Question: Is there really a disease that makes your blood look chocolate-colored?
Answer: Oxygen binds to the iron in heme, a protein in red blood cells, RBCs; this iron is normally in the reduced ferrous form, Fe2+, and this oxygenated ferrous iron is what makes the blood look red. The oxygen is then carried to the body’s cells, where it “unbinds” so it can be used in “cellular respiration,” allowing cells to harness energy to perform their necessary functions.
Methemoglobin is an altered state where the iron in the heme that binds the oxygen is in the ferric state — Fe3+. So, although the heme is correctly loaded with oxygen, the oxygen is unable to be “unbound.” RBCs with methemoglobin are chocolate brown, not red.
Normally less than 1% of RBCs have ferric iron, and this methemoglobin is reduced back to normal hemoglobin. In patients with methemoglobinemia, a higher than normal percentage of their RBCs have ferric iron in their heme. The net effect of this is that insufficient oxygen may be supplied to body cells — not because of insufficient numbers of RBCs, i.e. anemia, but because of the compromise of the RBC’s ability to deliver oxygen.
There are two major types of methemoglobinemia, a congenital kind, where the patient is born with it, and an acquired kind — they acutely develop the condition.
There are three “types” of congenital hemoglobinemia, all of which are rare. One is a milder form — inherited autosomal recessively, meaning the patient must get an affected gene from both parents — where the patient has minimal symptoms, although they may have cyanotic, bluish/purplish/gray tinged, skin/mucous membranes; they have a normal life expectancy. The second type — inherited autosomal dominantly, so they only need to get an affected gene from either parent — is more severe and the infant’s early development is compromised, often causing severe disabilities and leading to the infant’s death. Finally, there is a very rare form that has only been described in a few families. As of now, there are no treatments for any of these congenital methemoglobinemias.
Acquired methemoglobinemia occurs in a susceptible patient due to exposure to certain medicines or chemicals. One medicine, dapsone — an antibiotic used for certain bacterial infections — is a common cause, as are certain topical “numbing” medicines including lidocaine and similar medications. Other causes include other medications, certain chemicals, and others.
Acquired methemoglobinemia is much more common than the congenital forms, although it is unknown how many people are affected — most cases are not severe and resolve on their own when the medication/chemical initiating the flare-up is discontinued. There are about 100 severe cases per year that are treated with methylene blue — see below.
Symptoms of acquired methemoglobinemia depend on the number of RBCs affected and are more pronounced in patients with anemia where the number of RBCs are low:
• When 3% to 15% of cells are affected the patient’s skin may be slightly cyanotic, but they are usually otherwise OK.
• If 15% to 20% of RBCs are affected the cyanosis is more pronounced, but again they usually have minimal symptoms, for example they may tire more easily when exerting themselves.
• If 25% to 50% of RBCs are affected the patient typically has symptoms from vital end organs not getting enough oxygen, such as confusion, headache, or lightheadedness from insufficient oxygen to their brain, or chest pain, palpitations, weakness, or shortness of breath from insufficient oxygen to heart cells or other symptoms.
• Once 50% to 70% of RBCs are affected the symptoms are severe, such as altered mental status, come, delirium, seizures, heart arrhythmia or others.
• If 70% or more of the patient’s RBCs are affected the patient has a high likelihood of dying.
Since the affected RBCs are “loaded” with oxygen as is normal — it is the “unbinding” of the oxygen that is compromised — giving supplemental oxygen is not effective, and the “oxygen saturation” measurements appear to be normal. Specialized blood tests are needed to confirm the diagnosis.
Treatment of acute acquired methemoglobinemia depends on the severity and symptoms. A case of acute, severe hemoglobinemia may be life threatening and requires emergency treatment. Methylene blue is one medication used emergently in severe cases. Some patients may require treatment with an exchange transfusion — some of their blood is removed and they are transfused with non-affected blood. Other treatments may be indicated. Prevention of this condition in patients found to be susceptible includes avoidance of possible inciting agents.
Jeff Hersh, Ph.D., M.D., can be reached at DrHersh@juno.com.