BLOOD COMPONENT THERAPY

BLOOD COMPONENT THERAPY

Current Diagnosis

• Fever greater than 1°C rise during or within 4 hours following transfusion should prompt evaluation of the patient and consideration of a transfusion reaction.

• Fever and pain are the most common manifestations of an acute hemolytic transfusion reaction.

• The point of the transfusion reaction laboratory investigation is to evaluate for hemolysis, either intravascular or extravascular. The majority of reactions are negative for hemolysis.

• The differential diagnosis of a transfusion reaction with respiratory symptoms includes febrile nonhemolytic and circulatory overload (common), allergic or anaphylactic reaction, transfusion-related acute lung injury, acute hemolytic reaction, and bacterial contamination (rare).

Current Therapy

•  The decision to transfuse red cells to a patient should depend more on the clinical state of the patient than on an absolute trigger for hemoglobin or hematocrit.

•  A transfusion trigger of less than 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients. A transfusion trigger of 8 g/dL is recommended for patients undergoing orthopedic or cardiac surgery, and those with preexisting cardiovascular disease.

•  For severe autoimmune hemolytic anemia, maintenance of hemoglobin at greater than 4 g/dL in younger patients and greater than 6 g/dL in older patients or patients with cardiovascular disease is appropriate.

•  Platelets are not typically indicated in thrombotic thrombocytopenic purpura, autoimmune thrombocytopenic purpura, and heparin- induced thrombocytopenia (HIT) unless the patient has significant bleeding.

•  Currently available coagulation tests are not very useful for predicting bleeding in patients with end-stage liver disease. These patients establish a new equilibrium between coagulation, anticoagulation, and fibrinolysis that results in relatively less bleeding than predicted by the international normalized ratio.

•  The goal during massive transfusion scenarios should be to prevent marked acidosis, hypothermia, and coagulopathy. The latter is often achieved with replacement of coagulation factors using plasma and/or cryoprecipitate within the first hour of the resuscitation.

•  Cryoprecipitate is useful as a source of concentrated fibrinogen. In a patient who is actively bleeding and has a fibrinogen less than 100 mg/dL, cryoprecipitate is indicated.

•   Fibrinogen concentrates are available for select patient populations.

Therapeutic Use of Blood Components

The community blood supply depends on two types of donors: whole blood donors and apheresis donors. Units of whole blood are centrifuged and then separated into components within a closed system. Using apheresis techniques, individual components of whole blood can be collected. Citrate is used to keep blood components from clotting.

The decision to transfuse blood to a patient should always include a consideration of the risks versus the benefits. Risks of transfusion- transmitted diseases are small with current testing standards.

Transfusion reactions do occur; the most common ones are not life- threatening unless the patient cannot tolerate tachycardia or hypertension. Rarely, a patient experiences a life-threatening reaction. Thus it is important to ensure that the need for the blood component outweighs the risks. Additionally, in a bleeding patient, it is important to check coagulation parameters (platelet count, prothrombin time [PT], international normalized ratio [INR], activated partial thromboplastin time [aPTT], fibrinogen) in addition to hematocrit (Hct) to ensure that the component that will best address the bleeding is being used.

Red Cells

Indications

Red cells should be given to increase oxygen-carrying capacity. The hemoglobin (Hb) and Hct levels alone should not be used to determine the need for transfusion; rather, the patient’s clinical picture should drive the decision to transfuse. The patient’s intravascular volume status, cardiopulmonary function, and baseline vital signs in the presence of anemia should all be considered. When anemia has persisted over weeks and months, transfusion is often not indicated because compensatory mechanisms have had time to work.

Transfusion Triggers

The most recent clinical practice guideline from AABB (formerly known as American Association of Blood Banks) has the following recommendations: in hospitalized adult patients who are hemodynamically stable, including critically ill patients, a transfusion threshold of 7 g/dL is acceptable. In patients undergoing orthopedic or cardiac surgery, and those with pre-existing cardiovascular disease, a transfusion threshold of 8 g/dL is recommended. The recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia, or chronic transfusiondependent anemia, due to insufficient evidence.

Dosage

One unit of packed red cells will increase the hemoglobin by 1 g/dL and hematocrit by 3% in the patient who is not bleeding or experiencing hemolysis (Table 1).

Table 1

Component Therapy: Dosage and Expected Increment

Abbreviations: Hb = hemoglobin; Hct =  hematocrit.

