This section will review best practices for investigating suspected transfusion complications from a clinical perspective. The discussion is not meant to be definitive or all inclusive.

Patient and Donor Identity

As discussed, identification errors may occur when identifying the patient/donor unit prior to transfusion.

Accordingly, when a transfusion reaction or any transfusion adverse event or complication is suspected, checking that the right blood went to right patient should be one of the first steps after stopping the transfusion:

  • Check the identity and compatibility of patient and donor
    • Confirm that the patient's name and hospital number on the blood bag label match the information on the patient's ID wristband.
    • Verify that the blood component donor number is correct and intended for the patient and that blood groups (and crossmatch, if done) are compatible between patient and donor

Immediate Investigation Protocols

Recognizing the signs and symptoms of a transfusion reaction and acting promptly and appropriately are critical to reducing serious consequences to transfusion recipients.

When a transfusion reaction or any transfusion adverse event or complication is suspected, best practice includes these process steps:

Immediately investigate the suspected transfusion reaction.

  1. Stop the transfusion immediately
  2. Maintain intravenous access maintained with 0.9% saline
  3. Check the identity and compatibility of patient and donor ("right blood to right patient" as above)
  4. Seek medical help
  5. Notify the transfusion service that a suspected transfusion reaction has occurred and briefly describe the adverse event
  6. Investigate according to hospital policies and procedures related to the identification and management of transfusion reactions.

Further investigation

How to investigate reactions further depends on the type of complication. For example, some symptoms suggest a probable reaction type and can be acted upon. For example, if the only symptoms are urticaria and pruritus , the transfusion may be temporarily interrupted, a physician may prescribe an antihistamine and, if the reaction subsides, the transfusion may be continued at a slow rate of infusion. Note: Because it is hard to tell if early symptoms and signs are the beginning of something more serious, it is often prudent to just stop the transfusion without plans to carry on unless the transfusion is very urgent or the product is very "special" (e.g., rare red cells negative for high frequency or multiple antigens to which the patient has antibodies.

However, because some symptoms may be common to different types of complications, for several complications all possibilities must be considered initially until a differential diagnosis leads to the final diagnosis.

Standards and Regulations

Standards and regulations exist for investigating suspected transfusion complications. Here are a few sample Canadian standards showing selected clauses only (not the entire standard).

CSTM Standards (Z902-04 references as superscripts)


N2.1 A list of common signs and symptoms of suspected adverse reactions shall be included in both the nursing and TS manuals. 17.2.1
N2.2 All serious adverse reactions shall be immediately reported to the TS.
N2.3 The TS shall investigate all reports of significant adverse reactions. The aim of the investigation shall be to determine the probable cause and shall include appropriate laboratory tests. 17.2.2
N2.6 The original report of an adverse reaction investigation, including recommendations for management of future transfusions, shall be placed in the recipient's permanent medical record. The TS shall retain a copy,
and the information shall be accessed if the recipient requires further transfusion. 17.2.3/17.2.4

Clauses exist for how to investigate and report:


Sections N3 - N5 include explicit investigative requirements, whereas N6 specifies that other clinically significant adverse reactions shall be investigated as outlined in the policy and procedure manual and in consultation with the TS medical director.

This Case

Upon discovering the patient in extreme respiratory distress, the nurse's immediate actions followed the procedures detailed in the facility's nursing manual:

  • stopped the transfusion
  • kept the IV open
  • examined the blood bags and accompanying records to ensure that the plasma was the correct ABO group and was intended for HL (right blood went to right patient )
  • sought medical help
  • called the transfusion service to report the reaction

Differential Diagnosis

The differential diagnosis of patients who have transfusion-related respiratory distress includes

  • transfusion-associated circulatory overload (TACO)
  • transfusion related acute lung injury (TRALI)
  • anaphylactic transfusion reactions
  • bacterially contaminated blood products.

Cause. Circulatory overload may result from

  • Impaired cardiac function
  • Excessive rate of transfusion
  • Combination of impaired cardiac function and excessive transfusion rate

Incidence. The incidence of TACO is unknown and varies with patient population, surveillance vigilance, and whether the major sequelae (acute respiratory distress) was differentiated from TRALI. Reported incidences vary widely and are in the range of 1 in 100 to 1 in 3000 patients transfused. Patients over 60, infants, and patients with severe euvolemic anemia (hemoglobin <50 g/L) are more susceptible.

Note. Patients with severe euvolemic anemia are usually patients who have developed anemia very gradually so that the anemia is chronic. The typical clinical example of this phenomenon is patients with Vitamin B12 deficiency. Vitamin B12 deficiencyis usually an extremely chronic type of deficiency as people have lots of B12 stores. Therefore, by the time patients present with anemia, they may have been malabsorbing B12 for years and have excellent volume compensation.

Clinical Presentation. TACO presents within minutes to hours of the start of transfusion as acute respiratory distress and congestive heart failure. Clinical presentation includes dyspnea, orthopnea, tachypnea, cyanosis, tachycardia, increased venous pressure, and hypertension.

The last two symptoms help to differentiate TACO from TRALI (see below).As well, an early portable chest X-ray helps differentiate TACO from TRALI: Cardiac enlargement and pleural effusions or dependent edema in patients with TACO versus bilateral non-cardiogenic pulmonary edema in TRALI.

