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Today, blood transfusions nearly always consist of the ad-ministration of 1 or more components of blood. Whole blood transfusion is now limited to situations involving massive resuscitation (trauma). The most commonly used component is packed RBC, but several others, including platelets, plasma, and cryoprecipitate, are used as well. In this review, we will discuss the processing, uses, indications, contraindications, and other important features of blood components.

Packed RBCsPacked RBCs (pRBCs) are prepared from 1 unit of a

whole blood donation by centrifugation. From 1 unit (450- 500 mL) of whole blood, 200 mL of RBCs are obtained (Figure 1).

Various anticoagulant-preservative solutions (50 to 100 mL) are used to prolong the shelf-life of the cells. One solution is CPDA-1, which allows pRBCs to be stored for 35 days at 1-6°C. ADSOL is another solution that extends the life of the unit to 42 days. During storage, RBCs age in processes similar to in vivo aging. Therefore, the spleen rapidly clears a portion of the cells on transfusion. Another process during storage is leakage of intracellular potassium into the unit. Although measured levels of potassium in 1 unit can be alarmingly high, hyperkalemia is rare following a pRBCs transfusion.

Red blood cell transfusions must be serologically com-patible (Table 1). The most important blood typing system involves the ABO antigens, present on all RBCs. As an infant, humans develop IgM antibodies to the antigens that they do not have.

For example, a person with the blood type A has anti-B antibodies, and vice versa. People with the blood type O contain no antigens, therefore they have anti-A and anti-B antibodies. These antibodies are in the recipient’s plasma and will attack donor RBCs if the antigen is presented. A recipi-ent may receive RBCs with any antigen that they already have (because they do not have an antibody to it), so AB patients can receive type A, B, AB, or O blood.

Update and Utilization of Component Therapy in Blood Transfusions Stacy A. Gurevitz, MD (Department of Pathology, Baylor University Medical Center, Dallas, TX)DOI: 10.1309/LMQHWOGYICR84M8Q

Abstract Transfusion medicine has undergone diverse and fascinating advancements since its initiation in the early 20th century. One of these was the discovery that blood can be divided into individual components and delivered

separately. This is imperative in this field, where there is high demand but little supply. In this review, we strive to elucidate the most important elements of 4 commonly used components.

Keywords: component therapy, blood banking, transfusion medicine, packed RBCs, plasma, platelets, cryoprecipitate, ABO compatibility

After reading this article, readers should have improved understanding of new and updated concepts in blood component therapy, while continuing to understand the theories and history of this diverse treatment.

Hematology exam 51002 questions and corresponding answer form are located after this CE Update on page 241.

AbbreviationspRBCs, packed red blood cells; TRAP, Trial to Reduce Alloimmunization to Platelets; DIC, disseminated intravascular coagulation; TTP, thrombotic thrombocytopenic purpura; vWF, von Willebrand factor; FFP, fresh-frozen plasma; TRALI, transfu-sion-related acute lung injury; AHF, antihemophilic factor; DDAVP, desmopressin

Corresponding AuthorStacy A. Gurevitz, MDStacyGurevitz@gmail.com

Submitted 6.4.10 | Revision Received 7.19.10 | Accepted 8.23.10

Note from the Editor-in-ChiefDespite the best efforts of our Reviewers and Editorial staff, errors can occur in articles published in

LabMedicine that warrant more than just publication of an “Erratum,” including republishing an article with the errors corrected. The corrected CE Update below on a transfusion medicine-related topic is a case in point. Fortunately, these circumstances occur with rare frequency; however, when they do occur, the Editorial staff of LabMedicine review carefully the circumstances and act based on the best interests of the author, LabMedicine, and its readership.

The right thing to do never requires any subterfuge, it is always simple and direct. ~Calvin Coolidge~

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ABO incompatibility leads to complement activation against the donor RBCs, leading to intravascular hemoly-sis. This is extremely dangerous and can lead to mortality. Unfortunately, the most common cause of this situation is clerical error, such as misidentification of a patient.2

Another important blood group is the Rh system, named for the rhesus monkeys that aided in the discovery.3,4 The Rh system includes several antigens, but the terms Rh positive or negative refer only to the D antigen, also known as the Rh factor. About 80% of Cau-casians are positive for the D antigen. Those who are not may have developed an anti-D antibody from previous expo-sure, most commonly via pregnancy or transfusion. Because anti-D antibodies are mostly IgG, which does not activate complement, a patient with anti-D antibodies who is given D positive (Rh positive) blood is likely to undergo ex-travascular hemolysis. It is important to avoid immunization of females to the D antigen by giving Rh-negative females only Rh-negative pRBCs because, un-like the IgM antibodies found against the ABO antigens, IgG antibodies do cross the placenta. This can lead to a very harmful condition during pregnancy (even several years after immunization) called hemolytic disease of the newborn.

