The use of prothrombin complex concentrate in chronic liver disease: A review of the literature.

Patients with chronic liver disease (CLD) and cirrhosis present a rebalanced hemostatic system in the three phases of haemostasis. This balance is however unstable and can easily tip towards bleeding or thrombosis. Management of both spontaneous bleeding and bleeding during invasive procedures remains a challenge in this patient population. Transfusion of blood products can result in circulatory overload and thereby worsen portal hypertension. As an alternative to fresh frozen plasma (FFP), prothrombin complex concentrates (PCC) may have merit in patients with liver disease because of their low volume. The impact of PCC in in-vitro spiking experiments of cirrhotic plasma is promising, but also warrants cautious use in light of thromboembolic risk. The majority of existing studies carried-out in CLD patients are retrospective or do not have an adequate control arm. A prospective study (the PROTON trial) was set up in 2013 to investigate the utility of PCC in patients undergoing liver transplantation. However, the study has never recruited the planned number of patients. Robust data on PCC safety in CLD is also required. The limited existing evidence does not seem to indicate an excessive thromboembolic risk. Currently, the utilisation of PCC in CLD cannot be routinely recommended but can provide an option for carefully selected cases in which other measures were not sufficient to control bleeding and after delicately weighing risks and benefits.

Prevalence and specificity of red blood cell antibodies in patients transfused in tertiary hospitals in Burkina Faso.

BACKGROUND: Sub-Saharan African countries face the challenge of immunological transfusion safety that puts many patients at risk of post-transfusion hemolytic reactions. This is because pre-transfusion testing for irregular/unexpected antibodies that helps to prevent these risks are neither universally available nor accessible. The aim of our study was to determine the prevalence of red blood cell alloantibodies and their specificity in patients transfused in Burkina Faso. MATERIALS AND METHODS: This was a cross-sectional study including patients who had received at least one blood transfusion. Indirect antiglobulin testing using LISS-enhanced medium gel column agglutination technique was used for antibodies screening and identification. Enzymatic technique with papain-treated red cell reagent was performed in attempt to solve some difficulties if necessary as well as auto-control test and RH-KEL phenotyping when possible to help antibodies identification. RESULTS: A total of 832 patients were included, 51.6% of whom were female, and the median (IQR) age was 34 (20-49) years. Of these, 43.7% had chronic kidney disease and 20.4% were sickle cell patients. The median (IQR) number of immunisation episodes (blood transfusion and pregnancies) was 3 (2-6) with the median (IQR) number of blood units received per patient of 2 (1-5). The proportion of patients with RBCs antibodies was 6.4% (53/832), with mainly anti-Rh antibodies. A combination of 2 antibodies was found in 7 patients and a combination of 3 antibodies in one patient. Antibodies of unknown specificity (AUS) were encountered in 29%. Independent factors associated with antibody positivity were age (OR = 1.02; p = 0.026), sickle cell disease (OR = 3.23; p = 0.017) and receiving more than 10 blood units (OR = 7.33; p = 0.01). CONCLUSION: In this study, the proportion of patients with RBC antibodies was quite similar to that observed in Sub-Saharan African countries. However, the availability and accessibility of pre-transfusion compatibility tests as well as the quality of methods used should be improved to ensure the safety of blood transfusions.

Improvement of transfusion practice and reduction in red blood cell utilization in Belgian hospitals: Results of a national survey and benchmarking.

BACKGROUND AND OBJECTIVES: Belgian health authorities launched a national platform in 2011 to improve the quality of transfusion practices and blood use in Belgian hospitals. No data were available about the quality of hospital transfusion practice at the national level. MATERIALS AND METHODS: Three consecutive national surveys (2012, 2014 and 2016) were performed in all 111 Belgian hospitals to assess the degree of implementation of standards in four process domains related to red blood cell (RBC) transfusion: general quality aspects, ordering of RBC, electronic traceability and reporting of adverse events. The surveys were part of a methodology based on informing, feedback and benchmarking. Responses to questions were analysed semi-quantitatively, and hospitals could score 10 points on each of the domains. RESULTS: The proportion of hospitals scoring below 5 per domain decreased from 16%, 70%, 14% and 11% (2012) to 2%, 17%, 1% and 1% (2016), respectively. Similarly, scores above 7.5 increased from 25%, 1%, 23% and 36% (2012) to 64%, 30%, 68% and 81% (2016), respectively. In 2016, overall quality of transfusion practices, including the four pre-specified domains, improved continuously with an average total score (max = 40) increasing from 24.2 to 30.5 (p = 0.0005). In addition, there was a decrease in the number of distributed and transfused RBC per 1000 population between 2011 and 2019 from 47.0 to 36.5 and 43.5 to 36.1, respectively. CONCLUSION: These data show that the applied methodology was a powerful tool to improve quality of transfusion practices and to optimize utilization of RBC at the national level.

