Hemostatic capability of ultrafiltrated fresh frozen plasma compared to cryoprecipitate.

This in vitro study evaluated the potential hemostatic effect of fresh frozen plasma (FFP) ultrafiltration on clotting factors, coagulation parameters, and plasma properties. ABO-specific units of FFP (n = 40) were prepared for the concentrated FFP and cryoprecipitate. Plasma water was removed from FFP by ultrafiltration using a dialyzer with a pump running at a 300 mL/min. The aliquot of each concentrated FFP after 50, 100, 200, and 250 mL of fluid removal were measured the standard coagulation assay, clotting activity, and plasma properties to compare those parameters of cryoprecipitate. Concentrated FFP contained 36.5% of fibrinogen in FFP with a mean concentration of 7.2 g/L, lower than the cryoprecipitate level. The levels of factor VIII (FVIII), von Willebrand factor (VWF):antigen (Ag), and VWF:ristocetin cofactor (RCo) were also lower in concentrated FFP, whereas the levels of factor V, factor IX, factor XIII, antithrombin and albumin was higher in concentrated FFP. Maximum clot firmness (MCF) in thromboelastometry was approximately one-half of that in cryoprecipitate. Although the levels of VWF:Ag, VWF:RCo, and FVIII differed depending on the ABO blood types, fibrinogen levels, and MCF were not significantly different among the ABO blood groups in FFP and concentrated FFP.

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.

Effects of room temperature and cold storage on the metabolic and haemostatic properties of whole blood for acute normovolaemic haemodilution.

BACKGROUND: Acute normovolaemic haemodilution (ANH), as a blood-conservation technique, avoids the need for allogeneic blood transfusions. The historic practice of cold-storing type-O whole blood (WB) in military fields popularised the transfusion of refrigerated WB to treat acute bleeding. In this study, we compared the effects of room temperature (RT) and refrigeration up to 24 hours on the coagulation properties of WB for ANH. MATERIALS AND METHODS: Each WB sample, collected from 12 male volunteers, was divided into two parts, one stored at RT and the other refrigerated for 24 hours. Complete blood counts (CBC), blood gas levels, and coagulation profiles were measured, and rotational thromboelastometry (ROTEM) measurements were performed at the initial collection time point (baseline) and at 6, 12, and 24 hours after initial collection. RESULTS: The preservation of platelet aggregation response induced by arachidonic acid and adenosine diphosphate was better in cold-stored WB compared to that in RT-stored WB. The platelet aggregation response induced by thrombin receptor-activating peptide 6 was significantly decreased in all samples after 24 hours of storage when compared with that at baseline. The lactate levels in WB stored at RT increased significantly after 6 hours of storage compared to that of cold-stored samples. There were no significant differences in CBC, coagulation parameters, and ROTEM variables between the cold-stored and RT-stored WB samples. CONCLUSION: WB for ANH stored in the refrigerator showed better metabolic characteristics after 6 hours of storage and better aggregation response after 12 hours of storage than WB stored at RT.

Storage-Related Changes in Autologous Whole Blood and Irradiated Allogeneic Red Blood Cells and Their Ex Vivo Effects on Deformability, Indices, and Density of Circulating Erythrocytes in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass.

OBJECTIVES: Blood-processing techniques and preservation conditions cause storage lesions, possibly leading to adverse outcomes after transfusion. The authors investigated the metabolic changes and deformability of red blood cells (RBCs) during storage and determined the effect of storage lesions on circulating RBCs during cardiac surgery. DESIGN: Prospective study. SETTING: Tertiary care center affiliated with a university hospital. PARTICIPANTS: Adults who underwent elective cardiac surgery requiring cardiopulmonary bypass. INTERVENTIONS: The authors collected aliquots of autologous and irradiated allogeneic RBCs and blood samples from seven patients who received autologous whole blood and nine patients who received irradiated allogeneic RBCs before incision (baseline), at the start and end of cardiopulmonary bypass, and at completion of surgery. MEASUREMENTS AND MAIN RESULTS: The authors analyzed RBC deformability, erythrocyte indices, and density distribution to evaluate blood banking-induced alterations of autologous and allogeneic RBCs and changes in circulating RBCs in recipients, after blood transfusion. Time-dependent biochemical changes and significant decreases in deformability during storage occurred in both groups; however, homologous RBCs had significantly lower deformability than autologous RBCs. Trends in mean corpuscular volume and mean corpuscular hemoglobin concentration differed in both groups. In the homologous transfusion group, during cardiac surgery, RBC deformability, mean corpuscular volume, and mean corpuscular hemoglobin concentration showed significant changes compared with baseline values, and a greater number of denser subpopulations was observed at surgery completion. CONCLUSIONS: Blood-processing techniques contribute to storage lesions, suggesting that transfusion of autologous whole blood, rather than allogeneic RBCs, could maintain the ability of circulating RBCs to deform and lead to potentially better transfusion outcomes.