Autoimmune Hemolytic Anemia

Special Situation

When the autoantibody responsible for autoimmune hemolytic anemia reacts at body temperature, all red cell units can appear incompatible. This is because the antibody binds to an epitope common to all red cells, such as the band 3 protein. The clinician needs to decide when to transfuse the (apparently) incompatible units. In a patient who has never received a transfusion or been pregnant, there is little possibility of red cell alloantibodies in circulation, and the chance of hemolysis (beyond that being caused by the autoantibody) is low. For the patient who has received a transfusion or who has been pregnant in the past, the risk that a circulating red cell alloantibody is present and is being masked by the autoantibody is higher; special studies are available to reduce the risk of an alloantibody being overlooked. The transfusion trigger depends on whether the anemia is acute or chronic. For acute anemia, maintenance of hemoglobin at greater than 4 g/dL in younger patients and greater than 6 g/dL in older patients or patients with cardiovascular disease is appropriate.

Platelets

Platelets are required as part of normal clotting. The first stage of clot formation is development of a platelet plug over the site of endothelial injury.

Indications

The indications for platelet transfusion may be divided into prevention of bleeding and treatment of bleeding in the setting of thrombocytopenia or platelet dysfunction.

Transfusion Triggers Prevention of Bleeding

In a stable patient with normal platelet function, transfusion is appropriate if the platelet count is less than 10,000/µL. One randomized, controlled trial has shown that transfusion at platelet counts of 5000/µL to 10,000/µL prevents bleeding in the stable patient. In a stable patient with other hemostatic abnormalities (e.g., on anticoagulation), transfusion is appropriate with a platelet count less than 50,000/µL.

Before a planned invasive procedure such as lumbar puncture, transfusion is appropriate with a platelet count of 50,000/µL. A patient undergoing major surgery should receive platelets if the count is less than 50,000 to 100,000/µL. The transfusion should take place as close to the procedure as possible so the platelets remain in circulation while the procedure is occurring.

Treatment of Bleeding

Platelets may be transfused with a major hemorrhage (e.g., gastrointestinal or genitourinary) and a platelet count less than 30,000 to 50,000/µL. For bleeding with major surgery or trauma, transfusion is appropriate for counts less than 80,000/µL. For bleeding into critical areas (e.g., central nervous system bleeding or diffuse alveolar hemorrhage), platelets may be given for counts less than 100,000/µL.

Dosage

Dosage is determined on the basis of the baseline platelet count, desired platelet count, and estimated blood volume. For a 70-kg patient, 3 × 1011 platelets (four to six units of pooled whole blood platelets or one unit of apheresis platelets) increases platelet count by approximately 30,000 to 50,000/µL in the absence of alloimmunization or excessive consumption. For prophylactic therapy, lower dosages have been shown to be as effective as higher dosages in the prevention of bleeding.

Out of ABO Group Platelet Transfusion

Because platelets can only be stored for a maximum of 5 days following collection, and the community platelet supply is collected from volunteer donors, a platelet product that is identical to the patient’s ABO type might not be available (Table 2 and Box 1). Thus it may be necessary to infuse a small volume of incompatible plasma (suspending the platelets) to the patient. There is, therefore, a small risk of hemolysis of the patient’s red cells if the isoagglutinin (anti-A or anti-B) titer in the donated plasma is high. Studies of healthy blood donors indicate that these antibody titers are typically low and do not precipitate hemolysis. Transfusion services often have policies that limit the amount of incompatible plasma a patient has received with platelet transfusion. Alternatively, some centers measure the antibody titer in the donated product and give high-titer products only to patients whose red cells lack the corresponding ABO antigen.

Box 1
Rh(D) compatibility
Rh(D) negative patients should receive Rh negative red cell and platelet units.*†

Rh(D) positive patients can receive Rh positive or Rh negative red cells and platelet units.

Rh compatibility does not apply to acellular components (plasma and cryoprecipitate).

Only 15% of blood donors are Rh negative.

* In times of shortage, it becomes necessary to preserve the Rh(D) negative red cell inventory for females of childbearing potential (< 50 years  old).

† Platelet components contain very few red cells; Rho(D) immune globulin (RhoGAM)   may be administered if prevention of anti-D formation is deemed appropriate. Consult with a transfusion medicine physician if further discussion is  needed.

Table 2

ABO Compatibility*

*  For platelet compatibility, see text.

Unresponsiveness to Platelet Transfusion

A number of clinical factors can result in a patient’s less-than-optimal response to platelet transfusion. In addition to consumption, some of these factors include splenomegaly, fever, and antifungal therapy.

Patients who have been sensitized to foreign human leukocyte antigens through prior pregnancy or transfusion can also have a poor response to platelet transfusion. Transfusion medicine consultation regarding the evaluation of refractoriness to platelet transfusion may be indicated.

