Consensus guidelines for the management of adult immune thrombocytopenia in Australia and New Zealand.

INTRODUCTION: The absence of high quality evidence for basic clinical dilemmas in immune thrombocytopenic purpura (ITP) underlines the need for contemporary guidelines relevant to the local treatment context. ITP is diagnosed by exclusions, with a hallmark laboratory finding of isolated thrombocytopenia. MAIN RECOMMENDATIONS: Bleeding, family and medication histories and a review of historical investigations are required to gauge the bleeding risk and possible hereditary syndromes. Beyond the platelet count, the decision to treat is affected by individual bleeding risk, disease stage, side effects of treatment, concomitant medications, and patient preference. Treatment is aimed at achieving a platelet count > 20 × 109 /L, and avoidance of severe bleeding. Steroids are the standard first line treatment, with either 6-week courses of tapering prednisone or repeated courses of high dose dexamethasone providing equivalent efficacy. Intravenous immunoglobulin can be used periprocedurally or as first line therapy in combination with steroids. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: There is no consensus on choice of second line treatments. Options with the most robust evidence include splenectomy, rituximab and thrombopoietin receptor agonists. Other therapies include azathioprine, mycophenolate mofetil, dapsone and vinca alkaloids. Given that up to one-third of patients achieve a satisfactory haemostatic response, splenectomy should be delayed for at least 12 months if possible. In life-threatening bleeding, we recommend platelet transfusions to achieve haemostasis, along with intravenous immunoglobulin and high dose steroids.

Quality of evidence-based guidelines for platelet transfusion and use: A systematic review.

BACKGROUND: Guidelines for platelet (PLT) transfusion are an important source of information for clinicians. Although guidelines intend to increase consistency and quality of care, variation in methodology and recommendations may exist that could impact the value of a guideline. We aimed to determine the quality of existing PLT transfusion guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument and to describe the inconsistencies in recommendations. STUDY DESIGN AND METHODS: A systematic search was undertaken for evidence-based guidelines from January 1, 2013, to January 25, 2019. Citations were reviewed in duplicate for inclusion and descriptive data extracted. Four physicians appraised the guideline using the AGREE II instrument and the scaled score for each item evaluated was calculated. The protocol was registered in PROSPERO. RESULTS: Of 6744 citations, 6740 records were screened. Seven of 28 full-text studies met the inclusion criteria. The median scaled score (and the interquartile range of the scaled score) for the following items were as follows: scope and purpose, 94% (8%); stakeholder involvement, 63% (18%); rigor of development, 83% (14%); clarity of presentation, 94% (6%); applicability, 58% (20%); and editorial independence, 77% (4%). Overall quality ranged from 4 to 7 (7 is the maximum score). Inconsistent recommendations were on prophylactic PLT transfusion in hypoproliferative thrombocytopenia in the presence of risk factors and dose recommendations. CONCLUSION: Inconsistencies between guidelines and variable quality highlight areas for future guideline writers to address. Areas of specific attention include issues of stakeholder involvement and applicability.

Evaluating the appropriateness of platelet transfusions compared with evidence-based platelet guidelines: An audit of platelet transfusions at 57 hospitals.

BACKGROUND: Platelet transfusions are used to prevent or control bleeding in patients with thrombocytopenia or platelet dysfunction. The pretransfusion platelet count threshold has been studied extensively in multiple patient settings yielding high-quality evidence that has been summarized in several comprehensive evidence-based platelet guidelines. STUDY DESIGN AND METHODS: A prospective 12-week audit of consecutive platelet transfusions using validated and evidence-based adjudication criteria was conducted. Patient demographic, laboratory, and transfusion details were collected with an electronic audit tool. Each order was adjudicated either electronically or independently by two transfusion medicine physicians. The aim was to determine platelet transfusion appropriateness and common scenarios with deviations from guidelines. RESULTS: Fifty-seven (38%) of 150 hospitals provided data on 1903 platelet orders, representing 90% of platelet usage in the region during the time period. Overall, 702 of 1693 adult (41.5%) and 133 of 210 pediatric orders (63.3%) were deemed inappropriate. The most common inappropriate platelet order was for prophylaxis in the absence of bleeding or planned procedure in patients with hypoproliferative thrombocytopenia and a platelet count over 10 x 109 /L (53% of inappropriate orders in adults and 45% in pediatrics). Platelet transfusions ordered with either a preprinted transfusion order set (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.44-2.73) or technologist prospective screening (OR, 1.40; 95% CI, 1.10-1.78) were more likely to be appropriate. CONCLUSION: There is a discrepancy between clinical practice and evidence-based platelet guidelines. Broad educational and system changes will be needed to align platelet transfusion practice with guideline recommendations.

