Blood Product Safety

Article Author:
Jaryse Harris
Article Editor:
Kendall Crookston
Updated:
3/31/2019 6:19:23 PM
PubMed Link:
Blood Product Safety

Introduction

Blood product safety has been an improving area of focus for many countries over recent decades. The World Health Organization promotes efforts for improving access to safe transfusion and safe blood products across the world. Safety of blood products begins with blood donor recruitment and includes[1]:

  • Emphasis on pre-donor information
  • Component collection, preparation, and testing
  • Post-donation information
  • Labeling of the products for distribution
  • Blood products in hospital inventory
  • Blood transfused into the patient by hospital staff, and
  • Culminates with hemovigilance and clinical quality improvement to ensure patient safety and reduce morbidity and mortality associated with transfusion of blood and blood products

Several methods have been employed to reduce the risk of blood transfusions and improve blood product safety.  There have been interventions in every step of the process from before blood donation collection through post-procedure follow-up of blood product recipients. There have been improvements made in the collection, storage, management, distribution, utilization, and monitoring of transfusions.

The measures for improved safety begin even before blood collection. It is important to have government and professional organization commitment to improving blood product safety. Other important aspects of improving safety include proper training of staff along with a dedicated and diligent blood transfusion team overseeing donation, testing, and transfusion.  Blood donor recruitment is the next important piece in securing blood product safety. Voluntary unpaid donors have the lowest rates of transfusion-associated infections and are the ideal population from which to recruit donors. Donor screening questions add a layer of defense to improve blood product safety. These screening questions are responsible for the single most significant reduction in transfusion-transmitted infections. Donors are deferred based on criteria to enhance safety for both the donor and the potential recipient. Donors can be deferred for a period (as in the case of anemia) or indefinitely such as in the case of a donor screened positive for HIV and confirmed to have HIV. Testing of blood donations also adds a layer of protection against transfusion-associated adverse events. Blood group compatibility testing along with additional antibody testing and serological testing for known transfusion-transmitted infections occurs. Guidelines to ensure the diligent and appropriate use of blood transfusion improves safety and reduces adverse outcomes for patients receiving a transfusion. Close clinical correlation and symptomatic responsiveness also improve patient outcomes. Monitoring of transfusion has also improved over time with more emphasis placed on accurate monitoring for evaluation of transfusion reactions. Alternatives and extended shelf life options have expanded the scope of transfusion and possibilities to reduce collections and augment alternatives to transfusion. A summary of the strategies for reducing the risks associated with blood and blood products are in Figure 1 below.

Indications

The indications for blood transfusion consist of increasing hemoglobin and oxygenation of tissues, maintaining adequate blood volume to avoid ischemia and hypovolemic shock, and to replace platelets, coagulation factors, and other plasma proteins to reconstitute blood to a functional status. Hemoglobin and hematocrit along with clinical symptoms of anemia have been the traditional markers used to determine the threshold for transfusion of red blood cells. Hemoglobin of less than 10 g/dL or a hematocrit of less than 30% has traditionally been the benchmark as the laboratory indication for transfusion in the right clinical context. Recently, there has been increasing evidence that a lower threshold is associated with better outcomes and conservation of precious blood resources even in critically ill populations [2]. There is some evidence that the transfusion trigger level may be slightly higher in certain conditions such as sepsis with inadequate oxygen delivery, acute coronary syndrome with ischemia, and surgical hemorrhage (reference) or in specific populations such as the elderly; however, due controlled trials and meta-analysis data there has been a decrease in the implementation of liberal transfusion protocols [3]. Restrictive transfusion even in patients with cardiovascular disease, acute illness, and traumatic brain injury using a threshold of Hgb 7 to 8 g/dL has shown no increased risk of morbidity and mortality.[4][5] There is still variability globally in transfusion thresholds for particular patient populations.[6][7]

Fresh frozen plasma is used to replace coagulation factors in specific coagulopathies such as in liver disease when bleeding is present, reversal of warfarin effect when prothrombin complex concentrate is unavailable, thrombotic thrombocytopenia purpura, plasmapheresis, and other coagulation inhibitor deficiencies where specific concentrates of each are not available. Cryoprecipitate can be useful as an alternative for factor concentrates in inherited deficiencies such as von Willibrand disease, and hemophilia A and B only when concentrates are unavailable. It can also be used to replenish fibrinogen in acquired coagulopathies such as DIC. These and additional indications and contraindications as well as important safety profile information to remember are also in Table 1.[2]

Contraindications

Several contraindications listed by specific blood product are in Table 1. Significant contraindications that merit consideration include the risk of transfusion in a patient who is volume overloaded, platelet administration in microangiopathic hemolytic anemias, untreated DIC, and thrombocytopenia in septicemia and hypersplenism. Another important consideration is to avoid transfusion of blood without prior compatibility testing and antibody screening.

