DBA Fact #1: REMISSION
Approximately 20% of those affected with DBA have a chance of going into spontaneous remission. These can be long lasting. It is possible to go into and out of remission at any point of your life. Remission for DBA is when no treatment (steroids or transfusion) are required for 6 months or more.

DBA Fact #2: IRON CONTENT
One unit of blood contains 200mg of iron, which would be the same amount of iron as eating 69 lean 3oz steaks.

One 3oz steak contains 2.9mg of iron.

Food restrictions of iron are unnecessary in preventing iron overload, however supplemental vitamins should be avoided. (Women's One a Day vit contains 18mg iron/ Men's One a Day vit contains 0mg iron)

DBA Fact #3: RED BLOOD CELL PRODUCTION AND MEDICATION
Red blood cells (RBCs) are produced in the bone marrow. The RBCs carry hemoglobin to all the cells of the body, providing oxygen for function.

Reticulocytes (retics) are immature red blood cells. The % will tell us how hard the bone marrow is working. It is not uncommon in a bone marrow failure syndrome such as DBA to have a retic of less than 1%.

Drugs which have been studied to improve red blood cell production include:

Corticosteroids (prednisone, prelone, prednisolone) Has been the standard drug for treating DBA with a response rate of 80%. Many side effects with long term use, or at high doses, including growth stunting, high blood pressure, cataracts, diabetes, and osteoporosis to name a few. With an initial trial of high doses, there is a risk of infection, especially a serious form of pneumonia. Bactrim can be given to prevent this from happening. If there is a response in hemoglobin and retics, the dose is tapered to a more tolerable lower dose (ideally 0.5 mg/kg every other day)

Cyclosporine A (CSA) and Antithymocyte Globulin (ATG) has been studied in DBA patients with limited success. An NIH-sponsored protocol combining CSA and ATG closed due to poor responses. These drugs are associated with serious side effects, including compromising the immune system and kidney failure.

Epogen (procrit, epo, erythropoietin) Erytropoietin is produced naturally by the kidney to help improve production of RBCs. It can be supplemented by injection for low levels in the system. Patients with DBA have no problem with production, in fact usually have very high levels. Even giving high doses will not increase RBC production in DBA. Proven not to work.

Metoclopramide (Reglan) Has shown to be effective in DBA. A 33% hematologic response rate in a small group of patients with DBA using metoclopramide, an inexpensive, commonly used drug for reflux, induces the release of prolactin from the pituitary gland, thereby increasing prolactin levels. It was proposed that prolactin likely improves erythropoiesis by stimulating cells in the microenvironment of erythroblasts. Unfortunately other studies in the US and Europe did not confirm these responses but showed a 10% response rate.

Leucine (L-leucine) Leucine is a branched chain amino acid (BCAA) used by muscle for energy. Amino acids are the building blocks of protien and commonly found in food. Recently, leucine has been tried in one patient in the literature with DBA. A complete response was associated with its administration (discontinuation of transfusion). In unpublished data 5 more patients have been placed on a leucine trial with partial responses in 4 of the 5 patients (either decreased need for treatment or discontinuation of treatment). Recently we have secured funding, from the Department of Defense (DOD) with the help of the DMAF, to study the safety and possibility of giving leucine to 50 DBA patients on transfusion. This study is soon to open, once the protocol goes through the approval process of the DOD, FDA and hospital review board.

Other drugs undergoing investigation presently or in the near future are: lenalidomide (Revlimid), and drugs used for cancer treatment with a side effect of increased hemoglobin. No results are available yet.

DBA Fact #4: MANAGEMENT OF IRON WITH TRANSFUSION

Criteria for starting chelation:

At transfusion # 10- 20- measure serum ferritin.

If between 10 and 20 transfusions serum ferritin is greater than 1000- 1500 ng/ml, on 2 seperate occasions (a month apart), start chelation.  Ferritin levels are elevated with any stress on the body...the flu, a cold, virus, etc...... It is considered 'an acute phase reactant'.  Need to monitor ferritin as a trend, slowly going up or down, not a jump.

If ferritin is high for age or with number of transfusions, you should be tested for the hemochromatosis gene (HFE) which is another disorder which the body retains iron, causing the same problems as transfusions.  Combine with transfusion- double trouble.

Before starting chelation, should have hearing and vision testing as well as an echocardiocram and EKG as a baseline and then once a year.

- Dosing of Desferal (Deferoxamine, DFO) 40mg/kg 7 nights a week, then may taper to 5 nights a week.

