneic transfusion requirements. Older studies suggested that ANH is associated with reduced transfusions; however, its effectiveness in the modern era of PBM remains unclear. DESIGN: This was a retrospective cohort study. SETTING: The study was held at a single university hospital. PARTICIPANTS: 542 patients who underwent elective cardiac surgery with cardiopulmonary bypass (CPB) using low-priming-volume circuits between January 2017 and March 2022. INTERVENTIONS: Patients who received ANH were matched with those who did not receive ANH, using propensity scores. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion of patients who received perioperative red blood cell (RBC) transfusion. Of the 542 eligible patients, 49 ANH cases were propensity-score matched to 97 controls. The median ANH volume was 450 mL (IQR, 400-800 mL). There was no significant difference in perioperative RBC transfusion rates between the 2 groups (24.5% in the ANH group vs 30.9% in the control group, p = 0.42). The odds ratio for perioperative RBC transfusion in the ANH group versus the control group was 0.72 (95% CI, 0.32-1.55, p = 0.42). CONCLUSIONS: Low-volume ANH was not associated with a significant reduction in perioperative allogeneic RBC transfusion during cardiac surgery with CPB using low-priming-volume circuits. The benefits of low-volume ANH in reducing the requirement for RBC transfusion in the modern era of PBM may be smaller than reported previously.

Effect of acute normovolemic hemodilution in patients undergoing cardiac surgery with remimazolam anesthesia.

PURPOSE: The reduced effects of allogeneic transfusion with acute normovolemic hemodilution (ANH) have been reported. Harvesting a large volume of blood may maximize the effect in patients with low body weight, and the prevention of hypotension is important. Remimazolam is an anesthetic with few circulatory responses. Our aim was to evaluate whether high-volume ANH reduces the need for transfusion in cardiac patients under remimazolam anesthesia. METHODS: In this retrospective single-center study, we enrolled cardiopulmonary bypass (CPB) patients who received remimazolam anesthesia. Changes in hemodynamic parameters were assessed. The numbers of blood transfusions and chest tube outputs were also evaluated. RESULTS: In a total of 51 patients, ANH was performed in 27 patients with a mean body mass index of 23.2 (ANH volume: 740 ± 222 mL). No significant differences were observed in mean blood pressure during blood collection. The intraoperative amount of red blood cell (RBC) transfusion was significantly lower in the ANH group than in the control group (431 ± 678 and 1260 ± 572 mL, p < 0.001). The avoidance rates of RBC were 66.7 and 4.2%, respectively. The multivariate analysis result revealed that ANH correlated with RBC, with an odds ratio of 0.067 (95% confidence interval 0.005-0.84, p < 0.05). The postoperative bleeding at 24 h was significantly lower in the ANH group (455 ± 228 and 797 ± 535 mL, p < 0.01). CONCLUSION: In patients undergoing CPB, ANH reduced intraoperative transfusion amount and postoperative bleeding. Hemodynamic changes during blood collection were minimal under remimazolam anesthesia and high-volume ANH was feasible.

Effects of acute normovolemic hemodilution and allogeneic blood transfusion on postoperative complications of oral and maxillofacial flap reconstruction: a retrospective study.