Evaluation of coagulation status using clot waveform analysis in general ward patients with COVID-19.

Coronavirus disease (COVID-19)-related systemic cytokine response induces the production of procoagulant factors, which predisposes patients to a prothrombotic state. Viscoelastic testing can identify the degree of hypercoagulability, which is related to outcomes. We aimed to study the changes in clot waveform analysis (CWA) parameters in COVID-19 patients on hospital admission compared to those in a group of healthy individuals. We conducted a retrospective study of COVID-19 patients admitted to general wards and evaluated demographic and clinical parameters as well as laboratory parameters, including coagulation parameters. CWA data from patients (n = 62) with COVID-19 prior to the initiation of anticoagulation therapy were compared with those from healthy controls (n = 67). The measured CWA parameters were min1, min2, max2, and delta change. CWA, fibrinogen, and D-dimer values were higher in COVID-19 patients than in healthy controls (p < 0.001). CWA profiles were consistent with hypercoagulability and characterized by an increase in density, velocity, and acceleration of clot formation. Activated partial thromboplastin time, fibrinogen, D-dimer, and C-reactive protein (CRP) values were higher in patients in whom all CWA parameters were raised than in patients with just a few elevated CWA parameters, while Sequential Organ Failure Assessment scores, prothrombin time, fibrin degradation product levels and platelet counts did not differ between the two groups. CWA variables showed hypercoagulopathy on admission in COVID-19 patients who were hospitalized in the general ward, and this pattern was more pronounced in critically ill patients with elevated fibrinogen, D-dimer, and CRP levels. Our results may help identify patients at high risk of thromboembolism.

Left atrial thrombus formation within a few days of hospitalization in semi-acute ischemic heart disease despite no atrial fibrillation and mitral stenosis: a case report.

BACKGROUND: Currently, the occurrence of left atrial thrombus despite the provision of heparinization within a few days of hospitalization without atrial fibrillation (AF) and mitral stenosis (MS) is rarely reported. CASE PRESENTATION: A 71-year-old woman presented with chest discomfort and dyspnea. Examination revealed ST elevation with sinus rhythm, congestive heart failure, and moderate mitral regurgitation (MR) by transthoracic echocardiography (TTE). Diuretics, a coronary vasodilator, and unfractionated heparin (15,000 units/day) were administered. Four days after hospitalization, her C-reactive protein level had increased; therefore, TTE was repeated, revealing a thrombus in the left atrial appendage, which was probably affected by heparin resistance because of low antithrombin (49%). On day 5, the patient underwent emergency removal of the thrombus, mitral valve replacement, and coronary artery bypass. CONCLUSION: Patients can exhibit low left ventricular contractility, even sinus rhythm without MS. Thus, TTE and subsequent coagulation tests including antithrombin must be performed to prevent thrombus.

Refractory ventricular arrhythmias during aortic valve replacement and cardiac artery bypass requiring 16 attempts of electrical cardioversion: a case report.

BACKGROUND: We report a patient in whom we failed to suppress ventricular fibrillation (VF) using nifekalant but succeeded using amiodarone during cardiopulmonary bypass (CPB). CASE PRESENTATION: A 65-year-old male with hemodialysis complained of dyspnea and was diagnosed with aortic valve stenosis and angina pectoris; he was opted for elective aortic valve replacement. When the aortic forceps were declamped during CPB, immediate VF was observed; several attempts of electrical cardioversion (EC) with lidocaine and landiolol and three administrations of nifekalant were temporarily effective. However, the rhythm subsequently changed to torsades de pointes. We administered 2 g of magnesium sulfate followed by three doses of amiodarone and initiated continuous infusion. Furthermore, we initiated the pacemaker and intra-aortic balloon pumping. These procedures seemed to be effective; the sinus rhythm was sustained until the end of the surgery. CONCLUSION: We experienced a cardiac surgery requiring 16 EC attempts to terminate the life-threatening arrhythmias using amiodarone.

Thromboelastometry and a hemostasis management system are most beneficial for guiding hemostatic therapy in cardiac surgery patients with a EuroSCORE II of ≥1.83%: a randomized controlled two-step trial.

