Human red cell membranes are estimated to
con-tain at least 300 different antigenic determinants, and at least 20
separate blood group antigen sys-tems are known. Fortunately, only the ABO and
the Rh systems are important in the majority of blood transfusions. Individuals
often produce antibodies (alloantibodies) to the alleles they lack within each
system. Such antibodies are responsible for the most serious reactions to
transfusions. Antibodies may occur “naturally” or in response to sensitization
from a previous transfusion or pregnancy.
ABO blood group typing is determined by the pres-ence or absence of A or
B red blood cell (RBC) surface antigens: Type A blood has A RBC antigen, type B
blood has B RBC antigen, type AB blood has both A and B RBC antigens, and type
O blood has neither A nor B RBC antigen present. Almost all individuals not
having A or B antigen “naturally” produce antibodies, mainly immunoglobulin
(Ig) M, against those missing antigens within the first year of life.
Th ere are approximately 46 Rhesus group red cell surface antigens, and
patients with the D Rhesus antigen are considered Rh-positive. Approximately
85% of the white population and 92% of the black population has the D antigen,
and individuals lack-ing this antigen are called Rh-negative. In contrast to
the ABO groups, Rh-negative patients usually develop antibodies against the D
antigen only after an Rh-positive transfusion or with pregnancy, in the
situation of an Rh-negative mother delivering an Rh-positive baby.
Other red cell antigen systems include Lewis, P, Ii, MNS, Kidd, Kell,
Duffy, Lutheran, Xg, Sid, Car-tright, YK, and Chido Rodgers. Fortunately, with
some exceptions (Kell, Kidd, Duffy, and Ss), alloan-tibodies against these
antigens rarely cause serious hemolytic reactions.
The purpose of compatibility testing is to predict and to prevent
antigen–antibody reactions as a result of red cell transfusions.
The most severe transfusion reactions are due
to ABO incompatibility; naturally acquiredantibodies can react against the
transfused (foreign) antigens, activate complement, and result in
intra-vascular hemolysis. The patient’s red cells are tested with serum known
to have antibodies against A and against B to determine blood type. Because of
the almost universal prevalence of natural ABO anti-bodies, confirmation of
blood type is then made by testing the patient’s serum against red cells with a
known antigen type.
The patient’s red cells are also tested with
anti- antibodies to determine Rh status. If the subject is Rh-negative, the presence
of anti-D antibody is checked by mixing the patient’s serum against Rh-positive
red cells. The probability of developing anti-D antibodies after a single
exposure to the Rh antigen is 50–70%.
The purpose of this test is to detect in the
serum thepresence of the antibodies that are most commonly
associated with non-ABO hemolytic reactions.
The test (also known as the indirect Coombs test) requires 45 min and involves
mixing the patient’s serum with red cells of known antigenic composi-tion; if
specific antibodies are present, they will coat the red cell membrane, and
subsequent addition of an antiglobulin antibody results in red cell
aggluti-nation. Antibody screens are routinely done on all donor blood and are
frequently done for a potential recipient instead of a crossmatch (below).
A crossmatch mimics the transfusion: donor
red cells are mixed with recipient serum. Crossmatching serves three functions:
(1) it confirms ABO and Rh typing, (2) it detects antibodies to the other blood
group systems, and (3) it detects antibodies in low titers or those that do not
In the situation of negative antibody screen
without crossmatch, the incidence of serious hemolytic reac-tion with ABO- and
Rh-compatible transfusion is less than 1:10,000. Crossmatching, however,
assures optimal safety and detects the presence of less com-mon antibodies not
usually tested for in a screen. Because of the expense and time involved (45
min), crossmatches are often now performed before the need to transfuse only
when the patient’s antibody screen is positive, when the probability of
transfu-sion is high, or when the patient is considered at risk for
patient is exsanguinating, the urgent need to transfuse may arise prior to
completion of a crossmatch, screen, or even blood typing. If the patient’s
blood type is known, an abbreviated cross-match, requiring less than 5 min,
will confirm ABO compatibility. If the recipient’s blood
type and Rhstatus is not known with certainty and transfu-sion must be started
before determination, typeRh-negative (universal donor) red cells may be used.
Blood donors are screened to exclude medical
con-ditions that might adversely affect the donor or the recipient. Once the
blood is collected, it is typed, screened for antibodies, and tested for
hepatitis B, hepatitis C, syphilis, and human immunodeficiency virus (HIV). A
preservative–anticoagulant solu-tion is added. The most commonly used solution
is CPDA-1, which contains citrateasan anticoagulant(by binding calcium), phosphate
as a buffer, dex-trose as a red cell energy source, and adenosine asprecursor
for adenosine triphosphate (ATP) syn-thesis. CPDA-1-preserved blood can be
stored for 35 days, after which the viability of the red cells rapidly
decreases. Alternatively, use of either AS-1 (Adsol) or AS-3 (Nutrice) extends
the shelf-life to 6 weeks.
Nearly all units collected are separated into their component parts (ie,
red cells, platelets, and plasma). In other words, whole blood units are rarely
available for transfusion in civilian practice. When centrifuged, one unit of
whole blood yields approxi-mately 250 mL of packed red blood cells (PRBCs) with
a hematocrit of 70%; following the addition of saline preservative, the volume
of a unit of PRBCs often reaches 350 mL. Red cells are normally stored at 1–6°C, but may be frozen in a
hypertonic glyc-erol solution for up to 10 years. The latter technique is
usually reserved for storage of blood with rare phenotypes.