OBJECTIVE: Patients undergoing oral and maxillofacial flap reconstruction often need blood transfusions due to massive blood loss. With the increasing limitations of allogeneic blood transfusion (ABT), doctors are considering acute normovolemic hemodilution (ANH) because of its advantages. By comparing the differences in the (Δ) blood indices and postoperative complications of patients receiving ABT or ANH during the reconstruction and repair of oral and maxillofacial tumor flaps, this study's purpose was to provide a reference for the clinical application of ANH. METHODS: The clinical data of 276 patients who underwent oral and maxillofacial flap reconstruction from September 25, 2017, to October 11, 2021, in the Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, were retrospectively analyzed. According to the intraoperative blood transfusion mode, the patients were divided into two groups: ABT and ANH. The differences in the (Δ) blood indices and the incidence of postoperative complications between the groups were analyzed. RESULTS: Among the 276 patients who had ANH (124/276) and ABT (152/276), there were no differences in (Δ) Hb, (Δ) PT, or (Δ) FIB (P > 0.05), while (Δ) WBC, (Δ) PLT, (Δ) APTT and (Δ) D-dimer were significantly different (P < 0.05). The blood transfusion method was not an independent factor for flap crisis (P > 0.05). The wound infection probability in patients with high post-PTs was 1.953 times greater than that in patients with low post-PTs (OR = 1.953, 95% CI: 1.232 ∼ 3.095, P = 0.004). A normal or overweight BMI was a protective factor for pulmonary infection, and the incidence of pulmonary infection in these patients was only 0.089 times that of patients with a low BMI (OR = 0.089, 95% CI: 0.017 ∼ 0.462). Moreover, a high ASA grade promoted the occurrence of pulmonary infection (OR = 6.373, 95% CI: 1.681 ∼ 24.163). The blood transfusion mode (B = 0.310, ß = 0.360, P < 0.001; ANH: ln hospital stay = 2.20 ± 0.37; ABT: ln hospital stay = 2.54 ± 0.42) improved the length of hospital stay. CONCLUSION: Preoperative and postoperative blood transfusion (Δ) Hb, (Δ) PT, and (Δ) FIB did not differ; (Δ) WBC, (Δ) PLT, (Δ) APTT, and (Δ) D-dimer did differ. There was no difference in the effects of the two blood transfusion methods on flap crisis, incision infection or lung infection after flap reconstruction, but ANH resulted in a 3.65 day shorter average hospital stay than did ABT.

Transfusion-free Strategies in Liver and Pancreatic Surgery: A Predictive Model of Blood Conservation for Transfusion Avoidance in Mainstream Populations.

OBJECTIVE: The objective of this study is to (1) describe the techniques and prove the feasibility of performing complex hepatobiliary and pancreatic surgery on a Jehovah Witness (JW) population.  (2) Describe a strategy that offsets surgical blood loss by the manipulation of circulating blood volume to create reserve whole blood upon anesthesia induction. BACKGROUND: Major liver and pancreatic resections often require operative transfusions. This limits surgical options for patients who do not accept major blood component transfusions. There is also growing recognition of the negative impact of allogenic blood transfusions. METHODS: A 23-year, single-center, retrospective review of JW patients undergoing liver and pancreatic resections was performed. We describe perioperative management and patient outcomes. Acute normovolemic hemodilution (ANH) is proposed as an important strategy for offsetting blood losses and preventing the need for blood transfusion. A quantitative mathematical formula is developed to provide guidance for its use. RESULTS: One hundred one major resections were analyzed (liver n=57, pancreas n=44). ANH was utilized in 72 patients (liver n=38, pancreas n=34) with median removal of 2 units that were returned for hemorrhage as needed or at the completion of operation. There were no perioperative mortalities. Morbidity classified as Clavien grade 3 or higher occurred in 7.0% of liver resection and 15.9% of pancreatic resection patients. CONCLUSIONS: Deliberate perioperative management makes transfusion-free liver and pancreatic resections feasible. Intraoperative whole blood removal with ANH specifically preserves red cell mass, platelets, and coagulation factors for timely reinfusion. Application of the described JW transfusion-free strategy to a broader general population could lessen blood utilization costs and morbidities.

Identification of critical hemodilution by artificial intelligence in bone marrow assessed for minimal residual disease analysis in acute myeloid leukemia: The Cinderella method.

