The 1960S

Transfusion medicine has undergone enormous changes in the last 60 years, but the consensus of whether to use whole blood, its components, or both has vacillated every decade or so. In the l960s, most blood given was in the form of whole blood, whereas fresh frozen plasma (FFP) was available for the treatment of coagulopathies.

The 1970S Through The 1980S

Transfusion therapy was characterized in this period by “giving the patient only the component of blood that was needed.” Component transfusion therapy rather than whole blood transfusion was the standard of care. For example, if the patient was anemic, only packed red blood cells (PRBCs) would be transfused, or if thrombocytopenia existed, only platelet concentrates would be given. Caution regarding administration of blood transfusions increased during this time period in part because of concern regarding the infectivity of blood (e.g., hepatitis and human immunodeficiency virus [HIV]). Furthermore, individual clinical decisions regarding blood transfusions were and continue to be monitored by local hospital transfusion committees (as required by regulatory agencies of various countries including the United States). These committees have the responsibility of monitoring the individual and institutional transfusion practices by evaluating clinical appropriateness of transfusion triggers.

1990S Through The 2000S

With improved screening techniques for HIV and other blood-borne pathogens during this decade, the incidence of blood transfusion–related infectious disease transmission decreased 10,000-fold. The focus of blood product safety now shifted to noninfectious serious hazards of transfusion . These hazards include hemolytic transfusion reactions, transfusion-related acute lung injury (TRALI), and transfusion-associated circulatory overload (TACO), to name a few. With an increased awareness of the potential morbidity and mortality associated with blood product administration, research focused on the concept of liberal versus restrictive blood transfusion strategy. Attention now turned to balancing the threats posed by two independent (yet related) risk factors of patient outcome—anemia and transfusion.

Although the strategy of specific component therapy was still prominent, the concept of reconstituted “whole blood” was introduced during this decade. Led by trauma hospitals and the military, FFP and platelets were transfused along with PRBCs, resulting in a transfusion ratio that was similar to that of whole blood. Because the concept of transfusing components that reconstitute whole blood rouses the prior practice of transfusing whole blood, that concept is being reexamined again in the literature and may yet prove beneficial in patients with life-threatening bleeding.

2010 to The Present

The 2010s saw a shift away from simply correcting anemia and coagulopathy, to a more patient-centered, multipronged approach to transfusion medicine. As a result, the term patient blood management (PBM) has become synonymous with modern, evidence-based transfusion medicine. The Society for the Advancement of Blood Management defines PBM as “the timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis and minimize blood loss in an effort to improve patient outcome.” PBM recognizes transfusions are but a temporary solution to an often complex, multifactorial process that requires attention to the underlying cause of anemia.

Integration of PBM into clinical pathways has reduced the reliance on allogenic blood product transfusion as the only means to avoid anemia and likely explains the continued decrease in transfusions noted in U.S. hospitals over the last decade. In a recent retrospective analysis, implementation of a PBM system with a reduced transfusion threshold from 8 g/dL to 7 g/dL Hb in orthopedic surgical patients reduced the use of erythrocytes by 32% while improving clinical outcomes. Most notably, patients 65 years and older demonstrated the most improved clinical outcomes, including 30-day readmission rates. Comprehensive PBM programs also can include evaluation of preoperative anemia, clinical decision support, educational efforts, improved surgical techniques, and blood conservation strategies.

PBM in many countries has been facilitated by computerized data systems and supply guidelines. A limitation of most of the PBM publications is that they describe mostly nonbleeding, anemic patients and the decision to initiate transfusion. Very little information addresses what guidelines should be used for repetitive transfusions. The anesthesia provider offers insight into these issues and can provide guidance as to how PBM fits into the perioperative clinical environment.

Source of Donors

Significant global disparities exist regarding access to “safe” blood, or blood that is properly collected and tested. According to World Bank definitions, low- and middle-income countries collect 53% of all blood donations worldwide, yet represent 81% of the world’s population. In addition, the prevalence of transfusion-transmissible infections in blood donations from low- and middle-income countries is significantly higher than those from high-income countries, yet low-income countries have less access to basic quality screening procedures. Another issue, particularly in low-income countries, is incentivized donors. The World Health Organization’s (WHO) decision-making body, the World Health Assembly, has issued resolutions and consensus statements that emphasize the need for all member states to develop national blood systems based on voluntary, unpaid donations as a means to ensure a safe, secure, and sufficient supply of blood products. Some experts have suggested that offering economic incentives or rewards to donors should be seriously considered, because limited empirical research exists to support the assumption that incentivized donations, including noncash incentives, either improve recruitment of donors or pose a risk to blood product safety. However, the WHO strongly defends voluntary nonremunerated blood donation as a vehicle to a safer blood supply and increased donor participation.

In the United States, the Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research provides the regulatory oversight for blood banks and donation centers, with most voluntarily obtaining accreditation from the AABB (formerly, American Association of Blood Banks). In Europe, the European Commission sets standards for blood products and their components in the European Blood Directive (Directive 2002/98/EC). These regulatory and professional societies set standards with regard to the donation, collection, testing, processing, storage, and distribution of products.

In the United States, those over the age of 16 and who weigh at least 110 pounds are eligible for screening for potential blood donation. Vital signs are assessed, including temperature, heart rate, and blood pressure. Hb levels are measured, with minimum cutoffs of 13 g/dL for men and 12.5 g/dL for women. Blood is collected either as whole blood and separated by centrifugation or by apheresis, in which only specific components are collected while other components are returned to the donor. An outline of the separation scheme by which various blood components are derived is shown in Fig. 49.1 . Apheresis is particularly helpful in donors with blood type AB, as they represent a rare blood type yet serve as the universal plasma donor. As recipients, patients with blood type AB rarely require AB specific blood, as they can be transfused with any type of red cell. Therefore, if plasma is collected from AB donors while red cells are immediately returned, this may allow for more frequent plasma donation from this small but vitally important group of donors.

Scheme for separation of whole blood for component therapy.

Transfusion-Transmissible Infections

Donor screening attempts to reduce the risk of a transfusion-transmissible disease and to protect the donor from an adverse reaction due to donation. Deferment based on medical history includes those considered to be in high-risk categories for potential transmission of an infectious agent, including those with a significant travel history, history of injection drug use, recent tattoos, or men who have had sex with men (MSM) in the previous 12 months. The latter deferment category has been controversial in recent years, given the changing epidemiology of the HIV epidemic and improved screening methods. In this population, some advocate for reducing the time interval between potential exposure and donation to 3 months.

