Volume Of Fresh Frozen Plasma Research Articles

Evaluation of the effect of fresh-frozen plasma transfusion on circulating hyaluronic acid concentration in critically ill dogs: a pilot study.

To describe changes in circulating hyaluronic acid (HA) concentration, a biomarker of endothelial glycocalyx degradation, after administration of fresh-frozen plasma (FFP) in critically ill dogs. 12 client-owned dogs receiving an FFP transfusion due to underlying disease. Plasma samples were collected for HA concentration measurement pre-FFP transfusion (T0) and 10 minutes (T10) and 90 minutes (T90) following completion of FFP transfusion of a minimum volume of 7 mL/kg. Hyaluronic acid was also measured in the transfused FFP units following in-house validation of a commercial HA assay on citrate phosphate dextrose-anticoagulated plasma. Potential associations of the difference between pre-FFP and post-FFP HA plasma concentrations with the volume of FFP transfused, the cumulative volume of IV fluids administered during the study period, and the HA concentration in the transfused unit were explored. Concentrations of HA were not significantly different between pre- and post-FFP transfusion measurements. The volume of FFP transfused, the cumulative volume of other IV fluids administered during the study time, and the concentration of HA in the FFP units had no significant effect on the change in HA concentration following FFP transfusion in this study. This pilot study did not demonstrate an association between FFP administration and changes in plasma HA concentration. The results of this study may serve to help design future research. A commercial assay was validated to measure HA in citrate phosphate dextrose-anticoagulated plasma.

Need for Blood Transfusion Volume Is Associated With Increased Mortality in Severe Traumatic Brain Injury

IntroductionMany patients suffering from isolated severe traumatic brain injury (sTBI) receive blood transfusion on hospital arrival due to hypotension. We hypothesized that increasing blood transfusions in isolated sTBI patients would be associated with an increase in mortality. MethodsWe performed a trauma quality improvement program (TQIP) (2017-2019) and single-center (2013-2021) database review filtering for patients with isolated sTBI (Abbreviated Injury Scale head ≥3 and all other areas ≤2). Age, initial Glasgow Coma Score (GCS), Injury Severity Score (ISS), initial systolic blood pressure (SBP), mechanism (blunt/penetrating), packed red blood cells (pRBCs) and fresh frozen plasma (FFP) transfusion volume (units) within the first 4 h, FFP/pRBC ratio (4h), and in-hospital mortality were obtained from the TQIP Public User Files. ResultsIn the TQIP database, 9257 patients had isolated sTBI and received pRBC transfusion within the first 4 h. The mortality rate within this group was 47.3%. The increase in mortality associated with the first unit of pRBCs was 20%, then increasing approximately 4% per unit transfused to a maximum mortality of 74% for 11 or more units. When adjusted for age, initial GCS, ISS, initial SBP, and mechanism, pRBC volume (1.09 [1.08-1.10], FFP volume (1.08 [1.07-1.09]), and FFP/pRBC ratio (1.18 [1.08-1.28]) were associated with in-hospital mortality. Our single-center study yielded 138 patients with isolated sTBI who received pRBC transfusion. These patients experienced a 60.1% in-hospital mortality rate. Logistic regression corrected for age, initial GCS, ISS, initial SBP, and mechanism demonstrated no significant association between pRBC transfusion volume (1.14 [0.81-1.61]), FFP transfusion volume (1.29 [0.91-1.82]), or FFP/pRBC ratio (6.42 [0.25-164.89]) and in-hospital mortality. ConclusionsPatients suffering from isolated sTBI have a higher rate of mortality with increasing amount of pRBC or FFP transfusion within the first 4 h of arrival.

Postoperative pulmonary complications in patients undergoing aortic surgery: A single-center retrospective study.

