Evidence for indications of fresh frozen plasma

There continues to be a general but unfounded enthusiasm for fresh frozen plasma (FFP) usage across a range of clinical specialties in hospital practice. Clinical use of plasma has grown steadily over the last two decades in many countries. In England and Wales, there has not been a significant reduction in the use of FFP over the last few years, unlike red cells. There is also evidence of variation in usage among countries--use in England and Wales may be proportionately less per patient than current levels of usage in other European countries and the United States. Plasma for transfusion is most often used where there is abnormal coagulation screening tests, either therapeutically in the face of bleeding, or prophylactically in non-bleeding subjects prior to invasive procedures or surgery. Little evidence exists to inform best therapeutic plasma transfusion practice. Most studies have described plasma use in a prophylactic setting, in which laboratory abnormalities of coagulation tests are considered a predictive risk factor for bleeding prior to invasive procedures. The strongest randomised controlled trial (RCT) evidence indicates that prophylactic plasma for transfusion is not effective across a range of different clinical settings and this is supported by data from non-randomised studies in patients with mild to moderate abnormalities in coagulation tests. There are also uncertainties whether plasma consistently improves the laboratory results for patients with mild to moderate abnormalities in coagulation tests. There is a need to undertake new trials evaluating the efficacy and adverse effects of plasma, both in bleeding and non-bleeding patients, to understand whether the "presumed" benefits outweigh the "real risks". In addition, new haemostatic tests should be validated which better define risk of bleeding.     

Clinical effects of different types of red cell concentrates in patients with thalassemia and sickle cell disease

The treatment of thalassemia is still essentially based on continuous transfusion supporting using red cell concentrates (RCC) prepared in different ways. For patients with sickle-cell disorders, either urgent or chronic red blood cell transfusion therapy, is widely used in the management of sickle cell disease (SCD) because it reduces HbS level and generally prevents recurrent vaso-occlusive disease (VOD). Recently, the introduction of pre-storage filtration to remove leukocytes and the use of techniques for multicomponent donation have increased the types of blood components available for transfusion purposes. The clinical effects of different types of blood components in thalassaemic and sickle-cell patients have not been extensively studied so far. We evaluated the impact of the various different blood components currently available on transfusion needs, transfusion intervals and adverse reactions in order to determine which is the most advantageous for transfusion-dependent thalassaemic and sickle-cell patients followed in our centre. We believe that the optimal characteristics of the RCC are aged less than 10 days from time of collection; Hb content greater than 56 g per unit; Hct: 55-60%; volume (including additive) 300 mL+/-20%; leucodepleted to less than 200,000 leukocytes per unit; low cytokine content (achievable by pre-storage filtration carried out between two and 24 hours after the collection); lack of microaggregates (achievable by pre-storage filtration or filtration in the laboratory) and protein content less than 0.5 g per unit for patients allergic to plasma proteins (achievable with manual or automated washing). It is still recommended that the blood transfused should be as fresh as possible, compatible with the centre's product availability and the centre's organisation should be continuously adapted to this aim. We always transfuse blood within 10 days of its collection, respecting Rh and Kell system phenotypes. Pre-storage filtration is strongly recommended, both in order to prevent adverse reactions through the marked leucodepletion (less than 200,000 leukocytes per unit) and for a better standardisation of the final product, including the certainty that the product does not contain clots, an assurance that bed-side filtration cannot give. The RCC should be produced using a method causing as little as possible stress to the red cell membrane. The use of RCC with a high content of Hb (less than 56 g per unit) is strongly recommended, because our study clearly shows that this reduces the number of exposures to donors and the number of accesses to hospital, thus improving the patient's quality of life.     