Minimal tactical impact and maximal donor safety after a buddy transfusion: A study on elite soldier performances in both laboratory and field environments.

BACKGROUND: The major causes of death of combat casualties in austere environments are related to hemorrhage and occur early after injury. The implementation of a walking blood bank may overcome the logistical issues raised using blood component therapy. Nonetheless, it is important to ensure that this buddy transfusion is not going to compromise the mission success by altering the donor's performance. The results available so far cannot rule out this issue with certainty. Therefore, this study aimed at investigating the immediate effect of a 450-ml blood donation on the performances of elite soldiers in laboratory and field environments. STUDY DESIGN AND METHODS: This double-blind, randomized controlled study included two experiments. For both experiments, subjects were randomly assigned either to a control group (n1  = n2  = 7) or to a 450-ml-blood-bag donation group (n1  = 7 and n2  = 8). All participants underwent before and after a potential blood donation a multifactorial assessment including adapted physical tasks, hematological variables, vigilance parameters, and subjective assessments. RESULTS: No significant results were evidenced in this study. There was no impact of blood donation on the participants' performances in both the hospital and the combat-like environments. CONCLUSION: From a donor's point of view, a 450-ml blood donation has no impact on the required abilities of our elite soldiers to fulfill a demanding tactical mission. Thus, the results of this study support the fact that buddy transfusions could be part of the operational clinical armamentarium in austere environments for elite soldiers when no blood components are available.

Seroprevalence and factors associated with IgG anti-DENV positivity in blood donors in Burkina Faso during the 2016 dengue outbreak and implications for blood supply.

OBJECTIVES: Our study aimed to update the seroprevalence and factors associated with anti-dengue virus (DENV) antibody positivity among blood donors and to discuss their implications for blood supply. BACKGROUND: Questions on the potential transmission of DENV by transfusion increased after the documentation of the risk of transmission of the West Nile virus. This risk was estimated after transfusion of DENV RNA-positive blood units of up to 37.5%. In Burkina Faso, very few studies on DENV in blood donors have been conducted. As a result, there were no reliable data on DENV to allow the implementation of appropriate measures to control the risk of transmission of the dengue virus by blood transfusion. METHODS: We conducted a 4-week cross-sectional study from December 4 to 30, 2016. Blood donors of both genders, aged 18-60 years, accepted for blood donation after medical selection were consecutively enrolled. RESULTS: Our study included a total of 1007 blood donors, in which donors living in urban areas represented 78.2%. The mean age was 26.1 ± 8.1 years. After adjustment in a multiple regression logistic model, the odds of having IgG anti-DENV increased as age increased. The odds of DENV was 53% lower in rural areas (OR = 0.47; P = .000) compared to urban settings and 42% lower in mobile sites (OR = 0.58; P = .03) compared to fixed ones. CONCLUSION: Our study provides new and useful insights for future research on the risk of TT-DENV throughout blood transfusion.

Distribution of ABO and RHD blood group antigens in blood donors in Burkina Faso.