PURPOSE: We evaluated the efficacy of hemostatic therapy based on point-of-care (POC) testing in patients undergoing cardiac surgery. METHODS: This was a single-institution, prospective, randomized, double-blinded study. In step 1, 90 patients scheduled for elective cardiac surgery underwent complete blood count and fibrinogen measurements at baseline, after cardiopulmonary bypass (CPB) initiation (CPB start), just after CPB end, and in the intensive care unit (ICU). In step 2, 72 patients scheduled for elective cardiac surgery underwent conventional laboratory coagulation tests (control group) or POC coagulation tests (POC group). Transfusions were prepared using the fibrinogen and platelet values at mainly "CPB start" for the control group, and using the ROTEM values at mainly "CPB end" for the POC group. Consequently, the step 2 patients were divided into high- and low-risk subgroups based on the EuroSCORE II by logistic regression analysis; transfusion data and bleeding volumes were compared between the control and POC groups within the high- and low-risk subgroups. RESULTS: In step 1, all blood components were significantly decreased at CPB start compared with baseline, and platelet and fibrinogen levels remained almost constant from CPB start to end. In step 2, the transfusion rates and perioperative bleeding volumes did not significantly differ between the control and POC groups. Subgroup analysis suggested that only the high-risk subgroup significantly differed regarding perioperative red blood cell transfusion and total bleeding volume in the ICU. CONCLUSIONS: POC testing is beneficial for cardiac surgery patients with a EuroSCORE II of ≥1.83%.

Changes in Erythrocyte Morphology at Initiation of Cardiopulmonary Bypass Without Blood Transfusion Were Not Associated With Less Deformability During Cardiac Surgery.

OBJECTIVES: During cardiac surgery, circulating red blood cells (RBCs) are at risk of exposure to environmental factors during extracorporeal circulation and transfusion of stored RBCs. For this study, the authors observed morphological differences, deformability, density distribution, and erythrocyte indices of RBCs during cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: Prospective study. SETTING: Tertiary care center affiliated with a university hospital. PARTICIPANTS: Adults who underwent elective cardiac surgery requiring CPB. INTERVENTIONS: Blood samples were obtained from 13 patients before incision (baseline), at initiation of CPB, after separation from CPB, and at completion of surgery. MEASUREMENTS AND MAIN RESULTS: The morphological index (MI) in RBCs using light microscopy and the maximum deformability index (DImax) using an ektacytometer were evaluated. In addition, the fractionation of RBCs and erythrocyte indices were measured. The MI at initiation of CPB was significantly higher without blood transfusion compared with baseline, although the DImax did not significantly decrease simultaneously. The DImax after separation from CPB and at completion of surgery were significantly lower than that at baseline. This lowered DImax was accompanied by a significantly reduced mean corpuscular volume and elevated mean corpuscular hemoglobin concentration compared with baseline. Dense RBC subpopulations increased after initiating CPB. The MI after separation from CPB and at completion of surgery partially recovered. Administered stored RBCs showed a high MI and the lowest DImax. CONCLUSIONS: Morphological changes at initiation of CPB are considered potentially reversible transformations without loss of the membrane surface area and do not have a significant effect on the DImax. A decrease in deformability likely is due to transfusion of stored RBCs.

Effects of crystalloids and colloids on microcirculation, central venous oxygen saturation, and central venous-to-arterial carbon dioxide gap in a rabbit model of hemorrhagic shock.

OBJECTIVE: The effects of hydroxyethyl starch (HES) on microcirculation, central venous oxygen saturation (ScvO2), and the central venous-to-arterial carbon dioxide gap (dCO2) are studied in a rabbit model of hemorrhagic shock for elucidating the advantages and drawbacks of resuscitation with HES compared with crystalloids. METHODS: An ear chamber and sublingual mucosa were used to examine blood vessels by intravital microscopy. Hemorrhagic shock was induced by removing nearly half of the blood volume. Twenty-two rabbits received 20 mL of HES by intravenous infusion immediately after bloodletting. Additional HES was then administered intravenously to a total volume of 100 mL. The other 22 rabbits (control) were intravenously given 40 mL of normal saline solution (NSS), followed by additional NSS to a total volume of 200 mL, administered under the same conditions as HES. RESULTS: After the infusion, the vessel density and perfusion rate of the sublingual microcirculation recovered in the HES group. The arteriolar diameter, blood flow velocity, and blood flow rate of the ear microcirculation were maintained in this group, and microcirculatory failure did not develop. In the NSS group, however, all 5 of the aforementioned measured variables were significantly smaller than those in the HES group after the completion of infusion. The recovery of ScvO2 and dCO2 to the respective baseline values was significantly better in the HES group than in the NSS group. CONCLUSION: Intravenous infusion of HES effectively maintains adequate tissue oxygenation and perfusion in hemorrhagic shock.

