overview of recommended blood transfusion therapy in thalassaemia major professor john porter red...

Overview of recommended Blood Transfusion Therapy

in Thalassaemia Major

Professor John PorterRed Cell Disorders UnitUniversity College London Hospitals and UCL [email protected]

Outline

• Goals of transfusion• Basic requirements

– Blood products for transfusion– Blood storage– Donor selection and sample testing– Compatibility testing

• Adverse reactions– Alloimunisation and other adverse reactions– Minimising infection and non-infection risks– Future approaches to reducing infection risk

• Recommended transfusion regime – Optimise

• Oxygen carriage• Supression of IE

– Minimise - Iron loading

Goals of transfusion

• Maintenance of red cell viability and function during storage, to ensure sufficient transport of oxygen

• Use of donor erythrocytes with a normal recovery and half-life in the recipient

• Achievement of appropriate haemoglobin level– To minimise effects of anaemia and ineffective

erythropiesis while minimising iron overload

• Avoidance of adverse reactions, including transmission of infectious agents.

Outline

• Goals of transfusion• Basic requirements



• Recommended transfusion regime – Optimise



Blood Products for Transfusion

• Leuco-reduced packed red cells recommended• reduction of leucocytes to 5 X 106 • critical threshold for eliminating adverse reactions attributed to contaminating white cells and

for preventing platelet alloimmunisation [Sprogoe-Jakobsen 1995]

• Methods for leucoreduction include:– Pre-storage filtration of whole blood

• carried out with an in-line filter within eight hours after blood collection. • the delay in filtration may allow some phagocytosis of bacteria (e.g. Yersinia enterocolitica)

[Buchholz 1992]. • high efficiency filtration , consistently low residual leucocytes in the processed RBC• high red cell recovery• ‘Packed’ red cells are obtained by centrifugation of the leucoreduced whole blood

– Pre-transfusion, laboratory filtration: • Packed RBC prepared from donor whole blood then filtered prior to release from blood bank

– Bedside filtration: • packed red cell unit is filtered at the bedside. • may not allow optimal quality control

Blood products for special patient populations

• Washed red cells – may be beneficial for repeated severe allergic transfusion reactions. – Saline washing removes plasma proteins in the donor product that are the target for

antibodies in the recipient. – Other clinical states that may require washed red cell products include immunoglobulin A

(IgA) deficiency, in which the recipient’s preformed antibody to IgA may result in an anaphylactic reaction.

– Washing usually does not result in adequate leucocyte reduction and therefore should be used in conjunction with filtration.

• Frozen red cells – used to maintain a supply of rare donor units for certain patients who have unusual red

cell antibodies of who are missing common red cell antigens. – The Council of Europe is promoting an international network of rare blood donor units

• Neocyte or young red cell transfusion – may modestly reduce blood requirements. However, patients are exposed to a higher

number of donors

Storage of donor red cell units

• Nutrient additives AS-1 & AS-3 has permitted storage of red cells for up to 42 days

• Post-transfusion recovery is 73-83% after maximal storage. • High levels of ATP are maintained up to the 28th day of

storage• 2,3-DPG levels and P50 values may not be fully maintained. • Little is known about the red cell half-life in the recipient after

prolonged storage of donor blood. • Decreased recovery and a shortened half-life may increase

transfusion requirements and the rate of iron loading. • So …….. the current recommended practice is to use red cells

stored in additive solutions for <2 weeks.

Are the guidleines about age of transfused red cells in line with the evidence?

• Effectiveness and survival of RBC– Neocyte transfusion reduces blood requirement in Thal Major– Effect of storage on RBC function and survival

• Safety – Increased risk of alloimunisation ? (hendrickson)– Increased bacterial infection risk in stored blood? (Hogman, 1999)

(McDonald, 1996)– Increased toxic iron formation and inflammation (hod)– Indirect evidence about morbidity and mortality for major operations

Dzik, W. (2008). "Fresh blood for everyone?.Almac, E. and C. Ince (2007). "The impact of storage on red cell function in blood transfusion." Best practice & research. Clinical anaesthesiology 21(2): 195-208.

By how much does the transfusion of young red cells (neocytes) reduce

blood transfusion requirement in Thal Major? • Marcus, R. E., B. Wonke, et al. (1985). "A prospective trial of young red cells in 48 patients

with transfusion-dependent thalassaemia." British journal of haematology 60(1): 153-159. A minor but statistically significant decrease in blood consumption was observed in the group receiving YRBC.

