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 use of next-generation sequencing for the determination of rare blood group genotypes.

OBJECTIVES: Next-generation sequencing (NGS) for the determination of rare blood group genotypes was tested in 72 individuals from different ethnicities. BACKGROUND: Traditional serological-based antigen detection methods, as well as genotyping based on specific single nucleotide polymorphisms (SNPs) or single nucleotide variants (SNVs), are limited to detecting only a limited number of known antigens or alleles. NGS methods do not have this limitation. METHODS: NGS using Ion torrent Personal Genome Machine (PGM) was performed with a customised Ampliseq panel targeting 15 different blood group systems on 72 blood donors of various ethnicities (Caucasian, Hispanic, Asian, Middle Eastern and Black). RESULTS: Blood group genotypes for 70 of 72 samples could be obtained for 15 blood group systems in one step using the NGS assay and, for common SNPs, are consistent with previously determined genotypes using commercial SNP assays. However, particularly for the Kidd, Duffy and Lutheran blood group systems, several SNVs were detected by the NGS assay that revealed additional coding information compared to other methods. Furthermore, the NGS assay allowed for the detection of genotypes related to VEL, Knops, Gerbich, Globoside, P1PK and Landsteiner-Wiener blood group systems. CONCLUSIONS: The NGS assay enables a comprehensive genotype analysis of many blood group systems and is capable of detecting common and rare alleles, including alleles not currently detected by commercial assays.

Vox Sanguinis International Forum on the use of prehospital blood products and pharmaceuticals in the treatment of patients with traumatic haemorrhage.

While specific practices and transported blood products vary around the world, most of the respondents in this International Forum transported at least one blood product for the transfusion to bleeding patients en route to the hospital. The most commonly carried product was RBCs, while the use of whole blood will likely increase given the recent reports of its successful use in the civilian setting, and because of the change in the AABB's Standards regulating its use. It will be interesting to see if plasma use in the prehospital setting becomes more widely used given today's enhanced appreciated of the coagulopathy of trauma and plasma's beneficial effect in reversing it, and if blood products are transported to the scene of injury by more vehicles, that is, not just predominantly in helicopters. It was not surprising that TXA is being widely administered as close to the time of injury as possible given its potential benefit in these patients. This International Forum highlights the importance of focusing attention on prehospital transfusion management with a need to further high­quality research in this area to guide optimal resuscitation strategies.

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.

Femtogram Resolution of Iron Content on a Per Cell Basis: Ex Vivo Storage of Human Red Blood Cells Leads to Loss of Hemoglobin.

The magnetic characteristics of hemoglobin (Hb) changes with the binding of dioxygen (O2) to the heme prosthetic groups of the globin chains: from paramagnetic ferrous Hb to diamagnetic ferrous oxyhemoglobin (oxyHb) with reversibly bound O2, or paramagnetic ferric methemoglobin (metHb). When multiplied over the number of Hb molecules in a red blood cell (RBC), the effect is detectable through motion analysis of RBCs in a high magnetic field and gradient. This motion is referred to as magnetophoretic mobility, which can be conveniently expressed as a fraction of the cell sedimentation velocity. In this Article, using a previously developed and reported instrument, cell tracking velocimetry (CTV), we are able to detect difference in Hb concentration in two RBC populations to a resolution of 1 × 107 Hb molecules per cell (4 × 107 atoms of Fe per cell or 4-5 femtograms of Fe). Similar resolution achieved with inductively coupled plasma-mass spectrometry requires on the order of 105-106 cells and provides an average, whereas CTV provides a measurement for each cell. CTV analysis revealed that RBCs lose, on average, 17% of their Hb after 42 days of storage, the maximum FDA-approved length of time for the cold storage of RBCs in additive solution. This difference in Hb concentration was the result of routine RBC storage; clinical implications are discussed.

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.

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.

Blood banks meet the paradox of Gabriel's Horn: what are the options to maintain supply as demand decreases?

Blood services worldwide have observed a decline in the demand for red blood cells (RBC). Despite this general decline, the demand profile has changed significantly with the demand for O D negative RBCs being maintained; whereas B D positive and AB D positive RBC demand has been reduced. In 2015, the blood type O D negative was seen in 6·3% of the combined first time donors among the five American Blood Centres involved in this study and 7·4% of first time Australian donors in 2014/2015, whereas O D negative distributions accounted for 10·5% of all red cell units issued by the American centres and 13·9% by the Australian centres. Inventory can therefore be of sufficient overall quantity but may not be adequate for the demand for units with specific blood types. Recruitment of new donors may need to become more targeted and/or financial or inventory control measures could also be required to ensure inventory matches demand. Blood Services will need to consider the available options in order to ensure that sufficiency of supply is secure and the donor panel is optimised to meet the new demand paradigm.

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.

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.

A novel cis-AB variant allele arising from a de novo nucleotide substitution c.796A>G (p.M266V) in the B glycosyltransferase gene.

BACKGROUND: Cis-AB, a rare ABO variant, is the result of a mutated ABO gene that produces a glycosyltransferase enzyme with dual A and B glycosyltransferase activity. It may lead to ABO discrepancies and a delay in establishing the blood group. To date, there have been no reports of a de novo mutation leading to a cis-AB allele. OBJECTIVES AND METHODS: Sequencing of the ABO gene using blood and hair follicle cells from the proposita were performed along with blood from her parents. To establish maternity and paternity, short tandem repeat (STR) analysis was also performed. The A and B enzyme activities of the novel enzyme were measured in an in vitro expression study. RESULTS: A novel cis-AB allele arising from nucleotide substitution c.796A>G (p.M266V) in the B glycosyltransferase gene were discovered in the blood and hair follicle cells from the proposita, which was absent from her parents. In all 15 autosomal STR loci analysed, the probability of maternity and paternity were 0.999999 and 0.999989, respectively. The novel enzyme created 33.1% and 60.2% of A and B antigen compared to wild type A and B glycosyltransferases. CONCLUSION: A novel mechanism leading to a cis-AB allele was discovered.

Relative IgA-deficient recipients have an increased risk of severe allergic transfusion reactions.

BACKGROUND: Absolute IgA deficiency is the most common immunodeficiency in the Western world. These patients are at risk of severe allergic reactions when receiving a transfusion with a plasma-containing blood product. However, it is unclear whether patients with relative IgA deficiency, that is levels below detection on routine assays, are also at risk of severe reactions. This retrospective study evaluated the number of severe allergic transfusion reactions in relative IgA-deficient patients who were transfused with unwashed blood products. STUDY DESIGN AND METHODS: Patients who had an IgA measurement performed for any reason over a 10-year period were compared with a list of transfusion recipients over the same period. Those who had both an IgA measurement and a transfusion were then compared with the transfusion reaction database to determine whether an allergic reaction had been reported, and if so, the severity of the reaction. Patients with IgA concentrations of <7 mg/dL were defined as relative IgA deficient. RESULTS: Of the 22 362 IgA measurements performed on 19 737 patients over 10 years, a total of 168 relative IgA-deficient patients were identified; 39 of these patients were also transfusion recipients and 4 of 39 (10%) experienced a severe allergic transfusion reaction (SALTR). Eight SALTRs were reported amongst 1545 (0·52%) IgA replete transfusion recipients. CONCLUSION: The significantly increased risk of SALTRs in relative IgA-deficient patients warrants consideration of premedications and/or washing of plasma-containing blood products.