Long-term clinical outcomes and management of hypertriglyceridemia in children with Apo-CII deficiency.

BACKGROUND AND AIM: APO CII, one of several cofactors which regulate lipoprotein lipase enzyme activity, plays an essential role in lipid metabolism. Deficiency of APO CII is an ultra-rare autosomal recessive cause of familial chylomicronemia syndrome. We present the long-term clinical outcomes of 12 children with APO CII deficiency. METHODS AND RESULTS: The data of children with genetically confirmed APO CII deficiency were evaluated retrospectively. Twelve children (8 females) with a mean follow-up of 10.1 years (±3.9) were included. At diagnosis, the median age was 60 days (13 days-10 years). Initial clinical findings included lipemic serum (41.6%), abdominal pain (41.6%), and vomiting (16.6%). At presentation, the median triglyceride (TG) value was 4341 mg/dL (range 1277-14,110). All patients were treated with a restricted fat diet, medium-chain triglyceride (MCT), and omega-3-fatty acids. In addition, seven patients (58.3%) received fibrate. Fibrate was discontinued in two patients due to rhabdomyolysis and in one patient because of cholelithiasis. Seven (58.3%) patients experienced pancreatitis during the follow-up period. One female experienced recurrent pancreatitis and was treated with fresh frozen plasma (FFP). CONCLUSIONS: Apo CII deficiency is an ultra-rare autosomal recessive condition of hypertriglyceridemia associated with significant morbidity and mortality. Low-fat diet and MCT supplementation are the mainstays of therapy, while the benefit of TG-lowering agents are less well-defined.

Association of perioperative transfusion of fresh frozen plasma and outcomes after cardiac surgery.

BACKGROUND: Fresh frozen plasma (FFP) transfusion is used to manage coagulopathy and bleeding in cardiac surgery patients despite uncertainty about its safety and effectiveness. METHODS: We performed a propensity score matched analysis of the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database including patients from 39 centres from 2005 to 2018. We investigated the association of perioperative FFP transfusion with mortality and other clinical outcomes. RESULTS: Of 119,138 eligible patients, we successfully matched 13,131 FFP recipients with 13,131 controls. FFP transfusion was associated with 30-day mortality (odds ratio (OR), 1.41; 99% CI, 1.17-1.71; p < .0001), but not with long-term mortality (hazard ratio (HR), 0.92; 99% CI, 0.85-1.00; p = .007, Holm-Bonferroni α = 0.0004). FFP was also associated with return to theatre for bleeding (OR, 1.97; 99% CI, 1.66-2.34; p < .0001), prolonged intubation (OR, 1.15; 99% CI, 1.05-1.26; p < .0001) and increased chest tube drainage (Mean difference (MD) in mL, 131; 99% CI, 120-141; p < .0001). It was also associated with reduced postoperative creatinine levels (MD in g/L, -6.33; 99% CI, -10.28 to -2.38; p < .0001). CONCLUSION: In a multicentre, propensity score matched analysis, perioperative FFP transfusion was associated with increased 30-day mortality and had variable associations with secondary clinical outcomes.

Fresh Frozen Plasma Versus Solvent Detergent Plasma for Cardiopulmonary Bypass Priming in Neonates and Infants Undergoing Cardiac Surgery: A Retrospective Cohort Study.

OBJECTIVE: Compared with fresh frozen plasma (FFP), Omniplasma has been attributed to an increased coagulation potential and an increased fibrinolytic potential. This study aimed to compare Omniplasma and FFP used for cardiopulmonary bypass (CPB) priming regarding the incidence of postoperative thrombotic or hemorrhagic complications and outcomes in pediatric patients undergoing cardiac surgery. DESIGN: A retrospective observational cohort study SETTING: This single-center study was performed at the University Medical Center Groningen. PARTICIPANT: All pediatric patients up to 10 kg undergoing cardiac surgery with CPB. INTERVENTIONS: Procedures in which FFP was used for CPB priming were compared with those in which Omniplasma was used. MEASUREMENTS AND MAIN RESULTS: The primary outcome parameter was a composite endpoint consisting of the following: (1) pediatric intensive care unit (PICU) mortality, (2) thromboembolic complications, and (3) hemorrhagic complications during PICU stay. The authors included 143 procedures in the analyses, 90 (63%) in the FFP group and 53 (37%) in the Omniplasma group. The occurrence of the combined primary endpoint (FFP 20% v Omniplasma 11%, p = 0.18) and its components did not differ between the used CPB priming agent). Omniplasma for CPB priming was associated with decreased unfractionated heparin administration per kg bodyweight (585 IU v 510 IU, p = 0.03), higher preoperative and postoperative activated clotting times (ACT) discrepancy (90% v 94%, p = 0.03), a lower postoperative ACT value (125 v 118 seconds, p = 0.01), and less red blood cell transfusion per kilogram bodyweight (78 v 55 mL, p = 0.02). However, none of the variables differed statistically significantly in the multivariate logistic regression analyses. CONCLUSIONS: The authors did not find an association between the plasma used for CPB priming and thromboembolic and hemorrhagic complications and death in neonates and infants undergoing cardiac surgery. Omniplasma seems to be safe to use in this population.

