Transfusion Adverse Events Research Articles

The signaling role of CD40 ligand in platelet biology and in platelet component transfusion.

The CD40 ligand (CD40L) is a transmembrane molecule of crucial interest in cell signaling in innate and adaptive immunity. It is expressed by a variety of cells, but mainly by activated T-lymphocytes and platelets. CD40L may be cleaved into a soluble form (sCD40L) that has a cytokine-like activity. Both forms bind to several receptors, including CD40. This interaction is necessary for the antigen specific immune response. Furthermore, CD40L and sCD40L are involved in inflammation and a panoply of immune related and vascular pathologies. Soluble CD40L is primarily produced by platelets after activation, degranulation and cleavage, which may present a problem for transfusion. Soluble CD40L is involved in adverse transfusion events including transfusion related acute lung injury (TRALI). Although platelet storage designed for transfusion occurs in sterile conditions, platelets are activated and release sCD40L without known agonists. Recently, proteomic studies identified signaling pathways activated in platelet concentrates. Soluble CD40L is a good candidate for platelet activation in an auto-amplification loop. In this review, we describe the immunomodulatory role of CD40L in physiological and pathological conditions. We will focus on the main signaling pathways activated by CD40L after binding to its different receptors.

Strengthening of the Blood Safety System in the National Blood Transfusion Service - Implementation of the European Union IPA Project - at the Institute for Transfusion Medicine of the Republic of Macedonia

The Safety of the Blood Supply in any country is of utmost importance to safeguard patients from serious adverse events of blood transfusion. Implementation of a Quality System in the Blood Transfusion Service, with support of Government and Ministry of Health is a key element to guarantee safe blood. The IPA TAIB 2009 project - Strengthening of the Blood Safety System executed in 2013/14 provided the means to start implementing a Quality System in the Institute for Transfusion Medicine of the Republic of Macedonia. This project aimed to ultimately bring the Blood Transfusion Service to European Union standards, allowing the exchange of blood components and all other types of collaboration with other European Union countries in future. The project put the basis for unification of blood transfusion standards and operating procedures in the whole country as well as set up essential education of blood transfusion personnel.

Strengthening of the Blood Safety System in the National Blood Transfusion Service - Implementation of the European Union IPA Project - at the Institute for Transfusion Medicine of the Republic of Macedonia

The Safety of the Blood Supply in any country is of utmost importance to safeguard patients from serious adverse events of blood transfusion. Implementation of a Quality System in the Blood Transfusion Service, with support of Government and Ministry of Health is a key element to guarantee safe blood. The IPA TAIB 2009 project - Strengthening of the Blood Safety System executed in 2013/14 provided the means to start implementing a Quality System in the Institute for Transfusion Medicine of the Republic of Macedonia. This project aimed to ultimately bring the Blood Transfusion Service to European Union standards, allowing the exchange of blood components and all other types of collaboration with other European Union countries in future. The project put the basis for unification of blood transfusion standards and operating procedures in the whole country as well as set up essential education of blood transfusion personnel.

Adverse Events of Exchange Transfusion in Neonatal Hyperbilirubinemia

Introduction: Jaundice is an important problem during neonatal period. When total serum bilirubin (TSB) level exceeds a critical limit, it crosses the blood brain barrier and results into bilirubin encephalopathy. The main aim of therapy for neonatal hyperbilirubinemia is prevention of bilirubin encephalopathy by phototherapy and/or exchange transfusion. The aims of this study were to evaluate the efficacy of exchange transfusion (ET) and observe the adverse events during and following three days of ET in neonates with hyperbilirubinemia. Materials and Method: Hospital based cross-sectional descriptive study. All neonates admitted to neonatal intensive care unit and /or paediatric wards of a tertiary- care centre between September 2010 to March 2012, requiring ET were enrolled. Results: A total of 139 ETs were performed in 120 neonates. The common causes were ABO incompatibility (30.8%), prematurity (30.8%), idiopathic (27.5%), Rh isoimmunization (6.7%) and cephalhematoma (4.2%). Mean pre- ET total serum bilirubin (TSB) was 24.2 mg% dL. There was 58% reduction in TSB in post ET and 31% net reduction in 6 hr post ET. Term and preterm neonates showed equal percentage of TSB reduction. Respiratory distress (10.8%) and bradycardia (6.7%) were the common adverse events during, and hypocalcemia (98.3%) and thrombocytopenia (34.2%) in 3 days following ET. The sick neonates had significantly higher incidence of thrombocytopenia (p= 0.031), respiratory distress (p=0.009), apnea (p<0.001) and cardiorespiratory arrest (p<0.001). Overall mortality was 4.2%, and non-survivors were mostly low birth weight, born outside the present hospital and had higher incidence of adverse events. Conclusion: Exchange transfusion is an effective intervention in reducing the serum bilirubin level. However, these neonates require monitoring of ionised calcium and thrombocytopenia. Sick neonates had higher incidence of adverse events than healthy and close clinical monitoring is needed to improve the outcome. DOI: http://dx.doi.org/10.3126/jnps.v34i1.9030 J Nepal Paediatr Soc 2014;34(1):7-13

