Combined Administration of Fibrinogen and Factor XIII Concentrate Does Not Improve Dilutional Coagulopathy Superiorly Than Sole Fibrinogen Therapy: Results of an In-Vitro Thrombelastographic Study.
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SUBMITTER: Schneck E
PROVIDER: S-EPMC8150940 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:There is currently a contrast between the demonstrated benefits of fibrinogen concentrate in correcting bleeding and reducing transfusion, and its perceived thrombogenic potential. This analysis evaluates the effects of fibrinogen concentrate on coagulation up to 12 days after administration during aortic surgery.We performed a post hoc analysis of a prospective, randomized, double-blind, controlled trial of fibrinogen concentrate as first-line haemostatic therapy in aortic surgery. After cardiopulmonary bypass (CPB) and protamine administration, subjects with coagulopathic bleeding received fibrinogen concentrate or placebo. The placebo group received allogeneic blood products, including fresh-frozen plasma (FFP; n=32); the fibrinogen concentrate group received fibrinogen concentrate alone (FC; n=14), or fibrinogen concentrate followed by allogeneic blood products (FC+FFP; n=15). Plasma fibrinogen, fibrin-based clotting (ROTEM(®)-based FIBTEM assay), and peri- and postoperative haematological and coagulation parameters were compared.Plasma fibrinogen and FIBTEM maximum clot firmness (MCF) decreased ?50% during CPB but were corrected by FC or FC+FFP. At last suture, the highest values for plasma fibrinogen (360 mg dl(-1)) and FIBTEM MCF (22 mm) were within normal ranges--below the acute phase increases observed after surgery. In patients receiving only FFP as a source of fibrinogen, these parameters recovered marginally by last suture (P<0.001 vs FC and FC+FFP). All groups displayed comparable haemostasis at 24 h post-surgery. Fibrinogen concentrate did not cause alterations of other haemostasis parameters.Fibrinogen concentrate provided specific, significant, short-lived increases in plasma fibrinogen and fibrin-based clot firmness after aortic surgery.
| S-EPMC3657602 | biostudies-literature
Project description:BACKGROUND:Hypofibrinogenaemia is associated with increased morbidity and mortality, but the optimal treatment level, the use of preemptive treatment and the preferred source of fibrinogen remain disputed. Fibrinogen concentrate is increasingly used and recommended for bleeding with acquired haemostatic deficiencies in several countries, but evidence is lacking regarding indications, dosing, efficacy and safety. OBJECTIVES:We assessed the benefits and harms of fibrinogen concentrate compared with placebo or usual treatment for bleeding patients. SEARCH METHODS:We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8); MEDLINE (1950 to 9 August 2013); EMBASE (1980 to 9 August 2013); International Web of Science (1964 to 9 August 2013); CINAHL (1980 to 9 August 2013); LILACS (1982 to 9 August 2013); and the Chinese Biomedical Literature Database (up to 10 November 2011), together with databases of ongoing trials. We contacted trial authors, authors of previous reviews and manufacturers in the field. SELECTION CRITERIA:We included all randomized controlled trials (RCTs), irrespective of blinding or language, that compared fibrinogen concentrate with placebo/other treatment or no treatment in bleeding patients, excluding neonates and patients with hereditary bleeding disorders. DATA COLLECTION AND ANALYSIS:Three review authors independently abstracted data; we resolved any disagreements by discussion. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effects of fibrinogen concentrate in adults and children in terms of various clinical and physiological outcomes. We presented pooled estimates of the effects of intervention on dichotomous outcomes as risk ratios (RRs) and on continuous outcomes as mean differences, with 95% confidence intervals (CIs). We assessed the risk of bias through assessment of trial methodological components and the risk of random error through trial sequential analysis. MAIN RESULTS:We included six RCTs with a total of 248 participants; none of the trials were determined to have overall low risk of bias. We found 12 ongoing trials, from which we were unable to retrieve any data. Only two trials provided data on mortality, and one was a zero event study; thus the meta-analysis showed no statistically significant effect on overall mortality (2.6% vs 9.5%, RR 0.28, 95% CI 0.03 to 2.33). Our analyses on blood transfusion data suggest a beneficial effect of fibrinogen concentrate in reducing the incidence of allogenic transfusions (RR 0.47, 95% CI 0.31 to 0.72) but show no effect on other predefined outcomes, including adverse events such as thrombotic episodes. AUTHORS' CONCLUSIONS:In the six available RCTs of elective surgery, fibrinogen concentrate appears to reduce transfusion requirements, but the included trials are of low quality with high risk of bias and are underpowered to detect mortality, benefit or harm. Furthermore, data on mortality are lacking, heterogeneity is high and acute or severe bleeding in a non-elective surgical setting remains unexplored. Currently, weak evidence supports the use of fibrinogen concentrate in bleeding patients, as tested here in primarily elective cardiac surgery. More research is urgently needed.