Consensus and controversies in platelet transfusion: Trigger for indication, and platelet dose

Platelet transfusion is about to commemorate its 50th year since its introduction in therapeutics. It is then surprising to see, that in spite of reaching this respectful age, we have not been able to definitely establish all the aspects related to its clinical use. Some of these facets are platelet transfusion threshold and the platelet dose to administer. Historically, two different transfusion triggers have been used for prophylactic and therapeutic platelet transfusions. For prophylactic platelet transfusion an increasing body of evidences suggests that a transfusion trigger of 10 x 10(9) per liter is appropriate for most clinical settings. In contrast, evidence for supporting a certain therapeutic transfusion trigger is lacking. Nevertheless, there is consensus that the platelet count should not be allowed to fall below 50 x 10(9) per liter in patients with acute bleeding. Another important aspect still pending of clear definition is the issue of the platelet dose to be transfused. It has been addressed by some small studies but a definite answer to this important clinical issue is, at least so far, still pending. The results of two ongoing trials, one sponsored by NIH through the Clinical Trials Network in Transfusion Medicine and Hemostasis and the other promoted by the BEST Collaborative Group are expected to help us to clearly defining the more effective and efficient way to transfuse platelet concentrates.     

Apheresis versus whole-blood-derived platelets: pros and cons

Platelet concentrates for prophylactic or therapeutic treatment of patients can be isolated from whole blood using the platelet-rich plasma-method or the buffy coat-method on one hand, or can be collected by apheresis with return of unwanted blood cells to the donor on the other hand. A number of variables among the methods, including the anticoagulant, centrifugation and processing after collection, and pre- or post storage pooling, affect storage characteristics of platelets. Data suggest, however, that most differences balance out, both based on in vitro studies, and on recovery and survival studies. A marginal difference in corrected count increment in favor of apheresis platelets was observed, but the practical consequence is likely to be small. The need for pooling of whole-blood-derived platelet concentrates increases donor exposure, and thereby potentially increases the risks associated with transfusion of whole-blood-derived platelet concentrates. Indeed, risk of viral and variant Creutzfeldt-Jakob disease transmission is at least two-fold higher for whole-blood-derived platelet concentrates, but allo immunization rates, acute reaction rates, and transfusion related acute lung injury rates are not different. Apheresis donation procedures have fewer adverse events. The various benefits and disadvantages of the methods have to be balanced when choosing a preferred way of platelet collection.     

Contamination bactérienne de concentrés de plaquettes à Propionibacterium acnes

In this study, three incidents of platelet contamination by s and an investigation of and an investigation of the transfusion process have been reported, which occurred at the Nord-Pas-de-Calais Blood Center over a period of several months. s is a ba is a bacterium that is present in the cutaneous flora; it does not produce any toxin, and is rarely considered as a pathogenic agent; its occurrence is widespread, in particular in those regions that are rich in sebum (face, back, scalp), and it is extremely apparent during adolescence. The three incidents occurred following the transfusion of a pool of leucodepleted platelet concentrates obtained from immunodeficient patients. The clinical outcome was in all cases positive. It was considered that the bacterial contamination of platelet concentrates could reflect insufficient skin disinfection at the site of the venipuncture and a minimal bacterial risk involving the blood collection procedure.     

CD40 ligand (CD154) involvement in platelet transfusion reactions

Platelet transfusions are commonly used treatments that occasionally lead to adverse reactions. Clinical trials, in vitro and animal studies have been performed to try to understand the causes of such reactions. Multiple studies have shown that the supernatant fraction of platelet concentrates contain prothrombotic and pro-inflammatory mediators. The origin of these mediators was first ascribed to white blood cells contaminating the platelet preparation. However, the accumulation of bioactive mediators after leukoreduction focused attention on platelets themselves during storage. Numerous cytokines, chemokines and prostaglandins are released in stored platelet concentrates. We have focused on a powerful mediator called soluble CD40 ligand (sCD40L, formally known as CD154) as a seminal contributor to adverse reactions. sCD40L can bind and signal the surface receptor, CD40, which is present on various types of human cells including white blood cells, vascular cells and fibroblasts. Downstream results of sCD40L/CD40 signaling include pro-inflammatory cytokine and chemokine production, prothrombotic mediator release, adherence and transmigration of leukocytes to endothelium and other undesirable vascular inflammatory events. Increased plasma levels of sCD40L can be detected in conditions such as myocardial infarction, stroke, unstable angina, high cholesterol, or other cardiovascular conditions. In retrospective studies, correlations were made between increased sCD40L levels of platelet concentrates and adverse transfusion reactions. We hypothesize that transfusion of partially activated, CD40L-expressing platelets along with sCD40L into a recipient with damaged or dysfunctional vascular tissue results in a “double-hit”, thus inciting inflammation and vascular damage in the recipient.     

