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.

A resonance sonorheometry guided dose reduction of plasma transfusion in repetitive hip surgery in a patient with a severe factor XI deficiency: a case report.

Factor XI deficiency is a rare disorder with an unpredictable bleeding tendency. Here, we report the successful use of the sonic estimation of elasticity via resonance sonorheometry for guiding the management of haemostasis in a patient with a severe factor XI deficiency in repeated revision hip surgeries. Regardless of an administration of fresh frozen plasma, a significant haemorrhage occurred at the first of three hip surgeries. The repeat application of fresh frozen plasma normalised the prolonged activated partial thromboplastin time and the resonance sonorheometry clot time values; the factor XI activity increased to a sufficient level. No significant bleeding occurred in the second and third hip surgery. Using a resonance sonorheometry guided approach in haemostasis management has the potential to improve safety for patients with factor XI deficiency undergoing surgery by ensuring sufficient clotting and preventing side effects.

Evaluation of the effectiveness of fresh frozen plasma transfusion as adjuvant treatment in acute organophosphate-poisoned patients: A randomized clinical trial.

Organophosphorus (OP) poisoning is a significant cause of morbidity and mortality worldwide. Recent research has explored new approaches to improving treatment options, which present several challenges. This study aimed to evaluate the role of fresh frozen plasma (FFP) as an adjunctive therapy for acute OP intoxication. A prospective single-blinded randomized clinical trial was conducted on patients of both sexes admitted to the Intensive Care Unit (ICU) of the Poison Control Center at Ain Shams University Hospital (PCC-ASUH) with acute OP toxicity during the period from the beginning of August 2022 to the end of July 2023. According to the Peradeniya score, Group I consisted of 48 patients (52%) with moderate OP poisoning, and Group II consisted of 44 patients (48%) with severe OP poisoning. Patients in the moderate group were assigned to receive either standard treatment (Group Ia, n = 24) or standard treatment plus FFP (Group Ib, n = 24). In addition, patients in the severe group were assigned to receive either standard treatment (Group IIa, n = 22) or standard treatment plus FFP (Group IIb, n = 22). A total of 46 patients received FFP transfusion. The authors demonstrated that the early use of a total of nine packs of FFP (250 mL each) over three consecutive days significantly reduced the total doses of atropine and oximes, the total hospitalization period, and the requirement for mechanical ventilation in patients with OP poisoning, both in the moderate and severe groups.

Complications of therapeutic plasma exchange: A retrospective, single-center study of 2505 procedures performed in 338 patients over 15 years.

INTRODUCTION: Therapeutic plasma exchange (TPE) may involve complications. We aimed to review the demographic data, indications, technical information, and complications. METHODS: Data for TPE procedures (TPEPs) performed between 2004 and 2018 were retrospectively. RESULTS: This study covered 2505 TPEPs performed on 338 patients; 55% of them were female (n = 186), and the median age was 36 years (range, 11-93 years). Most TPEPs were administered for hematological (40.6%) indications. The incidence of complications on the first procedure was 3.2% (n = 80); only 16 procedures (0.6%) were failed. The complication incidence was 19.8% (n = 497), with 789 total complications. Most of the complications were patient-related (90.4%), and the most of them were urticaria (29.1%), occlusion (3.2%), and faulty systems (1.01%), respectively. The use of only fresh frozen plasma as replacement fluid caused a higher complication rate (22.1%, p < 0.01). CONCLUSION: The number of TPEPs is increasing every day. Hematologic indications for TPE and the use of fresh frozen plasma may increase the risk of complications.

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.

Efficacy of fresh frozen plasma transfusion in decompensated cirrhosis patients with coagulopathy admitted to ICU: a retrospective cohort study from MIMIC-IV database.