• Berdoukas, V. A., Y. L. Kwan, et al. (1986). "A study on the value of red cell exchange transfusion in transfusion dependent anaemias." Clinical and laboratory haematology 8(3): 209-220. Using RC Ex, red cell transfusion requirement was reduced by 30%, reducing the iron load, and the transfusion interval was increased by 43%.

• Collins, A. F., C. Goncalves-Dias, et al. (1994). "Comparison of a transfusion preparation of newly formed red cells and standard washed red cell transfusions in patients with homozygous beta-thalassemia." Transfusion 34(6): 517-520. Significant extension of transfusion interval in 16 patients receiving neocyte transfusions (38.7 +/- 34 days; vs 32.9 +/- 2.5 days). Mean reduction in transfused iron of 15 percent/y per patient. Substantial increases in donor exposure and in component preparation costs.

Effects of storage on RBC function

• Morphology, Deformability, and Viability– Depletion of ATP– Sodium Potassium Pump– Vesicle formation– Loss of CD47– Recovery of RBC

• Depletion of 2,3-DPG on O2 delivery

• Vasodilatory Capacity1. Almac,. & Ince (2007) Best practice & Res. Clin anaesth 21(2): 195-208

Morphology, Deformability, and Viability on storage

• In vivo natural ageing– RBC lose area, volume, Hb through vesiculation of 50–200 nm particles [29].

• 10–14% of membrane area is lost during reticulocyte maturation• 16–17% during the remaining lifespan [30, 31].

– PS/Annexin V found on 30–70% of the microvesicles– 50% are coated with Ig with prompt removal by Kupffer cells

• On Storage– Micro-vesiculation occurs in particular of the younger cells [37],– Echinocytes form because of ATP depletion, initially reversible [38]

– Loss of CD47• a 50-kDa surface transmembrane glycoprotein reduces by 10–65% [41, 42].• when expression falls < 50%, RBCs susceptible to phagocytosis [41, 43].

Effect of storage onRBC survival after transfusion

• RBC 20–30% are non-viable, removed from the circulation within a few h– If survive 24 h, normal lifespan, irrespective of storage duration

• Luten, et al. (2008). Transfusion 48(7): 1478-1485– 24h post-transfusion RBC recovery

• higher after short storage (0-10d) • than long storage (25-35d)

– RBC, survival of remaining cells are similar .

Effect of blood storage age on anaemia in thalassaemia patients

• Difference in pre-transfusion Hb when using fresh blood vs standard issue blood ?– 9 adult patients, 2 x 6 month periods

• 2009 (period 1) – standard issue Mean 18 days old• 2010 (period 2)- ‘fresh’ blood (<14days old) mean 9.5d

– Mean pre-transfusion Hb higher by (0.5g/dl) in period 2– Transfusion interval and number of units not different

Priddee, et al. (2011) Transfusion medicine 21(6): 417-420.

Depletion of 2,3-DPG

– After 14d storage 2,3-DPG virtually depleted– Left shifter O2 dissociation- poor O2 delivery– 1hour after transfusion,

• 25–30% of 2,3-DPG was[15]• after 24 h recovery it is 50%, • full restoration may take up to 3 days [16]

– Animal studies suggest that levels are not key to O2 delivery however

Vasodilatory Capacity of stored blood

• Blood flow in microcirculation is regulated by NO • NO is produced by endothelial cells• RBC act as sink for NO• In RBC low O2 is sensed by Hb & NO is released rapidly causing

vasodilatation • INOBA hypothesis for stored blood

– Hb release from damaged RBC scavenges NO– inappropriate vasoconstriction occurs– leading to reduced blood flow and insufficient O(2) delivery to

end organsRoback, . (2011). ASH Education Program 2011: 475-479.

• Ozment, Biochimica et biophysica acta 1790(7), 694-701. (2009)

• Progressive release of iron from RBC associated with storage time

• suggests that morbidity following acute transfusion, like that seen in chronic transfusion, may be due in part to elevated levels of NTBI.

