Chapter 137. Transfusion Therapy

The goal of transfusion is to improve oxygen delivery to tissues, provide intravascular volume expansion, and to replace missing or depleted clotting factors in patients with clinically significant hemorrhage, anemia, thrombocytopenia or coagulopathy. Great care must be taken to ensure that the correct blood product is delivered to the correct patient.

There are few indications for the use of whole blood transfusion. Although whole blood can provide volume expansion and oxygen-carrying capacity, the same can usually be accomplished more efficiently by using individual blood components.

Packed red blood cells (PRBC) are prepared from whole blood by removing most platelets and/or white cells. A typical unit of PRBC has 250 mL of RBCs and raises an adult's hemoglobin by 1 gram/dL (hematocrit by 3%). PRBCs increase oxygen-carrying capacity in anemic patients.

The decision to transfuse PRBC is based on individual clinical judgment, taking into account patient's hemodynamic status, underlying medical condition, tolerance for anemia, and risk of end-organ ischemic injury. Adequate oxygen delivery in healthy normovolemic patients can be maintained with hemoglobin levels as low as 7 grams/dL, although patients with comorbid conditions may require transfusion at higher levels of hemoglobin. The usual indications for PRBC transfusion include: (a) acute hemorrhage, defined as blood loss >25% of blood volume, (b) hemorrhagic shock, (c) surgical blood loss greater than 2 L; and (d) symptomatic anemia or being at-risk for ischemic events, ie, patients with hemoglobin <6 grams/dL who have symptoms of end-organ ischemia, ≥55 years of age, have cardiac disease, sepsis, severe infection, or APACHE II score >20.

Type and crossmatch assesses ABO/Rh blood type, the presence of antibodies, and patient and donor blood compatibility. It takes 15 to 30 min to perform and is ordered if the likelihood of transfusion is high. Type and screen assesses the ABO/Rh blood typing and the presence of antibodies. It takes 15 to 30 min to perform and is ordered if the likelihood of transfusion is low.

In critical situations, where there is no time to perform a complete ABO/Rh-typing, group O/Rh-negative blood ("universal donor") can be given to patients without waiting for a complete type and crossmatch. Type O/Rh-positive blood may be used if Rh-negative blood is unavailable but is generally avoided in girls and women of childbearing age. Before transfusion, blood for baseline laboratory tests, type, and crossmatching should be obtained.

PRBC may be further treated to minimize complications in special patient populations, such as neonates, transplant and patients on transplant list, patients who have received prior transfusions, pregnant patients, immunocompromised patients, and patients with hypersensitivity to plasma. Options include leukocyte reduced, irradiated, frozen deglycerolized, washed, and CMV negative PRBC.

A unit of PRBC is usually transfused over 2 hours but can be given much faster using a pressure infusing device or over 4 hours, if needed. Micropore filters are used to filter out microaggregates of platelets, fibrin, and leukocytes. Normal saline solution is the only crystalloid compatible with PRBC. Blood warmers or concurrently administered warmed saline solution (39°C to 43°C or 102.2°F to 109.4°F) can be used to prevent hypothermia.

Platelet transfusions may be used in thrombocytopenic patients to prevent bleeding or to help stop active bleeding. Platelet transfusion is usually not helpful in cases of bleeding from platelet dysfunction (eg, uremia) or from thrombocytopenia due to increased consumption/sequestration until the underlying disorder (eg, DIC) is corrected. General indications for platelet transfusion include platelet count <10,000 mm3 in asymptomatic patients, platelet count <15,000/mm3 with a coagulation disorder or minor bleeding, platelet count <20,000/mm3 with major bleeding, platelet count <50,000/mm3 with an invasive procedure, general surgery or during massive transfusion, or platelet count <100,000/mm3 with neurologic or cardiac surgery.