Equipment

Per the American Association of Blood Banks, all blood donation equipment is sterile, used once, and then discarded to avoid contamination from donor to donor that could later affect multiple recipients of transfusion. The equipment used for blood donation collection such as blood pressure monitors, scales, blood collection monitors/mixers, blood bag tube sealers, transportation boxes, and refrigerators are calibrated, cleaned, and serviced routinely. The chairs and couches used in the area of blood donation are to be of cleanable surfaces such as vinyl. Transport supplies and containers are also cleanable according to the World Health Organization guidelines. All blood bags should undergo routine inspection for sterility, expiration date, appearance, and any evidence of leakage or defects at the time of donation collection.

Personnel

Phlebotomy and collection should be via qualified personnel trained in transfusion services and blood donation. Donation monitoring is under the overall responsibility of a medical practitioner or authorized personnel who can manage adverse reactions. Transfusion is also performed with adequate oversight and under the purview of a medical practitioner or other qualified health care professional. Real-time monitoring of patients during transfusion reactions ensures that accurate information is available for the work-up of suspected transfusion reactions. Laboratory technicians are trained and educated on the importance of appropriate and precise testing for possible infectious agents before transfusion, blood group and compatibility, potential antibodies, and post-transfusion work-up for hemolysis. Transfusion service personnel when committed to following guidelines and determining and monitoring thresholds for transfusion have significantly impacted the safety of blood product utilization.

Preparation

To assure blood product safety, several measures require implementation during product collection, manufacturing, and storage. The World Health Organization has supported a global initiative to improve access to safe and sufficient blood supply. Once collected, the blood donation is tested for blood type and screening for any clinically significant antibodies. The collecting facility typically holds the blood until appropriate preparation, and routine screening of potential transfusion-transmitted infections is complete.

Wide-spread prioritization of testing for transfusion-transmitted infections has improved blood product safety worldwide. There is a summary of information on countries who responded to questionnaires about their particular policies and guidelines surrounding testing of donor blood in Graph 1 according to the World Health Organization 2016 Global Status Report on Blood Safety and Availability. The survey found that the majority of countries responding had policies for testing the most common and clinically relevant transfusion-transmitted infections including HIV, hepatitis C, hepatitis B, and syphilis. Eighteen nations in Latin America reported having a policy for testing all blood donations for Trypanosoma cruzi along with twelve countries implementing selective testing for T cruzi for donors who have traveled to high-risk areas or have defined risk factors. Thirty-seven nations reported having a policy of testing all blood donations for human T-lymphotropic virus (HTLV-I/II) antibody along with seven countries reporting selective testing for new donors.

Following collection of a blood donation, several procedures can take place for the preparation of blood for transfusion. Leukodepletion is a procedure to reduce the number of white blood cells in a blood product to reduce the risk of febrile reactions, HLA sensitization, and CMV transmission. Bacterial contamination testing can be performed prior to transfusion to avoid septic transfusion reactions. Plasma fractionation provides the opportunity to derive specific factors concentrates and intravenous immune globulin. Irradiation of blood products can also be performed to reduce the risk of transfusion-associated graft-versus-host disease which is universally fatal.[8] Plasma reduction or washing of blood products reduces the number of immunoglobulins within the blood product which reduces the risk of allergic transfusion reactions; this can also be used to reduce excess potassium and cytokines which can cause electrolyte imbalance and febrile non-hemolytic transfusion reactions respectively.[9][10] Blood typing and screening of donor and recipient antibodies as well as compatibility testing are also important aspects of preparation for transfusion. Antibody screening is essential in the prevention of hemolytic transfusion reactions.