We aimed to explore the association between FFP transfusion and outcomes of DC patients with significant coagulopathy. A total of 693 DC patients with significant coagulopathy were analyzed with 233 patients per group after propensity score matching (PSM). Patients who received FFP transfusion were matched with those receiving conventional therapy via PSM. Regression analysis showed FFP transfusion had no benefit in 30-day (HR: 1.08, 95% CI 0.83-1.4), 90-day (HR: 1.03, 95% CI 0.80-1.31) and in-hospital(HR: 1.30, 95% CI 0.90-1.89) mortality, associated with increased risk of liver failure (OR: 3.00, 95% CI 1.78-5.07), kidney failure (OR: 1.90, 95% CI 1.13-3.18), coagulation failure (OR: 2.55, 95% CI 1.52-4.27), respiratory failure (OR: 1.76, 95% CI 1.15-2.69), and circulatory failure (OR: 2.15, 95% CI 1.27-3.64), and even associated with prolonged the LOS ICU (ß: 2.61, 95% CI 1.59-3.62) and LOS hospital (ß: 6.59, 95% CI 2.62-10.57). In sensitivity analysis, multivariate analysis (HR: 1.09, 95%CI 0.86, 1.38), IPTW (HR: 1.11, 95%CI 0.95-1.29) and CAPS (HR: 1.09, 95% CI 0.86-1.38) showed FFP transfusion had no beneficial effect on the 30-day mortality. Smooth curve fitting demonstrated the risk of liver failure, kidney failure and circulatory failure increased by 3%, 2% and 2% respectively, for each 1 ml/kg increase in FFP transfusion. We found there was no significant difference of CLIF-SOFA and MELD score between the two group on day 0, 3, 7, 14. Compared with the conventional group, INR, APTT, and TBIL in the FFP transfusion group significantly increased, while PaO2/FiO2 significantly decreased within 14 days. In conclusion, FFP transfusion had no beneficial effect on the 30-day, 90-day, in-hospital mortality, was associated with prolonged the LOS ICU and LOS hospital, and the increased risk of liver failure, kidney failure, coagulation failure, respiratory failure and circulatory failure events. However, large, multi-center, randomized controlled trials, prospective cohort studies and external validation are still needed to verify the efficacy of FFP transfusion in the future.

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.

Comparative Analysis of AB vs. ABO-specific Plasma for Desensitization in Blood Group O Recipients: An In Vitro Study.

Neutralizing capacity measurement (NCM) of soluble ABH substances (SAS) in plasma was assessed to guide the selection of the appropriate ABO group of fresh-frozen plasma (FFP) for plasma exchange (PE) in blood group O recipients with ABO-incompatible transplantations. Neutralizing capacity was assessed by measuring anti-A and/or anti-B titers in samples comprising one unit of O FFP and 10 O EDTA plasma samples and subtracting the binary logarithm of the titer in each group with a saline dilution. Ten EDTA plasma samples with Lewis b (Leb) antigen positivity and 10 sets of pooled FFP from each blood group were used as diluents. In O FFP, the NCM values (mean±SD) were 3.4±0.52 (2.6±0.52) and 2.6±0.52 (1.5±0.3) in B and AB for IgM (total antibody) anti-B (both P<0.001), and in the 10 O EDTA plasma samples, they were 3.9±0.88 (3.1±0.88) and 3.2±0.79 (2.4±0.97) for IgM (P=0.0013) and total anti-B (P=0.025), respectively. In vitro analysis revealed that B FFP is more effective than AB FFP in reducing IgM and total anti-B antibody titers in O recipients, regardless of Leb antigen positivity.

Transfusion of non-red blood cell blood products does not reduce survival following cardiac surgery.