| S-EPMC6517136 | biostudies-literature
Project description:BackgroundUse of intraoperative prothrombin complex concentrates (PCC) and fibrinogen concentrate administration has been linked to thrombotic events. However, it is unknown if its use is associated with thrombotic events after liver transplant.Methods and analysisWe conducted a post hoc analysis of a prospectively conducted registry database study on patients who underwent liver transplant between 2004 and 2017 at Heidelberg University Hospital, Heidelberg, Germany. Univariate and multivariate analyses were used to determine the association between PCC and fibrinogen concentrate administration and thrombotic complications.ResultsData from 939 transplantations were included in the analysis. Perioperative PCC or fibrinogen administration was independently associated with the primary composite endpoint Hepatic artery thrombosis (HAT), Portal vein thrombosis (PVT), and inferior vena cava thrombosis [adjusted HR: 2.018 (1.174; 3.468), p = 0.011]. PCC or fibrinogen administration was associated with the secondary endpoints 30-day mortality (OR 4.225, p < 0.001), graft failure (OR 3.093, p < 0.001), intraoperative blood loss, red blood cell concentrate, fresh frozen plasma and platelet transfusion, longer hospitalization, and longer length of stay in intensive care units (ICUs) (all p < 0.001). PCC or fibrinogen administration were not associated with pulmonary embolism, myocardial infarction, stroke, or deep vein thrombosis within 30 days after surgery.ConclusionA critical review of established strategies in coagulation management during liver transplantation is warranted. Perioperative caregivers should exercise caution when administering coagulation factor concentrate during liver transplant surgery. Prospective randomized controlled trials are needed to establish causality for the relationship between coagulation factors and thrombotic events in liver transplantation. Further studies should be tailored to identify patient subgroups that will likely benefit from PCC or fibrinogen administration.
| S-EPMC9745140 | biostudies-literature
Project description:BACKGROUND Postpartum hemorrhage (PPH) is related to several factors but is frequently associated with coagulopathy with maternal mortality. Fibrinogen is a very important agent for bleeding. When its concentration is decreased, severe surgical blood loss may occur. Here, we investigate the association of postpartum bleeding characteristics with evolution of PPH in patients who were taking fibrinogen concentrate (FC). MATERIAL AND METHODS PPH patients' demographic parameters, outcome variables, and laboratory findings before and at ICU were recorded between January 2015 and July 2017. The duration of ICU stay and plasmapheresis, renal replacement therapy, maternal-fetal deaths, RBC, FFP, and PC replacement were calculated. RESULTS Group I: Fibrinogen levels were ≤150 mg/dl (n: 31), Group II: Fibrinogen levels were >151 mg/dl (n: 18). In the peroperative period, there was no difference between the 2 groups in terms of RBC, FFP, or PC transfussion. In intraoperative and ICU admission period, patients in Group I had higher INR, APTT, and PT values than in the other group. FC replacement according to fibrinogen level was given, ranging from to 1 to 6 gr in Group I and 1-2 gr in Group II intraoperatively and at ICU 2-8 gr FC was given in both groups. In the intraoperative and ICU admission period, blood transfusion requirements of patients after fibrinogen replacement were evaluated and there was no statistically significant difference between groups. There were no differrences between groups in duration of intensive care unit stay, hospital stay, and mechanical ventilation. CONCLUSIONS Adequate FC therapy prevents unnecessary RBC, FFP, and PC replacement and prevents complications and volume overload.
