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Background: In severely injured trauma patients, hypofibrinoginaemia is associated with increased mortality. There is no evidence-based consensus for what constitutes optimal fibrinogen therapy, treatment dose or timing of administration. The aim of this systematic review was to evaluate the effects of early fibrinogen replacement, either cryoprecipitate or fibrinogen concentrate (FgC) on mortality, transfusion requirements and deep venous thrombosis (DVT). Methods: A systematic search of studies was performed on MEDLINE, EMBASE and clinicaltrials.gov databases using standardised search criteria. All clinical studies which examined the use of either cryoprecipitate or FgC in patients with traumatic haemorrhage within 4 h of admission to hospital were included. Primary outcome was mortality (28-day, 30-day or in-hospital). Secondary outcomes were DVT incidence and blood component transfusions. A narrative synthesis was performed for all observational studies. Meta-analysis was completed for all included RCTs for mortality with pre-defined sub-group analysis of FgC and cryoprecipitate use. Grading of Recommendations Assessment, Development, and Evaluation was used to assess the quality of evidence. Results: Overall, 1906 studies were screened with 12 studies included and five RCTs (all suitable for meta-analysis) totalling 1758 participants. Three RCTs reported FgC therapy, and two used cryoprecipitate. Four out of five RCTs examined empiric fibrinogen replacement for suspected traumatic haemorrhage. There was no difference in the primary outcome of mortality: early fibrinogen replacement (24%) vs control (25%), OR 1.03 (95% CI; 0.68–1.56). Subgroup analysis found no difference in outcome between the FgC and control: 18.1% vs 10.9% respectively, OR 1.99 (95% CI; 0.80–4.94). Similarly for cryoprecipitate, there was no difference in mortality between groups: cryoprecipitate (24.9%) vs control (26.1%), OR 0.71 (95% CI, 0.25–2.01). Reporting of transfusion data precluded meta-analysis. There was no difference in DVT incidence: fibrinogen replacement (3%) vs control (4%), OR 0.73 (0.43, 1.25). Overall, the quality of evidence was graded as low due to indirectness and imprecision. Conclusions: There is no association between early fibrinogen replacement and mortality, DVT or transfusion requirements. We found no superiority between FgC or cryoprecipitate. This systematic review highlights the urgent need for further RCTs to assess the efficacy of early fibrinogen replacement, preferred strategy (goal-directed vs empiric) as well as optimal therapeutic product for both patient outcome and cost effectiveness. [ABSTRACT FROM AUTHOR]

Objectives Cryoprecipitated antihemophilic factor (cryo) has been used for fibrinogen replacement in actively bleeding patients, dysfibrinogenemia, and hypofibrinogenemia. Cryo has a shelf life of 4 to 6 hours after thawing and a long turnaround time in issuing the product, posing a major limitation of its use. Recently, the US Food and Drug Administration approved Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex [IFC]) for the treatment of bleeding associated with fibrinogen deficiency, which can be stored at room temperature and has a shelf life of 5 days after thawing. Methods We identified locations and specific end users with high cryoprecipitate utilization and waste. We partnered with our blood supplier to use IFC in these locations. We analyzed waste and turnaround time before and after implementation. Results Operative locations had a waste rate that exceeded nonoperative locations (16.7% vs 3%) and were targeted for IFC implementation. IFC was added to our inventory to replace all cryo orders from adult operating rooms, and waste decreased to 2.2% in these locations. Overall waste of cryoprecipitated products across all locations was reduced from 8.8% to 2.4%. The turnaround time for cryoprecipitated products was reduced by 58% from 30.4 minutes to 14.6 minutes. Conclusions There has been a substantial decrease in waste with improved turnaround time after IFC implementation. This has improved blood bank logistics, improved efficiency of patient care, and reduced costly waste. [ABSTRACT FROM AUTHOR]

Background and Objectives: The post‐thaw shelf‐life of cryoprecipitate is 6 h, leading to high wastage. Storage of thawed cryoprecipitate at refrigerated temperatures may be feasible to extend the shelf‐life. This study aimed to evaluate the quality of thawed cryoprecipitate stored at 1–6°C for up to 14 days. Materials and Methods: Cryoprecipitate (mini‐ and full‐size packs derived from both apheresis and whole blood [WB] collections) was thawed, immediately sampled and then stored at 1–6°C for up to 14 days. Mini‐packs were sampled at 6, 24, 48 and 72 h, day 7 and 14; full‐size cryoprecipitate was sampled on day 3, 5 or 7. Coagulation factors (F) II, V, VIII, IX, X and XIII, von Willebrand factor (VWF) and fibrinogen were measured using a coagulation analyser. Thrombin generation was measured by calibrated automated thrombogram. Results: FVIII decreased during post‐thaw storage; this was significant after 24 h for WB (p = 0.0002) and apheresis (p < 0.0001). All apheresis and eight of 20 WB cryoprecipitate met the FVIII specification (≥ 70 IU/unit) on day 14 post‐thaw. Fibrinogen remained stable for 48 h, and components met the specification on day 14 post‐thaw. There were no significant differences in VWF (WB p = 0.1292; apheresis p = 0.1507) throughout storage. There were small but significant decreases in thrombin generation lag time, endogenous thrombin potential and time to peak for both WB and apheresis cryoprecipitate. Conclusion: Whilst coagulation factors in cryoprecipitate decreased after post‐thaw storage, the thawed cryoprecipitate met the Council of Europe specifications when stored at refrigerated temperatures for 7 days. [ABSTRACT FROM AUTHOR]