OBJECTIVES: The literature supports the assertion that patients undergoing cardiac surgery who receive perioperative packed red blood cell (pRBC) transfusions have increased associated mortality. The aim of the current study is to assess whether there is an association between non-pRBC blood product transfusions and increased mortality. METHODS: Data from our center's Society of Thoracic Surgeons database included patients who underwent cardiac surgery from 2010 to 2018. Patients with pRBC transfusions or circulatory arrest were excluded. Propensity matching was performed (1:1; caliper = 0.2 times the standard deviation of logit of propensity score). Kaplan-Meier estimates and Cox regression were used. Cardiac transplant, ventricular assist devices, transcatheter aortic valves, and patients who had experienced circulatory arrest were excluded from this analysis. RESULTS: A total of 8042 patients met criteria for analysis. Following propensity matching (1:1), 395 patients requiring perioperative non-pRBC blood products (platelets, fresh-frozen plasma, and cryoprecipitate) were matched with 395 nontransfusion patients, yielding equitable patient cohorts. Median follow-up was 4.5 (3.0-6.4) years. Patients received platelets (327 [82.8%]), fresh-frozen plasma (141 [35.7%]), and cryoprecipitate (60 [15.2%]). There was no significant difference in the postoperative mortality (6 [1.5%] vs 4 [1.0%]; P = .52). Reoperation (20 [5.0%] vs 8 [2.0%]; P < .02) and prolonged ventilation (36 [9.1%] vs 19 [4.8%]; P < .02) were greater in the transfusion group. Emergent operation (odds ratio [OR] 2.86 [1.72-4.78]; P < .001), intra-aortic balloon pump (OR 3.24 [1.64-6.39]; P < .001), and multivalve operation (OR 4.34 [2.83-6.67]; P < .001) were significantly associated with blood product use. Blood product transfusion (hazard ratio; 1.15 [0.89-1.48]; P = .3) was not significantly associated with increased mortality risk. There was no significant long-term survival difference between cohorts. CONCLUSIONS: Patients who undergo cardiac surgery requiring blood products alone, without pRBC transfusion, have similar postoperative and long-term survival compared with patients not requiring blood products. These data are based on a limited patient sample, and future studies will aid in improving the generalizability of these results.

Deleterious effects of plasma-derived cellular debris in a porcine model of hemorrhagic shock.

BACKGROUND: Recent studies identify large quantities of inflammatory cellular debris within Fresh Frozen Plasma (FFP). As FFP is a mainstay of hemorrhagic shock resuscitation, we used a porcine model of hemorrhagic shock and ischemia/reperfusion to investigate the inflammatory potential of plasma-derived cellular debris administered during resuscitation. METHODS: The porcine model of hemorrhagic shock included laparotomy with 35 % hemorrhage (Hem), 45 min of ischemia from supraceliac aortic occlusion with subsequent clamp release (IR), followed by protocolized resuscitation for 6 h. Cellular debris (Debris) was added to the resuscitation phase in three groups. The four groups consisted of Hem + IR (n = 4), Hem + IR + Debris (n = 3), Hem + Debris (n = 3), and IR + Debris (n = 3). A battery of laboratory, physiologic, cytokine, and outcome data were compared between groups. RESULTS: As expected, the Hem + IR group showed severe time dependent decrements in organ function and physiologic parameters. All animals that included both IR and Debris (Hem + IR + Debris or IR + Debris) died prior to the six-hour end point, while all animals in the Hem + IR and Hem + Debris survived. Cytokines measured at 30-60 min after initiation of resuscitation revealed significant differences in IL-18 and IL-1ß between all groups. CONCLUSIONS: Ischemia and reperfusion appear to prime the immune system to the deleterious effects of plasma-derived cellular debris. In the presence of ischemia and reperfusion, this model showed the equivalency of 100 % lethality when resuscitation included quantities of cellular debris at levels routinely administered to trauma patients during transfusion of FFP. A deeper understanding of the immunobiology of FFP-derived cellular debris is critical to optimize resuscitation for hemorrhagic shock.

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.

Congenital factor XI deficiency with multiple tooth extractions (Case report).

Congenital factor XI deficiency (CFXI) is a rare blood disorder that occurs in one of every one million individuals. Given its rarity, there are very few reports of surgical procedures performed in the oral region CFXI patients. The present study reports the case of a 43-year-old man with CFXI who experienced multiple tooth extractions. It also conducted a review of the literature and treatment outline. We preoperatively administered fresh frozen plasma (FFP) before the tooth extraction and continued to transfuse FFP at the rate of 2 units per day from day 1 to 4 of admission. The extractions were divided into two parts, maxillary and mandibular and the teeth extracted on days 2 and 4 of admission. The patient was discharged on day 6 of admission because there was good progress and no postoperative bleeding. Therefore, it was possible to perform multiple tooth extractions without abnormal bleeding in the oral cavity; the chance of bleeding was reduced by administering FFP and increasing local hemostasis in CFXI patients.

Antithrombin concentrates may benefit cardiopulmonary bypass patients with suspected heparin resistance: A retrospective analysis of real-world data.

