Anemia in Pregnancy

Kari M. Horowitz, MDa,*, Charles J. Ingardia,

Adam F. Borgida, MDb

MD

KEYWORDS
 Anemia  Pregnancy  Hemoglobin  Iron  Folate
KEY POINTS
 Physiologic anemia occurs in pregnancy because plasma volume increases more quickly
than red cell mass.
 Anemia in pregnancy is defined as hemoglobin and hematocrit lower than 11% and 33%
in the first trimester, 10.5% and 32% in the second trimester, and 11% and 33% in the
third trimester.
 An increase of 60 mg of elemental iron daily is recommended in the second and third trimesters because an average diet cannot meet the increased iron demand in pregnancy.
 Iron deficiency anemia accounts for 75% of all anemia in pregnancy.
 It is recommended to screen for and treat iron deficiency anemia in pregnancy because
treatment to maintain maternal iron stores may be beneficial to neonatal iron stores.

INTRODUCTION

Numerous adaptations occur in women to accommodate pregnancy. One of the most

profound changes is a complex interaction among the renal, hematologic, and endocrine systems to prepare for the expected blood loss that occurs at the time of delivery. Fluid retention begins early in pregnancy with a lag in the production of red blood
cells (RBCs) causing a physiologic anemia of pregnancy in most women. With a
focus on singleton gestations this article discusses the physiologic changes in the
hematologic system. Also discussed are this physiologic anemia and other common
causes of anemia in pregnancy.
HEMODYNAMIC PHYSIOLOGY OF PREGNANCY
Plasma Volume Changes

In response to early renal homeostatic changes, maternal blood volume begins to

increase by 6 weeks of gestation. As a result of free body water retention, the maternal

Department of Maternal Fetal Medicine, University of Connecticut Health Center, 263

Farmington Avenue, Farmington, CT 06030, USA; b Department of Maternal Fetal Medicine,
Hartford Hospital, 85 Jefferson Street, Suite 625, Hartford, CT 06102, USA
* Corresponding author.
E-mail address: khorowitz@resident.uchc.edu

Clin Lab Med 33 (2013) 281291

http://dx.doi.org/10.1016/j.cll.2013.03.016
labmed.theclinics.com
0272-2712/13/$ see front matter 2013 Elsevier Inc. All rights reserved.

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volume can rapidly increase likely because of changes in the renin-angiotensinaldosterone system causing a change in the osmotic set-point.
Plasma volume continues to rise until the third trimester when it plateaus at 32 to
34 weeks. The average pregnancy has nearly a 50% increase in blood volume, which
occurs from an expansion of plasma volume and RBC mass.
Red Cell Mass Changes

Whereas free body water can be retained rapidly by the kidneys, the production of red
cells cannot occur as quickly. Because of this lag of increased red cell production,
there is a disproportionate increase in intravascular volume causing the physiologic
anemia of pregnancy. The red cell mass increases by approximately 25% (300 mL)
by the last month of pregnancy.1
PHYSIOLOGIC ANEMIA OF PREGNANCY

Maternal hemoglobin levels decline progressively from 6 weeks gestation to approximately 35 weeks gestation, then increase in the month before delivery (Fig. 1). In the
absence of iron supplementation, the nadir is approximately 10.5 g/dL at 27 to
30 weeks of gestation.
The Centers for Disease Control and Prevention has published levels of hemoglobin
and hematocrit to define anemia as less than the fifth percentile of a healthy reference
population. These are 11% and 33% in the first trimester, 10.5% and 32% in the
second trimester, and 11% and 33% in the third trimester.1
Iron Requirements in Pregnancy

Most women of reproductive age have marginal iron stores. This has been shown in
iron assessments of bone marrow in healthy young women. Given the demand for
increased red cell mass in pregnancy, iron needs are increased. Because an average
diet cannot meet the increased iron demand in pregnancy, the Institute of Medicine
recommends an increase of 60 mg of elemental iron daily in the second and third
trimesters.2
Physiologic retention of fluid early in pregnancy may lead to anemia being a very
common diagnosis. It is important to recognize laboratory changes that may indicate
true iron deficiency. The red cell mass, hemoglobin, and hematocrit are all relatively
lower in pregnancy. The mean corpuscular volume (MCV) and mean corpuscular

Fig. 1. Blood volume changes during pregnancy. Data from Gordon MC. Maternal physiology. In: Gabbe SG, Niebyl JR, Simpson JL, et al, editors. Obstetrics: normal and problem
pregnancies. Philadelphia: Churchill Livingstone; 2007.