Management. Strategies for managing TACO include:

  • Stopping the transfusion
  • Administering oxygen and diuretics as needed under direction of a physician.

Placing the patient in a sitting position

TACO - more...


TRALI symptoms usually begin within 1-2 hours of transfusion and typically are present by 4–6 hours. Clinical findings include the rapid onset of dyspnea, tachypnea, cyanosis, pulmonary rales, hypotension (mild to moderate), fever (1-2°C) and chills, tachycardia, severe hypoxemia, and acute non-cardiogenic pulmonary edema.

TRALI - more...

Anaphylactic transfusion reactions

Anaphylactic transfusion reactions may begin after infusion of only a few mL with mild symptoms that can rapidly progress to shock and death. Reactions usually occur within 1-45 minutes of the start of transfusion. Severe allergic transfusion reactions involve respiratory distress related to bronchospasm manifested by tachypnea, wheezing, cyanosis, severe hypotension, and can involve multiple body systems (cutaneous, pulmonary, gastrointestinal, cardiovascular). The respiratory distress from anaphylactic transfusion reactions is related to laryngeal edema rather than pulmonary edema as in TRALI.

Anaphylactic - more...

Bacterial sepsis

Bacterial sepsis includes symptoms similar to immediate hemolytic transfusion reactions and TRALI, and milder reactions may exhibit symptoms identical to febrile non-hemolytic transfusion reactions. Severe reactions manifest as fever, hypotension, and vascular collapse, which may include respiratory distress.

Bacteria - more...


As discussed in an editorial1 in Transfusion, although the differential diagnosis of transfusion complications involving respiratory distress includes allergic and anaphylactic reactions, intravascular hemolysis, bacterial contamination, and more, the most important diagnoses are TRALI and TACO, which in most cases are readily distinguishable:

"In TRALI, moderate hypotension and low to normal pulmonary artery wedge pressure are prominent features. With TACO, hypertension (with widened pulse pressure), tachycardia, and elevated central venous and pulmonary artery wedge pressure are typical. There is overlap, however, between these two entities, which represents a challenge to the clinician. Most instances of TRALI occur within 2 hours of transfusion, a timeline approximating that of TACO. Onset of signs and symptoms, however, may be as late as 6 hours. Hypertension is found at the outset of up to 15 percent of TRALI cases. Finally, TRALI and TACO can occur in the same patient; one can precede the other or manifest concurrently. For all these reasons, TACO and TRALI can be either misdiagnosed or unrecognized."

Future possibility

Because the typical symptoms and signs associated with TACO are neither sensitive nor specific, some researchers have investigated using B-natriuretic peptide (BNP) in the differential diagnosis of TACO2 . BNP is a polypeptide secreted from cardiac ventricles in response to ventricular volume expansion and pressure overload. In a small study of patients with suspected TACO (n=21) and controls (n=19), they found BNP to have a sensitivity 81%, a specificity of 89%; a positive predictive value of 89%; and a negative predictive value of 81% in diagnosing patients with suspected TACO. The authors concluded that in patients who present with TACO-like symptoms, BNP can be a useful adjunct marker.

This case

The on-call resident used patient history, clinical presentation, physical examination, chest X-ray, and other results to diagnose the complication as TACO secondary to plasma transfusion. Despite treatment, the patient went into cardiac arrest and died.

Learning Points

  • Recognizing the signs and symptoms of a transfusion reaction and acting promptly and appropriately are critical to reducing serious consequences to transfusion recipients.
  • A list of common signs and symptoms of suspected adverse reactions must be included in both nursing and transfusion service manuals.
  • When any transfusion complication is suspected, checking that the right blood went to right patient should be one of the first steps after stopping the transfusion.
  • Best practice for the immediate actions to take whenever a transfusion complication is suspected include
    • stopping the transfusion
    • maintaining IV access
    • checking identity and compatibility ("right blood to right patient")
    • notifying the physician and transfusion service
    • investigating according to hospital policies and procedures.
  • Standards and regulations exist for investigating suspected transfusion complications, including explicit requirements for hemolytic transfusion reactions, bacterial sepsis, and transfusion-transmitted diseases.

Practical Notes

  • Signs and symptoms of transfusion complications with related investigative actions must be present and easily accessible at nursing stations.
  • Clinical staff who administer transfusion must be trained and assessed in investigating suspected transfusion complications.
  • Sometimes an apparent drop in O2 saturation using an oximeter may be related to severe rigors in a febrile reaction which spuriously reduces the apparent O2 saturation. For this reason, early arterial blood gas (ABG) measurement via arterial puncture is also useful to confirm hypoxemia that might be expected based on symptoms or signs.

*If you have comments on this section, please contact Pat: This email address is being protected from spambots. You need JavaScript enabled to view it.

TraQ self study questions

1. Transfusion-related respiratory distress is mainly associated with which types of transfusion complications?


2. List the immediate steps to take whenever a transfusion reaction is suspected.


3. Which manuals must contain a list of the common signs and symptoms of suspected adverse reactions?


More Discussion....

  • Part 1: Clinical uses of FFP
  • Part 2. Compatibility requirements for plasma
  • Part 3. Administering blood products
  • Part 4: Investigating adverse events  <--You are here
  • Part 5. Reporting adverse events