Buffy coat platelets coming to America: Are we ready?

BACKGROUND: Buffy coat (BC) platelets (PLTs) have been used globally for many years. In 2004 Canadian Blood Services (CBS) made the decision to transition from PLT-rich plasma (PRP) to BC PLTs. We reviewed the benefits and manufacture process of BC and the implementation challenges involved. STUDY DESIGN AND METHODS: A literature review was performed in the following areas: BC efficacy, donor population shifts, production and good stewardship of PLTs, logistic considerations with overnight holds, advantages of the overnight hold, the CBS experience, licensure and standards, and changes needed to produce BC PLTs in the United States. The aim was to analyze current practice and identify possible actions for blood centers and hospitals. RESULTS: Implementation of BC would offer an additional source of PLTs to address the growing elderly population and the declining apheresis donor base. Substantial logistic, operational, and financial benefits were seen when CBS transitioned to BC with overnight hold. CONCLUSIONS: Buffy coat blood products are widely used throughout the world. Recent conversion from PRP to BC by CBS showed that conversion can be accomplished with planning, communication, and partnership from all stakeholders. In conclusion, BC PLTs are worth serious consideration in the United States, but regulatory barriers in the United States will need to be addressed.

How do we implement pathogen reduction technology, while maintaining an adequate platelet inventory for our patients?

Despite the significantly reduced infectious disease risk through robust and sensitive laboratory assays, comprehensive donor screening and good manufacturing practices, new and emerging infectious agents and bacterial contamination continue to pose a threat to the blood supply. Pathogen Reduction (PR) technology is an option to mitigate the risk of platelet transfusion transmitted infections. Here we describe our structure and strategies to implement PR technology. Pre-implementation and phased approach implementation processes from our hospital-based donor center, components processing laboratory, transfusion service, clinicians, nursing, and patient perspectives are described. Communication and reassessment of collection settings occurred between the donor center and components processing laboratory (CPL). During Phase 1, CPL consistently processed approximately 56% of monthly apheresis platelets (AP) collections by PR and the remaining 44% as conventional platelets (CP). Phase 2 increased the amount of AP undergoing PR from 56% to approximately 78%. A phased implementation and maintenance of a dual inventory may provide flexibility to blood collection, blood manufacturing, and transfusion service processes. Our dual inventory of PR and CP allows our transfusion service a readily available platelet inventory. A collaborative hospital-based donor center, component processing laboratory, and transfusion service are essential to the productivity and maintenance of the dual platelet inventory.

The impact of the sample time of secondary bacterial culture on the risk of exposure to contaminated platelet components: A mathematical analysis.

BACKGROUND: The US Food and Drug Administration (FDA) issued a guidance for bacterial risk control strategies for platelet components in September 2019 that includes strategies using secondary bacterial culture (SBC). While an SBC likely increases safety, the optimal timing of the SBC is unknown. Our aim was to develop a model to provide insight into the best time for SBC sampling. STUDY DESIGN AND METHODS: We developed a mathematical model based on the conditional probability of a bacterial contamination event. The model evaluates the impact of secondary culture sampling time over a range of bacterial contamination scenarios (lag and doubling times), with the primary outcome being the optimal secondary sampling time and the associated risk. RESULTS: Residual risk of exposure decreased with increasing inoculum size, later sampling times for primary culture, and using higher thresholds of exposure (in colony-forming units per milliliter). Given a level of exposure, the optimal sampling time for secondary culture depended on the timing of primary culture and on the expiration time. In general, the optimal sampling time for secondary culture was approximately halfway between the time of primary culture and the expiration time. CONCLUSION: Our model supports that the FDA guidance is quite reasonable and that sampling earlier in the specified secondary culture windows may be most optimal for safety.

