A transfusion reaction is any unfavorable event occurring in a
patient during or following transfusion of blood products that can be related
to that transfusion. Since compatibility testing is performed for the detection
of antibodies to red blood cell antigens, adverse effects of transfusion are
most commonly caused by leukocytes, platelets and plasma proteins. In addition,
every transfusion carries a risk of alloimunization as well as transmission of
disease.
Major groups of transfusion reactions
I. Immediate Transfusion Reaction
A.
Non–immunologic complications
1.
Circulatory overload
Sudden increase in circulating
blood volume are not well–tolerated by certain patients particularly patients
with cardiac pulmonary disease, very anemic patients or infants. Whole blood
transfusion in these patients may cause dyspnea, coughing, pulmonary edema and
cyanosis. If these symptoms develop, the transfusion should be stopped and
treatment for circulatory overload instituted. If the transfusion has to be
continued, patients with severe anemia should be transfused with concentrated
red cells at a rate no faster than 70 – 100 ml/hr.
2.
Hypothermia
Hypothermia can result from the
rapid (more than 100 ml/minute) transfusion of refrigerated blood. Large
volumes of rapidly infused cold blood can lower the temperature of the
sinoatrial node to below 30oC at which point ventricular arrhythmias
occur.
Warming blood during massive
transfusion can avoid the adverse effects of hypothermia, such as cardiac
arrhythmia and enhance the body’s homeostatic mechanisms, which is being
stressed. Warming of blood must be carefully controlled and should slow the
rate of infusion significantly.
3.
Bacterial contamination
Bacteria may cause transfusion
reaction in two ways: by producing febrile reactions due to pyrogens and
toxins which are breakdown products of bacteria; or by causing serious, often
fetal reactions, when the donor blood is contaminated with large
numbers of living organisms. Even when the best possible precautions
are taken during collections, it has been reported that approximately 2% of
units are contaminated at the time of collection. Fortunately, most of these
organisms do not survive the bactericidal action of the fresh donor blood
stored at 4oC.
Septic reactions are often caused
by psychrophilic organisms, that is, those capable of growing at low
temperatures, e.g. Pseudomonas, Coliforms and Achromobacters. They are usually
endotoxin–producing gram negative bacilli that can metabolize citrate as a sole
source of carbon.
Contamination of the blood with
bacteria may be grossly obvious, as the supernatant plasma may be dark brown or
red and the cells may be obviously discolored. However, the infected blood may
look normal both macroscopically and microscopically. Platelets stored at room
temperature have been reported to cause bacterial sepsis following transfusion.
When bacterial contamination is suspected, microscopic examination and culture
of donor blood is indicated. When infected blood is transfused, symptoms appear
quickly (10–30 minutes): chills, headache, vomiting, muscle pain, diarrhea and
high fever. Prompt, energetic treatment is required.
Room temperature storage of
platelet concentrates may increase the risk of significant bacterial growth.
When fever and chills complicated transfusion of platelet which have been
stored at room temperatures, contamination must be considered and investigated.
B.
Immunologic complications
1.
Febrile non–hemolytic reactions
This is due to cytotoxic
antibodies or leukoagglutinins (leukocyte antibodies). If these antibodies are
present in the recipient’s plasma, a reaction occurs between the antibodies and
the antigens present on the cell membrane of transfused leukocytes or platelets
Non–specific leukoagglutinins, as
well as those of HLA origin have been implicated in febrile reactions.
Leukoagglutinins have also been implicated in a specific type of delayed
reaction referred to as non– cardiac pulmonary edema syndrome.
The most common symptom is fever,
often accompanied by chills, which begins during or soon after transfusion.
With or without documentation of the existence of specific antibodies, the use
of leukocyte poor preparations is recommended only after a patient has had two
or more febrile non–hemolytic reactions.
2.
Anaphylactic reactions
Anaphylactic reactions occur in
IgA deficient patients who have developed anti–IgA antibodies. Patients lacking
the IgA have an increased risk of forming anti–IgA antibodies. Anti–IgA
antibody formation can result from immunization due to previous transfusion or
pregnancy.
Other potential cause of
anaphylactic reaction is the presence of antibodies to soluble plasma antigens
or to drugs contained in transfused blood such as penicillin.
Symptoms include nausea,
abdominal cramps, emesis and diarrhea. Transient hypertension is followed by
hypotension. Shock and loss of consciousness follows. Symptoms become obvious
after the infusion of only a few millimeter of blood or plasma and fever is
absent. These reactions can be prevented only use of blood preferably from
donors lacking IgA or rendered free of IgA by thorough washing.
3.
Urticarial – non–specific
allergic reactions
Allergic reactions are the second
most common type of transfusion reaction. When the reaction is extensive or
produces edema, it is referred to as anaphylactoid.
Allergic reactions are manifested
by urticaria (hives) due to histamine release of mast cells, itching and local
erythema but usually no fever. If the cutaneous reaction is extensive or
produces oral, pharyngeal or laryngeal edema, it is known as anaphylactoid
reaction.
