Anemia and Thrombocytopenia in Pregnancy 

With normal pregnancy, blood volume increases, which results in a concomitant hemodilution. Although red blood cell (RBC) mass increases during pregnancy, plasma volume increases more, resulting in a relative anemia. This results in a physiologically lowered hemoglobin (Hb) level, hematocrit (Hct) value, and RBC count, but it has no effect on the mean corpuscular volume (MCV).

Many centers define anemia in a patient who is pregnant as an Hb value lower than 10.5 g/dL, as opposed to the reference range of 14 g/dL in a patient who is not pregnant. Treatment with 1 mg folic acid and daily iron is helpful when deficiencies are noted.^[1]

Go to Anemia, Emergent Management of Acute Anemia, and Chronic Anemia for complete information on these topics.

Iron deficiency anemia

Iron deficiency anemia accounts for 75-95% of the cases of anemia in pregnant women. A woman who is pregnant often has insufficient iron stores to meet the demands of pregnancy. Encourage pregnant women to supplement their diet with 60 mg of elemental iron daily. An MCV less than 80 mg/dL and hypochromia of the RBCs should prompt further studies, including total iron-binding capacity, ferritin levels, and Hb electrophoresis if iron deficiency is excluded.

Clinical symptoms of iron deficiency anemia include fatigue, headache, restless legs syndrome, and pica (in extreme situations). Treatment consists of additional supplementation with oral iron sulfate (320 mg, 1-3 times daily). Once-daily administration is preferable because more frequent iron supplementation can cause constipation.

The clinical consequences of iron deficiency anemia include preterm delivery, perinatal mortality, and postpartum depression. Fetal and neonatal consequences include low birth weight and poor mental and psychomotor performance.^[2]

Go to Iron Deficiency Anemia for complete information on this topic.

Folate and vitamin B-12 deficiency anemia

Folate deficiency is much less common than iron deficiency; however, taking 0.4 mg/d to reduce the risk of neural tube defects is recommended to all women contemplating pregnancy. Patients with a history of neural tube defect should take 4 mg/d. An increased MCV can be suggestive of folate deficiency; in this case, determine serum levels of vitamin B-12 and folate. If the levels are low, the patient may require oral folate at a dose of 1 mg 3 times daily.

Patients with vitamin B-12 deficiency need further workup to determine the level of intrinsic factor to exclude pernicious anemia. The Schilling test is not recommended during pregnancy, because of the radionuclide used in testing. Treatment of vitamin B-12 deficiency includes 0.1 mg/d for 1 week, followed by 6 weeks of continued therapy to reach a total administration of 2 mg.

Go to Pernicious Anemia for complete information on this topic.

Infectious causes of anemia

In rare instances, anemia can be caused by infections such as parvovirus B-19, cytomegalovirus (CMV), HIV, hepatitis viruses, Epstein-Barr virus (EBV), malaria, babesiosis, bartonellosis, and clostridium toxin. If the patient’s history suggests exposure to any of these infectious agents, appropriate laboratory studies should be performed.

Diamond-Blackfan anemia

Diamond-Blackfan anemia is a rare (7 per 1 million) autosomal dominant disorder of pure red cell aplasia necessitating life-long transfusion. Women who are contemplating or who are pregnant require the consultation and care of a hematologist in conjunction with a maternal-fetal medicine specialist. Concerns during pregnancy include maintaining adequate hemoglobin while decreasing the risk of fetal exposure to the iron chelating agent (deferoxamine) used during transfusions.^[2]

Sickle cell hemoglobinopathies include those abnormalities resulting from an alteration in the structure, function, or production of hemoglobin (Hb). Hemoglobin S (HbS) results from substitution of thymine for adenine in the beta-globin gene, which leads to the substitution of the neutral amino acid valine for the negatively charged glutamic acid at the sixth position from the N terminus in the beta chain. Hemoglobin C (HbC) results from substitution of lysine for glutamic acid.

HbS is also known as sickle cell trait and occurs in 1 in 12 African Americans. HbS is also found in other populations, such as Greeks, Italians (particularly Sicilians), Turks, Arabs, Southern Iranians, and Asian Indians.

Major sickle disorders with severe clinical symptoms include sickle cell anemia (HbSS), sickle cell hemoglobin C (HbSC) disease, and sickle cell beta-thalassemia (HbS beta-Thal). HbSS is the most common of these, occurring in 1 in 625 African Americans. Minor disorders include hemoglobin C disease (HbAC), hemoglobin SE (HbSE), hemoglobin SD (HbSD), and hemoglobin S-Memphis (HbS-Memphis). Heterozygosity for hemoglobin A and hemoglobin S (HbAS) is the most common disorder. These hemoglobinopathies are diagnosed by hemoglobin electrophoresis.

