HS is divided into mild, moderate, and severe forms of the disease. Classification is based on the amounts of hemoglobin, reticulocytes, and bilirubin and the amount of spectrin in red blood cells. Hemoglobin transports oxygen in the blood. Reticulocytes are immature red blood cells. Bilirubin is formed in the liver when hemoglobin is broken down. Spectrin is a protein that helps keep the shape of a cell. Decreased hemoglobin and spectrin and increased reticulocytes and bilirubin are associated with more severe HS. People with severe HS are usually diagnosed at younger ages than those with moderate or mild disease. Those with mild HS may have compensated hemolysis. This means that red blood cells are created at the same rate as they are destroyed. These individuals may not have noticeable symptoms, and thus be diagnosed later in life.
People with HS have red blood cells that are round like a ball (spherocytes) instead of the typical donut shape. These cells are more likely to break down under stress than normal red blood cells (osmotic fragility). The most common findings in people with HS are anemia, an Enlarged spleen (splenomegaly), and a yellow tone to the skin or eyes (jaundice and icterus, respectively). Anemia can cause extreme Tiredness (fatigue) and a pale tone of the skin (pallor). Splenomegaly can cause stomach pain. People with HS often present to care with recent or ongoing Fever or infection. Other findings in people with HS are less common. These include an enlarged liver (hepatomegaly), growth failure, and allergic diseases. Some people with HS who are diagnosed in infancy may require regular blood transfusions (transfusion dependency). However, typically they grow out of transfusion dependency as they get older.
The most common problem seen in people with HS is gallstone development (cholelithiasis). Gallstones can be detected by ultrasound, which allows early diagnosis and treatment. People with HS may also have hemolytic, aplastic, and megaloblastic crises. Hemolytic crises are often triggered by viral illness and cause more destruction of red blood cells. Blood transfusions may be needed, but hemolytic crises are typically mild. Aplastic crises are less common and more severe than hemolytic crises, but are also triggered by viral illness, particularly parovirus B19. After an individual has been infected with parovirus B19, they are immune for the rest of their lives. Megaloblastic crises are caused by not having enough folate. Children, pregnant women, and people recovering from aplastic crises need more folate, so they are more susceptible. Folate supplementation can prevent megaloblastic crises.
In people with HS, the tissue that creates blood cells may grow outside of the bone marrow, where it is typically found (extramedullary hematopoiesis). There have also been reports of leg ulcers, cancers of the blood, and small cracks in a layer of the retina at the back of the eye (angioid streaks). However, these problems are not believed to be common and have only been reported in a few people with HS.