Allogeneic Platelet Transfusions Research Articles

Impact of Intraoperative Allogeneic Platelet Transfusion on Healthcare-Associated Infections in Cardiac Surgery: Insights From a Large Single-Center Cohort Study

ObjectivesDespite significant improvement in patient blood management-cardiac surgery remains a high hemorrhagic risk procedure. Platelet transfusion is commonly used to treat thrombocytopenia-induced perioperative bleeding. Allogeneic platelet transfusion may induce transfusion-related immunomodulation. However, its association with postoperative healthcare-associated infections is still a matter of debate. Our objective was to evaluate the impact of allogeneic platelet transfusion during cardiac surgery on postoperative HAI incidence. DesignRetrospective cohort study SettingTertiary referral academic center ParticipantsPatients undergoing cardiac surgery from 2012 to 2018. InterventionsNone Measurements and Main ResultsIntraoperative platelet transfusion was defined as exposure in a causal model. The primary outcome was the incidence of healthcare-associated infections-comprised of bloodstream infection-hospital-acquired pneumonia and surgical-site infection. Among 7662 included patients, 528 (6.8%) were exposed to intraoperative platelet transfusion and 329 (4.3%) developed 454 postoperative infections. Bloodstream infection affected 106 (1.4%) patients, hospital-acquired pneumonia 174 (2.3%) and surgical-site infection 148 (1.9%). Intraoperative platelet transfusion was associated with an increased risk of bloodstream infection after adjustment by multivariable logistic regression (OR 2.85; 95%CI (1.40-5.8); p=0.004; n=7662), propensity score matching (OR 3.95; 95%CI (1.57-12.0), p=0.007; n=766) and propensity score overlap weighting (OR 3.04; 95%CI (1.51-6.1), p=0.002; n=7762). Surgical-site infection and hospital-acquired pneumonia were not significantly increased by platelet transfusion. ConclusionsOur results suggest that intraoperative allogeneic platelet transfusion is a risk factor for bloodstream infection after cardiac surgery. These results support the development of patient blood management strategies aiming at minimizing perioperative platelet transfusion in cardiac surgery.

Preservation of recipient plasma sphingosine-1-phosphate levels reduces transfusion-related acute lung injury.

Cold-stored (CS) platelets are once again being reintroduced for clinical use. Transfused CS platelets offer benefits over room temperature-stored (RTS) platelets such as increased hemostatic effects and prolongation of shelf-life. Despite these advantages little is known about their association with transfusion-related acute lung injury (TRALI). TRALI is associated with prolonged storage of RTS platelets and has a mortality of >15%. Determining the safety of CS platelets is important considering their proposed use in TRALI-vulnerable populations with inflammation such as surgical patients or patients with trauma. Donor platelet-derived ceramide causes TRALI, whereas donor platelet sphingosine-1-phosphate (S1P) is barrier protective. Females have higher plasma levels of S1P than males. Cold temperatures increase S1P levels in cells. Therefore, we hypothesized that female (donors or recipients) and/or CS platelets would decrease TRALI. To test this, we compared how male and female donor and recipient allogeneic platelet transfusions of CS (4°C) versus RTS (23°C) platelets stored for 5 days influence murine TRALI. Transfusion of CS platelets significantly reduced recipient lung tissue wet-to-dry ratios, bronchoalveolar lavage total protein, lung tissue myeloperoxidase enzyme activity, histological lung injury scores, and increased plasma sphingosine-1-phosphate (S1P) levels compared with RTS platelet transfusions. Female as opposed to male recipients had less TRALI and higher plasma S1P levels. Female donor mouse platelets had higher S1P levels than males. Mouse and human CS platelets had increased S1P levels compared with RTS platelets. Higher recipient plasma S1P levels appear protective considering females, and males receiving platelets from females or male CS platelets had less TRALI.NEW & NOTEWORTHY Transfusion-related acute lung injury (TRALI) though relatively rare represents a severe lung injury. The sphingolipid sphingosine-1-phosphate (S1P) regulates the severity of platelet-mediated TRALI. Female platelet transfusion recipient plasmas or stored platelets from female donors have higher S1P levels than males, which reduces TRALI. Cold storage of murine platelets preserves platelet-S1P, which reduces TRALI in platelet-transfused recipients.