Anemia occurs as a result of the sickle hemoglobinopathies. Deoxygenation of the abnormal red blood cells (RBCs) results in sickling. These permanently damaged RBCs are then removed by the reticuloendothelial system, with the average RBC lifespan reduced to 17 days. The result is a chronic compensated anemia, with Hb typically measured between 6.5 and 9.5 g/dL.

The sickle shape also results in altered motion through the microvasculature. This altered motion can predispose the patient to vascular stasis, hypoxia, acidosis, and increased 2,3-diphosphoglycerate, which perpetuates the cycle by resulting in further deoxygenation and, thus, more sickling. The microvascular injury can result in ischemic necrosis and end-organ infarction.

Organs affected by chronic sickling include the spleen, lungs, kidneys, heart, and brain. Patients with sickle cell anemia are functionally asplenic. Therefore, immunization for encapsulated organisms (pneumococcus and meningococcus) is recommended. Likewise, aggressive treatment should be instituted when encapsulated bacterial infections are diagnosed in sickle cell disease.

Maternal and fetal morbidity

In general, treating a pregnant woman who has sickle cell disease requires close observation. Obtain blood cell counts frequently because anemia can worsen quickly. Folic acid supplementation is recommended because of the quick turnover of erythrocytes. Monitor the pregnancy with serial sonograms for fetal growth, and implement weekly fetal surveillance at 32 weeks’ gestation. Offer the patient pneumococcal and meningococcal vaccines before pregnancy, if possible.

Prophylactic RBC transfusion was once standard in patients who were pregnant and had sickle cell disease; however, it is no longer routinely advised. In 1988, a National Institutes of Health (NIH)–sponsored, multicenter, randomized, controlled trial of 72 patients with HbSS disease showed no significant difference in overall maternal or perinatal outcome of patients who received transfusions and those who did not, except for a lower incidence of painful crises in patients who received transfusions.^[3]

The risks incurred with multiple blood transfusions include infection and alloimmunization, which have their own implications for pregnancy. Similar findings have been reported in a more heterogenous group of patients from the United Kingdom (including patients with HbSS, HbSC, and HbS beta-Thal), although some evidence indicates that the subset of women with sickle hemoglobinopathies carrying twins or higher-order multiples may benefit from prophylactic transfusion.

A woman who is pregnant is at risk of developing sickle cell crisis (SCC). These crises typically are vasoocclusive and may be precipitated by infection. They may be associated with thrombophlebitis or preeclampsia. Commonly, a pattern of sudden recurrent attacks of pain involving the abdomen, chest, vertebrae, or extremities occurs. These crises are somewhat more common in HbSS disease than in HbSC and HbS beta-Thal disease.

Laboratory tests that may be helpful to distinguish between SCC and other possible etiologies of pain include a white blood cell (WBC) count with differential and lactic dehydrogenase (LDH) determinations. An elevated WBC count may be observed in cases of SCC, but a left shift should not be observed. Patients with SCC have elevated LDH levels. Other laboratory tests that should be ordered upon patient admission include a complete blood count (CBC) count, type and cross-match, and arterial blood gas determinations as indicated.

Therapeutic measures for SCC are primarily supportive, with the initiation of intravenous (IV) fluid administration to decrease blood viscosity and pain control as standard pillars of care. If a sudden drop in hematocrit (Hct) occurs, therapeutic transfusion may be advisable. Identification and treatment of any underlying infection is of paramount importance. If the fetus is viable, continuous fetal heart rate monitoring is necessary if maternal oxygenation is compromised. The mother and fetus may benefit from supplemental oxygen.

Remember that during crisis, fetal heart rate tracings may be nonreactive and the blood pressure and pulse may be abnormal; blood pressure and pulse typically revert to normal when the crisis resolves. Umbilical artery Doppler study findings have also been noted as frequently being normal during crisis, even in the setting of abnormal uterine artery Doppler study results.