Geographical distribution of ABO and RHD antigens is important for blood transfusion services and population genetics studies. There are few data on this topic in Burkina Faso, a multi-ethnic country. Our study aims at reporting phenotypic and allelic frequencies of ABO and RHD blood groups among voluntary blood donors from various ethnical regions of Burkina Faso. We conducted a cross-sectional study including 81,486 blood donors. ABO allelic frequencies were determined using the Bernstein method. Differences in phenotypic distribution of blood groups were assessed using the chi-square test; a p value <0.05 being considered as statistically significant. We noticed that O+>B+>A+>AB+>O->B->A->AB- in our population. Phenotypic frequencies of blood groups A, B, O and AB were respectively 22.54%, 28.56%, 43.30% and 5.60%. RHD+was 92.24%. The allelic frequencies of A, B, O and D were respectively 0.1524; 0.1887; 0.6590 and 0.7214. We noticed statistical differences (p < 0.05) between these administrative regions which corresponded roughly to some natural ethnic areas. Indeed, the phenotype O was more frequent in the Central-west, Central and East regions corresponding to "Mossi," "Gourounsi," "Gourmantché" areas while the phenotype A and AB were more reported in "Boucle du mouhoun" and "Hauts-Bassins" regions where we have "Bwaba" and "Bobo." The phenotype O negative was less frequent in "Bwaba." Our study provides interesting information to blood services that will allow them to better refine their donor recruitment strategies.

Efficiency of autologous stem cell collection: Comparison of three different cell separators.

Peripheral blood progenitor cells (PBPC) infusion allows rapid haematological recovery after high dose chemotherapy. Efficient PBPC collection is therefore essential as rescue therapy for transplantation. In order to validate a new equipment (ComTec®, Fresenius Kabi), we compared the efficiency of three cell separators for PBPC collection in patients with haematological malignant diseases. From June 2014 to December 2015, 83 PBPC were collected in 48 patients. Three aphaeresis machines were used: Cobe Spectra® (Terumo BCT, 11), Amicus® (Fenwall, 30), and ComTec® (Fresenius Kabi, 42). The median collection efficiency was similar between the three separators. The evaluation of cell contamination in the final product revealed a lower red cell contamination with Spectra® and ComTec®, whereas the platelet contamination was lower with Amicus®. The new equipment has been validated and can be further used in routine, with a total running cost that turned out to be quite lower. Each separator has its own characteristics and advantages. Further study is needed to suggest that the choice of separator could be guided following the patient's blood characteristics.

A systematic review of indications when and how a military walking blood bank could bridge blood product unavailability.

BACKGROUND: Blood supply problems in remote areas are well known. To overcome this shortage, many countries have developed innovative walking blood bank (WBB) protocols. However, no common standards have yet been set for their use and common actions. Given that these procedures involve a certain risk, it would be interesting to analyse the activating criteria that lead to using this unusual protocol. Thus, this review aimed to identify indications for a WBB and the common risk mitigation measures. MATERIAL AND METHODS: This PRISMA-compliant review only included studies published from 1985 to 25th of January 2023 that describe adult male military casualties requiring blood transfused locally using a walking blood transfusion protocol. All relevant data (i.e., activation and contextual factors and risk mitigation measures) were tabulated to retrieve information from the selected military studies. RESULTS: Our results indicated that activation criteria were homogeneous across the 12 reviewed studies. Whole blood was collected from a WBB when there was a shortage of blood products and when platelets were needed. In the literature reviewed, the main risks associated with such a protocol, namely hemolytic adverse events and transfusion transmitted diseases, are mitigated by the use of typing and screening measures if they are reported. However, there is less consistency in the implementation of those risk mitigation measures. DISCUSSION: This unusual protocol needs to be integrated into the medical support plan until conventional transfusion support can take over, and should include on-site blood collection from a donor, whether a WBB or an emergency donor panel. The benefits of such a protocol outweigh the risks in a life-threatening situation, especially since these risks can be anticipated and minimised by planning to pre-screen all potential donors before their deployment. Finally, educating and training the staff who must implement this unusual procedure can also improve the safety and survival rate of future patients.

Optimizing O red blood cell concentrate usage in the emergency department in the era of patient blood management.

