salwa hindawi. guidelines and updates in blood transfusion for ß -thalassemia patients salwa...

Salwa HindawiSalwa Hindawi


Guidelines and Updates in Blood Guidelines and Updates in Blood Transfusion for Transfusion for ßß -Thalassemia -Thalassemia

PatientsPatients

Salwa HindawiSalwa Hindawi MSc, MRCPath, CTMMSc, MRCPath, CTM

Medical Director of Blood Transfusion ServicesMedical Director of Blood Transfusion ServicesKAUH, JeddahKAUH, Jeddah

KSAKSA


IntroductionIntroduction

Transfusion is the mainstay of the care of Transfusion is the mainstay of the care of individuals with thalassemia majorindividuals with thalassemia major . .

The purpose of transfusion is to improve the The purpose of transfusion is to improve the anemia and to suppress the ineffective anemia and to suppress the ineffective

erythropoiesiserythropoiesis . .

Chronic transfusions prevent most of the Chronic transfusions prevent most of the serious growth, skeletal, and neurological serious growth, skeletal, and neurological complications of thalassemia majorcomplications of thalassemia major..


IntroductionIntroduction

The decision to start transfusions is based on inability to The decision to start transfusions is based on inability to compensate for the low hemoglobincompensate for the low hemoglobin

signs of increased cardiac effort, tachycardia, sweating, signs of increased cardiac effort, tachycardia, sweating, poor feeding, and poor growth due to increasing poor feeding, and poor growth due to increasing symptoms of ineffective erythropoiesis : bone changes, symptoms of ineffective erythropoiesis : bone changes, massive splenomegalymassive splenomegaly..


GuidelinesGuidelines

Schedule transfusions at three to four week Schedule transfusions at three to four week intervals to maintain hemoglobin level greaterintervals to maintain hemoglobin level greater

than or equal to 9-9.5 gm/dl prior to the next than or equal to 9-9.5 gm/dl prior to the next transfusiontransfusion..

Evaluate hemoglobin prior to each transfusion, If Evaluate hemoglobin prior to each transfusion, If the pre-transfusion hemoglobin is less than 9.0 the pre-transfusion hemoglobin is less than 9.0 gm/dl, the patient may need more frequent (every gm/dl, the patient may need more frequent (every two to three weeks) transfusions or increased two to three weeks) transfusions or increased volume of transfusionvolume of transfusion..



Perform extended red cell phenotyping prior to Perform extended red cell phenotyping prior to initiating the transfusion regimeinitiating the transfusion regime..

The use of phenotypically matched blood products, The use of phenotypically matched blood products, from the beginning of chronic transfusion, can from the beginning of chronic transfusion, can prevent most cases of alloimmunizationprevent most cases of alloimmunization..


• DONE ON FIRST SAMPLE• DONE ON THE RETICS



The decision to start regular transfusions depends on The decision to start regular transfusions depends on clinical and laboratory assessmentclinical and laboratory assessment::

worsening anemia, inability to tolerate anemia, massive worsening anemia, inability to tolerate anemia, massive splenomegaly worsening bone disease, increasing splenomegaly worsening bone disease, increasing

nucleated red blood cells and dropping hemoglobinnucleated red blood cells and dropping hemoglobin . .

Skeletal malformation can be severe in thalassemia Skeletal malformation can be severe in thalassemia intermedia and should be considered in the decision to intermedia and should be considered in the decision to start transfusionstart transfusion..



Assess spleen size at each visit, splenomegaly could Assess spleen size at each visit, splenomegaly could account for increased blood requirementaccount for increased blood requirement . .

Calculate all blood given to the patient (total cc’s) and Calculate all blood given to the patient (total cc’s) and divided by an average weight over the past 6 months divided by an average weight over the past 6 months

(cc / kg / year)(cc / kg / year) . .