Abstract Background Intraoperative hemorrhage in cardiac surgery increases risk of morbidity and mortality. Low pre-operative and perioperative levels of fibrinogen, a key clotting factor, are associated with severity of hemorrhage and increased transfusion of blood components. The ability to supplement fibrinogen during hemorrhagic resuscitation is delayed 45–60 min because cryoprecipitated antihemophilic factor (cryo AHF) is stored frozen, due to a short post-thaw shelf life. Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex, IFC) can be kept thawed, at room temperature, for up to 5 days, making it possible to be immediately available for hemorrhaging patients. This trial will investigate if earlier correction of acquired hypofibrinogenemia with IFC in hemorrhaging cardiac surgery patients reduces the total number of perioperatively transfused allogeneic blood products (red blood cells, plasma, and platelets) as compared to cryo AHF. Methods This is a single center, prospective, cluster randomized trial with an adaptive design. Acquired hypofibrinogenemia will be assessed by rotational thromboelastometry (ROTEM) and the threshold for cryo AHF/IFC transfusion defined as FIBTEM A10 ≤ 10 mm in bleeding patients. IFC/cryo AHF will be randomized by 1-month blocks. Cardiac surgery patients will be enrolled in the study if they have an eligible procedure and at least one dose of a cryo AHF/IFC product (approximately 2 g fibrinogen) is transfused. Data from the electronic health record, including the blood bank and lab information systems, will be prospectively collected from the health system’s data warehouse. Discussion This trial aims to provide evidence of the clinical efficacy of utilizing readily available thawed IFC during acute bleeding in the cardiac surgery setting compared to traditional cryo AHF. Trial registration ClinicalTrials.gov NCT05711524. Feb 3, 2023.

At our quaternary teaching hospital in Queensland, Australia, there has been a rapid increase from 2019 to 2022 in the usage of fibrinogen concentrate (FC) in preference to cryoprecipitate for cardiac surgery. FC is indicated for patients having major trauma requiring haemostatic resuscitation, major intraoperative haemorrhage, or liver transplant patients with major intraoperative haemorrhage. These patients must exhibit severe hypofibrinogenaemia, which is assessed using assay cut‐offs of thromboelastogram (TEG) (citrated functional fibrinogen [CFF] ≤ 10 mm) or rotational thromboelastometry (ROTEM) (FIBTEM A5 ≤ 8 mm). FC usage over cryoprecipitate for cardiac surgery is an ongoing debate due to advantages such as dose predictability, rapid reconstitution, viral inactivation, and minimal transfusion‐related adverse events; however, it is expensive. The aim of this study was to capture prescribing patterns of FC and appropriateness against local guidelines. Retrospective data were analysed, and the practice was compared to hospital guidelines. Data from 52 patients over a 4‐year period (2019–2022) showed intraoperative haemorrhage was the leading indication for FC use (65%, n = 34), followed by liver transplantation (27%, n = 14), and major trauma (8%, n = 4). When breaking down the cause of intraoperative haemorrhage, cardiothoracic surgery, both elective (50%, n = 17) and emergency procedures (41%, n = 14), accounted for 91% of all operative bleeding requiring FC. There were 34 (65%) of 52 patients who received a differing dose of FC compared to what was recommended in the hospital guideline, with 50% (n = 17) receiving a higher than recommended dose and 50% (n = 17) receiving lower than recommended doses. This project was exempt due to the local policy requirements that constitute research by the Metro South Human Research Ethics Committee (Reference no: CM2305202303). The justification for this exemption was as follows: the study presented no foreseeable risk of patient harm as it involved evaluation of standard care involved the use of existing non‐identifiable patient records. [ABSTRACT FROM AUTHOR]

Background: Group AB plasma does not contain anti‐A or anti‐B antibodies and is therefore considered universal but is in limited supply (4% of the population). There is currently no licensed universal plasma available, and therefore current clinical guidelines for transfusion require the donor and recipient to be blood group compatible. We sought to understand the benefits of universal plasma to hospitals in England, to inform R&D priorities going forward. Study Design and Methods: To understand the benefits of universal plasma (cryoprecipitate included), we distributed two surveys to hospitals (267 in total) in England. Results: Safety was the perceived top benefit of universal plasma (95%), with cost identified as the main barrier to adoption (82%), although the majority of respondents were willing to pay more for universal components. Ninety‐five respondents felt they would replace all or part of their stock holding with universal plasma, with 91% anticipating that their overall stock holding of plasma would reduce as well as there will be a reduction in their plasma wastage (by up to 25%). Hospitals (56%) thought that the availability of universal plasma would support more rapid provision of plasma for transfusion, particularly in emergency situations, with the emergency/trauma department deemed to be the area that would see the greatest benefit from these universal blood components. Discussion: The response to both the potential clinical and operational benefits of a universal plasma and cryoprecipitate was positive. [ABSTRACT FROM AUTHOR]

Background: Intraoperative hemorrhage in cardiac surgery increases risk of morbidity and mortality. Low pre-operative and perioperative levels of fibrinogen, a key clotting factor, are associated with severity of hemorrhage and increased transfusion of blood components. The ability to supplement fibrinogen during hemorrhagic resuscitation is delayed 45–60 min because cryoprecipitated antihemophilic factor (cryo AHF) is stored frozen, due to a short post-thaw shelf life. Pathogen Reduced Cryoprecipitated Fibrinogen Complex (INTERCEPT Fibrinogen Complex, IFC) can be kept thawed, at room temperature, for up to 5 days, making it possible to be immediately available for hemorrhaging patients. This trial will investigate if earlier correction of acquired hypofibrinogenemia with IFC in hemorrhaging cardiac surgery patients reduces the total number of perioperatively transfused allogeneic blood products (red blood cells, plasma, and platelets) as compared to cryo AHF. Methods: This is a single center, prospective, cluster randomized trial with an adaptive design. Acquired hypofibrinogenemia will be assessed by rotational thromboelastometry (ROTEM) and the threshold for cryo AHF/IFC transfusion defined as FIBTEM A10 ≤ 10 mm in bleeding patients. IFC/cryo AHF will be randomized by 1-month blocks. Cardiac surgery patients will be enrolled in the study if they have an eligible procedure and at least one dose of a cryo AHF/IFC product (approximately 2 g fibrinogen) is transfused. Data from the electronic health record, including the blood bank and lab information systems, will be prospectively collected from the health system's data warehouse. Discussion: This trial aims to provide evidence of the clinical efficacy of utilizing readily available thawed IFC during acute bleeding in the cardiac surgery setting compared to traditional cryo AHF. Trial registration: ClinicalTrials.gov NCT05711524. Feb 3, 2023. [ABSTRACT FROM AUTHOR]