Incidence and pattern of 12 years of reported transfusion adverse events in Zimbabwe: a retrospective analysis.

Haemovigilance hinges on a systematically structured reporting system, which unfortunately does not always exist in resource-limited settings. We determined the incidence and pattern of transfusion-related adverse events reported to the National Blood Service Zimbabwe. A retrospective review of the transfusion-event records of the National Blood Service Zimbabwe was conducted covering the period from 1 January 1999 to 31 December 2011. All transfusion-related event reports received during the period were analysed. A total of 308 transfusion adverse events (0.046%) were reported for 670,625 blood components distributed. The majority (61.6%) of the patients who experienced an adverse event were female. The median age was 36 years (range, 1-89 years). The majority (68.8%) of the adverse events were acute transfusion reactions consisting of febrile non-haemolytic transfusion reactions (58.5%), minor allergies (31.6%), haemolytic reactions (5.2%), severe allergic reactions (2.4%), anaphylaxis (1.4%) and hypotension (0.9%). Two-thirds (66.6%) of the adverse events occurred following administration of whole blood, although only 10.6% of the blood was distributed as whole blood. Packed cells, which accounted for 75% of blood components distributed, were associated with 20.1% of the events. The incidence of suspected transfusion adverse events was generally lower than the incidences reported globally in countries with well-established haemovigilance systems. The administration of whole blood was disproportionately associated with transfusion adverse events. The pattern of the transfusion adverse events reported here highlights the probable differences in practice between different settings. Under-reporting of transfusion events is rife in passive reporting systems.

The effect of platelet‐derived microparticles in stored apheresis platelet concentrates on polymorphonuclear leucocyte respiratory burst

Platelet-derived microparticles (PMPs) and other proinflammatory mediators, which are accumulated during the storage process, might induce transfusion adverse events. We hypothesized that the PMP primed polymorphonuclear neutrophil (PMN) respiratory burst after the transfusion, which could be linked to the transfusion-related acute lung injury (TRALI). The PMPs were isolated by centrifugation of the platelet-free plasma from 10 apheresis platelet concentrates (A-PLTs) at 20,000×g for 1 h. The PMPs were counted by flow cytometric analysis, followed by Western blotting, that were performed on isolated PMPs. The soluble CD40 ligand (sCD40L, sCD154) was assayed with ELISA. The priming of the formyl-Met-Leu-Phe (fMLP)-activated PMN respiratory burst was measured with the hydrogen peroxide production. The PMP counts increased by 1·7-folds after 3 days of storage. Meanwhile, sCD40L also significantly increased in PMP fraction isolated from the 3-day stored A-PLTs. Furthermore, Western blotting indicated that sCD40L was involved and concentrated in PMP. The PMPs were able to effectively prime the fMLP-activated PMN respiratory burst, which was partly inhibited by CD154 monoclonal antibody or by filtration with 0·1 μM membrane. Significant relativity was existed between the PMP counts, sCD40L and priming activity during the A-PLT storage. The platelet-derived microparticles, which carried the sCD40L, accumulated in the apheresis platelet concentrates during the 5 days of storage. They primed the fMLP-activated PMN respiration burst, which might be relative to TRALI.

