Successful Implementation of a Packed Red Blood Cell and Fresh Frozen Plasma Transfusion Protocol in the Surgical Intensive Care Unit

BackgroundBlood product transfusions are associated with increased morbidity and mortality. The purpose of this study was to determine if implementation of a restrictive protocol for packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusion safely reduces blood product utilization and costs in a surgical intensive care unit (SICU).Results829 total patients were included in the analysis (PRE, n=372; POST, n=457). Despite higher mean age (56 vs. 52 years, p=0.01) and APACHE II scores (12.5 vs. 11.2, p=0.006), mean units transfused per patient were lower for both packed red blood cells (0.7 vs. 1.2, p=0.03) and fresh frozen plasma (0.3 vs. 1.2, p=0.007) in the POST compared to the PRE cohort, respectively. There was no difference in inpatient mortality between the PRE and POST cohorts (7.5% vs. 9.2%, p=0.39). There was a decreased risk of urinary tract infections (OR 0.47, 95%CI 0.28-0.80) in the POST cohort after controlling for age, illness severity and amount of blood products transfused.ConclusionsImplementation of a restrictive transfusion protocol can effectively reduce blood product utilization in critically ill surgical patients with no increase in morbidity or mortality.     

Clinical use of blood,blood components and blood products.

The goal of modern transfusion therapy is to provide appropriate replacement therapy with blood components as opposed to whole blood for patients with specific hematologic deficiencies. A prerequisite of component therapy is, therefore, correct identification of the deficiency. Appropriate use of components avoids many of the hazards associated with the use of whole blood, and at the same time makes maximal use of this valuable resource. Blood components separated from whole blood soon after collection and appropriately stored can, in combination, provide all the factors present in fresh whole blood. Red cell concentrates prepared from multiple packs have a hematocrit of approximately 70%. They may be stored for up to 3 weeks at 4 degrees C and are recommended for most situations requiring red cell transfusions. Platelet concentrates, which can be stored for up to 72 hours at 22 degrees C, may be used for thrombocytopenic patients. Fresh frozen plasma, stored plasma, cryoprecipitated factor VIII, factor VIII concentrate and factor IX complex concentrate are available for the proper treatment of patients with hemorrhagic disorders due to coagulation factor deficiencies. Similarly, albumin and immune serum globulin are available for their oncotic and antibody properties respectively. Thus, the availability and appropriate use of the various blood products allows not only optimal transfusion therapy for each patient, but also fuller utilization of national blood resources.     

Leukocyte-depleted blood: a comparison of available preparations.

Febrile nonhemolytic transfusion reactions due to leukoagglutinins are frequently seen in patients who have been given multiple blood transfusions. To prevent or reduce the severity of these reactions, leukocyte-poor blood (that containing fewer than 0.3 X 10(9) leukocytes per unit) is frequently requested by clinicians. Four methods commonly used in Canada to produce leukocyte-poor blood were examined for their relative effectiveness and appropriate use. The mean total leukocyte count per unit was reduced to 0.22 X 10(9) in buffy-coat-poor red blood cell preparations produced by centrifugation with the blood bag inverted, to 0.19 X 10(9) by perfusion through an Imugard filter, to 0.21 X 10(9) by the use of an IBM 2991 automated cell washer and to 0.13 X 10(9) with the use of frozen blood. The proportion of red cells recovered varied from 62% with the inverted-spin method to 85% with the use of frozen blood. Comparison of these data and the percentage of leukocytes removed, the shelf life of the product, the cost of supplies and the preparation time indicated that the use of sophisticated machinery, such as the IBM cell washer, or of glycerolization plus washing of frozen cells is not warranted for most patients. Instead, patients who have febrile nonhemolytic transfusion reactions should initially be treated with a leukocyte-poor red cell preparation produced by the inverted-spin method; only if such reactions recur should the blood bank be requested to provide filtered, washed or frozen red cells.     

Association between transfusion of whole blood and recurrence of cancer.