Background: Transfusion‐related acute lung injury (TRALI) remains a major contributor to transfusion‐associated mortality. While the pathogenesis of TRALI remains unclear, there is evidence of a role for blood components. We therefore investigated the potential effects of fresh frozen plasma (FFP), cryoprecipitate, and extracellular vesicles (EVs) derived from these blood components, on the viability of human lung microvascular endothelial cells (HLMVECs) in vitro. Methods: EVs were isolated from FFP and cryoprecipitate using size‐exclusion chromatography and characterized by nanoparticle tracking analysis, western blotting, and transmission electron microscopy. The potential effects of these blood components and their EVs on HLMVEC viability (determined by trypan blue exclusion) were examined in the presence and absence of neutrophils, either with or without prior treatment of HLMVECs with LPS. Results: EVs isolated from FFP and cryoprecipitate displayed morphological and biochemical properties conforming to latest international criteria. While FFP, cryoprecipitate, and EVs derived from FFP, each reduced HLMVEC viability, no effect was observed for EVs derived from cryoprecipitate. Conclusion: Our findings demonstrate clear differences in the effects of FFP, cryoprecipitate, and their respective EVs on HLMVEC viability in vitro. Examination of the mechanisms underlying these differences may lead to an improved understanding of the factors that promote development of TRALI. [ABSTRACT FROM AUTHOR]

Background: Persistent cryoglobulinemia after the completion of antiviral treatment is an important consideration of clinical management in chronic hepatitis C patients. We aimed to investigate the occurrence of serum cryoglobulinemia in chronic hepatitis C patients without cryoglobulinemia at the initiation of antiviral treatment. Methods: In total, 776 patients without cryoglobulinemia were assessed for serum cryoglobulinemia after the completion of anti-HCV treatment. Serum cryoglobulinemia precipitation was assessed upon both the initiation and the completion of the treatment and analyzed for the clinical laboratory factors associated with chronic hepatitis C. Results: One hundred eighteen (118) patients were checked for serum cryo-precipitation after the completion of the treatment, and eight patients (4.6%) were positive for serum cryoglobulinemia. The patients who tested positive for cryoglobulinemia included a higher proportion of liver cirrhosis patients (4/50%, p = 0.033) and other organ cancer patients (5/62.5%, p = 0.006) than patients who showed no signs of cryoglobulinemia after treatment. In a multivariate analysis, liver cirrhosis (odds ratio [OR]—17.86, 95% confidence interval [95% CI]—1.79–177.35, p = 0.014) and other organ cancer (OR–25.17 95% CI—2.59–244.23, p = 0.005) were independently and significantly associated with positive cryoglobulinemia 3 months after antiviral treatment. Conclusions: Three months after the antiviral DAA therapy had concluded, eight patients tested positive for cryoglobulinemia, representing a 6.7% prevalence. Liver cirrhosis and other organ cancer were independently and significantly associated with positive cryoglobulinemia after antiviral treatment. Further investigation into the causes of positive cryoglobulinemia after DAA antiviral therapy is warranted. [ABSTRACT FROM AUTHOR]

Aim: Cryoprecipitate (CRYO) is a concentrated preparation of coagulation factors formulated from fresh frozen plasma (FFP), which can replenish coagulation factors rapidly. Preeclampsia (PE) is frequently associated with postpartum hemorrhage (PPH), and the rapid replenishment of coagulation factors is vital in the management. We conducted a retrospective cohort study to determine the efficacy of administering CRYO irrespective of fibrinogen levels in patients with PE who experienced severe PPH. Methods: Patients with PPH accompanied by PE and those who required red blood cell (RBC) transfusion were included. Cases were divided into two groups: those treated with CRYO (N = 16) and those not treated with CRYO (N = 10). The total transfusion volume, blood loss before and after transfusion initiation, duration of hospitalization, presence of pulmonary edema, and performance of either interventional radiology or hysterectomy were compared. Results: The median fibrinogen levels before transfusion were 2.24 and 2.34 g/L in the CRYO group and the not using group, respectively. Although blood loss before transfusion was comparable between the two groups, blood loss after transfusion was significantly less in the CRYO group (median: 520 vs. 2352 mL, p = 0.015), as well as the total blood loss (median: 2285 vs. 3825 mL, p = 0.005) and total transfusion volume (median: RBC 6 vs. 16 U, p = 0.01, FFP 10 vs. 20 U, p = 0.017). Conclusion: Prompt replenishment of coagulation factors using CRYO to patients with PE who experience severe PPH could decrease further bleeding. [ABSTRACT FROM AUTHOR]

Background: Evidence to support cryoprecipitate for reversal of alteplase-related hemorrhagic conversion of acute ischemic stroke is limited. Guidelines recommend cryoprecipitate as first line treatment, followed by aminocaproic acid as a conditional recommendation with very low-quality evidence. The purpose of this case series was to describe the use of cryoprecipitate for alteplase-related hemorrhagic conversion of acute ischemic stroke. Methods: This was an IRB-approved retrospective case series of adults who received cryoprecipitate for an alteplase-related hemorrhagic conversion of acute ischemic stroke at two comprehensive stroke centers within a large academic medical center. Thromboembolism at 14 days and hemostasis within 24 hours were collected. The outcomes of cryoprecipitate alone vs cryoprecipitate with aminocaproic acid (C + A) were also described. Results: A total of 19 patients were included. Thrombosis occurred in 1/19 (5%) and hemostasis occurred in 4/14 (29%) of evaluable patients. In-hospital mortality was seen in 9/19 (47%) patients. Seventy four percent (14/19) of patients received concomitant blood products other than cryoprecipitate and 63% received a concomitant reversal agent. Thirteen patients received cryoprecipitate alone and six received C + A. Thrombosis was seen in 1/13 (8%) vs 0/6 (0%) and hemostasis occurred in 2/11 (18%) and 2/3 (67%) evaluable cryoprecipitate vs C + A patients respectively. Conclusion: Cryoprecipitate was associated with a low rate of thrombosis and hemostasis for alteplase-associated hemorrhagic conversion of acute ischemic stroke. There was significant heterogeneity in treatment regimens, including the use of and dosing of adjunctive aminocaproic acid and monitoring of fibrinogen levels. [ABSTRACT FROM AUTHOR]

