Blood Transfusions – Indications, Contraindications

Blood transfusions are a relatively common medical procedure and while typically safe, there are multiple complications that practitioners need to be able to recognize and treat. This activity reviews the indications for blood transfusion, including for special patient populations, the pre-transfusion preparation and the potential complications of blood transfusions. This activity highlights the role of the interprofessional team in caring for patients undergoing blood transfusions.

Indications of Blood Transfusions

While standard hemoglobin values some by gender and race and normal value for hemoglobin and hematocrit vary slightly by the laboratory, anemia is usually defined as a hemoglobin level less than 13 g/dL in males and less than 12 g/dL in females. While currently, a more restrictive threshold is used to determine the indication for transfusion, previously a liberal strategy, typically using a cutoff of hemoglobin less than 10 g/dL was used, regardless of symptoms. Currently, guidelines for transfusion of red blood cells (RBC), generally follow a restrictive threshold. While there is some variation in the number for the threshold, 7 g/dL is an agreed-upon value for asymptomatic healthy patients. Multiple studies have shown that this is an acceptable threshold in other patients populations as well, including in those with gastrointestinal (GI) bleeding as well as in critically ill patients. The guidelines recommend a value of 8 g/dL as the threshold in patients with coronary artery disease or those undergoing orthopedic surgeries, but this may be secondary to the lack of literature on using a threshold of 7 g/dL in the evaluation studies of these patient populations. The guidelines and clinical trials (TRICC) also recommend a value of 7 g/dl as the threshold for patients who are critically ill. [rx][rx][rx][rx]

Transfusion may also be indicated in patients with active or acute bleeding as well as in patients with symptoms related to anemia (for example, tachycardia, weakness, dyspnea on exertion) and hemoglobin less than 8 g/dL.[rx]

Unless the patient is actively bleeding, it is recommended to transfuse 1 unit of packed red cells at a time, which will typically increase the hemoglobin value by 1 g/dL and hematocrit by 3%. Follow up by checking post-transfusion hemoglobin.[rx]

Whole blood is often divided into component parts for ease of storage and administration.  These typically include Red Blood Cells (RBC), Platelets (thrombocytes), and Plasma.  Plasma can be further fractionated into Cryoprecipitate (i.e. cryoprecipitate antihemophilic factor) and many other clotting factor concentrates of variable purity.

The indications for whole blood and blood component transfusion consist of increasing hemoglobin and oxygenation of tissues, maintaining adequate blood volume to avoid ischemia and hypovolemic shock, and reconstituting platelets, coagulation factors, and other plasma proteins to a functional status.  Hemoglobin and hematocrit along with clinical symptoms of anemia have been the traditional markers used to determine the threshold for transfusion of red blood cells. Hemoglobin of less than 10 g/dL or a hematocrit of less than 30% has traditionally been the benchmark as the laboratory indication for transfusion in the right clinical context.  Recently, there has been increasing evidence that a lower threshold is associated with better outcomes and conservation of precious blood resources, even in critically ill populations.[rx]  There is some evidence that the transfusion “trigger” level may be slightly higher in certain conditions such as sepsis with inadequate oxygen delivery, acute coronary syndrome with ischemia, and surgical hemorrhage or in specific populations such as the elderly.  However, due controlled trials and meta-analysis data there has been a decrease in the use of liberal transfusion protocols.[rx] Restrictive transfusion, even in patients with cardiovascular disease, acute illness, and traumatic brain injury using a threshold of hemoglobin of 7 to 8 g/dL has shown no increased risk of morbidity and mortality.[rx][rx]  There is still variability globally in transfusion thresholds for particular patient populations.[rx][rx]  Refer to specific articles on Indications for Red Blood Cell Transfusion for more information.

Platelets are typically given when patients have a low platelet count (thrombocytopenia) or have platelets that are dysfunctional, due to medications or other acquired or inherited lesions.  Refer to specific articles on Indications for Platelet Transfusion for more information.