Platelet Reactivity Testing for Aspirin Patients Who Sustain Traumatic Intracranial Hemorrhage.

BACKGROUND: Patients who take aspirin and sustain traumatic intracranial hemorrhage (tICH) are often transfused platelets in an effort to prevent bleeding progression. The efficacy of platelet transfusion is questionable, however, and some medical societies recommend that platelet reactivity testing (PRT) should guide transfusion decisions. The study hypothesis was that utilization of PRT to guide platelet transfusion for tICH patients suspected of taking aspirin would safely identify patients who did not require platelet transfusion. METHODS: This was a retrospective study of patients with blunt tICH who received PRT for known or suspected aspirin use between June 2014 and December 2017 at a level I trauma center. Chart abstraction was conducted to determine home aspirin status, and PRT values were used to classify patients as therapeutic or nontherapeutic on aspirin. Differences were assessed with Kruskal-Wallis and chi-square tests. RESULTS: 157 patients met study inclusion criteria, and 118 (75%) patients had documented prior aspirin use. PRT results were available approximately 1.7 h (IQR: 0.9, 3.2) after arrival. Upon initial PRT, 70% of patients were considered inhibited and 88% of those patients had aspirin documented as a home medication. Conversely, 18% of patients with home aspirin use had normal platelet reactivity. Clinically significant worsening of the tICH did not significantly differ when comparing those who received platelet transfusion with those who did not (8% versus 7%, P = 0.87). CONCLUSIONS: Platelet reactivity testing can detect platelet inhibition related to aspirin and should guide transfusion decisions for head injured patients in the initial hours after trauma.

Platelets from donors with consistently low HLA-B8, -B12, or -B35 expression do not undergo antibody-mediated internalization.

Patients refractory to platelet transfusions because of alloimmunization require HLA-matched platelets, which is only possible if a large HLA-typed donor pool is available. However, even then, patients with broad immunization or rare haplotypes may not have suitable donors. In these patients, transfusions with platelets showing low HLA class I expression may be an alternative to fully HLA-matched transfusions. In this study, we quantified the proportion of donors with consistently low HLA-B8, -B12, and -B35 expression on platelets using human monoclonal antibodies specific for these antigens. Furthermore, as model for in vivo clearance, antibody-mediated internalization of these platelets by macrophages was investigated. The expression of HLA-B8, -B12, or -B35 on platelets was extremely variable between individuals (coefficients of variation, 41.4% to 73.6%). For HLA-B8, but not for HLA-B12 or -B35, this variation was in part explained by zygosity. The variation was most pronounced in, but not exclusive to, platelets. Expression within one donor was consistent over time. Remarkably, 32% of 113 HLA-B8, 34% of 98 HLA-B12, and 9% of 66 HLA-B35 donors showed platelet antigen expression that was not or only minimally above background. Antibody-mediated internalization of platelets by macrophages correlated with antibody opsonization and antigen expression and was absent in platelets with low or minimal HLA expression. In conclusion, our findings indicate that a substantial proportion of donors have platelets with consistently low expression of specific HLA class I antigens. These platelets may be used to treat refractory patients with antibodies directed against these particular antigens, despite HLA mismatches.

How do you decide which platelet bacterial risk mitigation strategy to select for your hospital-based transfusion service?

The United States Food and Drug Administration Final Guidance for Industry titled, "Bacterial Risk Control Strategies for Blood Collection Establishments and Transfusion Services to Enhance the Safety and Availability of Platelets for Transfusion" provides nine strategies for platelet bacterial risk mitigation. Even if it is assumed all strategies are comparable in terms of safety and efficacy, the decision of which to implement remains challenging. Some additional factors that warrant evaluation before selecting a strategy include the financial impact, process for implementation, logistics upon implementation, institutional acceptance by blood bank staff, administration and clinicians, and effect on platelet availability. To assist with this difficult choice, a panel of transfusion service physicians who have expertise on the topic and have already selected strategies for their transfusion services were recruited to provide varied perspectives. In addition, the use of a decision-making tool that objectively evaluates defined criteria for assessment of the nine strategies is described.

Ensuring HLA-matched platelet support requires an ethnic diverse donor population.