The use of more sensitive screening tests in conjunction with changes in transfusion medicine practices have made infectious risks quite rare. The FDA requires blood products to be tested for hepatitis B and C, HIV (types 1 and 2), human T-lymphotropic virus (HTLV; types 1 and 2), and treponema pallidum (syphilis), West Nile virus, and Zika virus. Testing is recommended for Trypanosoma cruzi (Chagas disease) for first-time donors. Historically, the FDA has published tables on the risks for infectivity, Table 49.1 but because the rates are so infrequent, the last tables published were for data from 2011.

Several blood-safety changes made between the years of 1982 and 2008 have decreased the risk for disease transmission by allogenic blood so that the demand for autologous blood has declined as well. The West Nile virus story illustrates how rapidly our blood banks can respond. In 2002, West Nile virus caused the largest outbreak of arboviral encephalitis ever recorded in the United States (i.e., approximately 4200 patients). Twenty-three cases of transfusion-transmitted infections resulted in seven deaths. In 2003, testing became available that now makes that infection very rare (see Table 49.1 ). The FDA’s response to the 2015 to 2016 Zika virus outbreak was similarly swift—the blood supply was immediately shifted from areas with low risk of infections to areas of known infection; authorization for screening tests was issued within months, and universal screening with a qualitative nucleic acid test (NAT) for the detection of Zika virus ribonucleic acid (RNA) was mandated.

The changes in blood transfusion testing can be appreciated when comparing tests used in 1998 ( Box 49.1 ) with those used in 2018 ( Table 49.2 . The use of nucleic acid technology has decreased the window of infectivity (i.e., time from being infected to a positive test result), which is a major reason for the decrease in infectivity with hepatitis, HIV, West Nile virus, and Zika virus.

Biochemical Changes in Stored Blood

Units of blood collected from donors are usually separated into components (e.g., RBCs, plasma, cryoprecipitate, and platelets; see Fig. 49.1 ). Citrate phosphate dextrose adenine-1 (CPDA-1) is an anticoagulant preservative that is used for blood stored at 1°C to 6°C. Citrate prevents clotting by binding Ca ²⁺ . Phosphate serves as a buffer, and dextrose is a red cell energy source, allowing the RBCs to continue glycolysis and maintain sufficient concentrations of high-energy nucleotides (adenosine triphosphate [ATP]) to ensure continued metabolism and subsequent viability during storage. The addition of adenine prolongs storage time by increasing the survival of RBCs, allowing them to resynthesize the ATP needed to fuel metabolic reactions. This extends the storage time from 21 to 35 days. Without adenine, RBCs gradually lose their ATP and their ability to survive after transfusion. Finally, storage at 1°C to 6°C assists preservation by reducing the rate of glycolysis approximately 40 times the rate at body temperature.

The shelf life of PRBCs can be extended to 42 days when AS-1 (Adsol), AS-3 (Nutricel), or AS-5 (Optisol) is used. Adsol contains adenine, glucose, mannitol, and sodium chloride (NaCl). Nutricel contains glucose, adenine, citrate, phosphate, and NaCl. Optisol contains only dextrose, adenine, NaCl, and mannitol. On a national level, 85% of RBCs are collected in AS-1. In Europe, a solution similar to AS-1 containing saline, adenine, glucose, and mannitol is used. As of 2015, the FDA approved a new additive solution, AS-7, which increases storage time to at least 56 days; however, the solution is not yet commercially available in the United States.

The hematocrit (Hct) of the transfused product depends on the storage method. When CPDA is the anticoagulant used, the Hct is greater than 65%, because most of the plasma is removed, and the resulting volume is approximately 250 mL. When AS-1 is used, most of the plasma is also removed, but 100 mL of storage solution is added, resulting in an Hct of 55% to 60% and volume of 310 mL. The duration of storage is set by U.S. federal regulation and is based on the requirement that at least 70% of the transfused RBCs remain in circulation for 24 hours after infusion.

During storage of whole blood and PRBCs, a series of biochemical reactions occur that alter the biochemical makeup of blood and account for some of the complications. Collectively, these are known as red cell storage lesions and may be responsible for the organ injury associated with red cell transfusion. During storage, RBCs metabolize glucose to lactate; hydrogen ions accumulate, and plasma pH decreases, while increases in oxidative damage to lipids and proteins are noted. The storage temperature of 1°C to 6°C inhibits the sodium-potassium pump, resulting in a loss of potassium ion (K ⁺ ) from the cells into the plasma and a gain of intracellular sodium. Although K ⁺ concentrations appear elevated in 35-day stored RBC concentrates, the total plasma volume in the concentrates is only 70 mL, so total K ⁺ is not markedly elevated. Over time, there are progressive decreases in RBC concentrations of ATP, nitric oxide (NO), and 2,3-diphosphoglycerate (2,3-DPG).

The osmotic fragility of RBCs increases during storage, and some cells undergo lysis, resulting in increased plasma Hb levels. In addition, deformability of RBCs appears impaired in patients who receive allogenic blood cell transfusion, potentially resulting in micro-occlusive events. Frank and associates studied the blood of patients undergoing posterior spinal fusion surgery and found that increased duration of blood storage was associated with decreased RBC deformability, which was not “readily” reversible after transfusion. They speculated that these deformed cells may be defective in delivering oxygen (O ₂ ) to the cells and concluded that both the “age of blood storage” and “amount” of blood given should be considered when giving blood ( Table 49.4 ).

Changes in Oxygen Transport

RBCs are transfused primarily to increase transport of O ₂ to tissues. Theoretically, an increase in the circulating red cell mass will produce an increase in O ₂ uptake in the lungs and a corresponding increase in O ₂ delivery to tissues, but RBC function may be impaired during preservation, making it difficult for them to release O ₂ to the tissues immediately after transfusion.

The O ₂ dissociation curve is determined by plotting the partial pressure of O ₂ (P o ₂ ) in blood against the percentage of Hb saturated with O ₂ ( Fig. 49.2 ). As Hb becomes more saturated, the affinity of Hb for O ₂ also increases. This is reflected in the sigmoid shape of the curve, which indicates that a decrease in the arterial partial pressure of oxygen (Pa o ₂ ) makes considerably more O ₂ available to the tissues. Shifts in the O ₂ dissociation curve are quantitated by the P ₅₀ , which is the partial pressure of O ₂ at which Hb is half saturated with O ₂ at 37°C and pH 7.4. A low P ₅₀ indicates a left shift in the O ₂ -dissociation curve and an increased affinity of Hb for O ₂ . The left shift of the curve indicates that a lower than normal O ₂ tension saturates Hb in the lung, but the subsequent release of O ₂ to the tissues is more difficult, as it occurs at a lower than normal capillary O ₂ tension compared with an unshifted curve. In other words, the increased affinity of Hb for O ₂ makes it more difficult for Hb to release O ₂ to hypoxic tissues. This leftward shift is likely a result of decreased levels of 2,3-DPG in stored RBCs, which can remain low for up to 3 days posttransfusion.

