INTRODUCTION
Modern transfusion practice uses blood that has been separated into specific components (Table 238-1). Coagulation factors, either derived from human plasma or manufactured with recombinant technology, are used treat hemorrhage associated with a deficiency of one or more factors (Table 238-2). Transfusion in the ED typically is done for acute blood loss and/or circulatory shock. As medical care is moved to outpatient settings, emergency physicians may be responsible for transfusion therapy or complications previously relegated to inpatient settings.1
Component | Shelf Life | Volume/Unit (mL) | Approximate Content/Unit* | Initial Dose | Dosage Effect |
---|---|---|---|---|---|
Packed red blood cells (PRBCs) | 21–42 d | 250–350 | Red cells 65%–80% Plasma 10–20 mL | Adult: 2 units Pediatrics: 10–15 mL/kg | Raises hemoglobin concentration approximately 2 grams/dL (20 grams/L) or hematocrit by 6% in adults (2–3 grams/dL [20–30 grams/L] or 7%–9% in children) |
Platelets (apheresis-collected single-donor platelet concentrate) | 5 d | 250–300 | Platelets 3–6 × 1011 | 1 unit or 5 mL/kg | Raises platelet count by up to 50,000/mm3 (50 × 109/L), but less in many cases |
Platelets (pooled donor platelet concentrate, rarely used in the United States) | 5 d | 50–60 | Platelets 8–9 × 1010 | 6 units or 5 mL/kg | Raises platelet count by up to 50,000/mm3 (50 × 109/L), but less in many cases |
Fresh frozen plasma (FFP) | 1 y frozen and up to 5 d after thawing | 200–250 | Each coagulation factor about 200–250 units Fibrinogen 400–500 milligrams | Four units or 15 mL/kg | Raises most coagulation factors levels approximately 20%; volume issues may make factor correction difficult; benefits are transient |
Cryoprecipitate | 1 y frozen and 4 h thawed | 20–50 | Factor VIII 80–140 units Fibrinogen 225–420 milligrams von Willebrand factor in variable amounts Factor XIII and fibronectin in some amounts | 0.2 units/kg or 10–15 units in an adult | Increases fibrinogen 50–100 milligrams/dL (0.5– 1.0 grams/L) |
Type of Product* | Initial Dose | Comments and Approved Indications |
---|---|---|
Fibrinogen concentrate (human) RiaSTAP® (CSL Behring) | Dosed to increase fibrinogen level from baseline to over 150 milligrams/dL (1.5 grams/L) If baseline fibrinogen level unknown, administer 70 milligrams/kg | Each vial contains 900–1300 milligrams of fibrinogen Acute bleeding episodes in patients with congenital fibrinogen deficiency |
Three-factor prothrombin complex concentrate (human) Profilnine SD® (Grifols Biologicals) Bebulin VH® (Baxter Healthcare Corporation) | Dosed according to desired factor IX increase | Contains factors II, IX, and X Treat hemophilia B (factor IX deficiency) |
Four-factor prothrombin complex concentrate (human) Kcentra® or Beriplex® P/N (CSL Behring) Octaplex® (Octapharma) | Dosed in factor IX units according to pretreatment INR | Contains factors II, VII, IX, and X Urgent reversal of bleeding due to vitamin K antagonist (e.g., warfarin)–induced coagulation factor deficiency in adult patients |
Anti-inhibitor coagulant complex FEIBA NF® (Baxter) | 50–100 units/kg | Contains factors II, IX, and X, mainly nonactivated, and factor VII mainly in activated form Bleeding in patients with hemophilia A or B with inhibitors |
Coagulation factor VIIa (recombinant) NovoSeven® RT (Novo Nordisk) | 90 micrograms/kg | Bleeding episodes and perioperative management in adults and children with hemophilia A or B with inhibitors Congenital factor VII deficiency Glanzmann’s thrombasthenia with refractoriness to platelet transfusions Bleeding episodes and perioperative management in adults with acquired hemophilia |
Blood products are provided using standardized preparations as “units” (Table 238-1). Provide information to patients about the risks, benefits, and alternatives to transfusion prior to the initial infusion of red blood cells, plasma, or platelets.2,3 Obtain informed consent or document that the patient was unable to consent if a medical emergency exists.2 Use great care to assure that the correct blood product is delivered to the correct patient because of the consequences of transfusing the wrong unit; use two individuals to verify the identification of the patient and the unit before transfusion. Bar-code identification along with verification by one individual is an alternative to two-person verification.4
TRANSFUSION OF BLOOD PRODUCTS
Adult total blood volume is approximately 2.5 L/m2, 75 mL/kg, or about 5 L in a 70-kg person. Whole blood transfusion would seem ideal to replace acute blood loss; however, storage of whole blood inactivates platelets and other factors. Therefore, whole blood is fractionated to its components for storage and transfusion. Packed red blood cells (PRBCs) are prepared by the centrifugation of whole blood to remove approximately 80% of the plasma; then a preservative solution is added (most commonly, citrate-phosphate-dextrose) with the additional nutrients adenosine, and mannitol (Table 238-1).