If transfusion requirement is greater than 200 cc / kg / If transfusion requirement is greater than 200 cc / kg / year, the cause for such a high transfusion requirement year, the cause for such a high transfusion requirement should be exploredshould be explored..


splenectomysplenectomy

In the face of marked splenomegaly or other evidence In the face of marked splenomegaly or other evidence of significant hypersplenismof significant hypersplenism

))leukopenia, thrombocytopenialeukopenia, thrombocytopenia .( .(

splenic embolization, splenectomy or partialsplenic embolization, splenectomy or partial

splenectomy may be consideredsplenectomy may be considered..


SplenectomySplenectomy

Splenectomy is generally not recommended for Splenectomy is generally not recommended for thalassemia patients because of the risk of the thalassemia patients because of the risk of the

complicationscomplications . .

Splenectomy is associated with significant risk of Splenectomy is associated with significant risk of serious short and long term complications Infectious, serious short and long term complications Infectious, pulmonary, hepatic, and thromboticpulmonary, hepatic, and thrombotic..



Pre splenectomyPre splenectomy::

VaccinationVaccinationObtain pneumococcal IgG titers. If the titers are Obtain pneumococcal IgG titers. If the titers are inadequate, immunize to maximize coverage of all inadequate, immunize to maximize coverage of all serotypes (7-valent conjugate vaccine recommended serotypes (7-valent conjugate vaccine recommended in children under five years (Prevnar)in children under five years (Prevnar)

2323 valent (Pneumovax) as a booster at five years of age valent (Pneumovax) as a booster at five years of age or later. Reimmunize patients with inadequate IgG or later. Reimmunize patients with inadequate IgG responsesresponses..



Post splenectomyPost splenectomy:: --Monitor the platelet count and treat with an anti-Monitor the platelet count and treat with an anti-

platelet aggregate (low dose Aspirin) if platelet platelet aggregate (low dose Aspirin) if platelet count is 1 x 106 or greatercount is 1 x 106 or greater . .

--Consider chronic low dose anticoagulation Consider chronic low dose anticoagulation (coumadin) or anti-platelet agent (aspirin) in older (coumadin) or anti-platelet agent (aspirin) in older splenectomized patients reduce the risk of splenectomized patients reduce the risk of pulmonary thrombotic events and pulmonary pulmonary thrombotic events and pulmonary hypertensionhypertension..

- - All post splenectomy thalassemia patients require All post splenectomy thalassemia patients require treatment with prophylactic penicillintreatment with prophylactic penicillin..

--Intensive family education should be providedIntensive family education should be provided..


Iron OverloadIron Overload

Regular blood transfusion can lead to Iron overloadRegular blood transfusion can lead to Iron overload..

Serum iron & ferritin, TIBC, and/or liver IronSerum iron & ferritin, TIBC, and/or liver Iron..

Chelation should be considered after one to two years Chelation should be considered after one to two years of transfusion therapy, when the serum ferritin is of transfusion therapy, when the serum ferritin is greater than 1000 ng/dL, or when the hepatic iron is greater than 1000 ng/dL, or when the hepatic iron is approximately 7 mg /gram dry weightapproximately 7 mg /gram dry weight


Determination of liver iron by biopsy is recommended Determination of liver iron by biopsy is recommended prior to initiation of desferrioxamine therapy as well prior to initiation of desferrioxamine therapy as well as every 12 to 24 months (or as clinically indicated)as every 12 to 24 months (or as clinically indicated)..

Though not routinely available, liver iron can be also Though not routinely available, liver iron can be also determined by ferritometry (SQUID)determined by ferritometry (SQUID) . .

Evaluate ferritin level quarterlyEvaluate ferritin level quarterly..