Quality of freeze‐dried (lyophilized) quarantined single‐donor plasma

Transfusion of plasma is a basic treatment for complex coagulopathies as well as in major blood loss. Early transfusion of plasma after trauma with major hemorrhage has been recommended by retrospective studies. However, the use of plasma is often hampered by the need to maintain a cold chain and the time needed for thawing fresh-frozen plasma (FFP). With freeze-dried (lyophilized) plasma (FDP) both difficulties can be avoided. Here, we describe the production, quality characteristics, and our experiences with FDP. Quarantine plasma samples were freeze-dried. The clotting factors fibrinogen, Factor (F)V, FVIII, FXI, von Willebrand factor (vWF), protein S, antithrombin, plasminogen, and plasmin inhibitor were determined after manufacturing and after storage at room temperature and refrigeration. Reported adverse transfusion events were evaluated and compared to that of FFP. Clinical effectiveness was estimated by inquiry among experienced users. Lyophilization resulted in a loss of coagulation factor activity between 0% and up to 20% to 25% (FVIII, vWF). When stored refrigerated, coagulation factors did not lose more than 10% of their activities. Storage at room temperature for 24 months mainly affected vWF/ristocetin cofactor activity and fibrinogen activity. From 2007 to 2011 more than 230,000 units of FDP were delivered. There were no reports about clinical ineffectiveness. The frequency of transfusion reactions was not different from that of FFP. Lyophilized plasma showed characteristics similar to FFP. Since FDP requires neither complex logistics nor time-consuming thawing, it allows rapid treatment of coagulopathies.

Application of root cause analysis in the management of pediatric transfusion adverse events

Objective To investigate the application of root cause analysis (RCA) in the management of pediatric transfusion adverse events,in order to reduce the occurrence rate of adverse events in pediatric transfusion.Methods Root cause analysis method was used from October 2011 to March 2012.Occurrence rate of adverse events,double check and accuracy of transfusion were compared before and after the implementation of RCA.Results Six months before RCA,the occurrence rate of adverse events was 0.32％ and six months after RCA was 0.03％,and the difference was statistically significant (x2 =19.146,P ＜ 0.01).The rate of double check and accuracy of transfusion were respectively 100％ and 98％ after RCA,which were higher than those before RCA (74％ and 83％),and the differences were statistically significant (x2 =29.885,13.085,respectively; P ＜ 0.01).Conclusions Root cause analysis can effectively control related factors during pediatric transfusion,reduce the occurrence rate of adverse events and improve transfusion safety. Key words: Hospital, pediatrics; Safety management; Root cause analysis; Transfusion adverse events

Expression of Platelet (PLT) P-Selectin and PLT-Neutrophil (PMN) Interaction After Treatment of Whole Blood with Mirasol® PRT.