The new frontier in blood product safety is pathogen reduction/pathogen inactivation which is a broad term for various methodologies applied to blood products post-collection to reduce the risk of transmission of infectious agents.[11] Many of these technologies confer protection across different classes of infectious agents including viruses, bacteria, and parasites. Another potential benefit is that some of these technologies also inactivate donor white blood cells which have allowed some to gain approval for the prevention of transfusion-associated graft-versus-host disease as an alternative to irradiation. Pathogen reduction is currently an approved policy in some countries for platelets and plasma.[12] These novel technologies can increase the shelf life of platelets and decrease the incidence of adverse transfusion reactions and bacterial contamination. These approaches are increasingly common in practice and with usage approval will help improve blood product safety profiles.[13]

Technique

An important aspect of the donation process is the donor screening questionnaire. Donor recruitment represents an essential front line mechanism for ensuring blood safety. The highest rates of transfusion-transmitted infections are present among donors receiving monetary compensation, and conversely, the lowest rates of infection are among unpaid volunteer donors.[14][15] A great reduction in the risk of transfusion-transmitted HIV, HCV, HBV, and syphilis infections has transpired with the initial donor screening questions and improved testing including serology and nucleic acid amplification testing.[16][17] According to the United States Food and Drug Administration, estimates are that highly sensitive donor screening validation questionnaires designed to defer high-risk donors for infection transmission exclude 90% of potentially infectious donors from blood donation.

Individual blood service organizations may have subtle variations in the collection procedure, but the World Health Organization has guidelines on the proper technique for venepuncture for blood donation purposes.  These processes standardize the process and are in place to prevent transfusion-transmitted infections. The process is very similar for blood collection for other testing purposed; however, there are some differences and additional measures with donor safety and minimizing contamination potential of high priority. A safe collection is paramount to ensuring blood products remain safe through collection, storage, and transfusion.

Contaminants typically come from normal skin flora; therefore, proper antiseptic technique before the collection is paramount. The recommended procedure by the World Health Organization includes application of combination 2% chlorhexidine gluconate and 70% isopropyl alcohol for 30 seconds followed by 30 seconds drying time.  A closed collection system is used to ensure sterility even further. This procedure means that the anticoagulant-containing collection bag has intrinsically attached tube and needle. The first 15 to 20 mL of blood is collected in a diversion bag so that in the case of skin contamination the initial blood collected is discarded. This discarded blood is the most likely to be contaminated by skin flora and the skin plug, therefore discarding this collection minimizes contamination risk.[18]  Blood volumes collected vary by the technique used. According to the World Health Organization, generally for whole blood transfusion, 350 milliliters of blood is collected, and for double or triple bags to make packed red cells, fresh frozen plasma, and platelet concentrations, a volume of 450 milliliters is necessary. The volume is selected to prevent donor transfusion-associated anemia and other adverse events.

Blood donations can be separated into four main components (red blood cells, white blood cells, plasma, and platelets) or left as whole blood. Once the blood has undergone processing, it is stored +2 C to +6 C at appropriate temperatures.[19][20] Platelets and fresh frozen plasma (FFP) require preparation within 8 hours of collection. Platelets are stored at room temperature and on agitation for generally five days unless additional shelf life extending mechanisms are employed.[21] Fresh frozen plasma can remain stored at −18 C for one year, −25 C for 36 months, or at −65 C for seven years.[19] The temperature and duration of storage depend on blood service guidelines and storage capabilities of individual institutions. Sterility is maintained during processing and storage steps to avoid contamination. Blood units are unavailable for transfusion until undergoing appropriate testing including ABO and Rh blood group typing, antibody screening, as well as serologic testing for transfusion-transmitted infections.

Complications

According to the World Health Organization Guidelines on Drawing Blood: Best Practices in Phlebotomy, complications of blood donation include from most likely to least likely a hematoma, vasovagal reaction or syncope, delayed syncope, arterial puncture, and nerve damage. Complications of transfusion include transfusion reactions and transfusion-transmitted infections. The risk of transfusion-transmitted infection has become very low in developing countries with a risk of less than 1 in 1 million for most of the most concerning pathogens such as HIV, HCV, and HBV.[16] The donor screening to select blood from only low-risk donors has had the most significant impact on the reduction of pathogens transmitted through transfusion. Exclusion criteria include medical history, high-risk behaviors, physical examination findings, geographic and travel exclusions. There are also serologic and nucleic acid amplification tests that have reduced the risk of infectious agent transmission. Although the risk of transfusion-transmitted infectious has decreased substantially, bacterial contamination in platelets stored at room temperature is still a concern for the risk of septic transfusion reactions. Bacterial contamination is typically from commensal bacteria normally found on the skin of donors or from transient bacteremia in donors. Another increasing concern is transfusion-transmitted emerging pathogens such as Zika virus and babesiosis.