Factors that shift the oxygen dissociation curve. 2,3-DPG, 2,3-Diphosphoglycerate.

From Miller RD. The oxygen dissociation curve and multiple transfusions of ACD blood. In: Howland WS, Schweizer O, eds. Management of Patients for Radical Cancer Surgery: Clinical Anesthesia Series. Vol. 9. Philadelphia: FA Davis; 1972:43.

Many of the advances in blood processing and storage are centered on the material of the collections and storage containers. Innovative methods of storing blood are being developed. For example, storing blood in an electrostatic field of 500 to 3000 V decreases hemolysis and attenuates the decrease in pH associated with prolonged storage. Current blood collection and storage systems are made of disposable plastic; these materials must have properties compatible with collection, processing, storage, and administration. Polyvinylchloride (PVC) with use of different plasticizers is commonly used because it is nontoxic, has flexibility, mechanical strength, water impermeability, resistance to temperature extremes for sterilization and freezing, compatibility with blood components, and selective permeability for cellular gas exchange.

Recent animal data suggest that red cells in stored blood can be rejuvenated with solutions of inosine prior to administration, reversing storage lesions and mitigating the potential for organ damage. This could be a promising technique to restore ATP and 2,3-DPG levels, while reducing a recipient’s immune response and transfusion-associated organ injury. However, small clinical trials in humans demonstrating clinical benefit are lacking. Larger trials are ongoing.

Clinical Implications: Duration of Blood Storage

The fact that blood can be stored for 42 days is a mixed blessing. The obvious advantage is the increased availability of blood, but the clinical evidence regarding safety has not been consistent, reflecting the difficulty of conducting a systematic study of patients in varied clinical settings. For decades, many clinicians have tried to establish a firm relationship between the 2,3-DPG levels associated with stored blood and patient outcome. In 1993, Marik and Sibbald found that the administration of blood that had been stored for more than 15 days decreased intramucosal pH, suggesting that splanchnic ischemia had occurred. In addition, an increased incidence of postoperative pneumonia in cardiac patients has been associated with the use of older blood. Yet prolonged storage of blood was not associated with increased morbidity after cardiac surgery. Purdy and colleagues found that patients who received 17-day-old blood (range, 5-35 days) versus 25-day-old blood (range, 9-36 days) had higher survival rates. Koch and colleagues concluded that giving erythrocytes (PRBCs) older than 14 days was associated with an increased risk for postoperative complications, along with reduced short-term and long-term survival in patients undergoing coronary artery bypass surgery. This article also had an accompanying editorial that concluded, “to the extent possible, newer blood might be used in clinical situations that seem to call for it.” In addition, a meta-analysis concluded that older stored blood is associated with an increased risk for death.

However, there is equal data arguing the contrary, and other researchers have not arrived at a clear conclusion and recommended more studies. Weiskopf and associates performed studies in healthy volunteers who were evaluated by a standard computerized neuropsychologic test 2 days and 1 week after acute isovolumic anemia was induced. When correcting the anemia, they concluded that erythrocytes stored for 3 weeks are as efficacious as those stored for 3.5 hours. Spahn wrote an accompanying editorial agreeing with Weiskopf and associates and, furthermore, postulated that 2,3-DPG levels may not be the key factor in determining the delivery of O ₂ (i.e., 2,3-DPG levels are reduced in older blood, but the blood still delivers O ₂ ). Cata and associates also concluded that no change in outcome occurred in patients undergoing radical prostatectomy and receiving older blood. Saager and colleagues also found no relationship between duration of blood storage and mortality in nearly 7000 patients undergoing noncardiac surgery.

Since the publication of the eighth edition of this text, several randomized control trials evaluating the influence of the duration of blood storage have been published. In 2016, Heddle and colleagues published results from the INFOMR trial, a large, pragmatic, randomized controlled trial enrolling adult hospitalized patients in six centers from four countries. Patients were randomized to receive either blood that had been stored for the shortest duration (mean duration of storage 13 days) versus blood stored for the longest duration (mean duration of storage 23 days). Only patients with A and O blood types were included as the less common blood types could not achieve an appropriate difference in mean duration of storage. More than 20,000 patients were included in the primary analysis. No significant differences in mortality were noted between the two groups. In prespecified high-risk categories, including patients undergoing cardiovascular surgery, patients admitted to the intensive care unit (ICU), and those with cancer, the results remained the same.

Similarly, the results of the recent RECESS trial published in 2015 revealed similar mortality rates among those transfused with blood stored less than 10 days (median storage time 7 days) compared with those transfused with blood stored for more than 21 days (median storage time 28 days). Changes in preoperative to 7 days postoperative Multiple Organ Dysfunction Score (MODS) were similar between the two groups, as well. Finally, two randomized controlled trials in critically ill adults evaluating the age of transfused blood on mortality and other outcomes, such as new bloodstream infections, duration of mechanical ventilation, and the use of renal replacement therapy, failed to demonstrate differences between groups transfused with fresher blood compared with those transfused with older blood.

These recent randomized controlled trials demonstrate the safety and noninferiority of “older” versus “younger” blood, but the complete answer may still need further data. First, the measures of outcome may be insufficiently sensitive to detect important and meaningful clinical outcomes. Many studies use mortality as their primary outcome measure. Although this is obviously a critical benchmark, it may not be sensitive enough to detect clinical differences regarding the safe or optimal length of time for the storage of blood. Important adverse clinical outcomes could occur without a change in mortality per se (e.g., duration of hospitalization, cardiovascular events, quality of life, neurocognitive decline). Second, these studies compare moderately young with moderately old blood. Ethical and logistical issues preclude a trial comparing “very” young and “very” old blood or even comparing moderately aged blood to very old blood (e.g., stored for 35-42 days). Because the quality of blood decreases with length of storage, increased morbidity with exposure to more aged red cells is physiologically plausible, but the debate regarding the effectiveness of a blood transfusion and its duration of storage continues. More prospective studies are likely required.

Allogeneic (Homologous) Blood

PRBCs contain the same amount of Hb as whole blood, but much of the plasma has been removed. The Hct value of PRBCs is approximately 60% ( Table 49.5 ). Other than severe hemorrhage, most indications for RBCs can be effectively treated with PRBCs, conserving the plasma and the components for other patients (see Fig. 49.1 ). Many blood banks have conscientiously followed this principle, and whole blood is not available or only available in trauma centers or by special arrangement.