The primary reason for PRBC transfusion is to increase oxygen-carrying capacity.1,4 Emergency PRBC transfusion is usually performed for acute blood loss or, occasionally, profound anemia with impaired oxygen delivery. Transfusion thresholds assist the physician in assessing whether PRBC transfusion will benefit the patient. Current evidence is substantial that a restrictive threshold for PRBC transfusion is appropriate for most patients.5,6,7,8,9 In previously healthy adults, transfusion should be considered at hemoglobin concentrations less than 7 grams/dL (70 grams/L), and for patients with sepsis or ischemic heart or brain injury, transfusion should be considered at a hemoglobin concentration less than 8 to 9 grams/dL (80 to 90 grams/L).10,11,12,13 Transfusion threshold values for children may be higher and depend on the etiology of their anemia.14 Some patients with severe sepsis receiving early, goal-directed therapy may benefit from transfusion up to a hemoglobin of 10 grams/dL (100 grams/L) when the central venous oxygen saturation is less than 70%.15
For actively bleeding patients, transfusion is based on clinically estimated blood loss rather than hemoglobin levels, because the fall in measured hemoglobin will lag behind the clinical impact of acute blood loss. A loss of about 30% blood volume (1500 mL in an adult) generally produces symptoms and signs, but young, healthy patients can tolerate this degree of loss when treated with crystalloid. However, patients with chronic illness such as underlying anemia, cardiac diseases, or pacemakers or those on β-blockers or similar medications may not tolerate blood loss. Consider emergency PRBC transfusion for unstable trauma patients based on an inadequate response to an initial 2-L bolus of IV crystalloid or 40 mL/kg in children. The anticipated clinical course also guides the decision to transfuse the patient with acute hemorrhage; the transfusion threshold is lower if the source of bleeding cannot be controlled immediately compared to a patient whose acute hemorrhage has stopped.
Use the minimum amount of PRBCs to accomplish the desired clinical outcome.7,12 A single PRBC unit will raise the hemoglobin by 1 gram/dL (10 grams/L) and hematocrit by 3% in adults. In children, 10 to 15 mL/kg of PRBCs will raise the hematocrit by 6% to 9% and the hemoglobin level by approximately 2 to 3 grams/dL (20 to 30 grams/L).14
One unit of PRBCs, approximately 250 mL in volume, is generally transfused over 1 to 2 hours. PRBCs should be transfused more rapidly in patients with hemodynamic instability. Single-unit PRBC transfusions should not exceed 4 hours to prevent contamination. If a slow transfusion is desired (e.g., in a patient at risk for volume overload), the blood bank should be asked to split a unit so that the first half can be transfused over 4 hours while the second half waits in the blood bank refrigerator. During standard transfusions, the initial infusion rate is slower over the first 30 minutes so that if there is a transfusion reaction, the infusion may be stopped.
