Transfusion in

specific
situations Presented by: Reem Eshra
Supervised by: Prof Dr. Nadia
Zaki
1. Autoimmune haemolytic anaemia
2. Sickle cell disease
3. Thalassemias
4. Aplastic Anaemia
5. MDS
6. DIC
 AIHA
Transfusion in patients with AIHA can be challenging.
Autoantibodies to RBCs can result in multiple
incompatible crossmatches, which may lead blood
banks to inform clinicians that no compatible RBC
units are available. If the patient has not been
previously transfused or pregnant, alloantibodies to
non-A BO antigens are unlikely to be present, and
patients can usually be transfused safely with ABO-
compatible blood. Even in patients who have been
previously transfused or pregnant, withholding
transfusions due to incompatible crossmatches may
preclude the administration of lifesaving
transfusions.
Multiply transfused patients with AIHA are at risk of
alloimmunization. Thus, if a patient has received a
transfusion or been pregnant, the transfusion service
must perform specific testing to determine whether
alloantibodies are pre sent concurrently with the
panagglutinating autoantibodies associated with
AIHA. The term panagglutinating refers to the fact
that most autoantibodies that cause AIHA
agglutinate most or all RBCs, including reagent RBCs
and RBCs for transfusion because the antigenic
target is typically an antigen present on the RBCs of
a large proportion of the population. This antigen is
often a common Rh epitope.
The technique for detecting alloantibodies in the presence of
autoantibodies is called adsorption. With the autoadsorption
technique, an aliquot of the patient’s plasma is adsorbed
repeatedly with the patient’s own RBCs. This step removes
autoantibody on the autologous RBCs and leaves any RBC
alloantibody in the plasma. The remaining plasma is then
tested for alloreactivity with a panel of donor RBCs in a
standard antibody screen. The technique is time-intensive,
and results can take several days if the antibody specificity is
unusual. If the patient has under gone transfusion
recently, autoadsorption cannot be reliably interpreted
b ecause the transfused RBCs pres ent in the patient’s
circulation could adsorb the very same alloantibodies
that the laboratory is attempting to detect. In this
situation, a method called differential alloadsorption is used.
Differential alloadsorption, sometimes called triple adsorption,
involves adsorbing aliquots of patient serum against RBCs of
In the clinical case described above, the patient’s
reticulocyte count was low. A substantial minority of
patients manifest at least transient
reticulocytopenia early in the course of AIHA, a
phenomenon that may be due to autoantibody
titers that increase more quickly than the bone
marrow’s reticulocyte response or due to rapid
destruction of reticulocytes by the autoantibody.
Reticulocytopenia with brisk AIHA is an emergency
situation and transfusion should not be
delayed.
Compatibility testing in cold
antibody AIHAs
Compatibility testing in cold antibody AIHAs is less
labour intensive than in warm antibody AIHA. In
cold agglutinin syndrome, the autoantibody does
not often react up to a temperature of 37°C,
whereas clinically significant RBC alloantibodies
will react at this temperature. Accordingly, the
compatibility test can be performed strictly at
37°C .
 SCD

Indications for transfusion in SCD include

● stroke
● acute chest syndrome
● aplastic crisis
● preoperative preparation to reduce the risk of
postoperative respiratory complications and vaso-
occlusive events.