Background: Cryoprecipitate is used primarily to replenish fibrinogen levels in patients. Little is known about the presence of micro‐ or nano‐sized particles in cryoprecipitate. Therefore, we aimed to quantify these particles and investigate some pre‐analytical considerations. Materials and Methods: Particle concentration and size distribution were determined in 10 cryoprecipitate units by nanoparticle tracking analysis (NTA). The effects of freeze–thawing cryoprecipitate and 0.45 μm filtration with either regenerated cellulose (RC) or polytetrafluoroethylene (PTFE) filters before sample analysis were examined. Results: Neither the size nor concentration of particles were affected by two freeze/thaw cycles. PTFE filtration, but not RC filtration, significantly reduced particle mean and mode size compared to RC filtration and mode size compared to unfiltered cryoprecipitate. The 10 cryoprecipitate units had an average particle concentration of 2.50 × 1011 ± 1.10 × 1011 particles/mL, a mean particle size of 133.8 ± 7.5 nm and a mode particle size of 107.9 ± 11.1 nm. Conclusion: This study demonstrated that preanalytical filtration of cryoprecipitate units using RC filters was suitable for NTA. An additional freeze/thaw cycle did not impact NTA parameters, suggesting that aliquoting cryoprecipitate units prior to laboratory investigations is suitable for downstream analyses. [ABSTRACT FROM AUTHOR]

Background: Platelets play a key role in the treatment of thrombocytopenia. Nowadays, platelets (PLTs) are only obtained through blood donation. However, due to the limitations in their preparation and storage, they are produced in laboratories, especially through bioreactors that convert megakaryocytes from stem cells into large-scale injectable PLTs. Materials and Methods: In this study, the CD34 cells isolated from cord blood were differentiated into megakaryocytes. A 6-chamber bioreactor with a two-layer collagen scaffold, several ECM factors, and human cryoprecipitate were used to simulate the structure of the bone marrow. After the addition of megakaryocytes to the scaffold, PLTs were produced due to the flow pressure and the interaction between the scaffold structure and the ECM factors. Results: CD41 + cells were expanded 100 times as much as CD34 + cord blood stem cells. The mean PLT release from one megakaryocyte in the pure collagen scaffold was 17.42 PLTs. Once fibrin, fibronectin, hyaluronic acid, and cryoprecipitates were added to collagen, the mean PLT release was 21.4, 22.4, 23.9, and 27.37, respectively. With the simultaneous addition of three factors to collagen (CFFH) and then four factors (CFFHC), the number of PLTs reached 30.52 and then 34. Conclusion: Functional PLTs can be produced on a large scale with a multi-chamber bioreactor using a combination of ECM and cryoprecipitate with collagen scaffolding. [ABSTRACT FROM AUTHOR]

The development of new human leukocyte antigens (HLAs) and donor-specific antibodies (DSAs) in patients are associated with worse outcomes following lung transplantation. The authors aimed to examine the relationship between blood product transfusion in the first 72 hours after lung transplantation and the development of HLA antibodies, including DSAs. A retrospective observational study. At a single academic tertiary center. Adult lung transplant recipients who underwent transplantation between September 2014 and June 2019. None. A total of 380 patients were included in this study, and 87 (23%) developed de novo donor-specific antibodies in the first year after transplantation. Eighty-five patients (22%) developed new HLA antibodies that were not donor-specific, and 208 patients (55%) did not develop new HLA antibodies in the first year after transplantation. Factors associated with increased HLA and DSA development included donor pulmonary infection, non-infectious indication for transplant, increased recipient body mass index, and a preoperative calculated panel reactive antibody value above 0. Multivariate analysis identified platelet transfusion associated with an increased risk of de novo HLA antibody development compared to the negative group (odds ratio [OR; 95% CI] 1.18 [1.02-1.36]; p = 0.025). Cryoprecipitate transfusion was associated with de novo DSA development compared to the negative group (OR [95% CI] 2.21 [1.32-3.69] for 1 v 0 units; p = 0.002). Increased perioperative transfusion of platelets and cryoprecipitate are associated with de novo HLA and DSA development, respectively, in lung transplant recipients during the first year after transplantation. [ABSTRACT FROM AUTHOR]

Objectives. To identify the peculiarities of blood components consumption by hospitals in the Mogilev region during five years and to determine trends in their use in connection with the pandemic of COVID-19 infection. Material and methods. Retrospectively for 2017-2021, the volumes of transfusion of erythrocyte blood components (EBC), fresh frozen plasma (FFP), the number of transfused doses of platelet blood components (PBC), cryoprecipitate (CP) in hospitals throughout the Mogilev region were studied depending on the number of treated patients, the number of bed-days spent by them in the hospital and the number of cases of COVID-19 infection. Also these indicators were analyzed in a single health care institution “Mogilev Regional Clinical Hospital”, in which in 2020-2021 care to patients with COVID-19 infection was provided. Results. Consumption of EBC, FFP and CP in 2017-2019 per 1000 inhabitants of the Mogilev region did not change statistically significantly, there was an increase in the use of PBC in 2019 compared to 2017 (p

