Transcript Salwa Hindawi MSc, MRCPath, CTM Medical Director of Blood

Salwa Hindawi
Guidelines and Updates in Blood
Transfusion for ß -Thalassemia
Patients
Salwa Hindawi
MSc, MRCPath, CTM
Medical Director of Blood Transfusion Services
KAUH, Jeddah
KSA
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Introduction
Transfusion is the mainstay of the care of
individuals with thalassemia major.
The purpose of transfusion is to improve the
anemia and to suppress the ineffective
erythropoiesis.
Chronic transfusions prevent most of the
serious growth, skeletal, and neurological
complications of thalassemia major.
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Introduction
The decision to start transfusions is based on inability to
compensate for the low hemoglobin
signs of increased cardiac effort, tachycardia, sweating,
poor feeding, and poor growth due to increasing
symptoms of ineffective erythropoiesis : bone changes,
massive splenomegaly.
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Guidelines
Schedule transfusions at three to four week
intervals to maintain hemoglobin level greater
than or equal to 9-9.5 gm/dl prior to the next
transfusion.
Evaluate hemoglobin prior to each transfusion, If
the pre-transfusion hemoglobin is less than 9.0
gm/dl, the patient may need more frequent (every
two to three weeks) transfusions or increased
volume of transfusion.
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Guidelines
Perform extended red cell phenotyping prior to
initiating the transfusion regime.
The use of phenotypically matched blood products,
from the beginning of chronic transfusion, can
prevent most cases of alloimmunization.
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• DONE ON FIRST SAMPLE
• DONE ON THE RETICS
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Guidelines
The decision to start regular transfusions depends on
clinical and laboratory assessment:
worsening anemia, inability to tolerate anemia, massive
splenomegaly worsening bone disease, increasing
nucleated red blood cells and dropping hemoglobin.
Skeletal malformation can be severe in thalassemia
intermedia and should be considered in the decision to
start transfusion.
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Guidelines
Assess spleen size at each visit, splenomegaly could
account for increased blood requirement.
Calculate all blood given to the patient (total cc’s) and
divided by an average weight over the past 6 months
(cc / kg / year).
If transfusion requirement is greater than 200 cc / kg /
year, the cause for such a high transfusion requirement
should be explored.
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splenectomy
In the face of marked splenomegaly or other evidence
of significant hypersplenism
(leukopenia, thrombocytopenia).
splenic embolization, splenectomy or partial
splenectomy may be considered.
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Splenectomy
Splenectomy is generally not recommended for
thalassemia patients because of the risk of the
complications.
Splenectomy is associated with significant risk of
serious short and long term complications Infectious,
pulmonary, hepatic, and thrombotic.
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Splenectomy
Pre splenectomy:
Vaccination
Obtain pneumococcal IgG titers. If the titers are
inadequate, immunize to maximize coverage of all
serotypes (7-valent conjugate vaccine recommended
in children under five years (Prevnar)
23 valent (Pneumovax) as a booster at five years of age
or later. Reimmunize patients with inadequate IgG
responses.
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Splenectomy
Post splenectomy:
-Monitor the platelet count and treat with an antiplatelet aggregate (low dose Aspirin) if platelet
count is 1 x 106 or greater.
-Consider chronic low dose anticoagulation
(coumadin) or anti-platelet agent (aspirin) in older
splenectomized patients reduce the risk of
pulmonary thrombotic events and pulmonary
hypertension.
-All post splenectomy thalassemia patients require
treatment with prophylactic penicillin.
-Intensive family education should be provided.
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Iron Overload
Regular blood transfusion can lead to Iron overload.
Serum iron & ferritin, TIBC, and/or liver Iron.
Chelation should be considered after one to two years
of transfusion therapy, when the serum ferritin is
greater than 1000 ng/dL, or when the hepatic iron is
approximately 7 mg /gram dry weight
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Determination of liver iron by biopsy is recommended
prior to initiation of desferrioxamine therapy as well
as every 12 to 24 months (or as clinically indicated).
Though not routinely available, liver iron can be also
determined by ferritometry (SQUID).
Evaluate ferritin level quarterly.
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CHRONIC IRON OVERLOAD
):
Desferrioxamine Toxicity
TOXICITY
Hearing Loss
Blindness
Growth Failure
Optimal Hepatic Iron Level
Risk of Endocrine
Complications
Risk of Cardiovascular
Complications
HEPATIC IRON
< 3 mg/g dry wt
4 to 7.5 mg/g dry wt
Diabetes Mellitus
Hypogonadism
Hypoparathyroidism
Cirrhosis
Cardiomyopathy
Dysrythmia
7.5 to 15mg/g dry wt
> 10 mg / g dry weight
> 15 mg/g dry wt.
Olivieri and Brittenham Blood 89:3,1997,739-761
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Alloimmunization
The factors which contributing to
alloimmunization :
1-The RBC antigenic difference between the blood
donor and the recipient.
2-the recipient's immune status.
3-the immunomodulatory effect of the allogeneic blood
transfusions on the recipient's immune system.
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ALLOANTIBODIES AND
AUTOANTIBODIES
If an autoantibody or/and alloantibody is detected, the
specific antibodies causing the
transfusion reaction should be determined by the blood
bank or by a reference laboratory.
The use of blood matched by extended antigen is usually
indicated. Other treatment modalities, as steroids or
immunosuppressive agents may be considered as well.
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ALLOANTIBODIES AND
AUTOANTIBODIES
Autoimmunization or alloimmunization should be
considered if the hemoglobin is less
than 9.0-9.5 gm/dl or is significantly less than usual for
the particular patient prior to the
transfusion on two occasions.
Hemoglobin level and direct and indirect Coombs test
should be determined 24 to72 hours after the
transfusion.
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antibodies screening and identification
Perform antibodies screening test (all patients &
donors ) Using 3 cells panel screening cells
If antibody screening negative -NAD
If antibodies screening positive do antibody
identification and autocontrol
PANEL CELLS POS AUTOCONTROL NEG
PANEL CELLS POS AUTOCONTROL POS
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REAGENT CELL PANEL POS
AUTO CONTROL NEG
SOME CELLS NEG 
SOME CELLS POS ( SAME STRENGTH & PHASES )
Suspect Single Antibody