Minimal residual disease (MRD) detection is a strong predictor for survival and relapse in acute myeloid leukemia (AML). MRD can be either determined by molecular assessment strategies or via multiparameter flow cytometry. The degree of bone marrow (BM) dilution with peripheral blood (PB) increases with aspiration volume causing consecutive underestimation of the residual AML blast amount. In order to prevent false-negative MRD results, we developed Cinderella, a simple automated method for one-tube simultaneous measurement of hemodilution in BM samples and MRD level. The explainable artificial intelligence (XAI) Cinderella was trained and validated with the digital raw data of a flow cytometric "8-color" AML-MRD antibody panel in 126 BM and 23 PB samples from 35 patients. Cinderella predicted PB dilution with high accordance compared to the results of the Holdrinet formula (Pearson's correlation coefficient r = 0.94, R2  = 0.89, p < 0.001). Unlike conventional neuronal networks Cinderella calculated the distributions of 12 different cell populations that were assigned to true hematopoietic counterparts as a human in the loop (HIL) approach. Besides characteristic BM cells such as myelocytes and myeloid progenitor cells the XAI identified discriminating populations, which were not specific for BM or PB (e.g., T cell/NK cell subpopulations and CD45 negative cells) and considered their frequency differences. Thus, Cinderella represents a HIL-XAI algorithm capable to calculate the degree of hemodilution in BM samples with an AML MRD immunophenotype panel. It is explicable, transparent, and paves a simple way to prevent false negative MRD reports.

Effects of acute normovolemic hemodilution on allogeneic blood transfusion & coagulation in orthognathic surgery: A randomized study.

BACKGROUND: Acute normovolemic hemodilution (ANH) is one of the important techniques predominantly used in cardiac, hepatic, and vascular surgery for decreasing allogeneic blood transfusion. However, the effect of ANH in orthognathic surgery has been rarely studied. Therefore, this study aims to assess the ANH-mediated reduction in the allogeneic red blood cell transfusion for orthognathic surgery patients. STUDY DESIGN AND METHODS: In this single-center study, 18-80 years old patients were recruited. Patients with hemoglobin ≥11 g/dL and normal coagulation function were randomly divided into ANH or standard treatment group. RESULTS: Ninety six patients underwent ANH, and 101 patients received standard treatment. No differences in demographic or major pre-operative characteristics were observed between the two groups. One patient in the ANH and three patients in the standard treatment group received allogeneic blood [3(2.97%) vs. 1(1.16%), control vs. ANH, p = .395]. Multivariate logistic regression analysis revealed that ANH treatment was not associated with transfusion of allogeneic blood (p = .763). After retransfusing autologous blood, PT and APTT in the ANH group significantly increased compared to standard treatment group (PT: -1.73 ± 1.09 vs. -2.15 ± 1.06, p = .035; APTT: -6.39 ± 5.76 vs. -8.16 ± 5.70, p = .031; control vs. ANH). No significant differences between the two groups were observed for changes in coagulation parameters at first postoperative day. However, platelet counts in the ANH group decreased compared to the standard group. No significant difference in major adverse outcomes was observed between the two groups. CONCLUSION: ANH did not reduce the incidence of allogeneic transfusion in patients undergoing orthognathic surgery.

Autologous versus allogeneic blood transfusion: A comparative study of the peri-operative outcomes in a tertiary care hospital in South India amidst the COVID-19 pandemic.

Autologous blood transfusion is known to have advantages over allogeneic transfusion. The COVID-19 pandemic intensified the already existing shortage of allogeneic blood supply. We carried out a study during this period with the aim to elicit the effects of autologous blood collection and transfusion, to compare the peri-operative outcomes of autologous and allogeneic transfusion practices and also to assess the influence of the autologous transfusion programme in the Blood Centre inventory. It was prospective observational comparative study among neurosurgical and vascular surgical patients in a tertiary care centre in South India. 141 patients were allocated into Group I (n = 71) who received autologous transfusion and those who received conventional allogeneic transfusion were clustered as Group II (n = 72) for analysis. We employed Acute Normovolemic Hemodilution (ANH), Pre-deposit Autologous Donation (PAD) and Intra-operative Cell Salvage (ICS) as various modalities for autologous blood collection. In our study, 43 (60.6%) from Group I received exclusive autologous blood transfusion, whereas 28 (39.4%) required additional allogeneic transfusion. No significant difference in hemoglobin, hematocrit, platelet count and INR were observed between the groups post transfusion. Significant difference was observed in the thoracoabdominal aortic aneurysm (TAAA) patients with respect to duration of ICU stay (2.7 ± 1.1 days in Group I and 6.2 ± 0.8 days in Group II; p = 0.002) and re-exploration due to bleeding (16.7% in Group I and 40% in Group II; p = 0.048). Autologous blood transfusion is safe and effective. It can be employed as routine practice and also during any acute shortage or pandemic.

