Download Acute Intraoperative Hemolysis Following Rapid

Immunohematology
Acute Intraoperative Hemolysis Following
Rapid Infusion of Hypotonic Solution
Richard J. Davey, MD; Brenda J. Lee, BB(ASCP); and Sandra M. Coles, SBB(ASCP)
A patient undergoing intraoperative .radiation was noted to have marked
hemoglobinemia and hemoglobinuria after the transfusion of 2 units of packed
red cells. Laboratory investigation revealed no evidence of immune hemolysis, and the patient recovered uneventfully following diuresis. The patient
had received 280 mL of a radiopotentiating agent, misonidazole, immediately
prior to the hemolysis. The drug had been suspended in sterile water, was
markedly hypotonic (118 mosm/L), and completely lysed red cells in vitro.
Other causes of nonimmune hemolysis related to transfusion were ruled
out. Whenever unexplained hemolysis occurs in the absence of immunologic findings, the infusion of hypotonic solutions should be considered as
a cause.
A
34-year-old man underwent an
esophagogastectomy for a malignant gastric neoplasm. As part of the
surgical procedure, radiation was administered to the tumor bed through
the operative site. When the radiation had been almost completely administered, the anesthesiologist noted
that the patient's urine had changed
from yellow to dark red. No free cells
were found in the urine sample, and
a blood specimen revealed bright red
plasma. The patient's vital signs remained stable.
Before the onset of hemoglobinuria
and hemoglobinemia, the patient had
received 2 units of packed red cells
during surgery. Preoperative serologic data were as follows: The patient's blood type was A, Rh positive,
and the direct antiglobulin test (DAT)
was negative using polyspecific antisera. The serum was negative for unexpected antibodies, according to the
37 °C saline and indirect antiglobulin
test, and 8 units of red cells were compatible, as determined by the albumin to indirect antiglobulin phase
crossmatch.
From the Department of Transfusion Medicine, National Institutes of Health, Bethesda, MD 20205.
Diagnosis and Treatment
Planning
In the case reported herein, a presumptive diagnosis of an acute hemolytic transfusion reaction should be
made. The blood bank should be notified, and postreaction samples should
be obtained. Prompt diuresis should
be initiated to prevent renal failure,
which may accompany massive immune red cell destruction. In this case,
the patient was given furosemide and
mannitol, which resulted in brisk diuresis. The patient's vital signs were
closely monitored and remained stable. The surgeon noted no excessive
bleeding or oozing from the operative
sites. Such bleeding would suggest
diffuse i n t r a v a s c u l a r c o a g u l a t i o n
(DIC). The p a t i e n t recovered uneventfully.
An evaluation for evidence of a hemolytic transfusion reaction should be
performed, 1 including a clerical check
of all transfused products. A DAT must
be performed on a postreaction specimen, and the serum/plasma must be
examined for hemolysis; a prereaction sample should be used for comp a r i s o n . If t h e r e is e v i d e n c e of
hemoglobinemia or a positive DAT
282 LABORATORY MEDICINE • VOL. 17, NO. 5, MAY 1986
caused by the transfusion, then additional studies to determine the cause
should be undertaken. To evaluate for
possible i m m u n e - m e d i a t e d hemolysis, an ABO and Rh typing should
be repeated on samples both before and
after the reaction. Screening tests for
unexpected antibodies and donor-recipient compatibility tests should also
be repeated. In the case reported, there
was no indication that a clerical error
had been made, and the post-transfusion DAT was negative. Free hemoglobin, however, was present in the
serum obtained after the reaction; the
results of further serologic tests indicated that this hemoglobinemia was
not immune mediated.
Nonimmune causes of acute intravascular hemolysis should be considered once a clerical error has been
ruled out and there is no evidence of
an i m m u n o h e m a t o l o g i c problem.
Nonimmune hemolysis may be caused
by infusion of hypotonic solution, mechanical trauma to red cells, glucose6-phosphate d e h y d r o g e n a s e deficiency, the heating or freezing of blood,
drugs added to the blood line, and
bacterial c o n t a m i n a t i o n of the infused unit. The patient received no
blood under pressure and was not sustained using a cardiopulmonary bypass m a c h i n e , m a k i n g mechanical
trauma unlikely. The residual blood
in the transfused units was examined
and showed no evidence of hemolysis
or bacterial contamination. No medication had been added to the admini s t r a t i o n line. A r a d i o p o t e n t i a t i n g
agent, misonidazole, had been infused
immediately prior to the intraoperative radiation.
•
M iso nidazole /Water
ion n /
Albumin
III
to n n /
~~**
IUUTO
• - m m
Misonidazole/Saline
Albumin
inn'v
0%
-•100%
Effect of decreasing concentrations of misonidazolel water solution and misonidazolel normal saline solution on red cell hemolysis. Equal volumes of diluent and red cells in each
tube.
