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Advances in blood transfusion

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Keeping up with advances in transfusion medicine is crucial for nurses, who often are responsible for transfusing blood components. This article discusses modern blood-collection technology, hemo­vigilance efforts, transfusion-associated adverse events, and the continuing search for blood substitutes.

Manual collection vs. apheresis

When people think of blood donation, they picture donors with needles in their arms and an attached blood bag hanging near the floor to take advantage of gravity and boost blood flow into the bag. These manually collected whole-blood units are transported to the component laboratory of the blood collection center, where they’re centrifuged; separated into plasma, platelets, and red blood cells (RBCs); and placed in separate plastic storage bags. During processing, white blood cells (WBCs) usually are removed from RBCs (a process called leukoreduction) via filtering through special filters. Leukoreduction mitigates febrile nonhemolytic transfusion reactions and reduces the risks of cytomegalo­virus transmission and alloimmunization to human leukocyte antigens (HLAs).

Next, the blood units are tested, labeled, and stored appropriately until they are distributed to hospital transfusion services, which release the components to the appropriate patient. Each component has different storage requirements designed to maintain viability.

Today, most of the approximately 14 million blood units collected annually in the United States are obtained through this manual method. But apheresis technologies, which allow operators to select and collect specific components, are coming into wider use. Donors may donate whole blood through the manual method, or they may be able to donate a specific component through apheresis.

Blood components collected by apheresis offer several advantages over manually collected whole blood. Because apheresis separates the components, the blood doesn’t need further processing. Most platelet components transfused in this country are single-donor platelets; many apheresis devices allow collection of plasma and RBCs simultaneously with platelets. Although components still need to be tested, labeled, and stored appropriately, apheresis eliminates one processing step. Some apheresis devices also leukoreduce RBCs and platelets, eliminating the need to filter them in the laboratory.

Platelet apheresis

Platelet transfusions, used to prevent and treat bleeding, are given to patients undergoing chemotherapy, hematopoietic progenitor-cell and solid-organ transplantation, and surgery, as well as those with hematologic disease, sepsis, or other conditions that cause thrombocytopenia. When patients become refractory to platelet transfusion (most commonly from antibodies to HLA), HLA-matched platelets are collected from matched donors or family members using apheresis technology.

Over the last 15 years, we’ve seen a shift from whole blood–
derived platelets obtained through whole-blood collection to single-donor platelets obtained through apheresis, due largely to prestorage leukoreduction and bacterial testing requirements. Also, platelet products now must be tested or must come from donor blood at low risk of causing transfusion-related acute lung injury (TRALI). TRALI typically results from antibodies to donor WBCs, so platelet and plasma products can be collected only from low-risk or tested donors.

Until recently, whole blood–derived platelets were leukoreduced at the bedside. But the bedside method doesn’t mitigate febrile reactions; what’s more, quality control is hard to maintain. Transfused platelets are more likely than other components to lead to septic reactions because they’re stored at room temperature, allowing bacteria to multiply rapidly. Bacteria can be detected through multiple methods; until recently, though, detection was problematic. Acrodose™, a relatively new system in the United States, now allows prestorage leukoreduction and pooling, as well as bacterial detection, with systems used mainly for apheresis platelets.

Whole blood–derived platelets must be pooled together with platelets from four to six units of whole blood to obtain an acceptable therapeutic adult dose capable of increasing the patient’s platelet count to a safe level. Pooled platelets must be transfused within 4 hours. In contrast, new technologies allow pooling, leukoreduction, and bacterial testing before storage, as described earlier.

RBC apheresis

RBC transfusions are indicated for patients experiencing RBC loss and severe anemia not caused by nutritional deficiency. Patients with sickle cell disease and thalassemia may need lifelong intermittent transfusions; many develop antibodies to RBCs, complicating transfusion.

Unlike platelet apheresis machines, whose large size makes them difficult to transport to mobile blood-drive sites, automated RBC machines are much smaller and can be used at blood drives held outside of blood-center donor rooms. Generally, these machines collect two leukoreduced RBC components during one sitting.

Plasmapheresis

Plasma is transfused to correct coagulation abnormalities in patients when specific coagulation factor components are unavailable. Plasma products such as platelets must be collected from low-risk TRALI donors or from those tested for antibodies that may cause TRALI in recipients. Plasma products aren’t leukoreduced routinely because they’re stored frozen and thawed before use.

Transfusion-associated adverse events

The primary causes of transfusion-associated deaths are TRALI, transfusion-associated sepsis, and hemolytic transfusion reactions. Other adverse events include allergic reactions and transfusion-transmitted diseases.