BACKGROUND: Patients refractory for platelet transfusions benefit from human leukocyte antigen (HLA)-matched platelet transfusions. Differences in ethnic background of patients and donors could hamper the availability of sufficient numbers of HLA-matched donors for all patients. We evaluated our HLA-matched donor program and explored the role of ethnic background of patients related to the number of available donors. METHODS: We performed a cohort study among consecutive patients who received HLA-matched platelet concentrates in the Netherlands between 1994 and 2017. The number of available matched donors was determined per patient. Haplotypes were constructed from genotypes with computer software (PyPop). Based on haplotypes, HaploStats, an algorithm from the National Marrow Donor Program, was used to assess the most likely ethnic background for patients with 5 or fewer and 30 or more donors. RESULTS: HLA typing was available for 19,478 donors in September 2017. A total of 1206 patients received 12,350 HLA-matched transfusions. A median of 83 (interquartile range, 18-266) donors were available per patient. For 95 (10.3%) patients, 5 or fewer donors were available. These patients were more likely to have an African American background, whereas patients with 30 or more donors were more often from Caucasian origin, compared with Caucasian origin for patients with 30 donors. CONCLUSION: Adequate transfusion support could be guaranteed for most but not all refractory patients. More non-Caucasian donors are required to ensure the availability of HLA-matched donors for all patients in the Netherlands.

Neonatal and pediatric platelet transfusions: current concepts and controversies.

PURPOSE OF REVIEW: In this review, we focus on three specific concepts related to platelet transfusion in the neonatal and pediatric population: choice of transfusion threshold; use of ABO-mismatched platelets; transfusion of pathogen-reduced or inactivated platelets. RECENT FINDINGS: Recent trials support the use of lower platelet transfusion thresholds (25 000/µl) in preterm neonates, although data is limited to guide transfusion among more mature neonates. In children, there is low-level evidence as to what the prophylactic platelet transfusion threshold should be in many situations of thrombocytopenia, revealing major variability in platelet transfusion practices. Most pediatric guidelines are extrapolated from adult studies with the most evidence in treatment-associated hypoproliferative thrombocytopenia varying between a platelet transfusion threshold of 10 000/µl to 20 000/µl. Although pathogen-reduced platelets may lower the risks of transfusion-transmitted infection, the effects on platelet refractoriness and transfusion burden in this population warrant additional study. SUMMARY: Our review highlights recent advances in neonatal and pediatric platelet transfusion and also emphasizes the urgent need for better evidence to guide practice given recent studies showing the potential harms of platelet transfusion, particularly with liberal use.

Transfusion of pathogen-reduced platelet components without leukoreduction.

BACKGROUND: Leukoreduction (LR) of platelet concentrate (PC) has evolved as the standard to mitigate risks of alloimmunization, clinical refractoriness, acute transfusion reactions (ATRs), and cytomegalovirus infection, but does not prevent transfusion-associated graft-versus-host disease (TA-GVHD). Amotosalen-ultraviolet A pathogen reduction (A-PR) of PC reduces risk of transfusion-transmitted infection and TA-GVHD. In vitro data indicate that A-PR effectively inactivates WBCs and infectious pathogens. STUDY DESIGN AND METHODS: A sequential cohort study evaluated A-PR without LR, gamma irradiation, and bacterial screening in hematopoietic stem cell transplant (HSCT) recipients. The first cohort received conventional PC (control) processed without LR, but with gamma irradiation and bacterial screening. The second cohort received A-PR PC (test) processed without: LR, bacterial screening, or gamma irradiation. The primary efficacy outcome was the 1-hour corrected count increment. The primary safety outcome was treatment-emergent ATR. Secondary outcomes included clinical refractoriness, and 100-day status for engraftment, TA-GVHD, HSCT-GVHD, infections, and mortality. RESULTS: Mean corrected count increment (× 103 ) of 33 test PC recipients was similar (18.9 ± 8.8 vs. 16.6 ± 8.4; p = 0.296) to that of 31 control PC recipients. Test recipients had a reduced, but nonsignificant, incidence of ATR (test = 9.1%, Control = 19.4%; p = 0.296). The frequencies of clinical refractoriness (0 of 33 vs. 4 of 31 patients) and refractory transfusions (6.6% vs. 19.3%) were lower in the test cohort (p = 0.05 and 0.02), respectively. No patient in either cohort had TA-GVHD. Day 100 engraftment, HSCT-GVHD, mortality, and infectious disease complications were similar between cohorts. CONCLUSIONS: This study indicated that A-PR PC without LR, gamma irradiation, or bacterial screening is feasible for support of HSCT.