• No standardized guideline exists for preparing cryoprecipitate from 350 ml of whole blood. • The thawing method of plasma for the preparation of cryoprecipitates is also controversial. • The cryobath method of plasma thawing resulted in a better factor VIII yield, and the blood bank refrigerator method resulted in a higher fibrinogen yield. • Over 75% of the cryoprecipitates prepared from 350 ml whole blood passed the quality criteria. • 350 ml whole blood collection from low body weight (<55 kg) donors could be utilized to prepare cryoprecipitates. Cryoprecipitate is used in conditions like hypofibrinogenemia, massive transfusion with bleeding, and factor XIII deficiency. The current guidelines support the preparation of cryoprecipitate from 450 ml whole blood. But 350 ml of whole blood collection is expected from low body weight (<55 kg) donors. However, no standardized criteria exist for preparing cryoprecipitate from 350 ml of whole blood. This study compared the fibrinogen and factor VIII levels in cryoprecipitate units prepared from 350 ml versus 450 ml whole blood collection. The study also compared the fibrinogen and factor VIII levels prepared by circulating water bath versus blood bank refrigerator (BBR) thawing method. A total of 128 blood bags were equally divided into groups A and B for 450 and 350 ml whole blood collection further subdivided into subgroups based on thawing methods. The fibrinogen and factor VIII yield were analyzed in the cryoprecipitates prepared from both groups. The factor VIII levels were significantly higher in cryoprecipitate made from 450 ml whole blood collection (P = 0.02). The BBR method of plasma thawing resulted in better fibrinogen recovery than the cryo bath method. Whereas vice versa in the case of factor VIII recovery. A weak but significant positive correlation was noted in factor VIII levels with the plasma volume. Over 75% of the cryoprecipitates prepared from 350 ml whole blood passed the fibrinogen and factor VIII quality control criteria. So, 350 ml whole blood collection from low body weight (<55 kg) donors could be utilized to prepare cryoprcipitates. However, future clinical studies should focus on the cryoprecipitate's clinical efficacy prepared from 350 ml of whole blood. [ABSTRACT FROM AUTHOR]

Introduction: Uncontrolled hemorrhage accounts for up to 40% of trauma-related mortality. Previous reports demonstrate that decreased fibrinogen levels during traumatic hemorrhage are associated with worse outcomes. Cryoprecipitate is used to replace fibrinogen for patients in hemorrhagic shock undergoing massive transfusion (MT), though the optimal ratio of cryoprecipitate to fresh frozen plasma (FFP), packed red blood cells (PRBCs), and platelets remains undefined. The purpose of this study is to investigate the effect of admission fibrinogen level and the use of cryoprecipitate on outcomes in trauma patients undergoing MT. Methods: A prospective practice management guideline was established to obtain fibrinogen levels on adult trauma patients undergoing MT at a level I trauma center from December 2019 to December 2021. Ten units of cryoprecipitate were administered every other round of MT. Thromboelastography (TEG) was also obtained at the initiation and completion of MT. Patient demographic, injury, transfusion, and outcome data were collected. Hypofibrinogenemic (<200 mg/dL) patients at initiation of MT were compared to patients with a level of 200 mg/dL or greater. Results: A total of 96 out of 130 patients met criteria and underwent MT with a median admission fibrinogen of 170.5 mg/dL. Hypofibrinogenemia was associated with elevated INR (1.26 vs 1.13, P <.001) and abnormal TEG including decreased alpha angle (68.1 vs 73.3, P <.001), increased K time (1.7 vs 1.1, P <.001), and decreased max amplitude (58 vs 66, P <.001). Patients with hypofibrinogenemia received more PRBC (10 vs 7 U, P =.002), FFP (9 vs 6 U, P =.003), and platelets (2 vs 1 U, P =.004) during MT. Hypofibrinogenemic patients demonstrated greater mortality than patients with normal levels (50% vs 23.5%, P =.021). Older age, decreased GCS, and elevated injury severity score (ISS) were risk factors for mortality. Increased fibrinogen was associated with lower odds of mortality (P =.001). Age, ISS, and fibrinogen level remained significantly associated with mortality in a multivariable analysis. Overall, fibrinogen in post-MT survivors showed an increase in median level compared to admission (231 vs 177.5 mg/dL, P <.001). Conclusion: Trauma patients undergoing MT with decreased admission fibrinogen demonstrate increased mortality. Other mortality risk factors include older age, decreased GCS, and higher ISS. Patients with increased fibrinogen levels had lower odds of mortality in a multivariable model. Post-MT survivors demonstrated significantly higher fibrinogen levels than pre-MT patients. Hypofibrinogenemic patients also had worse TEG parameters and required more PRBCs, FFP, and platelets during MT. Further studies are needed to assess the optimal volume of fibrinogen replacement with cryoprecipitate during MT to improve trauma patient mortality. [ABSTRACT FROM AUTHOR]

Aims: The aim was to define the source of contamination of cryoprecipitate intercepted during visual inspection before transfusion. Materials and Methods: A clot was observed in one unit of cryoprecipitate before blood transfusion at the Dongyang People's Hospital. Bacterial cultures were performed using the BacT/ALERT system (BacT/ALERT 3D, bioMerieux, Durham, NC). The isolated bacteria were identified through conventional biochemical identification, matrix‐assisted laser desorption ionization‐time of flight mass spectrometry, and molecular analysis based on 16sr RNA. Samples from all individuals who came into direct contact with the cryoprecipitate were cultured, and the positive samples were then referred for bacterial identification. Results: A leak was found at the edge of a blood bag containing the cryoprecipitate. Cupriavidus paucula was identified both in the cryoprecipitate and water from the water bath. However, there was no growth of C. paucula in the samples obtained from the red blood cell suspension co‐component, puncture site of the blood donor, blood storage refrigerator, transport case, and centrifuge. Conclusion: C. paucula in the water from the water bath contaminated the cryoprecipitate through the invisible slit in the blood bag during thawing. Regular disinfection of water baths, double‐bagging of blood products during thawing, and careful screening of blood products before transfusion should be performed to prevent the transfusion of contaminated cryoprecipitate. [ABSTRACT FROM AUTHOR]

Objective To explore the therapeutic effect of fibrinogen concentrate and cryoprecipitate on severe postpartum hemorrhage in puerpera with placenta accreta under the condition of transfusion of suspended red blood cells and fresh frozen plasma. Methods The clinical data of puerpera with placenta accreta whose blood loss was more than or equal to 50% of the total blood volume within 3 hours in our hospital from January 2009 to June 2021 were retrospectively analyzed. Based on the blood transfusion components, they were divided into fibrinogen concentrate group (group A) and cryoprecipitate group (group B). The coagulation function, blood transfusion units and adverse outcomes of the two groups were analyzed. Results A total of 201 puerpera with severe postpartum hemorrhage due to placenta accreta were included in this study, including 102 cases in group A and 99 cases in group B. The levels of prothrombin time, activated partial thromboplastin time and fibrinogen in group A and group B after blood transfusion were not significantly different from those before delivery (P>0.05). There was no significant difference in blood transfusion volume of suspended red blood cells [(8.18±2.72)U vs (7.90±2.19) U] and fresh frozen plasma [(823.53±258.39)mL vs (804.04±224.94)mL] between group A and group B (P>0.05). There was no significant difference in the incidence of DIC (18.6% vs 21.2%), hysterectomy (26.5% vs 28.3%) and hemorrhagic shock (10.8% vs 13.1%) between group A and group B (P>0.05). Conclusion If puerpera with placenta accreta received both suspended red blood cells and fresh frozen plasma, similar therapeutic effect in severe postpartum hemorrhage was observed between fibrinogen concentrate vs cryoprecipitate. Fibrinogen concentrate has the advantages of rapid preparation, convenient storage and transportation, and can lower the demand for blood products.