Transfusion affects the immune response to renal transplantation and may be associated with recurrence of various human neoplasms. Data from patients with colonic, rectal, cervical, and prostate tumours showed an association between transfusion of any amount of whole blood or larger amounts of red blood cells at the time of surgery and later recurrence of cancer. Recipients of one unit of whole blood had a significantly higher incidence of recurrence (45%) than recipients of a single unit of red cells (12%) (p = 0.03). Recipients of two units of whole blood also had a higher rate of recurrence (52%) than those receiving two units of red cells (23%) (p = 0.03). Recipients of any amount of whole blood had similar recurrence rates (38-52%). Recipients of four or more units of red blood cells had a higher rate of recurrence (55%) than those receiving three or fewer units of red blood cells (20%) (p = 0.005). Mortality due to cancer in patients receiving three or fewer units of red blood cells (2%) was similar to that in patients who did not have transfusions (7%) and significantly lower than that observed in patients receiving three or fewer units of whole blood (20%) (p = 0.003). A proportional hazards risk analysis showed that transfusion of any whole blood or more than three units of red blood cells was significantly associated with earlier recurrence and death due to cancer. These data support an association between transfusion and recurrence of cancer. They also suggest that some factor present in greater amounts in whole blood, such as plasma, may contribute to the increased risk of recurrence in patients who have undergone transfusion. Until the questions raised by retrospective studies of cancer recurrence and transfusion can be answered by prospective interventional trials with washed red blood cells, red blood cells should be transfused to patients with cancer in preference to whole blood when clinically feasible.     

Improved method for the cryopreservation of human red cells in liquid nitrogen with hydroxyethyl starch.

Refinement of a method described previously (Cryobiology12, 110–118, April, 1975) made possible routine freezing of full units of packed erythrocytes after separation of platelet rich plasma, and buffy coats. The volume frozen was 405 ml which included packed red cells (190–220 ml), plasma (43–73 ml), and cryo-HES (142 ml, final concentration 14% $\text{w}\text{v}$). The units could be frozen with or without shaking by direct immersion in liquid nitrogen. Thawing was accomplished by transferring units quickly from liquid nitrogen storage to a shaking water bath at 54 °C. The average yield from units of red cells was 98.4%. The stability to a 50-fold dilution in 0.15 m NaCl was 87.8%. Thawing rate was the critical variable in producing the most stable thawed cells. Plasma expander HES was usable but the thawed units were more viscous and about 7% less stable. Red cells prewashed with 0.15 m NaCl and frozen without plasma showed no significant changes in cellular yield or stability. The optimum resuspension medium was 3% glucose. A morphologic study of cells fixed in 1% glutaraldehyde revealed that before freezing red cells were partially dehydrated in 14% HES. These were smooth, flat discs. Cells fixed on thawing were extensively dehydrated and seen as large, thin, smooth, flat discs with approximately 10% echinocytes. On dilution with 6% glucose (1:1) these swelled and reverted to biconcave discocytes except for approximately 5% echinocytes. Storage in liquid nitrogen measured in groups of three units of 15 units for 0, 3, 6, 9, and 12 weeks revealed normal postthawed oxygen delivery (P-50). The greatest measurable effect of freezing red cells in HES was a loss of cellular K⁺ compensated by a corresponding increase in Na⁺.     

Occurrence of non-A, non-B post-transfusion hepatitis in heart surgery. Prospective study on the value of the determination of serum alanine aminotransferase and detection of anti-HBc antibodies in blood donors

We studied a group of 64 patients undergoing cardiac surgery for the occurrence of post-transfusion hepatitis during a follow-up period of 5 months. They received blood units (packed red cells in saline-adenine-glucose medium and/or fresh frozen plasma exclusively) from 447 volunteer donors. Post-transfusion hepatitis was identified in 5 patients: 1 patient had cytomegalovirus hepatitis and the remaining 4 cases were defined, by exclusion, as non-A, non-B hepatitis (with prevalence and incidence rates of 80% and 6.25% respectively). We found no statistically significant differences between the numbers of transfused blood product units in patients who developed non-A, non-B hepatitis as compared to those who did not. Our analysis of the predictive effectiveness of alanine aminotransferase and anti-HBc antibodies screening in blood donors to prevent non-A, non-B post-transfusion hepatitis led to the following conclusions: we failed to confirm the association between anti-HBc in blood donors and enhanced risk of non-A, non-B hepatitis in recipients since no case developed among patients receiving blood products from anti-HBc positive donors. So, 20 donors (4.5%) would have been discarded without any reduction of the incidence of non-A, non-B hepatitis. we could not confirm nor exclude the possibility that screening donor blood for elevated alanine aminotransferase levels would have reduced the number of non-A, non-B hepatitis in recipients.     