In this case, serial blood samples
were obtained from the patient in the
period surrounding the hemolytic episode. The plasma remained clear after
the red cell infusion but turned deep
red immediately following the rapid
infusion (10 minutes) of 280 mL of the
misonidazole solution. Investigation
revealed that the misonidazole had
been suspended in 280 mL of sterile
water prior to infusion. The clear, colorless misonidazole solution had an
osmolarity of 118 mosm/L. Serial dilutions in albumin of misonidazole/
water and misonidazole/normal saline showed that the drug/water combination was clearly hemolytic
(Figure).
Discussion
The sudden appearance of hemoglobinuria and hemoglobinemia in temporal proximity to blood transfusion
during surgery should be regarded as
a hemolytic transfusion reaction until
proved otherwise. In this case, a completely negative serologic evaluation
in a clinically stable p a t i e n t suggested a nonimmune hemolytic
process.
There are several causes of nonimmune red cell destruction. 2 Donor
red cells may be damaged by improper blood administration. Drugs or
other medications added to the blood
line may cause oxidant or osmotic
damage to the red cells as may im-
proper red cell washing or deglycerolyzing techniques. Dilution of the red
cells in solutions other than normal
saline, such as 5% dextrose and water,
also results in osmotic damage. Accordingly, drugs or medications, including those for intravenous (D7) use,
must not be added to blood or blood
components; 0.9% sodium chloride injection, however, may be added to increase t h e volume and facilitate
mixing and administration. 3 Forcing
red cells through a small-bore needle
under high pressure will mechanically lyse the red cells.
Bacterial contamination of the unit
rarely occurs because of the strict adherence to proper aseptic venipunct u r e t e c h n i q u e , as w e l l as t h e
bacteriocidal activity of donor neutrophils in the freshly drawn unit. A
grossly contaminated unit, however,
can c a u s e c a t a s t r o p h i c r e s u l t s if
transfused. The hemolyzed red cells
will cause immediate hemoglobinemia and hemoglobinuria. In addition,
the infusion of bacterial organisms and
endotoxin will produce an immediate
clinical syndrome of "warm" septic
shock, with flushing, fever, hypotension, and DIC, followed by rapid clinical deterioration.
Enzyme deficiencies in donor red
cells may produce nonimmune hemolysis if these cells are exposed to an
oxidant drug present in the recipie n t ' s c i r c u l a t i o n . Glucose-6-phosp h a t e d e h y d r o g e n a s e deficiency,
however, the most common of all red
cell enzyme defects, h a s not been
shown conclusively to cause clinically
significant hemolysis of affected donor red cells upon transfusion. 4
The storage of red cells in unmonitored refrigerators or freezers or the
inappropriate use of blood-warming
devices can cause thermal injury and
resultant hemolysis of donor cells. The
infusion of free hemoglobin from these
units will result in hemoglobinemia
and hemoglobinuria but will rarely
cause clinical problems.
Recipient red cells can be mechanically t r a u m a t i z e d by cardiopulmonary bypass machines or by strong
suction devices attached to red cell
salvage machines. The appearance of
hemoglobinemia in such patients can
be especially confusing, since blood,
IV solutions, and medications are often
administered simultaneously.
In the patient described, investigation revealed that the rapid infusion of a hypotonic solution resulted
in i n t r a v a s c u l a r h e m o l y s i s . T h e
Pharmacy Department had followed
the manufacturer's instructions for
d i l u t i n g t h e d r u g (misonidazole),
which specified the use of either sterile water or normal saline. However,
since misonidazole was being used in
a research protocol that dictated rapid
infusion of a large volume of the diluted drug, normal saline was the only
acceptable diluent.
A hypotonic solution can also accidentally be infused if the solution
containers are mislabeled or if an inappropriate product is selected. Fatalities have been reported with the
inadvertent infusion of large volumes
of distilled water. 6 Whenever unexpected acute hemolysis occurs in a patient with no evidence of an immune
hemolytic process, the infusion of hypotonic solutions should be considered as a cause.
References
1. American Association of Blood Banks: Technical
Manual, ed 9. Arlington, Va, 1985.
2. Davey RJ: Mechanism of premature red cell destruction, in Judd WJ, Barnes A (eds): Clinical
and Serological Aspects of Transfusion Reactions.
Arlington, Va, American Association of Blood
Banks, 1982, pp 18-27,
3. American Association of Blood Banks: Standards
for Blood Banks and Transfusion Services, ed 11.
Arlington, Va, p 31.
4. McCurdy PR, Morse EE: Glucose-6-phosphate dehydrogenase deficiency and blood transfusion. Vox
Sang 1975;28:230.
5. Mollison PL: Blood Transfusion in Clinical Medicine, ed 7. Oxford: Blackwell Scientific Publications, 1983,p 564.
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