Patients who require chronic transfusion therapy

accumulate iron much less rapidly if the transfusion
occurs in the form of exchange procedures rather than
simple transfusions
Transfusions can be administered as a simple transfusion or as an
exchange transfusion.
The aims of transfusion in SCD are both to increase oxygen-carrying
capacity and to decrease the proportion of sickle hemoglobin
(HbS) relative to hemoglobin A (HbA) to prevent or reverse the
complications of vaso-occlusion.
In the acute situation, simple transfusion will increase oxygen-carrying
capacity but with a risk of hyperviscosity if the Hb is increased to
significantly over the patient’s baseline. Therefore, the target Hb should
be 10 g/dL in patients with homozygous HbS (HbSS).
Exchange transfusion has the advantage of both increasing oxygen
carrying capacity and reducing HbS%. In patients on long-term
transfusion, both repeated simple or exchange transfusion can maintain
a low HbS%, and if HbS% is maintained below 30% to 40%, Hb can
safely be maintained at a higher level with less risk of hyperviscosity.
Simple transfusion is the most common method of transfusion used in
chronic transfusion programs, particularly in children, but at the cost of
high rates of iron loading. Most patients on long-term simple transfusion
will need iron chelation therapy after approximately 1 year of
transfusion, and lack of adherence to iron chelation will result in iron
Exchange transfusions can be performed as a manual
procedure or as an automated procedure using an
apheresis machine. Manual exchanges are performed
using repeated alternating isovolumetric phlebotomy and
blood transfusion.13,14 This can be a useful procedure,
particularly in the acute situation to enable increase in
Hb and oxygen-carrying capacity with concurrent
removal of HbS-containing red cells to prevent
hyperviscosity, but is time-consuming and needs skilled
staff and constant medical supervision during the
procedure
Automated red cell exchange (RCE) is well tolerated in
patients with SCD and results in good control of S%
without increase in viscosity. It is a rapid procedure,
taking only 90 to 120 minutes, and can be performed in
children as young as 5 years and as small as 20 kg. Its
other main advantage is the decreased rate of iron
loading associated with this procedure, with a reduction
of iron loading of ~85% compared with simple
transfusion
Preoperative blood transfusion

Surgery and general anesthesia are associated with an

increased rate of sickle-related complications
The conservative regimen (aiming for Hb 10 g/dL) was as
effective as the aggressive regimen (aiming for Hb of 10 g/dL
and HbS <30%) in preventing perioperative complications,
although alloimmunization was more common in the aggressive
transfusion group.

Patients having high-risk surgery (eg, cardiac or neurologic

surgery) should have preoperative exchange transfusion aiming
for HbS% of ,30%. Similarly, in patients having moderate risk
surgery but a very severe phenotype, exchange transfusion
may be appropriate. In patients with sickle cell hemoglobin
(HbSC), a mild phenotype and Hb. 9 g/dL, it may be appropriate
 APL

Transfusions play a key role in the management of APL

complications.
National Comprehensive Cancer Network (NCCN) goals for
supportive measures include hemoglobin (Hgb) > 8 g/dL,
platelet counts > 50 × 109/L, fibrinogen > 150 mg/dL, and
PT (sec) and PTT (sec) values “close to normal,” 
 DIC

The cornerstone of the treatment of DIC is

treatment of the underlying condition
● Transfusion of platelets or plasma (components) in patients
with DIC should not primarily be based on laboratory results
and should in general be reserved for patients that
present with bleeding.
● In patients with DIC and bleeding or at high risk of bleeding
(e.g. postoperative patients or patients due to undergo an
invasive procedure) and a platelet count of count of <50
x10^9/l, transfusion of platelets should be considered
● In non-bleeding patients with DIC, prophylactic platelet
transfusion is not given unless it is perceived that there is a
high risk of bleeding
● In bleeding patients with DIC and prolonged PT and aPTT
administration of FFP may be useful. It should not however
be instituted based on laboratory tests alone but should be
considered in those with active bleeding and in those
requiring an invasive procedure. There is no evidence that
infusion of plasma stimulates the ongoing activation of
coagulation
● If transfusion of FFP is not possible in patients with bleeding
because of fluid overload, consider using factor concentrates
such as prothrombin complex concentrate, recognising that
these will only partially correct the defect because they
contain only selected factors, whereas in DIC there is a
global deficiency of coagulation factors
● Severe hypofibrinogenaemia (< <1 g/l) that persists despite
FFP replacement may be treated with fibrinogen concentrate
or cryoprecipitate
 MDS