Postoperative pulmonary complications (PPCs) are among the most common complications after cardiovascular surgery. This study aimed to explore the real incidence of and risk factors for PPC in patients with acute type A aortic dissection (ATAAD) who underwent total aortic arch replacement combined with the frozen elephant trunk (TAR + FET). In total, 305 ATAAD patients undergoing TAR + FET from January 2021 to August 2022 in a single-center were divided into PPCs or non-PPCs group. The incidence of PPCs was calculated, risk factors of PPCs were analyzed, and postoperative outcomes were compared between these 2 groups. The incidence of any PPC was 29.2%. And the incidence of respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, acute respiratory distress syndrome, aspiration pneumonitis, pulmonary edema and bronchospasm was 23.0%, 12.5%, 10.5%, 1.0%, 0.7%, 1.0%, 0%, 0.7%, 0%, respectively. The logistic regression analysis revealed that the history of diabetes, history of renal dysfunction, preoperative SpO2 <90%, cardiopulmonary bypass duration, fresh frozen plasma volume and platelet concentrates volume were independent risk factors for PPCs. Among 2 groups, postoperative ventilation duration, postoperative length of stay in intensive care unit and hospital were (73.5 ± 79.0 vs 24.8 ± 35.2 hours; P < .001), (228.3 ± 151.2 vs 95.2 ± 72.0 hours; P < .001) and (17.9 ± 8.8 vs 11.5 ± 6.2 days; P < .001). There was no difference between 2 groups of in-hospital mortality rate. Additionally, other short-term outcomes were also significantly poorer in patients with PPCs. PPCs are common in ATAAD patients undergoing TAR + FET, and could be multifactorial. PPCs occurrence are associated with poor patient outcomes postoperatively and worth further investigation.

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

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. 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. 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 402mL. Patients in the group of ratio = 0 ∼ 0.5 had a higher chance than those without transfusion (OR = 7.487, p < 0.001). 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.

Outcomes of Patients Who Undergo Transfusion of Fresh Frozen Plasma: A Prospective, Observational, Multicentre Cohort Study in Hiroshima, Japan

PurposeGiven the chronic shortage of blood for transfusion in Japan, promotion of appropriate use of fresh frozen plasma (FFP) urgently needs to be addressed by the national blood project in Japan. Whether FFP transfusions are administered appropriately in Japan is currently unclear. In this study, we aimed to investigate the outcomes of patients who undergo FFP transfusion and the appropriateness of use of FFP.Patients and MethodsThis multicentre, prospective, observational cohort study was conducted from September 2017 to April 2019 at the 15 medical institutions in Hiroshima Prefecture that are the top providers of FFP. All patients who underwent FFP transfusion during the study period were included, relevant data being extracted from the medical records. The indications for FFP transfusion were classified in accordance with the Guidelines of the Ministry of Health, Labour and Welfare of Japan. Factors associated with patient outcomes at day 28 after FFP transfusion were subjected to multivariable logistic regression analysis.ResultsIn total, data of 1299 patients were eligible for analysis. At least 63.8% of indications for FFP were in accordance with the guideline for FFP transfusions. The mortality rate at day 28 after FFP transfusion was 16.2%. Older age (65–74 years: adjusted odds ratio [AOR]=4.3, ≥75 years: AOR=4.1), non-perioperative use (AOR=4.5), coagulopathy associated with liver damage (AOR=2.7), large volume of FFP transfused (AOR=2.5), and lack of improvement in blood coagulation following FFP transfusion were independently and significantly associated with death within 28 days after FFP transfusion.ConclusionOur findings do not support the simple conclusion that FFP transfusions contribute to prognosis. However, given that coagulopathy in patients with end-stage liver disease is infrequently improved by FFP transfusion, “inappropriate” use of FFP should be avoided. It is important to promote appropriate use of FFP so as not to waste blood resources.

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

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. An experimental in vitro study with blood products, crystalloids, magnesium, and calcium in a rapid infuser with a reservoir using a closed-loop system. Anesthesia research laboratory at an urban academic tertiary medical center PARTICIPANTS: Not applicable. 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. 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. 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.