Polyinosinic: polycytidylic acid induced inflammation enhances while lipopolysaccharide diminishes alloimmunity to platelet transfusion in mice.

Alloimmune responses against platelet antigens, which dominantly target the major histocompatibility complex (MHC), can cause adverse reactions to subsequent platelet transfusions, platelet refractoriness, or rejection of future transplants. Platelet transfusion recipients include individuals experiencing severe bacterial or viral infections, and how their underlying health modulates platelet alloimmunity is not well understood. This study investigated the effect of underlying inflammation on platelet alloimmunization by modelling viral-like inflammation with polyinosinic-polycytidylic acid (poly(I:C)) or gram-negative bacterial infection with lipopolysaccharide (LPS), hypothesizing that underlying inflammation enhances alloimmunization. Mice were pretreated with poly(I:C), LPS, or nothing, then transfused with non-leukoreduced or leukoreduced platelets. Alloantibodies and allogeneic MHC-specific B cell (allo-B cell) responses were evaluated two weeks later. Rare populations of allo-B cells were identified using MHC tetramers. Relative to platelet transfusion alone, prior exposure to poly(I:C) increased the alloantibody response to allogeneic platelet transfusion whereas prior exposure to LPS diminished responses. Prior exposure to poly(I:C) had equivalent, if not moderately diminished, allo-B cell responses relative to platelet transfusion alone and exhibited more robust allo-B cell memory development. Conversely, prior exposure to LPS resulted in diminished allo-B cell frequency, activation, antigen experience, and germinal center formation and altered memory B cell responses. In conclusion, not all inflammatory environments enhance bystander responses and prior inflammation mediated by LPS on gram-negative bacteria may in fact curtail platelet alloimmunization.

Enhanced alloresponse to platelet transfusion due to immune dysregulation following ablative chemotherapy in mice.

Alloimmunization is common following platelet transfusion and can result in negative outcomes for recipients such as refractoriness to subsequent transfusions and rejection of transplants. Healthy people do not receive blood transfusions, and the diseases and therapies that result in a need to transfuse have significant impacts on the immunological environment to which these alloantigens are introduced. Ablative chemotherapies are common among platelet recipients and have potent immunological effects. In this study, we modeled the impact of chemotherapy on the alloresponse to platelet transfusion. As chemotherapies are generally regarded as immunosuppressive, we hypothesized that that they would result in a diminished alloresponse. Mice were given a combination chemotherapeutic treatment of cytarabine and doxorubicin followed by transfusion of allogeneic platelets, and compared to controls given no treatment, chemotherapy alone, or transfusion alone. Alloantibody responses were measured 2 weeks after transfusion, and cellular responses and growth factors were monitored over time. Contrary to our hypothesis, we found that chemotherapy led to increased alloantibody responses to allogeneic platelet transfusion. This enhanced response was antigen-specific and was associated with increased CD4+ and CD8+ T cell responses. Chemotherapy led to rapid lymphocyte depletion followed by reconstitution, non-specific activation of transitional B cells with the highest levels of activation in the least mature subsets, and increased serum levels of B cell activating factor (BAFF). These data suggest that ablative chemotherapy can increase the risk of alloimmunization and, if confirmed clinically, that additional measures to protect these patient populations may be warranted.

Preoperative autologous platelet pheresis reduces allogeneic platelet use and improves the postoperative PaO2/FiO2 ratio in complex aortic surgery: a retrospective analysis.