AbstractAbstract 2288 IntroductionPlatelet concentrates develop biologically active compounds during storage which may play a role in adverse events of transfusion. Although many studies have focused on release of soluble pro-inflammatory compounds, changes in cells such as platelets may contribute to the response or pro-inflammatory effects of transfusion products. In previous studies we have shown that pathogen reduction with Mirasol PRT of apheresis PLT concentrates induced changes in PLTs which increased during storage including expression of P-selectin and the capacity to form PLT-PMN aggregates. These changes were also associated with increased adherence of stored PLTs in a microfluidic chamber. In the current study we evaluated P-selectin and PLT-PMN aggregate formation in whole blood after treatment with Mirasol PRT. MethodsTen units of whole blood from healthy donors were drawn into CPD under an IRB approved protocol. Five units where treated with Mirasol PRT and five units remained untreated. Aliquots were taken before and after treatment (or at same times for untreated units) on Day 0 and 24–27 hours after draw on Day 1 after storage at 22–24°C. Platelet rich plasma (PRP) was produced by standard technique and PLTs isolated on a Sepharose 2B column. PLTs were incubated with APC-CD62P and FITC-CD41a for comparison with P-selectin expressed as percent positive increase over isotype control. PMNs were isolated from 50 ml of heparinized peripheral blood drawn from healthy, ABO-matched donors. After a 5 min pre-incubation at 37°C in a shaking water bath, untreated, treated PLTs, and PMNs were incubated separately or together for 3 min then quenched at 4°C. FITC-CD41a and FITC-IgG1 isotype for platelet-PMN aggregate quantitation or PE-CD11b for CD11b expression on neutrophils were added. Platelet-PMN aggregates was expressed as percent of all PMN events above CD41a isotype control. CD11b expression was determined for PMNs after exposure to PLTs by flow cytometry. ResultsP-selectin positive cells did not change significantly over time in samples from untreated products (Table 1). After Mirasol PRT treatment, cells positive for P-selectin increased on Day 0 and 1 (p<0.005, two-tailed t-test). Treated products, compared to untreated products demonstrated significantly increased P-selectin expression on Day 1.Table 1P-selectin Expression on PLTsSample% PLTs positive for P-selectinUntreated WBDay 0, earlyDay 0, lateDay 110.2 ± 2.2*15.2 ± 3.312.3 ± 2.3Mirasol PRT treatedDay 0, preDay 0, postDay 17.6 ± 1.119.0 ± 2.521.7 ± 2.6***Numbers represent mean ± SEM for 5 separate products each**Treated cells different than untreated cells, p<0.05Results for PMN-PLT aggregates parallel expression of P-selectin (Table 2). No increase in aggregate formation was seen for untreated samples; however, treated samples showed increased aggregates at Day 0 and 1 (p<0.005). Aggregates with PMNs were increased in treated samples in comparison to untreated samples on Day 1.Table 2PLT-PMN AggregatesSample% PMNs with associated PLTsUntreated WBDay 0, earlyDay 0, lateDay 17.8 ± 4.49.8 ± 3.37.1 ± 3.8Mirasol PRT treatedDay 0, preDay 0, postDay 14.8 ± 3.015.5 ± 3.519.3 ± 6.9**No differences were seen with CD11b expression on PMNs after exposure of treated or untreated PLTs at any of the times studied.*Numbers represent mean ± SEM for 5 separate products each**Treated cells different than untreated cells, p<0.05 ConclusionTreatment of whole blood with Mirasol PRT results in increased expression of P-selectin on PLTs and capability of forming aggregates with PMNs. The changes occur soon after initiation of treatment, and the implications for clinical response to of platelet infusion and adverse events of transfusion need to be established. Disclosures:Ambruso:Terumo BCT: Research Funding. Seewald:Terumo BCT: Research Funding. Marschner:Terumo BCT: Employment. Goodrich:Terumo BCT: Employment.

The Pro-Inflammatory Activity of Microparticles in Red Blood Cell Concentrates (RBC)