A Desferal challenge may be done before starting DFO, which is admission to the hospital, collecting urine for 24 hrs to measure iron without DFO and then start DFO, collecting urine for another 24 hrs for iron quantification.  If not enough iron is being excreted, may need to hold off starting due to high possiblity of toxicity from DFO.

Desferal only works while it is being infused.  Once it is disconnected, the free iron has nothing to bind to in order to be eliminated from the body.

- Some doctors like to use vitamin C with chelation.  Must be used with caution.  It should not be taken when the DFO is not being infused!!!  The vitamin C pulls iron from the tissues into circulation.  If there is nothing there to attach to (DFO), it will deposit somewhere else- possibly the heart!!!

- Exjade (deferasirox) dosing is 20 mg/kg and may be escalated to 40 mg/kg maximum dose.  Exjade works well to maintain iron balance, does not bring ferritin levels down very quickly.  May be used at the same time as DFO ie. DFO 12 hrs over night, then Exjade in the morning.

So as not to make this posting a book, I will continue next week with management of severe iron overload.

Iron Overload is a Serious Health Condition with no symptoms until it is too late.  Some complications include:

cirrhosis or fibrosis of the liver
cardiac arrythmias, which can be lethal
diabetes
reproductive organ failure
growth stunting
endocrine failure affecting the thyroid
as well as others.

Please call me with any questions.  Iron overload is reversible, even if in trouble with cardiac issues.  Diabetes and reproductive failure may not be reversed.

1-877-DBA-NURSe (322-6877)

DBA Fact #5: WHAT YOU SHOULD CONSIDER BEFORE SCT (stem cell transplantation/bone marrow transplant)

Decide what your reasons are for transplant. Is it because you want it?  Are you sick and tired of transfusion and chelation or steroid therapies enough that it is affecting your quality of life? Or is it because you need it?  Maybe you have developed antibodies, making it impossible to find a compatible blood donor and are resistant to steroids. Maybe you have developed aplastic anemia or myelodysplastic syndrome (MDS) - which are other bone marrow failure syndromes affecting red cells, white cells and platelets.  Maybe steroids do not work and you also have the hemochromatosis gene (which makes you load iron even if not transfused).

 

You should talk with someone who has been through the transplant process and absolutely speak to your hematologist in detail. Please call the DBAR (877-DBA-NURSe), as we have the most experience and information about the outcomes of these types of transplants. Dr. Vlachos has spoken to transplant doctors in other states and has even stopped transplant from taking place, if she felt it was too much of a risk.  Complete information regarding transplant can be found at www.marrow.org. 

 

Risks vs. benefits. The benefits must outweigh the risks.

Risks:  

Death may occur due to complications including: GVH, rejection, infection.

Graft vs. Host Disease (GVHD) - the donor cells can actually attack different parts of the recipient's body, the body's natural defense tries to fight the donor marrow, as it is seen as "foreign." Skin - GVH can cause a rash, discoloration, peeling and sloughing.  Gastrointestinal - can cause the GI tract (from the mouth to the anus) to slough off causing sores and diarrhea.

Rejection - your own immune system is strong enough to reject the donor cells, this happens sometimes with "mini transplant."

Infection - may be severe, even life threatening, if you get something as simple as a cold or virus. Even your food needs to be well cooked, no fresh fruits or vegetables, no fast food, until the immune system comes completely back to normal.

Cancer - DBA has a risk of cancer to begin with, even if it is a small risk. The transplant requires chemotherapy, which in itself can actually cause possible cancer in the future.

Infertility - Chemotherapy can cause the inability of the reproductive organs to work correctly.

Return of DBA -This can happen with a related donor who has "silent" DBA. That is, they have the same gene as the patient, but never knew because they never had anemia or congenital anomalies which sometimes go along with DBA. This is why the donor needs to be carefully screened.

Benefits:

A successful transplant eliminates the need for transfusion and steroids for treatment of anemia in the future. It does not eliminate the 50% possibility of passing it on to your children or the other risks associated with DBA. DBA is in all your genes. Transplant "fixes" the bone marrow production of red blood cells, but does NOT "cure" all aspects of DBA.