Safety of stored RBCStorage of RBC and iron

Safety of stored RBCStorage of RBC and iron

• Hod et al, Blood 2010,118, 4284-92– a murine RBC storage and transfusion model – transfusion of stored RBCs, or washed stored RBCs but

not fresh RBC or supernatant• increase (NTBI)• produces acute tissue iron deposition• initiates inflammation. • synergizes with subclinical endotoxinemia• producing clinically overt signs and symptoms.• increased plasma NTBI also enhances bacterial growth in

vitro.

Safety of stored bloodComplications in patients

receiving cardiac intervention

• Age of RBC storage (< or > 14d) associated with outcome after cardiac surgery (prospective randomised, n= 6,002)1

– Significant difference in: hospital mortality, intubation period, renal failure , sepsis

• Age of RBC storage (< or > 14d) is not associated with outcome after cardiac surgery (retrospective, n=1153) 2

– No difference in; early mortality, postoperative ventilation , renal failure, pulmonary and infectious complications, length of intensive care stay, and postoperative ventilation time

• Higher mortality after percutaneous coronary intervention in patients given older RBC (>28d) (HR 2.49) 3

1. Koch, C. G., L. Li, et al. (2008). NEJM 358(12): 1229-1239.2. McKenny, M., T. Ryan, et al. (2011) British journal of anaesthesia 106(5): 643-649.3. Robinson & Jesnsen AHJ, 2010

Safety in other conditionsold vs fresh blood

• Storage RBC age and 1y mortality – all transfused Leiden patients retrospective over 5y– < or > 17 days storage- no difference– 2-fold increase < 10d vs >24d. Worse with fresh ! (Middleberg, Transfusion

medicine 2012)• Reduction of myocardial infarct size with fresh blood Hu, H., A. Xenocostas, et al.

(2012). Critical care medicine 40(3): 740-74• Blood storage duration and cancer recurrence after prostatectomy Cata, et al.

(2011) Mayo Clinic Proc. 86(2): 120-127• Deep vein thrombosis. Spinella,, et al. (2009) Critical care 13(5): R151• No difference in pulmonary effects, or coagulation <5d vs ‘standard issue’

(randomised, n=50) Cornet, et al. (2010). Transfusion medicine 20(4)• No effect on outcome of stem cell transplantation. Kekre, et al. (2011).

Transfusion 51(11): 2488-2494

Conclusions about blood storage and age in Thal Major

• Young cell decrease transfusion requirement• A proportion of stored cells are destroyed within 24h

after transfusion• Older stored red cells may increased may have small

effect on transfusion requirement in TM• Conflicting data on survival in transfused non-

thalassaemics, may relate to volume of blood transfused in different studies

• Safety unlikely to be an issue <14 days old with ≤4 units transfed

Compatibility Testing• Before embarking on transfusion therapy

– patients should have extended red cell antigen typing – at least C, c, E, e, and Kell

• Blood selection– transfused with ABO and Rh(D) compatible blood. – Some clinicians recommend the use of blood that is also matched for at least the C, E

and Kell antigens in order to avoid alloimmunisation against these antigens. – Some centres use even more extended antigen matching.

• Before each transfusion– it is necessary to perform a full crossmatch and screen for new antibodies

• If new antibodies appear, they must be identified so that blood missing the corresponding antigen(s) can be used

• A complete record of– antigen typing, – red cell antibodies and transfusion reactions – should be readily available if the patient is transfused at a different centre.

• Transfusion of blood from first-degree relatives should be avoided because of the risk of developing antibodies that might adversely affect the outcome of a later bone marrow transplant

Adverse reactions

• Acute haemolytic reactions• Delayed transfusion reactions • Autoimmune haemolytic anaemia• Non-haemolytic febrile transfusion reactions• Allergic reactions • Transfusion-related acute lung injury (TRALI) • Graft versus host disease (GVHD)

Alloimunisation

• Development of one or more specific red cell antibodies (alloimmunisation) is a common complication of chronic transfusion therapy [Spanos 1990].

• Important to monitor patients carefully for the development of new antibodies

• Eliminate donors with the corresponding antigens. • Anti-E, anti-C and anti-Kell alloantibodies are most

common.• 5-10% of patients present with alloantibodies against

rare erythrocyte antigens or with warm or cold antibodies of unidentified specificity.