Dose-dependent effect of stored-blood transfusions on recipient red blood cell indices, deformability and density.

We prospectively studied the dose-dependent effect of transfused stored red blood cells (RBCs) on recipient RBC indices, deformability and cell density in 10 patients administered stored RBCs for blood transfusion during general surgery. There were dose-dependent decreases in mean corpuscular volume and increases in mean corpuscular haemoglobin concentration after completion of 4- and 6-unit stored RBC transfusions. The amount of dense populations increased proportionately with the amount of stored RBCs transfused. The maximal deformability index value was significantly and dose-dependently decreased, suggesting that hemodynamic blood flow, especially the microcirculation may be impaired in patients who receive large amounts of stored RBCs.

Complete Genome Sequence of Sphingobium sp. Strain YG1, a Lignin Model Dimer-Metabolizing Bacterium Isolated from Sediment in Kagoshima Bay, Japan.

Sphingobium sp. strain YG1 is a lignin model dimer-metabolizing bacterium newly isolated from sediment in Kagoshima, Japan, at a depth of 102 m. Here, we report the complete genome nucleotide sequence of strain YG1.

Complete Genome Sequence of Altererythrobacter sp. Strain B11, an Aromatic Monomer-Degrading Bacterium, Isolated from Deep-Sea Sediment under the Seabed off Kashima, Japan.

Altererythrobacter sp. strain B11 is an aromatic monomer-degrading bacterium newly isolated from sediment under the seabed off Kashima, Japan, at a depth of 2,100 m. Here, we report the complete nucleotide sequence of the genome of strain B11.

Introduction of thromboelastometry-guided administration of fresh-frozen plasma is associated with decreased allogeneic blood transfusions and post-operative blood loss in cardiopulmonary-bypass surgery.

BACKGROUND: Cardiac surgery is frequently associated with excessive blood loss requiring multiple blood transfusions which are, in turn, associated with increased morbidity and mortality. We evaluated the effectiveness of rotational thromboelastometry (ROTEM®)-guided administration of fresh-frozen plasma (FFP) with regards to blood loss, transfusion requirements, and major post-operative complications. MATERIALS AND METHODS: Coagulation management in 68 prospective patients undergoing cardiac surgery with cardiopulmonary bypass was based on a treatment algorithm guided by ROTEM® measurements. The primary end-point was blood loss at 24 hours after surgery. Secondary end-points were: (i) need for allogeneic blood products after cardiopulmonary bypass and 24 hours post-operatively, and (ii) post-operative complications until discharge. The results were compared with those of a retrospective, control group of 69 patients who received empirical coagulation management before implementation of the ROTEM®-guided algorithm. RESULTS: Although patients with significantly lower haemoglobin levels received less packed red blood cells (PRBC) (840 vs 1,120 mL; p=0.031) and FFP (480 vs 720 mL; p=0.007) after introduction of the ROTEM® algorithm, the intra-operative blood loss and post-operative haemoglobin levels were similar in the ROTEM® and the retrospective control groups. In addition to significantly reduced blood loss and decreased requirements for PRBC (30.8 vs 62.3%; p<0.001) and FFP (25.0 vs 56.5%; p<0.001), the amounts of PRBC (315 vs 840 mL; p<0.001) and FFP (480 vs 840 mL; p=0.001) received during the first 24 hours after surgery were significantly reduced in the ROTEM® group, as was the duration of post-operative hospitalisation. DISCUSSION: Compared with empirical treatment, timely ROTEM®-guided FFP administration during cardiac surgery can reduce not only overall blood product use and blood loss but also the duration of hospitalisation.

Association Between Platelet Count and Postoperative Blood Loss in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass and Fresh Frozen Plasma Administration Guided by Thromboelastometry.

BACKGROUND: Coagulopathy after cardiopulmonary bypass (CPB) is caused by multiple factors, including reduced coagulation factors and a low platelet count.Methods and Results:In this study, we undertook a post hoc analysis to identify factors associated with increased postoperative blood loss in 97 patients undergoing cardiac surgery with CPB, with fresh frozen plasma administered according to a ROTEM-guided algorithm. We identified 24 patients for the top quartile of postoperative blood loss, >528 mL and defined as having excessive blood loss. Using Spearman's rank correlation test and multivariable linear regression, we reanalyzed the participants' demographic, surgical and anesthetic variables, laboratory test results, blood loss, and transfusion data. Univariate analysis indicated that patients who experienced higher postoperative blood loss received a significantly higher heparin dose, had a higher requirement for fresh frozen plasma transfusion during surgery, and had a significantly lower hematocrit and platelet count at the end of surgery compared with patients without excessive blood loss. Multivariate analysis showed that platelet count at the end of surgery (odds ratio 0.780, 95% confidence interval 0.629-0.967; P=0.024) was an independent factor for excessive blood loss. CONCLUSIONS: Low platelet count at the end of surgery was associated with excessive postoperative bleeding during cardiac surgery with CPB.

