The United States has a pluralistic system of blood collection rather than the single national system that exists in other developed countries. In the United States during 2011, approximately 15,721,000 units of blood were available for use (Table 138–1). This was a 9 percent decrease from 2008. Approximately 94 percent of the blood was collected in regional blood centers and hospitals collected 7 percent.¹ Less than 1percent of the units donated in the United States were autologous donations or directed donations, that is, blood given by family or friends for a specific patient. Both autologous and directed donations decreased substantially from 2008.¹ Of red cells collected, 97.7 percent of allogeneic, 59.0 percent of autologous, and 72.0 percent of directed donor red cells were transfused to the intended recipient.

All whole blood for transfusion in the United States is donated by unpaid volunteers; however, costs are incurred in the collection, testing, production, and distribution of blood components. Blood banks pass on these costs to hospitals. Some areas of the United States are able to collect more blood than is needed locally and other areas are unable to collect enough blood to meet their local needs. Several inventory-sharing systems are used to move blood around the United States so as to alleviate the shortages.

Blood is considered a drug and all aspects of the selection of donors, collection, processing, testing, preservation, and dispensing are regulated by the FDA. The FDA requirements define the procedures, record-keeping, staff proficiency, specific testing, and donor medical requirements that blood banks must follow. Blood banks meet these requirements using the FDA-defined good manufacturing practices that are similar to those used by pharmaceutical manufacturers.² Additional standards are formulated by the American Association of Blood Banks (AABB), a voluntary organization that accredits blood banks.

Approximately 107 million units of blood are collected annually worldwide. Considerable differences in the availability of blood and blood components throughout the world are related to the extent of development in the country and the country’s healthcare system.³ The amount of blood collected in relation to the population ranges from 50 donations per 1000 population in industrialized countries to five to 15 per 1000 population in developing countries and one to five per 1000 population in the least-developed countries.³ Thus, industrialized countries utilize transfused blood products far more commonly. In developed countries, especially Western Europe and parts of Asia, a governmental agency usually oversees the blood collection activities, although the extent to which the government sets requirements and monitors or inspects the blood collection system varies. In developed countries, the basic processes of donor medical screening, blood collection, laboratory testing, and preparation of blood components are similar to the system found in the United States. In virtually all developed countries, blood is donated by volunteers because paid donors are associated with a higher risk of disease transmission.⁴ The basic blood components—red cells, platelets, and plasma—usually are available and apheresis instruments are used to collect platelets. Plasma derivatives such as albumin, coagulation factor VIII, other plasma protein concentrates (coagulation factors or inhibitors, or complement factor-1 inhibitor) and immune globulins are available.

However, in the developing world the blood supply is very limited and components are often not available. Patients may be required to arrange for the blood they need so donors may be friends or family members of patients or even individuals who have been paid by the patient’s family to donate the blood needed. Donor screening may not be as extensive, transmissible disease testing may be lacking, and equipment may be reused. These difficulties may be compounded by the presence of endemic transfusion-transmissible diseases for which screening is difficult or expensive and thus not performed as extensively as in more developed countries. Great strides have been made during the last decade primarily from the U.S.-funded President’s Emergency Plan for AIDS Relief (PEPFAR) program.⁵ Thus, the availability of blood and its components around the world varies widely, from inadequate supplies and uncertain safety to sophisticated supply systems and component availability equal to or surpassing those of the United States.

The plasma industry is separate from the blood banking system described above. Plasma can be subjected to a fractionation process to produce several medically valuable products referred to as plasma derivatives. Plasma fractionation is performed in manufacturing plants in batches of up to 10,000 L involving the pooling of plasma from a large number of donors. Plasma for manufacture or fractionation into derivatives can be obtained from units of whole blood, but this amount of plasma is inadequate to meet the needs for plasma derivatives. Consequently, large amounts of plasma are obtained by plasmapheresis in which only the plasma and not red cells or platelets are retained from the donor. Individuals can donate plasma up to two times per week and usually are paid because of the more extensive time commitment. This plasma collection system usually is operated by for-profit organizations and functions separately from the system for whole-blood donation.

Approximately 29 million liters of plasma were collected in the United States in 2013. Twenty-six plasma derivatives are approved for licensure by the FDA. Disruption in the sources of plasma or in one manufacturer’s plant can have serious consequences and create shortages of certain derivatives.

The remainder of this chapter describes the blood collection system operated by voluntary community organizations to provide cellular and whole-blood–derived components.

