Page 2468 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 151 Hematologic Changes in Pregnancy 2205

pregnancy superimposed on chronic hemolysis, hemolytic crisis, and placenta. Patients with autoimmune hemolytic anemia are treated
aplastic crisis. 44,45 The results of two small series suggest that preg- with glucocorticoids and, if necessary, intravenous immunoglobulin
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nancy outcomes for women with hereditary spherocytosis are gener- (IVIg). Supportive transfusions are administered when needed. In
ally good, with improvements in outcomes for splenectomized rare instances, pregnancy appears to precipitate the development of
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patients. Care is primarily supportive. autoimmune hemolytic anemia in a previously unaffected woman.
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The etiology of this phenomenon is not known. Women in this
circumstance have been treated in the standard fashion with favorable
Glucose 6-Phosphate Dehydrogenase Deficiency results.
Favorable pregnancy outcomes observed in women with hereditary
spherocytosis and pyruvate kinase deficiency stand in contrast to THROMBOCYTOPENIA
those in women with glucose 6-phosphate dehydrogenase (G6PD)
deficiency. The deficiency of G6PD leads to hemolytic anemia in the Thrombocytopenia during pregnancy is quite common. It occurs in
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face of oxidative stress (see Chapter 45). The condition increases the approximately 10% of pregnancies. Although there is not one clear
risk of spontaneous abortion, low-birth-weight fetuses, and neonatal value to define thrombocytopenia in pregnancy, generally a platelet
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jaundice. Women with G6PD deficiency should be instructed to count less than 100,000 is considered cause for concern. There is
strictly avoid medications with oxidative potential. Complications some physiologic thrombocytopenia that occurs during pregnancy.
after the ingestion of oxidative drugs can even occur in a carrier of Gestational thrombocytopenia (GT) is the most common cause of
the G6PD deficiency gene if her male fetus has inherited the disease. 48 thrombocytopenia in pregnancy followed by preeclampsia and
immune thrombocytopenia. Much rarer causes include disseminated
intravascular coagulation (DIC), thrombotic thrombocytopenic
Paroxysmal Nocturnal Hemoglobinuria purpura (TTP) and hemolytic uremic syndrome (HUS), and medica-
tion induced. The evaluation of thrombocytopenia is essential to rule
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder out any systemic disorders that may affect pregnancy management
caused by somatic mutation in the membrane-anchoring protein
PIGA (see Chapter 32). PIGA mutation leads, in turn, to deficient
function of critical membrane proteins that in wild-type individuals Gestational Thrombocytopenia
are anchored by the gene product of PIGA. Features of the clinical
phenotype include hemolysis, thrombosis, and bone marrow failure. GT is quite common during pregnancy. The platelet count is gener-
Hemolysis results from deficiency in the membrane proteins CD55 ally never lower than 70,000/µL. This occurs mainly in the third
and CD59, which renders affected individuals susceptible to trimester. Patients are asymptomatic and have no history of throm-
complement-mediated intravascular hemolysis. bocytopenia. The platelet count normalizes within 3 months of
The clinical manifestations of PNH can have a devastating impact delivery but often normalizes within 1 week. The etiology of GT
on pregnancy. Reported cases highlight the significant pregnancy- remains unclear, but it is thought in part to be autoimmune in nature
associated morbidity and mortality in women with this condition. and demonstrates a clear overlap with mild idiopathic thrombocyto-
Complications include severe anemia, thrombocytopenia, thrombotic penic purpura (ITP).
events, preterm delivery, low-birth-weight infants, neonatal death, The management of patients with GT is uncomplicated. Typi-
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and maternal death. 49,50 A study by Ray and colleagues reviewed cally, they can receive epidural anesthesia. However, practice varies at
pregnancy outcomes in 24 women with PNH and found a 20% each institution in terms of platelet threshold for epidural anesthesia.
maternal mortality rate. Platelet counts greater than 100,000/µL are considered safe for epi-
Owing to the high-risk nature of these pregnancies, women with dural anesthesia. There are studies demonstrating safe administration
PNH require close medical attention in the antenatal, perinatal, and of epidural anesthesia in pregnant patients with platelet counts as low
postnatal periods. Prophylactic anticoagulation is recommended as 70,000/µL. 56
because of the high incidence of thrombotic events during pregnancy.
Warfarin is contraindicated because of its teratogenicity. Low-
molecular-weight heparin (LMWH) is favored over unfractionated Immune Thrombocytopenia
heparin (UFH) because it less frequently causes heparin-induced
thrombocytopenia (HIT). Anticoagulation should be interrupted ITP is responsible for pregnancy-associated thrombocytopenia in
during the perinatal period but, in the absence of contraindications, approximately 3% of cases (Chapter 132). It is the most common
reinitiated thereafter and continued for 6 weeks postpartum. 51 cause of thrombocytopenia during the first two trimesters of preg-
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Results of a phase III trial by Hillmen and colleagues demon- nancy. ITP can recur in women with previously documented disease
strated that eculizumab, a humanized monoclonal antibody against or can develop de novo during pregnancy.
the terminal complement protein C5, can reduce levels of hemolysis, ITP is usually not diagnosed during pregnancy. Pregnant patients
stabilize hemoglobin, minimize transfusion requirement, and improve with ITP usually have a long-standing history of thrombocytopenia.
quality of life in patients with PNH. There are case reports describing ITP may be difficult to distinguish from GT because patients with
success in patients chronically receiving eculizumab throughout these conditions can present with similar clinical and laboratory
pregnancy with uncomplicated deliveries. However, a large random- findings. Elevated levels of platelet-associated IgG and antibody titers
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ized trial has not been performed. Supportive care is used as needed can be found in both conditions. Furthermore, assays that detect
throughout pregnancy. RBC transfusions are used in the treatment antibodies against the glycoprotein receptors IIb/IIIa and Ib/IX are
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of anemia. In the setting of thrombocytopenia and bleeding, platelet not specific for ITP. Whereas thrombocytopenia in the first trimester
transfusions may also be necessary. or early portion of the second trimester should raise suspicion for
ITP, thrombocytopenia that develops later in pregnancy should raise
suspicion for GT. A preconception platelet count can also be helpful
Autoimmune Hemolytic Anemia in distinguishing between the two. It is important to attempt to
distinguish between ITP and GT because there is a small but signifi-
Autoimmune hemolysis can occur during pregnancy and lead to cant risk of neonatal thrombocytopenia in the setting of ITP. 60
anemia (see Chapter 47). The relatively small size of immunoglobulin In terms of diagnostic evaluation, human immunodeficiency
(Ig)G immunoglobulin molecules allows them to cross the placenta; virus, hepatitis, and lupus should be tested for if clinically indicated.
thus the IgG subtype of autoimmune hemolytic anemia can adversely Platelet antibody testing is not considered helpful. The peripheral
affect fetuses. In contrast, the larger IgM antibodies do not cross the smear may demonstrate an increased platelet size but should otherwise