Adult extracorporeal membrane oxygenation: an international survey of transfusion and anticoagulation techniques.

BACKGROUND AND OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is a method of life support for either isolated cardiac failure or respiratory failure, with or without cardiac failure. When used for hemodynamic support, the ECMO circuit presents a non-endothelialized, artificial surface to blood inciting an inflammatory response which activates haemostatic pathways. Anticoagulation may complicate a pre-existing coagulopathy and/or inadequate surgical hemostasis of varying severity. There is no standardized method to achieve and monitor anticoagulation or guide transfusion therapy during ECMO. We tested the hypothesis that institutions across the world conduct similar management of anticoagulation and transfusion during adult ECMO support. METHODS: This is a descriptive, self-reporting cross-sectional survey of anticoagulation and transfusion practice for patients age 18 or older on ECMO. This 38 multiple-choice question survey was sent to 166 institutions, internationally, utilizing adult ECMO. About 32·4% (54) of institutions responded. Responses were anonymously collected. Descriptive analyses were calculated. RESULTS: Our findings indicate there appears to be a significant practice variation among institutions regarding anticoagulation and transfusion during adult ECMO support. DISCUSSION: The lack of standard practices among institutions may reflect a paucity of data regarding optimal anticoagulation and transfusion for patients requiring ECMO. Standardized protocols for anticoagulation and transfusion may help increase quality of care for and reduce morbidity, mortality and cost to patients and healthcare centres. Further study is required for standardized, high quality care.

Incidence and clinical characteristics of transfusion-associated circulatory overload using an active surveillance algorithm.

BACKGROUND: The concordance of haemovigilance criteria developed for surveillance of transfusion-associated circulatory overload (TACO) with its clinical diagnosis has not been assessed. In a pilot study to evaluate an electronic screening algorithm, we sought to examine TACO incidence and application of haemovigilance criteria in patients with post-transfusion pulmonary oedema. STUDY DESIGN AND METHODS: From June to September 2014, all transfused adult inpatients at four academic hospitals were screened with an algorithm identifying chest radiographs ordered within 12 h of blood component release. Patients with post-transfusion pulmonary oedema underwent case adjudication by an expert panel. TACO incidence was calculated, and clinical characteristics were compared with other causes of post-transfusion pulmonary oedema. RESULTS: Among 4932 transfused patients, there were 3412 algorithm alerts, 50 cases of TACO and 47 other causes of pulmonary oedema. TACO incidence was 1 case per 100 patients transfused. TACO classification based on two sets of haemovigilance criteria (National Healthcare Safety Network and proposed revised International Society for Blood Transfusion) was concordant with expert panel diagnosis in 57% and 54% of reviewed cases, respectively. Although the majority of clinical parameters did not differentiate expert panel adjudicated TACO from other cases, improved oxygenation within 24 h of transfusion did (P = 0·01). CONCLUSIONS: The incidence of TACO was similar to that observed in prior studies utilizing active surveillance. Case classification by haemovigilance criteria was frequently discordant with clinical diagnoses of TACO in patients with post-transfusion pulmonary oedema. Improvements in oxygenation within 24 h of transfusion merit further evaluation in the diagnosis of TACO.

Measurement of haemolysis markers following transfusion of uncrossmatched, low-titre, group O+ whole blood in civilian trauma patients: initial experience at a level 1 trauma centre.

BACKGROUND/OBJECTIVES: The safety of administering uncrossmatched, group O, cold-stored, whole blood (cWB) during civilian trauma resuscitation was evaluated. METHODS/MATERIALS: Male trauma patients with haemorrhage-induced hypotension who received leuko-reduced uncrossmatched group O+, low titre (<50) anti-A and -B, platelet-replete cWB during initial resuscitation were included. The biochemical markers of haemolysis (lactate dehydrogenase, total bilirubin, haptoglobin, creatinine, serum potassium) were measured on the day of cWB receipt (day 0), and over the next 2 days, reports of transfusion reactions and total blood product administration in first 24 h of admission were recorded. RESULTS: There were 27 non-group O and 17 group O cWB recipients. The median number of cWB units transfused was 1 [interquartile range (IQR): 1-2] in both groups. The median day 0 post-transfusion serum total bilirubin concentration, although still in the normal range, was higher in the non-group O versus group O recipients (1·4 versus 0·5 mg/dL, P < 0·01). There were no significant differences in any of the other biochemical parameters at any other time point. Non-group O recipients received a median of 3 times more red blood cell (RBC) units compared with group O recipients (P = 0·01 RBCs), likely explaining the bilirubin difference on day 0. The median volume of ABO-incompatible plasma transfused to non-group O recipients was 600 mL (IQR: 300-1140 mL). There were no reports of adverse events related to the cWB transfusion in either group. CONCLUSIONS: Administration of ≤2 units of cWB in civilian trauma resuscitation was not associated with clinically significant changes in laboratory haemolysis markers. Efficacy will be determined when larger quantities are transfused.