Implementation of a patient blood management program in hematopoietic stem cell transplantation (Editorial, p. 2763).

BACKGROUND: Recipients of hematopoietic stem cell transplantation (HSCT) are among the highest consumers of allogeneic red blood cell (RBC) and platelet (PLT) components. The impact of patient blood management (PBM) efforts on HSCT recipients is poorly understood. STUDY DESIGN AND METHODS: This observational study assessed changes in blood product use and patient-centered outcomes before and after implementing a multidisciplinary PBM program for patients undergoing HSCT at a large academic medical center. The pre-PBM cohort was treated from January 1 through September 31, 2013; the post-PBM cohort was treated from January 1 through September 31, 2015. RESULTS: We identified 708 patients; 284 of 352 (80.7%) in the pre-PBM group and 225 of 356 (63.2%) in the post-PBM group received allogeneic RBCs (p < 0.001). Median (interquartile range [IQR]) RBC volumes were higher before PBM than after PBM (3 [2-4] units vs. 2 [1-4] units; p = 0.004). A total of 259 of 284 pre-PBM patients (91.2%) and 57 of 225 (25.3%) post-PBM patients received RBC transfusions when hemoglobin levels were more than 7 g/dL (p < 0.001). The median (IQR) PLT transfusion quantities was 3 (2-5) units for pre-PBM patients and 2 (1-4) units for post-PBM patients (p < 0.001). For patients with PLT counts of more than 10 × 109 /L, a total of 1219 PLT units (73.4%) were transfused before PBM and 691 units (48.8%) were transfused after PBM (p < 0.001). Estimated transfusion expenditures were reduced by $617,152 (18.3%). We noted no differences in clinical outcomes or transfusion-related adverse events. CONCLUSION: Patient blood management implementation for HSCT recipients was associated with marked reductions in allogeneic RBC and PLT transfusions and decreased transfusion-related costs with no detrimental impact on clinical outcomes.

A novel approach using ancillary tests to guide treatment of Glanzmann thrombasthenia patients undergoing surgical procedures.

BACKGROUND: Glanzmann thrombasthenia (GT) is a disorder of platelet function. Standard therapy includes platelet transfusions, which may be hampered by antiplatelet antibodies. AIMS: To assess potential correlation between bleeding and number of active platelets in GT patients undergoing surgery. Clinical peri- operative patients' hemostasis was compared with flow cytometry analysis (FC), and whole blood clot formation. METHODS: GT patients undergoing surgery were included. Blood counts, platelet activation studies, FC and rotational thromboelastography (ROTEM) were performed as ancillary tests to estimate the effectiveness of treatment. RESULTS: A total of 4 GT patients undergoing 5 surgeries were included. Consecutive FC analysis following platelet transfusions showed gradual decrease of donor platelets with a nadir of 3280 platelets in patients who experienced no post procedural bleeding following minor procedures. After major surgery, bleeding occurred when donor platelets decreased to 2600-4280. Decline in donor platelets was associated with reduced clot firmness as noted by ROTEM. CONCLUSION: Results suggest that very low number of active donor platelets may suffice to achieve proper hemostasis in certain procedures. Our study points to the potential role of consecutive FC examinations to demonstrate the number of donor platelets as an ancillary tool for decision making in GT patients undergoing surgery.

Standardization of prophylactic platelet transfusion dosing in a pediatric oncology population: a quality improvement project.