BACKGROUND: Emergency transfusion may require the availability of O-negative red blood cell concentrates without pre-transfusion testing. At the Cliniques Universitaires Saint-Luc, the emergency department was used to having access to two decentralized O-negative red blood cell concentrates. This study aims to analyze the consumption of O-negative red blood cell concentrates in emergency situations both before and after the implementation of a novel strategy aiming at optimizing stocks. This strategy provides a combined allocation of one unit of O-positive red blood cell concentrate and one unit of O-negative red blood cell concentrate decentralized in the emergency department and reserve the transfusion of the negative unit only to under 45-year-old women and under 20-year-old men. MATERIALS AND METHODS: A retrospective study was conducted of the transfusion and medical records of all patients who received immediate transfusions in the emergency department without pre-transfusion testing between 2008 and 2022. RESULTS: A total of 193 patients received O red blood cell concentrates without pre-transfusion testing in emergency situations between 2008 and 2022. During the first 24 h of hospitalization, 354 O-negative units were transfused. Mean ratios of number of O-negative bags between 2008 and 2020 was 1.98 unit/patient. After implementation of the new strategy, the ratio in 2021 was 1.46 unit/patient and drastically decreased in 2022 to 0.79 unit/patient. CONCLUSION: In situations of emergency, allocating O-negative units only for women younger than 45 years and men younger than 20 years could have saved 85% of O-negative red blood cell concentrates transfused (303/354) yet balancing the immunological risk. Limiting the number of delocalized units of O-negative red blood cell concentrates in the emergency department seems to lower O-negative consumption. With this strategy, the units spared could have been transfused to patients with greater needs (e.g., sickle cell patients or chronically transfused patients).

O-negative blood shortage management in a university hospital: Impact of transfusing RhD-positive red blood cells to RhD-negative patients.

BACKGROUND: Shortages of O-negative red blood cells are becoming increasingly common, forcing hospitals' blood transfusion services to find solutions to conserve this blood group for patients who need it most. The present study aimed to retrospectively evaluate the practice of transfusing selected RhD-negative patients with RhD-positive red blood cells and to assess the impact of this measure on patients and blood transfusion service management. METHODOLOGY: Transfusion data of 1199 RhD-negative patients hospitalised at Cliniques Universitaires Saint-Luc between 2019 and 2022 were analysed. For patients who received RhD-positive red blood cells, age, gender, reason for hospital admission, indication for transfusion, and immunohematology analyses were recorded. These data enabled an assessment of transfusion practices over the years, characterisation of patients who received RhD-mismatched transfusions, determination of the alloimmunisation rate, and calculation of the total number of RhD-negative red blood cells saved. RESULTS: During the study period, 141 RhD-negative patients received 604 RhD-positive red blood cells. A change in transfusion practices was observed over the years, with a greater proportion of RhD-negative patients being transfused with RhD-positive red blood cells in 2022 (28%) compared to 2019 (2%). The overall alloimmunisation rate was at least 20%, and 416 red blood cells were saved without any consequences. Patients undergoing cardiovascular surgery received the highest number of RhD-positive red blood cells. CONCLUSION: The transfusion of selected RhD-negative patients with RhD-positive red blood cells is a low-risk practice that helps conserve RhD-negative red blood cells. However, there is a minimum 20% risk of alloimmunisation, which could have clinical and transfusion-related consequences in the future.

Biological investigations of transfusion reactions: Contribution of symptom-based decisional algorithms.

OBJECTIVES: While transfusion is a common and safe therapeutic procedure in health care facilities, transfusion reactions can occur, whether acute or delayed, mild or life-threatening. In face of these reactions, the biological analysis laboratory plays a central role in their diagnosis. The objective of this article is to develop decisional algorithms for laboratory tests to be performed according to the clinical symptoms developed by the patient during or after transfusion. METHODS: Based on the information collected by reviewing the literature and the procedures used in our hospital, we then developed biological investigation algorithms according to the symptoms presented by the patient, rather than the presumed reaction. RESULTS AND CONCLUSION: We have developed symptom-based algorithms for acute transfusion reactions management that streamline laboratory testing and simplify the differential diagnosis.

There is an urgent need to adopt a pull-flow logic for the supply of RBCs to meet patients' needs: A single center study.