CHRONIC IRON OVERLOADCHRONIC IRON OVERLOAD

:):)

TOXICITY HEPATIC IRONTOXICITY HEPATIC IRONDesferrioxamine Toxicity Hearing Loss < 3 mg/g dry wtDesferrioxamine Toxicity Hearing Loss < 3 mg/g dry wt

BlindnessBlindness Growth FailureGrowth Failure

Optimal Hepatic Iron Level 4 to 7.5 mg/g dry wtOptimal Hepatic Iron Level 4 to 7.5 mg/g dry wt

Risk of EndocrineRisk of EndocrineComplications Diabetes Mellitus 7.5 to 15mg/g dry wtComplications Diabetes Mellitus 7.5 to 15mg/g dry wt

HypogonadismHypogonadism HypoparathyroidismHypoparathyroidism

Cirrhosis > 10 mg / g dry weightCirrhosis > 10 mg / g dry weightRisk of CardiovascularRisk of CardiovascularComplications CardiomyopathyComplications Cardiomyopathy

Dysrythmia > 15 mg/g dry wtDysrythmia > 15 mg/g dry wt..

Olivieri and Brittenham Blood 89:3,1997,739-761Olivieri and Brittenham Blood 89:3,1997,739-761


AlloimmunizationAlloimmunization

The factors which contributing to The factors which contributing to alloimmunizationalloimmunization : :

11--The RBC antigenic difference between the blood The RBC antigenic difference between the blood donor and the recipientdonor and the recipient . .

22--the recipient's immune statusthe recipient's immune status..

33--the immunomodulatory effect of the allogeneic blood the immunomodulatory effect of the allogeneic blood transfusions on the recipient's immune systemtransfusions on the recipient's immune system . .


ALLOANTIBODIES AND ALLOANTIBODIES AND AUTOANTIBODIESAUTOANTIBODIES

If an autoantibody or/and alloantibody is detected, the If an autoantibody or/and alloantibody is detected, the specific antibodies causing thespecific antibodies causing the

transfusion reaction should be determined by the blood transfusion reaction should be determined by the blood bank or by a reference laboratorybank or by a reference laboratory..

The use of blood matched by extended antigen is usually The use of blood matched by extended antigen is usually indicated. Other treatment modalities, as steroids or indicated. Other treatment modalities, as steroids or immunosuppressive agents may be considered as wellimmunosuppressive agents may be considered as well..


ALLOANTIBODIES AND ALLOANTIBODIES AND AUTOANTIBODIESAUTOANTIBODIES

Autoimmunization or alloimmunization should be Autoimmunization or alloimmunization should be considered if the hemoglobin is lessconsidered if the hemoglobin is less

than 9.0-9.5 gm/dl or is significantly less than usual for than 9.0-9.5 gm/dl or is significantly less than usual for the particular patient prior to thethe particular patient prior to the

transfusion on two occasionstransfusion on two occasions..

Hemoglobin level and direct and indirect Coombs test Hemoglobin level and direct and indirect Coombs test should be determined 24 to72 hours after the should be determined 24 to72 hours after the transfusiontransfusion..


antibodies screening and identificationantibodies screening and identification

Perform antibodies screening test (all patients & Perform antibodies screening test (all patients & donors ) Using 3 cells panel screening cellsdonors ) Using 3 cells panel screening cells

If antibody screening negative -NADIf antibody screening negative -NAD

If antibodies screening positive do antibody If antibodies screening positive do antibody identification and autocontrolidentification and autocontrol

PANEL CELLS POS AUTOCONTROL NEGPANEL CELLS POS AUTOCONTROL NEG

PANEL CELLS POS AUTOCONTROL POSPANEL CELLS POS AUTOCONTROL POS


REAGENT CELL PANEL POSREAGENT CELL PANEL POSAUTO CONTROL NEGAUTO CONTROL NEG

SOME CELLS NEGSOME CELLS NEGSOME CELLS POS ( SAME STRENGTH & PHASES )SOME CELLS POS ( SAME STRENGTH & PHASES )

Suspect Single AntibodySuspect Single Antibody

Test other selected cells to eliminate other specificitiesTest other selected cells to eliminate other specificities Test the patient cell to confirm they lack antigen ( phenotyping )Test the patient cell to confirm they lack antigen ( phenotyping )