Effects of Fibrinogen Concentrate Supplementation on Postoperative Bleeding in Infants Undergoing Complex Cardiac Surgery.

The use of allogeneic blood products to restore hemostasis during pediatric cardiac surgery is associated with major risks. Consequently, there has been a growing interest in new patient blood management strategies, such as those based on the use of fibrinogen concentrate (FC). Accumulating evidence has shown FC supplementation to be safe and effective. Nevertheless, no guidelines are available on using FC in the pediatric setting, and few objective evaluations have been provided in clinical practice. The endpoint of this monocenter retrospective study was the hemostatic effect of additional FC in infants undergoing complex cardiac surgery with cardiopulmonary bypass to manage persistent clinically relevant bleeding. After weaning from cardiopulmonary bypass and after protamine administration, patients were transfused with conventional allogeneic products such as packed red blood cells, fresh frozen plasma (FFP), and platelets. In the case of redo surgery, according to the institutional protocol, patients also received tranexamic acid. In case of clinically persistent relevant bleeding, according to the anesthesiologist's judgment and thromboelastography, patients received FC supplementation (group with FC) or further FFP transfusions without receiving FC supplementation (group without FC). The primary endpoint was the hemostatic effects of FC. Secondary endpoints were the functional hypofibrinogenemia threshold value (expressed as maximum amplitude fibrinogen, MA-Fib) and postoperative MA-Fib, fibrinogenemia, intraoperative transfusions, and adverse events (AEs). In total, 139 patients who underwent cardiac surgery with CPB and aged less than 2 years were enrolled: 70 patients received allogeneic blood products and FC supplementation (group FC); 69 patients received allogeneic products without FC supplementation (group without FC). Patients that received FC supplementation were characterized by a significantly longer time of extracorporeal circulation (p < 0.001) and aortic cross-clamping (p < 0.001), a significantly lower minimum temperature (p = 0.011), increased use of concentrated prothrombin complex (p = 0.016) and tranexamic acid (p = 0.010), and a significantly higher amount of packed red blood cells, platelets (p < 0.001) and fresh frozen plasma (p = 0.03). Postoperative bleeding and severe bleeding were not statistically different between patients treated with FC and those not treated with FC supplementation (p = 0.786 and p = 0.695, respectively); after adjustment, a trend toward reduced bleeding can be observed with FC (p = 0.064). Overall, 88% of patients with severe bleeding had MA-Fib < 10 mm; a moderate association between severe bleeding and MA-Fib (odds ratio 1.7, 95% CI 0.5-6.5, p = 0.425) was found. Increased MA-Fib and postoperative fibrinogen were higher in the FC group (p = 0.003 and p < 0.001, respectively) than in FFP. AEs in the FC group were comparable to those observed in less complicated surgeries. Our results suggest a potential role of FC in complex surgery in maintaining postoperative bleeding at a level comparable to less complicated surgical procedures and favoring the increase in postoperative MA-Fib and fibrinogen.

Plasma resuscitation improves and restores intestinal microcirculatory physiology following haemorrhagic shock.

