Emily Miraflor, MD, Louise Y. Yeung, MD, Brian C. George, MD, and Alden H. Harken, MD
Ephraim Hatfield IV is a 70-year-old male from Tug Fork, West Virginia, whose chief complaint is “bad blood.” One week ago the patient recounts an attempt on his life where “I left a bunch of blood on the pavement.” At your hospital, he received multiple blood transfusions. Following discharge, the patient noted that “my eyes turned yellow and my urine turned brown.” The patient believes that he received “bad blood”—perhaps even from a McCoy donor.
1. Explain the primary reason to transfuse blood.
2. Name an alloantigen that, when present in donor blood, can precipitate a transfusion reaction.
3. Did the patient in the vignette above have an acute or delayed reaction?
1. The only reason to transfuse blood is to increase oxygen-carrying capacity via hemoglobin. So, what we’d really like to do is transfuse pure hemoglobin. That has been tried. The 64,000 molecular weight hemoglobin tetramer breaks up to provoke an osmotic diuresis that rapidly abbreviates the therapeutic effect. So, we transfuse hemoglobin encapsulated in red cells.
One unit of packed red blood cells can be expected to increase a patient’s hemoglobin by approximately 1 g/dL, or the hematocrit by approximately 3%.
2. Unfortunately, 1 U of transfused blood contains a whole lot more than hemoglobin—and most of this stuff, you don’t want. The stuff you don’t want comes in 2 categories:
A. The stuff the donor was born with
B. The stuff the donor acquired
A. Born with: Red blood cells come in multiple flavors. We focus on the A and B red cell antigens, but a short list of additional proteins includes C, D, E, c, e, K, k, JKa, JKb, s, Fya, Fyb, and M. Therefore, every unit of transfused blood is at least a little mismatched.
B. Acquired: What you do not want to do, when you receive a blood transfusion, is to dwell on the possible escapades of donors during the weeks before they offered up their blood. Perhaps the donor was a Mr. Rogers or a Mother Teresa who spent his or her life in church or school, but more likely, the donor enjoyed a more stimulating life. Now, in the absence of a Facebook page on the social antics of your blood donor, you—the blood recipient—are at the mercy of the blood bank laboratory technicians. Fortunately, the people who work in transfusion laboratories do not go to wild parties; their idea of excitement is to identify an arcane antibody in a crossmatch. These protectors of the faith can recite alloantibodies as effortlessly as their church catechisms.
The usual suspects are:
A. Bacteria—most bacteria survive happily in blood.
B. Viruses—CMV, Epstein-Barr, hepatitis A, B, and C, HIV-1 and HIV-2, and human T-cell lymphotropic virus (HTLV)-1 and HTLV-2.
C. Parasites—Chagas and malaria.
D. Others: Creutzfeldt-Jakob disease has been associated with lots of things, including blood transfusions.
2. Non–red blood cell culprits:
3. Transfusion reactions can be categorized as acute or delayed. Some, like hemolytic transfusion reactions, can be both. This patient had a delayed reaction with likely hemolysis.
Acute Transfusion Reactions
The Centers for Disease Control and Prevention (CDC) have characteristically catalogued these reactions into a sociobiological spectrum:
Level I: No big deal
Presentation: Maculopapular rash, flushing, pruritus, and urticaria.
Response: Give antihistamine and proceed.
Level II: Start to worry
Presentation: Bronchospasm, laryngeal tightness, hoarseness, and stridor.
Response: If possible, abort the transfusion and give β- and α-adrenergic agonists.
Level III: Drama
Presentation: Hypotension, disseminated intravascular coagulation (DIC), and hemoglobinuria.
Response: Stop the transfusion immediately! Give calcium gluconate or calcium chloride (it doesn’t matter which), warm the patient, and give an α- or β-adrenergic agonist.
Delayed Transfusion Reactions
Like people, formed blood elements (leukocytes and platelets) can be happy, irritated, or overtly hostile. Much like a hibernating polar bear, most marginating neutrophils are tough to arouse. But, when you irritate them, they are capable of stirring up a lot of trouble—especially at home. Not surprisingly, self-satisfied quiescent white cells become aggrieved when they are drawn unceremoniously into a plastic, calcium-depleted bag. They get testy. And the longer they hang out in this foreign environment, the less neighborly they get. Your typical blood bank director will therefore not keep blood longer than a 42-day stay.
A transfused activated neutrophil expresses a sticky Velcro of adhesion molecules that facilitates lodging in the pulmonary endovasculature, where they blow big holes and promote interstitial fluid loss. This is the pathogenesis of transfusion-related acute lung injury (TRALI). These same neutrophils can also result in graft-versus-host disease, another type of delayed transfusion reaction that can be seen several weeks after a transfusion. A third type of delayed transfusion reaction is termed “posttransfusion purpura,” which is simply a delayed thrombocytopenia (usually 1 or 2 weeks later). There is no reason to inflict this kind of damage on any patient, so all blood transfusions should be leukodepleted with a filter.
Hemolytic Transfusion Reactions
When an unfortunate patient already has (acute) or develops (delayed) antibodies to ABO-incompatible or other allotypic red cell antigens, rapid red blood cell destruction will ensue. The clinical manifestations of this hemolysis include chills, fever, hypotension, hemoglobinuria, and DIC, which can be most easily recognized by oozing at the IV site.
DON’T BE INTIMIDATED TO GIVE BLOOD
Blood bank directors thrive on detailed complexity. Surgeons like things simple. When your patient requires additional oxygen-carrying capacity, give blood. If you perseverate yourself into paralysis by conjuring all of the catastrophic and cataclysmic components of the contagious colostrum we, with inspirational innocence, term a “blood transfusion,” your patient will succumb to deficient oxygen delivery—while you watch!
TIPS TO REMEMBER
The sole reason to transfuse blood is to increase oxygen-carrying capacity.
All blood transfusions are at least a little mismatched.
Treat minor transfusion reactions with an antihistamine.
Treat major transfusion reactions with α- and β-adrenergic agonists.
With a suspected transfusion reaction, send blood specimens from both the patient and the transfused blood specimens to the lab.
Acute DIC is most easily recognized as oozing at the IV site.
1. A 55-year-old male is still on the ventilator 3 days following an open aortobifemoral graft. His Hbg is 7 g/dL. You decide to give him 2 U of packed red blood cells. The most likely benefit will be an increase in which of the following?
A. PO2 95 → 110 mm Hg
B. O2 saturation 95% → 98%
C. CaO2 by 25%
D. Hbg 7 → 14 g/dL
E. Hct 20% → 35%
2. DIC can be most easily recognized by which of the following?
A. Low platelet counts
B. Bleeding around a peripheral IV site
C. Low hematocrit
D. Elevated D-dimers
3. You should stop a transfusion if the patient develops which of the following?
A. A rash
4. Pharmacologic treatment of an acute transfusion reaction could include any of the following except which of the following?
1. C. More red blood cells increase the content of oxygen being carried in the blood. The oxygen saturation of that blood remains the same, as does the partial pressure of oxygen. The Hgb should rise by 1 g/dL for each unit, while the Hct will rise just 3% for each unit.
2. B. While these other elements can also be present, they are nonspecific and require a lab test. It is worth first checking the peripheral IV site.
3. C. A rash and pruritus are CDC level I–type reactions. You should give an antihistamine and then monitor the patient while you continue the transfusion.
4. A. Antihistamines such as diphenhydramine are first-line pharmacologic agents for all levels of transfusion reactions. For more severe reactions, α- and β-agonists are also indicated.