Several other clinically significant antibodies present in the recipient’s serum must be eluci-dated by a test called the antibody screen. A posi-tive antibody screen requires additional testing to determine the identity of the antibodies present.5

Indications for transfusion of pRBCs include symptomatic anemia, which manifests as high pulse rate, increased respiratory rate, dizziness, and weakness. While there is no standard hemo-globin or hematocrit used to define a need for transfusion, most institutions set one. A hemoglo-bin of less than 7 g/dL or 8 g/dL are commonly used cutoffs. Packed RBC transfusions should not be used to treat nutri-tional deficiencies or to expand blood volume.6

Several institutions are adopting measures to ensure physicians are ordering pRBCs and other blood components appropriately. One way of doing this is to encourage the physician to determine and state the indication on the order form. An example of this form is seen in Figure 2.

One unit of pRBCs should increase the hemoglobin by 1 g/dL to 1.5 g/dL and the hematocrit by 3%-5%.5 One unit should typically be transfused in less than 4 hours. As with all blood components, only normal saline should be adminis-tered in conjunction with pRBCs to protect the cells against osmolarity disruption.7,8 Solutions with calcium (ie, lactated Ringer’s) should be avoided because the effectiveness of the citrate anti-coagulant could be reduced in the presence of high levels of calcium. Medications should not be added and a blood warming device should be used if necessary.9

Platelets

Platelets are prepared by centrifugation of plasma and removal of the platelet-poor component.5 This process yields a unit of approximately 50 mL and is termed random donor platelets. Four to 6 of these units are nearly always pooled prior to transfusion. Alternatively, in an apheresis process called plateletpheresis, platelets are separated from whole blood at the time of donation and the remainder of the blood is transfused back to the donor. The advantage of this process is that it can yield a single donor platelet unit of 200-500 mL. One single donor unit must contain a minimum of 3.0 × 1011 platelets. It is possible to obtain 3 single donor units from 1 donor during 1 apheresis session.9

In the United States, plasma is retained in the unit for pres-ervation; also, the anticoagulant used during the whole blood collection or apheresis procedure serves as preservation media.5,10 Platelets are stored at room temperature (20-24°C) with gentle agitation for 5 days. The purpose of the agitation

Figure 1_Blood Component Processing Summary. Whole blood is separated into pRBCs and platelet-rich plasma. The plasma component can be further separated into platelets and platelet-poor plasma. Cryoprecipitate can be extracted from plasma via a slow thaw.

Table 1_Recipient Antibodies and Compatible Donor RBC Blood Types

IgM Antibody in pRBCs Donor Blood Type Recipient Blood Type Recipient Plasma Compatible for Recipient

O Anti-A, B OA Anti-B O, AB Anti-A O, BAB None O, A, B, AB

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is to prevent platelet packing and increase oxygenation of platelets, favoring aerobic metabolism.11

Platelets contain the ABO antigens; however, the concen-tration is only about 5% of that in RBCs. Recipient anti-A or anti-B antibodies may affect platelet survival, but should not cause a harmful reaction to the patient.12 It is acceptable prac-tice to administer unmatched platelets.6

Rh is not expressed in platelets and therefore a mis-match should have no effect on platelet survival,12 but Rh-negative women of child-bearing age should receive only Rh-negative platelets to prevent isoimmunization because platelets do contain a small number of RBCs that can be Rh positive.6

More clinically relevant are the HLA class-I antigens present on the WBCs in the platelet unit.13 Transfusion, especially with pooled-platelets (multiple donors), leads to alloimmunization to the HLA antigens. Future platelet (and other component) transfusions are subject to these antibodies, possibly deeming the patient refractory to platelet transfu-sion.14,15 The landmark Trial to Reduce Alloimmunization to Platelets (TRAP)16 study showed that leukocyte reduction is an extremely useful process to prevent alloimmunization by platelet transfusion. Also, single-donor platelets vastly decrease exposure to HLA antigens.

Patients should obtain a rise of 20,000 to 40,000 plate-lets/uL following 1 unit, measured at 10 to 60 minutes following

Figure 2_Blood Transfusion Order Form. In order to increase the appropriate use of blood products, several institutions have adopted forms such as this one, used at Baylor University Medical Center in Dallas, TX. Physicians are encouraged to identify which of the indications has been identified in their patients. This form also allows for easier review of the reasons for transfusion in an institution.