Anemia in Pregnancy

hemoglobin (MCH) should not change with normal iron. Changes in these indices
should heighten the suspicion of the diagnosis of anemia related to iron deficiency.3
CLASSIFICATION OF ANEMIAS

There are several methods of classification of anemia: pathogenesis, clinical presentation, and red cell morphology.
Pathogenesis Classification

Pathogenesis classification is divided into two causes relating to bone marrow

production: hyporegenerative and regenerative. In hyporegenerative anemia there is
failure to increase either erythrocyes or reticulocytes despite increase in erythropoietin. This is caused by alteration of the pluripotent stem cells, which results in a pancytopenia. This alteration displaces normal hematopoesis. This can be the result of
myelodysplasia, leukemia, fibrosis, and several infectious or hereditary disorders.
Regenerative anemia occurs in response to loss of erythrocytes (acute or chronic).
There is an increased production of erythropoietin that subsequently increases
erythrocytes and reticulocytes.
The reticulocyte count is helpful in differentiating causes of anemia with decreased
bone marrow response from those where there is an appropriate bone marrow
response. This can be particularly helpful when the MCV is normal. Reticulocytes
are measured as the absolute number per millimeter or as the proportion of the total
number of erythrocytes. Because reticulocytes are released early and have a longer
lifespan than mature RBCs, another method to more accurately assess production
is the reticulocyte production index (RPI), which corrects for these confounding
factors. RPI is calculated by the following formula: reticulocyte count  hemoglobin
observed/normal hemoglobin  0.5. Normal values range from 1% to 2%.
Clinical Presentation Classification

Clinical presentation is classified as acute (eg, acute blood loss, hemolysis) or chronic
(eg, infection, chronic disease).
Red Cell Morphology Classification

The World Health Organization classification by red cell morphology (normocytic,

microcytic, and macrocytic) is more widely used because of its relationship to more
easily understood laboratory analysis of red cell indices. MCV is used to differentiate
these anemias. In this classification anemias are divided into microcytic (MCV <82 fL);
normocytic (MCV 5 8298 fL); or macrocytic (MCV >98 fL).
MCV is related to MCH, which reports the mean hemoglobin per RBC (normal range,
2732 pg). Microcytic anemias are also hypochromic, and most macrocytic anemias
are hyperchromic.
The mean MCH concentration reports on the average hemoglobin in each RBC as a
percentage (normal, 32%36%), which varies little in most anemias and provides little
additional clinical usefulness. Because the MCV represents an average of the total
RBC population analyzed, it does not provide information about the homogeneity of
the RBC population. Normally RBCs are a standard size (68 mg), but in certain disorders the larger portion of cells are not in the normal cell size range. This aspect can be
analyzed through the red cell distribution width. As the RBC population exceeds the
normal range in RBC size there is an increase of the red cell distribution width (anisocytosis). The normal range for the red cell distribution width is 11% to 15%. Red cell

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distribution width and MCV together can often be used to differentiate anemias of
mixed causes from those with a single cause.
MICROCYTIC ANEMIA

Microcytic anemias arise as a result of hemoglobin synthesis failure or insufficiency.

The cause of these anemias falls into three broad categories: (1) heme synthesis deficiency, (2) globin synthesis deficiency, and (3) sideroblastic defects. The anemias
associated with these categories include the following:
Heme synthesis deficiency
 Iron deficiency
 Anemia of chronic disease
Globin synthesis deficiency
 a-Thalassemia
 b-Thalassemia
 Sickle cell disease
 Hemoglobin E defect
 Hemoglobin C defect
Sideroblastic defects
 Hereditary sideroblastic anemia
 Acquired sideroblastic anemia
The impact of these disorders in pregnancy is discussed in detail next and elsewhere in this issue.
NORMOCYTIC ANEMIA