Objective To retrospectively analyze the guiding significance and effect of thromboelogram (TEG) in the clinical use of cryoprecipitation. Methods A total of 289 patients with fibrinogen reduction, admitted to our hospital between January 2018 and December 2021, were collected. They was divided into control group (using coagulation examination and clinical feature as the transfusion criteria) and observation group (above parameters plus TEG). The TEG index in the observation group before and after transfusion and Fg, APTT, PT, and TT in 2 groups of patients before and after transfusion were monitored. The efficacy and prognosis of different blood products and cryoprecipitate were compared between 2 groups of patients.) Results The efficacy of choprecipitate transfusion was better in the observation group than the control[Fg index after transfusion (g / L) 1.92±0.92 vs 1.80±1.00, P

Objective To analyze the changes of fibrinogen (Fg) and Ⅷ factor levels of cryoprecipitated coagulation factors prepared by different methods and post-preparation quick-freezing time. Methods The fresh frozen plasma (FFP), prepared from 400mL whole blood, was randomly divided into 6 groups(group A1, A2, A3, B1, B2, B3) with 20 eliquots each, to prepare cryoprecipitate coagulation factors. Group A1, B1 were prepared by automatic cryoprecipitation preparation instrument. group A2, B2 applied the instrument after centrifugation and group A3, B3 were prepared manually. The quick-freezing time after preparation in group A1-A3 and B1-B3 were different(within 1 hour vs. more than 1 hour after preparation). The automated coagulation analyzer was used to measure Fg and Ⅷ factor levels in six groups, and further statistical analysis was carried out. Results The Fg content (mg) of six groups were 245.29±27.44 in group A1, 227.13±18.68 in group A2, 221.11±20.95 in group A3, 182.12±9.15 in group B1, 163.68±15.50 in group B2, and 155.61±19.28 in group B3, respectively. The Ⅷ factor levels(IU) were of six groups were 115.86±27.99 in group A1, 93.79±36.29 in group A2, 91.92±34.75 in group A3, 83.04±18.82 in group B1, 66.33±19.57 in group B2, and 69.34±13.26 in group B3, respectively. There were no significant differences in gender or age between group As and groups Bs. The levels of Fg and Ⅷ factors in group A1 were significantly higher than those in group A2 and group A3 (P

Abstract Background Fibrinogen is the first coagulation protein to reach critical levels during traumatic haemorrhage. This laboratory study compares paired plasma samples pre- and post-fibrinogen replacement from the Fibrinogen Early In Severe Trauma studY (FEISTY; NCT02745041). FEISTY is the first randomised controlled trial to compare the time to administration of cryoprecipitate (cryo) and fibrinogen concentrate (Fg-C; Riastap) in trauma patients. This study will determine differences in clot strength and fibrinolytic stability within individuals and between treatment arms. Methods Clot lysis, plasmin generation, atomic force microscopy and confocal microscopy were utilised to investigate clot strength and structure in FEISTY patient plasma. Results Fibrinogen concentration was significantly increased post-transfusion in both groups. The rate of plasmin generation was reduced 1.5-fold post-transfusion of cryo but remained unchanged with Fg-C transfusion. Plasminogen activator inhibitor 1 activity and antigen levels and Factor XIII antigen were increased post-treatment with cryo, but not Fg-C. Confocal microscopy analysis of fibrin clots revealed that cryo transfusion restored fibrin structure similar to those observed in control clots. In contrast, clots remained porous with stunted fibres after infusion with Fg-C. Cryo but not Fg-C treatment increased individual fibre toughness and stiffness. Conclusions In summary, our data indicate that cryo transfusion restores key fibrinolytic regulators and limits plasmin generation to form stronger clots in an ex vivo laboratory study. This is the first study to investigate differences in clot stability and structure between cryo and Fg-C and demonstrates that the additional factors in cryo allow formation of a stronger and more stable clot.

Objective To understand the current situation of blood components distribution in domestic prefecture-level blood stations through analyzing the components distribution data of 24 prefecture-level blood stations in China. Methods The data of components distribution of 24 blood stations from 2017 to 2020 as well as the data of blood deployment of 24 blood stations from 2019 to 2020 were collected and analyzed. Results From 2017 to 2020, positive annual growth in red blood cells, plasma and cryoprecipitate was observed in 22, 19 and 15 out of the 24 blood stations, and the annual growth median rate of above three components was 5.24%, 3.80% and 3.25%, respectively. Among the 24 prefecture-level blood stations, 23 carried out the preparation of cryoprecipitate. Conclusion The distribution of red blood cells, cryoprecipitate and plasma in prefecture-level blood stations is increasing year by year. However, there is a overstock of plasma, and most blood stations need blood employment.

Background: Plasma factor XIII is a proenzyme that gets activated in the final step of the coagulation cascade. Its physiological role is to stabilize clot formation by catalyzing the cross-linkage of fibrin. Factor XIII deficiency is a rare autosomal recessive disorder. Clinical Description: A 10-year-old boy presented with acute-onset swelling of the arm following a minor fall. There were no constitutional symptoms. There was a significant history of similar swellings 2 years earlier that had required surgery. The past and family history were otherwise noncontributory. The child was hemodynamically stable. Local signs suggested a hematoma or tumor. There was no pallor, icterus, petechiae, or ecchymosis. The remaining examination was normal. Provisional diagnoses included nonaccidental trauma or an underlying primary or secondary bleeding diatheses, tumor, or chronic osteomyelitis. Management: Soft-tissue ultrasonography showed a hematoma. The radiograph was normal. Hemograms, first-line tests for coagulopathy, infective biomarkers, and liver and kidney function tests were normal. There were no stigmata of neglect or physical/emotional abuse in the child. Since the clinical phenotype was of a bleeding disorder, but supportive investigations were inconclusive, we suspected factor XII deficiency. Specific levels showed zero activity. Fresh frozen plasma was administered due to the nonavailability of factor XIII. The hematoma was managed surgically. The child was discharged after genetic counseling and is receiving monthly cryoprecipitate. He is asymptomatic till now. Conclusion: Factor XIII deficiency should be suspected when there are clinical indicators of a bleeding diathesis, but supportive tests are not deranged.