REAGENT CELL PANEL POSREAGENT CELL PANEL POSAUTO CONTROL NEGAUTO CONTROL NEG

SOME CELLS NEGSOME CELLS NEG

SOME CELLS POS ) DIFFERENT STRENGTH & OR PHASES )SOME CELLS POS ) DIFFERENT STRENGTH & OR PHASES )

Suspect Multiple AntibodySuspect Multiple Antibody

ALL CELLS POS ) DIFFERENT STRENGTH & OR PHASES )ALL CELLS POS ) DIFFERENT STRENGTH & OR PHASES )

Suspect Multiple AntibodySuspect Multiple Antibody


Multiple antibodies identificationMultiple antibodies identification::

Test selected cells to confirm and eliminate other Test selected cells to confirm and eliminate other specificitiesspecificities

Extended panel ( 15 or 20 cells panel )Extended panel ( 15 or 20 cells panel )

You may need another technique ( enzyme )You may need another technique ( enzyme )

Test the patient cell to confirm they lack antigen Test the patient cell to confirm they lack antigen ( phenotyping )( phenotyping )

May need help from reference laboratory for May need help from reference laboratory for identification and confirmationidentification and confirmation


MangementMangement

Compatible bloodCompatible blood

Frozen –deglycerated rbcsFrozen –deglycerated rbcs

Least incompatible bloodLeast incompatible blood**balanced decisionbalanced decision

**avoid the strong immunogenic Agsavoid the strong immunogenic Ags

**premeditations ,initial slow infusionpremeditations ,initial slow infusion

**close monitoring and follow haemolysis indicesclose monitoring and follow haemolysis indices


Other optionsOther options::

IvIgIvIg

CorticosteroidsCorticosteroids



--Use of hydroxyurea & ErthropiotinUse of hydroxyurea & Erthropiotin..Blood May,2003Blood May,2003..

--Use of 2units collection through Apheresis from Use of 2units collection through Apheresis from specific volunteer Donorspecific volunteer Donor..


HydroxyureaHydroxyurea

The use of hydroxyurea may eliminate the need for The use of hydroxyurea may eliminate the need for future blood transfusions in children with beta-future blood transfusions in children with beta-thalassemia majorthalassemia major

administration of hydroxyurea to patients with severe administration of hydroxyurea to patients with severe forms of beta-thalassemia would result in production forms of beta-thalassemia would result in production

of fetal hemoglobinof fetal hemoglobin..

WASHINGTON, DC - Blood August 12, 2003


Singer ST; Wu V; Mignacca R; Kuypers FA; Morel P; Singer ST; Wu V; Mignacca R; Kuypers FA; Morel P; Vichinsky EPVichinsky EP

Department of Hematology/Oncology at the Children's Hospital Oakland, Department of Hematology/Oncology at the Children's Hospital Oakland,

California, USACalifornia, USA

6464 transfused thalassemia patients (75% Asian) were evaluatedtransfused thalassemia patients (75% Asian) were evaluated . .1414) ) 22%22% ( (of 64 patients became alloimmunized. K, c, S, and Fyb of 64 patients became alloimmunized. K, c, S, and Fyb

accounts for 38% of the alloantibodies among Asian patientsaccounts for 38% of the alloantibodies among Asian patients . .Patients who had a splenectomy had a higher rate of Patients who had a splenectomy had a higher rate of alloimmunization than patients who did not have a alloimmunization than patients who did not have a splenectomy 36% vs 12.8%splenectomy 36% vs 12.8% . .

Erythrocyte autoantibodies developed in 25% or 16 of the 64 Erythrocyte autoantibodies developed in 25% or 16 of the 64 patientspatients . .

Transfusion of phenotypically matched blood for the Rh and Kell Transfusion of phenotypically matched blood for the Rh and Kell proved to be effective in preventing alloimmunizationproved to be effective in preventing alloimmunization

Blood. 2000; 96)10):3369-73Blood. 2000; 96)10):3369-73


Frequency of irregular red cell alloantibodies in Frequency of irregular red cell alloantibodies in patients with thalassemia major: a bicenter patients with thalassemia major: a bicenter

studystudy

study conducted at two centers from January to December 2001 a study conducted at two centers from January to December 2001 a total of 97 patients were included in the studytotal of 97 patients were included in the study . .

