Anemia and thrombocytopenia are common maternal hematologic disorders during pregnancy, both of which can pose risks to the mother and fetus.
Anemia
Anemia is one of the most common complications during pregnancy. Pregnancy is associated with an increase in blood volume, where plasma expansion exceeds the increase in red blood cell volume, resulting in a diluted state referred to as "physiological anemia." Anemia during pregnancy can have adverse effects on both the mother and fetus. In resource-limited regions, severe anemia is a significant contributor to maternal mortality. Iron deficiency anemia is the most common type of anemia during pregnancy.
Effects on the Mother and Fetus
Effects on the Mother
Pregnant women with anemia have reduced tolerance for labor, surgery, and anesthesia. Severe anemia may lead to anemia-related heart disease due to myocardial hypoxia. Women with anemia during pregnancy are at higher risk of hypovolemic shock in cases of blood loss and have reduced resistance to infection, predisposing them to puerperal infections.
Effects on the Fetus
Severe maternal anemia can impair placental oxygenation and the supply of nutrients to the fetus, increasing the risks of fetal growth restriction, fetal distress, preterm birth, stillbirth, and long-term adverse outcomes.
Diagnostic Criteria for Anemia in Pregnancy
Anemia during pregnancy is defined as hemoglobin (Hb) levels less than 110 g/L and hematocrit less than 0.33. Based on Hb levels, anemia is classified into:
- Mild anemia: Hb 100–109 g/L
- Moderate anemia: Hb 70–99 g/L
- Severe anemia: Hb 40–69 g/L
- Very severe anemia: Hb < 40 g/L
Iron Deficiency Anemia (IDA)
Iron deficiency anemia is the most common type of anemia during pregnancy, accounting for approximately 95% of cases.
Etiology
The primary cause of iron deficiency during pregnancy is the increased demand for iron. Inadequate dietary intake, impaired absorption, or excessive loss of iron may also contribute to anemia. Based on the estimate that each milliliter of blood contains 0.5 mg of iron, the total iron requirement during pregnancy is approximately 1,000 mg. This includes 650–750 mg for the expansion of blood volume and 250–350 mg for fetal growth and development. With progression of pregnancy, iron requirements increase, and during the mid-to-late stages of pregnancy, a daily intake of 30 mg of elemental iron is needed.
Diagnosis
Medical History
Some pregnant women have a history of chronic blood loss, such as heavy menstrual periods, or malnutrition caused by factors like long-term picky eating habits, vomiting in early pregnancy, or gastrointestinal disturbances. However, many patients do not have a clear medical history.
Clinical Manifestations
Mild cases may be asymptomatic or present with slight pallor of the skin, lips, mucosa, or palpebral conjunctiva. Severe cases may present with fatigue, dizziness, palpitations, shortness of breath, poor appetite, bloating, diarrhea, pale skin and mucosa, dry skin and hair, brittle and thin fingernails, oral inflammation, glossitis, and depressed mood.
Laboratory Tests
Complete Blood Count
Peripheral blood smear reveals microcytic hypochromic anemia. Findings include Hb < 110 g/L, red blood cells < 3.5 × 1012/L, hematocrit < 0.33, mean corpuscular volume (MCV) < 80 fl, and mean corpuscular hemoglobin concentration (MCHC) < 320 g/L. White blood cell and platelet counts are usually within normal ranges.
Serum Ferritin (SF)
SF is a reliable indicator of iron stores, making it the most effective and easily accessible marker for evaluating iron deficiency. SF levels < 30 μg/L suggest iron deficiency, even when Hb levels are normal.
Serum Iron, Total Iron Binding Capacity (TIBC), and Transferrin Saturation (TSAT)
These markers are susceptible to diurnal variations and other influencing factors.
Bone Marrow Examination
Mild to moderate erythroid hyperplasia with a predominance of intermediate or late normoblasts is observed. Bone marrow iron staining shows decreased intracellular and extracellular iron, with extracellular iron being particularly reduced. While bone marrow iron staining is the "gold standard" for evaluating iron stores, it is rarely used during pregnancy.
Treatment
The primary principles of treatment involve iron supplementation and addressing the underlying causes. General treatment includes improving nutrition, consuming iron-rich foods, and providing supportive treatment based on the etiology.
Diet
A diet rich in iron-containing foods, such as beef and pork liver, is recommended. Foods high in vitamin C, such as fruits and leafy green vegetables, may enhance iron absorption.
Iron Supplementation
Oral iron supplementation is the main approach for treatment when hemoglobin (Hb) levels are above 70 g/L. Common oral iron supplements include iron polysaccharide complex, ferrous fumarate, ferrous succinate, ferrous sulfate, and ferric protein succinylate. Vitamin C can be co-administered to improve iron absorption.
Intravenous iron therapy is an option for individuals with moderate to severe iron deficiency anemia, pregnant women in mid-to-late pregnancy who require rapid correction of iron deficiency (ID)/iron deficiency anemia (IDA), those with severe gastrointestinal side effects preventing oral iron use, uncertain adherence to oral therapy, or cases resistant to oral iron supplementation. Intravenous preparations include ferric sucrose, low-molecular-weight iron dextran, and ferric carboxymaltose, which can be administered via deep intramuscular injection or intravenous infusion.
Blood Transfusion
Blood transfusion is recommended for individuals with Hb levels below 70 g/L. For Hb levels between 70–100 g/L, the decision to transfuse depends on factors such as surgical needs and cardiac function.