AbstractAbstract 1178Microparticles (MP) are submicron size fragments produced from most cells. Although their role in disease is still not known, concern has been raised over their role in RBCs and the adverse events of RBC transfusion, particularly their pro-inflammatory effects on the host. We hypothesize that MP's increase during routine RBC storage, contribute to the priming activity that accumulates in the supernatant of RBCs, and that pre-storage leukoreduction affects these processes. Methods:RBC’s were separated from the whole blood of 8 healthy donors and stored in AS-5 via current U.S. industry standards. The first 5 units were split into two equal aliquots (weight) with 50% undergoing standard leukoreuction (LR) and the remaining was left as an unmodified control (NLR). The other three units were processed as standard LR-RBCs. RBC samples were taken at days (D) 1 and 42 and cell-free supernatants were separated by centrifugation and stored (-80°C). The supernatant was centrifuged at 100,000g – 120 minutes into MP and MP free (MPF) portions and MP’s resuspended in equal volume of 1.25 % HSA (MP-HSA) or cell-free plasma (MP-FFP). MP fractions were incubated with specific antibodies to RBCs (CD235), WBCs (CD45), and PLTs (CD41a) and analyzed by flow cytometry employing commercially obtained counting beads. Isolated neutrophils (PMNs) were incubated with the MP and MPF fractions [10%] FINAL for 5 min at 37°C followed by activation of the NADPH oxidase with fMLF. The maximal rate of O2− production was measured as the SOD-inhibitable reduction of cytochrome c. Results were analyzed as an ANOVA with a post-hoc Newman Keuls test for multiple comparisons. Results:The total number of MP's increased during storage in all units irrespective of LR. The predominant MPs came from RBCs with PLTs representing the least (Table 1). Although the total number of MPs increased in all units, the number of MPs that specifically marked for precursor cell types decreased over storage (Table 1). The MPF fractions from stored (D.42) NLR-RBCs and LR-RBCs caused significant priming of the PMN oxidase vs. both the MPF from D.1 and the fMLF controls (Table 1). The MP fraction from NLR-RBCs did not evidence priming activity (data not shown); however, the LR-MP-HSA fractions from both D.1 and D.42 caused significant priming of the oxidase. Resuspension in plasma (LR-MP-FFP) inhibited this priming activity (Table 1). We conclude that during storage of NLR- and LR-RBCs, MPs increase; however the number of MPs associated with a specific cell type decrease but not significantly. This loss of cellular markers may be due to non-specific loss, antigen capping, internalization or proteolysis because proteases are released and increase during RBC storage. The presence of MPs from leukocytes and platelets are likely due to filtration, which is known to cause release of WBC- and PLT-derived proteins. While the majority of the PMN priming activity is in the acellular MPF supernatant in all NLR- and LR-RBC units, there is a modest amount of priming activity in the MP fraction following LR (LR-MP-HSA), which is likely a function of LR and may be inhibited by resuspension of the MPs in plasma.Table 1Microparticle counts and Priming DataFlow Cytometry: CountsTotal (un labeled)RBC CD235 (% Total MP)PLT CD41a (% Total MP)WBC CD45 (% Total MP)NLR-D.1146,33641,293 (51.5%)11,443 (14.3%)27,431 (34.2%)NLR-D.42188,94425,836 (53.7%)7,374 (15.3%)14,954 (31.0%)LR-D.1157,49241,302 (47.8%)8,866 (10.3%)36,173 (41.9%)LR D.42173,42133,957 (48.5%)6,854 (10%)29,063 (41.5%)Priming (nmol O2-/min)Day 1Day 42fMLF1.97 ± 0.13MPF-NLR2.44 ± 0.225.05 ± 0.36*,†MPF-LR2.19 ± 0.873.06 ± 0.2*,†LR-MP-HSA3.315 ± 0.11†3.039 ± 0.13†LR-MP-FFP1.81 ± 0.292.23 ± 0.22*p<0.05 vs D.1; †p<.05 vs. fMLF. Disclosures:Silliman:Pall Corporation: Honoraria, Research Funding.

Lipids: Free Fatty Acids, Eicosanoids, and Lysophospholipids and the Pro-Inflammatory Effects of Transfusion

Abstract SCI-48Stored packed red blood cells (PRBCs) have been implicated in increased morbidity and mortality in critically ill patients, patients requiring cardiothoracic surgery, and injured patients following blunt and/or penetrating trauma. Lipids are generated during the routine storage of cellular blood components and have been implicated in transfusion-related acute lung injury (TRALI) and postinjury multiple organ failure (MOF). These lipids are comprised of two classes, as denoted by their retention times on normal-phase HPLC: 1) nonpolar lipids, including arachidonic acid, 5-hydroxy-eicosotetranoic acid (HETE), 12-HETE, 15-HETE, and 5-oxo-eicosotetranoic acid (5-oxo-ETE); and 2) a mixture of lysophosphatidylcholines (lyso-PCs), including stearoyl-, oleoyl-, or palmitoyl-lyso-PCs as well as C16 or C18 lyso-platelet activating factor. Importantly, all of these lipids were identified by quadrupole LC/MS/MS. The former are derived from red blood cells, because they are generated during the routine storage of prestorage leuko- and platelet-reduced PRBCs, while the latter are platelet-derived, and are generated during storage of platelet concentrates (PC) and unmodified PRBCs but not leukocyte-reduced PRBCs (LR-PRBCs). Generation of the nonpolar lipids requires an active phospholipase, such as peroxiredoxin-6, which accumulates during PRBC and LR-PRBC storage and appears to be active and T-phosphorylated. The nonpolar lipids do not accumulate during PC storage. These lipids are released into the plasma fraction of the stored component and have been shown to: 1) prime the polymorphonuclear leukocytes (PMN) oxidase; 2) activate primed PMNs; and 3) serve as the second event in a two-event model of TRALI in both rodents and sheep. This lipid priming of PMNs occurs through activation of specific receptors, for example G2A, for lyso-PCs, and causes activation of G-protein-linked cellular receptor, G-protein release, and stimulation of kinase cascades. This results in translocation of the cytosolic oxidase components and a change from a resting PMN phenotype to a hyperactive, adherent phenotype. Conversely, stored PRBCs have also been implicated in MOF. However, acute lung injury does not occur until 72 hours postinjury, implicating PRBCs as a first event(s). The nonpolar lipids that accumulate during routine storage activate primary human pulmonary microvascular endothelial cells (HMVECs) and primary human liver sinusoidal endothelial cells (LSECs), as quantified by increased surface expression of intercellular adhesion molecule-1 (ICAM-1) and the synthesis and release of chemokines, for example IL-8. This proinflammatory activation results in PMN adherence, and such HMVEC activation occurs through activation of the BLT2 receptor and activation of a PKC-dependent kinase cascade. Stored PRBCs (day 42) may serve as the first event in a two-event rodent model of acute lung injury. We conclude that lipids generated during the routine storage of cellular blood components have proinflammatory effects in vitro and in vivo, which may explain some of the adverse events of transfusion, including TRALI and postinjury MOF, and that inhibition and avoidance of these compounds may make transfusions safer. Further research is already under way in several prospective trials, including: 1) Age of Blood Components transfused in the PICU (ABC-PICU); 2) red cell storage duration and outcomes in cardiac surgery at the Cleveland Clinic; 3) Red Cell Storage duration Study (RECESS); and 4) the Age of Blood Evaluation trial (ABLE). Disclosures:Silliman:Pall Corporation: Honoraria, Research Funding.