Reactions can be well controlled
with anti–histamines. In repeated or severe reactions, washed or deglycerolized
frozen erythrocytes are recommended.
4.
Hemolytic transfusion reaction
Immune hemolysis is usually the
result of a reaction between an antibody in the recipient’s plasma and the red
cells of the donor. Occasionally, it may be the antibody in the donor’s plasma
that reacts with the recipient’s red cells. The red cell destruction may be intravascular,
where the red cells are hemolyzed directly in the blood stream, by the action
of antibody and complement, leading to the release of hemoglobin and other
portions of the red cell into the plasma (e.g. ABO) or extravascular,
when the red cells, after reactions with antibody, are removed by the reticuloendothelial
system. This leads to hyperbilirubinemia but there is little or no release of
hemoglobin into the plasma (e.g., Rho, Kell)
The clinical sign signaling
hemolytic transfusion reaction will vary according to what type of destruction
is involved. Intravascular hemolysis is accompanied by the
immediate clinical signs associated with the substances released by the action of
complement (e.g. histamine). There may be feeling of heat along the vein into
which the blood is being transfused, flushing of the face, pain the chest or
lumbar region, nausea and vomiting; vascular hemolysis may not be so dramatic;
it may be manifested only as chills and fever several hours after the
transfusion. In anesthetized patient, the only sign of a reaction may be an
unexplained increase in pulse or increased bleeding.
Hemoglobinemia and hemoglobinuria
may occur and severely affected patients can have complete renal shutdown. The
acute renal failure is due primarily to low renal blood flow, which seems to be
related to the antigen–antibody reaction and shock. Acute hemorrhagic diathesis
often can be an outcome of a hemolytic transfusion reaction. It may be the only
sign of such a reaction if the patient is anesthetized. Hemolysis may indicate
disseminated intravascular clotting leading to the consumption of coagulation
factors and fibrinolysis. Massive transfusions may also lead to bleeding by depletion
of platelets and dilution of coagulation factors. Since the early signs of
hemolytic reaction may be the same as those as febrile non–hemolytic reactions,
chills and fever, etc. blood infusion should be stopped if the signs appear and
investigation begins.
II. Delayed Transfusion Reaction
A.
Non–immunologic complications
1.
Iron overload
Hemosiderosis or hypersiderosis is a condition wherein a heavy
deposition of iron occurs due to hemoglobin breakdown. Patients at risk of iron
overload include those with hemoglobinopathies such as thalassemia and aplastic
or sideroblastic anemias. Every unit of erythrocytes contains approximately 250
mg of iron. Jaundice or cardiac dysfunction represents manifestations of this
condition. A recent approach to reducing the risk of transfusion–induced iron
overload is transfusion with erythrocytes that have been enriched with young
erythrocytes, neocytes. Neocytes survive longer in the
circulation and result in a greater interval between transfusions, with
subsequent reduction in the total iron infused over an extended period of time.
2.
Infections
a.
Cytomegalovirus
It is associated with
post–transfusion mononucleosis. The classical congenital cytomegalovirus
syndrome is manifested by a high incidence of neurologic symptoms such as
psychomotor, retardation and hearing loss. Occasionally, self–limited, heterophile
negative mononucleosis–like syndrome occurs. The symptoms include sore throat
and fever, chills, profound malaise and myalgia. Lymphadenopathy and splenomegaly
may be observed.
b.
Syphilis
The etiologic agent of syphilis,
Treponema pallidium is a thin, spiral– shaped bacterium which is acquired by
venereal route. It has a short survival in stored blood (spirochetes do not
appear to survive in citrated blood at 4oC for more than 72 hours).
T. pallidium is more likely to be present in the blood during the secondary
stage of syphilis, with symptoms of fever, skin rash and lymphadenopathy.
c.
Malaria
Malaria can be transmitted by the
transfusion of whole blood, packed red cells, platelets, concentrates or other
blood components which contain red blood cells. It is transmitted by any of the
four Plasmodium species. It has a life cycle both found in human
and Anopheles mosquito. It produces chills followed by a fever in a few hours.
A patient’s temperature may rise to 104oF or 105oF. The
symptoms last from 4 to 6 hours and seen at regular intervals depending on the
type of malaria. To prevent transfusion–induced malaria, chloroquine
prophylaxis is given routinely to all blood recipients.
d.
Post–transfusion hepatitis
Transmission of hepatitis virus
from donor blood to a recipient constitutes at the present time the most common
and serious problem of transfusion practice. Components such as platelets, AHF
cryoprecipitate, AHF concentrates, plasma and fibrinogen may be responsible for
hepatitis transmission with the risk proportional to the number of donors
involved.