Although most Americans will require a blood transfusion at some time in their lives, only about one-third of the U.S. population is eligible to donate blood,⁶ and only a small portion of those actually donate. Blood donors are more likely than the general population to be male, age 30 to 50 years, white, employed, and have more education and higher income.⁷ It is generally believed that the most effective way to get someone to donate blood is to ask him or her personally. Factors such as the convenience of donation, peer pressure, receipt of blood by a family member, and perceived community needs are important factors that are superimposed onto the individual’s basic social commitments.

The approach to the selection of blood donors is designed to (1) ensure the safety of the donor and (2) obtain a high-quality blood component that is as safe as possible for the recipient. Some specific steps that are taken to ensure that blood is as safe as possible are the use of only volunteer blood donors; questioning of donors about their general health before their donation is scheduled; obtaining a medical history, including specific risk factors, before donation; conducting a brief physical examination before donation; laboratory testing of donated blood; checking the donor’s identity against a donor deferral registry; and providing a method by which the donor can confidentially designate the unit as unsuitable for transfusion after the donation is completed.

HEALTH HISTORY, PHYSICAL EXAMINATION, AND LABORATORY EXAMINATION OF THE BLOOD

The health history is usually done by a computer-assisted self-interview. The questions designed to protect the safety of the donor include whether the donor is under the care of a physician or has a history of cardiovascular or lung disease, seizures, present or recent pregnancy, recent donation of blood or plasma, recent major illness or surgery, unexplained weight loss, unusual bleeding, or is taking medication(s). Some medications may make the donor unsuitable because of the condition requiring the medication, whereas other medications may be potentially harmful to the recipient. Questions designed to protect the safety of the recipient include those related to the donor’s general health, history of receipt of growth hormone, and occurrence of or exposure to patients with hepatitis or other liver disease, or a previous diagnosis of HIV or AIDS (or symptoms of AIDS), Chagas disease, or babesiosis. A history also is obtained regarding the injection of drugs; receipt of coagulation factor concentrates; blood transfusion; tattoos; acupuncture; body piercing; receipt of an organ or tissue transplant; recent travel to areas endemic for malaria; recent immunizations; ingestion of medications (especially aspirin); presence of a major illness or surgery; and previous notice of a positive test for a transmissible disease. In addition, several questions are related to AIDS risk behavior, including whether the potential donor has had sex with anyone with AIDS, given or received money or drugs for sex, (for males) had sex with another male, or (for females) had sex with a male who has had sex with another male.

The physical examination includes determination of the temperature, pulse, blood pressure, weight, and blood hemoglobin (Hgb) concentration. The donor’s general appearance is assessed for any signs of illness or the influence of drugs or alcohol. The skin at the venipuncture site is examined for signs of intravenous drug abuse, and local lesions that would make disinfecting the skin difficult and thus lead to contamination of the blood unit during venipuncture.

BLOOD CONTAINERS

Blood must be collected into single-use, sterile, FDA-licensed containers. The containers are made of plasticized material that is biocompatible with blood cells and allows diffusion of gases so as to provide optimal cell preservation. These blood containers are combinations of bags and integral tubing that allow separation of the whole blood into its components in a closed system, thus minimizing the chance of bacterial contamination while making storage of the components for days or weeks possible. Plasticizers from the bags accumulate in red cell components during storage and can be found in tissues of multitransfused patients but also in healthy nontransfused individuals. Although no evidence indicates that transfusion of this material causes clinical problems, containers without plasticizers are now used in some countries.

VENIPUNCTURE AND BLOOD COLLECTION

The blood should be drawn from an area free of skin lesions and the phlebotomy site should be decontaminated. The site is scrubbed with a soap solution, followed by the application of tincture of iodine or iodophor complex solution. The venipuncture is done with a needle that should be used only once in order to prevent contamination. The blood must flow freely and be mixed with anticoagulant frequently as the blood fills the container to prevent the development of small clots. The actual time for collection of 450 to 500 mL usually is approximately 7 minutes and almost always is less than 10 minutes. During blood donation, cardiac output falls slightly but heart rate changes little. A slight decrease in systolic pressure results with a rise in peripheral resistance and diastolic blood pressure.

Usually 500 mL is collected. The blood is mixed with 63 to 70 mL of anticoagulant composed of citrate, phosphate, and dextrose (CPD). The amount of blood withdrawn must be within prescribed limits so as to maintain the proper ratio with the anticoagulant; otherwise, the blood cells may be damaged and/or anticoagulation may be unsatisfactory.