An autologous platelet-rich plasma pheresis (aPP) strategy can harvest partial whole blood that is separated into erythrocytes, plasma and platelets, and can reduce blood loss and transfusion during cardiovascular surgery using cardiopulmonary bypass (CPB). However, the blood and organ conservation effects of this technique have not been confirmed in the context of complex aortic surgery. Perioperative records of 147 adult patients who underwent complex aortic surgery were analysed retrospectively. All patients received regular blood conservation treatment, and 57 patients received aPP. Whether or not the participants were propensity matched, decreased platelet and cryoprecipitate transfusions were found in the aPP group (both P < 0.001), but there were non-significant differences in erythrocyte transfusion, Sequential Organ Failure Assessment scores and other outcomes when compared with the same parameters in the non-aPP group. The aPP group had a higher arterial oxygen partial pressure to inhaled oxygen concentration ratio on postoperative days 1, 2 and 7 than the non-aPP group (P < 0.001, P < 0.001 and P = 0.048, respectively). The utilization of aPP was associated with a reduction in allogeneic platelet and cryoprecipitate transfusions as well as minor lung-protective effects during complex aortic surgery using CPB.

Generation and characterization of HLA-universal platelets derived from induced pluripotent stem cells

Platelet demand has increased around the world. However, the inadequacy of donors, the risk of transfusion-transmitted infections and associated reactions, and the refractory nature of platelet transfusions are among the limitations of allogeneic platelet transfusions. To alleviate these problems, we propose generating platelets in a laboratory that do not induce alloimmunity to human leukocyte antigen (HLA) class I, which is a major cause of immune reaction in platelet transfusion refractoriness. Induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) of a healthy Thai woman. We then knocked out the β2-microglobulin (β2m) gene in the cells using paired CRISPR/Cas9 nickases and sequentially differentiated the cells into haematopoietic stem cells (HSCs), megakaryocytes (MKs) and platelets. Silencing of HLA class I expression was observed on the cell surface of β2m-knockout iPSCs, iPSC-derived HSCs, MKs and platelets. The HLA-universal iPSC-derived platelets were shown to be activated, and they aggregated after stimulation. In addition, our in vivo platelet survival experiments demonstrated that human platelets were detectable at 2 and 24 hours after injecting the β2m-KO MKs. In summary, we successfully generated functional iPSC-derived platelets in vitro without HLA class I expression by knocking out the β2m gene using paired CRISPR/Cas9 nickases.

The blood protective effect of autologous platelet separation in aortic dissection.

This study aimed to retrospectively analyze the blood protective effect of autologous platelet separation in operations for acute aortic dissection. A total of 130 patients with acute aortic dissection were enrolled into the present study. The average age of these patients was 52.962±10.5061 years old. These patients underwent the modified aortic arch replacement with the elephant trunk technique or endovascular aortic exclusion with covered stent. Among these patients, 68 patients who underwent autologous platelet separation were assigned to the platelet separation group, while the remaining patients were assigned to the control group. All operations were performed under deep hypothermic circulatory arrest. After anesthesia, 1-2 therapeutic doses of autologous platelets were isolated from patients in the platelet separation group, and these platelets were quickly infused back to these patients after heparin was neutralized by protamine at the end of the cardiopulmonary bypass. The preoperative and postoperative indexes in these two groups were compared. There were no statistically significant differences in age, gender, smoking history, drinking history and hypertension history between these two groups. Compared with controls, the transfusion volume of allogeneic platelets in the perioperative period significantly decreased in the platelet separation group (1.919±1.6226 vs. 0.794±1.1789, P < #x003C;< #x200A;0.05), and the use rate of allogeneic platelets also significantly decreased (74.19% vs. 45.59%, P < #x003C;< #x200A;0.05). The intraoperative auto transfusion of platelets significantly reduced the volume of allogeneic platelet transfusion after the operation for aortic dissection, which has a significant blood protective effect.

Association of Platelet Count and Platelet Transfusion With Serotonin Level During Living Donor Liver Transplantation: Possible Connection to Graft Regeneration

