This case involves an acute hemolytic transfusion reaction of non-immune origin. Specifically, the reaction occurred due to variations in accepted practices and standards when

  • transporting the RBCs between hospitals
  • receiving the RBC in the second hospital
  • transfusing the RBC

The case will be discussed as follows:

  • Storage and transportation
  • Quality system - interhospital shipping
  • Visual inspection
  • Acute hemolytic transfusion reaction

Storage and Transportation

RBC must be stored at 1 – 6o C and RBC being transported must  maintain a temperature of 2 °C to 10 °C. Packaging should be of a sturdy construction to resist damage, and have a tamper proof seal.

In this case, Hospital A incorrectly shipped the RBC in dry ice. Transfusion service staff were not involved and clinical staff were unaware of shipping requirements.

  1. Is dry ice suitable for shipping any blood product?


To meet regulatory requirements the following shipping practices are required:

  • RBC and other blood components should be shipped in containers that have been validated prior to use.
  • Packaging should be of a sturdy construction to resist damage, and have a tamper proof seal.2
  • To prevent hemolysis by direct contact with a frozen ice or gel pack, cardboard must be placed between whole blood/red cell components and the ice pack.
  • Temperature monitors should be included in shipments as required, with regular temperature monitoring based on frequency of shipments, distances involved, and ambient temperatures.

Quality System - Interhospital Shipping

As with all aspects of the transfusion, safety is enhanced by use of a quality system. In the context of of inter-hospital shipping of blood, a quality system would include process monitoring of activities, quality indicators, and controls that must be in place:

  • at the sending hospital to ensure that the blood is safely packaged and sent;
  • at the receiving hospital to ensure that the blood that is received is safe for transfusion;
  • to ensure that the overall process is safe (includes both sending and receiving hospital responsibilities).
  1. Is it acceptable to ship RBC in the same container as other components such as platelets and fresh frozen plasma?


Visual Inspection

CSTM Standards require that blood products be inspected for abnormal appearance at several steps and, if abnormalities are detected, (1) the product must be quarantined until appropriate disposition is determined, and (2) the process must be documented and the shipper informed. The steps requiring inspection include:

  • upon receipt of the product by the transfusion service
  • before the product is issued for transfusion from the transfusion service
  • before the product is shipped to another facility
  • when the product is returned from another location within the hospital
If standard practices had been followed in this case,  the hemolysed RBC could have been detected at Hospital B before being transfused:
  • Upon receipt at Hospital B. Detection of the incorrect shipping coolant and frozen, hemolysing RBC by the transfusion service was not possible because the blood went directly to the OR, where staff did not realize that the coolant was incorrect and did not detect the frozen and hemolysed units. Receipt of the shipment likely provided the best chance for detection.
  • Upon issue to the patient from the OR refrigerator: staff did not detect the hemolysing RBC.
  • Upon transfusing the patient:staff beginning the transfusion did not notice that the RBC units were hemolysed.

For further information about visual inspection, see Visual Inspection of Blood, Blood Components and Fractionated Blood Products (Guideline: IM.003).

  1. What can cause a black or purplish red cell mass in a unit of RBC?


Acute Hemolytic Transfusion Reaction

Acute non-immune hemolytic transfusion reactions can occur when hemolysed red cells that are serologically compatible are transfused. Hemolysis can be caused by physical or chemical destruction of blood4, including

  • freezing (e.g., when transporting blood, placing  RBC against a frozen gel pack with no insulation between the frozen pack and the blood)
  • heating (e.g., using a blood warmer with too high a temperature)
  • hemolytic drug or solution added to blood (e.g., 5% and 50% dextrose solutions)
  • mechanical trauma (e.g.,  from cardiopulmonary pump-oxygenators) inadequate deglycerolization of frozen RBC

Transfusion of hemolysed red cells may result in an acute hemolytic transfusion reaction characterized by hemoglobinemia and hemoglobinuria. Lysed red cells may also lead to release of vasoactive or thrombogenic substances that can trigger hypovolemic shock, disseminated intravascular coagulation (DIC), and renal failure.


Most acute hemolytic transfusion reactions (immune and non-immune) result from human error, as shown by these reports:

Callum, JL, Kaplan, HS, Merkley, L L, Pinkerton, PH, Rabin Fastman, B, Romans, RA.  Reporting of near-miss events for transfusion medicine: improving transfusion safety. Transfusion 2001; 41: 1204-11. [ Medline ]

Linden JV, Wagner K, Voytovich AE, Sheehan J. Transfusion errors in New York State: an analysis of 10 years' experience. Transfusion 2000;40(10):1207-13. [ Medline ]

Williamson LM, Lowe S, Love EM, Cohen H, Soldan K, McClelland DB, et al. Serious hazards of transfusion (SHOT) initiative: analysis of the first two annual reports. Br Med J 1999;319:16-9.

Many transfusion complications are preventable, especially those caused by human error. Key strategies for preventing complications and minimizing their adverse effects include

  1. Proper patient - donor unit identification protocols
  2. Surveillance of patients being transfused:
    • during the first 15 minutes of transfusion
    • periodic patient observation during the transfusion
  3. Education of all personnel involved in transfusion
  4. Instituting a quality system
  1. Do most transfusion-related human errors occur inside or outside the transfusion service and what are the implications?


  2. Why is it important to monitor patients during transfusion?


In this case, the anesthesiologist in the OR monitored the patient's vital signs but nothing unusual presented before the frozen and hemolysed units were discovered.

Symptoms are often masked in the anesthetized patient. If present, the only signs may be one or more of falling blood pressure, uncontrolled bleeding, or hemoglobinuria.

If the hemolysis were detected upon starting the transfusion, the transfusion reaction could have been prevented.

  1. How are human errors handled in a quality system?