Changes in heparin dose response slope during cardiac surgery: possible result in inaccuracy in predicting heparin bolus dose requirement to achieve target ACT.

INTRODUCTION: The substantial interpatient variability in heparin requirement has led to the use of a heparin dose response (HDR) technique. The accuracy of Hepcon-based heparin administration in achieving a target activated clotting time (ACT) using an HDR slope remains controversial. METHODS: We prospectively studied 86 adult patients scheduled for cardiac surgery requiring cardiopulmonary bypass. The total dose of calculated heparin required for patient and pump priming was administered simultaneously to achieve a target ACT of 450 s for HDR on the Hepcon HMS system. Blood samples were obtained after the induction of anesthesia, at 3 min after heparin administration and after the initiation of CPB to measure kaolin ACT, HDR slope, whole-blood heparin concentration based on the HDR slope and anti-Xa heparin concentration, antithrombin and complete blood count. RESULTS: The target ACT of 450 s was not achieved in 68.6% of patients. Compared with patients who achieved the target ACT, those who failed to achieve their target ACT had a significantly higher platelet count at baseline. Correlation between the HDR slope and heparin sensitivity was poor. Projected heparin concentration and anti-Xa heparin concentration are not interchangeable based on the Bland-Altman analysis. CONCLUSION: It can be hypothesized that the wide discrepancy in HDR slope versus heparin sensitivity may be explained by an inaccurate prediction of the plasma heparin level and/or the change in HDR of individual patients, depending on in vivo factors such as extravascular sequestration of heparin, decreased intrinsic antithrombin activity level and platelet count and/or activity.

Rare de novo inversion-duplication case with pure 3qter duplication syndrome including an overlap of the dup(3q) critical region: A case report.

We report here a very rare case of de novo inversion-duplication chromosomal abnormality with a pure 3qter duplication syndrome. Interestingly, the 3q duplication includes an overlap of the syndromes critical region. Although there have only been 9 cases of this syndrome reported in the past, our patient had more severe neurological abnormalities than anticipated. In this regard, we have gathered the 3q chromosomal duplication abnormalities known to cause pure 3q duplication syndrome to date as a reference for comparisons and we discuss the particulars of our case.

Management of a Patient With Antiphospholipid Syndrome Undergoing Aortic Valve Replacement Using the Hepcon Hemostasis Management System Plus and Rotational Thromboelastometry: A Case Report.

A 72-year-old woman with antiphospholipid syndrome underwent aortic valve replacement. Her preoperative activated partial thromboplastin time was 61.7 seconds and activated clotting time was 219 seconds. During cardiopulmonary bypass, the Hepcon Hemostasis Management System (HMS) Plus determined the heparin dose needed to maintain whole-body heparin at 3 U/mL. After cardiopulmonary bypass, 100 mg of protamine was administered based on heparin-protamine neutralization, and the activated clotting time decreased. We applied rotational thromboelastometry (ROTEM) to diagnose residual heparin using the INTEM/HEPTEM clotting time ratio. The HMS and ROTEM are useful for heparin-protamine control in antiphospholipid syndrome.

[Empathy to be Shown by Pharmacists toward Home Patients - Initiatives Undertaken by Pharmacists to Promote the Proper Use of Pharmaceutical Products].

Separation of medical and dispensary services has taken root in Japan as a healthcare system;8 00 million prescriptions have been issued, and 70% of medical institutions now participate in this practice. Additionally, discussions are ongoing regarding patient-oriented family pharmacies from a"back-to-basics"perspective of the separation drug dispensing from medical practice. Through a series of such discussions, the Ministry of Health, Labour and Welfare published a paper entitled"Vision for Pharmacies Working for Patients"with a focus on 3 functions to be implemented by family pharmacists and pharmacies. In home healthcare, there have been cases so far, as shown in the Vision paper, of suggestions from and initiatives taken by pharmacists that have helped improve patient home care services. This paper explores home care-related initiatives undertaken by our pharmacy, including 2 cases in which our pharmacists intervened to prevent duplicate prescriptions and promoted adherence to a medication regimen, having noticed a change in a patient's physical abilities caused by the presence of drug residues. Our pharmacists will inform other relevant professionals about this issue. The study discusses our experience, which may help provide insight on the ideal roles of pharmacists in this time of partnerships among professionals.