Question 1

List the problems associated with massive transfusion  in the critically ill.  Outline your principles of management for each.

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College Answer

Massive transfusion (eg. replacement of more than 50% of blood volume in 12 to 24 hours, or  one  circulation blood volume in  24 hrs  [T Oh]) is  associated with  many potential problems which are related to a number of factors including the volume of resuscitation, factors related to the storage blood, and many other related issues. Problems include:

•    Volume  overload  (careful  monitoring  of  filling  pressure,  response  to  volume, diuresis)

•    Over-transfusion (monitor Hb regularly, titrate according to needs)

•    Hypothermia (use of fluid warmers and general measures to minimise heat loss)

•    Dilutional coagulopathy of both clotting factors and platelets (regular and early monitoring of coagulation, and involvement of haematology for replacement therapy [better than according to protocol])

•    Transfusion related lung injury (consider use of filters, leukodepletion)

•    Excessive citrate causing metabolic alkalosis and hypocalcemia (monitor pH and ionised calcium, replace calcium as necessary)

•    Hyperkalaemia (use of “younger” blood, monitor regularly, may require specific therapy)

•    Disease transmission (use of  products on  as  needed basis  only,  standard blood banking precautions)

•    Distractions resulting in not controlling source of haemorrhage, and risks of hurried cross-checking and incompatibility (allocation of sufficient resources and personnel, standard programs in place to facilitate process and anticipate needs)

•    Other problems include loss of identity (cross matching issues, loss of baseline haematological information etc.)


Massive transfusion is discussed in greater detail elsewhere. Several definitions exist, but the replacement of 1 blood volume is a popular one.

In fact, and excellent article from Chest (2010) has a nice table (Table 1) of complications from massive transfusion. That table was a strong (dominating) influence on the following list of complications:

Acute complications

  • Acute hemolytic transfusion reactions
  • Febrile nonhemolytic transfusion reactions
  • Tranfusion-associated lung injury (TRALI)
  • Transfusion-associated circulatory overload (TACO)
  • Allergic reactions to blood products
  • Bacterial sepsis due to contaminated blood products
  • Hypocalcemia due to citrate
  • Hyperkalemia due to high PRBC K+ content
  • Acidosis due to high PRBC lactate content
  • Hypothermia due to use of recently refrigerated PRBCs
  • Dilutional coagulopathy due to inappropriate blood product replacement proportions
  • Dilutional thrombocytopenia due to lack of platelet replacement

Delayed complications

  • Delayed hemolytic transfusion reactions
  • Transfusion-related immune modulation (TRIM)  
  • Microchimerism - the persistence of an allogeneic cell population of leucocytes
  • Transfusion-transmitted diseases, eg. HIV, Hep C
  • Posttransfusion graft-vs-host disease (due to non-leukodepleted PRBCs)
  • Posttransfusion purpura

The college allso asks the candidate to "outline your management for each".

This requires a large table. The Australian Red Cross Blood Service have a nice table for management steps of transfusion reactions.

Management of Massive Transfusion-Associated Complications
Acute hemolytic transfusion reactions
  • Stop transfusion
  • Re-crossmatch
  • Maintain blood pressure with vasopressors (there may be cytokine shock)
  • Maintain adequate urine output to prevent haem-associated ATN
Febrile nonhemolytic transfusion reactions
  • Stop transfusion
  • Antipyretic agents
Allergic reaction to blood products
  • Stop transfusion
  • Antihistamine and corticosteroid
Tranfusion-associated lung injury
Transfusion-associated circulatory overload
  • Stop transfusion
  • Administer a diuretic
  • Consider a venodilator (eg. GTN) to decrease preload
  • Ventilate with a higher PEEP
Bacterial sepsis
  • Management of sepsis as per usual routine
  • Inform blood bank regarding contaminated blood products
  • Perform a blood culture and Gram stain on the bag of PRBCs
  • Keep the bag and giving set
Hypocalcemia due to citrate
  • Calcium replacement
Hyperkalemia due to high PRBC K+ content
  • Routine management of hyperkalemia (eg. calcium gluconate, bicarbonate)
  • Tincture of time, if your liver is normal
  • Dialysis, if the clearance mechanisms are impaired
  • Aggressive rewarming
  • You should have used a blood warmer
Dilutional coagulopathy
  • Blood products will need to be replaced - FFP and cryoprecipitate to start with
Dilutional thrombocytopenia
  • Platelet transfusion
Delayed hemolytic transfusion reactions
  • Maintain blood pressure with vasopressors (there may be cytokine shock)
  • Maintain adequate urine output to prevent haem-associated ATN
Transfusion-related immune modulation
  • Using leukodepleted PRBCs, surprisingly, is not protective.
  • Monitor for GVHD and autoimmune diseases
Transfusion-transmitted diseases
  • Councelling of the affected
  • Post-exposure prophylaxis, if relevant
  • Antiviral therapies
Posttransfusion graft-vs-host disease
  • Immunosuppression
Posttransfusion purpura
  • IV immunoglobulin
  • Plasmapheresis
  • Generally, management resembles the management for TTP


Sihler, Kristen C., and Lena M. Napolitano. "Complications of massive transfusion." CHEST Journal 137.1 (2010): 209-220.


Capon, Stephen M., and Dennis Goldfinger. "Acute hemolytic transfusion reaction, a paradigm of the systemic inflammatory response: new insights into pathophysiology and treatment." Transfusion 35.6 (1995): 513-520.


Perrotta, P. L., and E. L. Snyder. "Non-infectious complications of transfusion therapy." Blood reviews 15.2 (2001): 69-83.


Beauregard, Patrice, and Morris A. Blajchman. "Hemolytic and pseudo-hemolytic transfusion reactions: an overview of the hemolytic transfusion reactions and the clinical conditions that mimic them." Transfusion medicine reviews 8.3 (1994): 184-199.


Reed, William, et al. "Transfusion-associated microchimerism: a new complication of blood transfusions in severely injured patients." Seminars in hematology. Vol. 44. No. 1. WB Saunders, 2007.


Anderson, Kenneth C., and Howard J. Weinstein. "Transfusion-associated graft-versus-host disease." New England Journal of Medicine 323.5 (1990): 315-321.


Yokoyama, Ana Paula Hitomi, et al. "Diagnosis and Management Of POST-Transfusion Purpura-Case Report." Blood 122.21 (2013): 4834-4834.