Background: Hypofibrinogenemia is an important risk factor for poor outcomes in children with severe bleeding. There is a paucity of data on the impact of cryoprecipitate transfusion on outcomes in pediatric patients with life‐threatening hemorrhage (LTH). Study Design and Methods: This secondary analysis of a multicenter prospective observational study of children with LTH investigated subjects who were categorized by receipt of cryoprecipitate during their resuscitation and according to the etiology of their bleeding: trauma, operative, and medical. Bivariate analysis was performed to identify variables associated with 6‐h, 24‐h, and 28‐day mortality. Cox Hazard regression models were generated to adjust for potential confounders. Results: Cryoprecipitate was transfused to 33.9% (152/449) of children during LTH. The median (Interquartile range) time to cryoprecipitate administration was 108 (47–212) minutes. Children in the cryoprecipitate group were younger, more often female, with higher BMI and pre‐LTH PRISM score and lower platelet counts. After adjusting for PRISM score, bleeding etiology, age, sex, RBC volume, platelet volume, antifibrinolytic use and cardiac arrest, cryoprecipitate administration was independently associated with lower 6‐h mortality, Hazard Ratio (95% CI), 0.41 (0.19–0.89), (p = 0.02) and 24‐h mortality, Hazard Ratio (95% CI), 0.46 (0.24–0.89), (p = 0.02). Conclusion: Cryoprecipitate transfusion to children with LTH was associated with reduced early mortality. A prospective randomized trial is needed to determine if cryoprecipitate can improve outcomes in children with LTH. [ABSTRACT FROM AUTHOR]

Objectives: To describe the protocol for a multinational randomised, parallel, superiority trial, in which patients were randomised to receive early high‐dose cryoprecipitate in addition to standard major haemorrhage protocol (MHP), or Standard MHP alone. Background: Blood transfusion support for trauma‐related major bleeding includes red cells, plasma and platelets. The role of concentrated sources of fibrinogen is less clear and has not been evaluated in large clinical trials. Fibrinogen is a key pro‐coagulant factor that is essential for stable clot formation. A pilot trial had demonstrated that it was feasible to deliver cryoprecipitate as a source of fibrinogen within 90 min of admission. Methods: Randomisation was via opaque sealed envelopes held securely in participating Emergency Departments or transfusion laboratories. Early cryoprecipitate, provided as 3 pools (equivalent to 15 single units of cryoprecipitate or 6 g fibrinogen supplementation), was transfused as rapidly as possible, and started within 90 min of admission. Participants in both arms received standard treatment defined in the receiving hospital MHP. The primary outcome measure was all‐cause mortality at 28 days. Symptomatic thrombotic events including venous thromboembolism and arterial thrombotic events (myocardial infarction, stroke) were collected from randomisation up to day 28 or discharge from hospital. EQ5D‐5Land Glasgow Outcome Score were completed at discharge and 6 months. All analyses will be performed on an intention to treat basis, with per protocol sensitivity analysis. Results: The trial opened for recruitment in June 2017 and the final patient completed follow‐up in May 2022. Discussion: This trial will provide firmer evidence to evaluate the effectiveness and cost‐effectiveness of early high‐dose cryoprecipitate alongside the standard MHP in major traumatic haemorrhage. [ABSTRACT FROM AUTHOR]

The association of cryoprecipitate transfusion with patient outcomes after cardiac surgery is unclear. We aimed to investigate the predictors of, and outcomes associated with, postoperative cryoprecipitate transfusion in cardiac surgery patients. We used the Medical Information Mart for Intensive Care III and IV databases. We included adults undergoing cardiac surgery, and propensity score matched cryoprecipitate-treated patients to controls. Using the matched cohort, we investigated the association of cryoprecipitate use with clinical outcomes. The primary outcome was in-hospital mortality. Secondary outcomes were infection, acute kidney injury, intensive care unit length of stay, hospital length of stay, and chest tube output at 2-hour intervals. Of 12,043 eligible patients, 283 (2.35%) patients received cryoprecipitate. The median dose was 5.83 units (IQR 4.17–7.24) given at a median first transfusion time of 1.75 hours (IQR 0.73–4.46) after intensive care unit admission. After propensity scoring, we matched 195 cryoprecipitate recipients to 743 controls. Postoperative cryoprecipitate transfusion was not significantly associated with in-hospital mortality (odds ratio [OR] 1.10; 99% confidence interval [CI] 0.43–2.84; p=0.791), infection (OR 0.77; 99% CI 0.45–1.34; p=0.220), acute kidney injury (OR 1.03; 99% CI 0.65–1.62; p=0.876) or cumulative chest tube output (adjusted mean difference 8 hrs post transfusion, 11 mL; 99% CI -104 to 125; p=0.804). Although cryoprecipitate was typically given to sicker patients with more bleeding, its administration was not associated with worse outcomes. Large, multicentred studies are warranted to further elucidate cryoprecipitate's safety profile and patterns of use in cardiac surgery. [ABSTRACT FROM AUTHOR]