BACKGROUND AND OBJECTIVES: Intestinal ischaemia-reperfusion injury following resuscitated haemorrhagic shock (HS) leads to endothelial and microcirculatory dysfunction and intestinal barrier breakdown. Although vascular smooth muscle machinery remains intact, microvascular vasoconstriction occurs secondary to endothelial cell dysfunction, resulting in further ischaemia and organ injury. Resuscitation with fresh frozen plasma (FFP) improves blood flow, stabilizes the endothelial glycocalyx and alleviates organ injury. We postulate these improvements correlate with decreased tissue CO2 concentrations, improved microvascular oxygenation and attenuation of intestinal microvascular endothelial dysfunction. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned to groups (n = 8/group): (1) sham, (2) HS (40% mean arterial blood pressure [MAP], 60 min) + crystalloid resuscitation (CR) (shed blood saline) and (3) HS + FFP (shed blood + FFP). MAP, heart rate (HR), ileal perfusion, pO2 and pCO2 were measured at intervals until 4 h post-resuscitation (post-RES). At 4 h post-RES, the ileum was rinsed in situ with Krebs solution. Topical acetylcholine and then nitroprusside were applied for 10 min each. Serum was obtained, and after euthanasia, tissues were harvested and snap-frozen in liquid N2 and stored at -80°C. RESULTS: FFP resuscitation resulted in sustained ileal perfusion as well as rapid sustained return to baseline microvascular pO2 and pCO2 values when compared to CR (p < 0.05). Endothelial function was preserved relative to sham in the FFP group but not in the CR group (p < 0.05). CONCLUSION: FFP-based resuscitation improves intestinal perfusion immediately following resuscitation, which correlates with improved tissue oxygenation and decreased tissue CO2 levels. CR resulted in significant damage to endothelial vasodilation response to acetylcholine, while FFP preserved this function.

Acute haemolytic transfusion reaction after transfusion of fresh frozen plasma in a neonate-Preventable by using solvent/detergent-treated pooled plasma?

BACKGROUND: Plasma is a commonly used blood product and is available in the form of fresh frozen plasma (FFP) or pooled solvent/detergent-treated plasma. In the Netherlands, solvent/detergent-treated plasma has become the standard product in the adult population since several years, but for neonatal use, FFP remains the product of preference. DESCRIPTION: A preterm neonate developed lung bleeding at day 8 postpartum, for which intubation and mechanical ventilation was required and transfusions with packed red blood cells and plasma, in the form of FFP, were given. Five hours after transfusion, a red discoloration of the urine occurred. An acute haemolytic transfusion was suspected, confirmed by laboratory investigations (fast decrease in haemoglobin, increased free haemoglobin, decreased haptoglobin, increased lactate dehydrogenase and a positive direct antiglobulin test [IgG 2+]). Additional research showed that the FFP product contained nonspecific auto-antibodies that reacted with the transfused erythrocytes, most test erythrocytes and the donor's own erythrocytes. CONCLUSION: A neonate experienced an acute haemolytic reaction, most probably caused by administrating a FFP product containing auto-antibodies. If transfused with solvent/detergent-treated plasma, such antibodies would have been diluted or captured. This case adds a new argument to the discussion on expanding the use of solvent/detergent-treated plasma to the paediatric population.

Detrimental effects of fresh frozen plasma transfusions on postoperative outcomes in patients undergoing liver resection for hepatocellular carcinoma.

BACKGROUND: Perioperative fresh frozen plasma (FFP) is commonly transfused to patients undergoing liver resection for hepatocellular carcinoma (HCC), but its impacts in this population remain unknown. This study aimed to investigate the association of perioperative FFP transfusion with short-term and long-term outcomes in these patients. METHODS: We retrospectively identified and retrieved clinical data for HCC patients undergoing liver resection between March, 2007 and December, 2016. Study outcomes included postoperative bacterial infection, extended length of stay (LOS) and survival. Propensity score (PS) matching was used to determine the association of FFP transfusion with each outcome. RESULTS: A total of 1427 patients were included, and 245 of them received perioperative FFP transfusions (17.2%). Patients received perioperative FFP transfusions were older, underwent liver resection in the earlier time period, and had more extensive resection, poorer clinical conditions, and higher proportions of receiving other blood components. Perioperative FFP transfusion was associated with higher odds of both postoperative bacterial infection (OR = 1.77, p = 0.020) and extended LOS (OR = 1.93, p=<0.001), and the results remained similar after PS-matching. However, perioperative FFP transfusion did not significantly affect survival in these patients (HR = 1.17, p = 0.185). A potential association of postoperative FFP transfusions and poorer 5-year but not overall survival was observed in a subgroup of patients with low postoperative albumin levels after PS-matching. CONCLUSION: Perioperative FFP transfusions were associated with poorer short-term postoperative outcomes in HCC patients undergoing liver resection, including postoperative bacterial infection and extended LOS. Reducing perioperative FFP transfusions has the potential to improve their postoperative outcomes.