The supernatant is centrifuged to yield
platelets and plasma. The unit of platelets obtained generally contains 50–70
mL of plasma and can be stored at 20–24°C for 5 days. The remaining plasma
super-natant is further processed and frozen to yield fresh frozen plasma;
rapid freezing helps prevent inac-tivation of labile coagulation factors (V and
VIII). Slow thawing of fresh frozen plasma yields a gelati-nous precipitate
(cryoprecipitate) that contains high concentrations of factor VIII and
fibrinogen. Once separated, this cryoprecipitate can be refrozen for storage.
One unit of blood yields about 200 mL of plasma, which is frozen for storage;
once thawed, it must be transfused within 24 h. Most platelets are now obtained
from donors by apheresis, and a single platelet apheresis unit is equivalent to
the amount of platelets derived from 6–8 units of whole blood. The use of
blood products has been rapidly adopted by many countries, including the United
States, in order to decrease the risk of transfusion-related febrile reac-tions,
infections, and immunosuppression.
Blood transfusions should be given as PRBCs, which allows optimal
utilization of blood bank resources. Surgical patients require volume as well
as red cells, and crystalloid or colloid can be infused simultane-ously through
a second intravenous line for volume replacement.
Prior to transfusion, each unit should be
care-fully checked against the blood bank slip and the recipient’s identity
bracelet. The transfusion tubing should contain a 170-µm filter to trap any clots or debris. Blood for intraoperative
transfusion should be warmed to 37°C during infusion, particularly when more than 2–3 units will be
transfused; failure to do so can result in profound hypothermia. The additive
effects of hypothermia and the typically low levels of 2,3-diphosphoglycerate
(2,3-DPG) in stored blood can cause a marked leftward shift of the
hemo-globin–oxygen dissociation curve
and, at least theoretically, promote tissue hypoxia.
Fresh frozen plasma (FFP) contains all plasma proteins, including most
clotting factors. Transfu-sions of FFP are indicated in the treatment of
iso-lated factor deficiencies, the reversal of warfarin therapy, and the
correction of coagulopathy asso-ciated with liver disease. Each unit of FFP
gener-ally increases the level of each clotting factor by 2–3% in adults. The
initial therapeutic dose is usu-ally 10–15 mL/kg. The goal is to achieve 30% of
the normal coagulation factor concentration.
FFP may also be used in patients who have received massive blood
transfusions and continue to bleed
following platelet transfusions. Patients with
antithrombin III deficiency or throm-botic thrombocytopenic purpura also
benefit from FFP transfusions. Each unit of FFP carries the same infectious
risk as a unit of whole blood. In addition, occasional patients may become
sensitized to plasma proteins. ABO-compatible units should generally be given
but are not mandatory. As with red cells, FFP should generally be warmed to
37°C prior to transfusion.
Platelet transfusions should be given to patients with thrombocytopenia
or dysfunctional platelets in the presence of bleeding. Prophylactic plate-let
transfusions are also indicated in patients with platelet counts below
10,000–20,000 × 109/L because
of an increased risk of spontaneous hemorrhage.
Platelet counts less than 50,000 × 109/L are associated with increased blood loss during surgery.
Thrombocytopenic patients often receive prophylac-tic platelet transfusions
prior to surgery or invasive procedures. Vaginal delivery and minor surgical
pro-cedures may be performed in patients with normal platelet function and
counts greater than 50,000 × 109/L.
Administration of a single unit of platelets may be expected to increase the
platelet count by 5000– 10,000 × 109/L,
and with administration of a platelet apheresis unit, by 30,000–60,000 × 109/L.
ABO-compatible platelet transfusions are
desir-able but not necessary. Transfused platelets gener-ally survive only 1–7
days following transfusion. ABO compatibility may increase platelet survival.
Rh sensitization can occur in Rh-negative recipients due to the presence of a
few red cells in Rh-positive platelet units. Moreover, anti-A or anti-B
antibod-ies in the 70 mL of plasma in each platelet unit can cause a hemolytic
reaction against the recipient’s red cells when a large number of
ABO-incompatible platelet units is given. Administration of Rh immu-noglobulin
to Rh-negative individuals can protect against Rh sensitization following
Rh-positive plate-let transfusions.
Granulocyte transfusions, prepared by leukapher-esis, may be indicated
in neutropenic patients with bacterial infections not responding to
antibiotics. Transfused granulocytes have a very short circu-latory life span,
so that daily transfusions of 1010granulocytes
are usually required. Irradiation ofthese units decreases the incidence of
graft-versus-host reactions, pulmonary endothelial damage, and other problems
associated with transfusion of leu-kocytes , but may adversely affect
gran-ulocyte function. The availability of granulocyte colony-stimulating
factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF)
has greatly reduced the use of granulocyte transfusions.
Blood products can be misused in surgical
settings. Use of a transfusion algorithm, particularly for com-ponents such as
plasma, platelets, and cryoprecipi-tate, and particularly when the algorithm is
guided by appropriate laboratory testing, will reduce unnec-essary transfusion
of these precious (but dangerous) resources . Derived from military experience,
there is a trend in major trauma care towards transfusing blood products in
equal ratios early in resuscitation in order to preempt or cor-rect
trauma-induced coagulopathy. This balanced approach to transfusion of blood
products, 1:1:1 (one unit of FFP and one unit of platelets with each unit of
PRBCs) is termed damage control resuscita-tion .