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Fresher blood products are not necessarily better for patients with beta thalassemia, according to a pair of experts.
Red blood cell units stored less than 2 weeks are ideal, but older units are acceptable, and phenotype matching should take priority over unit age, advised Ashutosh Lal, MD, and Elliott Vichinsky, MD, both of UCSF Benioff Children’s Hospital Oakland (Calif.). They discussed these and other recommendations for transfusing patients with thalassemia during a webinar hosted by the Centers for Disease Control and Prevention.
Indications for transfusion
Dr. Lal said patients with beta thalassemia major should be transfused if their hemoglobin is less than 7 g/dL on two occasions 2 weeks apart at baseline, or if their hemoglobin is greater than 7 g/dL and they have symptoms of anemia.
Patients with hemoglobin E beta thalassemia major should be transfused only if they have symptoms of anemia.
“The rationale is that, in beta thalassemia major, it is well established that, once the hemoglobin levels fall below 7 g/dL in young children, there is going to be massive bone marrow expansion, and there will be severe symptoms from anemia,” Dr. Lal said. “But the relationship of hemoglobin with symptoms in E beta thalassemia is less precise.”
The symptoms that should prompt transfusion include slowed growth, skeletal facial changes, splenomegaly, symptomatic or moderate to severe extramedullary hematopoiesis, cerebrovascular events, venous thromboembolism, pulmonary hypertension, osteoporotic fracture, and impaired quality of life in adults.
Dr. Lal said physicians should consider a 6-month trial of transfusions if the indication is unclear. He also noted that red cell antigen genotyping should be performed in all patients who may need transfusions.
Blood products
Dr. Lal said beta thalassemia patients should receive packed red blood cells that are leukoreduced prior to storage. The storage solution can be citrate-phosphate-dextrose solution with adenine (hematocrit 75%) or additive solution (hematocrit 60%).
“It’s important to note that the hematocrit of the two is quite different, and that needs to be inculcated into the decisions on how much volume to transfuse to younger children,” Dr. Lal said.
He noted that units should not be irradiated, as this damages the red cell membrane. And patients with severe allergic reactions should receive washed red blood cells because washing units removes residual donor plasma proteins.
Finally, units should be less than 2 weeks old if possible. Dr. Lal said using fresh units increases the survival of red blood cells post transfusion. However, he and Dr. Vichinsky both stressed that older units are acceptable, and phenotype matching is more important than the age of the unit.
Phenotype matching
Beta thalassemia patients who do not have preexisting alloantibodies or have transient autoantibodies should be matched to Rh and Kell, according to Dr. Lal.
Patients with preexisting alloantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and the specific alloantibody. Patients with persistent autoantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and any alloantibody.
Patients who start transfusions after 5 years of age should be matched to Rh, Kell, Duffy, Kidd, and S. Pregnant patients should be matched to Rh, Kell, Duffy, Kidd, and S, and units should be cytomegalovirus negative.
How to transfuse
Dr. Lal said the pretransfusion hemoglobin target is 10 g/dL, with a range of 9.5-10.5 g/dL in beta thalassemia major and a range of 9.0-10.5 g/dL for E beta thalassemia. A target of 10 g/dL is adequate for most individuals, Dr. Lal said, but he recommends individualization of hemoglobin target for patients with E beta thalassemia.
In general, patients should be transfused every 3 weeks, although 4 weeks is acceptable in younger children and those with hemoglobin E beta thalassemia.
As for the volume of a transfusion, children should receive 4 mL per kg of body weight, per gram increase in hemoglobin desired. Partial units can be used to avoid undertransfusion.
For adults, in general, those with pretransfusion hemoglobin less than 10 g/dL should receive three units, and those with pretransfusion hemoglobin of 10 g/dL or greater should receive two units.
The hemoglobin threshold should be adjusted based on fatigue or bone pain, Dr. Lal said. He also noted that patients with intact spleens have higher transfusion needs.
The rate of transfusion should be 5 mL/kg/hour in children and 200-300 mL/hour in adults, based on tolerance. Patients with impaired cardiac function should receive a reduced blood volume at a reduced rate.
