Why Does Hereditary Elliptocytosis Cause Gallstones?

It can be confusing to learn that a blood disorder like hereditary elliptocytosis (HE) can cause problems in your digestive system, such as gallstones. The connection comes down to how your body processes the waste from broken-down red blood cells. Because HE causes red blood cells to break down too quickly (a process called hemolysis), your body produces an excess of a yellow waste product called bilirubin. When too much bilirubin builds up in your gallbladder, it can solidify into gallstones ^[1].

The Journey from Blood Cell to Gallstone

To understand how HE leads to gallstones, it helps to follow the life cycle of a red blood cell:

1. Fragile red blood cells: In hereditary elliptocytosis, genetic changes cause the red blood cells to be oval or elliptical-shaped—which is where the condition gets its name—rather than flexible and round ^[2].
2. Premature breakdown (Hemolysis): As these rigid, elliptical cells travel through your blood vessels, they often get trapped and destroyed in the spleen ^[3]. This rapid and premature destruction of red blood cells is known as hemolysis ^[4]. (In severe cases of HE, removing the spleen—a surgery called a splenectomy—can reduce this destruction, which in turn lowers bilirubin levels and reduces the risk of new gallstones ^[5]).
3. Bilirubin production: When red blood cells break apart, they release their contents. Your body breaks these down into a yellowish-orange pigment called bilirubin ^[6]. Because cells are breaking down faster than normal in HE, your blood becomes flooded with this pigment ^[7]. This excess bilirubin is also what causes jaundice (a yellowing of the eyes and skin), a common symptom in people with HE ^[4].
4. Liver processing: Your liver’s job is to filter bilirubin out of the blood and mix it into bile, a digestive fluid that helps break down fats ^[1].
5. Gallbladder storage: The liver sends the bile to the gallbladder, where it is stored until you eat. However, in people with HE, the bile contains unusually high amounts of bilirubin ^[8].
6. Stone formation: When there is more bilirubin than the bile can keep dissolved, the excess bilirubin combines with calcium. Over time, these calcium-bilirubin particles stick together and harden into small, solid pebble-like masses ^[9].

Pigment Stones vs. Cholesterol Stones

Not all gallstones are the same. The gallstones caused by blood disorders like HE are called pigment gallstones (specifically black pigment stones) ^[10]. They are made almost entirely of calcium and bilirubin ^[1].

This is different from the most common type of gallstone found in the general public, which are cholesterol gallstones formed from excess fat and cholesterol ^[11]. Because pigment stones are driven by red blood cell breakdown rather than diet or metabolism, standard advice for preventing gallstones (like eating a low-fat diet) will not stop pigment stones from forming if you have ongoing hemolysis ^[12]. Additionally, while there are some medications that can slowly dissolve cholesterol stones, they do not work on pigment stones.

Who is Most at Risk?

Not everyone with HE will develop gallstones. Your risk depends largely on the severity of your hemolysis ^[8]. If you have a mild form of HE with very little red blood cell destruction, your liver can likely keep up with the bilirubin production.

However, your risk increases if:

• You have a more severe form of HE that causes rapid cell breakdown ^[13].
• You have another genetic trait, such as Gilbert’s syndrome, which slows down the liver’s ability to process bilirubin ^[14][15].

Because gallstones can form silently over years, doctors often recommend routine abdominal ultrasounds for people with HE to monitor for stones before they cause a crisis.

When Surgery is Needed

If pigment gallstones form and block the ducts of your gallbladder, they can cause sharp pain in the upper right side of your abdomen (belly), nausea, or infection. In these cases, doctors often recommend a cholecystectomy (surgery to remove the gallbladder) to treat the issue ^[10].

It is important to know that while removing the gallbladder permanently solves the gallstone problem, it does not cure hereditary elliptocytosis or stop the underlying rapid breakdown of red blood cells.

Safety Note: If you experience sudden, severe pain in your upper right abdomen accompanied by fever, chills, or new or worsening jaundice, seek immediate medical care (such as going to an Urgent Care or ER). These can be signs of a serious bile duct blockage or infection.