| S-EPMC6421935 | biostudies-literature
Project description:March 2013 represented the 50th anniversary of the first license granted for a fibrinogen concentrate. In this review, we look at the history of bleeding management that led to the development of fibrinogen concentrate, discuss its current use, and consider future developments for this product.
| S-EPMC4741261 | biostudies-other
Project description:BackgroundWe aimed to create a theoretical tool to model the effect of three haemostatic agents containing fibrinogen (therapeutic plasma, cryoprecipitate, and fibrinogen concentrate) on the patient's plasma fibrinogen level.MethodsA mathematical model was developed step-wise. The relationship between the amount of haemostatic agent and plasma fibrinogen level was plotted for each agent. A fibrinogen concentration simulator (FCS(amount)) was developed, where the amount of haemostatic agent was calculated from patient characteristics, agent characteristics, and target plasma fibrinogen level. Refinements were introduced so that (i) FCS(amount) would account for in vivo fibrinogen recovery, (ii) circulatory volume would not increase ad infinitum with increasing amounts, and (iii) red blood cells would be included in the simulation if haematocrit decreased below a certain level. A second FCS (FCS(level)) was created to calculate fibrinogen levels resulting from specified amounts of haemostatic agents.ResultsFibrinogen concentration in haemostatic agents has a critical impact on their ability to increase patients' fibrinogen levels. If the target plasma fibrinogen level approaches the concentration of the fibrinogen source, the required amounts increase exponentially; it is impossible to achieve a target above the concentration of the fibrinogen source.ConclusionsWe successfully developed two theoretical tools answering the questions: 'How much therapeutic plasma, cryoprecipitate, or fibrinogen concentrate would be needed to achieve a specified target fibrinogen level?' and 'What would be the resultant fibrinogen level for a specified amount of haemostatic agent?' The current tools are not intended for clinical application, but they are potentially useful for educational purposes.
| S-EPMC4166889 | biostudies-literature
Project description:BackgroundThe view that 2 l of crystalloid and 1.5 l of colloid can be infused while awaiting compatible blood for patients with major postpartum haemorrhage is based on expert opinion documents. We describe real-world changes in levels of coagulation parameters after the administration of different volumes of clear fluids to women suffering from major postpartum haemorrhage.MethodsWe performed a nationwide retrospective cohort study in the Netherlands among 1038 women experiencing severe postpartum haemorrhage who had received at least four units of red cells or fresh frozen plasma or platelets in addition to red cells. The volume of clear fluids administered before the time of blood sampling was classified into three fluid administration strategies, based on the RCOG guideline: <?2 L, 2-3.5 L and?>?3.5 L. Outcomes included haemoglobin, haematocrit, platelet count, fibrinogen, aPTT and PT levels.ResultsHaemoglobin, haematocrit, platelet count, fibrinogen and aPTT were associated with volumes of clear fluids, which was most pronounced early during the course of postpartum haemorrhage. During the earliest phases of postpartum haemorrhage median haemoglobin level was 10.1 g/dl (IQR 8.5-11.6) among the women who received <?2 L clear fluids and 8.1 g/dl (IQR 7.1-8.4) among women who received >?3.5 L of clear fluids; similarly median platelet counts were 181?×?109/litre (IQR 131-239) and 89?×?109/litre (IQR 84-135), aPTT 29 s (IQR 27-33) and 38 s (IQR 35-55) and fibrinogen 3.9 g/L (IQR 2.5-5.2) and 1.6 g/L (IQR 1.3-2.1).ConclusionsIn this large cohort of women with severe postpartum haemorrhage, administration of larger volumes of clear fluids was associated with more severe deterioration of coagulation parameters corresponding to dilution. Our findings provide thus far the best available evidence to support expert opinion-based guidelines recommending restrictive fluid resuscitation in women experiencing postpartum haemorrhage.Trial registrationNetherlands Trial Register ( NTR4079 ), registration date July 17, 2013.