Association of an In-House Blood Bank with Therapy and Outcome in Severely Injured Patients: An Analysis of 18,573 Patients from the TraumaRegister DGU?

IntroductionHemorrhagic shock remains one of the most common causes of death in severely injured patients. It is unknown to what extent the presence of a blood bank in a trauma center influences therapy and outcome in such patients.ResultsComplete data sets of 18,573 patients were analyzed. Of 457 hospitals included, 33.3% had an in-house blood bank. In trauma centers with a blood bank (HospBB), packed red blood cells (PRBCs) (21.0% vs. 17.4%, p < 0.001) and fresh frozen plasma (FFP) (13.9% vs. 10.2%, p <0.001) were transfused significantly more often than in hospitals without a blood bank (Hosp0). However, no significant difference was found for in-hospital mortality (standard mortality ratio [SMR, 0.907 vs. 0.945; p = 0.25). In patients with clinically apparent shock on admission, no difference of performed transfusions were present between HospBB and Hosp0 (PRBCs, 51.4% vs. 50.4%, p = 0.67; FFP, 32.7% vs. 32.7%, p = 0.99), and no difference in in-hospital mortality was observed (SMR, 0.907 vs. 1.004; p = 0.21).DiscussionIn HospBB transfusions were performed more frequently in severely injured patients without positively affecting the 24h mortality or in-house mortality. Easy access may explain a more liberal transfusion concept.     

Whole blood and component use in resource poor settings

Data on blood collection, testing and component preparation has improved worldwide; however, there is limited information on blood utilization from the developing countries. Blood requirement in the Southeast Asia region is 15 million units against a collection of 9.3 million. There is huge diversity in the management of blood transfusion services, the voluntary blood collection (range 40–100%) and proportion of blood separated into components (10–95%). The major indications for transfusion are for emergency obstetric care, surgery, pediatric and trauma patients. The prevalence of thalassemia in this region is high and in India alone 2 million units of packed red cells are required for transfusion to these patients. The Blood Safety Program in India has developed as a component of the National Aids Control Program and has lead to infrastructure development, blood component separation facilities and formulation of a National Blood Policy. In order to facilitate emergency obstetric care nearer home, blood storage centers are being established at primary health care centers. Emerging infectious threats like dengue hemorrhagic fever necessitate platelet transfusion therapy. A few centers in India issue NAT screened blood. It is envisaged to establish a nationally co-ordinated transfusion service for cost-effective quality blood/components for appropriate clinical use.     

不同比例新鲜冰冻血浆对大量输血患者凝血功能的影响

目的:探讨不同比例输注新鲜冰冻血浆对大量输血患者凝血功能的影响。方法:回顾性分析本院2018年1月至2018年12月收治的123例大量输血患者的临床资料,依据所输注新鲜冰冻血浆与红细胞比例不同,将其分为低比例组(1:3)、中比例组(1:2)、高比例组(1:1),比较三组患者输血前后凝血功能、血小板计数及电解质变化。结果:输血后,三组患者FIB较输血前明显降低,而PT、APTT较输血前显著升高(P0.05),高比例组PT和APTT明显低于中比例组和低比例组,FIB、血小板均高于中比例组和低比例组(P0.05),电解质水平优于低比例组和中比例组(P0.05)。结论:在大量输血时,提高血浆与红细胞比例有利于改善大量输血患者凝血功能障碍,减少电解质紊乱。     

Effects of blood products on inflammatory response in endothelial cells in vitro

Background

Transfusing blood products may induce inflammatory reactions within the vascular compartment potentially leading to a systemic inflammatory response. Experiments were designed to assess the inflammatory potential of different blood products in an endothelial cell-based in vitro model and to compare baseline levels of potentially activating substances in transfusion products.