Clinical and laboratory correlates of platelet alloimmunization and refractoriness in the PLADO trial.

BACKGROUND AND OBJECTIVES: Platelet alloimmunization and refractoriness to platelet transfusion are complications of platelet transfusion therapy. The platelet dose (PLADO) trial, as the largest prospective randomized trial of prophylactic platelet therapy to date, afforded an opportunity to analyse these two issues. MATERIALS AND METHODS: PLADO patient records were examined for evidence of platelet alloimmunization, defined as an increase in HLA Class I panel-reactive antibodies (PRA) to ≥20%, and clinical refractoriness, defined as two consecutive ≤4 h posttransfusion corrected platelet count increments (CCI) of <5000. Multivariate logistic regression, restricted to platelet-transfused subjects who received exclusively either in-process leucoreduction apheresis or whole blood-derived (WBD) leucocyte-reduced platelets, compared the frequency of these outcomes by platelet unit and patient characteristics. RESULTS: Forty of 816 evaluable platelet-transfused patients (5%) became alloimmunized during the trial. Prior pregnancy, chemotherapy only compared to progenitor cell transplant, and low platelet dose - all were associated with significantly higher rates of alloimmunization. Among 35 alloimmunized patients evaluated for refractoriness, 8 (23%) had two consecutive CCI < 5000/µl. Regardless of alloimmunization status, CCIs < 5000/µl were observed following 17% of platelet transfusions. Among 734 patients receiving at least two platelet transfusions, two consecutive CCIs of ≤5000 occurred in 102 (14%). CONCLUSIONS: The incidence of new platelet alloimmunization was low in the PLADO study, but follow-up was at most 30 days. Alloimmunization was present in only 8 of 102 (8%) of observed cases of refractoriness, suggesting that other causes of poor posttransfusion increments are frequent.

I am the 9%: Making the case for whole-blood platelets.

Over the last 15 years, there has been a trend in the United States towards the increasing use of apheresis platelet (AP) concentrates over whole-blood-derived platelets (WBP). Although 1-h- and 24-h-corrected count increments tend to be higher with AP, this does not translate into improved haemostatic efficiency when used to prevent bleeding in haematology/oncology patients. WBP expose the recipient to more donors than apheresis products. However, recent studies have shown no significant differences in the rates of bacterial contamination, human leukocyte antigen alloimmunisation, RhD alloimmunisation, transfusion-related acute lung injury or febrile non-haemolytic transfusion reactions between these two products. Given the overall low rates of virally contaminated units in the era of nucleic acid testing and rigorous donor screening, the difference in donor exposures of 4-6 vs 1 has minimal clinical relevance. Although studies point to a marginally increased risk of donor adverse events associated with WBP, the absolute risk is too miniscule to act as a deterrent to making whole-blood donations. Both types of platelet concentrates should therefore be considered clinically equivalent; in this light, the most responsible use of the community donor resource pool, which both optimises the utility of a whole-blood donation and meets the clinical needs of thrombocytopenic recipients, is to have a mix of both types of platelet products so as to mitigate the risk of shortages.

Whole blood for the acutely haemorrhaging civilian trauma patient: a novel idea or rediscovery?

The concept of whole blood (WB) as a treatment modality for trauma patients requiring transfusion therapy is not new. Successfully employed in the early 20 century, WB was the product of choice for military trauma resuscitation until the advent of component therapy changed the landscape of transfusion medicine. However, the recognition of the success of WB in the military operational setting has provided some enthusiasm to explore its revival as a cold-stored option in the civilian trauma resuscitation sector. Concerns continue to exist over potential limitations for its application in regards to the efficacy of platelets after cold storage, the risk of haemolytic transfusion reactions following the transfusion of un-cross-matched WB and the logistical issues for civilian blood banks in providing WB. This review aims to reconcile these concerns with data available in the literature, with a view to establishing that there is in vitro evidence supporting the haemostatic effects of cold-stored WB as a potential therapeutic option in both the pre-hospital and in-hospital civilian trauma resuscitation settings.