Plasma can be used to replace coagulation factors in specific coagulopathies (such as in liver disease when bleeding is present), reversal of warfarin effect (when coagulation concentrates are not available) and for treatment of diseases such as thrombotic thrombocytopenic purpura.  It is sometimes used as a replacement fluid in plasmapheresis and can be used for coagulation factor deficiencies where specific concentrates are not available.  Refer to articles on Indications for Plasma Transfusion for more information.

Cryoprecipitate is a blood product derived from plasma.  It can be used in emergencies as an alternative for supplying coagulation factors in inherited deficiencies such as von Willebrand disease, and hemophilia A (but only when specific concentrates are unavailable). It can also be used to replenish fibrinogen in acquired coagulopathies such as disseminated intravascular coagulation (DIC) and during trauma or childbirth.

Function

Red Blood Cells

The literature strongly supports adhering to a restrictive transfusion strategy (7 g/dL) in hospitalized adult and pediatric intensive care patients who are hemodynamically stable.[1][rx] The evidence is not as compelling for patients with cardiovascular disease, but recommendations are to adhere to a restrictive strategy (hemoglobin 8 gm/dL) for patients with preexisting cardiovascular disease. There is insufficient evidence to make recommendations for patients with the acute coronary syndrome.

RBC transfusion is indicated in actively bleeding patients. The amount should be based on clinical assessment[rx] and, if possible, by laboratory tests to guide targeted therapy. However, in patients with upper gastrointestinal bleeding, patients with a restrictive transfusion strategy may have better outcomes.[rx]

Plasma

There is minimal guidance for plasma transfusion. However, plasma is a frequently prescribed intervention, often for mild to moderate elevations in prothrombin time or an international normalized ratio (INR). This continues to occur despite numerous studies that failed to show a relationship between these elevations and the risk of bleeding or that INR has any ability to predict bleeding.[rx]

The Cochrane Reviews found no evidence to support plasma transfusions in patients who were not coagulopathic undergoing elective cardiac surgery or critically ill patients.

The British Society of Haematology (BSH) published recommendations in 2018 for various patient groups in the absence of major bleeding.[rx][rx]

• There is no evidence to support the prophylactic use of plasma in non-bleeding patients with abnormal standard coagulation tests pre-procedure
• The impact of commonly used doses to correct clotting results or to reduce the bleeding risk is very limited, especially when the PT ratio or INR is between 1.5 to 1.9.
• Vitamin K should be administered in patients with prolonged PT that is likely to be due to acquired vitamin K deficiency.

In patients with liver disease, plasma is often transfused to correct a prolonged INR. British Society of Haematology recommends these guidelines:

• PT and APTT do not reflect the true hemostatic status of patients with advanced liver disease.
• There is no good evidence to endorse the use of prophylactic plasma for correction of abnormal clotting tests in non-bleeding patients prior to interventions such as elective variceal bleeding.
• There is no good evidence to support a role for prophylactic plasma to reduce the risk of bleeding from a percutaneous liver biopsy.
• Prophylactic transfusion of plasma should not be given in low bleeding risk procedures.
• Do not use plasma for volume replacement.

And for sites that have 4-Factor Prothrombin Concentrates such as K-Centra and Bebulin, this should always be the first therapeutic of choice to reverse warfarin emergently.

Cryoprecipitate

There are little data on the use of cryoprecipitate in non-bleeding patients, and it is often used prophylactically but not based on good quality evidence.

The British Society of Haematology[rx] recommends:

• There is insufficient evidence on which to base a recommendation about the threshold of fibrinogen to transfuse cryoprecipitate, or the optimal dose, in patients with hypofibrinogenemia undergoing procedures.
• If fibrinogen is <1.0g/L (100 mg/dL) and other factors (i.e., personal/family bleeding history, drug history, bleeding risk associated with planned procedure) indicate a significant bleeding risk before a procedure, a starting dose of two five donor pools of cryoprecipitate [10 individual units] can be considered (but there is no evidence to support this).