The administration of PRBCs is facilitated by utilizing crystalloid or colloid as a carrier; however, not all crystalloids are suitable. Solutions containing Ca ²⁺ may precipitate clotting. Lactated Ringer solution is not recommended for use as a diluent or carrier for PRBCs because of the Ca ²⁺ ( Table 49.6 ), although several experimental studies found lactated Ringer solution and normal saline to be equally acceptable. A more important factor may be whether the diluent is hypotonic with respect to plasma. In hypotonic solutions, the RBCs will swell and eventually lyse. Solutions that cause hemolysis are listed in Table 49.6 . Recommended solutions compatible with packed erythrocytes are 5% dextrose in 0.45% saline, 5% dextrose in 0.9% saline, 0.9% saline, and Normosol-R with a pH of 7.4.

RBC transfusions are given to increase O ₂ -carrying capacity. Increasing intravascular volume in the absence of significant anemia is not an indication for blood transfusion because volume can be augmented with administration of intravascular fluids that are not derived from human blood (e.g., crystalloids). As such, a sole Hb value should not be the only basis for a transfusion decision. It should be the overall status of the patient that prompts transfusion therapy (e.g., hemodynamics, organ perfusion and oxygen delivery, and anticipated surgical needs). Even so, the Hb value has become the basis for many transfusion strategies. It is the prime criterion for defining restrictive versus liberal transfusion strategies.

When a patient is hemorrhaging, the goals should be to restore and maintain intravascular volume, cardiac output, and organ perfusion to normal levels. By using crystalloids, colloids, or both to treat hypovolemia, normovolemic dilutional anemia may be created. Increasing cardiac output enhances O ₂ delivery to the tissues only to a limited extent. In fact, during normovolemic anemia, Mathru and colleagues found inadequate splanchnic and preportal O ₂ delivery and consumption when the Hb level decreased to 5.9 g/dL. Although the current PBM emphasis is on fewer or even avoidance of blood transfusions, clearly an Hb value exists below which a blood transfusion should be given.

The basis for using the Hb or Hct value as the initial consideration for defining transfusion requirements followed a 1988 National Institutes of Health (NIH) Consensus Conference that concluded that otherwise healthy patients with Hb value more than 10 g/dL rarely require perioperative blood transfusions, whereas patients with acute anemia with a Hb value of less than 7 g/dL frequently require blood transfusions. They also recognized that patients with chronic anemia (as in renal failure) might tolerate an Hb concentration of less than 6 to 7 g/dL. Amazingly, despite many studies, publications, and debates, the fundamental guidelines have not changed substantially in the 30 plus years since this conference.

An excellent editorial by LeManach and Syed outlines key questions that should be considered regarding transfusion triggers, including what we need to learn and the role of databases. Of prime importance is identifying the variables that predict the need for erythrocyte transfusion and the approach that can most accurately estimate the impact of transfusions. Many studies use death rate as their main indicator. Although clearly an important indicator, there are additional obvious factors in between the extremes of life and death, including vital signs, key laboratory values, and other indicators used in critical care units. Several groups working with patients in ICUs have attempted to define the point at which blood transfusions should be given by measures of tissue oxygenation and hemodynamics (e.g., increase in O ₂ consumption in response to added O ₂ content). The O ₂ extraction ratio has been recommended as an indicator for transfusions; however, this technique requires invasive monitoring, and the results were not dramatic between groups who were or were not transfused. No specific measure can consistently predict when a patient will benefit from a blood transfusion. The ultimate determination of the Hb or Hct value at which blood should be given is a clinical judgment based on many factors, such as cardiovascular status, age, anticipated additional blood loss, arterial oxygenation, mixed venous O ₂ tension, cardiac output, and intravascular blood volume ( Table 49.7 ).

Additional Blood Transfusions

To determine whether subsequent units of blood are indicated after the initial administration, the overall condition of the patient and the clinical situation need to be reassessed. The following key components of information to consider include:

• 1.
  

  Measurement and trend of vital signs

  
  
• 2.
  

  Measurement of blood loss and assessment of anticipated blood loss

  
  
• 3.
  

  Quantitation of intravenous fluids given

  
  
• 4.
  

  Determination of Hb concentration

  
  
• 5.
  

  Surgical concerns.

Measurement of Blood Loss

Measuring blood loss is obviously important when assessing the need for both the initial and subsequent blood transfusions (see Table 49.7 ). A standard approach includes a combination of visualization and gravimetric measurements based on weight differences between dry and blood-soaked gauze pads. A study in patients undergoing spine surgery found that anesthesiologists tended to overestimate blood loss by as much as 40% ( Fig. 49.3 ). On the other hand, optical scanners tended to underestimate blood loss compared with the standard gravimetric calculations. The accuracy of measurements is not uniformly consistent and no “gold standard” for blood loss quantification exists.

Discrepancy between estimated and actual blood loss.

From Stovener J. Anesthesiologists vastly overstate bleeding. Anesthesiol News , May 14, 2012.

Predicting surgical blood loss is also an important component to intraoperative transfusion medicine. As part of the WHO preoperative guidelines to improve the safety of patients undergoing surgery, the anesthesiologist must consider the possibility of a large-volume blood loss prior to the induction of anesthesia. In a prospective trial evaluating both surgeons’ and anesthesiologists’ ability to predict the estimated blood loss prior to incision, members of both these medical professions underestimated the blood loss by greater than 500 mL in 10% of intermediate or major surgeries, which potentially placed those patients at risk for being without adequate intravenous access or appropriate resuscitative volume.

Platelet Concentrates

Platelet concentrates are obtained either as pooled concentrates from 4 to 6 whole-blood donations or as apheresis concentrates obtained from one donor. If platelets are stored at room temperature, they can be used up to 7 days after collection with constant and gentle agitation. Bacterial contamination, mainly from platelet concentrates, is the third leading cause of transfusion-related deaths ( Table 49.8 ), although the incident rate has steadily declined over the last 15 years. In a report of 10 contaminated platelet transfusions between 1982 and 1985, half were platelets stored for 5 days or more. A prospective analysis from 1987 to 1990 resulted in seven cases of sepsis in patients receiving platelets for thrombocytopenia secondary to bone marrow failure. Because the use of multidonor platelet products stored for 5 days results in an incidence of sepsis five times higher than use of those stored for 4 days, shorter storage times are being emphasized. In studies that actively survey transfused platelets, a rate of bacterial contamination has been identified of approximately 1 per 2500 units ( Table 49.9 ). Twenty-five percent of the patients exposed to contaminated platelet products developed a septic transfusion reaction, although these cases were only identified by active surveillance. Prior to this study, septic transfusion reactions associated with platelet transfusions were reported at a rate of 1 per 100,000 transfused platelets, suggesting this is likely an underreported event.