Dose-dependent effect of canine lyophilized platelet on an in vitro hemodilution model.

The transfusion of stored platelets has emerged as an efficient method for treating dogs with thrombocytopenia. However, the availability of fresh platelets is limited in veterinary medicine due to demanding storage conditions. Lyophilized platelets have long shelf lives and can be easily stored, increasing their accessibility for thrombocytopenic dogs. Due to the lack of research and information on the dose effect, canine lyophilized platelets are used at a clinical dosage without research-based evidence. This study was to evaluate the dose effect of lyophilized canine platelets on blood coagulability. Three different concentrations of lyophilized canine platelets were added to in vitro hemodilution blood model, increasing the platelet count by 25, 50, and 100 × 106/ml and coagulation profiles were analyzed. The coagulability was evaluated via the plasma fibrinogen concentration, coagulation time, thromboelastography (TEG), and platelet function analyzer (PFA). Higher concentrations of lyophilized platelets showed dose-dependent association with decreased aPTT and R-time of TEG and increased alpha angle and MA of TEG. These results showed the potential that the higher dose of canine lyophilized platelets better improve blood coagulability than the standard dose and provided the basis for further safety and clinical studies.

Effect of acute normovolemic hemodilution on anesthetic effect, plasma concentration, and recovery quality in elderly patients undergoing spinal surgery.

OBJECTIVE: To explore the effect of acute normovolemic hemodilution (ANH) on the anesthetic effect, plasma concentration, and postoperative recovery quality in elderly patients undergoing spinal surgery. METHODS: A total of 60 cases of elderly patients aged 65 to 75 years who underwent elective multilevel spinal surgery were assigned randomly into the ANH group (n = 30) and control group (n = 30). Hemodynamic and blood gas analysis indexes were observed and recorded before ANH (T1), after ANH (T2), immediately after postoperative autologous blood transfusion (T3), 10 min (T4), 20 min (T5), 30 min (T6), 40 min (T7), and 50 min (T8) after the transfusion, and at the end of the transfusion (i.e., 60 min; T9). At T3 ~ 9, bispectral index (BIS) and train-of-four (TOF) stimulation were recorded and the plasma propofol/cisatracurium concentration was determined. The extubation time and recovery quality were recorded. RESULTS: The ANH group presented a lower MAP value and a higher SVV value at T2, and shorter extubation and orientation recovery time (P < 0.05) compared with the control group. BIS values at T8 and T9 were lower in the ANH group than those in the control group (P < 0.05). TOF values at T7 ~ 9 were lower in the ANH group than those in the control group (P < 0.05). There were no statistically significant differences in the postoperative plasma concentrations of propofol and cisatracurium between the groups (P > 0.05). CONCLUSION: During orthopedic surgery, the plasma concentration of elderly patients is increased after autologous blood transfusion of ANH, and the depth of anesthesia and muscle relaxant effect are strengthened, thus leading to delayed recovery of respiratory function and extubation.

Revisiting the benefits of isovolemic hemodilution red cell exchange for sickle cell disease.