Fresh frozen plasma transfusion after cardiac surgery.

INTRODUCTION: Fresh frozen plasma (FFP) transfusion in the intensive care unit (ICU) is commonly used to treat coagulopathy and bleeding in cardiac surgery, despite suggestion that it may increase the risk of morbidity and mortality through mechanisms such as fluid overload and infection. METHODS: We retrospectively studied consecutive adults undergoing cardiac surgery from the Medical Information Mart for Intensive Care III and IV databases. We applied propensity score matching to investigate the independent association of within-ICU FFP transfusion with mortality and other key clinical outcomes. RESULTS: Of our 12,043 adults who met inclusion criteria, 1585 (13.2%) received perioperative FFP with a median of 2.48 units per recipient (interquartile range [IQR]: 2.04, 4.33) at a median time of 1.83 h (IQR: 0.75, 3.75) after ICU admission. After propensity matching of 952 FFP recipients to 952 controls, we found no significant association between FFP use and hospital mortality (odds ratio (OR): 1.58; 99% confidence interval (CI): 0.57, 3.71), suspected infection (OR: 0.72; 99% CI: 0.49, 1.08), or acute kidney injury (OR: 1.23; 99% CI: 0.91, 1.67). However, FFP was associated with increased days in hospital (adjusted mean difference (AMD): 1.28; 99% CI: 0.27, 2.41; p = .0050), days in intensive care (AMD: 1.28; 99% CI: 0.27, 2.28; p = .0011), and chest tube output in millilitres up to 8 h after transfusion (AMD: 92.98; 99% CI: 52.22, 133.74; p < .0001). CONCLUSIONS: After propensity matching, FFP transfusion was not associated with increased hospital mortality, but was associated with increased length of stay and no decrease in bleeding in the early post-transfusion period.

Autologous Platelet and Extracellular Vesicle-Rich Plasma as Therapeutic Fluid: A Review.

The preparation of autologous platelet and extracellular vesicle-rich plasma (PVRP) has been explored in many medical fields with the aim to benefit from its healing potential. In parallel, efforts are being invested to understand the function and dynamics of PVRP that is complex in its composition and interactions. Some clinical evidence reveals beneficial effects of PVRP, while some report that there were no effects. To optimize the preparation methods, functions and mechanisms of PVRP, its constituents should be better understood. With the intention to promote further studies of autologous therapeutic PVRP, we performed a review on some topics regarding PVRP composition, harvesting, assessment and preservation, and also on clinical experience following PVRP application in humans and animals. Besides the acknowledged actions of platelets, leukocytes and different molecules, we focus on extracellular vesicles that were found abundant in PVRP.

Haemostatic alterations and management of haemostasis in patients with cirrhosis.

Patients with cirrhosis frequently acquire complex changes in their haemostatic system including a decreased platelet count and decreased levels of various haemostatic proteins. Although historically patients with cirrhosis were thought to have a haemostasis-related bleeding tendency, it is now widely accepted that the haemostatic system of patients with cirrhosis remains in balance as a result of simultaneous changes in pro- and anti-haemostatic systems. The concept of rebalanced haemostasis has led to changes in clinical management, although firm evidence from well-designed clinical studies is largely lacking. For example, many invasive procedures in patients with cirrhosis and a prolonged prothrombin time are now performed without prophylaxis with fresh frozen plasma. Conversely, clinicians have become more aware of the need for anti-thrombotic therapy, even in those patients with abnormal routine coagulation tests. This paper will outline recent advances in pathogenesis, prevention and treatment of both bleeding and thrombotic complications in patients with cirrhosis. Among other topics, we will discuss the haemostatic status of acutely ill patients with cirrhosis, the various causes of bleeding in patients with cirrhosis, and how best to prevent or treat bleeding. In addition, we will discuss the hypercoagulable features of patients with cirrhosis, new insights into the pathogenesis of portal vein thrombosis, and how best to prevent or treat thromboses.

Effect of prolonged storage on quality characteristics of recovered plasma: Is there an expiration date?