PRBC transfusion requires matching the recipient’s and donor’s red blood cells according to blood type (ABO and Rh) and screening the recipient’s plasma for antibodies to the minor red blood cell antigens. Screening is done using a mixture of commercially available red blood cells that have all of the important minor antigens.12 If the screen is positive, then the recipient’s plasma is cross-matched against the specific PRBC unit intended for transfusion. Blood type can be determined in approximately 15 minutes, whereas it takes about 45 to 60 minutes to perform a serologic cross-match. If an anti–red blood cell antibody is found in the recipient’s plasma, cross-matching may take longer and require additional blood specimens from the patient. For most patients with no antibodies detected on the screen, serologic cross-matching can be foregone and ABO-Rh–compatible PRBC units can be released by the blood bank using a process termed electronic (or computerized) cross-match. This process has computer-based verifications to ensure the patient receives ABO-Rh–compatible blood.12 Electronic cross-matching typically takes 5 minutes or less to perform.
Type O Rh-negative (universal donor) blood may be used in critical circumstances because these transfused red cells do not contain major blood group antigens (A or B). Type O Rh-positive blood may be used if type O Rh-negative is not available, but should be avoided in girls and women of childbearing potential. Approximately 20% of Rh-negative patients transfused with 1 unit of Rh-positive PRBCs will develop anti-Rh(D) antibodies, creating the risk for hemolytic disease of the newborn with subsequent pregnancies. This is usually clinically inconsequential for men or postmenopausal women.
PRBCs may be further treated for specific clinical applications: leukocyte-reduced PRBCs, irradiated PRBCs, washed PRBCs, and frozen PRBCs.16 Leukocyte-reduced PRBCs have 70% to 85% of the white cells removed. Leukocyte-reduced PRBCs are used (1) to decrease the occurrence of nonhemolytic febrile reactions due to cytokines from transfused white cells, (2) to prevent sensitization to human leukocyte antigen antibodies found on white cells in patients who may be eligible for bone marrow transplantation, and (3) to minimize the risk of intracellular virus transmission, such as cytomegalovirus. Leukocytes can be reduced by filtration or other methods before storage of the PRBCs or during transfusion. Irradiation of PRBCs eliminates the capacity of T lymphocytes to proliferate, thereby preventing the donor’s T lymphocytes from reacting to the recipient’s cells and causing graft-versus-host disease. Irradiated cells are used in transplant patients, neonates, and immunocompromised patients, and with directed donations from relatives of the patient. Washed PRBCs are indicated in patients who have a hypersensitivity to plasma, such as immunoglobulin A deficiency or persistent febrile reactions. For rare blood types, red cells may be frozen and saved for up to 10 years for later use. Freezing red blood cells is more expensive than normal storage, and once thawed, the blood must be washed and transfused within 24 hours.
Massive transfusion is the replacement of one blood volume or approximately 10 units of PRBCs in an adult within a 24-hour period. If only PRBCs are used, platelets and coagulation factors lost or consumed will not be replaced, potentially producing increased bleeding. The military medical experience during the past decade finding good results with using fresh whole blood transfusion for trauma patients17 has led to the concept of incorporating the platelets and plasma in addition to PRBCs to closer mimic whole blood during a massive transfusion.18,19 Studies routinely using platelets and fresh frozen plasma (FFP) with PRBCs during massive transfusion have yielded mixed results on reducing mortality.20,21
Institution-specific massive transfusion protocol is recommended to guide the clinician in correct ordering of the individual products and facilitate release from the blood bank.22 The best ratio of PRBCs to platelets to FFP during a massive transfusion is controversial.23 Some experts advocate a 1:1:1 ratio, although lower ratios of platelets and FFP have been used without clear evidence of inferiority.24 Including cryoprecipitate,20 fibrinogen concentrate,24 or coagulation factor VIIa (recombinant)20,24 during a massive transfusion has produced mixed results, depending on the outcome measured.
If fixed ratios of platelets or FFP are not used, suggested indications for their administration during massive transfusion include the following: (1) when the platelet count is <50,000/mm3(<50 × 109/L), a platelet transfusion is warranted; (2) if the INR is >1.5, FFP may be given; and (3) if the fibrinogen level is <100 milligrams/dL (<1 g/L), it may be replaced with cryoprecipitate or fibrinogen concentrate.