TRALI

The leading cause of death from transfusions, TRALI most commonly develops when donor blood contains antibodies to the recipient’s human neutrophil antigens, HLA, or both. This condition is marked by rapid onset of dyspnea and hypoxia within 6 hours of transfusion, sometimes accompanied by fever, cya­no­sis, and hypotension. Clinical examination reveals respiratory distress; pulmonary crackles may occur with no signs of heart failure or volume overload. Chest X-rays show bilateral pulmonary edema not associated with heart failure (noncardiogenic pulmonary edema), along with bilateral patchy infiltrates that may progress rapidly to complete “white-out” indistinguishable from acute respiratory distress syndrome.

Currently, most plasma used for transfusion is collected from males to avoid donors with HLA antibodies that may develop in pregnant women. Use of all-male plasma has decreased TRALI incidence. Because single-donor platelets contain a volume of plasma similar to that in plasma products, TRALI-mitigation strategies extend to these components as well.

But complete exclusion of females from donating platelets would lead to platelet shortages, so blood centers have adopted other methods. In some centers, all female platelet donors who’ve ever been pregnant are screened for HLA antibodies and deferred from platelet donation if these are present. Other centers focus on recruiting male platelet donors preferentially to reduce the number of platelet components donated by females.

Transfusion-associated sepsis

Transfusion-associated sepsis results from bacteria in blood products, particularly platelet products. This condition results in fever, hypotension, and tachycardia. Since bacterial testing of platelets began in 2004, incidence of transfusion-associated sepsis has dropped by one-half to two-thirds.

Hemolytic transfusion reactions

Hemolytic transfusion reactions, which can be acute or delayed, occur when patients receive incompatible RBCs, meaning they have antibodies against donor RBC antigens. Transfused RBCs are hemolyzed, which can result in fever, coagulopathy, renal failure, and anemia.

Hemolytic reactions caused by incompatible RBC transfusions commonly result from errors in blood administration or phlebotomy. Failure to properly label patient samples drawn for typing and crossmatching, or failure to follow appropriate steps to ensure that a unit of RBCs is given to the appropriate patient leads to most hemolytic transfusion reactions related to ABO mismatches. Hospitals are striving to improve blood administration safety and eliminate these potentially fatal errors.

Allergic reactions

Allergic reactions occur in about 1% of transfusions. Urticaria is the most common reaction; some patients also experience dyspnea, swelling, and hypotension. In severe cases, just a few drops of blood can trigger an anaphylactic reaction. With more frequent transfusions, some patients may develop severe allergic reactions.

Transfusion-transmitted diseases

Donated blood currently is tested for infectious diseases, including human immunodeficiency virus, human T-lymphotropic virus, hepatitis B and C viruses, syphilis, and West Nile virus, as well as the parasite Trypanosoma cruzi (which causes Chagas disease). Since such testing began, the residual risk of acquiring one of these infections through transfusion is vanishingly small.

Emerging infections for which screening tests don’t exist include babesiosis and dengue fever. Increasing cases of transfusion-transmitted babesiosis have been reported in New York, Connecticut, Massachusettes, and Rhode Island. Dengue fever is endemic in Puerto Rico and has been reported in Key West and other parts of lower Florida.

RBC substitutes

The search for an acceptable alternative to RBCs has been the focus of extensive research and development over many decades. Multiple products have been developed and tested in clinical trials, spurred by such factors as the AIDS epidemic, the need for emergency transfusions in military and civilian trauma, periodic RBC shortages, transfusion needs in developing countries, and the need for a transfusion alternative for patients with religious objections. Still, no product is available in the United States—and none will be in the near future. (See An update on blood substitutes by clicking the PDF icon above.)

Tracking transfusion events

Tracking adverse transfusion events is a priority in the United States. Hemovigilance refers to the systematic monitoring of adverse incidents arising during the collection, processing, storage, and administration of blood from donor to recipient. Active use of hemovigilance can lead to a safer blood supply and safer transfusion practices. (See Hemovigilance Module: An adverse-event monitoring tool by clicking the PDF icon above.)

Combining efforts

Transfusion medicine is an active area of research and development directed toward improving the safety and availability of blood components. The combined efforts of device manufacturers, basic science, translational and clinical research, and the CDC’s hemovigilance initiative are changing methods of blood collection, testing, and processing and reporting of adverse events. Do your part to help ensure safe transfusion administration by preventing, recognizing, and reporting adverse reactions and events.

Visit www.AmericanNurseToday.com for a complete list of references.

Debra Kessler is a director and Beth Shaz is the chief medical officer at the New York Blood Center in New York City. Kathleen Grima is an executive medical officer at the American Red Cross and the blood bank medical director at the Brooklyn Hospital Center in Brooklyn, New York.

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