Excessive quantities of red blood cells are issued to the operating room.

OBJECTIVES: To determine what percentage of red blood cell (RBC) units that were issued to the operating room (OR) were returned unused, and to determine how often all of the RBCs that were issued for a patient were returned unused using the institution's maximum surgical blood ordering schedule (MSBOS) as a guide. BACKGROUND: The MSBOS provides guidelines for blood ordering, but is merely a suggestion for the ordering clinicians. This study examined how closely ordering practices followed the MSBOS, and how often ordered RBCs were actually transfused. METHODS: For a 4-week period, RBC issue and utilization data were collected on elective surgery patients who were eligible for electronic cross-match at a tertiary care hospital. These data were compared to the MSBOS. RESULTS: There were 1350 surgical procedures performed. Of these cases, 439 patients had a type and screen (T&S) performed, and 215/439 (49%) patients had at least 1 RBC issued during their case. To these 215 patients, 742 RBC units were issued and 537/742 (72%) of these units were returned to the blood bank unused. In 152/215 (71%) cases with issued RBCs, all of the RBCs were returned to the blood bank unused. Amongst the surgical categories in this study, the percentage of cases where none of the issued RBCs were transfused ranged from 38 to 93%. CONCLUSIONS: Significant numbers of RBC units are issued but not transfused during surgery. Involving the surgical team in the blood issuing process and using a data-driven MSBOS may reduce the number of unused units.

ABO-mismatched transfusions are not over-represented in febrile non-haemolytic transfusion reactions to platelets.

ABO-mismatched plasma and platelet (PLT) transfusion have been associated with worse outcomes, including haemolysis and other reactions, compared to recipients of ABO-identical products. The immune complexes that form in a mismatched transfusion have been demonstrated to stimulate pyrogenic cytokine release in vitro. Comparing ABO identical vs. ABO mismatched PLT transfusions, we found no significant difference in the ABO compatibilities between the PLT doses implicated in causing febrile non-haemolytic transfusion reactions (FNHTR) in 162 recipients and both the baseline PLT donor/recipient ABO compatibility (P = 0·67) or the PLTs issued in the 30 days preceding the FNHTR (P = 0·92). ABO-mismatched PLT transfusions do not appear to be aetiological agents of FNHTR in a population routinely receiving both ABO-identical and ABO-mismatched transfusions.

Detection of HHV-8 (human herpesvirus-8) genomes in induced peripheral blood mononuclear cells (PBMCs) from US blood donors.

BACKGROUND: Human herpesvirus-8 (HHV-8) causes Kaposi's sarcoma and can be detected and induced in peripheral blood mononuclear cells (PBMCs) from infected individuals. The prevalence of viral genomes in induced/cultured PBMCs from healthy blood donors has not been systematically studied. MATERIALS AND METHODS: PBMCs from 164 donors were purified and stored as two equal aliquots in liquid nitrogen. One aliquot was used for CD19+ B-cell purification with a fraction reserved for DNA extraction. The second aliquot was cultured for 2 or 4 days in culture media containing n-butyrate and tetradecanoyl phorbol acetate. DNA was extracted from all four cell sources: PBMCs, purified B cells, induced PBMCs harvested at days 2 and 4 of culture. A sensitive real-time PCR with a DNA equivalent of 3×10(5) cells per reaction was run in duplicate for all samples along with a quantitative HHV-8 DNA standard ranging from 1.6 to 200 copies. RESULTS: For all 164 donors, HHV-8 genomes were not detected in the DNA equivalent of 3-6×10(5) of PBMCs and induced/cultured PBMCs with a real-time PCR assay (95% CI: 0-3.5/164). HHV-8 DNA was not detected from DNA equivalent of 1.5 (0.5-5.6)×10(5) CD19+ B cells from 139/164 donors. HHV-8 antibodies were detected in 7 of the 164 donors (4.3%). CONCLUSIONS: HHV-8 genomes were not detected from PBMCs, induced/cultured PBMCs and CD19+ B cells from 164 blood donors. The level of detectable HHV-8 genomes in blood donors seems to be extremely low, if they exist.