Overall, great improvement has occurred in maternal and fetal outcome in patients with sickle cell disease. A widely quoted study from West Africa in the early 1970s reported an 11.5% mortality rate in mothers who are homozygous.^[4] Other investigators noted a decrease in maternal death rates at Los Angeles County Hospital, from 4.1% in the era before 1972 to 1.7% from 1972-1982, with all deaths occurring in patients with HbSS or HbS beta-Thal disease.^[5]

A decade later, the NIH-sponsored Cooperative Study of Sickle Cell Disease reported 2 deaths in 445 (0.6%) pregnancies; both of these deaths occurred in patients with HbSS.^[6] Few reported maternal deaths have been associated with HbSC disease in the past 2 decades.

The Cooperative Study also found earlier gestational ages at delivery, smaller birth weights, and an increased rate of stillbirths (0.9%) in the HbSS group, as well as a greater rate of painful crises (50%).^[6] No difference in the rates of preeclampsia existed among the different genotypes, and surprisingly little pyelonephritis occurred (< 1%). Most likely, an increase in first trimester fetal wastage occurs; however, correctly ascertaining this rate in the modern era is difficult, because many women with this disease electively terminate their pregnancies.

The most recent data on sickle cell disease in pregnancy come from a 2008 study by Chakravarty et al, which examined Nationwide Inpatient Sample data and found increased risks of antenatal hospitalization, hypertensive disorders, intrauterine growth restriction (IUGR), and cesarean delivery among women with sickle cell disease.^[7]

The improvement in both maternal and fetal survival notwithstanding, it is important to remember that patients with the sickle hemoglobinopathies remain at risk for renal insufficiency, cerebrovascular accident, cardiac dysfunction, leg ulcers, and sepsis, particularly from encapsulated organisms.

Go to Sickle Cell Anemia for complete information on this topic.

Thalassemia is a disease with many forms, all of which are characterized by impaired production of one of the normal globin peptide chains found in hemoglobin (Hb). Healthy adults should have more than 95% hemoglobin A (HbA), consisting of 2 alpha and 2 beta peptide chains. Other polypeptide chains are gamma, delta, epsilon, and zeta.

Hemoglobin F (fetal hemoglobin, HbF) consists of 2 alpha chains and 2 gamma chains. HbA2 consists of 2 alpha chains and 2 delta chains. Depending on the hemoglobinopathy, some of these other types of hemoglobin may be found on electrophoresis. Presence of these less common adult forms should signal the need for further investigation of a hemoglobinopathy.

The 2 major thalassemias, alpha-thalassemia and beta-thalassemia, result from decreased production of one or more of these peptide chains. The clinical consequences can be ineffective erythropoiesis, hemolysis, and anemia of varying degrees. Consultation with a maternal-fetal medicine specialist is often wise.

Inheritance is autosomal recessive. A lethal homozygous state results when an individual inherits genes for both alpha and beta chains. Various defects that may be responsible for the different thalassemia syndromes have been implicated on a molecular level. In most populations, the gene loci for the alpha-globin chains are located on the short arm of chromosome 16. The beta chain gene is located on the short arm of chromosome 11.

The disease is found throughout the world, but its highest prevalence is in areas endemic for malaria, where it may confer a heterozygote advantage. These regions include the Mediterranean, central Africa, and parts of Asia. Geographical variation exists with the various syndromes. Hemoglobin Bart’s (HbBart) and hemoglobin B (HbB) principally affect people of Asian descent.

Alpha-thalassemia

In alpha-thalassemia, a loss of 2 or more of the 4 alpha-globin genes occurs. Deletion of 1 alpha-globin gene is of no clinical consequence, and laboratory values are in the normal range. Four clinical syndromes have been described.

The homozygous condition results when all 4 genes for the alpha-globin chain are deleted and the fetus is unable to synthesize HbF or any adult Hbs. This condition results in HbBart as the predominant Hb. Because of its high oxygen affinity, little oxygen is released to the tissues. The fetus develops nonimmune hydrops and typically dies in utero or shortly after birth. Preeclampsia can develop in the patient carrying a fetus with alpha-thalassemia major.

Hemoglobin H (HbH) disease is a compound heterozygous state that results in the deletion of 3 of the 4 alpha-globin genes. The abnormal red cells at birth consist of both HbH and HbBart. The neonate appears healthy at birth but then develops hemolytic anemia. Ultimately, the HbBart is replaced with HbH. The result is anemia, which varies in severity and can worsen significantly during pregnancy.

Alpha-thalassemia minor or alpha-thalassemia trait exists when 2 alpha chain genes are missing. It is common in people of African, Southeast Asian, West Indian, and Mediterranean decent. The inheritance can be either cis (--/alpha, alpha)—that is, 1 chromosome without either copy and 1 with 2 copies—or trans (alpha,-/alpha,-), in which each chromosome has only 1 copy of the alpha-globin gene. Patients with the cis pattern are at greater risk of having a baby with HbBart or HbH disease.

