Summary
Donation of one unit of whole blood or apheresis can be used to obtain red blood cell (RBC) units. For apheresis RBCs, a donor is connected to an apheresis machine and RBCs are separated from other constituents which are returned to the donor; this process may yield 2 units of RBCs or a single unit of RBCs, along with a unit of platelets and/or plasma. RBC units are stored in polyvinyl chloride bags with the plasticizer di-2-ethylhexylphthalate (DEHP) to maintain RBC membrane integrity during storage. Preservation includes an anticoagulant-preservative (A-P) solution, and the current additive solutions maintain pH and other parameters needed to allow RBC storage shelf life of 42 days [1]. ABO typing and matching are required to avoid reactions due to mismatch (see Table 13.1).
Packed Red Blood Cells
Processing, Storage, and ABO Compatibility
Donation of one unit of whole blood or apheresis can be used to obtain red blood cell (RBC) units. For apheresis RBCs, a donor is connected to an apheresis machine and RBCs are separated from other constituents, which are returned to the donor; this process may yield 2 units of RBCs or a single unit of RBCs, along with a unit of platelets and/or plasma. RBC units are stored in polyvinyl chloride bags with the plasticizer di-2-ethylhexylphthalate (DEHP) to maintain RBC membrane integrity during storage. Preservation includes an anticoagulant-preservative (A-P) solution, and the current additive solutions maintain pH and other parameters needed to allow RBC storage shelf life of 42 days [Reference Vo, Roberts, Scher, Kaye, Liu, Perelman and Leavitt1]. ABO typing and matching are required to avoid reactions due to mismatch (see Table 13.1).
Table 13.1 ABO and rhesus compatibility of the various blood components
| Recipient blood type | Donor RBCs | Donor platelets | Donor FFP | Donor cryoprecipitate |
|---|---|---|---|---|
| Rh compatibility | Indicated | Indicated | Not indicated | Not indicated |
| O | O | O, AB, A, B | O, A, B, AB | O, A, B, AB |
| A | A, O | A, AB, Footnote aB, aO | A, AB | A, AB |
| B | B, O | B, AB, Footnote aA, aO | B, AB | B, AB |
| AB | AB, A, B, O | AB, Footnote aA, Footnote aB, Footnote aO | AB | AB |
a Consider other donors if known from apheresis process and resuspended in additive solutions.
RBC, red blood cell; FFP, fresh frozen plasma; Rh, rhesus.
Components
One unit of RBCs has approximately 2–5 billion leukocytes, which convey risks of adverse reactions, including transmission of cytomegalovirus (CMV), intracellular organisms, and inflammatory or immunologically mediated reactions. Leukocyte reduction or depletion is the process of blood filtration to remove leukocytes. Leukoreduction done prestorage is preferred over depletion as it removes more leukocytes, has better quality control, and is a standardized process. Universal leukoreduction strategies decrease the leukocyte load by about 99.9%. Benefits of leukoreduction include reducing the incidence of febrile nonhemolytic transfusion reactions, transfusion-related acute lung injury (TRALI), and transmission of CMV and prions [Reference Kleinman2].
Clinical Application
Informed consent should be obtained prior to transfusion, except in emergencies. In the United States, average storage of RBCs is 15–19 days; numerous randomized clinical trials demonstrated similar outcomes with fresh, standard issue, or long storage duration RBCs. RBC units require storage at 1–6°C to prevent bacterial growth and preserve viability. During any transport, RBCs must be kept between 1 and 10°C.
Indications for Transfusion
Symptomatic anemia and acute blood loss are indications for transfusion of RBCs. Physiologic triggers include orthostatic hypotension, shock with marginal hemoglobin levels, and evidence of end-organ damage due to inadequate tissue oxygenation. Clinical concerns of risks of transfusions led to studies revealing noninferiority of restrictive transfusion strategies aimed at hemoglobin levels of 7–8 g dL−1. Single-unit transfusions with reassessment prior to further transfusion and treatment of iron deficiency with iron are both recommended by the Choosing Wisely Campaign, which is promoted by clinical groups from over 20 countries on five continents [3]. Recommendations for most hospitalized patients include a restrictive threshold of 7–8 g dL−1, and for patients with preexisting cardiovascular disease, data support a threshold of 8 g dL−1. Current recommendations are to assess for symptoms, as well as hemoglobin level, prior to deciding to transfuse. Anesthesia-related studies, such as a meta-analysis by Chong et al. [Reference Chong, Krishnan, Cheng and Martin4], also support restrictive strategies in critically ill and surgical patients with improved outcomes, including reduced risk of stroke, transfusion reactions, hospital length of stay, and significantly reduced 30-day mortality in critically ill patients. Further studies are necessary to determine specific goals for perioperative stages and for varied surgical populations.