BackgroundWe recently showed that platelet counts and the amount of platelet transfusion during liver transplantation are positively associated with early graft regeneration. It was hypothesized that platelet-derived serotonin mediates liver regeneration. ObjectivesThis study aimed to evaluate the association between intraoperative platelet count, platelet transfusion, and serum serotonin level. MethodsThirty-two recipients undergoing living-donor liver transplantation were enrolled into this prospective observational study. Serum platelet counts and serotonin levels were measured at the following times: anesthetic induction, start of the anhepatic phase, before graft reperfusion, 5 minutes/1 hour/3 hours/5 hours after graft reperfusion, and before/after platelet transfusion. Serotonin was measured by using a liquid chromatography tandem mass spectrometry. ResultsSerotonin level at the anesthetic induction was 24.5 μg/mL (interquartile range, 14.6 to 38.1 μg/mL). During surgery, serial changes in platelet counts and serotonin levels showed a similar trend: they decreased during the anhepatic phase, increased during the first hour after graft reperfusion, and thereafter gradually decreased. Serotonin level was positively correlated with platelet counts (correlation coefficient = 0.620, P < .001). Allogeneic platelet transfusion significantly increased platelet count from 22 (19–31) × 109/L to 53 (50–81) × 109/L (P = .008) and it also increased serum serotonin from 11.04 (6.41–15.34) μg/mL to 34.26 (25.86–41.94) μg/mL (P = .008). ConclusionsOur findings indicate that allogeneic platelets could act as effector cells deriving serotonins. Also, our findings support the hypothesis that the association between platelets and post-transplantation graft regeneration is mediated by serotonin. Further studies are warranted regarding the respective role of serotonin and other platelet-derived molecules mediating liver regeneration.

Platelets Structure, Function and Modulator Capacity in Replacement Therapy.

Patients with severe thrombocytopenia are presumed to be at increased risk for bleeding, and consequently it has been a standard practice for the past four decades to give allogeneic platelet transfusions to severely thrombocytopenic patients as supportive care. Platelet transfusions may be given either prophylactically to reduce the risk of bleeding, in the absence of clinical hemorrhage (prophylactic transfusions), or to control active bleeding when present (therapeutic transfusions). Here we review the structure and function of platelets and discuss the mechanisms of alloimmunization to platelet transfusion.

Platelet Transfusion Therapy

Patients with severe thrombocytopenia are presumed to be at increased risk for bleeding, and consequently it has been standard practice for the past four decades to give allogeneic platelet transfusions to severely thrombocytopenic patients as supportive care. Platelet transfusions may be given either prophylactically to reduce the risk of bleeding, in the absence of clinical hemorrhage (prophylactic transfusions), or to control active bleeding when present (therapeutic transfusions). Platelets for transfusion can be prepared either by separation of units of platelet concentrates (PCs) from whole blood, which are pooled before administration, or by apheresis from single donors. Comparative studies have shown that the post transfusion increments, hemostatic benefit, and side effects are similar with either product. Thus, in routine circumstances, they can be used interchangeably. In most centers, pooled PCs are less costly. Single-donor platelets from selected donors are preferred when histocompatible platelet transfusions are needed. Both preparations can be stored for up to 5 days after collection at 20°C to 24°C with good maintenance of platelet viability. It is now uncommon for patients undergoing intensive chemotherapy or bone marrow transplantation to die of hemorrhage, but it is open to debate as to what degree platelet transfusions have been responsible for this change in outcome, given the many other advances in other aspects of supportive care.Anwer Khan Modern Medical College Journal Vol. 6, No. 2: July 2015, P 40-46

Alternatives to allogeneic platelet transfusion.

Allogeneic platelet transfusions are widely used for the prevention and treatment of bleeding in thrombocytopenia. Recent evidence suggests platelet transfusions have limited efficacy and are associated with uncertain immunomodulatory risks and concerns about viral or bacterial transmission. Alternatives to transfusion are a well-recognised tenet of Patient Blood Management, but there has been less focus on different strategies to reduce bleeding risk by comparison to platelet transfusion. Direct alternatives to platelet transfusion include agents to stimulate endogenous platelet production (thrombopoietin mimetics), optimising platelet adhesion to endothelium by treating anaemia or increasing von Willebrand factor levels (desmopressin), increasing formation of cross-linked fibrinogen (activated recombinant factor VII, fibrinogen concentrate or recombinant factor XIII), decreasing fibrinolysis (tranexamic acid or epsilon aminocaproic acid) or using artificial or modified platelets (cryopreserved platelets, lyophilised platelets, haemostatic particles, liposomes, engineered nanoparticles or infusible platelet membranes). The evidence base to support the use of these alternatives is variable, but an area of active research. Much of the current randomised controlled trial focus is on evaluation of the use of thrombopoietin mimetics and anti-fibrinolytics. It is also recognised that one alternative strategy to platelet transfusion is choosing not to transfuse at all.