DBA Fact #6: RECOMMENDED LABS FOR CHRONICALLY TRANSFUSED PATIENTS
We have been working closely with an adult endocrinologist, Dr. Irwin Klein, at the Feinstein Institute for Medical Research, who has done a lot of research studying heart disease in relation to thyroid dysfunction. Being that DBA patients who are chronically transfused have thyroid issues due to iron overload, he has taken an interest in working with us to prevent thyroid disease as well as cardiac failure due to thyroid dysfunction. As we know, other endocrine organs are also affected - pancreas, gonads, pituitary, as well as linear height. Here is a list of recommended labs to monitor and prevent the devastating effects of iron overload in the thyroid, heart, and the effects of diabetes:

total T3
total T4
TSH
T3 uptake (instead of free T4)
IGF-1(monitors acute fluctuations in insulin action and determines inadequate insulin treatment or poor control of dietary intake)
NT-proBNP (aids in diagnosis of left ventricular dysfunction in heart failure)
Antithyroid Abs (Antithyroglobulin and AntiThyroperoxidase)
Fructosamine (useful in situations where the A1C cannot be reliably measured - as with transfused persons)
Vitamin D

Any questions, please feel free to e-mail me emuir@nshs.edu or call 1-877-DBA-NURSe (322-6877).

DBA Fact #7: THE BONE MARROW EXAMINATION - WHAT IS IT AND WHY SHOULD IT BE DONE
The bone marrow is the "factory" where hematopoiesis takes place (that is a fancy word for the production of the cells in the blood - red blood cells, white blood cells and platelets). A bone marrow examination is a test that looks at the cells in the bone marrow, to see how many there are and what they look like. The bone marrow is found in the center of the bones and is made up of both spongy bone and liquid marrow.

Most of the time, the information from the bone marrow exam can be useful in diagnosing DBA and rule out other disorders which may cause a change in the marrow (such as leukemia, aplastic anemia or myelodysplastic syndrome [MDS]). A bone marrow examination is usually done to make the initial diagnosis of DBA. If this hasn't been done, it is recommended to be done before starting steroids as the medicine can change the appearance of the cells. Aplastic anemia, acute leukemia and MDS have been reported in DBA. For this reason, we perform a bone marrow evaluation if there is a change in blood counts seen on the complete blood counts (CBC), such as a steady decrease in white blood cell count or platelet count. We do not perform routine yearly bone marrow exams in patients whose blood counts are stable and have not changed.

A Bone Marrow Aspirate is usually done from the posterior (back) hip (iliac) bone. Rarely it can be done from the anterior (front) hip bone or the chest bone (sternum). The area to be used is numbed with a topical anesthetic, usually lidocaine. The area is then sterilely cleaned and a needle is placed into the bone. Liquid marrow is removed with a syringe and sent for the following tests:

Morphology of the bone marrow is usually done by the hematologist or the pathologist or both. This is where the bone marrow is spread on a slide and stained with special stains that will "color" the blood cells, making them easier to identify under the microscope. The cells are counted and viewed for their appearance. Abnormalities in the number of cells can give information about potential Aplastic anemia (too few cells of all three cell lines) and abnormalities in their shapes or sizes can be important to diagnose myelodysplastic syndrome or leukemia.

Cytogenetics is the study of the structure of DNA within the cell nucleus. This is done in two parts: Karyotype gives information about the number of chromosomes. A normal person has 23 pairs of chromosomes; one of those pairs is XX (female) or XY (male). An extra chromosome (trisomy) or a missing chromosome (monosomy) will indicate a disease process (for example, an extra chromosome 21 is associated with Down Syndrome). Fluorescence in situ hybridization (FISH) provides researchers with a way to see and map the genetic material in an individual's cells, including specific chromosomes or portions of chromosomes.

A Bone Marrow Biopsy can be done at the same time as the bone marrow aspirate. A piece of the spongy bone is removed, usually using the same needle and puncture area. The biopsy specimen is removed and sent to pathology for:

Cellularity - This is the percentage of cells in the specimen. Bone marrow contains hematopoietic stem cells and fat cells. If a sample is hypocellular, it has fewer than the expected number of hematopoietic cells (cells that mature into red blood cells, white blood cells and platelets). If a sample is hypercellular, it has more than the expected number of hematopoietic cells. Cellularity is age dependent - in newborns, all marrow is hematopoietic (shows 100% cellularity). With age, hematopoiesis (the number of cells) decreases, and the amount of fat increases. Normal cellularity of an adult bone marrow ranges between 30-70% and changes under pathological conditions- a marrow is reported as hypercellular (over 70%), normocellular (30-70%) or hypocellular (under 30%).

