T. Paul Tran
EPIDEMIOLOGY
Approximately 12 million packed red blood cells (PRBCs) are transfused in the United States each year. This number changes over time, reflecting the broader trends in US patient population, aging, practice guidelines, and perceived safety of blood products.
PATHOPHYSIOLOGY
The two common goals in transfusion therapy are volume expansion and improved oxygen-carrying capacity.
In shock, volume expansion takes priority over oxygen-carrying capacity.
Less common goals in transfusion therapy include correction of bleeding diathesis via replacement of clotting factors or platelet.
WHOLE BLOOD
The total blood volume of a 70-kg adult is approximately 75 mL/kg or 2.5 L/m2 (5 L). A unit of whole blood contains 500 mL of blood.
Although whole blood is the ideal blood product in acute hemorrhage, it is seldom performed in modern hospitals. The two main goals in transfusion, volume expansion and improved oxygen-carrying capacity, can be achieved more efficiently by using individual blood components.
PACKED RED BLOOD CELLS
PRBCs are used primarily to increase oxygen-carrying capacity.
One unit of PRBCs has a volume of 250 mL and raises the hemoglobin by 1 gram/dL (adult), or the hematocrit by 3%. One PRBC is usually transfused over 1 to 2 hours, but can be transfused faster if patient is in shock.
Major indications for PRBC transfusion include (1) acute blood loss greater than 25% to 30% blood volume (1500 mL) in otherwise healthy adults and (2) acute blood loss greater than 2 L in surgical patients. Crystalloid is usually infused concurrently with PRBC to achieve volume expansion.
Transfusion with PRBCs is also indicated in patients with chronic anemia (ie, slow blood loss conditions) and are symptomatic and in patients with underlying cardiopulmonary disease and hemoglobin levels less than 6 grams/dL.
A “type and screen” (involving ABO and Rh blood group typing, antibody screen) can be performed in about 30 minutes. Type and screen should be ordered if the anticipated likelihood of a transfusion is low (<1%).
A “type and cross” (ABO/Rh blood typing, antibody screen, patient’S blood, and donor blood are tested for compatibility) can be performed in approximately 1 hour. Type and cross should be ordered if the anticipated likelihood of a transfusion is high (>10%).
RBCs are available as leukocyte poor, frozen, or washed. Leukocyte-poor RBCs have up to 85% of the leukocytes removed and are indicated for transplant recipients or candidates, and for patients with a history of febrile nonhemolytic transfusion reactions.
Frozen RBCs are saved rare blood types and have reduced antigen loads. They are used in patients who are at risks for alloimmunization.
Washed RBCs are for patients who have hypersensitive reactions to plasma, for neonatal transfusions, and for those with paroxysmal nocturnal hemoglobinuria.
PLATELETS
Thrombocytopenia is a risk factor for spontaneous hemorrhage and transfusion of platelet is indicated for thrombocytopenic patients who are actively bleeding or at risk for significant bleeding (eg, intracranial bleeding).
Spontaneous bleeding is rare for platelet counts >50,000/μL, but significantly increased for platelet counts <10,000/μL. Prophylactic platelet transfusion is indicated for platelet counts <10,000/μL.
One unit of platelet contains 3 to 6 × 1011 platelets in a volume of 250 to 350 mL. It can raise the platelet count by 5000 to 10,000/μL.
Dosing is usually 1 unit/10 kg (approximately 6 units for an adult). ABO- and Rh-compatible platelets are preferable.
Transfused platelets survive 3 to 5 days. The platelet count should be checked 1 and 24 hours after infusion.
Major indications for prophylactic platelet transfusions include (1) an absolute platelet count <10,000/μL, (2) active bleeding with platelet counts between 10,000 and 50,000/μL, (3) patients with platelet counts <50,000/μL who are undergoing invasive procedures (eg, thoracentesis, paracentesis).
FRESH FROZEN PLASMA
Fresh frozen plasma (FFP) is indicated in (1) patients who are bleeding or at risk for significant bleeding from an acquired coagulopathy condition (eg, massive transfusion or antithrombotic intoxication), (2) patients who have an acquired coagulopathy condition and are undergoing an invasive procedure, (3) patients who have thrombotic thrombocytopenic purpura (TTP) and are undergoing plasma exchange, (4) patients who have antithrombin III deficiency but antithrombin III concentrate is not available, and (5) patients who have congenital isolated factor deficiencies but specific virally safe products are not available.
Coagulopathy is defined as prolongation of pro-thrombin time (PT) or partial thromboplastin time (PTT) 1.5 times of standards, or a coagulation factor assay <25% of normal.
One bag of FFP contains 200 to 250 mL, 1 U/mL of each coagulation factor, and 1 to 2 milligrams/mL of fibrinogen. Typical starting dose is 8 to 10 mL/kg, or two to four bags. One unit of FFP will increase most coagulation factors by 3% to 5%.
FFP should be ABO compatible.
CRYOPRECIPITATE
Cryoprecipitate is derived from FFP; one bag contains 80 to 100 U factor VIIIC, 80 U von Willebrand’s factor, 200 to 300 milligrams fibrinogen, 40 to 60 U factor XIII, and variable amounts of fibronectin.
The usual dose is two to four bags per 10-kg body weight (limit to 20 bags for a typical adult); ABO compatible bags are preferable.
