Questions on Thalassemia Syndromes: Intermedia and Hemoglobin H

February 1, 2012 – CAF Medical Advisory Board Chair Ellis Neufeld, MD, answers some of the questions which have been forwarded to CAF by individuals with thalassemia intermedia.

CAF: Why don’t intermedias qualify for bone marrow transplants, even if the diagnosis changes to major?

Ellis Neufeld

EN: Bone marrow transplantation can be a dangerous endeavor, and the danger increases as patients get older. The definition of the dividing line between major and intermedia is also somewhat vague. As the question supposes, some patients who have gone on for years managed as thalassemia intermedia begin to get regular transfusions for any of a number of reasons. It wouldn’t be fair to say that transplantation is always out of the question for patients who were getting by at some point without transfusions. But on a case by case basis, common reasons not to offer a transplant in this situation include any of the following.

a. For non-transfused thalassemia intermedia patients, the risk of transplant is rarely worth the potential benefits. Adult patients with thalassemia intermedia may well feel as if a curative procedure would be helpful, but their risks would be higher too.

b. For patients who have switched to transfusion management, sometimes the complication that led to the switch also raises the risk of transplantation to an unacceptably high level. For young patients in this situation, I would say transplantation is sometimes warranted, and we can and do sometimes offer transplant in this setting, some with great success.

c. For patients who aren’t transfused with thalassemia intermedia who have become sensitized to red blood cells of donors, the situation is complicated and must be considered individually.

I’d like more Information on thalassemia intermedia: how the body reacts, reasons for bone pain, etc.

This is where thalassemia intermedia is really different from thalassemia major. In patients with major, who cannot survive without transfusion, they are in a sense “not thalassemic” due to their transfusions, and iron overload and other problems from the transfusions themselves are the problem. In thalassemia intermedia, the thalassemia itself is the problem. The basic issue is the bone marrow working overtime, but not well enough, to make red blood cells. This exuberant marrow expansion can cause bone pain, as well as weak bones and bone deformities, and the anemia from insufficient effect can cause fatigue and other problems. At the mildest end, thalassemia intermedia needs little or no treatment. At the most severe end (able to survive but not thrive without transfusion), it can be better to switch to chronic transfusions. There are many other ways that the condition is different from thalassemia major.

I tend to see more information on intermedia when it causes moderate to severe effects; however, I rarely see information on the milder version. What implications does a milder version of it have in the longevity or progression of the disease? If intermedia can advance into major, can it also recede into minor?

This is an important line of questioning for those with mild thalassemia intermedia. At the milder end, beta thalassemia intermedia or a related condition, hemoglobin H disease (an alpha thalassemia intermedia), can be almost indistinguishable from thalassemia trait; sometimes it takes an expert to figure it out. Severe thalassemia intermedia never recedes into minor, but milder forms can have near normal blood counts and cause few problems. It isn’t as if some moderately affected individuals start getting transfused and others become normal later. Any one patient should be followed as an individual, and where there is a question as to the diagnosis, a visit to an expert center is probably worthwhile.

What are some of the complications that are more common in intermedia than in major? What can be done to help prevent these complications?

One is blood clots, especially in patients who have had their spleens out. Splenectomy and its attendant risks are common in thalassemia intermedia because once the spleen gets big, it lowers the blood count and patients don’t feel well. Pulmonary hypertension is also more common, with or without evidence of blood clots. “Extramedullary hematopoiesis”, little or big lumps of bone marrow tissue outside the bones, can grow in the chest, abdomen, near the spine, and other locations. Fractures are probably more common from the marrow working overtime.

Switching to transfusions can prevent or treat many of these complications. Blood thinners or treatment for pulmonary hypertension may be needed in patients with this complication. Calcium status and vitamin D are important to optimize. Patients should be on folic acid supplements. Iron overload can come a decade or two after it would in transfused patients, even without transfusions, and this iron can cause organ damage, so some patients need iron chelation therapy in adulthood. Some clinicians suggest aspirin for thalassemia intermedia patients, especially those splenectomized, because of very high platelet counts. Fatigue and anemia with even minor illnesses may necessitate intermittent transfusions.

What do you think are some things that a person with thalassemia intermedia needs to know but likely may NOT know ?

• The genetics can be tricky; not everyone with beta thalassemia intermedia has two mutant beta globin genes.
• There is a long-term risk of iron overload even without transfusions, so this needs monitoring as in transfused thalassemia.
• Bone status should be checked, along with Vitamin D status.
• Screening for pulmonary hypertension should be carried out regularly.
• A doctor needs to more or less look for each of the issues mentioned in the answer just above this one.
• Consultation at least once with an expert hematologist is worthwhile.
• Patients must be seen emergently for fevers in the context of no spleen. Patients should have vaccines against all the encapsulated bacteria, as well as hepatitis A and B.
• Most thalassemia intermedia patients who have had the experience know that when they go to the emergency department (ED) for fever, the ED doctors become alarmed at the very high white blood counts. The counts aren’t really that high, but nucleated red blood cells from the over-worked marrow appear that way to automated counters.

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