BACKGROUND: Although there are guidelines on industrial manufacture of plasma-derived medicinal products, there are no clear recommendations about plasma intended for fractionation, as there is no expiry time and the effect of prolonged storage on the activity of coagulation factors is unknown. STUDY AND DESIGN METHODS: A total of 237 units of plasma stored at -30°C in the National Blood Transfusion Centre for 1 year (62 units), 5 years (75 units), and 10 years (100 units) were studied. The effect of storage time was investigated by determining the activity of clotting factors FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIII using coagulometric methods and antithrombin III and fibrinogen with chromogenic assays, using System BCSR > XP (Siemens Healthcare diagnostics Marburg, Germany). Albumin was measured by Medilyzer (BX, Medicon). ABO blood group was recorded and correlated with the levels of FVIII. Comparison of values between one and five, 1 and 10 and 5 and 10 years of storage was performed via the SAS for Windows 9.4 software platform (SAS Institute Inc., NC, U.S.A.). RESULTS: Albumin, AT III, fibrinogen, FIX, FXI, FXII, and FXIII remain rather stable even after 10 years of storage. Levels of FII, FV, FVII, FVIII, and FX decreased after 5 years of storage. DISCUSSION: Our study is in agreement with all the previous studies and concludes that there is a putative usability of recovered plasma and some of its coagulation factors after many years of storage at the recommended temperature.

Evaluation of solvent/detergent-treated plasma safety and efficacy in orthotopic liver transplant and thrombotic thrombocytopenic purpura patients: A single center experience.

BACKGROUND: Solvent/detergent-treated, pooled plasma (SDP) is approved for use in orthotopic liver transplantation (OLT) and thrombotic thrombocytopenic purpura (TTP) patients; however, studies evaluating safety and effectiveness of SDP in these populations are limited. METHODS: This prospective study included two cohorts: OLT patients (n = 40) who received either SDP (n = 20) or FFP (control group) (n = 20), and TTP patients (n = 20) who received either SDP (n = 10) or FFP (control group) (n = 10) throughout hospitalization. Medical, laboratory, and blood bank records were retroactively assessed for both cohorts for differences in clinical outcomes, laboratory values, and transfusion data from admission to discharge. RESULTS: In the OLT cohort, significant changes in AST and ALP were observed in the control group as compared to SDP (p < .05 each), and creatinine levels improved significantly in the SDP group as compared to the control group (p < .05) from admission to discharge. In the TTP cohort, platelet counts were significantly improved within the control and SDP groups from admission to discharge, but there were no significant differences between groups (p = .31). LDH levels improved between admission and discharge for both groups (70% decrease in the control group, p < .001, and 80% decrease in the SDP group, p = .001). There were no significant differences detected in clinical outcomes in either cohort. CONCLUSIONS: As evidenced by the lack of adverse events in either cohort and similar clinical outcomes, we conclude that SDP is comparable in safety and effectiveness to FFP in OLT and TTP patients. Further studies are needed to evaluate the potential for improved safety with SDP.

Intraoperative transfusion management, antifibrinolytic therapy, coagulation monitoring and the impact on short-term outcomes after liver transplantation-A systematic review of the literature and expert panel recommendations.

BACKGROUND: Liver transplantation (LT) is frequently complicated by coagulopathy associated with end-stage liver disease (ESLD), that is, often multifactorial. OBJECTIVES: The objective of this systematic review was to identify evidence based intraoperative transfusion and coagulation management strategies that improve immediate and short-term outcomes after LT. METHODS: PRISMA-guidelines and GRADE-approach were followed. Three subquestions were formulated. (Q); Q1: transfusion management; Q2: antifibrinolytic therapy; and Q3: coagulation monitoring. RESULTS: Sixteen studies were included for Q1, six for Q2, and 10 for Q3. Q1: PRBC and platelet transfusions were associated with higher mortality. The use of prothrombin complex concentrate (PCC) and fibrinogen concentrate (FC) were not associated with reductions in intraoperative transfusion or increased thrombotic events. The use of cell salvage was not associated with hepatocellular carcinoma (HCC) recurrence or mortality. Cell salvage and transfusion education significantly decreased blood product transfusions. Q2: Epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA) were not associated with decreased blood product transfusion, improvements in patient or graft survival, or increases in thrombotic events. Q3: Viscoelastic testing (VET) was associated with decreased allogeneic blood product transfusion compared to conventional coagulation tests (CCT) and is likely to be cost-effective. Coagulation management guided by VET may be associated with increases in FC and PCC use. CONCLUSION: Q1: A specific blood product transfusion practice is not recommended (QOE; low | Recommendation; weak). Cell salvage and educational interventions are recommended (QOE: low | Grade of Recommendation: moderate). Q2: The routine use of antifibrinolytics is not recommended (QOE; low | Recommendation; weak). Q3: The use of VET is recommended (QOE; low-moderate | Recommendation; strong).

Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial.

BACKGROUND: Recently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy. METHODS: In the original RCT, patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 µg/kg/min received standard of care (SOC) or SOC + one single TPE. Here, we report all clinical and biological endpoints of this study. Multivariate mixed-effects modeling of NE reduction was performed to investigate characteristics that could be associated with clinical response to TPE. RESULTS: A continuous effect of TPE on the reduction in NE doses over the initial 24 h was observed (SOC group: estimated NE dose reduction of 0.005 µg/kg/min per hour; TPE group: 0.018 µg/kg/min per hour, p = 0.004). Similarly, under TPE, serum lactate levels, continuously decreased over the initial 24 h in the TPE group, whereas lactate levels increased under SOC (p = 0.001). A reduction in biomarkers and disease mediators (such as PCT (p = 0.037), vWF:Ag (p < 0.001), Angpt-2 (p = 0.009), sTie-2 (p = 0.005)) along with a repletion of exhausted protective factors (such as AT-III (p = 0.026), Protein C (p = 0.012), ADAMTS-13 (p = 0.008)) could be observed in the TPE but not in the SOC group. In a multivariate mixed effects model, increasing baseline lactate levels led to greater NE dose reduction effects with TPE as opposed to SOC (p = 0.004). CONCLUSIONS: Adjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. We identified that baseline lactate concentration as a potential response predictor might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints. Trial registration Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994 ).

Analysis of fresh frozen plasma utilization indications in children: An audit of a tertiary care hospital in Turkey.

BACKGROUND: Although indications of fresh frozen plasma (FFP) usage are limited to certain circumstances in children, there is an increasing trend towards inappropriate usage are reported in clinical practice. The aim of this study was to evaluate the appropriateness of pediatric FFP utilization in our tertiary care hospital. METHODS: This prospective observational study was conducted at a tertiary care academic pediatric hospital. All FFP orders were evaluated for appropriateness over a 4-monts period by 2 hematologists. Data collected include demographic information, diagnosis, FFP transfusion indication, pre-transfusion coagulation tests, surgical procedure or bleeding status, and transfusion reactions. RESULTS: Three hundred twenty-four patients (57 % males, 43 % females) were transfused in 987 episodes. The mean age of the patients was 5.4±5.7 years. The majority of the patients (33 %) were under 1 y of age and the products were primarily utilized by pediatric and cardiovascular intensive care units. Pre-transfusion coagulation testing was only available in 674 (68 %) of the transfusion episodes. The rate of appropriate FFP transfusion episodes was 59 % (587/987). Inappropriate usage was mostly related to sepsis and minor coagulation abnormalities without bleeding. The higher rates of inappropriate transfusion orders were observed in pediatric and neonatal intensive care units, and hematology/oncology departments. CONCLUSIONS: Inappropriate use of FFP in children remains a significant challenge. The regular audit and sustainable education programs targeting the efficient use of FFP for health professionals at the national level can improve transfusion practices.

Impact of efforts to prevent maternal deaths due to obstetric hemorrhage on trends in epidemiology and management of severe postpartum hemorrhage in Japan: a nationwide retrospective study.