If you have any questions, please don't hesitate to contact me or speak to your doctor. Ellen Muir, RN, MSN, CNS "DBA Nurse" 1-877-DBA-NURSe/ 1-877-322-6877emuir@nshs.edu

 

DBA Fact #8: SOME THINGS TO CONSIDER WHEN HAVING A PORT PLACED

Always weigh the risks and the benefits of any medical intervention.    

A port is a small medical device placed under the skin and is used to infuse fluids for medical treatment into the blood stream and to also withdraw blood from a large vein.  It is accessed with a special needle, in usually one stick.  Its parts include a reservoir with a septum (area where the needle is inserted), and catheter.  The special needle used to access it is called a 'huber' needle.  It has a 90 degree bend so it is comfortable when in use and is 'non coring,' which means it won't leave a hole when the needle is removed.

A port may sometimes be referred to as a port-a-cath, mediport, or passport.  Depending on the manufacturer, the name varies.  Just as the name varies, so does the size and materials it is made of.  Most port reservoirs are made of stainless steel, titanium or plastic. For anyone who may need to have a cardiac MRI to look for iron overload, we recommend a plastic port so it does not interfere with the results.  If it cannot be plastic, placement outside the scanning field is recommended (such as right side of chest).  If your hospital does not use plastic ports, they can be special ordered.

The reservoir has a silicone septum which allows it to be punctured with a special needle, hundreds of times.  It is self sealing so it does not leak when the needle is taken out.  The catheter, which attaches to the reservoir, is made of a soft, bendable silicone or polyurethane.  The surgeon must make a pocket for the reservoir under the skin, usually in the chest area.  Speak to your surgeon to decide on what area is best for you.  Your options for placement are upper chest, over the ribs (under the breast), or sometimes in the forearm.  The catheter is then threaded through a major vein and ends at the superior vena cava of the heart.

Poor IV access when receiving monthly blood transfusion is one reason for placing any type of central venous access device (CVAD).  Other reasons may include for delivery of chemotherapy, IV nutrition, antibiotics and for dialysis.   A Broviac (Hickman, Groshong) is another type of CVAD, where the access point is outside of the body.  This type of 'tunneled catheter' is what is used during stem cell transplantation.  A peripherally inserted central catheter (PICC) is another type of external catheter that is used for temporary IV access. 

Benefits:

IV's can be started quickly and relatively easily without repeated needle sticks.  You can continue to bathe and even swim with a port once the surgical incision has healed.  A numbing cream can be placed to the port site 30 minutes before accessing it so you don't feel the pinch.

Some homecare agencies will not provide 24/7 Deferral therapy with an IV that is not a central line.  A port is a good option.

Possible Complications:

Infection - a severe bacterial infection can compromise the device, require its surgical removal, and seriously jeopardize the health.   To prevent infection, these ports are accessed using sterile technique, the needle should be changed once a week.  If you experience fever, you need to seek medical attention immediately, so blood cultures can be taken (sometimes from the port and from a vein in the arm).  Antibiotics need to be given through the port right away to prevent sepsis, a serious life threatening blood infection.

If receiving 24/7 IV therapy, the dressing must stay dry and needle be changed weekly to prevent any bacteria from growing.

Thrombosis - formation of a blood clot in the catheter may clog the port.  To prevent clotting, the port is flushed with saline and heparin, usually by a nurse or other medical professional, or someone properly trained that is a family member or the patient, at least once every four weeks, if not being used and after it is used for treatment or blood draw.

If a thrombin sheath forms at the tip of the catheter (forms a kind of flap) blood is not able to be withdrawn.  The catheter can still infuse as it the flap is pushed away with pressure of the fluid.  In the future, this may become a complete blockage or be a source of infection.

Mechanical failure- sometimes when withdrawing blood the tip of the catheter is pulled against the wall of the vein and no blood is able to be withdrawn, due to too much suction.  The catheter can still infuse as it is pushed away from the vein wall with the pressure of the fluid.

Infiltration- if the needle is not placed through the port septum, fluid can leak and cause pain, swelling and sometimes redness.

Age - If the device is put into a child, the child's growth means that the catheter becomes relatively shorter and will move further away from the superiorvena cava - it may be necessary to remove or replace it.

Complications can occur during surgery, speak to your surgeon and anesthesiologist.

If you are trying to decide which port is right for your needs, you can contact me and I can help guide you on a more personal level.

 

Ellen Muir, RN, MSN, CNS
emuir@nshs.edu