Early postoperative effects of the hypothermia level during hypothermic circulatory arrest in patients with ascending aortic aneurysm

Aim. To compare the effectiveness and safety of ascending aortic hemiarch replacement performed during hypothermic circulatory arrest with different temperature regimens.Material and methods. The study included 104 patients with ascending aortic aneurysm, who underwent ascending aortic hemiarch replacement under hypothermic circulatory arrest and antegrade cerebral perfusion. Depending on the temperature regimen, all patients were divided into two comparable groups: group 1 (n=28) — patients operated on under mild hypothermia (29-31oС), group 2 (n=76) — patients operated on under moderate hypothermia (25-28oC).Results. Comparative analysis of intraoperative data between groups of patients with mild and moderate hypothermia revealed a significant difference in the duration of cardiopulmonary bypass (111 [97; 135] min vs 125 [108.5; 170] min, p=0,031) and surgery (240 [210; 270 ] min vs 275 [240; 330] min, p=0,003). In the early postoperative period, the best results were also obtained in patients of mild hypothermia group. In these patients, compared with moderate hypothermia group, there was a lower frequency of reoperation due to bleeding (3,5% vs 5,2%, p=0,572), a decrease in transfused fresh frozen plasma volume (2 [2; 4] vs 4 [2; 4], p=0,03), a decrease in the ventilatory support duration (10 [7; 16] hours vs 18 [10; 24] hours, p=0,002), as well as a bed-day decrease in intensive care unit (2 [2; 3] and 3 [2; 4] days, p=0,005). No neurologic deficit was found in any of the patients. In-hospital mortality had no significant intergroup differences (p=0,541).Conclusion. An increase in the temperature regimen during the ascending aortic hemiarch replacement performed under hypothermic circulatory arrest is relatively safe in relation to early postoperative complications. Mild hypothermia does not increase early postoperative surgical risks compared to moderate hypothermia.

Plasma resuscitation with adjunctive peritoneal resuscitation reduces ischemia-induced intestinal barrier breakdown following hemorrhagic shock.

Hemorrhagic shock (HS) and resuscitation (RES) cause ischemia-induced intestinal permeability due to intestinal barrier breakdown, damage to the endothelium, and tight junction (TJ) complex disruption between enterocytes. The effect of hemostatic RES with blood products on this phenomenon is unknown. Previously, we showed that fresh frozen plasma (FFP) RES, with or without directed peritoneal resuscitation (DPR) improved blood flow and alleviated organ injury and enterocyte damage following HS/RES. We hypothesized that FFP might decrease TJ injury and attenuate ischemia-induced intestinal permeability following HS/RES. Sprague-Dawley rats were randomly assigned to groups (n = 8): sham; crystalloid resuscitation (CR) (HS of 40% mean arterial pressure for 60 minutes) and CR (shed blood plus two volumes of CR); CR and DPR (intraperitoneal 2.5% peritoneal dialysis fluid); FFP (shed blood plus one volume of FFP); and FFP and DPR (intraperitoneal dialysis fluid plus two volumes of FFP). Fluorescein isothiocyanate-dextran (molecular weight, 4 kDa; FD4) was instilled into the gastrointestinal tract before hemorrhage; FD4 was measured by UV spectrometry at various time points. Plasma syndecan-1 and ileum tissue TJ proteins were measured using enzyme-linked immunosorbent assay. Immunofluorescence was used to visualize claudin-4 concentrations at 4 hours following HS/RES. Following HS, FFP attenuated FD4 leak across the intestine at all time points compared with CR and DPR alone. This response was significantly improved with the adjunctive DPR at 3 and 4 hours post-RES (p < 0.05). Resuscitation with FFP-DPR increased intestinal tissue concentrations of TJ proteins and decreased plasma syndecan-1. Immunofluorescence demonstrated decreased mobilization of claudin-4 in both FFP and FFP-DPR groups. Fresh frozen plasma-based RES improves intestinal TJ and endothelial integrity. The addition of DPR can further stabilize TJs and attenuate intestinal permeability. Combination therapy with DPR and FFP to mitigate intestinal barrier breakdown following shock could be a novel method of reducing ischemia-induced intestinal permeability and systemic inflammation after trauma. Prognostic/Epidemiologic, Level III.

Use of double filtration plasmapheresis for the treatment of acquired thrombocytopenic thrombotic purpura.