Special Situations Uremia

Patients who are dialysis dependent might have an acquired platelet defect as a result of the uremic environment. Transfusion of platelets into this environment will render the transfused platelets dysfunctional. Thus if optimal platelet function is desired, dialysis should be performed frequently. Consider performing dialysis without heparin if the patient is actively bleeding.

Purpura and Thrombocytopenia

In patients with autoimmune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), or heparin-induced thrombocytopenia (HIT), platelet transfusion is not indicated unless the patient has significant bleeding. Other therapies, such as steroid administration for ITP and plasma exchange for TTP, should be initiated to address the condition.

Plasma

Plasma contains all of the coagulation proteins needed for clot formation, as well as all of the fibrinolytic proteins that prevent systemic thrombosis. There are currently several kinds of plasma, such as fresh frozen, FP24, thawed, and liquid. All contain hemostatic levels of coagulation factors as long as they are stored appropriately. The effect of plasma transfusion on the PT and INR is 4 to 6 hours owing to the short half-life of coagulation factor VII. Thus other, longer-lasting means of restoring coagulation factors, such as vitamin K administration, should be undertaken.

When replacing coagulation factors with plasma, it is not necessary to have 100% factor replacement as the goal. Hemostasis is typically able to occur if circulating coagulation factor levels are between 40% and 50%. It is important to understand that the relationship between the INR and the percentage factor level is a logarithmic, rather than a linear, relationship (Figure 1). Thus whether the INR is 9 or 1.8, the initial dosage of plasma should be 10 to 20 mL/kg, with recheck of the laboratory values a few minutes after infusion. The more prolonged the INR, the more significant the impact of the dose on the INR.

FIGURE 1    American Association of Blood Banks  international normalized ratio (INR) compared with percentage factor  levels. (Reprinted with permission from Nester T, AuBuchon J: Hemotherapy decisions and their outcomes. In Roback JD (ed): AAB Technical Manual, 17th ed. Bethesda, MD, American Association of Blood Banks, 2011, p 592.)

Transfusion Triggers

For bleeding or imminent surgery that cannot be corrected in a timely manner by vitamin K administration, use plasma to correct an INR greater than 1.5 to 2.0. The exception is patients with end-stage liver disease (see later).

Dosage

At a dosage of 10 mL/kg, each unit has an average of 300 mL (3–5 units in a 70-kg adult). This dosage should increase circulating coagulation factors by 20% immediately after infusion.

Special Situations Liver Disease

The INR is a less useful test in patients with end-stage liver disease. The destruction of liver tissue leads to decreased production of coagulation and fibrinolytic proteins such that a new balance is established. Patients with end-stage liver disease have been shown to have normal levels of circulating thrombin and reduced levels of certain anticoagulant proteins (e.g., protein C), which could explain why they do not bleed as often as predicted with the elevation in INR. Thus the prophylactic use of plasma to correct a mildly prolonged laboratory value in the absence of bleeding is not indicated. It will lead to unnecessary plasma infusion, and the risk of volume overload and transfusion reactions outweighs the benefit in these patients.

Massive Transfusion

In trauma patients, patients with ruptured aortic aneurysms, and patients with other arterial bleeding, massive transfusion may be necessary. The basic principles of such a scenario include taking steps early into the resuscitation to prevent the patient from becoming too cold, acidotic, or coagulopathic to reverse the situation. Some plasma (and cryoprecipitate, if the fibrinogen is very low) should be infused early into the resuscitation in order to help prevent coagulopathy. Red cells and plasma should be infused through a blood warmer, if possible.

Isolated Prolonged aPTT

Other than a deficiency in coagulation factor XI, bear in mind that the differential of an isolated prolonged aPTT includes entities that do not typically require plasma (refer to Figure 2). Hemophilia A, hemophilia B, and von Willebrand disease are no longer treated by plasma but can require factor concentrates to prevent bleeding. Systemic administration of heparin must be reversed by protamine, if fast reversal is desired. Note that plasma transfusion will not reverse the effect of heparin. One of the most common causes of a prolonged aPTT is a lupus anticoagulant; this is an antibody directed against phospholipids that typically leads to thrombosis rather than hemorrhage.

FIGURE 2    Coagulation cascade.

Intracranial Hemorrhage or Life-Threatening Bleeding

Reversal of anticoagulation in the setting of intracranial hemorrhage or life threatening bleeding depends on the anticoagulant. For patients taking warfarin (Coumadin), refer to Box 2.