PRBC transfusion remains the mainstay of treatment of

anemia in MDS after failure of erythropoiesis stimulating
agents. The most common transfusion trigger in
transfusion-dependent MDS patients is 8g/dL. 
Transfusion associated circulatory overload (TACO) is the
first fatal complication of transfusion in MDS patients.
Prevention, in this high risk group (older people with
cardiac comorbidities) requires slow transfusion
rates and rigorous monitoring of systolic blood pressure.
Long-term transfusion in low risk MDS patients could also
induce iron overload complications that could be prevent
by iron chelating agents
 Iron overload

●Transfusional Iron overload, is a

condition in which the body receives
iron more than it excretes by repeated
transfusions, causing the mineral to
accumulate in specific areas of the
body with subsequent damage to
various organs.
● Under normal conditions, iron absorption and loss are
balanced at approximately 1 mg/day.
● Transfused blood contains 200-250 mg of iron per unit. Hence,
patients with β-thalassemia major (TM) or other refractory
anemias receiving 2-4 units of blood per month have an
annual intake of 5000-10,000 mg of iron or 0.3 –
0.6mg/kg/day.
● The body has no mechanism for excreting this excess iron.
● Moreover, patients with TM and other anemias characterized
by ineffective erythropoiesis, absorb excess iron despite iron
overload because of production of GDF15 and possibly other
proteins (eg TWSGI) from erythroblasts, which inhibit hepcidin
● In different forms of anaemia, iron overload
occurs when iron intake is increased over a
sustained period of time.
● This may be due either to
○ RBC transfusions, as in thalassaemia major or
transfusion-dependent thalassaemia (TDT), or
○ Increased iron absorption through the GIT,
because of inhibition of hepcidin synthesis by
proteins released from erythroblasts , as in NTDT.
Secondary iron overload:
● May occur in patients transfused for other forms
of inherited and acquired anaemias.
● It may be present in patients after successful
allogeneic bone marrow or HSC transplantation
for various hematological disorders who have
been heavily transfused.
25
Protective mechanisms (Against
iron overload)
• Iron absorption
highly regulated and
minimized
• Iron in cells and
plasma is tightly
bound to proteins
( transferrin,
ferritin, hemoglobin
etc).
26
Preventive mechanisms (Against
iron loss)

• Iron absorption
efficient and tightly
regulated
• Iron loss is minimized

27
• Transferrin binds iron in
blood
-free iron usually not
present
-saturated in iron
overload
• Ferritin surrounds iron in
storage
- elevated in iron overload
– Normal 20 to 300 g/L
28
Iron overload in transfusion-
dependent anemias:
● RBC transfusions lead to Ineffective
erythropoiesis and hemolysis (by stimulating the
body's regulatory mechanisms to inadvertently
increase intestinal absorption of iron.)
● Tissue iron accumulation leads to progressive
dysfunction of the heart, liver and endocrine
glands.
● Tissue iron deposition can begin within 1–2
years, but clinically evident cardiac or hepatic
dysfunction may not occur till 10 or more years
from initiation of transfusion therapy.
● End-organ damage can occur earlier in patients
with other risk factors
 Clinical picture and complications:

● Eventual fibrosis and organ failure

● Cardiac failure
● Liver cirrhosis/fibrosis/cancer
● Diabetes mellitus
● Infertility
● Arthritis

31
 Diagnosis:

● A Combination of Clinical manifestation and

laboratory abnormalities.
● Elevated serum transferrin saturation >45%
(earliest abnormality) and an elevated serum
ferritin.