BACKGROUND: Isovolemic hemodilution red cell exchange (IHD-RCE) is a modified form of the standard red cell exchange (STD-RCE), intended to reduce red cell requirements in patients with sickle cell disease (SCD). This retrospective crossover analysis of nine patients aims to add to the limited existing literature on IHD-RCE and address the equipoise regarding whether the benefits of (a) decreased RBC usage per exchange and (b) increased interprocedure interval (via lower fraction of cells remaining, FCR) can be observed at the same time, in the same patient. METHODS: At a single center, we identified 37 patients with SCD undergoing chronic RCE between 2014 and 2021. We excluded those patients who did not have at least six consecutive procedures of each type (STD- and IHD-RCE), arriving at nine patients for analysis. RESULTS: When using greater decreases in hematocrit than previously published, we did not find that IHD-RCE resulted in any clinically apparent adverse events. We did find greater decreases in diastolic blood pressure and increases in heart rate in some patients, as compared to STD-RCE. After correcting for total blood volume, seven of the nine patients had significantly reduced red cell requirements with each IHD-RCE. Because the pattern of achieving a lower FCR than programmed was seen to an equal extent with both IHD-RCE and STD-RCE, none of the nine patients showed any statistical difference in actual FCR between procedure types. DISCUSSION: Our data do not support the observation of both IHD-RCE benefits, decreased red cell usage per exchange and lower FCR/increased interprocedure interval, simultaneously.

Blood volume estimation in cardiac surgery - A comparative analysis.

INTRODUCTION: This paper seeks to identify which of three published formulas used for estimating the blood volume of normal human subjects correlates most closely with blood volumes measured in a published study where erythrocyte volume was determined by a method using 51Cr and a nonradioactive dye was used to determine the plasma volume. METHODS: Blood volumes predicted by three published algorithms were compared with blood volume estimates from a study by Retzlaff et al. using the two-tailed Wilcoxon signed rank test and a robust version of the Bland-Altman test. RESULTS: When applied to a sample of normal subjects selected from Mayo Clinic personnel and patients, the Nadler formula correlated more closely with blood volume measured using a radio nucleotide technique than did the Allen formula or one based on a saline haemodilution technique. CONCLUSIONS: The Nadler formula correlated more closely with blood volume measurements derived from Retzlaff's study than the other formulas for estimating blood volume in a population with height and weight distribution more consistent with that seen in North America. It should be used in preference to the Allen formula for estimating blood volume in adult patients currently undergoing cardiac surgical procedures. Saline haemodilution techniques used to measure blood volume require validation against more recently developed nuclear medicine techniques using statistical methods other than regression analysis. Until validated, they should be used with caution for estimating blood volume in adult patients currently undergoing cardiac surgical procedures. If a formula using height, weight and sex is used to estimate blood volume in the context of cardiac surgery, then it must be derived using a much more comprehensive sample of the population to which it is applied than has occurred to date. In particular, it should include broader distributions of height, weight and the presence or absence and type of significant valvular disease.

High-speed multi-parametric photoacoustic microscopy of cerebral hemodynamic and metabolic responses to acute hemodilution.

The ability of hemodilution to improve vascular circulatory impairment has been demonstrated. However, the effects of acute hemodilution on cerebral hemodynamics and oxygen metabolism have not been assessed at the microscopic level, due to technical limitations. To fill this void, we have developed a new, to the best of our knowledge, photoacoustic microscopy system, which enables high-speed imaging of blood hemoglobin concentration, oxygenation, flow, and oxygen metabolism in vivo. The system performance was examined in both phantoms and the awake mouse brain. This new technique enabled wide-field (4.5 × 3 mm2) multi-parametric imaging of the mouse cortex at 1 frame/min. Narrowing the field of view to 1.5 × 1.5 mm2 allowed dynamic imaging of the cerebral hemodynamic and metabolic responses to acute hypervolemic hemodilution at 6 frames/min. Quantitative analysis of the hemodilution-induced cerebrovascular responses over time showed rapid increases in the vessel diameter (within 50-210 s) and blood flow (50-210 s), as well as decreases in the hemoglobin concentration (10-480 s) and metabolic rate of oxygen (20-480 s) after the acute hemodilution, followed by a gradual recovery to the baseline levels in 1440 s. Providing comprehensive insights into dynamic changes of the cerebrovascular structure and function in vivo, this technique opens new opportunities for mechanistic studies of acute brain diseases or responses to various stimuli.

Hemodilution in high-risk cardiac surgery: Laboratory values, physiological parameters, and outcomes.