Ethical and deontological issues in Transfusion Medicine.

Ethical and deontological issues in Transfusion Medicine.

Diagnosis, Treatment, and Reporting of Adverse Effects of Transfusion

The risks of transfusion remain significant. Familiarity with the incidence, etiology, management, and prevention of commonly encountered transfusion reactions is integral to the practice of transfusion medicine. This review intends to serve as a practical guide reflecting the current understanding of adverse transfusion events, clinical features helpful for diagnosis, and recommended management strategies for typical scenarios. Severe and mild transfusion reactions are covered, with a focus on the distinguishing features of challenging clinical dilemmas. Topics include pulmonary complications of transfusion, hemolytic reactions, allergic and anaphylactic reactions, septic reactions, and febrile responses to transfusion. We also discuss a consultative approach to evaluation and reporting of transfusion reactions.

Transfusion reactions: a comparative observational study of blood components produced before and after implementation of semiautomated production from whole blood

A semiautomated method of component production from whole blood was implemented at Canadian Blood Services. To assess safety of the new components, the frequency of adverse transfusion events (ATEs) to platelet components (PCs) and red blood cell (RBCs) produced before and after implementation of the new method was surveyed and compared. This retrospective, observational, noninferiority study was conducted in 12 sentinel hospitals across Canada. The control group received RBCs in additive solution-3 (AS-3) and platelet-rich plasma (PRP)-produced platelets (PLTs) for 3 to 11 months before implementation of semiautomated production, and the study group received RBCs in saline-adenine-glucose-mannitol (SAGM) and buffy coat (BC)-produced PLTs for 3 to 11 months after implementation. ATE definitions at each hospital and standard practice for reporting did not change between control and study periods. Data for analysis were obtained from databases and original report forms. The pooled risk ratio of a reaction to SAGM versus AS-3 RBCs was 0.77 (95% confidence interval [CI], 0.66-0.90), suggesting that SAGM products had significantly lower reaction rates than AS-3 products (p < 0.01). Reported allergic reactions to RBCs decreased from 0.07% (AS-3) to 0.04% (SAGM). For PLTs, the difference in reaction rates between BC and PRP was not significant (p = 0.37), and the pooled risk ratio of BC versus PRP was 1.14 (95% CI, 0.86-1.50). The change in manufacturing method was associated with lower reaction rates to SAGM RBCs than to AS-3 RBCs. Pooled BC PLTs were noninferior to random-donor PRP PLTs with respect to ATEs.