Red Cell Allominisation and autoimmunisation in thalassaemia

• Alloantibodies– 14 /64 thalassaemia patients (22%) became alloimmunized– Mis- matched RBC phenotype between the donor population and Asian recipients

for K, c, S, and Fy accounting for 38% of alloantibodies in Asian patients – Splenectomised - higher alloimmunization than non-splenectomised (36% vs 12.8% P= 0 .06)

• Auto- antibodies (Coomb’s +ve)– 16 of the 64 ( 25% )– Causing severe hemolytic anemia in 3 of 16 patients.– Of these 16, 11 antibodies were typed immunoglobulin G [IgG], and 5 were typed IgM. – Autoimmunization associated with alloimmunization (44% ) and splenectomy ( 56 %)

• Prevention – More effective if phenotypic matching for Rh and Kell - alloimunisation - 2.8%– Vs phenotypically matched for the standard ABO-D system - alloimunisation -33%; P = .0005

Singer et al (Blood. 2000; 96:3369-3373)

Red Blood Cell Allo- and Autoantibodies in the Thalassemia Clinical Research Network

• Overall Rates– Of 502 regularly transfused TM– Alloimmunization were reported 104 - (21%) – Autoantibodies were reported in 46 - (9.2%) – Allo + autoantibodies in 26 (5.2%)

• Date of Initiation of transfusion – Alloantobodies

• before1990 - 27% (mean age 25.8 +/- 8.4 yrs )• after 1990 - 12.5% (p<.001) (mean age 9.3 +/- 6.8 yrs)

– Autoantobodies• before 1990 32/285 (11.2%)• after 1990 - 13/208 (6.3%) (p=.08)

• Splenectomy – Alloantibodies greater in spelectomised patients post 1990 cohort

• Splenectomized 14/49 (29%) of subjects who started transfusion after 1990, • Nonsplenectomized 12/159 (7.6%) in subjects (p<.001)• No differences in the pre -1990 cohort,

• Race– Rates of alloimmunization did not differ among races after controlling for age.

• Centre effects– Rates of alloimmunization between the cohorts varied among treatment centers, possibly related to

varying procedures for phenotypic antigen matching of RBCs.

M. J. Cunningham1, Eric A. Macklin et al Blood 2005 106: Abstract 1890

Adverse reactions

Transmission of infectious agents • Including viruses, bacteria and parasites, are a

major risk in blood transfusion. • New problems continue to emerge, such as the

new variant of Creutzfeldt-Jakob Disease and West Nile virus.

• Continued transmission of hepatitis B, hepatitis C and HIV underscore the importance of voluntary blood donations, careful donor screening, thorough donor testing, and, in the case of hepatitis B, immunisation.

Minimising infection riskDonor Selection & Product screening

• Blood should be obtained from carefully selected healthy voluntary donors who have undergone extensive questioning and laboratory screening for:

• Hepatitis B, hepatitis C, HIV, syphilis and other infectious diseases.

• Specific strategies for donor selection and product screening will be influenced by the prevalence of infectious agents in the donor population.

(See TIF Blood Kit)

Adverse reactionsMinimising infection risk

Future strategies

• Pre-Treatment of blood product

• Use of donor independent blood products

Pathogen reduction of blood components

Approachesplasma platelets

RBC• Methylene blue + - -• Riboflavin light treatment (mirasol) + +^ ?+• Nucleic Acid targeting (s303) Intercept +^ +^ (+)*• Solvent detergent treatment +^ - -

•Neoantigen formation•^ce mark EU

Production of red cells from ES cells or from somatic stem cells?

• Human erythropoiesis - a complex multistep process involving the differentiation of early erythroid progenitors to mature erythrocytes

• Human Embryonic Stem Cells (HES)– 2 recent papers show that viable mature functional

enucleated RBCs can be produced in vitro from ES cells in numbers - suitable for up-scaling

– Large recent investment by research bodies to develop these techniques

• HLA-haplotype banking and iPS cells?– Induced pluripotent stem cells (iPS) from human somatic

stem cells such as skin fibroblasts recently reported

Nature Biotchnology 26 (7) 2008

Lu et al Blood. 2008; 112(12): 4475–4484.

Biologic properties and enucleation of red blood cells from human embryonic stem cells

• Feasible to differentiate and to mature human embryonic stem cells (hESCs) into functional oxygen-carrying erythrocytes on a large scale (1010-1011 cells/6-well plate hESCs).

• Oxygen equilibrium curves of the hESC-derived cells are comparable with normal red blood cells and respond to changes in pH and 2,3-diphosphoglyerate.