Box 2
Guidelines for Correction of Excessive Warfarin Anticoagulation
INR Higher than Therapeutic but < 5, No Significant Bleeding

Lower anticoagulant dosage.

Temporarily discontinue drug, if necessary.

INR > 5 but < 9, No Significant Bleeding

Omit 1 or 2 doses, monitor INR, resume when INR is in therapeutic range.

Alternative if patient is at increased risk of hemorrhage:

•   Omit 1 dose

•   Give 1–2.5 mg vitamin K orally.

For rapid reversal before urgent surgery:

•   Give 2–4 mg vitamin K orally.

•   Give 1–2 mg at 24 hours if INR remains elevated.

INR > 9, No Significant Bleeding

Omit warfarin; give 2.5–5.0 mg vitamin K orally.

Closely monitor INR; give additional vitamin K, if necessary.

Resume warfarin at lower dose when INR is within therapeutic range.

Serious Bleeding at Any Elevation of INR

Omit warfarin.

Give 10 mg vitamin K by slow IV infusion.

Supplement with plasma or prothrombin complex concentrate depending on urgency of correction.

Vitamin K infusions may be repeated every 12 hours.

Life-Threatening Hemorrhage

Omit warfarin.

Give prothrombin complex concentrate with 10 mg vitamin K by slow IV infusion.

Repeat as necessary, depending on INR.

Abbreviation: INR = international normalized ratio.

From Nester T, AuBuchon J: Hemotherapy decisions and their outcomes. In Roback JD (ed): AAB Technical Manual, 17th ed. Bethesda, MD, American Association of Blood Banks, 2011, p 571–616.

Prothrombin complex concentrates (PCCs) may be used to replenish factors II, IX, and X rapidly. Two types of PCCs are available in the United States. A 4-factor PCC will replenish factors II, VII, IX, and X, and has been FDA approved for this indication. A 3-factor PCC lacks factor VII, thus a small dose of plasma will also be required. Inquire with a transfusion medicine physician or hematologist to determine if such a protocol exists in your facility. For other agents such as dabigatran (Pradaxa) and rivaroxiban (Xarelto), reversal may be significantly more difficult. See the guidelines by Cushman and colleagues (2011).

Cryoprecipitate

Cryoprecipitate contains fibrinogen, coagulation factors VIII and XIII, and von Willebrand factor. The most common current use is as a source of concentrated fibrinogen. It may also be used to treat hemorrhage in the rare patient with factor XIII deficiency.

Indications

Clinical scenarios that increase probability for low fibrinogen include any clinical situation where disseminated intravascular coagulation (DIC) may be present. These include obstetric bleeding, trauma involving head injury or crush injury, and sepsis. Clinical events that can lead to an isolated decrease in serum fibrinogen concentration include administration of l-asparaginase (Elspar) and surgeries that disrupt bladder or salivary gland endothelium. Fibrinogen concentrates are available for patients who will not accept cryoprecipitate.

Transfusion Triggers

Transfusion is appropriate in patients with low serum fibrinogen, typically less than 100 mg/dL. In cases of massive transfusion, a trigger of 150 mg/dL is considered practical, so that the patient becomes less coagulopathic in the time that it takes to draw and review new laboratory values. New evidence indicates that a fibrinogen level of less than 300mg/dL predicts severe post-partum hemorrhage, as a normal post-partum fibrinogen level is in the 600mg/dL range. As component therapy aims to replete coagulation factors to hemostatic (rather than completely normal) levels, consensus guidelines suggest maintaining a fibrinogen level greater than 200 mg/dL during a postpartum hemorrhage.

Dosage

Dosage depends on the type of cryoprecipitate available. If the product requires resuspension in saline prior to pooling, then one unit (average 15 mL volume) will increase fibrinogen by 5 mg/dL. If the product has been pooled in plasma before freezing, then one unit will increase fibrinogen by 7 to 8 mg/dL; a six-unit pool will increase fibrinogen by 45 mg/dL. Check with the transfusion service laboratory regarding which product is available and the expected increment.

Special Situation

DIC is a state where fibrinogen is consumed at a faster rate than other circulating coagulation factors. This is because DIC is typically a thrombin-generating process (thrombin cleaves fibrinogen into fibrin for clot formation). Thus, although all coagulation factors are being consumed in DIC, timely repletion of fibrinogen by use of cryoprecipitate can result in more-timely cessation of bleeding in a patient with active DIC. The target value is fibrinogen at least 100 mg/dL. If the PT and INR are still prolonged with fibrinogen greater than 100 mg/dL, administration of plasma will replete other coagulation factors being consumed.