CD8(low)CD28(-) T Cells: A Human CD8 T-Suppressor Subpopulation With Alloantigen Specificity Induced by Soluble HLA-A2 Dimer In Vitro.

CD8(+) suppressor T cells have been demonstrated to provide protection of allografts from rejection. We previously reported that soluble peptide/HLA-A2 dimer shows peptide-specific inhibitory effects on alloresponse in a coculture of peptide-pulsed T2 cells with HLA-A2 negative lymphocytes in vitro. Here we found a subset of CD8(low)CD28(-) T cells that was induced in the dimer-treated coculture. Importantly, this population showed hyporesponsiveness to the alloantigen restimulation as well as alloantigen-specific suppression on alloreactive T cells in a cell-cell contact-dependent fashion. The suppressive mechanisms of CD8(low)CD28(-) T cells involved an elevated expression of membrane-bound TGF-β1, but not Foxp3, CTLA-4, or IL-10. Furthermore, an overrepresention of CD8(low)CD28(-) T cells was observed in the patients after allogeneic platelet transfusion and positively correlated with the elevated concentrations of plasma HLA class I antigens. Our findings demonstrated that soluble HLA-A2 dimer could efficiently induce the tolerant CD8(low)CD28(-) T cells with alloantigen-specific suppression on alloreactive T cells. This study might provide a new strategy for preparation of donor-specific suppressor T cells and represent an attractive alternative for induction of allograft tolerance.

Allogeneic platelet transfusions prevent murine T-cell–mediated immune thrombocytopenia

AbstractPlatelet transfusions are life-saving treatments for many patients with thrombocytopenia; however, their use is generally discouraged in the autoimmune disorder known as immune thrombocytopenia (ITP). We examined whether allogeneic platelet major histocompatibility complex (MHC) class I transfusions affected antiplatelet CD61-induced ITP. BALB/c CD61 knockout mice (CD61−/H-2d) were immunized against platelets from wild-type syngeneic BALB/c (CD61+/H-2d), allogeneic C57BL/6 (CD61+/H-2b), or C57BL/6 CD61 KO (CD61−/H-2b) mice, and their splenocytes were transferred into severe combined immunodeficient (SCID) mice to induce ITP. When nondepleted splenocytes were transferred to induce antibody-mediated ITP, both CD61+ platelet immunizations generated immunity that caused thrombocytopenia independently of allogeneic MHC molecules. In contrast, when B-cell–depleted splenocytes were transferred to induce T-cell–mediated ITP, transfer of allogeneic MHC-immunized splenocytes completely prevented CD61-induced ITP development. In addition, allogeneic platelet transfusions into SCID mice with established CD61-induced ITP rescued the thrombocytopenia. Compared with thrombocytopenic mice, bone marrow histology in the rescued mice showed normalized megakaryocyte morphology, and in vitro CD61-specific T-cell cytotoxicity was significantly suppressed. These results indicate that antibody-mediated ITP is resistant to allogeneic platelet transfusions, while the T-cell–mediated form of the disease is susceptible, suggesting that transfusion therapy may be beneficial in antibody-negative ITP.

Primate Recipients of Porcine Livers Develop Fatal Coagulopathy Despite Prevention of Thrombocytopenia