• Cells mainly expressed fetal and embryonic globins, but they also possessed the capacity to express the adult β-globin chain on further maturation in vitro.

• .

Lu et al Blood. 2008 December 1; 112(12): 4475–4484.

• Cells underwent maturation events- progressive decrease in size, increase in glycophorin A , and chromatin and nuclear condensation. • Process resulted in extrusion of the pycnotic nuclei (> 60% of the cells) generating RBCs approximately 6 - 8 μm.

Outline • Goals of transfusion• Basic requirements



• Recommended transfusion regime in TM – Optimise



Standard Transfusion Regimen for Thalassaemia Major

• Regular blood transfusions administered every 2-5 weeks• Maintain the pre-transfusion Hb > 9-10.5g/dl• Rationale

– promotes normal growth– allows normal physical activities– adequately suppresses bone marrow activity in most patients– minimises transfusional iron accumulation [Cazzola 1995,1997]

• Modifications– A higher target 11-12 g/dl may be appropriate for patients with heart disease or

other medical conditions and for those patients who do not achieve adequate suppression of bone marrow activity at the lower haemoglobin level.

– Although shorter intervals between transfusions may reduce overall blood requirements, the choice of interval must take into account other factors such as the patient’s work or school schedule

Relationship between transfusion regimen and suppression of erythropoiesis

• 52 patients with thalassaemia major whose mean pre-transfusion haemoglobin levels ranged from 8.6 to 10*9g/dl

• Multiple regression analysis showed that serum transferrin receptor was the parameter more closely related to mean pretransfusion haemoglobin (r = -0.77, P < 0.001)

• Pretransfusion Hb 10-11g/dl- 1-2x normal

• Pretransfusion Hb 9-10 g/dl- 1-4x normal

• Pretransfusion Hb 8-9 g/dl- 2-6 x normal

• {Cazzola, 1995 #906}

When to start ?• Should be based on a definitive diagnosis of severe thalassaemia• Diagnosis should take into account the molecular defect, the

severity of anaemia on repeated measurement• The level of ineffective erythropoiesis, and clinical criteria such as

failure to thrive or bone changes • Regular transfusion therapy for severe thalassaemia usually

occurs in the first two years of life • Some patients with milder forms of thalassaemia who only need

sporadic transfusions in the first two decades of life may later need regular transfusions because of a falling haemoglobin level or the development of serious complications

Proportion of lifetime on transfusion (%) by disease and region

Viprakasit et al, Blood Transfusion 2012

% Receiving

% Not receiving

% o

f pa

tient

s%

of

patie

nts

Thal Major Thal Intermedia

MDS

Aplastic Anaemia

Sickle Cell Disease

1,744 patients with a variety of transfusion-dependent anaemias across 23 countries, 3 geographic regions

Guidelines for choosing how much blood to transfuse

Thalassaemia International Federation Guidelines

The post-transfusion Hb

• Should not be > 14-15 g/dl • Regular measurement of the post-transfusion

haemoglobin level is unnecessary • Occasional determinations allow assessment of

the rate of fall in the haemoglobin level between transfusions and may be useful in evaluating the effects of changes in the transfusion regimen, the degree of hypersplenism, or unexplained changes in response to transfusion

Hemoglobin Level and Blood Requirements?

• Evidence that maintenance of higher hemoglobin levels does not require more blood

• 166 splenectomized and non-splenectomized patients, transfusion requirements remained constant at mean transfusion Hb 10-14 g/dL (equivalent to pre-transfusion hemoglobin levels of approximately 8 to 12 g/dL) (Gabutti 1980)

• 392 patients from three Italian centers confirmed the earlier findings and concluded that the maintenance of higher hemoglobin levels in transfusion programs for TM did not require a higher blood requirement (Gabutti 1982).

• Additional supportive evidence came from a study of “supertransfusion” where maintenance of pre-transfusion hematocrits of 27% and 35% required similar amounts of blood (Propper Blood 1980)

Hemoglobin Level and Blood Requirements ?