As the risk of infectious complications has decreased, noninfectious transfusion complications have become the primary area of concern and focus for improvement. The efforts focused on detection, recognition, and reporting of transfusion-related adverse events has improved the safety of transfusion of blood and blood components. Transfusion reactions that can occur with the transfusion of blood and blood products range from life-threatening reactions to a reaction in which transfusion can continue. Some of the reactions that exist include the following:

  • Transfusion-associated circulatory overload (TACO)
  • Transfusion-related acute lung injury (TRALI)
  • Transfusion-associated dyspnea (TAD)
  • Allergic reaction
  • Hypotensive transfusion reaction
  • Febrile non-hemolytic transfusion reaction (FNHTR)
  • Acute hemolytic transfusion reaction (AHTR)
  • Delayed hemolytic transfusion reaction (DHTR)
  • Delayed serologic transfusion reaction (DSTR)
  • Transfusion-associated graft vs. host disease (TAGVHD)
  • Post-transfusion purpura (PTP)
  • Transfusion-transmitted infection (TTI)

With efforts to reduce TRALI, transfusion-associated circulatory overload (TACO) has been an emerging cause of morbidity and mortality in patients receiving blood transfusions.[22] Improved awareness around transfusion reactions and their etiology has improved blood product safety.[23][24][25][26] The incidence rates for several of the complications of transfusion and specific transfusion-related adverse events are in table 2.[27][28][29][30]

Clinical Significance

Blood product safety is an essential aspect of quality health care received throughout the world. Approximately 112.4 million units of blood are collected globally every year according to the World Health Organization. Nearly 14 million units of blood (whole blood and packed red blood cells) are transfused annually worldwide.[31] According to the American Red Cross, estimates are that 36000 units of blood are necessary every day in the United States. Blood transfusion is a lifesaving procedure that occurs every day in hospitals and institutions throughout the world.

There has been a push to move away from blood transfusion and requiring more stringent guidelines for blood and blood product utilization has had a big impact on usage. Per the National Blood Collection and Utilization Survey (NBCUS), there has been a steady decline in the rate of transfusions in the US without a significant adverse effect on morbidity and mortality.[32] This finding is likely due to advances in surgical management of patients as well as policies for judicious utilization of blood products in part due to evidence that liberal usage of blood products has correlated with poor patient outcomes.[33] Several studies have found a correlation between perioperative transfusion and increased morbidity and mortality as well as a longer length of stay during hospitalizations.[34][35][36] Considering these findings clinically restrictive transfusion protocols have shaped more recent guidelines across many countries.[37][38] However, there is a delicate balance treating symptomatic and perioperative anemia along with preventing transfusion-related adverse events.[39][40]

Transfusion reactions continue to be a significant cause of increased hospital stays, and adverse patient outcomes. Transfusion reactions occur in up to 1 in every 100 transfusions making transfusion reactions the highest frequency adverse event associated with transfusion and important clinical consideration of which to be aware for patients receiving transfusions.[41] Considering the number of transfusions that take place worldwide, blood product safety is an important part of improved patient care. The education of clinical staff surrounding symptoms for suspecting a transfusion reaction as well as efforts aimed at the judicious use of blood products has improved the safety of transfusion.[31] Blood and blood product transfusion is a life-saving procedure that has significantly improve patient outcomes with its utilization. However, efforts restricting the use of blood products to patients in need, improving isolation and storage of blood products, and improved alternatives are all ways for further improvements in the safety of this medical lifeblood procedure.

Enhancing Healthcare Team Outcomes

Nurses, trained technical staff, and phlebotomists, in collaboration or independently, are involved in screening, examining, and monitoring blood donors throughout the donation process in a safe and standardized manner. Laboratory personnel is crucial to the testing and handling of blood products to ensure safety. Nurses and other personnel play a pivotal role in verifying patient information and ensuring that the correct blood product gets to the designated patient. Nurses monitoring and documenting vital signs and patient symptoms during blood transfusions are a critical part of patient safety and work-up of possible transfusion reactions. Pharmacist clinicians assist in premedication for patients with known allergic reactions or febrile non-hemolytic transfusion reactions during blood transfusions, and in the case of mild allergic transfusion reactions, pharmacists help with medication so that the transfusion can resume. Laboratory technicians play a role in monitoring blood transfusion criteria and physician ordering of blood and blood products to contribute to transfusion mindfulness and hemovigilance efforts [42][43] (Level V evidence).


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