An untoward reaction occurs after approximately 2 to 5 percent of blood donations, but, fortunately, most of the reactions are not serious. Donors who have reactions are more likely to be younger, unmarried, have a higher predonation heart rate and lower diastolic blood pressure, lower weight, female, and first-time or infrequent donors. Donors who experience a reaction are less likely to donate in the future.

The most common reactions to blood donation are weakness, cool skin, and diaphoresis.⁸ More extensive, but still moderate, reactions are dizziness, pallor, hypertension, and bradycardia.⁹ Bradycardia usually is considered a sign of a vasovagal reaction rather than hypotensive or cardiovascular shock, where tachycardia would be expected. In a more severe form, a vasovagal reaction may progress to loss of consciousness, convulsions, and involuntary passage of urine or stool. Other reactions include nausea and vomiting; hyperventilation, sometimes leading to twitching or muscle spasms; hematoma at the venipuncture site; convulsions; and serious cardiac difficulties. Such serious reactions are rare. Injury of the brachial nerve and resulting pain and/or paresthesia may occur as a result of needle puncture of the nerve or compression from a hematoma.

Donors are advised to drink extra fluids to replace lost blood volume and to avoid strenuous exercise for the remainder of the day of donation. The latter advice is given to prevent fainting and to minimize the possibility of hematoma development at the venipuncture site. Some donors are subject to lightheadedness or even fainting if they change position quickly. Therefore, donors are advised not to return to work for the remainder of the day if they have an occupation where fainting would be hazardous to themselves or others.

AUTOLOGOUS DONOR BLOOD

Autologous blood for transfusion can be obtained by preoperative donation, acute normovolemic hemodilution, intraoperative salvage, and postoperative salvage, but only preoperative donation is discussed here. Most commonly, this situation occurs with elective surgery. Autologous blood accounts for a very low level (<1 percent) of the United States’ blood supply.¹

If patient candidates for autologous blood donation meet the usual FDA criteria for blood donation, their blood can be used for other patients if the original autologous donor has no need for the blood. However, this practice is not allowed by AABB standards and is usually not relevant because most patients do not meet the FDA donation criteria. If the autologous donor does not meet the FDA criteria for blood donation, the blood must be specially labeled, segregated during storage, and discarded if it is not used by that specific patient. Thus, the autologous blood donation should be collected only for procedures with a substantial likelihood that the blood will be used. Without this type of planning, a very high rate of wastage of autologous blood is observed, estimated at 59 percent in 2011.¹ Thus, the cost of autologous blood is high.

No age or weight restrictions exist for autologous donation. Pregnant women can donate, but this practice is not recommended routinely because these patients rarely require transfusion. The autologous donor’s Hgb may be lower (11 g/dL) than that required for routine donors (12.5 g/dL), although usually only 2 to 4 units of blood can be obtained before the Hgb falls below 11 g/dL. Autologous blood donors can be given erythropoietin and iron to increase the number of units of blood they can donate,^10,11 although this strategy has not been shown to reduce the need for allogeneic donor blood. Reactions in autologous donors are similar to allogeneic donors and are related to first-time donation, female gender, lower age, and lower weight.

Autologous blood must be typed for ABO and Rh antigens. If the unit is to be shipped to another facility for transfusion, it must be tested for transmissible diseases similar to allogeneic blood. If any of the transmissible disease tests are positive, the unit must be labeled with a biohazard label.

DIRECTED DONOR BLOOD

Directed donors are friends or relatives who wish to give blood for a specific patient because the patient hopes those donors will be safer than the regular blood supply. However, directed donors do not have a lower incidence of transmissible disease markers¹² and thus do not support a realistic rationale for these donations. Because the blood becomes part of the community’s general blood supply if it is not used for the originally intended patient, directed donors must meet all the usual FDA requirements for routine blood donation.

PATIENT-SPECIFIC DONATION

In a few situations, appropriate transfusion therapy involves collecting blood from a particular donor for a particular patient. Examples are donor-specific transfusions prior to kidney transplantation, maternal platelets for a fetus projected to have neonatal alloimmune thrombocytopenic purpura (NATP), or family members of a patient with a rare blood type. Usually, these donors must meet all the usual FDA requirements, except that they may donate as often as every 3 days so long as the Hgb remains above the normal donor minimum of 12.5 g/dL. An exception is donation of maternal platelets for a neonate with NATP. Patient-specific donated units must undergo all routine laboratory testing.