Evidence that maintenance of higher hemoglobin levels does require more blood– transfusion requirements of 14 French patients

were directly proportional to mean Hb and nearly doubled between 9.6 and 13.4 g/dL (Brunengo 1986 )

– 3468 patients in Greece and Italy, transfusion requirements proportional to mean Hb (Rebulla 1991)

– Only one study was the annual transfusion requirement measured repeatedly in the same patients under two different transfusion regimens (Cazzola 1997)

Effect of target Hb on transfusion (Tfn) requirements in thalassaemia

Years Pre-Tfn Hb Tfn given Ferritin (g/dl) (ml/kg/y) (µg/L)

mean ±S mean ±SD median

1981-86 11.3 ± 0.5 137± 26 2280

1987-92 9.4 ± 0.4 104 ± 23 1004

Blood requirements iron accumulation and chelation therapy

• Although it is self evident that the greater the blood transfusion, the greater the iron accumulation rate and the greater the need for chelation- this has not been studied until recently

• Recent studies show that taking into account the transfusion rate is important:– To decide an initial chelation dose– To identify potential ‘non-responders’

Iron accumulation

• A careful record of transfused blood should be maintained for each patient.

• Volume or weight of the administered units

• The haematocrit of the units or the average haematocrit of units with similar anticoagulant-preservative solutions,

• the patient’s weight. Thalassaemia International Federation Guidelines

Iron loading from transfusion

• 200mg iron in 1 blood unit (from 420ml of donor)– 0.47mg iron/ml of whole blood– 1.08mg iron/ml of ‘pure’ red cells

• In Thal Major (spelenctomised) if mean Hb 12g/dl– 300mls blood/kg body wt per annum – More if not splenectomised= average 0.4 mg iron / kg body wt/ day from transfusion– Add 1-4 mg/day from gut absorption– In practice wide range 0.3 to 0.7 mg/kg/day– 4 to 10 g of iron per year

Porter JB. Br J Haematol. 2001;115:239-252.Andrews NC. N Engl J Med. 1999;341:1986-1995Cohen, A. R. et al. Blood 2008;111:583-587

Highly variable iron excretion is required to balance transfusional iron loading

in Thalassaemia Major

Highly variable iron excretion is required to balance transfusional iron loading

in Thalassaemia Major • Iron accumulation from transfusion in TM (n = 586)

• 233mls/kg/y blood (if Hct 0.6)

• about 40 units/year for a 70 kg person

• 0.4 ± 0.11 mg/kg/day (mean) of iron

• < 0.3mg /kg day 19% of patients

• 0.3-0.5 mg/kg/day 61%

• > 0.5 mg/kg/day 20%

Cohen,Glimm and Porter. Blood 2008;111:583-7

Deferoxamine dose required for iron balance given s.c. x5/week

Deferoxamine dose required for iron balance given s.c. x5/week

Cohen AR, et al. Blood. 2008;111:583-7.

100%

0%

100%

Decrease

Increase

< 0.3 0.3–0.5 > 0.5Iron intake (mg/kg/day)

Initial DFO dose (mg/kg/day) 35–< 50 5025–< 35< 25

Decrease in LIC, 67 17 76 100 33 43 75 86 17 52 89% of patients

Change in LIC by deferasirox dose and ongoing transfusion burden

Change in LIC by deferasirox dose and ongoing transfusion burden


100100

00

Decrease (%)Decrease (%)

Increase (%)Increase (%)

< 0.3< 0.3 0.3–0.50.3–0.5 > 0.5> 0.5

Iron intake (mg/kg/day)Iron intake (mg/kg/day)

Deferasirox dose (mg/kg/day)Deferasirox dose (mg/kg/day) 55 1010 2020 3030

Phase III: Study 107

Decrease LIC (% patients) 0 29 75 96 9 14 55 83 0 0 47 82

Dosing to balance iron transfusional rateDosing to balance iron transfusional rate

Deferasirox

Deferasirox

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0 5 10 15 20 25 30

Mea

n t

ota

l bo

dy

iro

n e

xcre

tio

n

± S

D (

mg

Fe/

kg/d

ay)

Actual doses (mg/kg/day)

0 10 20 30 40 50 60

D eferoxamine

Studies 107 and 108

Deferoxamine (5 days/week)

Average transfusion iron intake SCD

Average transfusion iron intake thalassaemia


Conclusions

• Clear Guidelines available for minimising risks from alloiminisation, other transfusion reactions, infection risks

• Future developments may reduce infection risks• Optimal Hb still debated- may vary with patient

population• Large variability in iron content of a ‘unit’ –

important to understand because impacts on response to chelation therapy

overview of recommended blood transfusion therapy in thalassaemia major professor john porter red...

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