The Dead Sea needs salt water massively bleeding patients need whole blood: The evolution of blood product resuscitation.

Whole blood, that is blood that is not manufactured into its component red blood cells (RBC) plasma, and platelets (PLT) units, was the mainstay of transfusion for many years until it was discovered that the component parts of a blood donation could be stored under different conditions thereby optimizing the storage length of each product. The use of low anti-A and -B titer group O whole blood (LTOWB) has recently been rediscovered for use in massively bleeding trauma patients. Whole blood has several advantages over conventional component therapy for these patients, including simplifying the logistics of the resuscitation, being more concentrated than whole blood that is reconstituted from conventional components, and providing cold-stored PLTs, amongst other benefits. While randomized controlled trials to determine the efficacy of using LTOWB in the resuscitation of massively bleeding trauma patients are currently underway, retrospective data has shown that massively bleeding recipients of LTOWB with traumatic injury do not have worse outcomes compared to patients who received conventional components and, in some cases, recipients of LTOWB have more favourable outcomes. This paper will describe some of the advantages of using LTOWB and will discuss the emerging evidence for its use in massively bleeding patients.

The effects of a data driven maximum surgical blood ordering schedule on preoperative blood ordering practices.

OBJECTIVES: The maximum surgical blood ordering schedule (MSBOS) provides guidelines for pre-operative pre-transfusion testing for elective surgical procedures. This study compared blood ordering and utilization during the period when the MSBOS was created by achieving consensus between the blood bank and the various surgical specialties, and after the introduction of an MSBOS created by using department-specific red blood cell (RBC) transfusion data (data driven MSBOS, dMSBOS). METHODS: The dMSBOS was created by analyzing 12 months of RBC transfusion data for each procedure across a regional health system. Pre-transfusion testing and the RBC crossmatch:transfusion (C:T) ratios at 8 of the hospitals were compared between the 12 month period before the dMSBOS was introduced, and the 15 months after its introduction. RESULTS: There were significant reductions in the median monthly number of type and screens not associated with RBC crossmatches (10 714-10 061; p < 0.0001) and the median number of type and screens associated with RBC crossmatches (10 127-9 349; p = 0.0014) on surgical patients after dMSBOS implementation. There were significant decreases in the median number of monthly RBC units crossmatched (2 981-2 444; p < 0.0001) and transfused (890-791; p < 0.0001) to surgical patients after implementing the dMSBOS. The overall system-wide C:T ratio trended down after dMSBOS implementation (from 3.34 to 3.17, p = 0.067). DISCUSSION: Crossmatching fewer RBC units facilitates more efficient management of the blood bank's inventory. CONCLUSION: The dMSBOS was effective in reducing the extent of unnecessary pre-transfusion testing before surgery and reduced the number of RBCs that were crossmatched for specific patients.

Heteroagglutinins and their significance in baboon hepatic xenotransplantation.

The role of preformed xenoreactive antibodies in xenograft recipients is unknown. Humans and baboons possess red cell agglutinating activity associated with isohemagglutinins and heteroagglutinins (HA). We examined the role of HA in two patients who received ABO-identical baboon livers. Human antibaboon HA were assessed by correlating serial titers with studies for rejection. Serial direct antiglobulin testing (DAT) was used to detect baboon antihuman HA, potentially produced by transplanted passenger lymphocytes. Patient 1 survived 70 days. The human antibaboon HA titers remained essentially unchanged from preoperative values. Although hyperacute rejection did not occur, and there was only mild cellular rejection, liver function was suboptimal. Postreperfusion immunoglobulin and complement deposition and histologic changes suggested complement-mediated injury. DAT testing was negative except for passively acquired anti-A from transfusion. At autopsy there was marked bile stasis, but no rejection. Patient 2 survived 26 days with essentially unchanged HA titers until preterminal. Although there was no hyperacute rejection and only mild humoral rejection (without cellular rejection), suboptimal liver function and bile stasis were again noted. Postreperfusion immunoglobulin and complement deposition again suggested complement-mediated injury. DAT testing was negative. At autopsy there was no rejection. Human antibaboon HA do not appear to be associated with hyperacute or cellular rejection, but their role in the complement-mediated injury, suspected in both cases, cannot be definitively excluded. Baboon antihuman HA were not detected in either patient.