Transfusion‐related mortality after primary hip arthroplasty – an analysis of mechanisms and confounders

Bleeding and postoperative anaemia after total hip arthroplasty (THA) may trigger transfusion of red blood cells (RBC). However, large observational studies have reported associations between RBC transfusion and increased postoperative morbidity and mortality. As major bleeding or severe postoperative anaemia is intrinsically linked with RBC transfusion, direct causality between transfusion and adverse outcomes remains unclear. This study aimed to identify possible relations between RBC transfusion, severe bleeding or anaemia and mortality in all patients who died <90 days after THA in Denmark in 2008. Nationwide review of patient records. Cases of adverse transfusion events, infections following transfusion, severe perioperative bleeding or anaemia and possible causal relations to mortality were identified by two independent reviewers. Of 6932 THA patients, 45 (0·6%) were transfused within 30 days and died <90 days from surgery. Three patients (7%) died from causes possibly related to either severe anaemia, major bleeding alone or major bleeding with transfusion-related acute lung injury, while five (11%) died from infections occurring after RBC transfusion. Mortality in the remaining 37 patients (82%) was of unknown cause (nine patients) or related to patient or surgical factors (28 patients). Transfusion-related mortality after THA included cases of major perioperative bleeding or severe postoperative anaemia with delayed RBC transfusion in addition to possible complications to RBC transfusion per se. Future studies should account for pretransfusion haemoglobin and perioperative blood loss when evaluating RBC transfusion-associated outcomes after surgery.

Stir: a state approach to haemovigilance

Background/aim: Serious Transfusion Incident Reporting system (STIR) is the voluntary haemovigilance framework developed by Blood Matters program for Victoria, on behalf of the Department of Health and the Blood Service. It was developed in 2005 to capture serious transfusion incidents, including near misses. It provides a central system for reporting events related to administration and handling of fresh blood components and pre-transfusion samples. Method Health services submit initial notifications and the STIR office provides follow-up forms relevant to the event type (e.g., incorrect blood component transfused, IBCT) for completion. Information (de-identified) regarding the case is returned for data entry and review, including attribution of causality and severity, by an expert clinical group. STIR links with the Victorian Department of Health sentinel event program, where it is mandatory to report ABO incompatible transfusion events. Results Participation to date is 71 public and private hospitals and laboratories, across four jurisdictions (Victoria, Tasmania, Australian Capital Territory and Northern Territory). To date there have been 946 transfusion adverse events in 939 patients (both adults and children) notified. Conclusion STIR continues to evolve in its processes for transfusion data reporting while ensuring it provides ongoing feedback to those reporting and derives recommendations for better, safer transfusion practice. Background/aim: Serious Transfusion Incident Reporting system (STIR) is the voluntary haemovigilance framework developed by Blood Matters program for Victoria, on behalf of the Department of Health and the Blood Service. It was developed in 2005 to capture serious transfusion incidents, including near misses. It provides a central system for reporting events related to administration and handling of fresh blood components and pre-transfusion samples. Health services submit initial notifications and the STIR office provides follow-up forms relevant to the event type (e.g., incorrect blood component transfused, IBCT) for completion. Information (de-identified) regarding the case is returned for data entry and review, including attribution of causality and severity, by an expert clinical group. STIR links with the Victorian Department of Health sentinel event program, where it is mandatory to report ABO incompatible transfusion events. Participation to date is 71 public and private hospitals and laboratories, across four jurisdictions (Victoria, Tasmania, Australian Capital Territory and Northern Territory). To date there have been 946 transfusion adverse events in 939 patients (both adults and children) notified. STIR continues to evolve in its processes for transfusion data reporting while ensuring it provides ongoing feedback to those reporting and derives recommendations for better, safer transfusion practice.

TCT-391: Red Blood Cell Transfusion and Long-term Major Adverse Events in Patients Undergoing Percutaneous Coronary Interventions, Results from A Large Prospective Multicenter Registry – the STENT Group

TCT-391: Red Blood Cell Transfusion and Long-term Major Adverse Events in Patients Undergoing Percutaneous Coronary Interventions, Results from A Large Prospective Multicenter Registry – the STENT Group

Generation of neutrophil priming activity by cell‐containing blood components treated with pathogen reduction technology and stored in platelet additive solutions