Alpha-thalassemia minor causes a mild-to-moderate hypochromic microcytic anemia. Patients with this condition typically do well during pregnancy.

An article published by Leung et al describes the use of ultrasonographic markers during pregnancy to predict fetuses at risk for alpha-thalassemia major.^[8] This may prove to be a useful and attractive option for some patients.

Beta-thalassemia

The beta-thalassemias are the consequence of 1 of many point mutations that cause absence of or reduction in beta-chain production. HbA is usually absent in these individuals. Elevated levels of HbF can often be found.

Beta-thalassemia major, or Cooley anemia, is characterized by precipitation of the excessive alpha chains that results in ineffective erythropoiesis and hemolysis. The fetus is protected from this because of high levels of HbF; however, after birth, as HbF levels fall, the infant becomes anemic.

Although transfusion can prolong life, especially when combined with iron chelation therapy, females with this disorder historically have been infertile. However, the number of successful pregnancies in these patients has been increasing. These patients require frequent transfusions and deferoxamine iron chelation therapy throughout pregnancy.

Beta-thalassemia minor occurs in individuals who are heterozygous for the gene mutation and therefore have variable production of the beta-globin chain. As a consequence, beta-thalassemia minor has variable clinical effects, depending on the rate of beta-chain production. It may be unmasked during pregnancy or uncovered after a patient has delivered a homozygous infant.

Hb electrophoresis characteristically shows a minor fraction of adult hemoglobin (HbA2), which consists of 2 alpha and 2 delta chains, to be increased to greater than 3.5%. In the presence of iron deficiency anemia, the amount of HbA2 may be falsely normal. These patients do not have impaired fertility or pregnancy outcome; however, they may become disproportionately anemic and require iron or folate supplementation during pregnancy. The obstetric emphasis with these patients who are heterozygous is on prenatal diagnosis.

Like the alpha-thalassemias, the beta-thalassemias are common in individuals of Mediterranean, Asian, Middle Eastern, and West Indian descent. Hispanics have a higher prevalence for thalassemia than Caucasians; therefore, these disorders should be considered in the differential diagnosis for anemia in Hispanic patients as well.

Advances in genetic research that allow precise identification of mutations of the hemoglobin (Hb) genes make the process of identifying couples at risk for having offspring with the hemoglobinopathies increasingly important for obstetrician-gynecologists.^[9]

Although universal screening is not recommended, submit complete blood counts (CBCs) with red blood cell (RBC) indices for all pregnant women at the initiation of prenatal care. Pay particular attention to patients of Southeast Asian, Mediterranean, or African descent. Order Hb electrophoresis in patients with these ethnic backgrounds to evaluate for sickle hemoglobinopathies.

Also, refer patients who are from Southeast Asia or the Mediterranean and have anemia and reduced (< 80 fL) mean corpuscular volume (MCV) and normal iron study findings for Hb electrophoresis. Inquire about previous pregnancies and family history of adverse pregnancy outcomes.

If Hb is normal in patients who are of Southeast Asian descent, specifically evaluate for alpha-thalassemia. Offer to test the partner of any carrier of sickle hemoglobinopathies and any patient with elevated (>3.5%) hemoglobin A2 (HbA2) to assess the risk to the fetus. If both partners are identified as carriers, offer DNA-based tests for the fetus.

Tests for prenatal diagnosis of sickle cell anemia and thalassemia now include polymerase chain reaction (PCR) of fetal DNA extracted from amniotic cells, of trophoblasts from chorionic villus sampling, and of erythroblasts obtained from cordocentesis.

In many hemoglobinopathies, including sickle cell disease and most beta-thalassemias, point mutations exist for which specifically designed oligonucleotide probes can be used, especially in combination with knowledge of the patient’s ethnicity. For some thalassemias, performing indirect DNA testing by linkage analysis is still necessary.

Efforts to reduce the risks to the fetus incurred with invasive tests such as amniocentesis, chorionic villus sampling, and cordocentesis have been made by acquisition of fetal cells from the maternal circulation using magnetic cell sorting; however, this procedure is not standard. This technique can only work in hemoglobinopathies in which the mutation has been identified, because only a small amount of fetal cells can be purified. Many couples elect to continue an affected pregnancy.

Preimplantation genetics can now be offered to assure the placement of unaffected embryos in utero.