Potential Complications
Transfusion reactions are covered later in this chapter. Mistransfusion, iron overload, alloimmunization, and metabolic derangements can also occur. Some of these complications can be decreased by avoiding unnecessary transfusions or using electronic systems to ensure patient identification and blood matching for each patient.
Fresh Frozen Plasma
Processing, Storage, and ABO Compatibility
Plasma is centrifuged out from citrate-containing whole blood or apheresis donations. Plasma rises to the top. It is then collected and frozen to −18°C within 8 hours of collection. It should be noted that there are instances where collected plasma is frozen >8 hours, but <24 hours, from collection. This is termed PF24 for plasma frozen within 24 hours. The clinical difference is negligible, but there is a decrease in factor VIII and protein C levels during the thawing process [Reference Scott, Puca, Heraly, Gottschall and Friedman5]. FFP can be stored frozen for up to 1 year. ABO compatibility must be followed.
Components
FFP contains factors II, V, VII, VIII, IX, X, and XI. It also contains fibrinogen (400–900 mg per unit), albumin, protein C, protein S, antithrombin, tissue factor pathway inhibitor, and von Willebrand factor (vWF) [Reference Khawar, Kelley, Stevens and Guzman6].
Clinical Application
Once thawed, FFP must be used within 5 days for major hemorrhagic cases; otherwise it is recommended to transfuse FFP within 24 hours of thawing [Reference Green, Bolton-Maggs and Beattie7]. One unit of FFP is contained in approximately 250 mL of solution. Usual dose of 15–20 mL kg−1 is enough to raise clotting factors by approximately 20–30%. In general, raising clotting factors by 10% is enough for clinically significant hemostasis [Reference Hunt8].
Indications for Transfusion
Plasma is mainly used to correct for clotting factor deficiencies in actively bleeding patients, especially when specific clotting factor concentrates are not readily available. Patients with significant liver disease have deficiencies in multiple clotting factors. When they are actively bleeding or there is concern for clinically significant bleeding with upcoming invasive procedures, and the international normalized ratio (INR) is >1.5, transfusion of FFP is generally indicated. Other acquired deficiencies in clotting factors are expected in patients taking vitamin K antagonists, those with acute disseminated intravascular coagulation (DIC), and those undergoing massive transfusion protocol. The significance of active bleeding weighed against the unavailability of specific clotting factor concentrates would make FFP a reasonable option for transfusion. FFP has also been indicated with thrombotic microangiopathies as a replacement fluid [Reference Liumbruno, Bennardello, Lattanzio, Piccoli and Rossetti9].
Potential Complications
FFP has been implicated in TRALI at a rate of approximately 1 in 2000 plasma transfusions, although the incidence may be higher due to limitations in passive reporting of adverse events. It is the second leading cause of transfusion-associated mortality in the United States, with FFP being the most common cause for this complication [Reference Pandey and Vyas10]. Caution should be taken to avoid FFP in patients with a congenital deficiency in immunoglobulin A in the presence of anti-IgA antibodies. These patients can develop severe anaphylactic reactions. FFP from IgA-deficient donors are advised for this specific patient population. Less than 1% may develop significant anaphylactic allergic or febrile reactions. Approximately 1% may have mild allergic reactions manifested as urticaria. Other complications include transfusion-associated circulatory overload (TACO), transmission of viral infections, hemolytic transfusion reaction (HTR), and citrate toxicity [Reference Liumbruno, Bennardello, Lattanzio, Piccoli and Rossetti9].
Platelets
Processing, Storage, and ABO Compatibility
Platelets are obtained either from whole blood or through an apheresis donation. The clinical efficacy is similar, with the only difference being that the recipient of the transfusion is exposed to more donors with platelets obtained from whole blood [Reference Liumbruno, Bennardello, Lattanzio, Piccoli and Rossetti9]. The platelets are then stored at room temperature of approximately 22°C, with continuous agitation, for no more than 5 days. ABO compatibility is not required, but recommended if derived from whole blood. Rhesus (Rh) compatibility is necessary.
Components
In general, platelets obtained from whole blood produces approximately 0.45–0.85 × 1011 platelets. Therefore, multiple units are pooled together to produce a platelet concentrate of about 2.5 × 1011, whereas platelets obtained from an apheresis donation produces a concentrate of about 3 × 1011.
Clinical Application
One unit of pooled platelets from whole blood or one unit of platelets from apheresis will raise the platelet count by approximately 30,000–50,000 per microliter in an average adult. Once processed, platelets should be transfused within 4 hours of release.