At present, platelet concentrates are routinely tested for bacteria and are the only blood product stored at room temperature. For any patient who develops a fever within 6 hours after receiving platelets, sepsis from platelets should be considered.

Indications for the use of platelets are somewhat difficult to define. The most recent guidelines published in 2015 by the ASA Task Force on Perioperative Blood Management provide the following recommendations regarding management for platelet transfusions:

• 1.
  

  Monitor platelet count, except in situations of massive transfusion.

  
  
• 2.
  

  Monitor platelet function, if available.

  
  
• 3.
  

  Consider use of desmopressin in patients with excessive bleeding or suspected platelet dysfunction.

  
  
• 4.
  

  Platelet transfusion may be indicated despite an adequate platelet count if there is known or suspected platelet dysfunction (e.g., cardiopulmonary bypass, bleeding, recent use of antiplatelet therapy, congenital platelet dysfunction).

  
  
• 5.
  

  Prophylactic platelet transfusion is rarely indicated in surgical or obstetric patients when the platelet count is greater than 100 × 10 ⁹ /L and is usually indicated when the platelet count is less than 50 × 10 ⁹ /L. The determination of whether patients with intermediate platelet counts (50-100 × 10 ⁹ /L) require therapy should be based on the patient’s risk for bleeding.

Many institutions have strict thresholds targeted to the patient’s condition that outline the minimum platelet count needed for the categories of (1) prophylaxis, (2) periprocedural (based on type of procedure), and (3) active bleeding. In the first category, a required platelet count may be 10 × 10 ⁹ /L in patients receiving chemotherapy. In the second category, patients undergoing bone marrow biopsy or lumbar puncture should have platelet counts between 20 and 30 × 10 ⁹ /L. For neurosurgery, a platelet count of 100 × 10 ⁹ /L may be targeted. Such thresholds are often guided by professional societies. The American Society of Regional Anesthesia and Pain Medicine guidelines also include recommendations in the setting of therapy that may alter platelet function. A clinician’s institution will likely have precise platelet recommendations for most procedures.

Patients with severe thrombocytopenia (<20 × 10 ⁹ /L) and clinical signs of bleeding usually require platelet transfusion. However, patients may have very low platelet counts (much lower than 20 × 10 ⁹ /L) and not have clinical bleeding. These patients probably do not need platelet transfusions ( Table 49.10 ). The recent PATCH trial evaluated patients receiving antiplatelet therapy who presented with intracerebral hemorrhage (ICH). Such patients often receive platelet transfusions due to concern about the irreversible inhibition of platelet function and the high risk of morbidity and mortality associated with ICH. Study participants were excluded if their Glasgow Coma Scale score was less than 8 or if their treatment plan included expected surgical intervention within the first 24 hours of presentation. Platelet transfusion increased the risk of death or dependence at 3 months and the risk of a serious adverse event during the hospital stay compared with standard medical therapy without transfusion. Although this study excluded patients who were deemed surgical candidates at presentation, even in this high-risk patient population, platelet transfusions are not indicated unless there is active bleeding.

When possible, ABO-compatible platelets should be used. The need to use them, however, is not well documented, and specific testing is difficult. Aggregation cannot be used for matching, because platelets cause clumping. The platelet membrane has immunoglobulins, and any additional deposit of recipient antibodies is difficult to detect. Despite the fact that platelets can be destroyed by antibodies directed against class I human leukocyte antigen (HLA) proteins on their membranes and by antibodies against ABO antigens, platelets will continue to be chosen without regard to antigen systems for the majority of patients. ABO-incompatible platelets produce very adequate hemostasis.

The effectiveness of platelet transfusions is difficult to monitor. Under ideal circumstances, one platelet concentrate usually produces an increase of approximately 7 to 10 × 10 ⁹ /L at 1 hour after transfusion in the 70-kg adult. Ten units of platelet concentrates are required to increase the platelet count by 100 × 10 ⁹ /L. However, many factors, including splenomegaly, previous sensitization, fever, sepsis, and active bleeding, may lead to decreased survival and decreased recovery of transfused platelets.

Other various different types of platelet concentrates have been proposed, including leukocyte-depleted platelets and ultraviolet–irradiated platelets. The use of these products is reviewed by Kruskall.

Fresh Frozen Plasma

FFP is the most frequently used plasma product. It is processed shortly after donation, generally frozen within 8 hours or 24 hours (PF24). It contains all the plasma proteins, particularly factors V and VIII, which gradually decline during the storage of blood. PF24 is comparable to FFP, except for a slight reduction in factor V and approximately 25% decrease in factor VIII. Thawed plasma is stored at 1 °C to 6 °C for up to 5 days. The use of FFP carries with it the same inherent risks that are observed with the use of any blood product, such as sensitization to foreign proteins.

Although FFP is a reliable solution for intravascular volume replacement in cases of acute blood loss, alternative therapies are equally satisfactory and considerably safer. The risks of FFP administration include TRALI, TACO, and allergic or anaphylactic reactions.

In 2015 the ASA Task Force recommended the following guidelines regarding the administration of FFP:

• 1.
  

  Prior to the administration of FFP, coagulation studies should be obtained when feasible.

  
  
• 2.
  

  For the correction of coagulopathy when the international normalized ratio (INR) is greater than 2, in the absence of heparin.

  
  
• 3.
  

  For the correction of coagulopathy due to coagulation deficiencies in patients transfused with more than one blood volume (approximately 70 mL/kg) when coagulation studies cannot be easily or quickly obtained.

  
  
• 4.
  

  Replacement of known coagulation factor deficiencies with associated bleeding, disseminated intravascular coagulation (DIC), or both, when specific components are not available.

  
  
• 5.
  

  Reversal of warfarin anticoagulation when severe bleeding is present and prothrombin complex concentrations are not available.

FFP or plasma is often given to critical care patients before insertion of an intravascular catheter. Hall and associates studied 1923 patients admitted to 29 ICUs in the United Kingdom who underwent intravascular catheterization. They compared patients who did and did not receive FFP. Chronic liver disease and more abnormal coagulation tests increased the frequency of patients receiving FFP, but the severity of the prothrombin time (PT) alone was not a factor. Whether prophylactic FFP should be given in this situation is not well defined. In 2015, Muller and associates published results from a randomized, open-label trial of prophylactic FFP use prior to an invasive procedure in critically ill patients with an INR of 1.5 to 3. The trial ended before reaching target enrollment, because of slow recruitment. The occurrence of bleeding did not differ between the two groups, but the trial may not have had enough power to distinguish a statistical significance between groups. Also, an INR reduction below 1.5 only occurred in 54% of patients in the intervention group.

