بسم الله الرحمن الرحيم

بسم الله الرحمن الرحيم بسم الله الرحمن الرحيم 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 Salwa Hindawi

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. Salwa Hindawi

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. Salwa Hindawi

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. Salwa Hindawi

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. Salwa Hindawi

DONE ON FIRST SAMPLE • DONE ON THE RETICS Salwa Hindawi

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. Salwa Hindawi

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. Salwa Hindawi

splenectomy In the face of marked splenomegaly or other evidence of significant hypersplenism (leukopenia, thrombocytopenia). splenic embolization, splenectomy or partial splenectomy may be considered. Salwa Hindawi

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. Salwa Hindawi

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. Salwa Hindawi

Splenectomy Post splenectomy: -Monitor the platelet count and treat with an anti-platelet 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. Salwa Hindawi

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 Salwa Hindawi

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. Salwa Hindawi

CHRONIC IRON OVERLOAD ): TOXICITY HEPATIC IRON Desferrioxamine Toxicity Hearing Loss < 3 mg/g dry wt Blindness Growth Failure Optimal Hepatic Iron Level 4 to 7.5 mg/g dry wt Risk of Endocrine Complications Diabetes Mellitus 7.5 to 15mg/g dry wt Hypogonadism Hypoparathyroidism Cirrhosis > 10 mg / g dry weight Risk of Cardiovascular Complications Cardiomyopathy Dysrythmia > 15 mg/g dry wt. Olivieri and Brittenham Blood 89:3,1997,739-761 Salwa Hindawi

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 bloodtransfusions on the recipient's immune system. Salwa Hindawi

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. Salwa Hindawi

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. Salwa Hindawi

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 Salwa Hindawi

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 ) Salwa Hindawi

REAGENT CELL PANEL POSAUTO 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   Salwa Hindawi

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 Salwa Hindawi

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 Salwa Hindawi

Other options: IvIg Corticosteroids Splenectomy Salwa Hindawi

-Use of hydroxyurea & Erthropiotin. Blood May,2003. -Use of 2units collection through Apheresis from specific volunteer Donor. Salwa Hindawi

Hydroxyurea The use of hydroxyurea may eliminate the need for future blood transfusions in children with beta-thalassemia major administration of hydroxyurea to patients with severe forms of beta-thalassemia would result in production of fetal hemoglobin. Salwa Hindawi WASHINGTON, DC - Blood August 12, 2003

Singer ST; Wu V; Mignacca R; Kuypers FA; Morel P; Vichinsky EPDepartment 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 Salwa Hindawi

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

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. Salwa Hindawi

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. Salwa Hindawi

Recommendations 1) Extended rbc phenotyping Perform extended red cell phenotyping prior to initiating the transfusion regime. Salwa Hindawi

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. Salwa Hindawi

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. Salwa Hindawi

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 Salwa Hindawi

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. Salwa Hindawi

THANKS Salwa Hindawi

بسم الله الرحمن الرحيم