One more genetic test should be considered in patients with anemia who are of African, Mediterranean, Indian, and Southeast Asian descent: a test for glucose-6-phosphate dehydrogenase (G6PD) deficiency. This deficiency appears to be common in these populations because G6PD deficiency seems to confer relative protection from Plasmodium falciparum malaria.

The G6PD gene is on the X chromosome and therefore follows a sex-linked pattern. Because of lyonization in red blood cells, a variable proportion of RBCs are affected in women who are heterozygous for the deficiency. Therefore, heterozygous women can have mild, moderate, or severe anemia.

Thrombocytopenia in pregnancy is common and is diagnosed in approximately 7% of pregnancies. It is typically defined as a platelet count lower than 150,000/µL. The most common cause of thrombocytopenia during pregnancy is gestational thrombocytopenia, which is a mild thrombocytopenia with platelet levels remaining above 70,000/µL. Patients who are affected usually are asymptomatic and have no history of thrombocytopenia before pregnancy. Their platelet levels should return to normal within several weeks following delivery.

An extremely low risk of fetal or neonatal thrombocytopenia is associated with gestational thrombocytopenia. Gestational thrombocytopenia may result from increased platelet consumption and can be associated with antiplatelet antibodies. Gestational thrombocytopenia can be hard to distinguish from immune thrombocytopenia purpura (ITP) presenting during pregnancy.

Immune thrombocytopenic purpura

Acute immune thrombocytopenic purpura (ITP) is a disorder occurring in childhood; it has few implications for women who are pregnant, because it resolves spontaneously. Chronic ITP may occur in the second or third decade of life, affecting females 3 times as frequently as males. This condition is characterized by immunologically mediated platelet destruction. Antiplatelet antibodies (immunoglobulin G) attack platelet membrane glycoproteins and destroy platelets at a rate that cannot be compensated by the bone marrow.

ITP is usually associated with persistent thrombocytopenia (< 100,000/µL), normal or increased megakaryocytes on bone marrow aspirate, exclusion of other disorders associated with thrombocytopenia, and the absence of splenomegaly. Patients may report a history of easy bruising and petechiae or epistaxis and gingival bleeding preceding the pregnancy.

Although worsening of the disease is not typical during pregnancy, when it occurs, the mother is at risk for bleeding complications at the time of delivery. Therapies aimed at improving the maternal platelet count in anticipation of delivery include intravenous immunoglobulin (IVIg) and steroids. The patient may require platelet transfusion during delivery if the platelet count drops below 20,000/µL. Splenectomy is reserved for severe cases only.

Some controversy exists regarding the threat of intracranial hemorrhage (ICH) in neonates born to mothers with ITP. Although as many as 12-15% of infants born to mothers with ITP may develop platelet counts less than 50,000/µL, the risk of ICH is estimated at less than 1% in 2 recent prospective studies.

Neonatal alloimmune thrombocytopenia

In contrast to ITP, neonatal alloimmune thrombocytopenia may pose a serious risk to the newborn.^[10] It may occur in 1 in 1000 live births and often is unanticipated when it occurs in first pregnancies. The presentation may be in the setting of an unremarkable pregnancy and delivery.

Like Rhesus (Rh) disease, neonatal alloimmune thrombocytopenia results from maternal alloimmunization against fetal platelet antigens. The most severely affected antigen is human platelet antigen-1a, which has been described in approximately 50% of cases in white persons. A high risk of recurrence of neonatal alloimmune thrombocytopenia exists, and it tends to worsen with subsequent gestations in a manner similar to Rh disease.

Clinical manifestations in the neonate include generalized petechiae, ecchymoses, hemorrhage into viscera, increased bleeding at the time of circumcision or venipuncture, or, most gravely, ICH. ICH may occur in utero in as many as 25% of cases.

For patients who have a history of the disease and are experiencing their first pregnancy, referral to a maternal-fetal medicine specialist skilled in cordocentesis may be warranted because the fetus may need to have platelet counts or a transfusion while in utero. IVIg has been shown to improve fetal thrombocytopenia. Cesarean delivery is the preferred route of delivery for infants with platelet counts less than 50,000/µL to reduce the risk of ICH secondary to trauma incurred during labor.

von Willebrand disease

Von Willebrand disease is the most common inherited bleeding abnormality, with a prevalence rate of 0.8-1.3%. This disorder is secondary to a decrease or defect in the von Willebrand portion of the factor VIII complex, which plays a significant role in platelet aggregation.