In an effort to “expedite” the availability of plasma for patients who require massive transfusions, some trauma centers keep thawed plasma readily available. In one study, patients with severe trauma who had already received 1 unit of RBCs and plasma were then divided into two groups, one of which immediately received 4 units of thawed plasma. The patients who received the plasma had a reduction in overall blood product use and 30-day mortality. More recently, Sperry and colleagues randomized prehospital injured patients in flight transport who were at risk for hemorrhage to standard of care versus empiric administration of 2 units FFP. By 3 hours, Kaplan-Meier curves revealed early separation of the two groups, favoring empiric administration of FFP in the prehospital setting that persisted until their prespecified end point of 30 days following randomization.

Cryoprecipitate

Cryoprecipitate is prepared when FFP is thawed, and the precipitate is reconstituted. The product contains factor VIII:C (i.e., procoagulant activity), factor VIII:vWF (i.e., von Willebrand factor), fibrinogen, factor XIII, and fibronectin, which is a glycoprotein that may play a role in reticuloendothelial clearance of foreign particles and bacteria from the blood. All other plasma proteins are present in only trace amounts in cryoprecipitate.

Cryoprecipitate is frequently administered as ABO compatible; however, this probably is not very important because the concentration of antibodies in cryoprecipitate is extremely low. Cryoprecipitate may contain RBC fragments, and cryoprecipitate prepared from Rh-positive donors can possibly sensitize Rh-negative recipients to the Rh antigen. Cryoprecipitate should be administered through a filter and as rapidly as possible. The rate of administration should be at least 200 mL/h, and the infusion should be completed within 6 hours of thawing.

According to the 2015 ASA Task Force on Perioperative Blood Management, transfusion of cryoprecipitate is rarely indicated when the fibrinogen levels are greater than 150 mg/dL in nonobstetric patients. The following indications were provided regarding the administration of cryoprecipitate:

• 1.
  

  When testing of fibrinogen activity reveals evidence for fibrinolysis

  
  
• 2.
  

  When fibrinogen concentrations are less than 80 to 100 mg/dL in patients experiencing excessive bleeding

  
  
• 3.
  

  Obstetrical patients who are experiencing excessive bleeding despite a measured fibrinogen concentration greater than 150 mg/dL

  
  
• 4.
  

  In patients undergoing massive transfusion when the timely assessment of fibrinogen concentrations cannot be determined

  
  
• 5.
  

  In patients with congenital fibrinogen deficiencies and when possible, in consultation with the patient’s hematologist

  
  
• 6.
  

  In bleeding patients with von Willebrand disease types 1 and 2A who fail to respond to desmopressin or vWF/FVIII concentrates (or if not available)

  
  
• 7.
  

  In bleeding patients with von Willebrand disease types 2B, 2M, 2N, and 3 who fail to respond to vWF/FVIII concentrates (or if concentrates are not available)

Fibrin glue may be used by surgeons to create local hemostasis. It is prepared in a manner similar to that of cryoprecipitate. With added thrombin, it is applied locally to the surgical site. The efficacy of this product has been difficult to demonstrate in clinical trials.

Massive Transfusion and Transfusion Ratios

The transition from administration of whole blood to component therapy in the 1970s created new challenges in transfusion medicine, especially in patients undergoing trauma or any type of surgery associated with significant blood loss. FFP was not usually required as a separate component with the administration of whole blood, and significant thrombocytopenia usually occurred only after 15 to 20 units of blood. With the change from whole blood to PRBCs, the incidence of coagulopathies increased, especially in units responsible for trauma patients. Rather than basing transfusion decisions on clinical judgment or laboratory tests, the concept of developing ratios of FFP and/or platelet concentrates with PRBCs evolved. For example, a 1:1:1 ratio would be transfusion of 1 unit of plasma, and one-sixth unit of platelets to 1 unit of RBCs. A 1:1:2 ratio would be transfusion of 1 unit of plasma, and one-sixth unit of platelets to every 2 units of RBCs. The convention of one-sixth unit of platelets results from the common allocation of platelet products in 1 unit (apheresis) from a single donor or 1 pool (pooled) from six donors in a “six pack.” In review of the literature, ratios may be expressed as plasma/platelets/RBCs or RBCs/plasma/platelets.

Holcomb and associates concluded that increased platelet ratios were associated with improved survival after massive blood transfusions. Subsequently, Kornblith and associates concluded that the laboratory clotting profile of 1:1:1 plasma/platelets/RBC was significantly more hemostatic when examining activity of factors II, V, VII, VIII, IX, and X; antithrombin III, as well as protein C and higher fibrinogen levels when compared with a 1:1:2 ratio. Results of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study supported this idea. With data from 10 U.S. level-I trauma centers, the conclusion of the study was that higher plasma and platelet ratios early in resuscitation were associated with decreased mortality in patients who received transfusions of at least 3 units of blood products during the first 24 hours after admission. Among survivors at 24 hours, the subsequent risk for death by day 30 was not associated with plasma or platelet ratios. When comparing groups of patients with similar Injury Severity Scores, only a survival benefit was seen in ratios with high plasma to RBC resuscitation. However, no additional morbidity benefit of 1:1 over 1:2 ratios was identified.

More recently in the randomized control trial Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) study, Holcomb and associates found that among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio versus a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days.

These aggressive uses of FFP, platelets, and other blood products have only been shown to be beneficial in response to coagulopathies from massive blood transfusions. Aggressive plasma administration to other transfused patients was associated with an increased rate of serious complications, including acute respiratory distress syndrome (ARDS) and organ dysfunction. A retrospective study showed that a higher FFP-PRBC ratio was associated with the need for advanced interventional procedures in patients with postpartum hemorrhage.

HB-Based Oxygen Carriers

Various other substances that carry or facilitate the transport of O ₂ have been made. Oxygen therapeutics are labeled as Hb-based O ₂ carriers (HBOCs). HBOCs have advantages over human blood of not requiring type and crossmatch and not transmitting infectious viruses, typical characteristics of most synthetic blood products ( Table 49.11 ).

Two approaches have dominated attempts to develop synthetic blood. The first approach uses linear binding kinetics, unlike the nonlinear binding of Hb. The most notable is the perfluorochemical emulsion called Fluosol-DA. Fluosol-DA was initially approved by the FDA for perfusion of ischemic tissues in the setting of percutaneous coronary intervention. However, it had little use because it carried O ₂ only when the Pa o ₂ was more than 300 mm Hg. Fluosol was withdrawn from the market in 1994. Another perfluoro compound, perfluorooctyl bromide, carries three to four times more O ₂ , has a longer half-life, and presumably fewer problems than are associated with Fluosol-DA, but it is not available on the market.

