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...
Nội dung trích xuất từ tài liệu:
Chapter 101. Hemolytic Anemias and Anemia Due to Acute Blood Loss (Part 7) 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 presentin infancy with severe anemia, whereas mild cases may present in young adults oreven later in life. In women, HS is sometimes first diagnosed when anemia isinvestigated during pregnancy. The main clinical findings are jaundice, anenlarged spleen, and often gallstones; frequently it is the finding of gallstones in ayoung person that triggers diagnostic investigations. The variability in clinical manifestations that is observed among patientswith 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 thesame gene can also give very different clinical manifestations. In milder cases,hemolysis is often compensated (see above), and this may cause variation even inthe same patient, due to the fact that intercurrent conditions (e.g., infection) causedecompensation. The anemia is usually normocytic, with the characteristicmorphology that gives the disease its name. A characteristic feature is an increasein mean corpuscular hemoglobin concentration (MCHC): this is almost the onlycondition 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 mayhave a de novo mutation, i.e., a mutation that has taken place in a germ cell of oneof his parents or early after zygote formation; and (2) the patient may have arecessive form of HS (Table 101-3). In most cases the diagnosis is confirmed onthe basis of red cell morphology and a test for osmotic fragility, a modifiedversion of which is called the pink test. In some cases a definitive diagnosis canbe obtained only by molecular studies demonstrating a mutation in one of thegenes underlying HS. This is carried out only in laboratories with special expertisein this area. Hereditary Spherocytosis: Treatment There is currently no treatment aimed at the cause of HS; no way has yetbeen found to correct the basic defect in the membrane-cytoskeleton structure.However, it has been apparent for a long time that the spleen plays a special rolein HS, through a dual mechanism. On one hand, as in many other HAs, the spleenitself is a major site of destruction; on the other hand, transit through the spleniccirculation makes the defective red cells more spherocytic and thereforeaccelerates their demise, even though lysis may take place elsewhere. For thesereasons, splenectomy has long been regarded as a prime, almost obligatorytherapeutic measure in HS. However, it also increases the risk of certaininfections, and therefore current guidelines (not evidence-based) are as follows. 1. Avoid splenectomy in mild cases. 2. Delay splenectomy until at least 4 years of age, after the risk of severe sepsis has peaked. 3. Antipneumococcal vaccination before splenectomy is imperative, whereas penicillin prophylaxis postsplenectomy is controversial. 4. HS patients often may require cholecystectomy. It used to be considered mandatory to combine this procedure with splenectomy, but this may not be always necessary. Hereditary Elliptocytosis HE is at least as heterogeneous as HS, both from the genetic (Table 101-3)and from the clinical point of view. Again it is the shape of the red cells that givesthe name to these conditions, but there is no direct correlation between elliptocyticmorphology and clinical severity. In fact, some mild or even asymptomatic casesmay have nearly 100% elliptocytes, whereas in severe cases, all sorts of bizarrepoikilocytes may predominate (Fig. 101-3B, C). Clinical features andrecommended management are similar to those for HS. Although the spleen maynot have the specific role it has in HS, in severe cases splenectomy may bebeneficial. The prevalence of HE causing clinical disease is similar to that of HS.However, an asymptomatic form, referred to as Southeast Asian ovalocytosis, hasa frequency of up to 7% in certain populations, presumably as a result of malariaselection. Stomatocytosis This rare condition with autosomal dominant inheritance draws its name(mouth-like cells) from the fact that the normally round-shaped central pallor ofred cells is replaced by a linear-shaped central pallor. Hemolysis is usuallyrelatively mild. Splenectomy is contraindic ...