Page 2467 - Hematology_ Basic Principles and Practice ( PDFDrive )

2204 Part XIII Consultative Hematology

Diagnosis of vitamin B 12 deficiency can be aided by the assessment At the time of delivery, pregnant women with sickle cell disease
of homocysteine and methylmalonic acid. If a woman is found to be are managed in a manner similar to those with high cardiac output
deficient in vitamin B 12 during pregnancy, vitamin B 12 injections are anemia. Supplemental oxygen, hydration, and adequate oxygenation
indicated. These are usually injected weekly for 4 to 8 weeks and then during anesthesia should be given to prevent sickling of RBCs and
monthly. the associated complications. During the postpartum period, hemo-
globin levels are followed closely, and prophylaxis for VTE is admin-
istered unless contraindications preclude it.
HEMOGLOBINOPATHIES AND PREGNANCY
Sickle Cell Disease Thalassemias

Every year more than 300,000 children are born with either sickle Pregnant women with an underlying thalassemia typically have
cell disease or thalassemia. Prenatal counseling now exists in many β-thalassemia minor or α-thalassemia trait—conditions with a rela-
countries. In the United States, all newborns are screened for sickle tively benign clinical phenotype—rather than β-thalassemia major or
cell disease (see Chapters 42 and 43). Management of pregnant hemoglobin H disease (see Chapter 41). Because of delayed pubertal
patients with sickle cell disease requires coordination of care between growth or hypogonadism with associated anovulation, women with
the hematologist and obstetrician. Many women with sickle cell β-thalassemia major and hemoglobin H disease rarely become preg-
disease experience more frequent vasoocclusive crises and other sickle nant. Case reports indicate that when it does occur, pregnancy in
30
cell–related complications during pregnancy. The increased fre- women with hemoglobin H disease can be complicated by severe
quency of vasoocclusive crises, particularly during the latter half of hemolytic anemia and hepatosplenomegaly. However, in the setting
pregnancy, likely results from heightened metabolic requirements in of widespread transfusion and iron chelation therapy, pregnancy is
pregnancy, increased venous stasis, as well as the physiologic pro- more frequent in the thalassemia population. Pregnancy outcomes
thrombotic and inflammatory state associated with pregnancy. In among women with β-thalassemia major were recently examined in
addition, pathophysiologic changes in the renal and immune func- 10 patients with homozygous β-thalassemia. Of 15 pregnancies, there
tion of patients with sickle cell disease increase their susceptibility to were 14 live births, a 20% incidence of intrauterine growth restriction
urinary tract infections and pyelonephritis. By causing tissue hypoxia, (IUGR), and 21% were low-birth-weight children. In patients with
sickling of RBCs within the placental vasculature may cause deleteri- β-thalassemia intermedia, approximately 50% of pregnancies are
ous effects on the fetus. 31 complicated by preterm delivery, third-trimester stillbirth, or IUGR. 37
Additional significant complications occur in pregnant women Pregnancy is a common setting for the diagnosis of β-thalassemia
with sickle cell disease. The incidence of preeclampsia, thromboem- minor or α-thalassemia trait in previously asymptomatic women who
bolic events, placental abruption, intrauterine growth retardation, are found to be anemic on routine laboratory evaluation during
low birth weight, and postpartum infections are higher among pregnancy. Several studies indicate that the physiologic anemia of
women with hemoglobin SS, SC, and S β-thalassemia than among pregnancy may be exacerbated in women with thalassemia minor,
38
women without sickle cell disease. One study noted a higher inci- although findings from at least one study suggest otherwise.
dence of stillbirths and perinatal mortality among patients with sickle β-Thalassemia minor and α-thalassemia traits do not have an adverse
32
cell disease, but another study revealed an increased risk of preterm effect on fetal development, fetal morbidity and mortality, or mater-
labor and premature rupture of membranes in women with hemo- nal morbidity and mortality. 39
33
globin SS disease. Despite advances made in sickle disease, a recent Similar to those with sickle cell disease, women with thalassemia
meta-analysis highlights that risks for pregnancy in patients with SS require vigilant follow-up throughout their pregnancies. This includes
genotype remains high with regard to mortality, a fourfold higher risk interval monitoring of maternal vital signs and fetal heart rate,
of stillbirth and a 2.43 higher relative risk of preeclampsia. These risks maternal hemoglobin levels, and fetal growth as assessed by ultraso-
were amplified in low-income countries. Because of the increased risk nography beginning around the 24th week of gestation. Patients are
for such complications, women with sickle cell disease should receive screened for folate and iron deficiency. They should also be assessed
close medical attention throughout the prenatal period. This includes for iron overload, which can develop in individuals with thalassemia
counseling about intrauterine diagnosis of sickle cell disease when as a result of increased intestinal iron absorption, frequent blood
40
appropriate. Pregnant women can undergo chorionic villi sampling transfusions, and rapid turnover of plasma iron. Prenatal genetic
as early as the ninth week of gestation or amniocentesis in the 15th testing can be performed if desired, with results used to counsel
to 16th weeks. A reticulocyte count along with hemoglobin, iron, parents of the child and guide optimal care of the fetus. In terms of
and folate levels should be obtained to assess for deficiency states and therapy, there are no specific treatment recommendations for women
bone marrow suppression. Urinalysis with urine culture is performed with thalassemia during pregnancy, aside from folate supplementa-
as often as every trimester to monitor for asymptomatic bacteriuria. tion and supportive care. In pregnant women with evidence of iron
Finally, beginning around 28 weeks of gestation, patients should have overload, chelation therapy using deferoxamine has been used safely,
weekly clinic visits and begin serial ultrasonography. although the potential for teratogenicity associated with the agent
Treatment of sickle cell disease during pregnancy warrants careful must be considered in this setting. 41
consideration. Hydroxyurea should be avoided. If pregnancy is being
considered it should be discontinued. Women should receive 5 mg/
day of supplemental folic acid. Studies examining the benefit of OTHER HEMOLYTIC ANEMIAS
prophylactic blood transfusions or exchange transfusions have not led
34
to definitive conclusions. Although they may lead to alloimmuniza- Hereditary Spherocytosis
tion, prophylactic transfusions appear to decrease the incidence of
vasoocclusive crises and decrease maternal and fetal morbidity and Hereditary spherocytosis is the most common inherited hemolytic
35
mortality. A conservative approach reserves transfusions for patients anemia among people of northern European descent (see Chapter
42
whose hemoglobin levels fall below 6 g/dL, patients who develop 46). Few cases of pregnancy in individuals with hereditary sphero-
progressive complications related to sickle cell disease, and patients cytosis have been reported. Published reports indicate there may be
36
with obstetric complications. Following this approach, 60% to 75% an increased incidence of first trimester fetal loss in patients with
43
of women with sickle cell disease will require transfusion therapy hereditary spherocytosis. Because some patients have only low levels
during pregnancy. Patients with a sickle cell crisis during pregnancy of hemolysis under normal conditions, the disease may not become
should receive aggressive analgesic therapy, hydration, and oxygen clinically apparent until pregnancy. Pregnant women with hereditary
while undergoing evaluation for infection or other precipitating spherocytosis can exhibit a variety of clinical manifestations. These
influences. include folate deficiency related to the increased requirements of