BACKGROUND: The Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists have issued the guidelines and recommendations on postpartum hemorrhage since 2010 and have been conducted widespread educational activities from 2012. The aim of this study was to investigate the impact of these efforts by the Societies to prevent maternal deaths due to obstetric hemorrhage on trends in epidemiology and management of severe postpartum hemorrhage in Japan. METHODS: A national retrospective cohort study was conducted using the national database of health insurance claims for the period 2012 and 2018. The subjects were all insured women who received a blood transfusion for postpartum hemorrhage. The primary endpoints of this study were hysterectomy and maternal mortality. The etiology of hemorrhage, treatment facility, type of procedure, and blood transfusion volume were tabulated. RESULTS: Women with postpartum hemorrhage that underwent transfusion increased from 3.5 to 5.5 per 1000 deliveries between 2012 and 2018. The most common cause of postpartum hemorrhage was atonic hemorrhage. After insurance coverage in 2013, the intrauterine balloon tamponade use increased to 20.3% of postpartum hemorrhages treated with transfusion in 2018, while the proportion of hysterectomy was decreased from 7.6% (2013-2015) to 6.4% (2016-2018) (p < 0.0001). The proportion of postpartum hemorrhage in maternal deaths decreased from 21.1% (2013-2015) to 14.1% (2016-2018) per all maternal deaths cases (p = 0.14). Cases with postpartum hemorrhage managed in large referral hospitals was increased (65.9% in 2012 to 70.4% in 2018) during the study period (p < 0.0001). CONCLUSIONS: The efforts by the Societies to prevent maternal mortality due to obstetric hemorrhage resulted in a significant decrease in the frequency of hysterectomies and a downward trend in maternal mortality due to obstetric hemorrhage.

Tolerance and complications of therapeutic plasma exchange by centrifugation: A single center experience.

INTRODUCTION: Therapeutic plasma exchange (TPE) constitutes an important therapy for hematological, neurological, immunological, and nephrological diseases. Most studies have focused on efficacy, whereas tolerance and complications during sessions have been less well studied and not recently. MATERIAL AND METHODS: We conducted a single center retrospective study of all patients who underwent TPE between 2011 and 2018. TPE sessions using the centrifugation technique were performed by dedicated trained nurses. Specific side effects were identified through surveillance forms completed contemporaneously. The primary outcome was the rate of all-type adverse effects that occurred during the TPE sessions. RESULTS: In total, 1895 TPE sessions performed on 185 patients were analyzed. At least one adverse effect was reported for 805 sessions (42.5% [29.9%-70.1%]), corresponding to 171 patients (92.4% [87.6%-95.8%]). Hypotension occurred during 288 sessions (15.2%), was asymptomatic in 95.8% of cases, and more frequent with the use of 4% albumin than fresh frozen plasma (FFP) (19.8 vs 8.9%, P <.0001). Hypocalcemia occurred during 370 sessions (19.6%) and was more frequent with the use of FFP than with the use of albumin alone (FFP alone: 28.0%, albumin + FFP: 26%, albumin alone: 11.7%; P <.0001). Allergic reactions occurred during 56 sessions (3%), exclusively with FFP. Severe adverse effects were reported for 0.3% of sessions and 5.4% of patients. CONCLUSIONS: TPE is a safe therapy when performed by a trained team. Adverse effects were frequent but mostly not serious. The replacement fluid was the main determinant of the occurrence of complications. (ClinicalTrials.gov ID: NCT03888417).

Blood Products, Crystalloids, and Rapid Infusion: An Experimental Study With Magnesium.

OBJECTIVES: Calcium and magnesium are concentration-dependent pro- and anticoagulant cofactors, and magnesium behaves similarly to calcium in the presence of citrate. The authors hypothesized that magnesium can cause clot formation (primary objective) when mixed with coagulation factor-containing blood products diluted with different crystalloids in a rapid- infuser reservoir. A secondary objective was the observation of any infuser alarms and stops in the event of clotting. DESIGN: An experimental in vitro study with blood products, crystalloids, magnesium, and calcium in a rapid infuser with a reservoir using a closed-loop system. SETTING: Anesthesia research laboratory at an urban academic tertiary medical center PARTICIPANTS: Not applicable. INTERVENTIONS: Exposure of fresh frozen plasma (FFP) and packed red blood cells alone (control) or in combination with either normal saline (NS), lactated Ringer's solution (LR), or Plasma-Lyte A (PL) to increasing concentrations of magnesium sulphate (MgSO4) up to 1 g. After each incremental MgSO4 change, the authors applied a specific pump-flow sequence in a closed-loop system with a rapid-infuser reservoir, and if no clot was observed, the authors incrementally added calcium chloride (CaCl2) up to 1 g. MEASUREMENTS AND MAIN RESULTS: Observation of macroscopic clot and time to event, as well as occurrence and type of any pump alarms or stops. LR experiments resulted in clot observation in the reservoir by a dedicated observer after MgSO4 275 ± 206 mg (95% confidence interval [CI], 9-541). Adding MgSO4 1 g in the NS, PL, or the control experiments did not result in clot observation. Only when CaCl2 166.7 ± 51.64 mg (95% CI, 112.0-22.01) was added to the combination of blood products alone or mixed with NS and PL, clotting occurred. The mean FFP volume was 281 ± 48.6 mL (range, 204-340 mL) and was not different between groups (p = 0.44). Pump alarms and stops were inconsistent. CONCLUSIONS: The addition of magnesium to a combination of LR with coagulation factor- containing blood products consistently resulted in a visible blood clot in the rapid-infuser reservoir in the authors' experimental setup. In addition to MgSO4 1 g in the control, NS, and PL experiments, CaCl2 is needed before a clot can be observed.