Transfusion Reactions

Reactions to transfusion are relatively common; life-threatening reactions are rare (Tables 3 and 4).

Table 3

Transfusion Reactions

Most Common Reactions                                                                         Incidence
Allergic reaction of mild severity 1:33 to 1:100
Febrile  nonhemolytic reaction 1:100 to 1:1000 with leukocyte reduction
Transfusion-related  circulatory overload < 1:100
Most Dangerous Reactions                                                                      Incidence
Acute hemolytic reaction 1:38,000 to 1:70,000
Anaphylactic reaction 1:20,000 to 1:50,000
Transfusion-related acute lung injury 1:1200 to 1:190,000
Bacterial contamination of red cell unit with gram-negative organisms 1:1,000,000

Table 4

Transfusion Reactions with Respiratory Symptoms

Abbreviations: BP = blood pressure; DIC = disseminated intravascular coagulation; ICU = intensive care unit.

1  Not FDA approved for this indication.

Because fever is a feature of both common and dangerous reactions, a transfusion reaction evaluation should be initiated with fever greater than 1°C above patient’s baseline temperature at the start of the transfusion. The infusion of product should cease at least until the laboratory results are known and the patient has responded to treatment. The main point of the laboratory investigation is to evaluate the plasma for abnormal (usually red) color in an effort to detect intravascular hemolysis as quickly as possible. If the hemolysis, clerical, and direct antiglobulin test checks are negative, one might consider restarting the transfusion with careful surveillance of the patient. A direct antiglobulin test is also performed to detect the presence of antibody coating red cells in circulation; a positive result could indicate extravascular hemolysis, which is not as dangerous as intravascular hemolysis.

Most-Common Reactions

Febrile Nonhemolytic Reaction

Presentation

A febrile nonhemolytic transfusion reaction manifests as fever greater than 1°C rise above the patient’s baseline, often accompanied by rigors. Hypertension, tachypnea, and transient decrease in oxygen saturation can also occur until the symptoms are treated. Evidence of hemolysis will be absent on laboratory evaluation. These reactions can manifest during or 2 to 3 hours following the transfusion.

Pathophysiology

Cytokines produced by white cells present in cellular blood components (red cell and platelet units) are responsible for the clinical presentation. Platelets also secrete cytokines; thus, leukoreduction of platelet units might not be successful in preventing the reaction.

Acute Management

Administration of an antipyretic is the routine treatment; meperidine (Demerol)1 may be required to address severe rigors. Slow IV push of 25 mg as a first dose is recommended; an additional 25-mg dose can be given 10 to 15 minutes later if rigors persist.

Prevention with Future Transfusion

Antipyretic may be administered prior to transfusion. Ordering leukoreduced red cells and platelets (if the hospital inventory is not entirely composed of leukoreduced components) is also a preventive measure. For recurring reactions with platelets, volume reduction of the component can reduce the incidence.

Allergic Reaction of Mild Severity Presentation

Urticaria or flushing occurs during a transfusion. Evidence of hemolysis is absent on laboratory evaluation.

Pathophysiology

Allergic reactions are immunoglobulin (Ig)E-mediated reactions against some allergen in the donor plasma. Because all blood components have some amount of plasma, it is possible to experience an allergic reaction with any blood product.

Acute Management

Slowing the infusion rate may be all that is required to alleviate the reaction. Antihistamine administration also addresses the symptoms.

Prevention with Future Transfusion

A reaction of this type may be a one-time event. For patients with recurrent reactions, transfusing the blood product more slowly (maximum of transfusion over 4 hours) and/or premedication with antihistamines will reduce the incidence.

Transfusion Associated Circulatory Overload (TACO)

Presentation

The patient has respiratory distress, typically during the transfusion, and increase in blood pressure unless cardiac decompensation occurs. Tachycardia, tachypnea, and decrease in oxygen saturation are often present. Jugular venous distension may be seen. Radiographic findings include pleural effusions, perihilar edema, and increased vascular pedicle width.

Pathophysiology

The reaction results in cardiogenic pulmonary edema.

Acute Management

Diuretic should be administered. Supplemental oxygen may be required temporarily to improve oxygen saturation.

Prevention with Future Transfusion

Slowing the infusion rate with a maximum time of transfusion over 4 hours can prevent the reaction. Diuretic administration may be necessary in patients with poor heart function.