THERAPEUTIC BLEEDING

Blood can be collected as part of the therapy of diseases such as polycythemia vera or primary hemochromatosis. Usually such blood is not used for transfusion because the donors do not meet the FDA standards for donor health. As the genetic basis of hemochromatosis has become better understood, blood removed from these patients appears to be safe and red cells from patients with hemochromatosis are normal during blood bank storage,¹³ and although a blood collection program can operate successfully, this has not gained general acceptance.

Blood components can be obtained by apheresis rather than prepared from whole blood. In apheresis, the donor’s anticoagulated whole blood is passed through an instrument in which they use centrifugation to separate the blood components. Red cells, platelets, granulocytes, blood stem cells, mononuclear cells, and plasma can be obtained by apheresis.

PLATELETPHERESIS

In the United States, approximately 92 percent of platelet concentrates are produced by plateletpheresis (see Table 138–1). Plateletpheresis requires approximately 90 minutes, during which approximately 4000 to 5000 mL of the donor’s blood is processed through the blood cell separator. The process results in a platelet concentrate with a volume of approximately 200 mL and containing approximately 4.0 × 10¹¹ platelets and less than 0.5 mL red cells. Currently manufactured blood cell separators produce a platelet concentrate that contains less than 5 × 10⁶ leukocytes and thus can be considered leukocyte reduced. Following plateletpheresis, the donor’s platelet count declines by approximately 30 percent but returns to preplateletpheresis levels in approximately 4 days.

COLLECTION OF RED CELLS BY APHERESIS

Chronic shortages of group O red cells stimulated interest in the use of apheresis for collecting the equivalent of 2 units of red cells from some donors, especially group O.¹⁴ In 2011, 1,978,000 units of red cells were collected by apheresis.¹ The collection procedure is similar to other apheresis procedures, except that red cells are retained rather than returned to the donor. The red cells usually have a very high hematocrit (Hct) as they are removed from the instrument, but an additive solution is incorporated and the red cells can be stored for the usual 42 days. Red cells obtained by apheresis have the same characteristics as those produced from whole blood. Because 2 U of red cells are removed, donors may donate only every 4 months.

LEUKAPHERESIS

Leukapheresis has been used to produce a granulocyte concentrate for transfusion therapy of infections unresponsive to antibiotics. Because the efficiency of granulocyte extraction from whole blood is less than for platelets, the leukapheresis procedure involves processing 6500 to 8000 mL of donor blood for approximately 3 hours. To increase the separation of granulocytes from other blood components, hydroxyethyl starch is added to the blood-cell–separator flow system. In addition, glucocorticoids and granulocyte colony-stimulating factor (G-CSF) have been administered to granulocyte donors to increase the granulocyte count and the granulocyte yield.¹⁵

PLASMAPHERESIS

Plasmapheresis is used to obtain plasma for manufacture of derivatives but not plasma for transfusion. Plasmapheresis usually can be performed in approximately 30 minutes and produces up to 750 mL of plasma. Because few red cells are removed, the procedure can be repeated up to two times per week, so theoretically a donor could provide a large amount of plasma. Because of the nature and possible frequency of plasma donation, special donor criteria apply.

The selection of donors for apheresis uses the same criteria as for whole-blood donation with some additional donor requirements. No more than 15 percent of the donor’s blood should be extracorporeal during apheresis; thus, the donor’s size is considered when making decisions about specific apheresis procedures or instruments to be used. The platelet count must be monitored for frequent donors. Because a plateletpheresis concentrate would be the sole source of platelets for the transfusion, the donor must not have taken aspirin for at least 3 days.

The amount of blood components removed from apheresis donors must be monitored. Not more than 200 mL of red cells per 2 months or approximately 1500 mL of plasma per week can be removed. The laboratory testing of donors and apheresis components for transmissible diseases is the same as for whole-blood donation. Thus, the likelihood of disease transmission from apheresis components is the same as from whole blood.

Apheresis donors can experience the same kind of reactions as whole-blood donors. In addition, apheresis donors experience a higher incidence of paresthesias, probably because of the infusion of citrate (that may affect calcium levels) used to anticoagulate the donor’s blood while it is in the cell separator. This type of reaction is managed by slowing the blood flow rate through the instrument, which slows the rate of citrate infusion. In leukapheresis, donors can be given glucocorticoid and/or G-CSF to increase the granulocyte count, and the sedimenting agent hydroxyethyl starch is used in the cell separator to improve the granulocyte yield. When G-CSF and glucocorticoids are used, approximately 60 percent of donors experience side effects, usually myalgia, arthralgia, headache, or flu-like symptoms.¹⁵ The major side effect of hydroxyethyl starch is blood volume expansion manifested by headache and/or hypertension.