BACKGROUND: Oncology patients are frequent recipients of prophylactic platelet transfusions. Recent studies have demonstrated that lower prophylactic doses of platelets were not associated with a higher incidence of bleeding. At our institution, we found wide variation in platelet dosing due to lack of guidance and support for standardized dosing. STUDY DESIGN AND METHODS: A collaborative process improvement project between oncology, hematology, intensivists, and the transfusion service established guidelines for dosing of prophylactic platelet transfusions in nonbleeding oncology patients: 10 mL/kg or less of apheresis platelets for patients weighing up to 20 kg and 1 unit of apheresis platelets patients weighing 20 kg or more, with our stated goal of standardizing transfusion practice. A graphic data display tool that draws on the electronic medical record to monitor platelet ordering was created, with a target goal of greater than 80% compliance with the dosing guidelines. We implemented decision support for dosing consistent with the guideline, and provided educational materials to prescribers at various levels of training within oncology over multiple plan-do-study-act cycles. RESULTS: We were able to consistently achieve between 85 and 90% compliance of prophylactic platelet transfusion orders without an increase in the number of emergency department visits for bleeding or platelet transfusions or changing the time between platelet transfusions after guideline implementation. CONCLUSION: This project demonstrates that reducing the volume of prophylactic platelet transfusions to doses consistent with published studies was safe and that a process of guideline consensus based on published studies, well-designed decision support for computerized physician order entry, and targeted educational efforts, were effective in changing practice at a large academic hospital.

Factors related to the outcome of prophylactic platelet transfusions in patients with hematologic malignancies: an observational study.

BACKGROUND: A better knowledge of the connections between platelet concentrate (PC) characteristics and transfusion outcomes in day-to-day practice would help improve the selection process of the most appropriate PC. STUDY DESIGN AND METHODS: In this study of prophylactic platelet transfusions in patients with hematologic malignancies between 2002 and 2012, outcome criteria were corrected count increments (CCIs) and platelet transfusion intervals (TIs, in days). Studied characteristics were ABO matching status, platelet source, dose, storage duration, irradiation, washing, and transfusion sequence number (TSN). The analysis consisted of multivariable linear mixed-effects models with adjustments for patient diagnosis, sex, and type of treatment. RESULTS: Overall, 869 patients and 6662 platelet transfusions were analyzed. For each day after the second day of storage, the CCI and TI decreased by 0.88 and 0.06 day, respectively. Compared to ABO-identical, transfusion with major ABO-incompatible PCs decreased the CCI and TI by 0.79 and 0.21 day, respectively. Platelet washing reduced the CCI and TI by 2.28 and 0.24 day, respectively. There was no significant association between platelet source or irradiation and CCI or TI. TI increased as the platelet dose per kg increased. Both CCI and TI decreased as the TSN increased. CONCLUSION: Transfusion outcomes were significantly related to several PC-related factors. Associations for ABO matching status and storage duration were stronger than previously reported. Taking into account such factors when selecting a PC for transfusion could be beneficial to the recipient.

A multicentred study to validate a consensus bleeding assessment tool developed by the biomedical excellence for safer transfusion collaborative for use in patients with haematological malignancy.

BACKGROUND: There continues to be uncertainty about the optimal approach to documenting bleeding data in platelet transfusion trials, with a desire to apply a common assessment tool across all trials. With this in mind, a consensus bleeding assessment tool (BAT) has been developed by the Biomedical Excellence for Safer Transfusion (BEST) collaborative, based on review of data collection forms used in published randomized trials and following content validation with a range of healthcare professionals at seven haematology centres through BEST members. This study aimed to evaluate reliability and reproducibility of the consensus BAT. METHODS: Replicated clinical assessments of bleeding were undertaken by participants with haematological malignancies recruited at four haematology centres in an international, multicentred, observational study. Concordance of repeat assessments was calculated for agreement in site and grade of bleeding observed. RESULTS: Forty patients consented to participate, and 13 trained bleeding assessors collected these data. Bleeding assessments were carried out on 113 separate days. Of all 225 bleeding assessments, 204 were compared for grade concordance, and 160 were compared for site concordance. There was very good grade concordance (83%, 95% confidence interval 74-93%) and good bleeding site concordance (69%, 95% confidence interval 57-79%) in observations of bleeding. Discordance was primarily in relation to assessing skin bleeding. CONCLUSIONS: Alongside a structured training programme, levels of concordance for a consensus BAT were high. Researchers using assessment tools for bleeding need to balance comprehensive data collection against potential loss of accuracy for some types of bleeding, such as skin findings.

Platelet storage duration and its clinical and transfusion outcomes: a systematic review.