Normocytic anemias arise when there is anemia in the setting of normal RBC indices.
In normal pregnancy the increase in blood volume may lead to a dilutional anemia. In
the truly anemic patient there is increased blood loss or destruction; failure of bone
marrow function (aplastic anemia); nutritional deficiency; renal failure; or hemolysis.
Chronic disease may also be associated with a normocytic anemia. Hereditary disorders of RBC membranes (spherocytosis, elliptocytosis) and red cell enzyme deficiencies (glucose-6-phosphate dehydrogenase [G6PD], pyruvate kinase) can also
lead to a normocytic anemia.
In regenerative anemia (hemolysis and bleeding) and hyporegenerative anemias
(aplasia, chronic disease, nutritional deficiency) the reticulocyte activity, as measured
through the corrected RPI, can be diagnostic. In hemolysis other parameters are
elevated including lactic dehydrogenase, indirect bilirubin, and haptoglobin levels.
MACROCYTIC ANEMIA

Macrocystic anemias are classified as megaloblastic and nonmegaloblastic. Megaloblastic anemias are related to vitamin B12 or folate deficiencies and are characterized
by hypersegmented neutrophils. Neutrophils normally develop more segments with
aging (usually less than four segments). Hypersegmented neutrophils are those with
six or more segments. These anemias also have macro-ovalocytic RBCs. In nonmegablastic anemia these characteristic features are absent.4,5 The etiologies include
the following:
 Megaloblastic
 Nutritional deficiency
 Anticonvulsant use

Anemia in Pregnancy

 Enteral malabsortion
 Primary bone marrow disorders
 HIV medications
 Inherited disorders
 Nonmegaloblastic
 Medication side effects
 Hypothyroidism
 Hepatic disease
 Splenectomy
SPECIFIC ANEMIAS
Iron Deficiency Anemia

Iron deficiency anemia accounts for 75% of all anemias in pregnancy. Symptoms
include easy fatigue, lethargy, and headaches. It is associated with increased risk of
low birth weight, preterm delivery, perinatal mortality, lactation failure, and postpartum
depression.
Risk factors include diets poor in iron-rich foods (shellfish, beef, turkey, enriched cereals, beans, lentils); diets poor in iron absorption enhancers (orange juice, grapefruit
juice, strawberries, broccoli, peppers); diets rich in foods that diminish iron absorption
(diary, soy, spinach, coffee, tea); pica; gastrointestinal disease affecting absorption;
menorrhagia; and short pregnancy interval. The Centers for Disease Control and Prevention recommends screening for and treating iron deficiency anemia in pregnancy
because in addition to maternal benefits, treatment to maintain maternal iron stores
may be beneficial to neonatal iron stores.6
Laboratory evaluation reveals a microcytic, hypochromic anemia with low plasma
iron, high total iron-binding capacity, and low ferritin. The typical diet includes 15 mg
elemental iron per day. During pregnancy, the recommended daily iron consumption
is 60 mg of elemental iron. The most common treatment is 325-mg tablets iron
sulfate taken one to three times a day, which each contain 65 mg elemental iron.
Sustained-release and enteric-coated preparations dissolve poorly and are less
effective. Reticulocytosis is typically seen in 7 to 10 days. Hemoglobin can rise by
as much as 1 g per week in severely anemic women. Absorption can be improved
by adding 500 mg of ascorbic acid. Side effects of oral iron include nausea, vomiting,
diarrhea, and constipation. These symptoms are related to the dose of iron. Iron
therapy should be continued to replete iron stores for 6 months after symptoms
resolve.7,8
Parenteral iron is available for patients with malaborption syndrome and severely
anemic patients who refuse oral iron supplementation. Iron dextran, ferric gluconate,
and iron sucrose are the formulations available in the United States. Iron dextran can
be given intramuscularly or intravenously. Anaphylactic reactions have been reported
in 1% of patients receiving iron dextran. Ferric gluconate and iron sucrose are given
intravenously. The pharmacist can calculate the dose of parenteral iron required
based on hemoglobin deficit and lean body weight. Intravenous iron therapy has
been shown to replete iron stores and raises hemoglobin levels faster than oral
iron, but no long-term benefits have been observed.9,10 Erythropoietin with or without
iron supplementation can safely be used to treat severe iron deficiency anemia
in pregnancy. When compared with iron supplementation alone, the addition of
erythropoietin to iron supplement has been shown to increase reticulocyte count
and hematocrit faster, and decrease the time required to reach target hemoglobin
levels.11,12