Most HBOCs modify the Hb molecule from humans, animals, or recombinant technology. Original efforts required Hb to be stroma free to prevent nephrotoxicity. The stroma-free Hb needed to be modified to have a favorable O ₂ affinity (i.e., decreased O ₂ affinity/right shift in the O ₂ dissociation curve) and to extend its relatively short intravascular half-life. A variety of approaches have been used, including crosslinking, pyridoxylation and polymerization, and conjugation and encapsulation to accomplish this. Stroma-free Hb causes severe arteriolar vasoconstriction of microvascular structures from NO scavenging, which is not beneficial for organ perfusion. A human recombinant hemoglobin (rHb 1.1) was made in Escherichia coli and functions as normal Hb in terms of O ₂ -carrying capacity, but it, too, was plagued by microvascular vasoconstriction. Although a subsequent iteration, rHbg 2.0, minimized NO scavenging and caused little arteriolar vasoconstriction when compared with rHb 1.1 and diaspirin crosslinked Hb, vasoconstriction may still prove to be their ultimate downfall.

Most clinical trials have shown increased use of allogeneic blood transfusions; however, the outcome of the HBOCs have been similar: failure in clinical trials due to increased adverse events. Natanson and colleagues performed a cumulative meta-analysis on 16 trials involving 5 different products and 3711 patients. They concluded that there was a significant increased risk for myocardial infarction and death when HBOCs were given, an outcome that was found among all the technologies (e.g., cross-linked, polymerized, or conjugated). An accompanying editorial concluded that a 30% increased risk for death and a threefold increase in the risk for myocardial infarction should preclude any additional studies.

Several HBOCs are available clinically under the FDA’s Expanded Access (compassionate use) program. HBOC-201 hemoglobin glutamer-250 (bovine), Hemopure (Biopure Corporation) is developed from ultrapurified bovine RBCs that have been glutaraldehyde polymerized. It has a higher P ₅₀ (i.e., 43 instead of 26 mm Hg), which means that it may deliver O ₂ to the tissues at least as well, if not better, than human RBCs. A recent case series reported three cases of HBOC‐201, under the FDA’s Expanded Access to patients in severe sickle cell crisis (SCC) with multiorgan failure, who refused RBCs (Jehovah’s Witnesses) or for whom compatible RBCs were not available. A recent case report described use of bovine pegylated carboxyhemoglobin (Sanguinate) in a Jehovah’s Witness with a lymphoproliferative disorder, gastrointestinal bleeding, and resultant severe anemia who was bridged to hemostatic interventions. For now, HBOCs are likely to be reserved for situations in which RBC transfusion is not an option or as a bridge to stabilizing therapy.

Preoperative Autologous Donation

It is assumed that preoperative autologous blood transfusion is safer than allogeneic blood, mainly because of the decreased risk for transfusion-transmissible infections, such as HIV and hepatitis C. However, as blood safety has improved with a marked decrease in infectivity from allogeneic blood, the difference in safety compared with autologous blood is much less. Not surprisingly, the proportion of autologous blood collected has significantly decreased since the peak in the mid-1990s.

To be eligible, the AABB requires that most donor’s Hb be no less than 11 g/dL prior to donation. Repeated donations should be separated by a week with 72 hours between the last donation and the time of surgery. The latter recommendation is to ensure restoration of intravascular volume and appropriate testing and preparation of the donated blood. At 72 hours postdonation, while intravascular volume may be restored, red cell mass is not. According to the Hemoglobin and Iron Recovery Study (HEIRS), recovery of 80% red cell mass varies from 25 to more than 168 days. On average, for those who undergo PAD, Hb is 1.1 g/dL less than those who do not donate preoperatively. In a meta-analysis incorporating data from multiple surgical patient populations, while PAD decreased the absolute risk of receiving allogenic blood by 44%, the risk of receiving a transfusion from any source (i.e., allogenic or PAD), increased by 24%, which questions the procedure’s use as a transfusion-sparing practice.

Donation itself is not without risk. In a study of American Red Cross donors, PAD was associated with nearly 12 times the postdonation hospitalization rate as allogenic donors. The criteria for autologous donation are less stringent than those for allogenic donors, as historically 15% of autologous donors do not meet safety criteria for allogenic donation. As such, certain patient populations are poor candidates for PAD because of their underlying comorbidities. These populations include patients with severe cardiopulmonary disease (e.g., severe aortic stenosis, recent myocardial infarction, or cerebrovascular event) and those with bacteremia ( Box 49.2 ).

Acute Normovolemic Hemodilution

ANH is a procedure initiated before the start of significant blood loss, by which the anesthesiologist removes whole blood from a patient while simultaneously restoring intravascular volume with either crystalloid (3 mL/1 mL of blood removed) or colloid (1 mL/1 mL of blood removed) solutions to maintain adequate hemodynamics. Blood is collected in standard blood bags containing citrate anticoagulant and maintained at room temperature in the operating room for up to 8 hours or at 4°C for 24 hours. Bleeding that occurs following ANH sheds a lower percentage of RBCs per unit of total blood volume lost, constituting the presumed major benefit of this procedure.

When major bleeding has stopped or when clinically appropriate, the sequestered blood is then reinfused into the patient in the reverse order of collection because the first unit collected has the highest concentration of coagulation factors and platelets and the highest Hb level. Although some providers advocate that stored blood be gently agitated to preserve platelet function, most practitioners do not do this, and no formal recommendations exist requiring this procedure. Reassuringly, no differences in thromboelastography (TEG) measurements have been noted between samples agitated during storage compared with those left stationary.

The amount of blood saved by ANH is both of a function of the postdilutional Hb achieved and the amount of blood volume lost intraoperatively, the latter hopefully occurring after the blood salvage. Patients undergoing minimal ANH—less than 15% of a patient’s blood volume—would only save 100 mL of RBCs, equaling 0.5 units of PRBCs. However, increasing the ANH to target postdilutional Hct of 28% in the setting of 2600 mL blood loss resulted in savings of 215 mL of RBC compared with blood loss without prior hemodilution ( Fig. 49.4 ).

The relationship between whole blood volume (mL) lost (abscissa) and red blood cell (RBC) volume lost (ordinate) in a 100-kg patient undergoing hemodilution: RBC volume lost with 2800 mL whole blood intraoperatively after hemodilution of 1500 mL whole blood (solid blue line) ; RBC volume lost with 2800 mL whole blood lost during hemodilution at each of three 500 mL volumes (solid orange line) ; cumulative RBC volume lost intraoperatively, derived for 2800 mL whole blood lost if hemodilution had not been performed (blue dashed line) . A net of 215 mL reduction in RBC volume lost with hemodilution is illustrated by the divergence of the two curves.

From Goodnough LT, Grishaber JE, Monk TG, et al. Acute preoperative hemodilution in patients undergoing radical prostatectomy: a case study analysis of efficacy. Anesth Analg . 1994;78:932–937, with permission.