Test other selected cells to eliminate other specificities 
Test the patient cell to confirm they lack antigen ( phenotyping )
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
REAGENT CELL PANEL POS
AUTO CONTROL NEG

SOME CELLS NEG
SOME CELLS POS ( DIFFERENT STRENGTH & OR PHASES )
Suspect Multiple Antibody

ALL CELLS POS ( DIFFERENT STRENGTH & OR PHASES )
Suspect Multiple Antibody


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Multiple antibodies identification:
Test selected cells to confirm and eliminate other
specificities
Extended panel ( 15 or 20 cells panel )
You may need another technique ( enzyme )
Test the patient cell to confirm they lack antigen (
phenotyping )
May need help from reference laboratory for
identification and confirmation
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Mangement
Compatible blood
Frozen –deglycerated rbcs
Least incompatible blood
*balanced decision
*avoid the strong immunogenic Ags
*premeditations ,initial slow infusion
*close monitoring and follow haemolysis indices
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Other options:
IvIg
Corticosteroids
Splenectomy
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-Use of hydroxyurea & Erthropiotin.
Blood May,2003.
-Use of 2units collection through Apheresis from
specific volunteer Donor.
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Hydroxyurea
The use of hydroxyurea may eliminate the need for
future blood transfusions in children with betathalassemia major
administration of hydroxyurea to patients with severe
forms of beta-thalassemia would result in production
of fetal hemoglobin.
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WASHINGTON, DC - Blood August 12, 2003
Singer ST; Wu V; Mignacca R; Kuypers FA; Morel P;
Vichinsky EP
Department of Hematology/Oncology at the Children's Hospital Oakland,
California, USA
64 transfused thalassemia patients (75% Asian) were evaluated.
14 (22%) of 64 patients became alloimmunized. K, c, S, and Fyb
accounts for 38% of the alloantibodies among Asian patients.
Patients who had a splenectomy had a higher rate of
alloimmunization than patients who did not have a splenectomy
36% vs 12.8%.
Erythrocyte autoantibodies developed in 25% or 16 of the 64
patients.
Transfusion of phenotypically matched blood for the Rh and Kell
proved to be effective in preventing alloimmunization
Blood. 2000; 96(10):3369-73
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Frequency of irregular red cell alloantibodies in
patients with thalassemia major: a bicenter
study
study conducted at two centers from January to December 2001 a
total of 97 patients were included in the study.
Alloantibodies were found in 9 (9.2%). Mean age of patients who
developed red cell alloantibody was 11.9 years. Three (33.3%)
patients developed anti-K while two (22.2%) had non-specific
antibody.
One patient developed anti-D (11.1%) and anti-E (11.1%). Two had
anti-D (11.1%) and anti-C while the other one (11.1%) developed
anti-E and anti-K.
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Dec;55(12):563-5 2005J Pak Med Assoc
CONCLUSION
1-There is relatively high rate of
alloimmunization in their patients when
compared to data from the region.
2- Red cell alloimmunization should not be
overlooked in patients receiving regular
blood transfusions.
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BONE MARROW
TRANSPLANTATION
Bone marrow transplantation is the only cure for
thalassemia patients.
It should be considered in all patients who have an
acceptable donor.
Patients are classified on the basis of
their risk factors which include:
inadequate chelation, presence of liver fibrosis and
hepatomegaly.
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Recommendations
1) Extended rbc phenotyping
Perform extended red cell phenotyping prior
to initiating the transfusion regime.
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2) Red cell matching.
Select ABO matched red cell units, which are K
negative and matched for the common Rh
antigens (D, C, E, c, e).
If clinically significant red cell antibodies are
present, select antigen negative units and
issue blood compatible in the crossmatch by
IAT.
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3) Leucodepletion.
i) Bedside filtered red cells is not used routinely
nowadays.
ii) Pre-storage Leucodepletion
Leucodepleted red cells (WBC <5 x 106 per unit)
following filtration at the blood transfusion services
(at source) are recommended.
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4) Age of the red cell units
Ideally, the red cell units selected for
transfusion dependent patients should be
less than 2 weeks old to ensure maximum
possible survival in the recipient’s circulation
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5)Encourage central blood bank
With regular phenotype donors
Frozen blood
Frozen rare panel cell
6)Cooperation between Hospitals.
7)The use of new oral iron chelator for the
treatment of iron overload.
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