Hereditary Spherocytosis. Hemolytic anemias that compose this group of inherited membrane defects are among the most common hemolytic anemias found in gravidas. Mutations are usually an autosomally dominant, variably penetrant spectrin deiciency. Others are autosomally recessive or de novo gene mutations that result from deiciency of ankyrin) protein 4.2, moderate band 3, or combinations of these (Gallagher, 2010; Rencic, 2017; Yawara, 2000). The degrees of anemia and jaundice vary, and diagnosis is conirmed by identiication of spherocytes on peripheral smear and increased osmotic fragility.
Spherocytic anemias may be associated with a so-called crisis that is characterized by severe anemia from accelerated hemolysis, and it develops in patients with an enlarged spleen. Infection can also accelerate hemolysis or suppress erythropoiesis to worsen anemia. An example of the latter is infection with parvovirus B19 (Chap. 64, p. 1216). In severe cases, splenectomy reduces hemolysis, anemia, and jaundice.
Pregnancy. In general, women with inherited red-cell membrane defects do well during pregnancy. Folic acid supplementation of 4 mg daily is given orally to sustain erythropoiesis. Women with hereditary spherocytosis cared for at Parkland Hospital had hematocrits ranging from 23 to 41 volumes percent mean 31 (Maberry, 1992). Reticulocyte counts ranged from 1 to 23 percent. Among 50 pregnancies in 23 women, eight women miscarried. Four of 42 infants were born preterm, but none was growth restricted. Infection in four women intensified hemolysis, and three of these required transusions. Similar results were reported by Pajor and coworkers (1993).
Because these disorders are inherited, the newborn may be afected. Celkan and Alhaj (2008) report prenatal diagnosis via cordocentesis at 18 weeks' gestation and testing for osmotic fragility. Newborns with hereditary spherocytosis may manifest hyperbilirubinemia and anemia shortly after birth.
n intraerythrocytic deficiency of enzymes that permit anaerobic glucose metabolism may cause hereditay nonspherocytic anemia. Most of these mutations are autosomal recessive traits. As discussed earlier (p. 1078), most episodes of severe anemia with enzyme deficiencies are induced by drugs or infections.
Pyruvate kinase deficiency is associated with variable anemia and hypertensive complications (Wx, 2007). Due to recurrent transfusions in homozygous carriers, iron overload is frequent, and associated myocardial dysfunction should be monitored (Dolan, 2002). The fetus that is homozygous for this mutation may develop hydrops ttalis from anemia and heart failure (Chap. 15, p. 309).
Glucose-6-phosphate dehydrogenase (G6PD) deiciency is complex because there are more than 400 known enzyme variants. he most common are caused by a base substitution that leads to an amino acid replacement and a broad range of phenotypic severity (Luzzatto, 2015; Puig, 2013). In the homozygous or A variant, both X chromosomes are afected, and erythrocytes are markedly deicient in G6PD activity. Approximately 2 percent of African-American women are afected, and the heterozygous variant is found in 10 to 15 percent (Mockenhaupt, 2003). In both instances, random X-chromosome inactivation-yonization-results in variable enzyme activity.