BACKGROUND: Platelets (PLTs) are usually stored for up to 5 days prior to transfusion, although in some blood services the storage period is extended to 7 days. During storage, changes occur in both PLT and storage medium, which may lead to PLT activation and dysfunction. The clinical significance of these changes remains uncertain. METHODS: We performed a systematic review to assess the association between PLT storage time and clinical or transfusion outcomes in patients receiving allogeneic PLT transfusion. We searched studies published in English between January 2000 and July 2017 identified from MEDLINE, Embase, PubMed and the Cochrane Libraries. RESULTS: Of the 18 studies identified, five included 4719 critically ill patients (trauma, post-cardiac surgery and a heterogeneous population of critically ill patients) and 13 included 8569 haematology patients. The five studies in critically ill patients were retrospective and did not find any association between PLT storage time when PLTs were stored for up to 5 days and mortality. There was also no association between older PLTs and sepsis in the two largest studies (n = 4008 patients). Of the 13 studies in haematology patients, seven analysed prolonged storage time up to 6.5 or 7 days. Administration of fresh PLTs (less than 2 or 3 days) was associated with a significant increase in corrected count increment (CCI) compared to older PLTs in seven of the eight studies analysing this outcome. One single centre retrospective study found an increase in bleeding events in patients receiving older PLTs. CONCLUSIONS: PLT storage time does not appear to be associated with clinical outcomes, including bleeding, sepsis or mortality, in critically ill patients or haematology patients. The freshest PLTs (less than 3 days) were associated with a better CCI, although there was no impact on bleeding events, questioning the clinical significance of this association. However, there is an absence of evidence to draw definitive conclusions, especially in critically ill patients.

Bacterial contamination of platelets for transfusion: strategies for prevention.

Platelet transfusions carry greater risks of infection, sepsis, and death than any other blood product, owing primarily to bacterial contamination. Many patients may be at particular risk, including critically ill patients in the intensive care unit. This narrative review provides an overview of the problem and an update on strategies for the prevention, detection, and reduction/inactivation of bacterial contaminants in platelets. Bacterial contamination and septic transfusion reactions are major sources of morbidity and mortality. Between 1:1000 and 1:2500 platelet units are bacterially contaminated. The skin bacterial microflora is a primary source of contamination, and enteric contaminants are rare but may be clinically devastating, while platelet storage conditions can support bacterial growth. Donor selection, blood diversion, and hemovigilance are effective but have limitations. Biofilm-producing species can adhere to biological and non-biological surfaces and evade detection. Primary bacterial culture testing of apheresis platelets is in routine use in the US. Pathogen reduction/inactivation technologies compatible with platelets use ultraviolet light-based mechanisms to target nucleic acids of contaminating bacteria and other pathogens. These methods have demonstrated safety and efficacy and represent a proactive approach for inactivating contaminants before transfusion to prevent transfusion-transmitted infections. One system, which combines ultraviolet A and amotosalen for broad-spectrum pathogen inactivation, is approved in both the US and Europe. Current US Food and Drug Administration recommendations advocate enhanced bacterial testing or pathogen reduction/inactivation strategies (or both) to further improve platelet safety. Risks of bacterial contamination of platelets and transfusion-transmitted infections have been significantly mitigated, but not eliminated, by improvements in prevention and detection strategies. Regulatory-approved technologies for pathogen reduction/inactivation have further enhanced the safety of platelet transfusions. Ongoing development of these technologies holds great promise.

Pathogen reduction technologies: The pros and cons for platelet transfusion.

The transfusion of platelets is essential for diverse pathological conditions associated with thrombocytopenia or platelet disorders. To maintain optimal platelet quality and functions, platelets are stored as platelet concentrates (PCs) at room temperature under continuous agitation-conditions that are permissive for microbial proliferation. In order to reduce these contaminants, pathogen reduction technologies (PRTs) were developed by the pharmaceutical industry and subsequently implemented by blood banks. PRTs rely on chemically induced cross-linking and inactivation of nucleic acids. These technologies were initially introduced for the treatment of plasma and, more recently, for PCs given the absence of a nucleus in platelets. Several studies verified the effectiveness of PRTs to inactivate a broad array of bacteria, viruses, and parasites. However, the safety of PRT-treated platelets has been questioned in other studies, which focused on the impact of PRTs on platelet quality and functions. In this article, we review the literature regarding PRTs, and present the advantages and disadvantages related to their application in platelet transfusion medicine.