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Megaloblastic Anemia

Megaloblastic anemia is the second most common nutritional anemia seen in pregnancy. It is most commonly caused by folate deficiency, but it may also be caused
by vitamin B12 deficiency. These deficiencies are caused by poor nutrition or
decreased absorption. Folate and vitamin B12 deficiencies are becoming increasingly
common in pregnancy because of an increased number of pregnancies after bariatric
surgery.
Folate deficiency presents with symptoms of anemia, rough skin, and glossitis. The
complete blood count can show macrocytic, normocytic, or normochromic anemia
with hypersegmentation of polymorphonuclear leukocytes. The reticulocyte count
may be normal or low. White blood cell and platelet counts may also be decreased.
Folate levels are low and vitamin B12 levels are normal. The recommended treatment
is 1 mg oral folate daily. Parenteral folic acid at the same dose may be used in cases of
malabsorption. A reticulocyte response is seen in 2 to 3 days.
Vitamin B12 deficiency may present with neurologic defects from damage to the posterior columns of spinal cord in addition to symptoms of anemia. The most common
causes of vitamin B12 deficiency are autoimmune inhibition of intrinsic factor production
(pernicious anemia); inadequate production of intrinsic factor after gastrectomy; and
malaborption syndrome. Laboratory features are similar to folate deficiency, except
folate levels are normal and vitamin B12 levels are low. Treatment is 1 mg intramuscular
vitamin B12 every day for 1 week, followed by once a week for 4 weeks, and then once a
month thereafter. Reticulocyte response is seen after 3 to 5 days of therapy.7
Sideroblastic Anemia

Sideroblastic anemia is a diverse group of disorders with a common defect in heme

biosynthesis and defective iron use. The disorder may be hereditary or acquired. Acquired sideroblastic anemia is associated with malignancies; inflammatory disorders;
and drugs and toxins including ethyl alcohol, lead, and isonicotinic acid. It may also be
idiopathic with no identifiable cause.
The hallmark of sideroblastic anemia is the ringed sideroblast. Sideroblasts are
marrow erythroid precursors. The rings are perinuclear iron representing deposits of
iron phosphate that have not been used in heme synthesis. Sideroblastic anemia is
diagnosed by ringed sideroblasts found on bone marrow biopsy.
Recommended treatment begins with correcting the underlying disorder or
removing the causative agent. Patients are managed with periodic transfusions of
washed erythrocytes to maintain hemoglobin in the 9 to 10 range. Treatment includes
100 to 200 mg of vitamin B6 per day and oral folate supplementation of 1 to 2 mg per
day. Sideroblastic anemia is also associated with myelodysplastic syndromes, so
patients should be monitored for the development of acute leukemia.13
Hereditary Spherocytosis and Elliptocytosis

Hereditary spherocytosis is the most common form of inherited hemolytic anemia. It is

still rare with a prevalence of about 1 in 5000. Hereditary spherocytosis is a spectrum
of related hematologic disorders characterized by spherocytes, anemia, hemolysis,
and jaundice. Molecular defects in the RBC cytoskeleton caused by deficiencies in
membrane proteins lead to increased red cell fragility. Inheritance is autosomaldominant with variable penetrance. Hemolytic crisis can be precipitated by various
conditions including infection, trauma, and pregnancy. Diagnosis is suspected based
on family history and findings of hyperproliferative anemia and confirmed by osmotic
fragility test.

Anemia in Pregnancy

Pregnant women who have not previously had a splenectomy should be monitored
for hemolytic crisis and treated with folate supplementation. Hemolytic crisis is treated
with transfusion or splenectomy. Splenectomy may be performed during pregnancy to
control hemolysis and treat severe anemia. Hereditary spherocytosis does not
contribute to perinatal morbidity or mortality in absence of severe anemia. Perinatal
outcomes are generally good with no increase in complications as compared with
the general population.7,14
Hereditary elliptocytosis (autosomal-dominant inheritance) is a milder hemolytic
anemia caused by structural defects in the RBC wall. The signs and symptoms are
similar but less severe than hereditary spherocytosis. Cases of hereditary elliptocytosis in pregnancy are treated with supportive therapy, including treatment of any underlying condition, folate supplementation, and transfusions if needed.7
Autoimmune Hemolytic Anemia