A ground-based spectroscopic method for determining the trichlorofluoromethane (CCl3F) content from measurements of IR spectra of solar radiation using an IFS-125HR Fourier spectrometer (FTIR method) is considered. A detector based on mercury–cadmium–tellurium (HgCdTe), which is used for measurements in the CCl3F absorption spectral region, was cooled by liquid N2. An amorphous ice film grew on the detector crystal as the vacuum in the metal Dewar flask gradually deteriorated during cooling. The spectral absorption band of amorphous ice at liquid N2 temperature overlapped the CCl3F absorption band. The variability of the ice film thickness added additional uncertainty to the estimates of the CCl3F atmospheric content. A technique has been developed to estimate the thickness of the ice film, to account for its spectral absorption in the algorithm for solving the inverse problem, and to eliminate this uncertainty. The technique was applied to measuring the atmospheric concentration of CCl3F in 2017–2019 over the NDACC St. Petersburg station. The results were compared with those obtained earlier using a technique in which the thickness of the ice film was treated as an unknown parameter adjusted during solution of the inverse problem. Previously obtained CCl3F atmospheric contents were refined using the proposed technique. The difference reached 10%. [ABSTRACT FROM AUTHOR]

Introduction: Fibrin glue is widely used in spine surgery. Nevertheless, no report has demonstrated the feasibility of completely autologous fibrin glue (CAFG) in spine surgery. This study aims to investigate the safety, efficacy, and effect of bone fusion of CAFG on spine surgery. Methods: We retrospectively extracted data of patients who underwent primary spine surgery with preoperatively prepared CAFG. Primary outcomes were the incidence of wound-related unplanned reoperations within 90 days following primary surgery and the occurrence of reoperation for the management of cerebrospinal fluid (CSF) leakage in patients who had been treated with CAFG used as dural sealants. The effect of CAFG on bone fusion was also assessed by detecting implant failure at one year postoperatively in patients aged 25 years or less undergoing primary fusion for idiopathic scoliosis. Results: We identified 131 eligible patients (47 males and 84 females) with a mean age of 32.3 years. CAFG was used most frequently as an adhesive for fixation of graft bone (110 patients), followed by as a dural sealant for CSF leakage in 17 patients, and as a local hemostatic agent in four patients. Wound-related reoperations were identified in four patients (3.1%), which included three for surgical site infection, and one for postoperative epidural hematoma. There was no reoperation required for the management of CSF leakage among 17 patients with dural incision or incidental durotomy. Compared with the control cohort, the use of CAFG was not associated with early wound-related reoperations or implant failure in patients with spinal deformity. Conclusions: We demonstrated the clinical feasibility of CAFG in spine surgery. The use of CAFG was not associated with the incidence of reoperations for wound-related complications. CAFG worked effectively as a dural sealant for preventing CSF leakage. CAFG had no beneficial or adverse effect on spinal bone fusion.

Abstract Background Cryoprecipitate, which contains fibrinogen and factor VIII in large quantities, is concentrated from fresh frozen plasma, and it has hemostatic effects in severe bleeding. We retrospectively examined the effects of cryoprecipitate on the increase in fibrinogen levels in patients with excessive intraoperative blood loss. Methods Ninety-seven patients who were administered cryoprecipitate during surgery between June 2014 and May 2019 were enrolled in our study and categorized according to the volume of intraoperative blood loss as follows: group A, 2000–5000 mL; group B, 5000–10,000 mL; group C, > 10,000 mL. Data were extracted from electronic medical records and electronic anesthesia records. The primary endpoint was an increase in the fibrinogen level after the administration of cryoprecipitate. Results Nine patients with no fibrinogen data and four patients with a bleeding volume of less than 2000 mL were excluded; thus, 84 patients (A: n = 36, B: n = 37, C: n = 11) were evaluated. The mean intraoperative blood loss (mL) in groups A, B, and C were 3348 ± 791, 6688 ± 1225, and 14,281 ± 5142, respectively. The fibrinogen levels (mg/dL) before cryoprecipitate administration in groups A, B, and C were 189 ± 94, 113 ± 42, and 83 ± 29, respectively (p < 0.05 among the groups). The increase in fibrinogen level (mg/dL) after cryoprecipitate administration in group C was significantly greater than that in group A (84 ± 34 versus 50 ± 36, p < 0.01). Conclusions The results of this study indicate that the effect of cryoprecipitate on the increase in fibrinogen level was most apparent in patients with excessive intraoperative blood loss ≥ 10,000 mL. In addition, most patients with intraoperative blood loss ≥ 5000 mL had fibrinogen levels < 150 mg/dL which improved to ≥ 150 mg/dL after cryoprecipitate administration in approximately 70% of patients. Therefore, cryoprecipitate administration should be considered for patients with hypofibrinogenemia (≤ 150 mg/dL) experiencing severe bleeding (e.g., ≥ 5000 mL) and rapid administration of cryoprecipitate is necessary to maximize the hemostatic effect, especially when the bleeding volume exceeds 10,000 ml.

Objective: To assess the use of amniopatch – intraamniotic application of maternal platelets and cryoprecipitate, in patients after spontaneous previable rupture of membranes (sPPPROM) in terms of its effect on the course and outcome of pregnancy in the largest cohort so far. Since the amniopatch is currently used only to treat patients with iatrogenic preterm rupture of membranes, aim of this study was to find out, if amniopatch could be also used in case of sPPPROM as a safe alternative to currently used expectant management and to compare the results with published data on expectant management. Methods: The study included 53 patients with single-fetal pregnancy after sPPPROM who underwent amniopatch as an experimental method in the years 2008–2019. Authors evaluated individual characteristics for the whole group as well as a subgroup of live-born neonates who survived to discharge and abortions/live-born infants who did not survive to discharge. Results: The mean time of sPPPROM was 19 + 3 gestational week (gw) and of amniopatch performance 22 + 0 gw. Across the group, the miscarriage rate was 33.96%, survival rate 66.03%, mortality rate after delivery 8.57%, survival rate to discharge 60.37%. The mean time of latency period was 5 + 3 gw in the total group, 7 + 1 gw in the group of live births who survived to discharge. We did not find any maternal/fetal complications related directly to amniopatch procedure. Conclusion: Amniopatch is a safe treatment alternative in patients with sPPPROM who require an active approach. It is associated with high percentage of a success rate in terms of duration of pregnancy and neonatal survival. In order to elucidate the possible mechanism of amniopatch effect in sPPPROM despite failure of complete sealing of membrane defect, authors give novel hypothesis of antimicrobial effect of amniopatch based on literature data. [ABSTRACT FROM AUTHOR]