Double filtration plasmapheresis (DFPP) could be an alternative method to simple plasma exchange plasmapheresis in the treatment of acquired thrombotic thrombocytopenic purpura (aTTP). In a retrospective single center case series, we studied clinical presentation, management care, and prognosis of aTTP patients from our academic center treated with DFPP and IV infusion of fresh frozen plasma (FFP) between 2009 and 2018. Nine patients were included for 11 episodes. Median age was 38 years old (IQR 26-53) with 78% women. Six episodes (55%) required admission to the ICU, four of which required mechanical ventilation. Median FFP volume transfused was 35.2 mL/kg/d of session. Response was complete for nine episodes (82%). Four patients presented an early relapse, two a late relapse. Four patients died: one had an active untreated HCV infection, and two were over 80-year-old polymorbid patients. DFPP seems to be an efficient method of therapeutic plasmapheresis in TTP when combined with FFP transfusion and immunosuppressive treatments.

Rotational thromboelastometry-guided transfusion during lumbar pedicle subtraction osteotomy for adult spinal deformity: preliminary findings from a matched cohort study.

OBJECTIVESignificant blood loss and coagulopathy are often encountered during adult spinal deformity (ASD) surgery, and the optimal intraoperative transfusion algorithm is debatable. Rotational thromboelastometry (ROTEM), a functional viscoelastometric method for real-time hemostasis testing, may allow early identification of coagulopathy and improve transfusion practices. The objective of this study was to investigate the effect of ROTEM-guided blood product management on perioperative blood loss and transfusion requirements in ASD patients undergoing correction with pedicle subtraction osteotomy (PSO).METHODSThe authors retrospectively reviewed patients with ASD who underwent single-level lumbar PSO at the University of Virginia Health System. All patients who received ROTEM-guided blood product transfusion between 2015 and 2017 were matched in a 1:1 ratio to a historical cohort treated using conventional laboratory testing (control group). Co-primary outcomes were intraoperative estimated blood loss (EBL) and total blood product transfusion volume. Secondary outcomes were perioperative transfusion requirements and postoperative subfascial drain output.RESULTSThe matched groups (ROTEM and control) comprised 17 patients each. Comparison of matched group baseline characteristics demonstrated differences in female sex and total intraoperative dose of intravenous tranexamic acid (TXA). Although EBL was comparable between ROTEM versus control (3200.00 ± 2106.24 ml vs 3874.12 ± 2224.22 ml, p = 0.36), there was a small to medium effect size (Cohen's d = 0.31) on EBL reduction with ROTEM. The ROTEM group had less total blood product transfusion volume (1624.18 ± 1774.79 ml vs 2810.88 ± 1847.46 ml, p = 0.02), and the effect size was medium to large (Cohen's d = 0.66). This difference was no longer significant after adjusting for TXA (β = -0.18, 95% confidence interval [CI] -1995.78 to 671.64, p = 0.32). More cryoprecipitate and less fresh frozen plasma (FFP) were transfused in the ROTEM group patients (cryoprecipitate units: 1.24 ± 1.20 vs 0.53 ± 1.01, p = 0.03; FFP volume: 119.76 ± 230.82 ml vs 673.06 ± 627.08 ml, p < 0.01), and this remained significant after adjusting for TXA (cryoprecipitate units: β = 0.39, 95% CI 0.05 to 1.73, p = 0.04; FFP volume: β = -0.41, 95% CI -772.55 to -76.30, p = 0.02). Drain output was lower in the ROTEM group and remained significant after adjusting for TXA.CONCLUSIONSFor ASD patients treated using lumbar PSO, more cryoprecipitate and less FFP were transfused in the ROTEM group compared to the control group. These preliminary findings suggest ROTEM-guided therapy may allow early identification of hypofibrinogenemia, and aggressive management of this may reduce blood loss and total blood product transfusion volume. Additional prospective studies of larger cohorts are warranted to identify the appropriate subset of ASD patients who may benefit from intraoperative ROTEM analysis.