Draw sufficient specimens early in the course from massive transfusion patients because once the patient has received close to one blood volume of transfused products, new blood specimens will contain so much donor blood that it will confuse further cross-matching of subsequent units. Hypothermia is a risk during massive transfusion, so blood and crystalloid should be warmed, in addition to instituting warming measures for the patient. Hypocalcemia from the preservative citrate chelating calcium may occur with a massive transfusion.22
Platelet transfusions are used either prophylactically to prevent bleeding in thrombocytopenia or therapeutically when patients with thrombocytopenia are actively bleeding.25,26 One apheresis-collected, single-donor platelet concentrate is the standard product in developed countries (Table 238-1). Platelets collected from six different donors (a “six pack”) can be combined for transfusion but are not recommended because this increases the risk of disease transmission and transfusion reaction.
One apheresis single-donor platelet unit will increase the platelet count by up to 50,000/mm3 (50 × 109/L), an amount sufficient to stop most spontaneous and minor traumatic bleeding. Check platelet levels at 1 and 24 hours after transfusion completion because the response is variable. Failure of platelets to rise appropriately may be due to increased consumption of platelets from an underlying process, active thrombosis due to ongoing hemorrhage, destruction due to platelet antibodies, or sequestration due to hypersplenism. Transfused platelets should survive 3 to 5 days unless there is a platelet-consumptive process.
The decision to transfuse platelets depends on the severity of thrombocytopenia and clinical circumstances (Table 238-3).13,25,26,27 Patients with comorbid conditions, such as infection, fever, medications, and CNS involvement, may be more likely to bleed or be at higher risk if they bleed; therefore, the threshold for platelet transfusion is more liberal.13,28
Platelet count <5000/mm3 (<5 × 109/L) Platelet count <20,000/mm3 (<20 × 109/L) with a coagulation disorder, low-risk procedure, or during outpatient treatment Platelet count <50,000/mm3 (<50 × 109/L) with active bleeding or invasive procedure within 4 h Platelet count <100,000/mm3 (<100 × 109/L) with neurologic or cardiac surgery As part of a massive transfusion protocol |
There are no clear recommendations concerning platelet transfusions in patients with nonfunctioning platelets (antiplatelet medications, uremia, von Willebrand’s disease, or hyperglobulinemia) and active bleeding. In von Willebrand’s disease, normal platelets may help deliver von Willebrand factor to the bleeding site. Conversely, in uremic patients, the transfused platelets may not function any better than native platelets. In these complex cases, consult with a hematologist or transfusion medicine specialist for recommendations.
Relative contraindications to the transfusion of platelets are disorders associated with platelet activation, such as thrombotic thrombocytopenic purpura or heparin-induced thrombocytopenia, in which transfusion may worsen thrombosis. In these conditions, ongoing bleeding or the need to perform procedures may necessitate platelet transfusion in consultation with the appropriate specialist.
Platelet transfusions are usually ABO-type specific because the platelets are bathed in plasma, although a serologic cross-match is usually not done. As a result, patients receiving platelets are subject to many of the same complications described for plasma transfusion. Depending on availability, non–type-specific platelets may sometimes be transfused. This practice is usually avoided in children or patients receiving multiple transfusions because they are at higher risk for complications. Transfusing non–type-specific platelets may also shorten the half-life of the transfused platelets.
As with PRBCs, platelets can be leukocyte reduced or washed. Patients who have had repeated transfusions may become alloimmunized and refractory to platelet transfusion, noted by the lack of expected rise in platelet count after transfusion. Such patients need human leukocyte antigen–matched or cross-matched platelets. Other factors may affect the efficacy of platelet transfusion, including bacterial sepsis in the recipient, antibiotics forming an antigen complex epitope with the platelet, disseminated intravascular coagulation, and splenomegaly.
FFP is plasma obtained after the separation of whole blood from erythrocytes and platelets and then frozen within 8 hours of collection.29