Autoimmune hemolytic anemia is caused by warm-reactive and cold-reactive antibodies. Warm-reactive antibodies are IgG directed against Rh system. They are
seen in association with hematologic malignancies; lupus; viral infections; and drug
ingestion (penicillin and methyldopa). Cold-reactive antibodies are IgM; are anti-i or
anti-Ip; and are seen in association with mycoplasma infections, mononucleosis,
and lymphoreticular neoplasms. In many cases, no precipitating event is found. Cases
of pregnancy-induced hemolytic anemia with spontaneous remission after pregnancy
have been reported. Mild transient hemolysis lasting 1 to 2 months can be seen in
infants born to mothers with hemolytic anemia.15
Laboratory evaluation shows a hyperproliferative macrocytic anemia. Peripheral
blood smear is significant for microcytes, polychromatophilia, poikilocytosis, and
normoblasts. Diagnosis is confirmed by positive direct Coombs test.
Treatment is directed toward stopping hemolytic process and correcting the underlying disease. Blood transfusions, corticosteroids, immunosuppression, and splenectomy are the most common treatments. Eighty percent of patients with warm-reactive
antibodies respond to corticosteroids. Splenectomy is effective in 60% of patients.
Patients who are unresponsive to steroids and splenectomy can undergo a trial immunosuppression. Treatment of cold-reactive antibodies depends on the severity of the
disease. Patients with mild anemia may simply need to avoid cold temperatures. Corticosteroids and splenectomy are not effective treatments for cold-reactive antibodies.
In severe anemia, a trial of immunosuppression or plasmapheresis may be needed.7,16
G6PD Deficiency

G6PD deficiency is the most common hereditary RBC enzyme deficiency. G6PD
reduces nicotinamide adenine dinucleotide phosphate while oxidizing glucose-6phosphate, aiding in the detoxification of free radicals and peroxides. G6PD provides
the only means of generating the reduced form of nicotinamide adenine dinucleotide
phosphate, and its deficiency makes RBCs vulnerable to oxidative damage. All tissues
express the G6PD gene, but the effects of its deficiency are most severe in RBCs.
The G6PD gene is located on the X chromosome. Males carrying the defective gene
suffer hemolysis, especially if exposed to drugs that stress the pentose phosphate
pathway. Individuals are generally hematologically normal unless they are exposed
to precipitating drugs, or have metabolic disturbances to precipitate acute episode
of hemolysis. Drugs that can induce hemolysis include the following:
 Acetanilide
 Doxorubicin

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Methylene blue
Nalidixic acid
Nitrofurantoin
Phenazopyridine
Primaquine
Sulfamethoxazole

Female heterozygotes are generally unaffected, but may have G6PD activity levels
that fall in range of affected males. G6PD deficiency most commonly affects Africans,
Mediterranean populations, Sephardic Jews, Asiatic Jews, and some Asian populations. Most African Americans carry a variant that causes mild hemolytic anemia.
The Mediterranean variant causes a more severe anemia and may be precipitated
by fava beans.17
It is unusual for G6PD deficiency to affect pregnancy. Woman should be careful to
avoid known precipitants of hemolysis including sulfa drugs and some antimalarials. If
a hemolytic episode occurs during pregnancy, the precipitating medication should be
discontinued, any infections should be treated, and patients should be supported with
transfusion if necessary. Affected male infants of female carriers have increased incidence of hyperbilirubinemia.18 The incidence of severe jaundice is 11% in newborns
with G6PD deficiency, but may be up to 50% if the infant has an affected sibling.7
Aplastic Anemia

Aplastic anemia is characterized by pancytopenia in the presence of hypoplastic bone

marrow. If untreated, aplastic anemia leads to death by infection or bleeding. There
are three possible causes for this disease: (1) there may be insufficient stems cells
resulting in an intrinsic defect or a reduction in the number of stems after exposure
to a noxious agent, (2) a suppressor substance that inhibits stem cell maturation
may be present, and (3) an autoimmune reaction can cause the death of stem cells.
Agents and medications that can lead to marrow aplasia include












Benzene
Ionizing radiation
Nitrogen mustard
Antimetabolites
Antimitotic agents
Toxic chemicals
Chloramphenicol
Anticonvulsants (carbamazepine, phenytoin)
Analgesics
Gold salts
Paroxysmal nocturnal hemoglobinuria (discussed later)

Many other agents have also been implicated in cases of aplastic anemia, and in
50% of cases no causative agent can be found.7,19 There have also been reported
cases of pregnancy-associated aplastic anemia. Cases are classified as pregnancy
induced if they are identified after the onset of pregnancy, no other cause can be identified, there is a decrease in all blood cell counts, and there is hypoplastic bone
marrow.20,21
Patients with aplastic anemia present with symptoms related to severe anemia,
bleeding, and infection. Laboratory evaluation reveals pancytopenia with hypoproliferative reticulocyte count. Bone marrow biopsy shows hypoplastic bone marrow with
normoblastic erythropoiesis. The mortality rate is 50% in cases of severe aplastic