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters: P86. ROTEM-guided transfusion during pedicle subtraction osteotomy for adult spinal deformity: a propensity score-matched cohort analysis

BACKGROUND CONTEXT Surgical correction of adult spinal deformity (ASD) is often associated with significant blood loss and coagulopathy. Optimal intraoperative transfusion algorithm remains debatable. Rotational thromboelastometry (ROTEM), a functional viscoelastometric method for real-time hemostasis testing, may allow early identification of coagulopathy, and hence improve transfusion practices during surgery. PURPOSE To investigate the effects of ROTEM-guided therapy on intraoperative estimated blood loss (EBL) and transfusion requirements in patients who underwent pedicle subtraction osteotomy (PSO) for ASD. STUDY DESIGN/SETTING Retrospective chart review of a prospectively maintained, single-center, multisurgeon database. PATIENT SAMPLE Consecutive ASD patients. OUTCOME MEASURES Primary outcomes: intraoperative EBL and total volume of blood product transfused. Secondary outcomes: packed red blood cells (pRBC), platelets, cryoprecipitate, and fresh frozen plasma (FFP) transfused during surgery. METHODS All ASD patients who underwent single-level lumbar PSO with ROTEM-guided transfusion at our institution were matched in a 1:1 ratio to a historical cohort with the conventional clinical and point-of-care (POC) transfusion algorithm. Covariates for matching were age, body mass index, revision operation status, number of instrumented levels, number of transforaminal lumbar interbody fusions, number of Smith-Petersen osteotomies, and preoperative hemoglobin. RESULTS The matched groups comprised 17 patients each, and comparison of baseline demographic and surgical parameters demonstrated more women (p=.04) and a higher total intraoperative dose of intravenous tranexamic acid (TXA) administered (p=.03) in the ROTEM group. Although not significant, EBL was lower in the ROTEM group (3200.00±2106.24vs. 3874.12±2224.22 mL; p=.36), with small-to-medium effect size (Cohen's d=0.31). Prior to adjusting for TXA, ROTEM-based transfusion was associated with lower volume of total blood products transfused (1624.18±1774.79vs. 2810.88±1847.46 mL; p=.02), with medium-to-large effect size (Cohen's d=0.66). This difference was no longer significant after adjustment for TXA (β=−0.18; 95% CI [−1995.78 to 671.64]; p=.32). pRBC and platelet transfusions were comparable between the matched cohorts. The ROTEM group was associated with greater number of cryoprecipitate units (1.24±1.20vs. 0.53±1.01 units; p=.03) and lower FFP (119.76±230.82vs. 673.06±627.08 mL; p CONCLUSIONS Compared to the conventional transfusion criteria, the use of ROTEM-guided transfusion algorithm in lumbar PSO for surgical correction of ASD was associated with greater number of cryoprecipitate units and lower FFP volume transfused. ROTEM-guided transfusion allowed early identification and treatment of hypofibrinogenemia, and aggressive management of this complication may reduce intraoperative EBL and total volume of blood products transfused.

The effect of fluid resuscitation strategy on monocyte and T-cell surface markers

BackgroundDespite initial lifesaving benefits, posttraumatic resuscitation strategies have been associated with immunologic complications leading to systemic inflammatory response syndrome, sepsis, multiple organ failure, and late trauma death. Nevertheless, the direct effect on immunologic surface markers remains inadequately described. We hypothesized that changes in monocyte and T-cell surface markers were associated with initial posttraumatic fluid resuscitation. Materials and methodsData were extracted from the inflammation and host response to injury (Glue Grant) study. Blood samples were drawn from 492 patients on days 0, 1, 4, 7, 14, and 28 and analyzed for 31 monocyte and T-cell surface markers. Resuscitation strategies during the initial 48 h were quantified, including transfusion of packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, and crystalloids. Longitudinal surface marker concentration changes were quantified by the calculation of a within-patient signal intensity change and were associated with resuscitation strategy while controlling confounders. P-values were post hoc corrected using the false detection rate q-value. ResultsThe monocyte surface marker (CD83) trajectory (as measured by a within-patient signal intensity change) was found to be positively associated with volume of PRBCs transfused (q = 0.002) and negatively associated with the transfused volume of FFP (q = 0.004). T-cell surface marker (CD3) was found to be negatively associated with volume of PRBCs transfused (q = 854 × 10−9) and positively associated with the transfused volume of FFP (q = 0.022). Platelets and crystalloid transfusion volumes were not associated with any surface marker trajectories. ConclusionsPRBC and FFP transfusion was associated with opposing effects on CD3 and CD83 trajectories, which may in part explain some of the protective effects of a high FFP:PRBC ratio in trauma-related resuscitation.