Non–transfusion dependent thalassemia
Dr. Vichinsky discussed recommendations for non–transfusion dependent thalassemia (NTDT), noting that these patients may need transient transfusions to prevent morbidity.
Hemoglobin should not be the sole determinant of transfusion need in NTDT patients, he said. Their well-being – activity level, growth, and skeletal changes – is more important than hemoglobin levels. However, patients with hemoglobin levels less than 7 g/dL often have severe morbidity, and those with levels of 10 g/dL or greater are usually protected from severe morbidity.
Indications for transfusion in NTDT patients include:
- Growth failure.
- Hematopoietic tumors.
- Pulmonary hypertension.
- Silent brain infarcts.
- Skin ulcers.
- Severe bone pain.
- Poor quality of life.
- Frequent hemolytic crises.
- Marked and enlarging spleen.
- Failure of secondary sex development.
- Cosmetic and facial changes.
- Pregnancy.
“There is a risk to transfusing this population,” Dr. Vichinsky said. “They’re older, and when you transfuse them, they can get iron overloaded.”
He added that splenectomized NTDT patients have a high risk of alloimmunization, and the transfusion duration should be serially reevaluated in NTDT patients.
Alpha thalassemia major
For alpha thalassemia major, Dr. Vichinsky discussed the importance of prevention, screening, and fetal therapy. He said couples with a fetus at risk of alpha thalassemia major should be identified early and offered, in addition to termination, the option of early fetal transfusion.
Dr. Vichinsky recommended prenatal testing and monitoring of at-risk pregnancies with ultrasound. If the fetus requires a transfusion, monitoring hemoglobin Barts and hemoglobin A is necessary.
A fetus that requires a transfusion should receive packed red blood cells that are cytomegalovirus negative, are less than 7 days old, have been irradiated, have a hemoglobin mass greater than 75%, and have been optimally cross matched with the mother first.
“These babies appear, with serial transfusions, to survive and have a relatively normal neonatal period,” Dr. Vichinsky said.
He added, however, that postnatal management of alpha thalassemia major involves an aggressive transfusion protocol. These patients should be transfused to a higher hemoglobin level than patients with beta thalassemia – roughly 12 g/dL versus 10 g/dL.
These and Dr. Lal’s recommendations are based on information in the Standards of Care Guidelines for Thalassemia – Oakland 2011, the Thalassemia International Federation Guidelines – 2014, the Thalassemia Management Checklists: United States – 2018, the Thalassemia Western Consortium Consensus: US – 2019, and the International Collaboration for Transfusion Medicine Guidelines – 2019.
Dr. Lal and Dr. Vichinsky did not disclose any conflicts of interest.
Fresher blood products are not necessarily better for patients with beta thalassemia, according to a pair of experts.
Red blood cell units stored less than 2 weeks are ideal, but older units are acceptable, and phenotype matching should take priority over unit age, advised Ashutosh Lal, MD, and Elliott Vichinsky, MD, both of UCSF Benioff Children’s Hospital Oakland (Calif.). They discussed these and other recommendations for transfusing patients with thalassemia during a webinar hosted by the Centers for Disease Control and Prevention.
Indications for transfusion
Dr. Lal said patients with beta thalassemia major should be transfused if their hemoglobin is less than 7 g/dL on two occasions 2 weeks apart at baseline, or if their hemoglobin is greater than 7 g/dL and they have symptoms of anemia.
Patients with hemoglobin E beta thalassemia major should be transfused only if they have symptoms of anemia.
“The rationale is that, in beta thalassemia major, it is well established that, once the hemoglobin levels fall below 7 g/dL in young children, there is going to be massive bone marrow expansion, and there will be severe symptoms from anemia,” Dr. Lal said. “But the relationship of hemoglobin with symptoms in E beta thalassemia is less precise.”
The symptoms that should prompt transfusion include slowed growth, skeletal facial changes, splenomegaly, symptomatic or moderate to severe extramedullary hematopoiesis, cerebrovascular events, venous thromboembolism, pulmonary hypertension, osteoporotic fracture, and impaired quality of life in adults.