BACKGROUND: Despite major demographic changes, several decisions and initiatives, among which Patient Blood Management, have led to a significant reduction in the transfusion of packed red blood cells (RBCs) in Belgium, as it has been observed in many countries. Unfortunately, not all blood groups were proportionately impacted and shortage in O D-negative RBCs is regularly or chronically observed. The goal of this study was to examine how to optimize the use and the supply of O D-negative blood in our academic hospital. METHODOLOGY: All blood transfusions performed at Cliniques universitaires Saint-Luc between January 1, 2019 and December 31, 2021 were reviewed. The blood group of the patients was compared with the blood group of the RBCs actually supplied and transfused. RESULTS: 49.823 RBCs transfusions were analyzed. The patients' needs didn't reflect those of a Caucasian population, with an increase of O (47.9%) and B (10.3%) for the ABO blood group, and a quite high proportion of R0r (8.6%) for the Rh blood group. Only two thirds of O D-negative RBCs were transfused to O rr or R0r patients. CONCLUSION: The application of PBM and the ethnic imbalance between blood donor and patient populations are two important risk factors for chronic shortages of O D-negative blood. To adapt blood component resources, it is essential to have a complete picture of the real needs of patients according to their blood group profile. Blood donor centers must adapt to the evolving needs of hospitals in order to plan future supplies in a "pull-flow" approach.

Traceability of Blood Transfusions and Reporting of Adverse Reactions in Developing Countries: A Six-Year Postpilot Phase Experience in Burkina Faso.

Traceability is an essential tool for haemovigilance and transfusion safety. In Burkina Faso, the implementation of haemovigilance has been achieved as part of a pilot project from 2005 to 2009. Our study aims to evaluate the traceability of blood transfusions and reporting of adverse reactions over the 6-year postpilot phase. A cross-sectional study including all blood units ordered between 2010 and 2015 has been conducted in public and private health care facilities supplied with blood products by the transfusion center of Bobo-Dioulasso. The complete traceability was possible for 83.5% of blood units delivered. Adverse reactions were reported in 107 cases representing 2.1/1,000 blood units per annum. Transfusions of wrong blood to wrong patient were reported in 13 cases. Our study shows that the haemovigilance system in Burkina Faso must be improved. Healthcare workers have to be sensitized on how traceability and haemovigilance could impact the quality of care provided to patients.

Application of a clot-based assay to measure the procoagulant activity of stored allogeneic red blood cell concentrates.

BACKGROUND: Thrombotic effects are possible complications of red blood cell transfusion. The generation and accumulation of procoagulant red blood cell extracellular vesicles during storage may play an important role in these thrombotic effects. The objective of this study was to assess the value of a simple phospholipid-dependent clot-based assay (STA®-Procoag-PPL) to estimate the procoagulant activity of stored red blood cells and changes in this activity during storage of the blood component. MATERIALS AND METHODS: Extracellular vesicles from 12 red blood cell concentrates were isolated at 13 storage time-points and characterised by quantitative and functional methods: the degree of haemolysis (direct spectrophotometry), the quantification and determination of cellular origin (flow cytometry) and the procoagulant activity (thrombin generation and STA®-Procoag-PPL assays) were assessed. RESULTS: The mean clotting time of extracellular vesicles isolated from red blood cell concentrates decreased from 117.2±3.6 sec on the day of collection to 33.8±1.3 sec at the end of the storage period. This illustrates the phospholipid-dependent procoagulant activity of these extracellular vesicles, as confirmed by thrombin generation. Results of the peak of thrombin and the STA®-Procoag-PPL were well correlated (partial r=-0.41. p<0.001). In parallel, an exponential increase of the number of red blood cell-derived extracellular vesicles from 1,779/µL to 218,451/µL was observed. DISCUSSION: The STA®-Procoag-PPL is a potentially useful technique for assessing the procoagulant activity of a red blood cell concentrate.

Seroprevalence of Borrelia burgdorferi, Anaplasma phagocytophilum, and Francisella tularensis Infections in Belgium: Results of Three Population-Based Samples.