L’introduction de solutions de conservation dans les concentrés plaquettaires : vers une diminution des réactions transfusionnelles

Platelet concentrates (PC) are used in thrombocytopenia for curative or preventive treatment for hemorrhagic risk. Since five years, additive solutions have been added in PCs for several reasons; one of them is to present an interest in the intolerance in plasma reactions. The literature data have shown that these solutions entail fewer allergic reactions than PCs kept in plasma. This study was reviewed on three years of transfusion in France. The main objective of this study was to see if there was a difference in frequency when these PCs were in solution or not. All adverse reactions in recipients (ARR) occurring among PCs recipients (with and without additive solution) were analysed. The categories of ARR specifically studied were: allergies, febril non haemolytic reactions (FNHR) and the category “unknown”. This study shows that there is significantly lower incidence of allergies by introducing solution. For all ARRs, there is also a decrease in their frequency when PCs are in additive solution, it is significant except for the apheresis platelet concentrates. For categories FNHR and “unknown”, the results are opposed and/or not significant. This study confirms that introduction of additive solutions in PCs is able to reduce some allergic transfusion reactions.     

Platelet additive solutions: A future perspective

Platelet additive solutions (PASs) were first developed in the 1980s, and continued to be improved over the following years. The use of PASs as replacement for plasma has a number of benefits, both for the quality of the platelet concentrates and for the patients. However, some PASs have been associated with a lower platelet yield in the PCs, a shorter storage time, and a lower increment in the patient when compared to PCs in plasma. A number of reformulations of the PASs have taken place to counteract these disadvantages. Most PASs use acetate as nutrient for the platelets, which has the benefit of generating bicarbonate when oxidized by the platelets, thus supplying its own buffering capacity. Alternatively, glucose is used, but may cause deterioration of pH in the stored PCs due to the formation of lactic acid. Addition of other buffering substances, such as phosphate, can be added to ensure maintenance of neutral pH. An important finding was the inhibiting effect of potassium and magnesium on platelet activation. The initially developed PASs lacked these two ingredients and showed reduced storage times of the PCs in PAS when compared to those stored in plasma. However, when these constituents are included in the PAS, storage time is similar and even exceeds those seen for PCs in plasma. Considerable research is done in further formulating the optimal PAS. Bicarbonate is being considered as buffer for these PASs. Also, L-carnitine appears to have a favorable effect on stored platelets, including a reduction of platelet metabolism, and inhibition of apoptosis. Another area of optimization is lowering of plasma content needed for maintaining platelet quality. Where current PASs still need at least 30% residual plasma, there is a trend towards lowering the plasma content to less than 5% with the newer PASs. Preservation of purinergic platelet receptor functionality by ADP-degrading activities in plasma appears to play an important role in this respect. Development of PASs are usually based on in vitro studies alone. It is important to realize that only clinical studies can give definitive answers about the quality of platelets stored in PASs. Sofar, only limited clinical evaluations have been published that either studied the effectiveness of platelets in initially-developed PASs, or were specifically done in combination with pathogen reduction technologies. Thus, PASs seem to be an excellent replacement for (part of) the plasma when producing PCs, and allow extended storage with maintenance of quality, but more clinical studies are needed to substantiate in vitro results.     

In vitro and in vivo evaluation of platelet transfusions administered through an electromechanical infusion pump

The authors evaluated two platelet infusion pump systems, the Abbott Lifecare 5000 and the Omniflow 4000, for evidence of in vitro platelet damage and in vivo platelet recovery. When compared with gravity infusion, there was no significant difference in levels of LDH discharge, beta-thromboglobulin release, cell counts, or morphology score after platelet concentrates were infused through these pumps. When the pumps were compared to gravity infusion in thrombocytopenic oncology patients, no differences were noted in platelet-corrected count increments at 1-4 hours or 12-24 hours post-transfusion. The authors conclude that these infusion systems do not significantly injure or activate platelets and that they are efficacious for transfusing platelet concentrates to thrombocytopenic patients. These infusion pumps may be of clinical benefit to pediatric or adult patients with a history of prior transfusion reactions, when precise control of the rate and volume of platelet transfusion is desired.     