Most-Dangerous Reactions

Acute Hemolytic Transfusion Reaction (AHTR)

Presentation

The most common signs include fever with or without rigors and pain. The more commonly reported sites of pain include flank, back, chest, or abdomen. Nausea and vomiting and dyspnea can also occur. In more-severe presentations, hemodynamic instability is present, accompanied by oozing from line sites or petechial hemorrhage if DIC is occurring. Red or cola-colored urine is another manifestation of an acute hemolytic transfusion reaction and represents overwhelming of the kidneys’ ability to recirculate free heme.

Pathophysiology

Red blood cells have proteins and carbohydrates on the cell surface that are antigenic. These epitopes are categorized into blood groups based on structure and sharing of a parent protein. A patient who lacks particular epitopes can develop antibodies through pregnancy or transfusion. Such red cell alloantibodies can then lyse transfused red cells that possess the cognate antigen. When time allows for pretransfusion testing, the antibodies are identified and antigen- negative units are provided. The ABO blood group system is unusual in that almost all patients older than 4 months have naturally occurring antibodies to the A and B antigens that they did not inherit. These antibodies are capable of activating complement and causing intravascular lysis when bound to their cognate antigen. Thus it is of utmost importance to avoid transfusing red cells against the ABO antibody in circulation. Refer to the ABO compatibility table (see Table 1).

Acute Management

Management is largely supportive. The end result of intravascular hemolysis and activation of the complement cascade can be shock, uncontrolled bleeding secondary to DIC, and renal failure. Therefore, prompt infusion of intravenous crystalloid solutions are indicated to maintain blood pressure and renal perfusion. The goal for urine flow rate should be more than 1 mL/kg per hour. Coagulation laboratory values should be obtained to determine if DIC is present; if so, component therapy to reverse the DIC is indicated. If the reaction is severe, intensive care is appropriate, because cardiac monitoring and mechanical ventilation may be necessary to support the patient.

Prevention with Future Transfusion

An acute hemolytic reaction is one of the most feared complications of transfusion. It is also often one of the most preventable. Great care should be given to the pretransfusion blood sample draw, comparing the label to the patient’s unique identifiers, and labeling the tube at the patient’s bedside as soon as the blood is in the tube. Just before transfusion, the unit label attached to the blood product should be compared with the patient’s armband to ensure that the product is intended for this particular patient. To prevent intravascular hemolysis from antibodies directed against non-ABO antigens, pretransfusion testing (antibody screen or crossmatch) should be done in advance of the need for red cell transfusion for any patient whose clinical situation indicates a likelihood of needing blood. The exception is a patient who is hemodynamically unstable because of acute red cell loss, where uncrossmatched red cells are indicated. If the patient’s identity is known, a call to the hospital transfusion service in this situation is warranted; explain that the patient needs uncrossmatched red cells and ask if there are transfusion records that indicate a need for antigen-negative units.

Allergic Reaction of Marked Severity (Anaphylaxis) Presentation

Significant drop in blood pressure occurs, typically early into the transfusion. Wheezes, difficulty breathing, and stridor may be present. Tongue and/or facial edema as well as hives may be observed.

Pathophysiology

Anaphylaxis is an IgE-mediated reaction against an allergen in the donor plasma. In a patient with absolute IgA deficiency, naturally occurring anti-IgA can precipitate this reaction upon binding IgA in the plasma. Anti-haptoglobin antibodies can also induce a severe reaction.

Acute Management

Airway and blood pressure support should be provided with the patient recumbent and the lower extremities elevated. The treatment of choice is epinephrine (Adrenalin) 1 mg/mL, also labeled as 1:1000 or 0.1%, using an adult dosage of 0.3 to 0.5 mg per single dose, typically administered intramuscularly to the mid-quadriceps area. If symptoms persist, the dose may be repeated every 5 to 15 minutes for a maximum of three times, unless palpitations, tremors, or extreme anxiousness occurs. Supplemental oxygen should be administered and the airway maintained. Intravenous fluid administration is also recommended. Bronchodilators such as albuterol can be given as adjunctive treatment for bronchospasm that does not appear to respond to epinephrine. For patients on β-blockers, the addition of intravenous glucagon1 (GlucaGen) 1 to 5 mg administered over 5 minutes, followed by infusion of 5 to 15 µg/minute, may be required. The addition of glucocorticoids can help prevent the biphasic reaction that occurs in some patients.

Prevention with Future Transfusion

Slow administration with careful observation of any transfusion is required. Premedication with intravenous antihistamines is appropriate. Steroids may be administered, although their effectiveness has not been confirmed through controlled trials.

Epinephrine should be available at the bedside. For severe allergic reactions, a discussion with the transfusion service physician regarding washed components is appropriate.