| S-EPMC6180574 | biostudies-literature
Project description:ObjectiveTo evaluate the clinical effects of early administration of fibrinogen concentrate in patients with severe trauma and hypofibrinogenemia.MethodsWe conducted an open randomized feasibility trial between December 2015 and January 2017 in patients with severe trauma admitted to the emergency department of a large trauma center. Patients presented with hypotension, tachycardia, and FIBTEM findings suggestive of hypofibrinogenemia. The intervention group received fibrinogen concentrate (50 mg/kg), and the control group did not receive early fibrinogen replacement. The primary outcome was feasibility assessed as the proportion of patients receiving the allocated treatment within 60 min after randomization. The secondary outcomes were transfusion requirements and other exploratory outcomes. Randomization was performed using sequentially numbered and sealed opaque envelopes. ClinicalTrials.gov: NCT02864875.ResultsThirty-two patients were randomized (16 in each group). All patients received the allocated treatment within 60 min after randomization (100%, 95% confidence interval, 86.7%-100%). The median length of intensive care unit stay was shorter in the intervention group (8 days, interquartile range [IQR] 5.75-10.0 vs. 11 days, IQR 8.5-16.0; p=0.02). There was no difference between the groups in other clinical outcomes. No adverse effects related to treatment were recorded in either group.ConclusionEarly fibrinogen replacement with fibrinogen concentrate was feasible. Larger trials are required to properly evaluate clinical outcomes.
| S-EPMC8552954 | biostudies-literature
Project description:BACKGROUND:Congenital fibrinogen deficiency is an ultra-rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder. METHODS:Hemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA® , Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four-point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined. RESULTS:Twenty-five afibrinogenemia patients were treated with HFC: 24 for on-demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92-0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95-0.999). Mean ± standard deviation (SD) increase in MCF was 5.8 ± 2.5 mm one hour after the first HFC infusion (mean ± SD dose, 61.88 ± 11.73 mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80 mg/kg [34.09-225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82-1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies. CONCLUSIONS:Human fibrinogen concentrate was efficacious for on-demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia.
| S-EPMC7187153 | biostudies-literature
Project description:Background:Fibrinogen plays an important role in haemostasis during the early phase of trauma, and low fibrinogen levels after severe trauma are associated with haemostatic impairment, massive bleeding, and poor outcomes. Aggressive fibrinogen supplementation may improve haemostatic function, as fibrinogen levels deteriorate before other routine coagulation parameters in this setting. Therefore, we evaluated whether early administration of fibrinogen concentrate (FC) was associated with improved survival in severe trauma patients. Methods:This single-centre retrospective study evaluated patients with severe trauma (injury severity score ??16) who were admitted to our emergency department between January 2010 and July 2018. The exclusion criteria included age <?18?years, cardiac arrest before emergency department arrival, cervical spinal cord injury not caused by a high-energy accident, and severe burn injuries. The FC and control groups included trauma patients who received and did not receive FC within 1?h after emergency department arrival, respectively. Propensity scores were used to balance the two groups based on the trauma and injury severity score (TRISS), heart rate at emergency department admission, and age. The primary outcome was the in-hospital survival rate. Results:The propensity scoring model had a c-statistic of 0.734, the Hosmer-Lemeshow chi-squared value was 7.036 (degrees of freedom = 8), and the non-significant p value of 0.533 indicated a good model fit. The propensity score matching created 31 matched pairs of patients, who had appropriately balanced characteristics. The FC group had a significantly higher in-hospital survival rate than the control group (log-rank p = 0.013). The FC group also used significantly higher amounts of red blood cells and fresh frozen plasma within 6?h after emergency department admission. However, the two groups had similar transfusion amounts between 6 and 24?h after emergency department admission. Conclusions:The present study revealed that early FC administration was associated with a favourable survival rate among severe trauma patients. Therefore, FC may be useful for the early management of trauma-induced coagulopathy and may improve outcomes in this setting.
| S-EPMC6961302 | biostudies-literature