EDUCATION:: HEMATOLOGY


Most DBA patients also have an increase in fetal Hgb, a decrease in adenosine deaminase activity, and reticulocy- tosis. Ribosomal protein S19 accounts for up to 25 percent of the 11 proteins that undergo mutations in DBA. Of the four DBA patients who underwent proteomic analysis, abnormal proteins were found in all four including dysfer- lin and MHC class 1 proteins. Findings suggest that DBA protein mutations on RBC’s are special unto themselves.7 Incidence of cancer in DBA is highly elevated, more specifically acute myeloid leukemia (AML), and myelo- dysplastic syndrome (MDS). Clinical presentations and therapies vary greatly between individuals. Vlachos, Atsi- datos, Alter, and Lipton did a retrospective study where they took 608 individuals from the DBA registry in North America and measured incidence of MDS and AML. Of the 608 total patients studied, 17 patients with DBA had more than one type of cancer with 15 demonstrating solid tumors and two with AML. Four patients developed MDS. Eight patients were transfusion dependent at the time of cancer diagnosis, two were in remission, and four had never been treated for anemia. Of the 18 who had cancer, ten had a mutation in a ribosomal protein gene known to be associated with DBA. Three of the four most com- mon genotypes were represented: five with RPS19; two with RPL11 (mother and daughter); and two with RPL5. The median overall survival for all patients was 56 years.8


Immunohematology and chemistry


Iron is an important metal within the body responsible for DNA synthesis as well as oxygen binding. There is no method for ridding excess iron naturally so iron overload can be problematic in those receiving multiple transfu- sions. One unit of red cells has 200 mg of iron, which is more than double the daily recommended dose.10 Ferritin is often used as an indicator for overall iron stor- age in the body. Generally, ferritin levels are therapeutic in DBA patients at levels between 1,000 and 1,500 ng/ mL. These levels are measured every three months and if instability is seen, an MRI is usually ordered to rule out liver and/or tissue damage.5


Liver and cardiac damage is


not uncommon in those receiving multiple transfusions since the excess iron leads to deposits (called hemosid- erins) accumulating in liver and cardiac tissue.9


Shander,


Cappellini, and Goodnough reported on a retrospective study in 2009 that studied 152 patients who had a total of 4,875 units of red cells transfused from 1987-1998. The study found that those who demonstrated iron over- load had a much higher organ failure and mortality rate than those who did not show elevated ferritin.10


Treatment


Leucine is an amino acid that aids in protein syn- thesis regulation and is a possible future treatment for those suffering from transfusion dependent DBA. Jaako et al in 2012 looked at the effects of leu- cine in a mouse model who was RPS-19 deficient. Double the amount of leucine found in serum was given in drinking water to the mice. The study con- cluded that of those given the leucine there was a significant increase in red blood cells as well as hemoglobin concentrations. There appeared to be no adverse side effects.11


This has huge implica-


tions for those with DBA since the disease carries with it so many adverse secondary complications.


30 JUNE 2019 MLO-ONLINE.COM CBC


WBC RBC HGB HCT MCV MCH


MCHC RDW PLT


NEUT


LYMPH MONO EO


BASO MORPH PT


INR PTT


CHEM


GLU Na K


Cl CO2


116 137 4.1


104 29


ANION GAP 8.1 BUN


12


CREA Ca TP


ALB


A/G RATIO GLOBULIN TBILI AST ALK ALT


0.8 8.7 6.4 3.7 1.4 2.7 1.2 41 92 65


LACTIC ACID 13.5


3.1 3.5


10.1 28.6 82.7 29.1 35.2 18.6 300 54 32 10 3 0


MOD ANISO


15.4 1.18 40.9


11.8-15.2 sec 0.00-1.49


22.1-35.7 sec


REFERENCE RANGES 75-110 mg/dl


137-145 mmol/L 3.6-5.0 mmol/L 101-111 mmol/L 21-31 mmol/L 7.0-14.0


9.0-21.0 mg/dl 0.40-1.30 mg/dl 8.5-10.5 mg/dl 6.0-8.4 gm/dl 3.0-5.0 gm/dl 1.0-2.2 gm/dl 1.5-3.8 gm/dl 0.2-1.3 mg/dl 5-49 IU/L


38-126 IU/L 7-56 IU/L


6.5-19.3 mg/dl


Table 1: Patient’s CBC profile and coagulation parameters Lab values: Father


REFERENCE RANGES 4.5-11.0 thou/ul 4.5-5.9 mill/ul 13.5-17.5 gm/dl 41.0-53.0 % 80-95 fl


25-35 pg


25.0-35.0 gm/dl 11.5-14.5 %


150-450 thou/ul 40-70 % 15-45 % 1-8 % 0-6 % 0-2 %


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