Transfusion-Related Acute Lung Injury Presentation

The signs of transfusion-related acute lung injury (TRALI) are difficulty breathing, tachypnea, and hypoxia during or within 6 hours of a transfusion of any blood component. Ideally, signs of underlying lung disease or circulatory overload are absent. Chest radiograph may show diffuse bilateral opacities (white-out). Diuretic administration does not result in improvement. The hypoxemia can progress to the point that the patient requires mechanical ventilation, and thus the patient should be closely monitored while the reaction is occurring.

Pathophysiology

The factors that result in TRALI are not entirely known. In a portion of cases, antibodies against white cell antigens are present in donor plasma. These antibodies are believed to bind the cognate antigens on the patient’s white cells, leading to degranulation and a capillary leak syndrome involving the lungs. Other theories regarding the pathophysiology of TRALI exist. One such theory implicates biologically active substances such as lipids and cytokines in the stored blood products. These substances are believed to prime the patient’s granulocytes and activate pulmonary endothelium, setting the stage for an additional trigger to cause acute lung injury.

Regardless of the cause of TRALI, the end result is an increase in pulmonary vascular permeability and noncardiogenic pulmonary edema. The estimated mortality rate from TRALI is 5% to 8%.

Acute Management

Management consists of supportive care, with particular regard to respiratory support. With adequate supportive care, the process most often reverses over 48 to 96 hours.

Prevention with Future Transfusion

Marked respiratory compromise is occasionally due to white cell antibodies in the patient, which bind cognate antigens in the donated red cell or platelet unit (“reverse TRALI”). In these cases, leukoreduction of cellular blood products may reduce the severity of subsequent transfusions, although solid evidence to support this is lacking. For TRALI caused by white cell antibodies in the donated product, there are no preventive measures for the clinician to take.

The majority of U.S. blood suppliers provide plasma from only male donors, in an effort to reduce the incidence of TRALI caused by multiparous women with white cell antibodies.

Bacterial Contamination of a Blood Component

Presentation

The most-common presentation includes fever and rigors, nausea and/or vomiting, and possible onset of moderate hypotension during or after a platelet transfusion. Rarely, presentation includes signs of overt septic shock, including marked hypotension, typically early into the transfusion of a red cell or platelet component. Bacterial contamination of plasma or cryoprecipitate is extremely rare.

Pathophysiology

The most-common organisms to contaminate a platelet product are gram-positive organisms such as Staphylococcus epidermidis. These organisms are thought to be introduced into the collection bag via a skin plug that results from phlebotomy using a large-gauge needle when sterilization of the phlebotomy site has been ineffective.

The most common organisms to contaminate a red cell unit are gram-negative, endotoxin-producing organisms such as Yersinia enterocolitica. This organism is introduced into the blood product as a result of asymptomatic bacteremia in the donor, from sources such as the gastrointestinal tract. The donor-screening questionnaire and vital sign assessment at the time of donation help to make collection from such a donor a very rare event. Transfusion of a bacterially contaminated red cell unit is most often a fatal event. It is important to remember that platelets can also be contaminated by the same gram- negative, endotoxin-producing organisms; in this case, signs of septic shock may be manifest.

Acute Management

Blood cultures from the patient should be drawn and then prompt intravenous antibiotic administration should begin. Supportive care including inotropic agents and close nursing attention may be required.

Prevention with Future Transfusion

Bacterial contamination is associated with a donor product, and thus preventive measures for the patient do not apply. Blood suppliers perform bacterial detection tests on platelet components, and transfusion services have strict policies related to visual inspection of all blood products before they are issued to a patient-care area.

However, these measures are not completely effective. The FDA recently approved pathogen inactivation technology for platelets which may further lower the risk.

Other Reactions

Delayed Hemolytic Transfusion Reaction

Presentation

The main finding with a delayed hemolytic transfusion reaction is usually an unexplained decrease in hematocrit within 2 to 7 days following transfusion. The patient often remains asymptomatic unless the decline in hemoglobin is poorly tolerated. Jaundice can occur, and laboratory values consistent with hemolysis may be positive (elevated indirect bilirubin, elevated lactate dehydrogenase, decreased haptoglobin). Rarely, signs of intravascular hemolysis can occur.

Pathophysiology

The most common source of this reaction is a red cell alloantibody that the patient developed with prior transfusion or pregnancy; the antibody titer wanes over time such that pretransfusion testing does not detect the antibody. A unit of red cells positive for the cognate antigen is then transfused, and within a few days the patient’s memory B cell response produces the antibody again. Transfused cells are then cleared, most often by an extravascular mechanism.