Dr. Lal said physicians should consider a 6-month trial of transfusions if the indication is unclear. He also noted that red cell antigen genotyping should be performed in all patients who may need transfusions.
Blood products
Dr. Lal said beta thalassemia patients should receive packed red blood cells that are leukoreduced prior to storage. The storage solution can be citrate-phosphate-dextrose solution with adenine (hematocrit 75%) or additive solution (hematocrit 60%).
“It’s important to note that the hematocrit of the two is quite different, and that needs to be inculcated into the decisions on how much volume to transfuse to younger children,” Dr. Lal said.
He noted that units should not be irradiated, as this damages the red cell membrane. And patients with severe allergic reactions should receive washed red blood cells because washing units removes residual donor plasma proteins.
Finally, units should be less than 2 weeks old if possible. Dr. Lal said using fresh units increases the survival of red blood cells post transfusion. However, he and Dr. Vichinsky both stressed that older units are acceptable, and phenotype matching is more important than the age of the unit.
Phenotype matching
Beta thalassemia patients who do not have preexisting alloantibodies or have transient autoantibodies should be matched to Rh and Kell, according to Dr. Lal.
Patients with preexisting alloantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and the specific alloantibody. Patients with persistent autoantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and any alloantibody.
Patients who start transfusions after 5 years of age should be matched to Rh, Kell, Duffy, Kidd, and S. Pregnant patients should be matched to Rh, Kell, Duffy, Kidd, and S, and units should be cytomegalovirus negative.
How to transfuse
Dr. Lal said the pretransfusion hemoglobin target is 10 g/dL, with a range of 9.5-10.5 g/dL in beta thalassemia major and a range of 9.0-10.5 g/dL for E beta thalassemia. A target of 10 g/dL is adequate for most individuals, Dr. Lal said, but he recommends individualization of hemoglobin target for patients with E beta thalassemia.
In general, patients should be transfused every 3 weeks, although 4 weeks is acceptable in younger children and those with hemoglobin E beta thalassemia.
As for the volume of a transfusion, children should receive 4 mL per kg of body weight, per gram increase in hemoglobin desired. Partial units can be used to avoid undertransfusion.
For adults, in general, those with pretransfusion hemoglobin less than 10 g/dL should receive three units, and those with pretransfusion hemoglobin of 10 g/dL or greater should receive two units.
The hemoglobin threshold should be adjusted based on fatigue or bone pain, Dr. Lal said. He also noted that patients with intact spleens have higher transfusion needs.
The rate of transfusion should be 5 mL/kg/hour in children and 200-300 mL/hour in adults, based on tolerance. Patients with impaired cardiac function should receive a reduced blood volume at a reduced rate.
Non–transfusion dependent thalassemia
Dr. Vichinsky discussed recommendations for non–transfusion dependent thalassemia (NTDT), noting that these patients may need transient transfusions to prevent morbidity.
Hemoglobin should not be the sole determinant of transfusion need in NTDT patients, he said. Their well-being – activity level, growth, and skeletal changes – is more important than hemoglobin levels. However, patients with hemoglobin levels less than 7 g/dL often have severe morbidity, and those with levels of 10 g/dL or greater are usually protected from severe morbidity.
Indications for transfusion in NTDT patients include:
- Growth failure.
- Hematopoietic tumors.
- Pulmonary hypertension.
- Silent brain infarcts.
- Skin ulcers.
- Severe bone pain.
- Poor quality of life.
- Frequent hemolytic crises.
- Marked and enlarging spleen.
- Failure of secondary sex development.
- Cosmetic and facial changes.
- Pregnancy.
“There is a risk to transfusing this population,” Dr. Vichinsky said. “They’re older, and when you transfuse them, they can get iron overloaded.”
He added that splenectomized NTDT patients have a high risk of alloimmunization, and the transfusion duration should be serially reevaluated in NTDT patients.
Alpha thalassemia major
For alpha thalassemia major, Dr. Vichinsky discussed the importance of prevention, screening, and fetal therapy. He said couples with a fetus at risk of alpha thalassemia major should be identified early and offered, in addition to termination, the option of early fetal transfusion.