Background: While allogeneic liver transplantation has evolved to the standard of care for end-stage cirrhosis, it is severely limited by organ shortage. Previous attempts to pursue xenogeneic transplantation, placing GalT-KO swine livers into non-human primates, have yielded only short-term survival primarily ascribed to the immediate post-implantation thrombocytopenia observed leading to subsequent fatal coagulopathy. We have shown that aminocaproic acid (Amicar) dramatically preserves platelet levels, but that fatal hemorrhage still prevails. Methods: Three baboons received orthotropic hepatic xenografts from size-matched miniature swine under immunosuppression, proven adequate for xenotransplantation of other organs. Two baboons received, in addition, treatment with Amicar starting on POD 0 or 5 following transplantation. Results: The recipients survived, with good liver function, for 6, 8, and 9 days respectively. The platelet counts plummeted shortly after transplantation. In the first animal (B274), progressive platelet loss was unresponsive to transfusion of allogeneic platelets. In the second recipient (B291) Amicar was started on POD 5, following which platelet counts stabilized in the 30-60 k/μl range throughout a 9-day survival period, the longest reported to date. The third animal (B317) survived for 8 days with platelet numbers rescued to > 100 k/μl during continuous Amicar treatment started before reperfusion. Serial xenograft biopsies did not show any signs of rejection at any time point. Liver function parameters were within normal limits and the recipient animals appeared clinically well. Nevertheless, all animals eventually developed internal hemorrhage. The causes of death were therapy refractory coagulopathy, which in B291 and B317 possibly was exacerbated by enterococcal infection, detected in ascites cultures. Conclusions: These observations indicate for the first time that thrombocytopenia after liver xenotransplantation can be controlled by Amicar. The finding that fatal hemorrhage occurred despite satisfactory platelet levels, suggests that other incompatibilities between porcine and primate coagulation pathways may exist. Our results suggest that improved immunosuppressive regimens to reduce the risk of infection and additional measures to address coagulation factor incompatibilities will likely be required to achieve long-term survival of xenogeneic livers.Table: [Platelet count]

A journey to produce platelets in vitro

Allogeneic platelet transfusions protect patients from bleeding episodes and also make aggressive medical procedures such as those involving marrow transplants requiring chemotherapy and/or radiotherapy possible. These patients are dependent upon an unfailing supply of platelets that can sometimes be in short supply due to high demands coupled with an extremely short expiration date for platelet products of only 5 days. One approach that is under investigation to overcome platelet shortages is to harness the extraordinary capabilities of stem cells to proliferate and differentiate into various cell types and to use this ability to specifically produce clinical scale quantities of functional platelets in bioreactors. To accomplish such an enormous and complex task requires an appreciation of the regulatory mechanisms that occur during the development of megakaryocytes (MKs) and the subsequent biogenesis of functional platelets from mature MKs. This means understanding the complex network of intracellular and extracellular regulatory mechanisms that act at each phase of a developmental process that ushers stem cells along the MK lineage to produce billions of platelets per day in a healthy individual.

Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood transfusion

Concerns regarding the safety of transfused blood have generated considerable enthusiasm for the use of technologies intended to reduce the use of allogeneic blood (blood from an unrelated donor). Platelet-rich plasmapheresis (PRP) offers an alternative approach to blood conservation. To examine the evidence for the efficacy of PRP in reducing peri-operative allogeneic red blood cell (RBC) transfusion, and the evidence for any effect on clinical outcomes such as mortality and re-operation rates. We identified studies by searching MEDLINE (1950 to 2009), EMBASE (1980 to 2009), The Cochrane Library (Issue 1, 2009), the Internet (to March 2009) and the reference lists of published articles, reports, and reviews. Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to PRP, or to a control group which did not receive the intervention. Primary outcomes measured were: the number of patients exposed to allogeneic RBC transfusion, and the amount of RBC transfused. Other outcomes measured were: the number of patients exposed to allogeneic platelet transfusions, fresh frozen plasma, and cryoprecipitate, blood loss, re-operation for bleeding, post-operative complications (thrombosis), mortality, and length of hospital stay. Treatment effects were pooled using a random-effects model. Trial quality was assessed using criteria proposed by Schulz et al (Schulz 1995). Twenty-two trials of PRP were identified that reported data for the number of patients exposed to allogeneic RBC transfusion. These trials evaluated a total of 1589 patients. The relative risk (RR) of exposure to allogeneic blood transfusion in those patients randomised to PRP was 0.73 (95%CI 0.59 to 0.90), equating to a relative risk reduction (RRR) of 27% and a risk difference (RD) of 19% (95%CI 10% to 29%). However, significant heterogeneity of treatment effect was observed (p < 0.00001; I² = 79%). When the four trials by Boldt are excluded, the RR is 0.76 (95% CI 0.62 to 0.93). On average, PRP did not significantly reduce the total volume of RBC transfused (weighted mean difference [WMD] -0.69, 95%CI -1.93 to 0.56 units). Trials provided inadequate data regarding the impact of PRP on morbidity, mortality, and hospital length of stay. Trials were generally small and of poor methodological quality. Although the results suggest that PRP is effective in reducing allogeneic RBC transfusion in adult patients undergoing elective surgery, there was considerable heterogeneity of treatment effects and the trials were of poor methodological quality. The available studies provided inadequate data for firm conclusions to be drawn regarding the impact of PRP on clinically important endpoints.