Anemia in Pregnancy

anemia. Bone marrow transplant is the treatment of choice with a 50% to 70% longterm survival rate.7,20
Supportive therapy (see later) is the recommended treatment of aplastic anemia
during pregnancy, because bone marrow transplant in pregnancy is contraindicated.
With supportive treatments, maternal mortality rate is less than 15% and more than
90% survive in remission. The maternal risks in pregnancy are caused by infections
and hemorrhage. The goal of supportive treatment is to maintain hemoglobin levels
through periodic transfusions, prevent and treat infection, and stimulate hematopoiesis. This is done by using intravenous immunoglobulin, colony-stimulating factors, and
steroids.21,22 There are reports of women treated for aplastic anemia with immunosuppression before pregnancy. Half of all pregnancies were uncomplicated; however,
33% become transfusion dependent during pregnancy, 19% experienced a relapse,
and deaths occurred because of severe disease and thrombosis.22 Successful pregnancies have also been reported after bone marrow transplant after high-dose cyclophosphamide and total body irradiation regimens. Total body irradiation is associated
with an increased risk of spontaneous abortion. There is also an increased incidence
of preterm labor and low-birth-weight infants, but there does not seem to be an
increased incidence of congenital anomalies.23
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, nonhereditary hematopoietic

disorder characterized by nighttime hemolysis with dark morning urine. PNH is caused
by a somatic mutation of the phosphatidylinositol glycan class A gene on the X chromosome. Phosphatidylinoitsol glycan class A encodes for the glycosyltransferase
enzyme. This enzyme catalyzes the first step in production of phosphatidylinositolanchored complement regulatory proteins, which protect against complement
activation. Deficiencies of these proteins cause the RBCs to become susceptible to
compliment lysis, resulting in intravascular hemolysis.
PNH begins insidiously. There is variability in the severity and presentation of the
disease, and there is no familial tendency. The disease usually manifests in adulthood
beginning with skin pallor, periodic dark urine, and severe fatigue. Diagnosis is based
on flow cytometry confirming the deficiency of glycophophatidylinositol-anchored
membrane proteins on erythrocytes, leukocytes, and platelets. Exacerbations of
PNH are precipitated by infection, menstruation, transfusion, surgery, and iron ingestion. Complications of PNH include the following:








Intravascular hemolysis
Neutropenia
Thrombocytopenia
Infections
Aplastic anemia
Venous thrombosis
Embolism

Thrombosis accounts for 50% of deaths outside of pregnancy, often involving

intra-abdominal vessels including hepatic and mesenteric veins. If untreated, median
survival is 12 years with transformation into acute leukemia; progression to marrow
aplasia; or most commonly death from blood loss, infection, or thrombosis.
In pregnancies complicated by PNH, there is up to a 20% maternal mortality rate.
Half of all infants are delivered premature because of complications. The most serious
complication is thromboembolism, which occurs in 12% of patients. Of patients who

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developed thromboembolism, 75% developed Budd-Chiari syndrome or hepatic vein

thrombosis, which carries a 50% mortality rate. The most common complication of
PNH in pregnancy is anemia or hemolysis, occurring in 75% of patients.24 Thrombocytopenia can also occur, and there is an increased risk of infection caused by
leukopenia. Thromboprophylaxis is recommended, although still high risk of a thromboembolic event despite treatment.25
The definitive treatment for PNH is bone marrow transplant. Therapies for PNH in
pregnancy include iron therapy, transfusions, and corticosteroids. Iron can be given
orally to replace lost iron; however, it may lead to erythropoiesis and precipitate
complement lysis. If hemolysis occurs after iron supplementation, erythropoiesis
should be suppressed by treatment with transfusions or corticosteroids. Use of corticosteroids is also controversial because in some patients steroids can quickly stop
hemolysis by inhibiting components of the complement pathway, but steroids may
also suppress inflammation, which may stimulate complement. The treatment of
acute episodes is aimed at decreasing hemolysis. Women with PNH who become
pregnant should be monitored closely with attention to anemia and early detection
of infection, and should be treated with thromboprophylaxis.24 Women with a history of a thrombotic event should be treated with therapeutic anticoagulation.25
Detailed guidelines for anticoagulant use in pregnancy are discussed elsewhere in
this issue.
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