Dr. Vichinsky recommended prenatal testing and monitoring of at-risk pregnancies with ultrasound. If the fetus requires a transfusion, monitoring hemoglobin Barts and hemoglobin A is necessary.
A fetus that requires a transfusion should receive packed red blood cells that are cytomegalovirus negative, are less than 7 days old, have been irradiated, have a hemoglobin mass greater than 75%, and have been optimally cross matched with the mother first.
“These babies appear, with serial transfusions, to survive and have a relatively normal neonatal period,” Dr. Vichinsky said.
He added, however, that postnatal management of alpha thalassemia major involves an aggressive transfusion protocol. These patients should be transfused to a higher hemoglobin level than patients with beta thalassemia – roughly 12 g/dL versus 10 g/dL.
These and Dr. Lal’s recommendations are based on information in the Standards of Care Guidelines for Thalassemia – Oakland 2011, the Thalassemia International Federation Guidelines – 2014, the Thalassemia Management Checklists: United States – 2018, the Thalassemia Western Consortium Consensus: US – 2019, and the International Collaboration for Transfusion Medicine Guidelines – 2019.
Dr. Lal and Dr. Vichinsky did not disclose any conflicts of interest.
Fresher blood products are not necessarily better for patients with beta thalassemia, according to a pair of experts.
Red blood cell units stored less than 2 weeks are ideal, but older units are acceptable, and phenotype matching should take priority over unit age, advised Ashutosh Lal, MD, and Elliott Vichinsky, MD, both of UCSF Benioff Children’s Hospital Oakland (Calif.). They discussed these and other recommendations for transfusing patients with thalassemia during a webinar hosted by the Centers for Disease Control and Prevention.
Indications for transfusion
Dr. Lal said patients with beta thalassemia major should be transfused if their hemoglobin is less than 7 g/dL on two occasions 2 weeks apart at baseline, or if their hemoglobin is greater than 7 g/dL and they have symptoms of anemia.
Patients with hemoglobin E beta thalassemia major should be transfused only if they have symptoms of anemia.
“The rationale is that, in beta thalassemia major, it is well established that, once the hemoglobin levels fall below 7 g/dL in young children, there is going to be massive bone marrow expansion, and there will be severe symptoms from anemia,” Dr. Lal said. “But the relationship of hemoglobin with symptoms in E beta thalassemia is less precise.”
The symptoms that should prompt transfusion include slowed growth, skeletal facial changes, splenomegaly, symptomatic or moderate to severe extramedullary hematopoiesis, cerebrovascular events, venous thromboembolism, pulmonary hypertension, osteoporotic fracture, and impaired quality of life in adults.
Dr. Lal said physicians should consider a 6-month trial of transfusions if the indication is unclear. He also noted that red cell antigen genotyping should be performed in all patients who may need transfusions.
Blood products
Dr. Lal said beta thalassemia patients should receive packed red blood cells that are leukoreduced prior to storage. The storage solution can be citrate-phosphate-dextrose solution with adenine (hematocrit 75%) or additive solution (hematocrit 60%).
“It’s important to note that the hematocrit of the two is quite different, and that needs to be inculcated into the decisions on how much volume to transfuse to younger children,” Dr. Lal said.
He noted that units should not be irradiated, as this damages the red cell membrane. And patients with severe allergic reactions should receive washed red blood cells because washing units removes residual donor plasma proteins.
Finally, units should be less than 2 weeks old if possible. Dr. Lal said using fresh units increases the survival of red blood cells post transfusion. However, he and Dr. Vichinsky both stressed that older units are acceptable, and phenotype matching is more important than the age of the unit.
Phenotype matching
Beta thalassemia patients who do not have preexisting alloantibodies or have transient autoantibodies should be matched to Rh and Kell, according to Dr. Lal.
Patients with preexisting alloantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and the specific alloantibody. Patients with persistent autoantibodies should be matched to Rh, Kell, Duffy, Kidd, S, and any alloantibody.