Indications for cryoprecipitate therapy include (1) fibrinogen level less than 100 milligrams/dL, in association with disseminated intravascular coagulation or congenital fibrinogen deficiency; (2) von Willebrand’s disease with active bleeding when desmo-pressin is not effective or factor VIII concentrate containing von Willebrand’s factor is not available; (3) hemophilia A when virally inactivated factor VIII concentrates are not available; (4) use as fibrin glue surgical adhesives; and (5) fibronectin replacement.
INTRAVENOUS IMMUNOGLOBULINS
Indications for intravenous immunoglobulins include the treatment of primary and secondary immunodeficiency and treatment of immune or inflammatory disorders, such as immune thrombocytopenia and Kawasaki’s syndrome.
Adverse reactions include anaphylaxis, febrile reactions, headache, and renal failure.
There have been some documented cases of patients developing a positive serology to hepatitis C after intravenous immunoglobulin therapy.
ANTITHROMBIN III
Antithrombin III (ATIII) is a serum protein that inhibits coagulation factors, thrombin, and activated factors IX, X, XI, and XII.
Deficiency can be congenital or acquired.
ATIII is mainly used for prophylaxis of thrombosis or to treat thromboembolism in patients with hereditary ATIII deficiency.
SPECIFIC FACTOR REPLACEMENT THERAPY
Table 139-1 outlines therapy for congenital coagulation factor deficiencies.
TABLE 139-1 Replacement Therapy for Congenital Factor Deficiencies
COMPLICATIONS OF TRANSFUSIONS
Adverse reactions occur in up to 20% of transfusions and are usually mild.
Transfusion reactions can be immediate or delayed.
Table 139-2 summarizes the types of immediate reactions as well as methods of recognition, management, and evaluation.
TABLE 139-2 Selected Acute Transfusion Reactions: Recognition, Management, and Evaluation
DELAYED TRANSFUSION REACTIONS
Delayed hemolytic reactions can occur 7 to 10 days after transfusion.
Infection may result from transfusion. There is a small risk of transmission of HIV, hepatitis B and C, cytomegalovirus, parvovirus, and human T-cell lymphotropic viruses I and II.
Other rare but reported pathogens include Epstein-Barr virus, syphilis, malaria, babesiosis, toxoplasmosis, and trypanosomiasis.
Hypothermia may occur from rapid transfusions of refrigerated blood.
Noncardiogenic pulmonary edema may be caused by incompatible passively transferred leukocyte antibodies, and usually occurs within 4 hours of transfusion.
Clinical findings of noncardiogenic pulmonary edema are respiratory distress, fever, chills, tachycardia, and patchy infiltrates on chest radiograph without cardi-omegaly. There is no evidence of fluid overload.
Electrolyte imbalance may occur. Citrate is part of the preservative solution and chelates calcium. Significant hypocalcemia even with massive transfusion is rare because patients with normal hepatic function readily metabolize citrate into bicarbonate.
Hypokalemia can occur with large transfusions due to the metabolism of citrate to bicarbonate, leading to alkalosis, which drives potassium ions into the intracellular space.
Hyperkalemia can occur in patients with renal failure or in neonates.
Graft-versus-host disease, fatal in greater than 90% of cases, occurs when nonirradiated lymphocytes are inadvertently transfused into an immunocompro-mised patient.
Table 139-3 summarizes the types of delayed transfusion reactions as well as methods of recognition, management, and evaluation.
TABLE 139-3 Delayed Transfusion Complications
EMERGENCY TRANSFUSIONS
Use of type O or type-specific incompletely cross-matched blood may be life-saving but carries the risk of life-threatening transfusion reactions. Its use should be limited to the early resuscitation of patients with severe hemorrhage without adequate response to crystalloid infusion.
Before transfusing, blood should be obtained for baseline laboratory tests and type and crossmatching. Rh-negative blood is preferable if it is not fully cross-matched.
MASSIVE TRANSFUSION
Massive transfusion is the approximate replacement of a patient’S total blood volume within a 24-hour period.
Complications include bleeding, citrate toxicity, and hypothermia.
Bleeding may result from thrombocytopenia, platelet dysfunction, disseminated intravascular coagulation, or coagulation factor deficiencies.
Patients receiving more than 5 U of whole blood, those with liver disease, and neonates are at risk for hypocalcemia from citrate toxicity.
The QT interval is not a reliable indicator in this setting; an ionized calcium level is the preferred tool to assess possible symptomatic hypocalcemia.
Hypocalcemia should be treated with 5 to 10 mL of IV calcium gluconate infused slowly.
Physicians should be aware of the possibility of hypothermia when administering 3 U or more of blood rapidly.
BLOOD ADMINISTRATION
The correct identification of the patient and the unit to be transfused should always be ensured.
An 18-gauge or larger IV catheter is preferred to prevent hemolysis and to permit rapid infusion. Micropore filters should be used to filter out microag-gregates of platelets, fibrin, and leukocytes.
Normal saline solution is the only crystalloid compatible with PRBCs. Warmed saline solution (39°C-43°C or 102.2°F-109.4°F) may be given concurrently or a blood warmer used to prevent hypothermia. Blood will hemolyze if warmed to greater than 40°C(104°F).
Rapid transfusion may be facilitated by the use of pressure infusion devices.
Patients at risk for hypervolemia should receive each unit over 3 to 4 hours.
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 233, “Transfusion Therapy,” by Clinton J. Coil and Sally A. Santen.