The effect of resuscitation strategy on the longitudinal immuno-inflammatory response to blunt trauma

IntroductionResuscitation strategies following blunt trauma have been linked to immuno-inflammatory complications leading to systemic inflammatory syndrome (SIRS), sepsis and multiple organ failure (MOF). The effect of resuscitation strategy on longitudinal inflammation marker trajectories is, however, unknown. We hypothesized that the effect of resuscitation strategy extends beyond the trauma-related coagulopathy, perhaps affecting the longitudinal immuno-inflammatory response to injury. MethodsWe analyzed data prospectively collected for the Inflammation and Host Response to Injury (Glue Grant) study. Blood sampling for inflammation marker analyses from blunt trauma patients was done on admission days 0, 1, 4, 7, 14, 21 and 28 where applicable.Total volume transfused of packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets (PLT), and crystalloids during the initial 48h was extracted, along with an analysis for an array of cytokines by Enzyme Linked Immunosorbent Assay (ELISA) technique. A within patient concentration change (WPCC) was calculated to quantify longitudinal alterations in cytokine levels, while controlling for potential confounders. To account for the multiple comparisons performed, p-values obtained from the multivariate regression model were post-hoc corrected by the false detection rate (FDR) q-value. ResultsNo longitudinal trajectories of inflammatory markers were found to be associated with PRBC- or PLT transfusion. Three proinflammatory cytokines (Il-1β, MIP-1β, and TNFR2) were negatively associated with volume of FFP transfused (q=0.02, q<0.001 and q=0.007 respectively), and one proinflammatory cytokine (MIP-1β) was positively associated with crystalloid infusion (q=0.005). ConclusionsResuscitation strategy employed following blunt trauma has limited association to longitudinal inflammation marker trajectories, with a potential association between the strategy employed and IL-1β, TNFR2, and MIP-1β trajectories, respectively.

Case Report

Apixaban, an oral factor Xa inhibitor, has no commercially available assay to measure its activity and no specific antidote. To date, recommendations for managing bleeding associated with apixaban are based on studies with animal models and healthy volunteers (who do not have identified thrombogenic risk factors) and expert opinion. No clinical experience has been published in the literature. Ideally, apixaban would be reversed sufficiently to stop a perilous bleed without producing more thrombogenic risk than the patients’ underlying risk factors. Three-factor prothrombin complex concentrate (PCC3) is the least thrombogenic among the suggested reversal agents. Fresh frozen plasma (FFP) is sometimes recommended to add to PCC3, but it adds considerable volume. We describe successful management of an active left gluteal arterial extravasation due to trauma and associated apixaban, in a patient with aortic stenosis and atrial fibrillation, by administration of PCC3 alone, without the added volume of FFP.

Point-of-care haemostasis and coagulation monitoring in cardiac surgery at IRCCS Policlinico San Donato.

A rational management of perioperative and postoperative bleeding in modern cardiac surgery requires a thorough application of point-of-care (POC) monitoring in order to prevent and readily treat alterations of the haemostatic process. Preoperative platelet dysfunction, residual heparin after extracorporeal circulation, coagulation factors, and/or fibrinogen deficiency could be ruled out and specifically addressed with an appropriate treatment. Our approach includes preoperative platelet function testing of patients administered with thienopyridines or ticagrelor within 7-10 days before planned surgery and platelet function testing-based surgery timing. In the case of postoperative bleeding, residual heparin is tested and additional protamine is eventually administered. Simultaneously, an overall activity of coagulation factors (except fibrinogen) is assessed and, if significantly reduced, correction with prothrombotic complex concentrate is considered. If fibrinogen deficiency is suspected, a specific test is run, and in the case of severe reduction, the deficiency is compensated by fibrinogen concentrate or appropriate volume of fresh-frozen plasma. If both coagulation factors and fibrinogen activity are reduced, fibrinogen is usually considered for correction as first line, followed by prothrombin complex concentrate in the case of further bleeding. It is our clinical practice not to test nor to treat patients until postoperative bleeding appears clinically relevant. At IRCCS Policlinico San Donato, we firmly believe in the importance of the POC-based strategy for haemostatic treatment and constantly update our knowledge through research projects targeted in answering clinically relevant questions.