Patients who start transfusions after 5 years of age should be matched to Rh, Kell, Duffy, Kidd, and S. Pregnant patients should be matched to Rh, Kell, Duffy, Kidd, and S, and units should be cytomegalovirus negative.
How to transfuse
Dr. Lal said the pretransfusion hemoglobin target is 10 g/dL, with a range of 9.5-10.5 g/dL in beta thalassemia major and a range of 9.0-10.5 g/dL for E beta thalassemia. A target of 10 g/dL is adequate for most individuals, Dr. Lal said, but he recommends individualization of hemoglobin target for patients with E beta thalassemia.
In general, patients should be transfused every 3 weeks, although 4 weeks is acceptable in younger children and those with hemoglobin E beta thalassemia.
As for the volume of a transfusion, children should receive 4 mL per kg of body weight, per gram increase in hemoglobin desired. Partial units can be used to avoid undertransfusion.
For adults, in general, those with pretransfusion hemoglobin less than 10 g/dL should receive three units, and those with pretransfusion hemoglobin of 10 g/dL or greater should receive two units.
The hemoglobin threshold should be adjusted based on fatigue or bone pain, Dr. Lal said. He also noted that patients with intact spleens have higher transfusion needs.
The rate of transfusion should be 5 mL/kg/hour in children and 200-300 mL/hour in adults, based on tolerance. Patients with impaired cardiac function should receive a reduced blood volume at a reduced rate.
Non–transfusion dependent thalassemia
Dr. Vichinsky discussed recommendations for non–transfusion dependent thalassemia (NTDT), noting that these patients may need transient transfusions to prevent morbidity.
Hemoglobin should not be the sole determinant of transfusion need in NTDT patients, he said. Their well-being – activity level, growth, and skeletal changes – is more important than hemoglobin levels. However, patients with hemoglobin levels less than 7 g/dL often have severe morbidity, and those with levels of 10 g/dL or greater are usually protected from severe morbidity.
Indications for transfusion in NTDT patients include:
- Growth failure.
- Hematopoietic tumors.
- Pulmonary hypertension.
- Silent brain infarcts.
- Skin ulcers.
- Severe bone pain.
- Poor quality of life.
- Frequent hemolytic crises.
- Marked and enlarging spleen.
- Failure of secondary sex development.
- Cosmetic and facial changes.
- Pregnancy.
“There is a risk to transfusing this population,” Dr. Vichinsky said. “They’re older, and when you transfuse them, they can get iron overloaded.”
He added that splenectomized NTDT patients have a high risk of alloimmunization, and the transfusion duration should be serially reevaluated in NTDT patients.
Alpha thalassemia major
For alpha thalassemia major, Dr. Vichinsky discussed the importance of prevention, screening, and fetal therapy. He said couples with a fetus at risk of alpha thalassemia major should be identified early and offered, in addition to termination, the option of early fetal transfusion.
Dr. Vichinsky recommended prenatal testing and monitoring of at-risk pregnancies with ultrasound. If the fetus requires a transfusion, monitoring hemoglobin Barts and hemoglobin A is necessary.
A fetus that requires a transfusion should receive packed red blood cells that are cytomegalovirus negative, are less than 7 days old, have been irradiated, have a hemoglobin mass greater than 75%, and have been optimally cross matched with the mother first.
“These babies appear, with serial transfusions, to survive and have a relatively normal neonatal period,” Dr. Vichinsky said.
He added, however, that postnatal management of alpha thalassemia major involves an aggressive transfusion protocol. These patients should be transfused to a higher hemoglobin level than patients with beta thalassemia – roughly 12 g/dL versus 10 g/dL.
These and Dr. Lal’s recommendations are based on information in the Standards of Care Guidelines for Thalassemia – Oakland 2011, the Thalassemia International Federation Guidelines – 2014, the Thalassemia Management Checklists: United States – 2018, the Thalassemia Western Consortium Consensus: US – 2019, and the International Collaboration for Transfusion Medicine Guidelines – 2019.
Dr. Lal and Dr. Vichinsky did not disclose any conflicts of interest.