Storage of cell-containing blood components such as platelet concentrates (PCs) and red blood cells (RBCs) results in generation of biologically active compounds, many of which may be associated with adverse transfusion events. Priming of the neutrophil oxidase activity is a common characteristic of many of the biologically active compounds found in stored blood. We evaluated the priming activity of pathogen reduction technology (PRT)-treated PCs stored in plasma or platelet additive solution (PAS) and PRT-treated RBCs. PCs were collected with Trima or Amicus equipment and were PRT treated with the Mirasol PRT system or the Intercept Blood System. Some units were gamma irradiated. Products were stored in 100% plasma or 35% plasma plus PAS. RBCs were washed and PRT treated before storage. Samples were removed throughout storage and priming of the oxidase activity was measured. Platelets collected on Trima or Amicus equipment and stored in plasma or PAS demonstrated increasing priming activity during 5 to 7 days of storage. Gamma irradiation, but not PRT treatment with either technology, further enhanced this priming activity. Supernatants of RBCs stored for 42 days induced priming in untreated controls, but not in washed or Mirasol PRT-treated test products. Production of oxidase priming activity increased during storage in all blood products. No significant differences were associated with the collection method, storage in PAS, or PRT treatment. The generation of biologically active compounds, which may serve as an etiology for adverse events, appears to be independent of these processes for collection, storage, and pathogen reduction.

Expression of P-Selectin and Platelet-Neutrophil (PMN) Interactions In Untreated and Mirasol® PRT Treated Platelet Concentrates During Routine Storage.

AbstractAbstract 1123 Introduction:Platelet concentrates develop biologically active compounds during storage which may play a role in adverse events of transfusion. Although many studies have focused on release of soluble pro-inflammatory compounds, changes in cells such as platelets may contribute to the pro-inflammatory effects of transfusion products. We evaluated untreated and Mirasol Pathogen Reduction Technology (PRT) treated platelet concentrates for expression of P-selectin and interactions between platelets and PMNs. Methods:Four, double apheresis platelet products were collected from healthy volunteers with TRIMA system under an IRB approved protocol. One product of each pair was PRT treated with Mirasol PRT and both were stored under standard conditions. At various times, aliquots were sterilely removed from products. Expression of P-selectin on platelets was defined with a specific antibody. Neutrophils, isolated from ABO type specific peripheral blood of volunteers, were incubated with platelet concentrates for 3 min at 37° C, and labeled CD41 was added. PMNs were identified with flow cytometry by forward/side scatter and platelets by fluorescence and the % of PMNs associated with platelets determined. Inhibition of platelet/neutrophil interaction with antibodies to adhesion molecules was also examined. In parallel experiments, activation of neutrophils after incubation with platelets was determined by oxidation of dihydrorhodamine (DHR). Results:During storage, platelet expression of P-selectin increased in both untreated and Mirasol treated platelet concentrates (p<0.05) with greater expression on treated products (p<0.05). On day 0 of storage, PMNs associated with platelets was 9.7±1.1% (mean±SEM, n=4, untreated) and 12.1±1.3% (treated products), and on day 5 results were 16.8±4.3% and 27.1±4.3% respectively (significant, p<0.05). Platelet-PMN interactions were inhibited by ≥90% by antibodies to P-selectin or its PMN adhesion partner PSGL-1, but not Mac1, LFA-1, GPIb or ICAM-1. Platelet-PMN interactions were directly related to the stored platelets, not the effects of stored plasma. Activation of the PMN respiratory burst by oxidation of DHR was not shown in any product type over storage time. Conclusion:During storage, platelets exhibit increased P-selectin expression and the capability to adhere to PMNs. These effects were greater after Mirasol PRT treatment. The cell association depended on the interaction between P-selectin (platelets) and PSGL-1 (PMNs). These changes occurring during storage of platelet concentrates may explain platelet recovery patterns in patients requiring repeated transfusions with untreated and PRT treated products and could play a potential role in adverse events for either product type. Disclosures:Goodrich:CaridianBCT Biotechnologies: Employment, Patents & Royalties, Research Funding. Marschner:CaridianBCT Biotechnologies: Employment, Research Funding.

What's new in the blood crisis?

The news is filled with ways to economize on petrol, spending and by use of alternative energy sources. So how are we doing for the blood transfusion economy in provision of alternatives to conserve blood supplies? The answer is described in the four reviews in the symposium in this issue of BJHM. Less transfusion means reduced allogeneic blood exposure, fewer risks of adverse transfusion events and better outcomes. Conservation of the patient's own blood is a cheaper and less hazardous means of sustaining haemoglobin than treating anaemia with blood transfusion.