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transfusion.9 It is important to consider variables when determining expected rise, including number of platelets transfused, recipient surface area, and the time interval between transfusion and measure-ment.9,13,17 Refractoriness to platelets is defined as a platelet count that is less than expected.13 There are several causes. Infections shorten platelet sur-vival. Splenic uptake, bleeding, and disseminated intravascular coagulation (DIC) can reduce platelet counts. Alloimmunization by HLA antigens (see above), ABO mismatch, and anti-platelet antibodies are immunologic reasons for platelet destruction.17 Anti-platelet drugs already in the patient’s system can inactivate platelet function without reducing platelet number.

Bacterial contamination of blood products was responsible for 28 (13%) transfusion-associ-ated fatalities in the fiscal years of 2005 through 2008; of these, platelets (single-donor and pooled) were responsible for the majority (15 deaths).2 This is likely because platelets are stored at room temperature.18 Blood banks are required by the AABB, an international association of blood banking, to take preventative measures by detect-ing bacterial contamination in platelet units.19 The most frequently identified organisms are the gram-positive bacteria that contaminate the skin (Staphylococcus sp.). For this reason, several strategies to clean the skin and divert the first part of drawn blood (including the skin plug) are in place. Additionally, labs must screen platelets for contamination prior to transfusion. There are sev-eral options for doing so, including glucose moni-toring, pH testing, or culture-based systems. All, however, carry a risk of false-negative results.

Indications for platelet transfusion vary by stability of patients. In stable patients, a count of less than 10,000/uL is an indication for transfu-sion. In febrile patients, a cutoff of 20,000/uL can be used. Bleeding patients or those undergoing surgery or an invasive procedure can be transfused when their platelets are less than 40,000-50,000/uL. Finally, a cutoff as high as 100,000/uL should be used when patients have an intracranial bleed or bleeding of the retinal vessels.9

Platelet transfusion is an absolute contraindication in thrombotic thrombocytopenic purpura (TTP), an autoim-mune microangiopathic hemolytic anemia. Patients have inhibiting autoantibodies to the enzyme ADAMTS13, which is responsible for the breakdown of von Willebrand fac-tor (vWF).20 There are other causes, but the final common pathway is increased activation and aggregation of platelets, leading to microthrombi in vessels. These microthrombi shear the RBCs. Transfusion of platelets enhances the formation of microthrombi, drastically worsening the disease course.21 Alternatively, a plasma exchange transfusion should be started as soon as possible.

PlasmaPlasma is the supernatant of centrifuged whole blood. It

is then drawn off into its own unit bag, which measures 250 mL. Alternatively, apheresis technology allows for 2 units to

be drawn from 1 patient into a “double” unit bag of about 500 mL. If plasma is isolated from the unit of whole blood and frozen within 8 hours from donation, the unit is termed fresh-frozen plasma (FFP). If the plasma unit is frozen more than 8 hours but less than 24 hours from donation, it is named FP24. FFP and FP24 can remain at -18°C for up to 1 year. These units are thawed at 37°C, and then they are relabeled as thawed FFP or thawed FP24 and can be kept at refrigerated temperatures for 24 hours. After 24 hours, they are renamed thawed plasma and can be stored for up to 5 days.9

Recent studies have shown that thawed FP24 should be considered an acceptable alternative to thawed FFP.22,23 These studies were warranted by the idea of restricting plasma do-nors only to males due to the decreased chance of transfusion-related acute lung injury (TRALI).24 Transfusion-related acute lung injury is caused by antibodies in the plasma against anti-gens on recipient leukocytes.9,14,25 These antibodies are more likely in females because of past pregnancies. Either gender may obtain these antibodies during past blood transfusions. Although TRALI is much more common during plasma transfusions, it is possible during any blood component transfusion.14

Pretransfusion testing must include an ABO and Rh type. Patients with type A, B, or O contain antibodies to the

Glossary of Terms

CPDA-1: Citrate phosphate dextrose adenine, a preservative used in packed RBCs.

ADSOL: Adenine, dextrose, sorbitol, sodium chloride and mannitol; a preservative used in packed RBCs.

Anemia: Reduced number of RBCs or hemoglobin in the blood stream.

Antigens: A molecule recognized by the immune system.

HLA class-1: Human leukocyte antigen; the major histocompatibility complex in humans; present antigens to immune cells.

Antibodies: Immune system protein that identifies and neutralizes foreign objects, such as viruses and bacteria.

Immunization: Formation of antibodies against an antigen.

Complement: Biochemical cascade that aids the ability of antibodies to destroy pathogens.

DIC: Disseminated intravascular coagulation; pathologic activation of the coagulation cascade in which small blood clots are formed in the small vessels of the body; these clots consume coagulation proteins and platelets, leading to abnormal bleeding.