Transfusion-induced immunomodulation and its clinical consequences.

The bulk of experimental and clinical data support the theory that homologous transfusion causes significant down-regulation of immunologic functions in a number of settings. These changes in immune function may account for the beneficial associations of transfusion with increased renal allograft survival, and decreased recurrence in Crohn's disease. Conversely, these transfusion-induced effects may be responsible in part for the deleterious association of homologous transfusion with increased cancer recurrence, and increased posttransfusion bacterial and viral infection rates. Host defenses against malignancy and infection may in some instances be severely compromised by transfusions of homologous blood, but the circumstances under which this occurs need to be better defined. Likewise, the hypothesis that modification of blood components to contain fewer leukocytes or less plasma might ameliorate these effects is attractive, but little or no data exist to support or refute it. Future clinical studies will no doubt address these issues.

Centralized transfusion service: a novel approach to the delivery of transfusion services.

The development and expansion of the CTS in Pittsburgh shows the feasibility of this transfusion medicine delivery system. Few of the changes driven by health care reform both improve patient care and reduce costs. When properly implemented, a CTS achieves these objectives, benefits the community as a whole, and enhances the role of transfusion medicine specialists and the blood center in the region.

Stability of lymphocytes and Epstein-Barr virus during red blood cell storage.

BACKGROUND: The Epstein-Barr virus (EBV) establishes and maintains latent infection in B lymphocytes of the healthy adults. Lymphocytes remain viable during red blood cell (RBC) storage. The effect of RBC storage on the stability of EBV-infected B lymphocytes and EBV genome is not known. STUDY DESIGN AND METHODS: Eight randomly selected non-leukoreduced AS-5 RBC units were stored for 42 days under standard blood bank refrigerated at 1-6 degrees C. Cell count and EBV genomes in CD19+ B lymphocytes were measured in fresh products and weekly for 6 weeks. Total white blood cells (CD45+), T lymphocyte (CD3+), and B lymphocyte (CD19+) were quantified by a single platform flow cytometric assay. EBV genomes were quantified by real-time polymerase chain reaction using DNA purified from CD19+ B cells. RESULTS: Viable white blood cell, T and B lymphocytes followed a biphasic decline curve during RBC storage consisting of a steep steady decline during the first 3 weeks followed by a plateau for the remainder of the storage. At the end of the RBC shelf-life, 19% of the original T and B cells remained viable. EBV genomes per 10(5) CD19+ B lymphocytes remained constant during RBC storage. However, the total EBV genomes in the RBC units decline by more than 80% of their original value at the end of RBC storage due to loss of viable B lymphocytes. CONCLUSIONS: The results indicate that lymphocytes and EBV latently infected B cells can survive the normal storage conditions for RBC.

The RADAR repository: a resource for studies of infectious agents and their transmissibility by transfusion.

BACKGROUND: An ongoing issue in transfusion medicine is whether newly identified or emerging pathogens can be transmitted by transfusion. One method to study this question is through the use of a contemporary linked donor-recipient repository. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study Allogeneic Donor and Recipient (RADAR) repository was established between 2000 and 2003 by seven blood centers and eight collaborating hospitals. Specimens from consented donors were collected, components from their donations were routed to participating hospitals, and recipients of these units gave enrollment and follow-up specimens for long-term storage. The repository was designed to show that zero transmissions to enrolled recipients would indicate with 95 percent confidence that the transfusion transmission rate of an agent with prevalence of 0.05 to 1 percent was lower than 25 percent. RESULTS: The repository contains pre- and posttransfusion specimens from 3,575 cardiac, vascular, and orthopedic surgery patients, linked to 13,201 donation specimens. The mean number of RADAR donation exposures per recipient is 3.85. The distribution of components transfused is 77 percent red cells, 13 percent whole blood-derived platelet concentrates, and 10 percent fresh frozen plasma. A supplementary unlinked donation repository containing 99,906 specimens from 84,339 donors was also established and can be used to evaluate the prevalence of an agent and validate assay(s) performance before accessing the donor-recipient-linked repository. Recipient testing conducted during the establishment of RADAR revealed no transmissions of human immunodeficiency virus, hepatitis C virus, or human T-lymphotropic virus. CONCLUSIONS: RADAR is a contemporary donor-recipient repository that can be accessed to study the transfusion transmissibility of emerging agents.