Indications for Transfusion
Platelet transfusion is used for prophylactic and therapeutic treatment of significant bleeding in patients with severe thrombocytopenia or disorders of dysfunctional platelets [Reference Liumbruno, Bennardello, Lattanzio, Piccoli and Rossetti9]. For anesthesiologists, the suggested threshold for transfusion varies, but the general recommendation is to transfuse to a platelet count of above 50,000 per microliter for invasive procedures or major surgery. For surgeries where even microbleeds are devastating, such as ocular surgery or neurosurgery, it is recommended to transfuse to a platelet count of above 100,000 per microliter. During massive transfusions, it is recommended to transfuse to a threshold of 75,000 per microliter. Specific perioperative situations where platelet transfusions would be indicated include acute DIC with significant hemorrhage, disorders of platelet function with active bleeding, or during massive transfusions with active bleeding.
Potential Complications
Sepsis is a concern due to the storage of platelets at room temperature favoring an environment for bacterial growth. Therefore, the risk of bacterial infection is higher than viral transmission, with a rate of contamination of about 1 in 2000 transfusions. Mild allergic reactions can occur, as well as febrile nonhemolytic reactions, TRALI, TACO, alloimmunization to human leukocyte antigens (HLA) and human platelet antigens (HPAs), and posttransfusion purpura. Transfusion of platelets should be avoided in patients with thrombotic thrombocytopenic purpura and heparin-induced thrombocytopenia due to the risk of worsening thrombosis.
Cryoprecipitate
Processing, Storage, and ABO Compatibility
When FFP is thawed to 1–6°C, cryoprecipitate precipitates out from the solution. These cryoproteins are then suspended in a small volume of plasma and refrozen. It can be stored at −18°C for up to 1 year. To preserve the integrity of clotting factors, it takes approximately 20–30 minutes to thaw cryoprecipitate. ABO compatibility must be followed. Rh compatibility is not required.
Components
Cryoprecipitate contains fibrinogen, factors VIII and XIII, vWF, and fibronectin. The average fibrinogen content is 300 mg per unit. The average factor VIII content is 120 IU per unit, with the shortest half-life of 12 hours. The average factor XIII content is 60 IU per unit. The average vWF content is 125 IU per unit. Most facilities will pool multiple units together when distributing for transfusion [Reference Tobian11].
Clinical Application
Cryoprecitipate must be transfused within 4–6 hours of thawing. Cryoprecipitate is typically given as 5–10 pooled units. For correcting fibrinogen deficits, one unit of cryoprecipitate generally raises the plasma fibrinogen concentration by about 7–10 mg dL−1 in an average 70-kg adult. The target fibrinogen level is above 100 mg dL−1; thus 10 units of cryoprecipitate should be adequate to reach this target. It should be noted that there are insufficient data to recommend an optimal dose [Reference Green, Bolton-Maggs and Beattie7].
Indications for Transfusion
Cryoprecipitate is mainly used for clinically significant bleeding in patients with hematologic disorders consisting of deficiencies in clotting factors specific to components found in cryoprecipitate. These include patients with von Willebrand disease, DIC, liver disease, uremia with significant bleeding, and with low or dysfunctional fibrinogen. Cryoprecipitate is considered an alternative if first-line therapy is not available. Standard of care involves the use of specific recombinant or plasma-derived factor concentrates.
Potential Complications
There is a risk of viral transmission that is similar to packed RBC (PRBC) transfusion, but with the added effect of exposure to multiple donors due to pooled units typically being infused. Other risks are similar to that of FFP, but lower overall due to smaller total volumes of plasma transfused. These include TRALI, TACO, HTR, allergic reaction, and citrate toxicity.
Complications
Any suspected transfusion reaction should be reported to the local blood bank. With reactions being a rare event, their expertise is a valuable resource to help guide management, as well as provide details for further workup necessary to appropriately diagnose complications from a transfusion. Reporting is important to prevent future reactions to the patient, as well as for quality control measures. Table 13.2 summarizes and compares key elements of complications commonly associated with blood product transfusions.
Table 13.2 Complications commonly associated with transfusion of blood products
| Complication | Timeline | Risk factors | Major signs and symptoms | Treatment and further workup |
|---|---|---|---|---|
| TRALI | Within 6 hours of transfusion |
|
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| TACO | Within 12 hours of transfusion |
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| Hemolysis |
|
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|
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| Febrile reactions | Within 1–6 hours of transfusion |
|
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| Allergic reactions | Within minutes of transfusion |
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| Sepsis | Within 30 minutes to 5 hours of transfusion |
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TRALI, ; TACO, ; BNP, B-type natriuretic peptide; NT-proBNP, N-terminal pro-BNP.
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