Many US sites consider fibrinogen <2.0 g/L (<200 mg/dL) in a bleeding obstetric patient as an indication to transfuse cryoprecipitate.

Platelets

Common guidelines for platelet transfusions include:[rx]

• Prophylaxis against bleeding—PLT count <10,000 mg/dL
• Neonate—PLT count <50,000 mg/dL
• Bedside procedure—PLT count <50,000 mg/dL
• Kidney or liver biopsy—PLT count <50,000 mg/dL
• Bronchoscopy without biopsy—PLT count <50,000 mg/dL
• Bronchoscopy with biopsy—PLT count <75,000 mg/dL
• Intra-/postoperative bleeding—PLT count <50,000 mg/dL

• PLT count <50,000 mg/dL (medical)
• PLT count <100,000 mg/dL (surgical
• Neurosurgery—PLT count <100,000 mg/dL

Cell Salvage

The Association of Anaesthetists guidelines make the following transfusion recommendations: Use cell salvage when it can be expected to reduce the likelihood of allogeneic (donor) red cell transfusion and/or severe postoperative anemia. Collection of blood for potential cell salvage (‘collect only’ mode) should be considered for surgical procedures where blood loss may exceed 500 ml (or > 10% of calculated total blood volume) in adult patients or > 8 mL/kg (> 10% of calculated total blood volume) in children weighing > 10 kg.[rx]

Whole Blood

There has been increasing interest in using low titer group O whole blood (LTOWB) in military and civilian trauma, and there is evidence to show that it saves lives. [rx][rx] It has also been used in non-trauma massive hemorrhage cases. LTOWB provides all of the components of blood (RBCs, platelets, and plasma with fibrinogen) and provides a balanced resuscitation addressing oxygen needs and coagulopathy in a single bag of blood. The whole blood has a critical titer of anti-A and anti-B of less than 50 to 200). The transfusion of up to 4 units of whole blood has been shown to be safe.[rx]

Complications

There are multiple complications of blood transfusions, including infections, hemolytic reactions, allergic reactions, transfusion-related lung injury (TRALI), transfusion-associated circulatory overload, and electrolyte imbalance.[rx][rx][rx]

According to the American Association of Blood Banks (AABB), febrile reactions are the most common, followed by transfusion-associated circulatory overload, allergic reaction, TRALI, hepatitis C viral infection, hepatitis B viral infection, human immunodeficiency virus (HIV) infection, and fatal hemolysis which is extremely rare, only occurring almost 1 in 2 million transfused units of RBC.

Adverse Event and Approximate Risk Per Unit Transfusion of RBC

• Febrile reaction: 1:60
• Transfusion-associated circulatory overload: 1:100
• Allergic reaction: 1:250
• TRALI: 1:12,000
• Hepatitis C infection: 1:1,149,000
• Human immunodeficiency virus infection: 1:1,467,000
• Fatal hemolysis: 1:1,972,000

Febrile reactions are the most common transfusion adverse event. Transfusing with leukocyte-reduced blood products, which most blood products in the United States are, may help reduce febrile reactions. If this occurs, the transfusion should be halted, and the patient evaluated, as a hemolytic reaction can initially appear similar and consider performing a hemolytic or infectious workup. The treatment is with acetaminophen and, if needed, diphenhydramine for symptomatic control. After treatment and exclusion of other causes, the transfusion can be resumed at a slower rate.

Transfusion-associated circulatory overload is characterized by respiratory distress secondary to cardiogenic pulmonary edema. This reaction is most common in patients who are already in a fluid overloaded state, such as congestive heart failure or acute renal failure. Diagnosis is based on symptom onset within 6 to 12 hours of receiving a transfusion, clinical evidence of fluid overload, pulmonary edema, elevated brain natriuretic peptide, and response to diuretics.