経口抗凝固療法に関連する二大合併症（頭蓋内出血，血栓症／血栓弁）の治療，及び併発時の管理

Warfarinによる経口抗凝固薬療法には，効果不足に起因する血栓性合併症と，効果過剰に起因する出血性合併症という双方のリスクが伴う．後者の中で特に重大な合併症である頭蓋内出血の死亡率は50％を超える．予後改善には早急かつ完全なWarfarin拮抗が必須である．新鮮凍結血漿が第一選択だが，Vitamin K依存性凝固因子の含有量が製剤間で異なり必要量が一概に予測できない，拮抗に時間を要する，容量負荷が大きいという側面を有する．緊急時には血液凝固第IX因子複合体が有用だが，適応外使用である．Warfarin拮抗の際には同時に血栓塞栓症の予防も念頭に置かなければならず，特に機械弁挿入患者では完全な止血を確認後，早期からヘパリンを併用し，発症1～2週間でWarfarin再開を考慮する．また機械弁不全をみた場合，血栓溶解療法を行うか否かには血栓弁とパンヌスの鑑別が重要である．さらに頭蓋内出血既往例が血栓弁を生じた場合，血栓溶解療法は禁忌に準じると考えるべきである．

Use of tranexamic acid in craniosynostosis surgery

Background Intraoperative tranexamic acid (TXA) administration has been used to abate blood loss in a variety of surgical procedures. Several recent studies have supported its efficacy in reducing transfusion requirements in pediatric cranial vault reconstruction (CVR). Objective To conduct a retrospective chart review to determine whether a significant reduction in packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusions exists when TXA is used. Methods A retrospective cohort study of 28 patients who underwent CVR for sagittal craniosynostosis was performed. Transfusion requirements for 14 patients who did not receive TXA were compared with 14 patients who did. Predictors of increased blood product transfusion were also studied. Results Total volume of PRBC transfusion was reduced by 50% with the use of TXA (P=0.004) with a 34% reduction in intraoperative PRBC transfusion (P=0.017) and a 67% reduction in postoperative PRBC transfusion (P&lt;0.001). Total volume of FFP transfusion was reduced by 46% (P=0.002) and postoperative FFP transfusion was reduced by 100% (P=0.001). The use of TXA was associated with a lower total volume of PRBC (P=0.003) and FFP (P=0.003) transfusions. Older patient age was associated with lower total volume of PRBC transfused (P=0.046 and P=0.002), but not with FFP (P=0.183 and P=0.099) transfusion volumes. Increasing patient weight was associated with lower PRBC (P=0.010 and P=0.020) and FFP (P=0.045 and P=0.016) transfusion volumes. Conclusion TXA decreased blood product transfusion requirements in patients undergoing CVR for sagittal craniosynostosis, and should be a routine part of the strategy to reduce blood loss in these procedures.

Use of tranexamic acid in craniosynostosis surgery.

Intraoperative tranexamic acid (TXA) administration has been used to abate blood loss in a variety of surgical procedures. Several recent studies have supported its efficacy in reducing transfusion requirements in pediatric cranial vault reconstruction (CVR). To conduct a retrospective chart review to determine whether a significant reduction in packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusions exists when TXA is used. A retrospective cohort study of 28 patients who underwent CVR for sagittal craniosynostosis was performed. Transfusion requirements for 14 patients who did not receive TXA were compared with 14 patients who did. Predictors of increased blood product transfusion were also studied. Total volume of PRBC transfusion was reduced by 50% with the use of TXA (P=0.004) with a 34% reduction in intraoperative PRBC transfusion (P=0.017) and a 67% reduction in postoperative PRBC transfusion (P<0.001). Total volume of FFP transfusion was reduced by 46% (P=0.002) and postoperative FFP transfusion was reduced by 100% (P=0.001). The use of TXA was associated with a lower total volume of PRBC (P=0.003) and FFP (P=0.003) transfusions. Older patient age was associated with lower total volume of PRBC transfused (P=0.046 and P=0.002), but not with FFP (P=0.183 and P=0.099) transfusion volumes. Increasing patient weight was associated with lower PRBC (P=0.010 and P=0.020) and FFP (P=0.045 and P=0.016) transfusion volumes. TXA decreased blood product transfusion requirements in patients undergoing CVR for sagittal craniosynostosis, and should be a routine part of the strategy to reduce blood loss in these procedures.

