Transfusion Reactions

1) Differential Diagnosis of Fever during transfusion - this is a very common scenario, and important to have a ddx and approach!

• Immunologic Transfusion Reaction - i.e. Febrile, Hemolytic, Allergic.. - see below for more
• Transfusion-transmitted Bacterial Infection - actually not that uncommon, especially with platelets (they are stored at room temperature, vs PRBCs and plasma - refrigerated.  Plts are stored at room temp for several reasons, but mainly because when refrigerated they are cleared much more rapidly from circulation once transfused).  Organisms include both gram positives and gram negatives, and beware cold-loving organisms for PRBCs and plasma, i.e Yersinia.
• Fever unrelated to transfusion - i.e., this patient is having neutropenic fevers daily, may be just coincidental timing

A very important point is that for fevers during transfusion, YOU MUST STOP THE TRANSFUSION AND RULE OUT BAD THINGS LIKE AN ACUTE HEMOLYTIC REACTION.  The transfusion specialists actually say that all blood products should be sent back to the blood bank for further analysis.  DO NOT SIMPLY GIVE TYLENOL AND IGNORE WITHOUT THINKING ABOUT POTENTIAL BAD CONSEQUENCES.

2) Overview of Immunologic Transfusion Reactions

1. Febrile nonhemolytic reaction - the most common reaction, occurs in ~1:100 units transfused, due to cytokines that accumulate during blood storage, also from Abs vs donor WBCs.  Benign, but difficult to distinguish initially from more severe transfusion rxs.
2. Minor Allergic reaction - mild urticaria and pruritis, common as well (~1:100 units), due to soluble allergenic substances in the donor plasma.  Must rule out more severe, anaphylactic reaction before restarting transfusion.  Can treat with benadryl.
3. Acute Hemolytic reaction - the most feared complication, due to ABO incompatibility (also can be caused by Rh incompatibility).  Fortunately, is rare today due to multiple checks in place. Classically presents with fever, flank pain, hypotension, and red/brown urine (due to hemolysis), but often nonspecific with only fevers/chills.
4. Delayed Hemolytic reaction - due to anamnestic antibody response after reexposure to foreign RBC antigens previously encountered by transfusions or pregnancy.  These antigens typically are NOT ABO, but can be of Rh and other minor antigens.  Presents 2-10 days after transfusion with more gradual and mild signs of hemolysis.
5. Anaphylactic reaction - usually occurs in pts with IgA deficiency, due to preformed anti-IgA Abs.  Presents as bronchospasm, laryngeal edema, hypotension.
6. Transfusion-related Acute Lung Injury (TRALI) - occurs ~1:5000 units, the most common cause of transfusion-related mortality in U.S., due to donor Abs vs recipient WBCs causing cytokine release.  Presents as respiratory distress and noncardiogenic pulmonary edema.  Compare with TACO (transfusion-associated circulatory overload) which presents as cardiogenic pulmonary edema (i.e. simple volume overload from the high colloid volume from transfusion).

3) Overview of ABO and Rh Blood systems

1.  ABO - these are surface antigens present on the surface of RBCs, of unknown function.  Humans have naturally occurring antibodies against other ABO antigens (i.e., they do not need to be previously exposed to blood products to develop Abs).

• O-type - (most common) - has anti A and B Abs --> can only receive O type blood, but can be donated to anyone since does not have any antigens (O negative is universal donor)
• A-type - has anti-B Abs - can only receive A or O blood
• B-type - has anti-A Abs - can only receive B or O blood
• AB - (rarest) - can receive any blood (AB positive is universal recipient), but can only donate to AB type recipients

2.  Rh - this is another blood antigen system, different from ABO.  Rh antigens are also transmembrane proteins in RBCs.  The main one of interest is the D antigen.  

• Patients are either Rh(+) or Rh(-).  Unlike ABO, Rh(-) patients do NOT have naturally occuring Abs vs D antigen - they only develop Abs when exposed to Rh(+) blood, i.e. through prior transfusions, transplacental crossing of blood in pregnancy.  In women, this can cause problems with subsequent pregnancies when mother is Rh(-) but fetus is Rh(+) - antiD abs cross placenta and can cause Hemolytic Disease of the Newborn.  This is why there is this whole deal of giving pregnant women (who are Rh- but fetus is Rh +) prophylaxis with Rhogam during third trimester or when there is high risk of fetomaternal hemorrhage, or when baby is born.

4) Management of Acute Hemolytic Reaction

• Main complications to worry about are Acute renal failure (due to hemoglobinuria), Shock, and DIC.  Hemolysis can also result in hyperkalemia.
• Labs to check - CBC to look for rapid decrease in H/H, BMP to look for renal failure, hyperkalemia, Bilirubin and LDH and Haptoglobin and Direct Coomb's test to assess for hemolysis, and UA to look for signs of hemoglobinuria (positive blood on dipstick, but no RBCs on microscopic analysis).
• Always send blood back to the blood bank!  If this is due to ABO incompatibility, another patient's life may be in danger if they are getting the wrong blood unit!!
• Main management involves vigorous IVFs to maintain UOP, sometimes with forced diuresis with lasix or mannitol.  Manage DIC with cryo and FFP as needed, and often need pressors like dopamine for shock. Sometimes may need dialysis as well.

(Chanu Rhee MD, 9/24/10)