Methods

The inflammatory response from pre-activated (endotoxin-stimulated) and non-activated endothelial cells as well as neutrophil endothelial transmigration in response to packed red blood cells (PRBC), platelet concentrates (PC) and fresh frozen plasma (FFP) was determined. Baseline inflammatory mediator and lipid concentrations in blood products were evaluated.

Results

Following incubation with all blood products, an increased inflammatory mediator release from endothelial cells was observed. Platelet concentrates, and to a lesser extent also FFP, caused the most pronounced response, which was accentuated in already pre-stimulated endothelial cells. Inflammatory response of endothelial cells as well as blood product-induced migration of neutrophils through the endothelium was in good agreement with the lipid content of the according blood product.

Conclusion

Within the group of different blood transfusion products both PC and FFP have a high inflammatory potential with regard to activation of endothelial cells. Inflammation upon blood product exposure is strongly accentuated when endothelial cells are pre-injured. High lipid contents in the respective blood products goes along with an accentuated inflammatory reaction from endothelial cells.     

Benchmarking the use of blood products in cardiac surgery to stimulate awareness of transfusion behaviour

Introduction

Cardiac operations account for a large proportion of the blood transfusions given each year, leading to high costs and an increased risk to patient safety. Therefore, it is important to explore initiatives to reduce transfusion rates. This study aims to provide a benchmark for transfusion practice by inter-hospital comparison of transfusion rates, blood product use and costs related to patients undergoing coronary artery bypass grafting (CABG), valve surgery or combined CABG and valve surgery.

Methods

Between 2010 and 2013, patients from four Dutch hospitals undergoing CABG, valve surgery or combined CABG and valve surgery (n = 11,150) were included by means of a retrospective longitudinal study design.

Results

In CABG surgery the transfusion rate ranged between 43 and 54%, in valve surgery between 54 and 67%, and in combined CABG and valve surgery between 80 and 88%. With the exception of one hospital, the trend in transfusion rate showed a significant decrease over time for all procedures. Hospitals differed significantly in the units of blood products given to each patient, and in the use of specific transfused combinations of blood products, such as red blood cells (RBCs) and a combination of RBCs, fresh frozen plasma (FFP) and platelets.

Conclusion

This study indicates that benchmarking blood product usage stimulates awareness of transfusion behaviour, which may lead to better patient safety and lower costs. Further studies are warranted to improve awareness of transfusion behaviour and increase the standardisation of transfusion practice in cardiac surgery.

     

Where does blood go? Prospective observational study of red cell transfusion in north England

ObjectiveTo collect population based information on transfusion of red blood cells.DesignProspective observational study over 28 days.SettingHospital blood banks in the north of England (population 2.9 million).ParticipantsAll patients who received a red cell transfusion during the study period. Data completed by hospital blood bank staff.ResultsThe destination of 9848 units was recorded (97% of expected blood use). In total 9774 units were transfused: 5047 (51.6%) units were given to medical patients, 3982 (40.7%) to surgical patients, and 612 (6.3%) to obstetric and gynaecology patients. Nearly half (49.3%) of all blood is given to female recipients, and the mean age of recipients of individual units was 62.7 years. The most common surgical indications for transfusion were total hip replacement (4.6% of all blood transfused) and coronary artery bypass grafting (4.1%). Haematological disorders accounted for 15.5% of use. Overall use was 4274 units per 100 000 population per year.ConclusionIn the north east of England more than half of red cell units are transfused for medical indications. Demand for red cell transfusion increases with age. With anticipated changes in the age structure of the population the demand for blood will increase by 4.9% by 2008.

What is already known on this topic

There have been no systematic population based surveys on use of red cells in the United KingdomStudies in France and the United States have shown that more than half of transfused red cells go to surgical patients

What this study adds

In the north of England over half of red cells are given for medical indicationsRates of red cell transfusion rise steeply with advancing ageSmall increases in the number of elderly people will have large effects on demand     

Experience with a blood component program in surgical hemotherapy

Within the component concept applied during the past 6 years at the University Hospital in Berne (Switzerland), 85% of all red cell units are transfused as concentrates with a hematocrit of 70%, and the remaining 15% as fresh whole blood. The rationale in surgical patients is to exploit the different "critical levels" of the blood volume, hematocrit, total serum protein, plasmatic coagulation factors, and platelets. A colloid plasma substitute compensating for the plasma deficit of the red cell concentrates is an integral part of the system. A carefully checked, retrospective study in 372 patients revealed no disadvantages for the postoperative course. During the first 4 1/2 years after its introduction it did not increase the demand for human plasma protein solutions. With the red cells as a pacemaker for the number of blood donations, this system can simultaneously cover a reasonable national demand for albumin and factor VIII.     