32
Investigations:

Tests of body iron burden

1- Serum ferritin
Serum ferritin generally relates to body iron stores
and it is relatively inexpensive and easily
measured repeatedly. Serum ferritin is useful in
monitoring changes in body iron, although
measures do not always predict body iron or
trends in body iron accurately.
● This is partly because inflammation increases
serum ferritin, while other factors affect it, such
as vitamin C status, and partly because the
distribution of liver iron between macrophages
(Kupffer cells) and hepatocytes has a major
impact on plasma ferritin.
● A sudden increase in serum ferritin should
prompt a search for hepatitis, other infections, or
inflammatory conditions.
2- Liver iron
Liver iron may be measured chemically after liver biopsy or
by MRI.
Chemical estimation was the gold standard, but can be
inaccurate if fibrosis is present. Levels>7mg/g tissue
dryweight,and in non-transfusion-dependent anaemia
>5mg/g dry weight are almost always associated with organ
damage, while levels<3mg/g are not associated with clinical
complication.
Although no clear guidelines are available with liver iron
between 3–7 mg/g dry weight, the target of chelation
therapy should be to achieve a LIC <3 mg/g dry weight.
LIC
Biopsy MRI
● It is an invasive procedure but in
 It is more widely available and it
experienced hands it has a low
offers noninvasive estimation of LIC.
complication rate .
 MRI scanners generate images of
● Inadequate sample size or uneven
organs in which the signal seen
distribution of iron, particularly in the
depends on iron concentration.
presence of cirrhosis, may give
 T2* is the time needed for the organ
misleading results .
to lose approximately 2/3rd of its
● LIC can also be measured accurately
signal and is measured in
by superconducting quantum
milliseconds (ms).
interference device (SQUID).
 T2* shortens as iron concentration
● However, only 4 such machines are
increases. Its reciprocal, 1000/T2*, is
available worldwide: they are expensive
known as R2* and is measured in
to purchase and maintain, and require
units of inverse seconds (S-1).
dedicated trained staff.
 Sensitivity of > 85% and specificity
● The results correlate well with chemical
of > 92% up to an LIC of 15 mg/g
estimation of LIC unless fibrosis is
dw,
present. 36
37
 Cardiac iron

 Estimation of myocardial iron using T2* MRI requires

expertise in its use and standardization.
 A shortening of myocardial T2* to <20 milliseconds (ms)
(implying increased myocardial iron above normal) is
associated with an increased likelihood of decreased left
ventricular ejection fraction (LVEF) whereas patients with T2*
values >20 ms have a very low likelihood of decreased LVEF .
 T2* values of 10-20 ms indicate a 10% chance of decreased
LVEF.
 Therefore Cardiac T2* identifies those patients at risk of a fall
38 in LVEF whose chelation treatment should be intensified.
 Other measurements:
1. Measurement of non-transferrin bound iron (NTBI) is
carried out only in a few research laboratories.
2. Urine iron excretion after a single dose of a chelator gives
some measure of total iron stores in the case of DFP but not
for DFX or DFO where iron excretion is totally or partly by the
fecal route.
3. Measurement of the degree of saturation of the
plasma iron binding capacity gives a rough idea of iron
burden but is affected by recent iron chelation therapy or
inflammation. Values over100%, however, suggest
inadequate chelation and the need for cardiac39and liver iron
determination.
Transfusion associated anemias
guidelines:
● Estimation of LIC by liver biopsy or imaging is
recommended after 1 year of regular transfusions
to determine the need for iron-chelation therapy.
● Iron chelation is initiated once LIC rises above 3
mg per gm dry weight and is used to maintain
levels between 3-7 mg/gm.
● But no clear-cut guidelines for when to screen and
initiate therapy for iron overload ,Most studies use
40
ferritin >1000 .
41
 combination therapy
DFO and DFP combination therapy
● Urine iron excretion when DFO and DFP are given simultaneously is
equivalent to or greater than the sum of the excretion when the drugs
are given on separate days. There is evidence for a ‘shuttle’ effect in
which DFP enters cells, chelates iron and then returns to plasma,
where the iron is transferred to DFO for excretion in urine or bile and
DFP may re-enter cells.

DFX and DFO combination therapy

● Experience with this drug combination is relatively limited compared
with that of DFO and DFP. Recent prospective studies of combined DFO
and DFX therapy in patients with cardiac iron loading show it is
42 effective at lowering cardiac iron and improving cardiac function as
well as LIC in a follow-up of 2 years.