Restoration of Normal Prothrombin Time/International Normalized Ratio With Fresh Frozen Plasma in Hypocoagulable Patients.

Fresh frozen plasma (FFP) is an effective reversal agent for hypocoagulable patients. Its proven efficacy continues to prompt its usage as both a prophylactic and a therapeutic therapy. Although published guidelines encouraging the appropriate administration of FFP exist, overutilization continues. The purpose of these ex vivo studies was to determine the effects of succeeding volumes of FFP supplementation on hypocoagulable plasma prothrombin time/international normalized ratio (PT/INR). By analyzing the decline in PT/INR with varying volumes of FFP, a minimal required volume of FFP could be identified representing the optimal volume to administer while still providing therapeutic effect. A total of 497 plasma samples were screened for elevated PT/INR values and 50 samples were selected for inclusion in this experiment. The initial PTs/INRs ranged from 12.5 to 43.4 seconds/1.42 to 4.91. Subsequent declines in PT/INR values were analyzed following addition of 50, 100, and 150 µL of FFP to a fixed volume of 250 µL of plasma (26.4 ± 5.318 seconds/2.99 ± 0.603, 13.3 ± 1.077 seconds/1.51 ± 0.122, 11.2 ± 0.712 seconds/1.27 ± 0.081, and 10.3 ± 0.533 seconds/1.16 ± 0.06, respectively). A nonlinear relationship between decline in INR values and percentage of FFP supplementation was demonstrated. The greatest effect on INR was obtained after supplementation with 50 µL (49%). Doubling and tripling the volume of FFP lead to significantly lower declines in INR (16% and 8%, respectively). Analysis of variance indicated a statistical significance with subsequent volume supplementation of FFP, but marginal clinical benefits exist between the PTs/INRs obtainable with increased FFP volume administration.

Early treatment with lyophilized plasma protects the brain in a large animal model of combined traumatic brain injury and hemorrhagic shock

Combination of traumatic brain injury (TBI) and hemorrhagic shock (HS) can result in significant morbidity and mortality. We have previously shown that early administration of fresh frozen plasma (FFP) in a large animal model of TBI and HS reduces the size of the brain lesion as well as the associated edema. However, FFP is a perishable product that is not well suited for use in the austere prehospital settings. In this study, we tested whether a shelf-stable, low-volume, lyophilized plasma (LSP) product was as effective as FFP. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. A prototype, computerized, cortical impact device was used to create TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-millisecond dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was induced (40-45% total blood volume) concurrent with the TBI. After 2 hours of shock, animals were treated with (1) normal saline (NS, n = 5), (2) FFP (n = 5), and (3) LSP (n = 5). The volume of FFP and LSP matched the shed blood volume, whereas NS was 3 times the volume. Six hours after resuscitation, brains were sectioned and stained with TTC (2, 3, 5-Triphenyltetrazolium chloride), and lesion size (mm) and swelling (percent change in volume compared with the contralateral, uninjured side) were measured. This protocol resulted in a highly reproducible brain injury, with clinically relevant changes in blood pressure, cardiac output, tissue hypoperfusion, intracranial pressure, and brain tissue oxygenation. Compared with NS, treatment with LSP significantly (p < 0.05) decreased brain lesion size and swelling (51% and 54%, respectively). In a clinically realistic combined TBI + HS model, early administration of plasma products decreases brain lesion size and edema. LSP is as effective as FFP, while offering many logistic advantages.