Although larger volumes of hemodilution provide the largest benefit in terms of RBC mass saved and allogenic transfusions avoided, retrospective data suggest that even mild ANH may help to improve outcomes. Prospective, randomized trials demonstrate ANH as a means to decrease transfusion requirements in multiple types of surgeries, including hip replacement, hepatic resection, and vascular surgery. A recent meta-analysis evaluated 29 randomized controlled trials involving 1252 patients undergoing ANH (and 1187 controls) during cardiac surgery. They found patients who underwent ANH were transfused less frequently than those in the control groups, receiving on average three-fourths fewer allogenic blood units than those in the control groups. Not surprisingly, patients undergoing ANH experienced less postoperative blood cell mass loss with a mean loss of 388 mL in the ANH groups and 450 mL in the control groups. Another meta-analysis demonstrated similar findings in a broader patient population that included multiple surgical specialties, but the findings were criticized due to the heterogeneity of the studies included and the potential for publication bias, which would likely overestimate any true benefit. ANH has also been shown to decrease the need for other component therapy, because the removal of whole blood also removes and stores platelets and plasma. In cardiac surgery specifically, ANH may protect the sequestered blood from the effects of cardiopulmonary bypass and the platelet dysfunction that occurs.

Decisions regarding the use of ANH should be made with consideration given to the patient’s vital signs, Hct, blood volume, and the estimation of surgical blood loss and risk of transfusion ( Box 49.3 ). ANH is not without potential risk. A recent study in porcine animal models demonstrated significant adverse effects of ANH transfusions particularly in the adult compared with infant animal models. These effects included the development of bronchoconstriction and acute lung injury as a result of extravasation of fluid and deterioration of cardiopulmonary hemodynamics. Similarly, in dog models, ANH to a Hct of 30% demonstrated decreased oxygen delivery to the kidneys with preserved delivery to other organs, including the heart, brain, and spinal cord, suggesting ANH may place the kidneys at risk. Most studies evaluating ANH have focused on a reduction in RBC mass loss and the use of allogenic blood cell transfusions as the primary outcomes. Fewer studies have reported favorable findings with respect to end-organ damage in patients treated with ANH compared with those not treated, but studies in the future should look more closely at these important outcomes.

Intraoperative Cell Salvage

The term intraoperative blood collection or cell salvage describes the technique of collecting, processing, and reinfusing blood lost by a patient during surgery. It is a perioperative blood conservation technique to reduce use of allogenic blood and the risks associated with allogeneic blood exposure. It may be acceptable for use in patients that do not consent to allogeneic or preoperative autologous blood transfusions, such as Jehovah’s Witnesses. This technique should be discussed with such patients and acceptability should be determined on a case-by-case basis.

The AABB continues to recommend the following general indications for cell salvage use in their 2016 guidelines:

• 1.
  

  Anticipated blood loss is 20% or more than the patient’s estimated blood volume.

  
  
• 2.
  

  Crossmatch-compatible blood is unobtainable.

  
  
• 3.
  

  Patient is unwilling to accept allogeneic blood but will consent to receive blood from intraoperative blood salvage.

  
  
• 4.
  

  The procedure is likely to require more than one unit of RBCs.

Cell salvage involves the collection of blood from the surgical field through a specialized double-lumen suction tubing that delivers anticoagulant, commonly heparin or citrate, to the tip of the suction catheter ( Fig. 49.5 ). This prevents suctioned blood from clotting within the collection system. Blood from the surgical field is collected in a reservoir until enough fluid accumulates for processing. Processing involves specialized centrifugation that causes the lower density plasma and anticoagulant fluid to rise up and separate from the higher density RBCs, which are collected at the bottom of a conical- or cylindrical-shaped bowl. In general, 500 to 700 mL of collected blood is required for processing to produce 225 to 250 mL of salvaged saline-suspended PRBCs with a Hct of 50% to 60%. At this point, the salvaged PRBCs are ready for immediate or delayed transfusion. Microaggregate filters (40 μm) are most often employed during reinfusion because recovered and processed blood may contain tissue debris, small blood clots, or bone fragments. Some systems are able to continually process blood and can provide the equivalent of 12 units/h of banked blood to a massively bleeding patient.

Diagram of the setup of a standard cell salvage circuit.

RBC , Red blood cell.

From Ashworth A, Klein A. Cell salvage as part of a blood conservation strategy in anaesthesia. Br J Anaesth . 2010;105[4]:401–416. https://doi-org.easyaccess2.lib.cuhk.edu.hk/10.1093/bja/aeq244 .

The oxygen transport properties and survival of recovered RBCs appears to be equivalent to those of stored allogeneic RBCs. Levels of 2,3-DPG appear to be present at near normal levels in salvaged blood compared with stored allogenic blood cells, which have up to 90% reduction in 2,3-DPG levels. Similarly, the P50 of salvaged blood is similar to that of fresh venous blood drawn from the same patient and significantly higher than that of 2-week old banked blood, suggesting better oxygen-offloading capabilities. RBC deformability also appears improved compared with PRBCs.

Some practical considerations for cell recovery programs are listed in ( Box 49.4 ). If collected under aseptic conditions with a saline-wash device and if properly labeled, blood may be stored at room temperature for up to 4 hours or at 1°C to 6°C for up to 24 hours, provided storage at 1°C to 6°C is begun within 4 hours of ending the collection. The allowable interval of room temperature storage is shorter for recovered blood (4 hours) than for ANH blood (8 hours). Storage times are the same for recovered blood regardless of whether unwashed or washed.

Box 49.4

Practical Considerations for Intraoperative Cell Recovery, Storage, and Reinfusion

• 1.
  

  If not transfused immediately, units collected from a sterile operating field and processed with a device for intraoperative blood collection that washes with 0.9% saline should be stored under one of the following conditions before initiation of transfusion:

  
  
  
  
  • a.
    

    At room temperature for up to 4 h after terminating collection

    
    
  • b.
    

    At 1°C-6°C for up to 24 h, provided storage at 1°C-6°C is begun within 4 h of ending the collection

  
  
  
  
• 2.
  

  Transfusion of blood collected intraoperatively by other means should begin within 6 h of initiating the collection.

  
  
• 3.
  

  Each unit collected intraoperatively should be labeled with the patient’s first name, last name, and hospital identification number; the date and time of initiation of collection and of expiration; and the statement “For Autologous Use Only.”

  
  
• 4.
  

  If stored in the blood bank, the unit should be handled like any other autologous unit.

  
  
• 5.
  

  The transfusion of shed blood collected under postoperative or posttraumatic conditions should begin within 6 h of initiating the collection.

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