Each unit of whole blood or each apheresis component undergoes a standard battery of tests, including those for blood type, red cell antibodies (including ABO, Rh, minor antigens), and transmissible diseases (Table 138–2). Additional tests, such as those for cytomegalovirus (CMV) antibodies, may be done. During the last few years, testing for West Nile virus and Trypanosoma cruzi have been added. Babesia is another transfusion transmissible disease¹⁶ for which a donor screening test has been developed. It is not clear whether routine testing will be introduced.

Ironically, the improvements in blood safety have occurred at a time of the public’s increased fear of transfusion and the more cautious use of blood components by physicians. Each step in the overall process of donor evaluation and testing adds to blood safety in important ways, and the medical history is important as illustrated by the 90 percent reduction in HIV infectivity from the use of donor-selection criteria identifying HIV risk behavior.¹⁷ Tests for transmissible diseases further reduce the proportion of infectious donors.¹⁸ Donor deferral registries detect individuals who previously were deferred as blood donors but who for various reasons attempt to donate again. Currently, the risk of acquiring a transfusion-transmitted disease ranges from one per 150,000/unit for hepatitis B to one per 2,135,000/unit for HIV (Table 138–3). Thus, although the blood supply is safer than ever, transfusion is not risk free and should be undertaken only after careful consideration of the patient’s clinical situation and specific blood component needs.

Red blood cell (RBC) transfusions are indicated to increase oxygen carrying capacity in anemic patients. While oxygen extraction and delivery may be measured using invasive procedures, these methods are not available in most clinical settings. As a result, the decision to transfuse RBCs is often based on Hgb or Hct value(s).

Transfusing RBCs to a critically anemic patient will increase the oxygen-carrying capacity; however, the utility of RBC transfusions in an asymptomatic patient with a Hgb between 6 and 10 g/dL is less clear. Most of the large, prospective, randomized controlled studies looking at RBC usage and transfusion triggers did not specifically address the question of increased oxygen-carrying capacity at various Hgb/Hct levels. Instead they used the more practical markers of mortality, end-organ dysfunction, or adverse events to determine the efficacy and safety of restrictive (low Hgb threshold) versus liberal (higher Hgb threshold) transfusion strategies.

RED BLOOD CELL TRANSFUSION THRESHOLDS

The Transfusion Requirements in Critical Care (TRICC) trial was the first adequately powered study to compare a restrictive and liberal strategy for RBC transfusions in critically ill patients.¹⁹ A total of 838 ICU patients were randomized into two groups: a liberal arm, which maintained Hgb concentrations between 10 and 12 g/dL and gave transfusions when the Hgb concentration fell below 10 g/dL; and a restrictive arm, which maintained Hgb levels between 7 and 9 g/dL and used a Hgb value of 7 g/dL as the trigger for transfusion. The exclusion criteria included age younger than 16 years; active blood loss at the time of enrollment; admission after a routine cardiac procedure; chronic anemia; imminent death; and others. Thirty-day mortality from all causes was the primary outcome measure. Secondary outcomes included 60-day mortality, death during hospitalization, and multiple-organ dysfunction (MOD). The severity of a patient’s illness was classified using the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. This and other patient characteristics were statistically similar in the two study arms. This study was designed as an equivalency trial, and overall found similar results in the two groups for 30-day mortality (18.7 vs. 23.3 percent; p = 0.11), as well as for the secondary outcomes. Thirty-day mortality rates among patients in the restrictive transfusion arm who were less acutely ill (APACHE II ≤20) (8.7 vs. 16.1 percent; p = 0.03), or were younger than 55 years old (5.7 vs. 13.0 percent; p = 0.02). The restrictive group also received fewer transfusions (54 percent) than the liberal group. The authors concluded that “a restrictive strategy is as least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients.…”

Studies conducted after the TRICC trial have used various categories of high-risk patients to better define RBC transfusion thresholds in these populations (Table 138–4). Studies have focused on patients with upper gastrointestinal bleeding, cardiovascular risk factors, orthopedic surgery patients and other populations that usually require a large number of RBC transfusions. All studies followed the basic structure of the TRICC trial, randomizing patients into a restrictive versus liberal arm. Most studies also used mortality or end-organ dysfunction as end points.