Hemolysis: Destruction of RBCs.

dDAVP: 1-desamino-8-D-arginine vasopressin; a synthetic replacement for the hormone vasopressin. Apheresis: Procedure in which blood drawn from a donor or patient is passed through an apparatus separating the blood into constituents, some of which are returned back to the donor or patient.

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antigens that they do not have. Patients with blood type AB do not contain these antibodies (Table 2). An antibody screen is usually performed at the donor center, and plasma with known antibodies are labeled as such and possibly withheld from distribution. AB plasma is the universal donor plasma and may be transfused to patients of any blood type.

Plasma transfusion is indicated in settings where the patient is known to have multiple clotting factor deficiencies with active bleeding, such as liver disease and warfarin therapy, and not to supplement a known deficiency of 1 clotting factor if there is a factor concentrate available. Factor concentrates are safer.9 In treatment of TTP, an exchange transfusion removes the patient’s autoantibody by removing plasma. Donor plasma, containing valuable vWF protease activity, is transfused simultaneously.26,27 This sometimes emergent procedure can be lifesaving. Plasma transfusion should not be used as a volume-expander or in the setting of nutritional deficiency without factor deficiencies.9

CryoprecipitateCryoprecipitated antihemophilic factor, known as cryo-

precipitate or cryo, is extracted from frozen plasma (FFP or FP24) by slowly thawing a unit at 1°C-6°C.5 (When being prepared for transfusion, FFP or FP24 are thawed more rap-idly at 37°C.) This process produces a slushy-like substance, which is centrifuged to separate the insoluble component. Once removed, the cryo unit must be refrozen within 1 hour and expires 1 year later.

One unit of cryo is 15 mL. Cryo contains at least 150 mg of fibrinogen and at least 80 IU of factor VIII. These represent 20%-40% of the fibrinogen and 50% of the factor VIII of the original unit of plasma. Von Willebrand factor is another important component of cryo.9

ABO compatibility is suggested, but not required for cryo transfusion.6 One unit of cryo should lead to a rise in the re-cipient’s fibrinogen by 5-10 mg/dL.5 Often 8-10 units of cryo are pooled.

Historically, Dr. Judith Graham Pool’s discovery in 1965 that cryo is rich in factor VIII and can be transfused28 led to a major advancement in the treatment of hemophilia A. Only small volumes of cryo are needed, eliminating the volume-over-loading that came with transfusion of plasma units. Addition-ally, since the product could be stored in blood banks, patients with hemophilia A were granted access to elective surgeries and underwent much safer emergent surgeries. In the 1970s, factor concentrates became available, and now cryo should be used to treat hemophilia A only when these are not accessible.6

Von Willebrand disease, like hemophilia A, is an inher-ited bleeding disorder. Patients with the disease have mutations

making a defective version of vWF or make too little of it. Von Willebrand factor normally forms bridges between platelets and endothelial cells, an essential part of primary hemostasis. Another important role of vWF is as a carrier protein for factor VIII. Factor VIII has an extremely short half-life when not bound to vWF. Discovered in 1977, desmopressin (dDAVP), a synthetic analog of antidiuretic hormone, increases circulating fac-tor VIII and vWF by promoting release of vWF from endothelial cells.29 While this treatment is very effective in patients with a quantitative

deficiency in vWF (Type I vWD), it is essentially ineffec-tive in patients with a qualitative defect in or virtually absent numbers of vWF (Types II and III, respectively).30 Addition-ally, patients with Type I vWD can be refractory to dDAVP. While cryoprecipitate can be used to treat these patients, it is no longer the standard of care. Factor VIII concentrates that contain vWF are safer and more efficacious alterna-tives.6,31,32,33,34

Currently, cryo is used mainly as a replacement for fi-brinogen.5 This is required in several situations, including liver failure, DIC, or massive transfusions. However, in these situations it is important to examine patients for deficiencies in other clotting factors, in which case FFP would be pre-ferred. Cryo can be used when uremic patients are bleeding and when there are rare congenital deficiencies in fibrinogen.

SummaryComponent therapy is a fascinating use of a limited re-

source. Innovative discoveries regarding patient disease and technological advances to blood preservation and storage continue to expand this field of medicine, and therefore it is imperative to understand the basis of each component. LM

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Table 2_Antigens on Recipient RBCs and Compatible Donor Plasma

Antigen on Plasma Donor Blood Type Recipient Blood Type Recipient RBCs Compatible For Recipient

O None O, A, B, ABA A A, ABB B B, ABAB A, B AB

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31. Mannucci, PM. Treatment of von Willebrand disease. Haemophilia. 1998;4:661. 32. Mannucci PM, Chediak J, Hanna W, et al. Treatment of von Willebrand disease

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