BACKGROUND: Acute normovolemic hemodilution (ANH) is a blood conservation strategy in cardiac surgery, predominantly used in coronary artery bypass graft (CABG) and/or valve procedures. Although higher complexity cardiac procedures may benefit from ANH, concerns for hemodynamic instability, and organ injury during hemodilution hinder its wider acceptance. Laboratory and physiological parameters during hemodilution in complex cardiac surgeries have not been described. STUDY DESIGN AND METHODS: This observational cohort (2019-2021) study included 169 patients who underwent thoracic aortic repair, multiple valve procedure, concomitant CABG with the aforementioned procedure, and/or redo sternotomies. Patients who received allogeneic blood were excluded. Statistical comparisons were performed between ANH (N = 66) and non-ANH controls (N = 103). ANH consisted of removal of blood at the beginning of surgery and its return after cardiopulmonary bypass. RESULTS: Intraoperatively, the ANH group received more albumin (p = .04) and vasopressor medications (p = .01), while urine output was no different between ANH and controls. Bilateral cerebral oximetry (rSO2 ) values were similar before and after hemodilution. During bypass, rSO2 were discretely lower in the ANH versus control group (right rSO2 p = .03, left rSO2 p = .05). No differences in lactic acid values were detected across the procedural continuum. Postoperatively, no differences in extubation times, intensive care unit length of stay, kidney injury, stroke, or infection were demonstrated. DISCUSSION: This study suggests hemodilution to be a safe and comparable blood conservation technique, even without accounting for potential benefits of reduced allogenic blood administration. The study may contribute to better understanding and wider acceptance of ANH protocols in high-risk cardiac surgeries.

Characterization of 2 Different Prothrombin Complex Concentrates by Different Hemostatic Assays in an In Vitro Hemodilution Model.

BACKGROUND: Viscoelastically guided coagulation factor concentrate-based algorithms for the treatment of trauma-induced coagulopathy include the administration of prothrombin complex concentrates (PCCs). However, the exact role of PCC preparations in this context is a matter of debate. Particularly, the ideal diagnostic trigger for their administration and potential differences between heparin-containing and heparin-free preparations remain unclear. We investigated the hypothesis that 2 different PCCs might have distinct influences on in vitro blood coagulation. METHODS: We conducted a direct comparison of 2 commercially available PCC preparations (the heparin-containing Beriplex P/N and the heparin-free Cofact) in an in vitro hemodilution model. Sole fibrinogen substitution served as the control group. To characterize the hemostatic changes, we utilized conventional coagulation tests, a thrombin generation assay (TGA), and 2 different viscoelastic hemostatic assays (VHAs; ROTEM delta and ClotPro). RESULTS: Irrespective of the diagnostic assay used, no significant differences between the 2 PCC groups were observed. Fibrinogen levels remained stable from the baseline throughout every dilution level. The control group already showed an increased endogenous thrombin potential (ETP; nM·L -1 ·min -1 ) at all dilution levels compared to baseline (baseline, 2829.4 (432.8); 40% dilution, 4211.7 (391.6); 60% dilution, 4290.9 (300.8); 80% dilution, 3861.4 (303.5); all P < .001). Spiking with both PCC preparations led to a further-pronounced thrombin elevation in comparison to the control group (ETP at 40% dilution, PCC1: 4913.3 [370.2], PCC2: 4988.1 [265.7]; 60% dilution, PCC1: 5174.5 [234.7], PCC2: 5390.4 [334.9]; 80% dilution, PCC1: 5253.8 [357.9], PCC2: 5392.6 [313.4]; all P < .001). Conventional coagulation tests did not mirror the TGA results. Despite increased thrombin generation, prothrombin time was significantly prolonged at all dilution levels for the control group, and both PCC groups exhibited significant prolongations at the 60% and 80% dilution levels (all P < .001) compared to baseline. Similarly, VHA did not depict the thrombin elevation. Furthermore, descriptive analyses revealed relevant differences between the 2 VHA devices, particularly at baseline. CONCLUSIONS: Both PCC preparations (ie, irrespective of heparin content) induced significant elevation of thrombin generation, which was not depicted by conventional coagulation tests or VHA. Our in vitro results suggest that diagnostic assays routinely used to guide PCC administration might not adequately reflect thrombin generation in bleeding patients.