Alloantibodies were found in 9 (9.2%). Mean age of patients who Alloantibodies were found in 9 (9.2%). Mean age of patients who developed red cell alloantibody was 11.9 years. Three (33.3%) developed red cell alloantibody was 11.9 years. Three (33.3%) patients developed anti-K while two (22.2%) had non-specific patients developed anti-K while two (22.2%) had non-specific antibodyantibody . .

One patient developed anti-D (11.1%) and anti-E (11.1%). Two had 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-D (11.1%) and anti-C while the other one (11.1%) developed anti-E and anti-Kanti-E and anti-K..

J Pak Med Assoc 2005 Dec;55(12):563-5


CONCLUSIONCONCLUSION

11--There is relatively high rate ofThere is relatively high rate of

alloimmunization in their patients when alloimmunization in their patients when compared to data from the regioncompared to data from the region . .

22 - -Red cell alloimmunization should not be Red cell alloimmunization should not be overlooked in patients receiving regular overlooked in patients receiving regular

blood transfusionsblood transfusions..


BONE MARROW BONE MARROW TRANSPLANTATIONTRANSPLANTATION

Bone marrow transplantation is the only cure for Bone marrow transplantation is the only cure for thalassemia patientsthalassemia patients . .

It should be considered in all patients who have an It should be considered in all patients who have an acceptable donoracceptable donor . .

Patients are classified on the basis ofPatients are classified on the basis of

their risk factors which includetheir risk factors which include::

inadequate chelation, presence of liver fibrosis and inadequate chelation, presence of liver fibrosis and hepatomegalyhepatomegaly..


RecommendationsRecommendations

11 ( (Extended rbc phenotypingExtended rbc phenotyping

Perform extended red cell phenotyping prior Perform extended red cell phenotyping prior to initiating the transfusion regimeto initiating the transfusion regime..


22 ( (Red cell matchingRed cell matching.. Select ABO matched red cell units, which are K Select ABO matched red cell units, which are K negative and matched for the common Rh negative and matched for the common Rh antigens (D, C, E, c, e)antigens (D, C, E, c, e)..

If clinically significant red cell antibodies are If clinically significant red cell antibodies are present, select antigen negative units and present, select antigen negative units and issue blood compatible in the crossmatch by issue blood compatible in the crossmatch by IATIAT..


33 ( (LeucodepletionLeucodepletion.. i) Bedside filtered red cells is not used routinely i) Bedside filtered red cells is not used routinely nowadaysnowadays..

ii) Pre-storage Leucodepletionii) Pre-storage Leucodepletion

Leucodepleted red cells (WBC <5 x 106 per unit) Leucodepleted red cells (WBC <5 x 106 per unit) following filtration at the blood transfusion services following filtration at the blood transfusion services (at source) are recommended(at source) are recommended..


44 ( (Age of the red cell unitsAge of the red cell units

Ideally, the red cell units selected for Ideally, the red cell units selected for transfusion dependent patients should be transfusion dependent patients should be less than 2 weeks old to ensure maximum less than 2 weeks old to ensure maximum possible survival in the recipient’s possible survival in the recipient’s circulationcirculation


55((Encourage central blood bankEncourage central blood bank

With regular phenotype donorsWith regular phenotype donors

Frozen bloodFrozen blood

Frozen rare panel cellFrozen rare panel cell

66((Cooperation between HospitalsCooperation between Hospitals..

77((The use of new oral iron chelator for the The use of new oral iron chelator for the treatment of iron overloadtreatment of iron overload..

salwa hindawi. guidelines and updates in blood transfusion for ß -thalassemia patients salwa...

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transfusion regime

purpose of transfusion

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high transfusion requirement

partial splenectomy

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increased blood requirement