Preventive efforts, as well as treatment, including limiting the number of transfusions to the lowest amount necessary, transfusing over the slowest possible time, and administering diuretics before or between transfusions.

Allergic reaction, often manifested as urticaria and pruritis, occurs in less than 1% of transfusions. More severe symptoms, such as bronchospasm, wheezing, and anaphylaxis are rare. Allergic reactions may be seen in patients who are IgA deficient as exposure to IgA in donor products can cause a severe anaphylactoid reaction. This can be avoided by washing the plasma from the cells prior to transfusion. Mild symptoms, such as pruritis and urticaria can be treated with antihistamines. More severe symptoms can be treated with bronchodilators, steroids, and epinephrine.

Transfusion-related lung injury (TRALI) is uncommon, occurring in about 1:12,000 transfusion. Patients will develop symptoms within 2 to 4 hours after receiving a transfusion. Patients will develop acute hypoxemic respiratory distress, similar to acute respiratory distress syndrome (ARDS). Patients will have pulmonary edema without evidence of left heart failure, normal CVP. Diagnosis is made based on a history of recent transfusion, chest x-ray with diffuse patchy infiltrates, and the exclusion of other etiologies. While there is a 10% mortality, the remaining 90% will resolve within 96 hours with supportive care only.

Infections are a potential complication. The risk of infections has been decreased due to the screening of potential donors so that hepatitis C and human immunodeficiency virus risk are less than 1 in a million. Bacterial infection can also occur, but does so rarely, about once in every 250,000 units of red cells transfused.

Fatal hemolysis is extremely rare, occurring only in 1 out of nearly 2 million transfusions. It is the result of ABO incompatibility, and the recipient’s antibodies recognize and induce hemolysis in the donor’s transfused cells. Patients will develop an acute onset of fevers and chills, low back pain, flushing, dyspnea as well as becoming tachycardic and going into shock. Treatment is to stop the transfusion, leave the IV in place, intravenous fluids with normal saline, keeping urine output greater than 100 mL/hour, diuretics may also be needed, and cardiorespiratory support as appropriate. A hemolytic workup should also be performed which includes sending the donor blood and tubing as well as post-transfusion labs (see below for list) from the recipient to the blood bank.

• Retype and crossmatch
• Direct and indirect Coombs tests
• Complete blood count (CBC), creatinine, PT, and PTT (draw from the other arm)
• Peripheral smear
• Haptoglobin, indirect bilirubin, LDH, plasma free hemoglobin
• Urinalysis for hemoglobin

Electrolyte abnormalities can also occur, although these are rare, and more likely associated with large volume transfusion.

• Hypocalcemia can result as citrate, an anticoagulant in blood products binds with calcium.
• Hyperkalemia can occur from the release of potassium from cells during storage. Higher risk in neonates and patients with renal insufficiency.
• Hypokalemia can result as a result of alkalinization of the blood as citrate is converted to bicarbonate by the liver in patients with normal hepatic function.

Transfusion reactions

Transfusion reactions that can occur with the transfusion of blood range from life-threatening reactions to circumstances in which transfusion can continue, once the cause of the reaction is determined (e.g. simple allergic reaction).  The most common reactions include the following:[rx]

• Transfusion-associated circulatory overload (TACO)
• Transfusion-related acute lung injury (TRALI)
• Transfusion-associated dyspnea (TAD)
• Simple allergic reaction
• Anaphylactic reaction
• Hypotensive transfusion reaction
• Febrile non-hemolytic transfusion reaction (FNHTR)
• Acute hemolytic transfusion reaction (AHTR)
• Delayed hemolytic transfusion reaction (DHTR)
• Delayed serologic transfusion reaction (DSTR)
• Transfusion-associated graft vs. host disease (GVHD)
• Post-transfusion purpura (PTP)
• Transfusion-transmitted infection (TTI)

References

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