Acute Management

Most transfusion services have a policy to notify the clinician that a serologic delayed hemolytic transfusion reaction is present on testing a new plasma sample from the patient. If the patient’s hematocrit has declined, it may be useful to determine a clinical correlation by obtaining the laboratory values just described. This is of particular importance when the distinction between hemolysis and bleeding will lead to different management strategies for the patient. Although extravascular clearance of hemoglobin is fairly well tolerated by the kidneys, the conservative approach is to increase renal perfusion with intravenous crystalloid solutions if possible.

Prevention with Future Transfusion

For a patient who routinely receives care through one hospital system, the transfusion service will keep a record of the red cell alloantibody and provide antigen-negative cells for transfusion. The prevention, then, is to plan ahead for transfusion when possible, so that fully compatible units can be provided. Uncrossmatched red cells may be positive for the cognate antigen.

Allergic Reaction of Moderate Severity Presentation

The patient has labile blood pressure, either hyper- or hypotension, accompanied by at least one of the following: throat scratchiness, respiratory wheezes, or perioral or periorbital edema. Hives may be present. Gastrointestinal symptoms such as crampy abdominal pain may also be present.

Pathophysiology

This is an IgE mediated reaction against an allergen in the plasma of the donated product.

Acute Management

Treatment is administration of intravenous antihistamines. If the respiratory component does not resolve, consider epinephrine administration and treat similarly to anaphylaxis (see previous section).

Prevention with Future Transfusion

Slower infusion of blood products can reduce further episodes of this type of reaction. If the patient is atopic, intravenous antihistamines may be administered as a premedication. If the patient requires chronic transfusion and experiences this type of reaction on a repeated basis, discussion with the transfusion service regarding washed components may be warranted.

Hypotensive Transfusion Reaction Presentation

The patient has isolated hypotension (drop in systolic BP greater than 30 but less than 80 mm Hg) that responds quickly to cessation of the transfusion. The reaction classically occurs within the first 15 minutes of infusion of the blood product.

Pathophysiology

Pathophysiology is unclear. Some research indicates that the patient may have slower ability to metabolize bradykinin compared to other individuals.

Acute Management

Stop the transfusion.

Prevention with Future Transfusion

Prevention is unclear. In the author’s experience, rate of infusion has a role. Slower infusion may help to prevent this type of reaction.

Transfusion Associated Dyspnea Presentation

Mild respiratory distress that occurs within 24 hours of cessation of transfusion.

Pathophysiology

Pathophysiology is unclear.

Acute Management and Prevention with future transfusion

Management is supportive and presentation is unclear.

References

1.     Abdel-Wahab O.I., Healy B., Dzik W.H. Effect of fresh-frozen plasma transfusion on prothrombin time and bleeding in patients with mild coagulation abnormalities. Transfusion. 2006;46:1279–1285.

2.    Carson J.L., Guyatt G., Heddle N.M., et al. Clinical practice guidelines from the AABB: Red cell transfusion thresholds and storage. JAMA. 2016;316(19):2025–2035.

3.     Cushman M., Lim W., Zakai N.A. 2011 Clinical Practice Guide on Anticoagulant Dosing and Management of Anticoagulant- Associated Bleeding Complications in Adults. Washington, DC: American Society of Hematology; 2011.

4.    Kaatz S., Crowther M. Reversal of target-specific oral anticoagulants. J Thromb Thrombolysis. 2013;36(2):195–202.

5.     Lisman T., Porte R.J. Rebalanced hemostasis in patients with liver disease: Evidence and clinical consequences. Blood. 2010;116:878–885.

6.      Mazzei C., Popovsky M., Kopko P. Noninfectious complications of blood transfusion. In: Roback J.D., ed. AABB Technical Manual. ed 17th Bethesda, MD: American Association of Blood Banks; 2011:727–762.

7.    Nester T., Jain S., Poisson J. Hemotherapy decisions and their outcomes. AABB Technical Manual. 18th ed. Bethsda, MD: AABB Press; 2014.

8.    Kaufman R.M., et al. Platelet transfusion: a clinical practice guideline from the AABB. Ann Internal Med. 2015;162(3):205– 213.

9.       Holcomb J.B., et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs. a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial.  JAMA. 2015;313(5):471–482.

10.       Slichter S.J., Kaufman R.M., Assmann S.F., et al. Dose of prophylactic platelet transfusions and prevention of hemorrhage. N Engl J Med. 2010;362:600–613.

1  Not FDA approved for this  indication.

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