EDUCATION:: HEMATOLOGY


Diamond-Blackfan anemia: a familial case with emphasis on multi-diagnostic approach to diagnosis and treatment


By Floyd Josephat, EdD, MT(ASCP) and Katrina Goff, MS, MLS(ASCP) D


iamond-Blackfan anemia (DBA) is an autosomal dom- inant disorder of the bone marrow where an insuf- ficient amount of red blood cells are produced leading to anemia. The condition is named after the pediatricians Louis K. Diamond and Kenneth Blackfan, who described congenital hypoplastic anemia in 1938. This type of ane- mia usually presents within the first year of life and can lead to a multitude of secondary conditions which will be discussed within this case study.¹ DBA is rare and affects five to seven live births per million worldwide. Corticosteroids is the initial treatment but the Diamond Blackfan Anemia Registry found that 36 percent of those on steroids also require monthly blood transfusions.² This case study will explore a multi-diagnostic approach to testing and treating a familial case of DBA, including hematology, chemistry, and immunohematology. Secondary disorders and diseases such as myelodysplastic syndrome, hemochromatosis, and organ failure will be discussed, as well as gene therapy, bone marrow transplants, and leucine therapy treatments.


Anemia


According to the National Heart, Lung and Blood Institute (2012), anemia is any condition leading to a shortage of red blood cells.³ There are different types of anemia, some not life threatening and some that are very serious. DBA is a type of serious anemia that is chronic and has a strong genetic component. DBA is a failure of the bone marrow to produce an adequate supply of red blood cells. This shortage causes the anemic state in patients and leads to an overall depletion of oxygen throughout the body.4 There are some physical abnormalities that are sometimes associated with this disorder but will not be discussed here, since the patients involved did not demonstrate any such abnormality. Several mutations of ribosomal proteins have been found in those suffering from DBA with 25 percent showing a mutation on the RPS19 gene. This was surprising since the mutation was thought to be due to a deregula- tion in erythropoiesis.6


This disorder is also autosomal


dominant which means that only one copy of the gene is needed to cause the disease.4


Diagnostic criteria


Diagnostic criteria for DBA from the 2008 International Clinical Care Consensus Document are: age less than one year, macrocytic anemia with no other cytopenias, reticulo- cytopenia, normal bone marrow cellularity with a decrease in red cell precursors, and normal platelet and neutrophil counts.”2


side effects that come with steroid use are monitored (upset stomach, increased blood sugar, increased blood pressure, and increased risk for infection). The Diamond Black- fan Anemia Registry found that 82 percent were initially responsive to steroids. Thirty-six percent of that 82 percent also received monthly blood transfusions.2 Most patients suffering from DBA have to receive blood transfusions every three to six weeks. The patients hemo- globin is monitored (usually monthly) to ensure it is not dropping to a dangerous level. People with DBA usually have scheduled transfusions to ensure this doesn’t hap- pen. These patients sometimes present a problem for the healthcare worker since getting good access to a vein may be difficult in someone who receives chronic transfusions. It is also a challenge for the patient to receive appropri- ate blood when they begin developing antibodies to prior blood that they have received. Chronic transfusions are also dangerous since they increase the risk of a transfusion reaction. Those who are transfusion dependent are also at an increased risk of developing a disorder called hemochro- matosis, which is essentially iron overload.2 Hemochromatosis is monitored by ferritin levels which indicate the levels of iron in the body. If iron overload is found to be an issue, chelation therapy can be done to remove the excess iron. There are currently two chelation drugs approved by the FDA: Exjade and Desferal. Exjade is an oral drug that binds the iron and removes it through the stool. Desferal is an injectable treatment over eight hours that removes the excess iron through urine.2


Stem cell, or


bone marrow transplants are also a possible treatment for those suffering from DBA. If successful, the bone marrow then functions normally and makes an adequate amount of red blood cells. The risks for a bone marrow transplant are numerous, including death if a rejection occurs.2


Laboratory diagnosis Hematology


Treatment options for those suffering from DBA initially start with corticosteroid treatment. A large dose is given for the first two weeks after diagnosis to initiate the bone marrow to produce more red blood cells though the mechanism behind this is unknown. After the initial dose, a sustainable dose is given and the possible adverse


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Numerous tests performed in the hematology department are vital in a doctor’s treatment of a DBA patient. Those who are transfusion dependent have a CBC done every three to six weeks, usually coinciding with their transfu- sion protocol. Those on steroid therapy need fewer CBC’s, mainly to check for infections due to lowered immune response. Elevated adenosine deaminase is an enzyme that breaks reticulocytosis. When thrombocytopenia is seen, a bone marrow aspirate is usually performed to check for bone marrow failure or the development of myelodysplas- tic syndrome or aplastic anemia.5


Macrocytosis (red blood cells that are larger than nor- mal) is often seen with DBA. A study done by Pesciotta et al researched whether the macrocytosis was due to protein translation malfunctions by looking at the proteomes in patients with DBA versus samples from healthy patients.


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