Proteomics and transfusion medicine: future perspectives

Limited number of important discoveries have greatly contributed to the progresses achieved in the blood transfusion; ABO histo-blood groups, citrate as anticoagulant, fractionation of plasma proteins, plastic bags and apheresis machines. Three major types of blood products are transfused to patients: red cell concentrates, platelet concentrates and fresh frozen plasma. Several parameters of these products change during storage process and they have been well studied over the years. However, several aspects have completely been ignored; in particular those related to peptide and protein changes. This review presents what has been done using proteomic tools and the potentials of proteomics for transfusion medicine.     

Frozen-thawed red cells--standard article for hospital use?

The freezing and storing of glycerol protected red cells allows the present 20---40 day limitation of red cell storage to be indefinitely lengthened. Although frozen thawed cells are more expensive to prepare than ordinary packed cells, the longer shelf-life of the red cells, the reduced risk of hepatitis transmission, and the reduction of immunization against leuko- and thrombocytes, are all advantages which out-weighed this additional cost. To effect an increase in their use, frozen thawed cells could be distributed from central blood banks to hospitals were they would be stored until needed for transfusion. Thawing and washing would necessarily be done by the hospital blood bank personnel.     

Packed Red Blood Cells Are an Abundant and Proximate Potential Source of Nitric Oxide Synthase Inhibition

Objective

We determined, for packed red blood cells (PRBC) and fresh frozen plasma, the maximum content, and ability to release the endogenous nitric oxide synthase (NOS) inhibitors asymmetric dimethylarginine (ADMA) and monomethylarginine (LNMMA).

Background

ADMA and LNMMA are near equipotent NOS inhibitors forming blood’s total NOS inhibitory content. The balance between removal from, and addition to plasma determines their free concentrations. Removal from plasma is by well-characterized specific hydrolases while formation is restricted to posttranslational protein methylation. When released into plasma they can readily enter endothelial cells and inhibit NOS. Fresh rat and human whole blood contain substantial protein incorporated ADMA however; the maximum content of ADMA and LNMMA in PRBC and fresh frozen plasma has not been determined.

Methods

We measured total (free and protein incorporated) ADMA and LNMMA content in PRBCs and fresh frozen plasma, as well as their incubation induced release, using HPLC with fluorescence detection. We tested the hypothesis that PRBC and fresh frozen plasma contain substantial inhibitory methylarginines that can be released chemically by complete in vitro acid hydrolysis or physiologically at 37°C by enzymatic blood proteolysis.

Results

In vitro strong-acid-hydrolysis revealed a large PRBC reservoir of ADMA (54.5 ± 9.7 µM) and LNMMA (58.9 ± 28.9 μM) that persisted over 42-d at 6° or -80°C. In vitro 5h incubation at 37°C nearly doubled free ADMA and LNMMNA concentration from PRBCs while no change was detected in fresh frozen plasma.

Conclusion

The compelling physiological ramifications are that regardless of storage age, 1) PRBCs can rapidly release pathologically relevant quantities of ADMA and LNMMA when incubated and 2) PRBCs have a protein-incorporated inhibitory methylarginines reservoir 100 times that of normal free inhibitory methylarginines in blood and thus could represent a clinically relevant and proximate risk for iatrogenic NOS inhibition upon transfusion.     

Effects of citrated whole blood transfusion in response to hemorrhage.