The role and impact of the transfusion medicine consultation service in the management of patients in the hematopoietic transplant service: A retrospective analysis

BackgroundAdverse reactions secondary to transfusion of incorrect blood components can be fatal. We have established numerous processes to prevent these reactions in patients with cancer who continuously need blood component support, especially hematopoietic transplant recipients. The development of an active transfusion medicine consultation service at our institution to serve patients undergoing hematopoietic transplantation has led to more organized and simpler management of providing blood components to such patients.Study design and methodsSafety tools were employed to attain our goal of providing safe blood components to hematopoietic transplant recipients. These tools were consultation request forms, blood component selection stickers on the patients’ charts, and transfusion medicine physician consultation notes posted in the patients’ medical records. One hundred randomly selected hematopoietic transplant recipients were reviewed over 16 months. Fifty patients received blood components from ABO-compatible donors, whereas the other 50 patients received components from ABO-incompatible donors. Deviation reports regarding the issuance of blood components in these patients over the study period were reviewed retrospectively.ResultsWe identified eight reported deviations from the recommended blood components: red blood cells in one case, fresh frozen plasma in one case, single donor platelets in one case, and random donor platelets in five cases. Our transfusion service issued all eight components, but none of them were transfused. In all eight cases, the blood components were intended for transfusion to ABO-mismatched hematopoietic transplant recipients. Nurses identified the incorrect blood components by verifying the recommended blood groups on the patients’ chart stickers, returned the components to the transfusion service, and transfused the correct blood components.ConclusionUse of these safety tools has improved the safety culture regarding transfusion of blood components in hematopoietic transplant recipients at our institution.     

Platelet and TRALI: From blood component to organism

Even though used systematically with leukocyte reduction, platelet transfusions still cause adverse reactions in recipients. They include Transfusion-Related Acute Lung Injury (TRALI), respiratory distress that occurs within six hours of the transfusion. The pathophysiology of this transfusion complication brings complex cellular communication into play. The role, particularly inflammatory, played by blood platelets in TRALI pathophysiology has been demonstrated, but is still under debate. Blood platelets play a role in inflammation, particularly via the CD40/CD40L (sCD40L) immunomodulator complex. In this study, we examine in particular the specific involvement of the CD40/CD40L (sCD40L) complex in the inflammatory pathogenesis of TRALI. This molecular complex could be a major target in a TRALI prevention strategy. Improving the conditions in which the platelet concentrates (PC) are prepared and stored would contribute to controlling partly the risks of non-immune TRALI.     

Cognate MHC-TCR interaction leads to apoptosis of antigen-presenting cells

Antigen presentation to T lymphocytes has been characterized extensively in terms of T lymphocyte activation and eventual cell death. In contrast, little is known about the consequences of antigen presentation for the antigen-presenting cell (APC). We have determined the outcome of major histocompatibility complex class II-restricted peptide presentation to a specific T cell. We demonstrate that specific T lymphocyte interaction with peptide-presenting APCs led to apoptosis in the APC population. In contrast, T lymphocyte interaction with nonpeptide-loaded APCs or APCs loaded with monosubstituted peptide failed to induce T lymphocyte secretion of interleukin-2 and APC apoptosis. Phosphatidylserine externalization and mitochondrial depolarization were used to evaluate APC apoptosis. Fas/Fas ligand interactions were not required, but cytoskeletal integrity and caspase activation were essential for APC apoptosis. Antigen presentation leading to T lymphocyte activation is therefore coordinated with apoptosis in the APC population and could provide a mechanism of immune response regulation by eliminating APCs, which have fulfilled their role as specific ligands for T lymphocyte activation. This pathway may have particular importance for APCs, which are not sensitive to death receptor-induced apoptosis.     

