Clinical Presentation and Diagnosis The spectrum of clinical severity of HS is broad. Severe cases may present in infancy with severe anemia, whereas mild cases may present in young adults or even later in life. In women, HS is sometimes first diagnosed when anemia is investigated during pregnancy. The main clinical findings are jaundice, an enlarged spleen, and often gallstones; frequently it is the finding of gallstones in a young person that triggers diagnostic investigations. The variability in clinical manifestations that is observed among patients with HS is largely due to the different underlying molecular lesions (Table 101-3). Not only. | Chapter 101. Hemolytic Anemias and Anemia Due to Acute Blood Loss Part 7 Clinical Presentation and Diagnosis The spectrum of clinical severity of HS is broad. Severe cases may present in infancy with severe anemia whereas mild cases may present in young adults or even later in life. In women HS is sometimes first diagnosed when anemia is investigated during pregnancy. The main clinical findings are jaundice an enlarged spleen and often gallstones frequently it is the finding of gallstones in a young person that triggers diagnostic investigations. The variability in clinical manifestations that is observed among patients with HS is largely due to the different underlying molecular lesions Table 101-3 . Not only are mutations of several genes involved but individual mutations of the same gene can also give very different clinical manifestations. In milder cases hemolysis is often compensated see above and this may cause variation even in the same patient due to the fact that intercurrent conditions . infection cause decompensation. The anemia is usually normocytic with the characteristic morphology that gives the disease its name. A characteristic feature is an increase in mean corpuscular hemoglobin concentration MCHC this is almost the only condition in which high MCHC is seen. When there is a family history it is usually easy to suspect the diagnosis but there may be no family history for at least two reasons 1 The patient may have a de novo mutation . a mutation that has taken place in a germ cell of one of his parents or early after zygote formation and 2 the patient may have a recessive form of HS Table 101-3 . In most cases the diagnosis is confirmed on the basis of red cell morphology and a test for osmotic fragility a modified version of which is called the pink test. In some cases a definitive diagnosis can be obtained only by molecular studies demonstrating a mutation in one of the genes underlying HS. This is carried out only in laboratories with .