Each unit of single donor platelets contains approximately 3 to 6 × 1011 platelets in 250 to 300 mL of plasma and may increase the platelet count in an adult by up to 50,000/mm3, but less in many cases. Typical dose is 1 unit or 5 mL/kg. Typical dose of pooled donor platelet is 6 units or 5 mL/kg.

ABO- and Rh-compatible platelets are preferable. Platelets may also be washed or irradiated. The platelet count should be checked at 1 and 24 hours after transfusion. Transfused platelets survive 3 to 5 days in the absence of an ongoing platelet consumption process.

Fresh frozen plasma (FFP) contains all coagulation factors and fibrinogen. FFP is used to correct coagulation defects in bleeding patients with multiple coagulation deficiencies (liver disease, warfarin therapy/OD, massive transfusion) and to correct coagulation defects for which no factor is available. FFP is also administered prior to high-risk invasive procedures if PT/INR >1.5X normal, aPTT >1.5X top of normal range, or coagulation factor assay <25% normal activity. FFP is not indicated to treat a prolonged INR in the absence of active bleeding.

FFP needs to be thawed for 20 to 40 min before it can be used. Each 200 to 250 mL pack of FFP contains 1 unit/mL of each coagulation factor and 1 to 2 milligrams/mL fibrinogen. One pack will increase most coagulation factors by up to 5%. FFP should be ABO compatible. Starting dose is 15 mL/kg (approximately 4 bags). At certain medical centers, prothrombin complex concentrates or recombinant activated factor VII is used in lieu of FFP.

Cryoprecipitate is derived from FFP. One bag of cryoprecipitate contains 80 units factor VIII, 200 to 300 milligrams von Willebrand factor, 40 to 60 units fibrinogen, factor XIII, and variable amounts of fibronectin.

Cryoprecipitate is indicated for (a) active bleeding in patients with afibrinogenemia or hypofibrinogenemia (fibrinogen level <100 milligrams/dL) as a result of a pathological process (DIC, liver disease, abruptio placentae, amniotic fluid embolus, massive transfusion); (b) active bleeding in patients with von Willebrand disease when desmopressin (DDAVP) is not effective or in patients with von Willebrand disease type 2B, or if factor VIII concentrate containing von Willebrand factor is not available; and (c) hemophilia type A when virally inactivated factor VIII concentrates are not available. Cryoprecipitate can also be used as fibrin surgical adhesives in surgical patients.

Cryoprecipitate should be ABO-compatible. The volume of each unit is 20 to 50 mL. The usual dose is 1 unit/5 kg of body weight (10 to 14 units for an adult) and will raise fibrinogen concentration to 75 milligrams/dL.

Intravenous immunoglobulin (IVIG) is a pooled IgG product from numerous donors. Among several FDA approved and numerous off-label uses, IVIG is commonly indicated for the treatment of primary and secondary immunodeficiencies, immune-mediated thrombocytopenia; and Kawasaki syndrome. Adverse reactions include anaphylaxis, febrile reactions, headache, and renal failure.

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 used mainly for prophylaxis of thrombosis or to treat thromboembolism in patients with hereditary ATIII deficiency.

Table 137-1 outlines therapy for congenital coagulation factor deficiencies.

Massive transfusion is defined as replacement of a patient's total blood volume within a 24-hour period. The exact ratio of PRBC to platelets to FFP remains controversial; some experts recommend a 1:1:1 ratio. Complications of massive transfusion include coagulopathy, citrate toxicity, hypocalcaemia, hypomagnesaemia, and hypothermia. See Table 137-2 for evaluation and management of associated complications.

Acute complications of include febrile nonhemolytic transfusion reaction (most common), acute hemolytic reaction, ABO incompatibility, allergic reaction and anaphylaxis, and transfusion related acute lung injury (TRALI). Table 137-2 summarizes the clinical presentation, evaluation, and management of acute transfusion reactions.

Delayed transfusion complications present days or weeks after the index transfusion and include delayed hemolytic transfusion reaction, transfusion associated graft vs host disease, posttransfusion purpura, and infectious disease transmission.