BACKGROUND AND PURPOSE: Standard treatment for massive hemorrhage in dogs is infusion of whole blood or of packed red blood cells with fresh frozen plasma if whole blood is not available. Although most whole blood is collected using a citrate-based anticoagulant, knowledge of citrate's relevant non-anticoagulant effects is not widespread. Citrate's anticoagulant activity is achieved through chelation of divalent metal cations (e.g., magnesium, calcium), which may exacerbate cardiovascular and metabolic insults attributable to hemorrhage. METHODS: Blood pressures, gas tensions, metabolites, and electrolytes; myocardial metabolites, pressures, and contractility; cardiac output; and left cranial descending and circumflex coronary artery flows were measured in 21 anesthetized dogs after hemorrhage was induced by collection of blood into a citrated reservoir to mean arterial pressure of 45 mm Hg for approximately 60 min (until arterial lactate concentration was 7.0 mmol/L), followed by a 1-h transfusion and 2 h of maintenance. RESULTS: Arterial ionized calcium concentration, total peripheral resistance, and myocardial function decreased significantly during hemorrhage. All aforementioned responses but myocardial function continued to decrease during the initial 20 min of transfusion, then began to recover. Total peripheral resistance and end-systolic elastance were the only factors significantly related to calcium concentration. CONCLUSION: Transfusion with citrated whole blood may significantly alter calcium concentration, negatively affecting myocardial and vascular function.     

Transfusion Patterns in All Patients Admitted to the Intensive Care Unit and in Those Who Die in Hospital: A Descriptive Analysis

While it is known that the use of health care resources increases at the end of life in patients admitted to the Intensive Care Unit (ICU), the allocation of blood products at the end of life has not been described. The objective of this study was to describe overall transfusion patterns in the ICU, and specifically in patients who die in hospital. We conducted a retrospective cohort study of adult patients admitted to the ICU of a university-affiliated hospital, who were discharged or died between November 1, 2006 and June 30, 2012. During the study period, 10,642 patients were admitted at least once to the ICU. Of these patients, 4079 (38.3%) received red blood cells (RBCs), plasma or platelets in the ICU. The ICU mortality rate was 28.1% and in-hospital mortality rate was 32.3%. Among 39,591 blood product units transfused over the course of the study in the ICU (18,144 RBC units, 16,920 plasma units and 4527 platelet units), 46.2% were administered to patients who later died within the same hospitalization (41.2% of RBCs, 50.4% of plasma and 50.8% of platelets). Of all blood product units (RBCs, plasma and platelets) administered in the ICU over the study period, 11% were given within the last 24 hours before death. A large proportion of blood products used in the ICU are administered to patients who ultimately succumb to their illness in hospital, and many of these blood units are given in close proximity to death.     

Homologous blood use and conservation techniques for cardiac surgery in the United Kingdom.

The transfusion laboratories of 32 cardiothoracic surgical centres for adults were surveyed to determine the donor blood requirement for open heart surgery in the United Kingdom. Details of the transfusion practice and the use of blood conservation techniques were sought from a representative senior cardiac anaesthetist at each centre. Suitable data were received from 24 transfusion laboratories (75%) and 29 anaesthetists (90%). The mean (SD) blood use was 5.07 (1.53) units per operation. Seven centres routinely transfused fresh frozen plasma to all patients postoperatively. Experience with autologous deposit (three centres), "cell separators" (four centres), and the reinfusion of shed mediastinal blood (four centres) was limited. Prebypass phlebotomy for postbypass reinfusion (14 centres) and the infusion of residual oxygenator blood (27 centres) were the conservation techniques most commonly applied. In only nine centres was a postoperative normovolaemic anaemia to a haemoglobin concentration of less than 100 g/l accepted. Applying blood conservation techniques more widely would help to maintain blood supplies and reduce morbidity and mortality related to transfusion.     

Blood Transfusion: Use and Abuse of Blood Components

Transfusion of whole blood and some blood components may result in serious or fatal complications, among which hepatitis is most frequent (20,000 to 30,000 cases and 3,000 deaths a year). Although hepatitis B virus (HB Ag) sometimes is implicated in posttransfusion hepatitis, non-A non-B. virus(es) (hepatitis “C” virus) probably accounts for most posttransfusion hepatitis.Half of all blood transfusions may be unnecessary.Responsible transfusion practice requires use of appropriate blood components for which there is adequate justification. Transfusion of red blood cells should be given as packed cells in most instances and whole blood should seldom be used.