To estimate the seroprevalence of Borrelia burgdorferi (Bb), Anaplasma phagocytophilum (Ap), and Francisella tularensis (Ft) in Belgium, we tested sera from three population-based samples in which exposure to pathogen is assumed to vary: 148 samples from workers professionally exposed, 209 samples from rural blood donors, and 193 samples from urban blood donors. Sera were tested using ELISA or the immunofluorescence assay test. The seroprevalence of Bb was 5.4% in workers professionally exposed, 2.9% in rural blood donors, and 2.6% in urban blood donors, which is similar to other studies. The fraction of negative results decreases significantly from urban blood donors and rural blood donors to workers. Regarding the seroprevalence of Ap, the cutoff titer of 1:64 recommended by the manufacturer may be set too low and produces artificially high seroprevalence rates. Using a cutoff titer of 1:128, the seroprevalence of Ap was estimated at 8.1% for workers professionally exposed, 6.2% for rural blood donors, and 5.7% for urban blood donors. Tularemia sera confirmed the presence of the pathogen in Belgium at 2.0% for workers and 0.5% for rural and urban blood donors. Our study is one of the few providing an estimation of the seroprevalences of Bb, Ap, and Ft in three different populations in Belgium, filling the gap in seroprevalence data among those groups. Our findings provide evidence that the entire Belgian population is exposed to Bb, Ap, and Ft infections, but a higher exposure is noticed for professionals at risk. Education on the risk factors for tick bites and preventive measures for both professionals exposed and the general population is needed.

Time course of release of inflammatory markers after coronary stenting: comparison between bare metal stent and sirolimus-eluting stent.

BACKGROUND: High levels of release of inflammatory markers after coronary angioplasty are predictors of late restenosis. Sirolimus-eluting stent reduces the risk of restenosis. AIM OF THE STUDY: To compare the release of inflammatory markers after coronary angioplasty with sirolimus-eluting stent and bare metal stent. METHODS: Sixteen patients with a proximal left anterior descending coronery artery stenosis were randomly assigned to receive either bare metal stent (n = 8) or sirolimus-eluting stent (n = 8). We measured simultaneously aortic and coronary sinus concentrations of the von Willebrand factor antigen, tumor necrosis factor-alpha and interleukin-6 before, immediately and after 2 h after stenting. High-sensitivity C-reactive protein and troponin-I circulating levels were measured before and 6 and 24 h after coronary angioplasty. RESULTS: Before stenting, all values were similar in both groups. The coronary sinus change of the von Willebrand factor antigen level between baseline and 2 h after stenting was + 20.1 +/- 26.9% in the bare metal stent group and -5.7 +/- 23.02% in the sirolimus-eluting stent group (P < 0.05). We observed a significant increase in the von Willebrand factor antigen (from 132.8+/-58.8 to 169 +/- 40.7%, P < 0.05) systemic concentrations 24 h after stenting in the bare metal stent group but not in the sirolimus-eluting stent group (from 140.6+/-84% to 136 +/- 39.5%), P = NS). CONCLUSION: The present study shows that a difference in the release of inflammatory markers can be detected after coronary stenting with bare metal stent or sirolimus-eluting stent. The lower release of the von Willebrand factor antigen in the coronary sinus 2 h after the procedure and the lower systemic concentrations of the von Willebrand factor antigen 24 h after stenting in the sirolimus-eluting stent group are likely to reflect a reduced production of the von Willebrand factor antigen at the site of the vascular injury.

Factor VIII and fibrinogen recovery in plasma after Theraflex methylene blue-treatment: effect of plasma source and treatment time.

BACKGROUND: The quality of fresh-frozen plasma is affected by different factors. Factor VIII is sensitive to blood component storage processes and storage as well as pathogen-reduction technologies. The level of fibrinogen in plasma is not affected by the collection processes but it is affected by preparation and pathogen-reduction technologies. MATERIALS AND METHODS: The quality of plasma from whole blood and apheresis donations harvested at different times and treated with a pathogen-reduction technique, methylene blue/light, was investigated, considering, in particular, fibrinogen and factor VIII levels and recovery. RESULTS: The mean factor VIII level after methylene blue treatment exceeded 0.5 IU/mL in all series. Factor VIII recovery varied between 78% and 89% in different series. The recovery of factor VIII was dependent on plasma source as opposed to treatment time. The interaction between the two factors was statistically significant. Mean levels of fibrinogen after methylene blue/light treatment exceeded 200 mg/dL in all arms. The level of fibrinogen after treatment correlated strongly with the level before treatment. There was a negative correlation between fibrinogen level before treatment and recovery. Pearson's correlation coefficient between factor VIII recovery and fibrinogen recovery was 0.58. DISCUSSION: These results show a difference in recovery of factor VIII and fibrinogen correlated with plasma source. The recovery of both factor VIII and fibrinogen was higher in whole blood plasma than in apheresis plasma. Factor VIII and fibrinogen recovery did not appear to be correlated.