The incidence of hepatitis virus
carrier state in the blood donors is generally higher in commercial blood donor
than in voluntary blood donors. High morbidity and mortality result from post–transfusion
“serum” hepatitis caused by hepatitis B virus with an incubation period of 50–180
days. Transmission of hepatitis A virus causes “infectious” hepatitis within a short
incubation period of 15–50 days. Frequently, it is difficult to distinguish
between these two types of viral hepatitis. The discovery of Australian antigen
and its association with post–transfusion “serum” hepatitis has provided a
laboratory means of detecting the infectious blood.
B.
Immunologic complications
1.
Graft versus host disease
When immunocompentent lymphocytes
are transfused from a donor to a recipient who is not capable of rejecting
them, the transfused or grafted lymphocytes recognize the antigen of the host
as foreign and react immunologically against them. Instead of the usual
transplantation reaction of host against graft, the reverse graft versus host
reaction occurs and produces an inflammatory response.
In a normal lymphocyte transfer
reaction, the results of a graft versus host are usually not serious because
the recipient is capable of destroying the foreign lymphocytes. If the
recipient, however, cannot reject the transfused lymphocytes, the may cause
uncontrollable destruction of the host’s tissues and eventually death.
Post–transfusion symptoms begin
within 3 to 30 days of transfusion. Because of lymphocytic infiltration of the
intestine, skin and liver, mucosal destruction including ulcerative skin and
mouth lesions, diarrhea and liver necrosis occur. Other clinical signs include
jaundice, fever, anemia, weight loss, skin rash and splenomegaly.
2.
Acquired Immunodeficiency
Syndrome
There is no question as to the
infectivity of blood and components from individuals infected with HIV.
Recipients have developed AIDS after receiving a single contaminated unit of
whole on any of its components. Derivatives from human blood such as albumin
and immune globulin have not been reported to transmit HIV infection.
The mea incubation period between
the time of transfusion and diagnosis of AIDS has been estimated to be 4–5
years. This long incubation and a high mortality among transfusion recipients
(approximately 50% within six months) makes it difficult to determine the
actual risk in transfusion associated with AIDS.
3.
Hemolytic Transfusion Reaction
Delayed hemolytic transfusion
reactions can occur from two days to several months post–transfusion. This type
of hemolytic reaction is under –diagnosed, under–reported and under–rated in
terms of complications, and is far more frequent than the acute hemolytic
reactions.
It maybe of two types. They may
represent anamnestic antibody response in a previously immunized recipient or
secondary exposure to transfused erythrocytic antigens or result from primary
alloimmunization. In an anamnestic response, the antibodies are to antigens to
which recipients have been previously immunized by a transfusion or pregnancy.
Antibodies implicated are anti–E,
anti–C, anti–M, anti–Lua, anti–K, anti– Ce, anti–Jka,
anti–Jkb, anti–k, anti–Fya, anti–Cob.
The most common clinical sign is
fever. The triad anemia, fever and recent transfusion suggests a delayed
hemolytic reaction, symptoms can range from an asymptomatic state to oliguria
or renal shutdown.
Some of the signs and symptoms that may
accompany hemolytic transfusion reaction:
1.
Fever
2.
Chills
3.
Chest pains
4.
Hypotension
5.
Hemoglobinuria
6.
Nausea
7.
Dyspnea
8.
Flushing
9.
Shock
****** INVESTIGATION OF TRANSFUSION REACTION ******
I. Specimen needed
A.
Post–transfusion of blood of recipient which
should be obtained immediately
1.
Clotted blood specimen – for crossmatching,
re–typing
2.
Oxalated blood specimen – for detection of
hemolysis, free hemoglobin and direct Coomb’s test
B.
Post – transfusion urine specimen
1.
1st hour urine – obtained
immediately to compare with 5th hour urine for the presence of free
hemoglobin which usually develops on the 5th hour if there is
hemolysis.
2.
5th hour urine
C.
Donor unit – implicated in the transfusion
reaction to re–check the donor’s type, Rh and re–crossmatching with the patients
pre and post–transfusion samples.
D.
Blood transfusion reaction report – properly
filled up by the nursing staff and the resident in the ward.
II. Procedure
A.
Recheck all identification data on the blood
specimen and urine unit.
B.
Check the physical appearance of the blood
and urine specimen of the patient as well as the donor unit for hemolysis (free
hemoglobin)
C.
Repeat typing, Rh of patients’ blood sample
previously taken before transfusion.
D.
Repeat ABO typing, Rh typing, crossmatching
of both patients post – transfusion blood sample and donor’s blood sample.
E.
Repeat Coomb’s test of recipient and donor.
F.
Culture and gram’s stain of donor’s blood
specimen – to know if there was a bacterial contamination. Observe for bubbles
in the donor unit or if there is a change of color of the cells and plasma.
III. Follow up procedure
A.
Examine post–transfusion urine, 1st
hour and 5th hour, for the presence of free hemoglobin.
B.
Test serum sample for levels of unconjugated
bilirubin at intervals after the reaction.
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