Analyse des fiches d''incidents transfusionnels enregistrées par 15 établissements de transfusion sanguine et établissements de santé pendant 17 mois

The principal result of the development of hemovigilance since 1994 has been the declaration of undesirable effects likely to be due to transfusions of labile blood products. Using the 1694 cases of undesirable effects registered, it seemed worthwhile to us to analyze the distribution of the signs noticed, their frequency and the types of blood products responsible. This analysis allowed us to observe that the majority of reactions were shivery-feverish (47%) or allergic (24%). Most of them are linked to platelet concentrate transfusions especially simple donor platelets (with a frequency of ten reactions for thousand apheresis platelet concentrates transfused).In this study the frequency of undesirable effects reported is 2 per 1000 apheresis platelet concentrate transfusions. Further investigations are necessary to determine the physiological mechanisms of these reactions and to estimate the degree to which transfusions are responsible for their occurrence.     

Use of whole blood as the routine transfusion product in Africa

In many countries in sub‐Saharan Africa (sSA) whole blood is more commonly available from blood transfusion services than red cell concentrates. Although in recent years, many countries have made significant progress in the implementing component preparation, this has largely been facilitated by external funding support. The large majority of rather than none of the sSA countries are leucocyte‐reducing or irradiating blood for transfusion. Systems for the routine detection of adverse consequences of blood transfusions (haemovigilance) only exist where transfusion safety has been identified as a health priority by the government. As a resource, the availability of blood transfusion in these countries is limited since less than 5 units of blood were donated per 1000 population far below the recommended requirement of 20 units/1000 per year. Young children are the main users of blood for transfusion in these sSA regions, largely due severe anaemia secondary to infection and sickle cell anaemia. Outcomes for children with severe anaemia are poor, even in those receiving a transfusion. Although it has been speculated that this may be due to transfusion‐related cardiac or pulmonary events, available data from observational studies and clinical trials indicate that these are rare complications of transfusion. Evidence from clinical physiology studies including those examining myocardial functions before and after the receipt of whole blood provide reassuring evidence that volume overload is rare and clinical trials reporting outcomes in children receiving whole blood transfusion, including a Phase II trial examining higher volumes, indicate that there is no evidence of cardiac or pulmonary overload events.     

Platelet transfusion in adults: An update

Many patients worldwide receive platelet components (PCs) through the transfusion of diverse types of blood components. PC transfusions are essential for the treatment of central thrombocytopenia of diverse causes, and such treatment is beneficial in patients at risk of severe bleeding. PC transfusions account for almost 10% of all the blood components supplied by blood services, but they are associated with about 3.25 times as many severe reactions (attributable to transfusion) than red blood cell transfusions after stringent in-process leukoreduction to less than 10⁶ residual cells per blood component. PCs are not homogeneous, due to the considerable differences between donors. Furthermore, the modes of PC collection and preparation, the safety precautions taken to limit either the most common (allergic-type reactions and febrile non-hemolytic reactions) or the most severe (bacterial contamination, pulmonary lesions) adverse reactions, and storage and conservation methods can all result in so-called PC “storage lesions”. Some storage lesions affect PC quality, with implications for patient outcome. Good transfusion practices should result in higher levels of platelet recovery and efficacy, and lower complication rates. These practices include a matching of tissue ABH antigens whenever possible, and of platelet HLA (and, to a lesser extent, HPA) antigens in immunization situations. This review provides an overview of all the available information relating to platelet transfusion, from donor and donation to bedside transfusion, and considers the impact of the measures applied to increase transfusion efficacy while improving safety and preventing transfusion inefficacy and refractoriness. It also considers alternatives to platelet component (PC) transfusion.     

Transfusion Strategies: Opportunities for Improvement

Opportunities for improving transfusion practice that involve patient care, technological advancements, and technology changes in the clinical arena are discussed. Patient care should be enhanced by optimizing transfusion therapy and the source of donors of platelet concentrates, i.e., single donor platelets (obtained by plateletapheresis from a single donor) or to random donor platelets (containing a pool of six to eight platelet concentrates separated from whole blood donations). The availability of third-generation'' leukocyte-reduction filters provides the technology for significantly and consistently providing leukocyte reduced blood components. The potential benefits of using these filters is presented. Platelet crossmatching represents a technology change involving clinical practice. Suggestions for incorporating this test into platelet transfusion algorithms are included.     