Background: Heparin resistance is a common complication of surgical patients requiring anticoagulation, such as those undergoing cardiopulmonary bypass (CPB). Treatments to address heparin resistance include supplementation of antithrombin (AT) or fresh frozen plasma (FFP). This retrospective database analysis compared key outcomes in suspected heparin-resistant patients undergoing CPB treated with AT or FFP. Methods: De-identified United States electronic health records (Cerner Health Facts®) were queried. International Classification of Diseases (ICD-9/10) codes were used to determine CPB procedures and FFP administration. AT administration was identified using medication data, while a combination of lab and medication data examining activated clotting times detected heparin resistance in FFP patients. Adult inpatients (≥18 years old) seen between 2001 and 2018 were included. Differences in mortality, intensive care unit (ICU) length of stay (LOS), and hospital-free days (using a 30-day post-discharge period) were assessed with univariate models as well as adjusted logistic regression models controlling for patient characteristics and Charlson Comorbidity Index (CCI) scores. Results: Of the 502 patients identified, 247 received AT and 255 received FFP. The FFP cohort was associated with a higher CCI compared to the AT cohort (3.3 ± 2.4 vs. 2.3 ± 2.0, P < .001). The AT cohort was associated with a 71% (Odds Ratio [OR]: 0.29, 95% Confidence Interval [CI]: P = .003) and 66% (OR: 0.34, 95% CI: P = .01) reduction in mortality when compared to FFP using univariate and adjusted logistic regression models, respectively. Similarly, use of AT also showed a 22% shorter ICU LOS (P = .02) and 10% more hospital-free days in the 30 days following discharge (P = .004) according to the univariate models, though statistical significance was absent within adjusted models in both ICU LOS (P = .08) and hospital-free days (P = .53). Conclusions: Compared to FFP, AT use suggests a reduction in the odds of mortality in suspected heparin-resistant patients undergoing CPB, though larger prospective studies are necessary to elucidate potential differences in hospital-free days or ICU LOS across treatment modalities.

Combined medical and surgical approach in the management of ligneous conjunctivitis in a pediatric patient: A case report.

INTRODUCTION: Ligneous conjunctivitis (LC), a rare chronic conjunctivitis linked to plasminogen deficiency, poses challenges in research and management due to its complexity. This case report details the combined medical and surgical approach in managing LC in a 1.5-year-old female with congenital hydrocephalus, plasminogen deficiency, and glaucoma. CASE PRESENTATION: The patient's LC required a comprehensive treatment plan involving systemic and topical therapies, surgical intervention, and fresh frozen plasma (FFP) infusions via a central line. DISCUSSION: Managing LC necessitates a comprehensive, individualized approach due to its rarity and lack of standardized treatments. Various therapies have shown promise, but their availability, cost, and potential side effects vary. FFP infusions played a crucial role in managing plasminogen deficiency, but the potential complications associated with central lines must be considered. Ongoing clinical trials aim to improve LC treatment, but until results are available, clinicians must rely on existing evidence and clinical judgment. CONCLUSION: This case underscores the complexity of managing LC and the significance of adopting an individualized treatment strategy. Regular follow-ups are crucial for flexibility and adaptability in treatment plans to address potential recurrences. Further research is necessary to validate these findings and assess the long-term effectiveness of the combined approach.

Rotational ThromboElastometry-guided blood component administration versus standard of care in patients with Cirrhosis and coagulopathy undergoing Invasive ProcEdures (RECIPE): study protocol for a randomised controlled trial.

