This section will review best practices for investigating suspected transfusion complications, including the differential diagnosis of post-transfusion fever, a key part of Case O-6. Also see investigation protocols discussed in Case O-5. The discussion is not meant to be definitive or all inclusive.

  • Patient and donor identity
  • Immediate investigation protocols
  • Standards and regulations
  • This case
  • Self study questions
  • Further Reading

Patient and Donor Identity

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


The differential diagnosis of patients who experience fever during or shortly thereafter transfusion includes

  • Febrile non-hemolytic transfusion reactions
  • Immediate hemolytic transfusion reactions
  • Bacterially contaminated blood products

See CBS: Clinical Guide to Transfusion - Ch. 10 Adverse Reactions


FNHTR are one of the most common transfusion complications and have been defined as a rise of 1°C (with or without concurrent chills) for which no other cause can be identified. Signs and symptoms usually appear towards the end of  transfusion or sometimes 1-2 hours later.

Because fever may occur in hemolytic and bacteriogenic transfusion reactions, an investigation is required to eliminate these serious complications. The transfusion service (TS) should have policies for how to investigate suspected FNHTR and whether or not transfusions can be restarted. Due to the risk of more serious reactions, extreme caution should be used if restarting transfusion, which should be done only with a physician's orders and with the patient carefully observed throughout.

The most likely cause of FNHTR due to RBC transfusion is patient antibodies directed against leukocytes in the red cell unit, whereas FNHTR due to platelets are thought to be caused by cytokines that accumulate in the component during storage. Prestorage leukoreduction has reduced the frequency of FNHTR but has not entirely eliminated them.


IHTR are potentially life-threatening reactions typically caused by transfusion of ABO-incompatible RBC following misidentification of the blood recipient.

Signs and symptoms usually appear within minutes of the start of transfusion but can occur anytime during transfusion.  IHTR are characterized by fever, chills, anxiety, burning along site of transfusion, hypotension, back pain, and many more signs and symptoms.  Life-threatening complications include hypovolemic shock, disseminated intravascular coagulation, and renal failure.


Transfusion-related acute lung injury (TRALI) has emerged as a leading cause of transfusion-related morbidity and mortality. It is characterized by acute respiratory distress following transfusion with plasma-containing blood products. TRALI is believed to be caused by passive transfusion of donor leukocyte antibodies triggering complement activation and neutrophil sequestration and activation in pulmonary capillaries leading to lung injury. However, in up to one-third of cases no donor antibodies are implicated.

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.

BACTERIAL SEPSIS includes symptoms similar to immediate hemolytic transfusion reactions and TRALI. 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 in blood components may be due to a wide variety of causes, including

  • contamination during collection (inadequate aseptic technique in swabbing donor skin; needle coring of donor skin)
  • blood donor infection (transient, asymptomatic bacteremia or chronic low grade infection)
  • improper refrigeration during storage or transportation
  • contamination during pooling of products
  • defective blood bags
  • transfusing over too long a time

The incidence of transfusion-associated bacteremia is unknown. Because platelets are stored at RT, they present a greater risk than RBCs. In the USA bacterial contamination was the second most common cause of death from transfusion (after clerical errors). In 2004 the AABB Standard mandated platelet bacterial contamination detection testing.

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)

CSTM Standards for Hospital Transfusion Services, v 4 (Note: When Case O6 was created, it was v. 2)


  • 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. [see Case O-5: Reporting adverse events]
  • 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


  • N4.1 All cases of suspected transfusion-transmitted bacterial sepsis shall be investigated immediately. The transfusion shall be stopped, and the implicated blood and blood product returned to the TS. Care should be taken to avoid further contamination of the product. 17.4.1
  • N4.2 Investigation of the implicated blood and blood products shall include preparation of a gram stain and cultures of the product contents, not segments. Cultures should be performed on appropriate media with incubation at both 25oC and 35oC. 17.4.2
  • N4.3 Investigation should include recipient blood cultures.17.4.3
  • N4.4 Any bacteria isolated from the blood and blood product or recipient blood cultures should be retained for further typing if required. 17.4.4
  • N4.5 If bacterial contamination is confirmed, the blood supplier shall be notified for appropriate follow-up. 17.4.5

Clauses also exist for how to investigate and report

  • Suspected Hemolytic Transfusion Reactions (N3.0)
  • Other Suspected Transfusion-Transmitted Diseases (N5.0)
  • Other Adverse Reactions (N6.0)

This Case (Investigating Adverse Reactions)

Upon discovering the apparent reaction (patient had started shaking), 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 the patient (right blood went to right patient )
  • sought medical help
  • called the TS to report the reaction

The TS performed a transfusion reaction investigation according to its policy and procedure manual:

See Investigation of transfusion reactions (TraQ Technical Resource Manual)

  • Confirmation of patient and donor identity and a serologic investigation eliminated an immune hemolytic transfusion reaction as the cause.
  • Because a bacteriogenic reaction was suspected due to fever subsequent to a prolonged transfusion time (8 hrs.+), the returned units were examined for any abnormal appearance (e.g., clots, brownish, opaque, muddy, or purple discoloration). The microbiology laboratory performed gram stains and cultures of both PRBC contents, as well as recipient blood cultures. All were negative.
  • The patient's other signs and symptoms (e.g., increase in blood pressure to 150/99) did not fit TRALI.

Summary: In the absence of other credible causes, staff concluded that a febrile non-hemolytic reaction had likely occurred after the second PRBC and had triggered subsequent events (increased intracranial pressure, convulsions).

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.
  • When investigating possible bacterial contamination:
    • Treatment for suspected bacterial contamination should be based on clinical considerations, since delay in therapy may result in severe morbidity or death.
    • Care should be taken when collecting samples for culture from both product and recipient to avoid external contamination of samples.

    • Gram stain and cultures should be done on contents of the implicated blood bags, not segments.

TraQ self study questions

  1. Transfusion-related fever is 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: Administering blood products
  • Part 2: Investigating adverse events <--You are here
  • Part 3: Scope of practice issues
  • Part 4: Education for interdisciplinary healthcare teams