Adverse transfusion reactions with neurological signs in transfused patients

ObjectivesMany transfused patients present severe, sometimes critical, clinical conditions. The occurrence of adverse transfusion reactions may cause the clinical condition to deteriorate. A study was conducted aimed at establishing whether the presence of neurological signs during an adverse transfusion reaction increases its severity.MethodsFrom 1 January 2010 to 30 June 2019, adverse reactions with neurological signs were extracted from the French haemovigilance database system. Two signs observed at the time of the reaction were analysed: unconsciousness and convulsions. Stroke was excluded. The type of reaction, its severity, the blood product involved and its imputability were all studied.ResultsDuring the study period, 10,670 reactions were reported, including 20 (0.19%) imputed to the transfusion with unconsciousness and/or convulsions. Unconsciousness without convulsions was frequently observed (14 reports, 70.0%). Convulsions were reported in 5 cases (25.0%), with 1 case being associated with unconsciousness. Unconsciousness and/or convulsions were present in 9 allergic reactions (45.0%) and 4 transfusion-associated circulatory overloads (20.0%). Nine reactions were severe (45.0%), 7 were life-threatening (35.0%) and 1 case resulted in the recipient's death (5.0%). A red blood cell and a platelet concentrate transfusion were involved in 8 reactions (40.0%) each, although the imputability of the blood product was certain in only 2 of the reactions.ConclusionUnconsciousness and/or convulsions were rarely observed in adverse reactions reported in transfused patients. Nevertheless, the presence of these signs highlights the severity of the adverse reactions (17 reactions, 85.0%).     

Use of native or platelet count adjusted platelet rich plasma for platelet aggregation measurements

BACKGROUND: It is still not clear whether native or platelet count adjusted platelet rich plasma (PRP) should be used for platelet aggregation measurements.AIM: To evaluate the necessity of using adjusted PRP in platelet function testing. METHODS: Platelet aggregation with native PRP and adjusted PRP (platelet count: 250/nl, obtained by diluting native PRP with platelet poor plasma) was performed on the Behring Coagulation Timer (BCT(R)) using ADP, collagen, and arachidonic acid as agonists. Healthy subjects, patients on antiplatelet treatment, and patients with thrombocytosis (platelet counts in PRP > 1250/nl) were investigated. RESULTS: No significant differences in the maximum aggregation response were seen when using either native or adjusted PRP from healthy subjects and patients on antiplatelet treatment. Nevertheless, some patients taking aspirin or clopidogrel showed reduced inhibition of ADP and arachidonic acid induced aggregation in adjusted PRP but not in native PRP. The maximum velocity of healthy subjects and patients on antiplatelet treatment varied significantly as a result of the degree of dilution of the adjusted PRP. Surprisingly, the BCT provided good results when measuring platelet aggregation of native PRP from patients with thrombocytosis, whereas commonly used aggregometers could not analyse platelet aggregation of native PRP in these patients. CONCLUSION: The time consuming process of PRP adjustment may not be necessary for platelet aggregation measurements. Moreover, using adjusted PRP for monitoring aspirin or clopidogrel treatment may falsify results. Therefore, it may be better to use native PRP for platelet aggregation measurements, even in patients with thrombocytosis.     

Platelet components today

Platelet concentrates (PC) continues to be the only resource available to treat patients with qualitative and/or quantitative platelet defects. Currently we have three methods to prepare PC: platelet rich plasma (PRP), buffy coat (BC), and apheresis. In recent years, the characteristics of the products have improved significantly: greater yield of better platelets with less RBC and leucocyte content. At the present, BC and apheresis derived PC offer some advantages in comparison to PRP, as it can been prepared in additive solutions, culture them using sensitive methods or apply pathogen reduction technologies.