The Yin and Yang of Blood Transfusions in Cardiac Surgery

JAMA Variation and Use of Blood Transfusion in Coronary Bypass Graft Surgery Elliott Bennett-Guerrero, MD; Yue Zhao, PhD; Sean M. O’Brien, PhD; T. B. Ferguson Jr, MD; Eric D. Peterson, MD, MPH; James S. Gammie, MD; Howard K. Song, MD, PhD Context: Perioperative blood transfusions are costly and have safety concerns. As a result, there have been multiple initiatives to reduce transfusion use. However, the degree to which perioperative transfusion rates vary among hospitals is unknown. Objective: To assess hospital-level variation in use of allogeneic red blood cell (RBC), fresh-frozen plasma, and platelet transfusions in patients undergoing coronary artery bypass graft (CABG) surgery. Design, Setting, and Patients: An observational cohort of 102 470 patients undergoing primary isolated CABG surgery with cardiopulmonary bypass during calendar year 2008 at 798 sites in the United States, contributing data to the Society of Thoracic Surgeons Adult Cardiac Surgery Database. Main Outcome Measures: Perioperative (intraoperative and postoperative) transfusion of RBCs, fresh-frozen plasma, and platelets. Results: At hospitals performing at least 100 on-pump CABG operations (82 446 cases at 408 sites), the rates of blood transfusion ranged from 7.8% to 92.8% for RBCs, 0% to 97.5% for fresh-frozen plasma, and 0.4% to 90.4% for platelets. Multivariable analysis including data from all 798 sites (102 470 cases) revealed that after adjustment for patient-level risk factors, hospital transfusion rates varied by geographic location (P = .007), academic status (P = .03), and hospital volume (P Conclusion: Wide variability occurred in the rates of transfusion of RBCs and other blood products, independent of case mix, among patients undergoing CABG surgery with cardiopulmonary bypass in US hospitals in an adult cardiac surgical database.

Platelet transfusions have a negative impact on liver transplant survival

Background Intraoperative transfusion of red blood cells (RBC) is associated with adverse outcome after orthotopic liver transplantation (OLT). Although experimental studies have shown that platelets contribute to reperfusion injury of the liver, the influence of allogeneic platelet transfusion on outcome has not been studied in detail. In this study, we evaluate the impact of various blood products on outcome after OLT. Methods Twenty-nine variables, including blood product transfusions, were studied in relation to outcome in 433 adult patients undergoing a first OLT between 1989 and 2004. Data were analyzed using uni- and multivariate stepwise Cox's proportional hazards analyses, as well as propensity score-adjusted analyses for platelet transfusion to control for selection bias in the use of blood products. Results The proportion of patients receiving transfusion of any blood component decreased from 100% in the period 1989-1996 to 74% in the period 1997-2004. In uni- and multivariate analyses, the indication for transplantation, transfusion of platelets and RBC were highly dominant in predicting 1-yr patient survival. These risk factors were independent from well-accepted indices of disease, such as the Model for End-Stage Liver Disease score and Karnofsky score. The effect on 1-yr survival was dose-related with a hazard ratio of 1.377 per unit of platelets (P = 0.01) and 1.057 per unit of RBC (P = 0.001). The negative impact of platelet transfusion on survival was confirmed by propensity-adjusted analysis. Conclusion This retrospective study indicates that, in addition to RBC, platelet transfusions are an independent risk factor for survival after OLT. These findings have important implications for transfusion practice in liver transplant recipients.