BACKGROUND: Patients with cirrhosis often undergo invasive procedures both for management of complications of their advanced liver disease, including treatment for hepatocellular carcinoma, as well as underlying comorbidities. Despite a current understanding that most patients with cirrhosis are in a rebalanced haemostatic state (despite abnormalities in conventional coagulation tests, namely INR and platelet count), patients with cirrhosis are still often given prophylactic blood components based on these conventional parameters, in an effort to reduce procedure-related bleeding. Viscoelastic tests such as Rotational Thromboelastometry (ROTEM) provide a global measurement of haemostasis and have been shown to predict bleeding risk more accurately than conventional coagulation tests, and better guide blood product transfusion in a number of surgical and trauma-related settings. The aim of this study is to assess the utility of a ROTEM-based algorithm to guide prophylactic blood component delivery in patients with cirrhosis undergoing invasive procedures. We hypothesise that ROTEM-based decision-making will lead to a reduction in pre-procedural blood component usage, particularly fresh frozen plasma (FFP), compared with standard of care, whilst maintaining optimal clinical outcomes. METHODS: This is a multi-centre randomised controlled trial comparing ROTEM-guided prophylactic blood component administration to standard of care in patients with cirrhosis and coagulopathy undergoing invasive procedures. The primary efficacy outcome of the trial is the proportion of procedures requiring prophylactic transfusion, with the primary safety outcome being procedure-related bleeding complications. Secondary outcomes include the amount of blood products (FFP, platelets, cryoprecipitate) transfused, transfusion-related side effects, procedure-related complications other than bleeding, hospital length of stay and survival. DISCUSSION: We anticipate that this project will lead to improved prognostication of patients with cirrhosis, in terms of their peri-procedural bleeding risk. We hope to show that a significant proportion of cirrhotic patients, deemed coagulopathic on the basis of standard coagulation tests such as INR and platelet count, are actually in a haemostatic balance and thus do not require prophylactic blood product, leading to decreased and more efficient blood component use. TRIAL REGISTRATION: RECIPE has been prospectively registered with the Australia and New Zealand Clinical Trials Registry on the 30th April 2019 ( ACTRN12619000644167 ).

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.

Method to Alleviate Dilutional Coagulopathy Caused by Continuous Renal Replacement Therapy Introduction in a Low-Birth-Weight Neonate: A Case Report.

Continuous renal replacement therapy (CRRT) in neonates and children has recently been used to treat hyperammonemia and metabolic disorders. However, CRRT introduction in low-birth-weight neonates is still a challenge due to vascular access limitations, bleeding complications, and a lack of neonatal-specific devices. We present the case of a low-birth-weight neonate whose severe coagulopathy due to CRRT introduction with a red cell concentration-primed circuit was alleviated by priming the new circuit with blood from the current circuit. This male preterm infant (birth weight: 1,935 g) was admitted to the pediatric intensive care unit at two days old with metabolic acidosis and hyperammonemia, which required CRRT. Following CRRT introduction, he showed marked thrombocytopenia (platelet count: 305,000-59,000/µL) and coagulopathy (prothrombin time international normalized ratio (PT/INR) >10), necessitating platelet and fresh frozen plasma transfusions. Upon circuit exchange, we primed the new circuit with blood from the current circuit. This resulted in only a slight worsening of thrombocytopenia (platelet count: 56,000-32,000/µL) and almost no change in coagulation (PT/INR: 1.42-1.54). We also reviewed the literature regarding safe CRRT management in low-birth-weight neonates. Since there is no established method for the use of blood from the current circuit during circuit exchange, this should be addressed in future work.

The impact of using fresh frozen plasma in cardiopulmonary bypass preparation on thromboelastometric parameters and receiving blood products among pediatric patients undergoing cardiac surgery.

Introduction: The aim of this study was to determine the effect of fresh frozen plasma (FFP) for priming of cardiopulmonary bypass (CPB) circuit on rotational thromboelastometry (ROTEM) and transfusion in pediatric cardiac surgery. Methods: Eighty patients younger than seven years old, were divided into case (FFP) (n=40) and control (n=40) groups. In the case group,10-20 mL/kg fresh frozen plasm was used for priming the CPB. The control group received 10-20 mL/kg of hydroxyethyl starch. ROTEM was done before surgical incision and after separation from CPB. The amount of transfusion (platelet and FFP) in the operating room and 24 hours after surgery were recorded. Results: Statistically significant difference was found between the case and control group in terms of changes in the Rotem parameters. The amount of transfusion of platelets in the operating room was significantly higher in the control group than in the case group. Conclusion: It seems that adding FFP to the prime solution is more effective in young patients and infants due to the higher susceptibility of the infant coagulation system to coagulation and hemorrhagic disorders in comparison with other patients.