The impact of comprehensive blood conservation program on major complications after total aortic arch replacement.

INTRODUCTION: Patients undergoing total aortic arch replacement (TAAR) usually require blood products perioperatively. This cohort study aimed to investigate the impact of a comprehensive blood conservation program on the major complications in these patients. METHODS: Patients with traditional or comprehensive blood management intraoperatively from January 2017 to December 2018 were included. We compared the rates of major complications (cerebral vascular accident, acute kidney injury, or mortality) between the two groups after propensity score matching (PSM). The association between blood management and outcomes was assessed by logistic regression. Restricted cubic splines (RCS) were built to evaluate the impact of fresh frozen plasma (FFP) on complications. Patients were stratified by the ratio of FFP/RBC (red blood cell) to investigate the effect of the ratio on complications. RESULTS: After 1:1 PSM, 200 patients were selected. 35% (35/100) of patients suffered major complications in the traditional group, while it decreased to 22% (22/100) in the comprehensive management group (OR = 0.524, p = 0.043). Multivariable logistic regression showed that FFP was a risk factor (OR = 1.186, p = 0.014). RCS results indicated that with the increase of FFP, the risk of complications gradually increases. The cut-off value was 402 mL. Patients in the group of ratio = 0 ∼ 0.5 had a higher chance than those without transfusion (OR = 7.487, p < 0.001). CONCLUSIONS: Comprehensive blood conservation program in patients undergoing TAAR is safe and can reduce the incidence of major complications, which are associated with FFP volume and the ratio of FFP/RBC.

Impact of fresh frozen plasma transfusion on mortality in extracorporeal membrane oxygenation.

BACKGROUND: Patients who receive extracorporeal membrane oxygenation (ECMO) support require substantial transfusions. Red blood cell (RBC) and platelet (PLT) transfusions have been reported to be associated with adverse outcomes in ECMO patients. However, little is known about whether the transfusion of fresh frozen plasma (FFP) is associated with mortality and morbidity among patients receiving ECMO. The aim of this study was to examine the relationship between FFP transfusion and mortality in ECMO patients and assess risk factors for the transfusion of FFP. METHODS: The clinical parameters of 116 ECMO patients were collected. The machine learning approach of the Boruta algorithm was employed to select the variables associated with ECMO patients' in-hospital mortality. Univariate and multivariate logistic regression analyses were applied to identify the association between the selected variables and in-hospital mortality. Spearman correlation and backwards stepwise multiple linear regression analyses were used to examine parameters contributing to FFP transfusion. RESULTS: Among the 116 patients who received ECMO support, the in-hospital mortality was 32.8%. The median FFP (mL/kg/d) transfusion was higher in dead patients (5.07, IQR 1.78-8.90) when compared to alive patients (2.16, IQR 0.79-4.66) (p = 0.007). After adjustment for confounders, FFP transfusion (mL/kg/d) was associated with in-hospital mortality (OR 1.09, 95% CI, 1.01-1.18; p = 0.035). Further analysis found that higher activated partial thromboplastin time (APTT), higher levels of uric acid (UA) and lower PLT counts were significant risk factors for FFP transfusion, with estimated values of 0.06 (95% CI, 0.02-0.11; p = 0.009), 0.01 (95% CI, 0.00-0.02; p = 0.003) and -0.03 (95% CI, -0.05--0.01; p = 0.007), respectively. CONCLUSION: FFP transfusion is markedly associated with in-hospital mortality among patients receiving ECMO, and higher APTT, higher levels of UA and lower PLT counts are risk factors for FFP transfusion. This suggests that better management of patients' coagulation system and kidney function may reduce the utilization of FFP, thus improving ECMO patient outcomes.