Thrombin Generation in Cardiac Versus Noncardiac Surgical Cohorts.

BACKGROUND: Bleeding can be a significant problem after cardiac surgery. As a result, venous thromboembolism (VTE) or anticoagulation or both following mechanical valve implantation are often delayed in these patients. The calibrated automated thrombin (CAT) generation assay has become the gold standard to evaluate thrombin generation, a critical step in clot formation independent of other hemostatic processes (eg, platelet activation, fibrin cross-linking, and fibrinolysis), and is increasingly used to examine thrombotic and hemorrhagic outcomes. No study has currently used this assay to compare the thrombin generation profiles of cardiac surgical patients to noncardiac surgical patients. We hypothesize that noncardiac patients may be less prone to postoperative changes in thrombin generation. METHODS: A prospective, observational, cohort study was undertaken using blood samples from 50 cardiac and 50 noncardiac surgical patients preoperatively, immediately postoperatively, and on postoperative days 1 to 4. Platelet-poor plasma samples were obtained from patients preoperatively, on arrival to the postanesthesia care unit (PACU) or intensive care unit (ICU), and daily on postoperative days 1 to 4 if patients remained inpatient. Samples were evaluated for CAT measurements. Patient and surgical procedure characteristics were obtained from the electronic medical record. RESULTS: The primary outcome variable, median endogenous thrombin potential (ETP), measured in nanomolar × minutes (nM × min), was decreased 100% in cardiac surgical versus 2% in noncardiac patients (P < .001). All parameters of thrombin generation were similarly depressed. Cardiac (versus noncardiac) surgical type was associated with -76.5% difference of percent change in ETP on multivariable regression analysis (95% confidence interval [CI], -87.4 to -65.5; P value <.001). CONCLUSIONS: Cardiac surgical patients exhibit a profound decrease in thrombin generation postoperatively compared with noncardiac surgical patients evaluated by this study. Hemodilution and coagulation factor depletion likely contribute to this decreased thrombin generation after cardiac surgery.

Effects of Hemodilution on Clot Waveform Analysis Parameters, Clotting Factors, and Thrombin Generation Assays in a Dilutional Model Based on Analysis of 11 Healthy Male Blood Donors.

BACKGROUND Clot wave analysis (CWA) during activated partial thromboplastin time (aPTT) measures the speed and extent of fibrin polymerization in the plasma. This study aimed to evaluate the effects of hemodilution on CWA parameter, clotting factors, and thrombin generation assays in a dilutional model. MATERIAL AND METHODS Platelet-poor plasma obtained from 11 healthy male volunteers was diluted with 0.9% sodium chloride by 10-80% to analyze coagulation profiles, CWA, clotting factors, and thrombin generation assays. CWA includes 5 parameters: the time-dependent variable (aPTT), rate/acceleration (min1, min2, and max2), and magnitude of signal change (delta). RESULTS Critically low activities of 30% for clotting factors and 100 mg/dl of fibrinogen were determined at dilutions of 70% and 60%, respectively. Peak thrombin and endogenous thrombin potential were significantly lower compared with baseline after 50% and 80% dilution, respectively. aPTT did not correlate with the decrease in the clotting factors up to dilutions of 50% and subsequently became abnormal values. As the change in rate/acceleration parameters parallels the time course of clotting factor activity in a dilution-dependent linear manner, these parameters indicate an intervention threshold at critically low activities of clotting factors. The strongest correlations were observed between clotting factors and aPTT, clotting factors and min2, delta and peak thrombin (r=0.95), and delta and fibrinogen (r=0.98). CONCLUSIONS aPTT was significantly correlated with clotting factors, while the rate/acceleration parameters and delta changed with variation in thrombin and fibrinogen generation. These findings may help in evaluating coagulability.