Fig. 12.2 ). The excessive red cell destruction and resultant genitors in the marrow and an increase in red cell production markedbyreticulocytosis.Splenomegaly ismorecommonandprominentinhereditaryspherocytosisthaninanyotherformofhemolyticanemia.Thesplenicweightusuallyisbetween500and1000g.Theenlargementresultsfrommarkedcongestionofthespleniccordsandincreasesinthenumbersofmacrophages.Phagocytosedredcellsareseenwithinmacrophagesliningthesinusoidsand,inparticular,withinthecords.Theothergeneralfeaturesofhemolyticanemiaalsoarepresent,includingcholelithiasis, whichoccursin40%to50%ofpatientswithhereditaryspherocytosis.
Fig. 12.2 Hereditaryspherocytosis—peripheralbloodsmear.Notetheanisocytosisandseveralhyperchromicspherocytes.Howell-Jollybodies(smallnuclearremnants)arealsopresentintheredcellsofthisasplenicpatient.(Courtesy of Dr. Robert W. McKenna, Department of Pathology, University of Texas Southwestern Medical School,Dallas,Texas.)
Clinical Features. The characteristic features are anemia, splenomegaly, and jaundice. The anemia is variable in severity, ranging from subclinical to profound; most commonly it is moderate in degree. Because of their spherical shape, red cells in hereditary spherocytosis show increased osmotic fragility when placed in hypotonic salt solutions, a characteristic that can help establish the diagnosis.
The course is generally stable but may be punctuated by aplastic crises, the most severe of which are triggered by parvovirus B19 infection. This virus has a marked tropism for erythroblasts, which undergo apoptosis during viral replication. Until the immune response controls the infection (usually in 10–14 days), the marrow may be virtually devoid of red cell progenitors. Because of the shortened life span of red cells in hereditary spherocytosis, a lack of red cell production, even for a few days, results in rapid worsening of the anemia. Blood transfusions may be needed to support patients until the infection is cleared.
There is no specific treatment. Splenectomy improves the anemia by removing the major site of red cell destruction. The benefits of splenectomy must be weighed against the increased risk of serious bacterial infections, particularly in children. Partial splenectomy is gaining favor in children because this approach produces hematologic improvement while maintaining protection against sepsis. The downside is that because the partially resected spleen eventually regains its size, many patients will need a second resection.
The hope is that this can be delayed until adulthood, when the risk of serious infection is lower.
Hemoglobinopathies are a group of hereditary disorders caused by inherited mutations that lead to structural abnormalities in hemoglobin. Sickle cell anemia, the prototypic hemoglobinopathy, is caused by a mutation in β-globin that creates sickle hemoglobin (HbS). Numerous other hemoglobinopathies have been described, but these are infrequent and beyond the scope of this discussion.
Sickle cell anemia is the most common familial hemolytic anemia. In parts of Africa where malaria is endemic, the gene frequency approaches 30% as a result of a protective effect against Plasmodium falciparum malaria. In the United States, approximately 8% of blacks are heterozygous HbS carriers and about 1 in 600 have sickle cell anemia.