The Impact of Intraoperative Transfusion of Platelets and Red Blood Cells on Survival After Liver Transplantation

Intraoperative transfusion of red blood cells (RBC) is associated with adverse outcome after orthotopic liver transplantation (OLT). Although experimental studies have shown that platelets contribute to reperfusion injury of the liver, the influence of allogeneic platelet transfusion on outcome has not been studied in detail. In this study, we evaluate the impact of various blood products on outcome after OLT. Twenty-nine variables, including blood product transfusions, were studied in relation to outcome in 433 adult patients undergoing a first OLT between 1989 and 2004. Data were analyzed using uni- and multivariate stepwise Cox's proportional hazards analyses, as well as propensity score-adjusted analyses for platelet transfusion to control for selection bias in the use of blood products. The proportion of patients receiving transfusion of any blood component decreased from 100% in the period 1989-1996 to 74% in the period 1997-2004. In uni- and multivariate analyses, the indication for transplantation, transfusion of platelets and RBC were highly dominant in predicting 1-yr patient survival. These risk factors were independent from well-accepted indices of disease, such as the Model for End-Stage Liver Disease score and Karnofsky score. The effect on 1-yr survival was dose-related with a hazard ratio of 1.377 per unit of platelets (P = 0.01) and 1.057 per unit of RBC (P = 0.001). The negative impact of platelet transfusion on survival was confirmed by propensity-adjusted analysis. This retrospective study indicates that, in addition to RBC, platelet transfusions are an independent risk factor for survival after OLT. These findings have important implications for transfusion practice in liver transplant recipients.

New Strategies for the Optimal Use of Platelet Transfusions

Patients with severe thrombocytopenia are presumed to be at increased risk for bleeding, and consequently it has been standard practice for the past four decades to give allogeneic platelet transfusions to severely thrombocytopenic patients as supportive care. Platelet transfusions may be given either prophylactically to reduce the risk of bleeding, in the absence of clinical hemorrhage (prophylactic transfusions), or to control active bleeding when present (therapeutic transfusions). While no one would argue with the need for platelet transfusions in the face of severe bleeding, important questions remain about what constitutes clinically significant bleeding and whether a strategy of prophylactic platelet transfusions is effective in reducing the risk of bleeding in clinically stable patients. It is now uncommon for patients undergoing intensive chemotherapy or bone marrow transplantation to die of hemorrhage, but it is open to debate as to what degree platelet transfusions have been responsible for this change in outcome, given the many other advances in other aspects of supportive care. If a prophylactic strategy is followed, the optimal transfusion trigger or quantity of platelets to be transfused prophylactically per transfusion episode needs to be addressed in adequately powered clinical trials, but these remain highly controversial issues. This is because, until recently, there have been few high-quality, prospective, randomized clinical trial (RCT) data for evaluating the relative effects of different platelet transfusion regimens or platelet doses on clinical outcomes. Moreover, most of these RCTs have not used bleeding as the primary outcome measure. Two such studies on platelet dose have now been undertaken, the PLADO (Prophylactic PLAtelet DOse) and the SToP (Strategies for the Transfusion of Platelets) trials. Data from these RCTs are not contained in this overview, as these data have not yet been completely analyzed or submitted for peer review publication. In addition to the above, several recent observational studies have raised the possibility that there is not a clear association between the occurrence of a major clinical bleeding episode and the platelet count in thrombocytopenic patients. Such findings have led to the questioning of the efficacy of prophylactic platelet transfusions in all clinically stable patients, and whether a policy of therapeutic transfusions used only when patients have clinical bleeding might be as effective and safe for selected patients. At least two RCTs evaluating the relative value of prophylactic versus therapeutic platelet transfusions have been initiated in thrombocytopenic patients with hematological malignancies. One such study, known as the TOPPS (Trial of Prophylactic Platelets Study) study, is currently underway in the U.K.