Type I, which is inherited in an autosomal dominant fashion, is the most common subtype (>70% of cases). Patients may present with menorrhagia, easy bruising, gingival bleeding, and epistaxis or with abnormal bleeding following surgery or trauma. Laboratory findings in patients with type I disease typically show a prolonged bleeding time from decreased platelet aggregation, decreased von Willebrand factor (vWF), decreased factor VIII:C, and sometimes, a prolonged activated partial thromboplastin time. Mild thrombocytopenia may occur.

In patients with type II disease, normal amounts of abnormally functioning vWF may exist. Type III disease is very rare and is characterized by very low vWF. Type III disease tends to have a more severe course.

During pregnancy, a patient with type I disease may have improvement in the bleeding time secondary to an increase in factor VIII:C, although these beneficial effects are not seen until after the first trimester. Thus, patients are at the highest risk of bleeding problems early in pregnancy and in the puerperium.

In a series from the United Kingdom, 33% of patients had first trimester bleeding, and the miscarriage rate was 21%–comparable to rates observed in the healthy population.^[11] However, patients had increased rates of postabortal transfusion, persistent bleeding, and an increased need for repeat dilatation and curettage.

Measure factor VIII:C and bleeding time in patients at their first and third trimester. Historically, cryoprecipitate has been advised when factor levels fall below 80% of the reference level (approximately 50 IU/dL) or when anything but an uncomplicated vaginal delivery is anticipated.

Because of the concern of infection risk with products from pooled donors, deamino-8-D-arginine vasopressin (DDAVP) is now used in many patients, particularly those with type I disease. Another product that can be used at the time of anticipated bleeding is Humate-P, a concentrate of many high molecular proteins needed to replace vWF. A woman with mild disease may not need these measures in case of an uncomplicated vaginal delivery.

Avoid epidural and spinal anesthesia in all patients, except those with mild disease. In the case of cesarean delivery, transfusion generally is recommended. Patients are at increased risk of postpartum hemorrhage; monitor levels of factor VIII:C and bleeding. Because type I disease is autosomal dominant (although with variable penetrance), avoid fetal scalp electrodes during labor and evaluate the neonate before circumcision.

Hemophilia A

Hemophilia A is an X-linked recessive disorder characterized by a decrease in factor VIII:C. Women who are homozygous are extremely rare and require fresh frozen plasma or cryoprecipitate at the time of delivery to prevent postpartum hemorrhage. The main obstetric concern is the risk to the offspring. The risk to a male fetus is 50%. Chorionic villus sampling can help determine if the fetus is at risk by determining fetal sex and providing tissue for DNA analysis.

Hemophilia B

Hemophilia disease, also known as Christmas disease, is an X-linked recessive disorder. Patients have a deficiency in factor IX. Carriers typically have no clinical manifestations. Prenatal diagnosis is limited to determination of fetal sex.

Various medications and drug exposures can lead to anemia (see the Table below).^[12] Most pregnant women and their obstetricians are careful about what medicines are administered or ingested during pregnancy. On occasion, drugs that can cause anemia are required. A good example is the pregnant woman who is diagnosed with breast cancer in early pregnancy and requires chemotherapy, which is an increasingly common clinical scenario. Table. Drugs and Possible Underlying Causes of Anemia

(Open Table in a new window)

Unexplained maternal anemia can be a highly vexing problem for obstetricians and other medical specialists. In such cases, it is prudent to consider all potential causes for anemia, including (but not limited to) pharmacologic, infectious, and immunologic causes. Supportive measures for the pregnant woman should be instituted while pursuing the etiology for anemia.

Besides the use of drugs and medications, as discussed earlier (see above), alcohol consumption should be considered. There is a population of pregnant women who have alcoholism and consume alcohol without revealing this to their obstetricians. Women should be carefully queried regarding their alcohol use.

An example of unexplained anemia was cited in 2008 by Katsuragi et al, who described a Japanese woman with severe hemolytic anemia who had negative results on direct and indirect Coombs tests.^[13] Immunoglobulin G (IgG) levels on the patient’s red blood cells (RBCs) were increased during her pregnancy and resolved post partum. All other antibody test results were likewise negative; screening test results for all hemoglobinopathies were also negative. The patient was successfully treated with prednisolone and RBC transfusions and delivered at 35 weeks’ gestation.

Infectious causes, though rare, include viral etiologies such as HIV, cytomegalovirus (CMV), Epstein-Barr virus (EBV), parvovirus B-19, and the hepatitis viruses. Other infectious causes include brucellosis and tuberculosis.