Intrapartum and Postpartum Management
Close maternal and fetal monitoring is crucial during labor. Postpartum, follow-up and individualized iron supplementation therapy are essential.
Prevention
Addressing diseases that may cause anemia before pregnancy, improving nutrition, and encouraging the consumption of iron-rich foods are key strategies to increase iron reserves. Regular monitoring of complete blood count (CBC) and serum ferritin (SF) levels during pregnancy is important.
Thalassemia
Thalassemia is an inherited hemolytic anemia caused by mutations or deletions in globin genes, leading to impaired synthesis of one or more globin protein chains.
Classification
Thalassemia is an autosomal recessive disorder. Based on the type of globin gene affected, thalassemia can be categorized into α, β, γ, δ, and δβ types. The most common forms are α-thalassemia, caused by defects in α-globin chain synthesis, and β-thalassemia, caused by defects in β-globin chain synthesis.
Clinical Manifestations
The clinical presentation of thalassemia varies depending on genotype. In α-thalassemia, symptoms worsen with increasing numbers of defective α-globin genes and are classified as silent carrier, mild, intermediate (HbH disease), or severe (Hb Barts). In β-thalassemia, clinical severity depends on the genotype and is categorized as mild, intermediate, or severe.
- Silent carrier: Usually asymptomatic with no specific clinical features.
- Mild and intermediate forms: Characterized by varying degrees of microcytic hypochromic anemia.
- Severe forms: Associated with distinct clinical features and poor prognosis.
In severe α-thalassemia, affected fetuses may develop severe anemia, hydrops fetalis, hepatosplenomegaly, restricted growth, or even intrauterine death.
Severe β-thalassemia manifests as progressively worsening anemia after birth, requiring regular blood transfusions for survival. Without timely and effective treatment, affected individuals usually do not survive into adulthood.
Screening and Diagnosis
Thalassemia screening is ideally conducted before pregnancy or in early pregnancy, especially when one partner is known to have thalassemia, necessitating screening of the other partner.
Initial Screening
Complete blood count (CBC) is the simplest and most basic test for thalassemia screening. Findings such as normal or reduced Hb levels, mean corpuscular volume (MCV) < 82 fl, and mean corpuscular hemoglobin (MCH) < 27 pg indicate positive screening results for thalassemia.
Follow-up Testing
Positive screening results warrant further genetic testing to confirm the diagnosis and subtype. Hemoglobin A2 (HbA2) levels can assist in genetic classification: HbA2 < 2.5% suggests α-thalassemia, while HbA2 > 3.5% suggests β-thalassemia.
Couples with a history of delivering a baby with severe thalassemia and negative results for common thalassemia gene mutations may need additional testing for rare thalassemia genes.
Ultrasound can support the diagnosis of severe α-thalassemia, with indicators such as increased nuchal translucency (NT), heart-to-chest circumference ratio, and placental thickness serving as screening markers.
Genetic Counseling
Prevention of severe thalassemia largely focuses on avoiding the birth of affected children. Prenatal diagnosis remains the "gold standard" for determining whether a fetus has thalassemia and its subtype.
For couples known to be carriers of the same type of thalassemia gene, genetic counseling should take place before or early during pregnancy. Pre-conception counseling can assess the risk of offspring inheriting severe thalassemia, and options such as preimplantation genetic diagnosis (PGD) or early prenatal diagnosis after natural conception can be considered.
Preconception and Pregnancy Management
Before planning a pregnancy, individuals with thalassemia may benefit from folic acid supplementation (5 mg/day). Those with concurrent iron deficiency anemia may also need iron supplementation. Patients with intermediate and severe thalassemia require assessment of their condition and should adjust medication under the guidance of a specialist. Monitoring serum ferritin (SF) levels can help evaluate iron storage in thalassemia patients.
After conception, patients with mild thalassemia should undergo regular complete blood count (CBC) testing. Those with intermediate or severe thalassemia who develop severe anemia may require blood transfusions, along with assessment and prevention of venous thromboembolism (VTE). In severe thalassemia, the reduction or cessation of iron chelation therapy during pregnancy can increase the risk of developing or worsening conditions like diabetes and thyroid disorders, necessitating regular monitoring.
Aplastic Anemia
Aplastic anemia (AA), often referred to as aplasia, is a hematologic disorder characterized by impaired bone marrow function leading to pancytopenia (reduced levels of red cells, granulocytes, and megakaryocytes).
Mutual Effects of Aplastic Anemia and Pregnancy
The etiology of aplastic anemia remains unclear. Although pregnancy itself is not a direct cause of aplastic anemia, it may trigger relapse or progression of the disease, particularly in patients who have not achieved complete remission. Common causes of death in pregnant patients with aplastic anemia include intracranial hemorrhage, heart failure, and infection.
Mild anemia has minimal impact on the fetus, and newborns generally have normal CBC results with very rare occurrences of aplastic anemia. Moderate to severe anemia can lead to miscarriage, premature birth, fetal growth restriction, or stillbirth.
Clinical Features and Diagnosis
The primary clinical presentations include progressive anemia, bleeding in the skin or internal organs, and recurrent infections. Laboratory findings categorize the disease into severe and non-severe subtypes. Anemia is normocytic, with pancytopenia observed. Bone marrow examination typically shows markedly reduced or absent hematopoietic activity in multiple sites, with very few nucleated cells. There is a reduction in myeloblasts, erythroblasts, and megakaryocytes, with a relative increase in lymphocytes.
Management
Management should be conducted collaboratively by obstetricians and hematologists, with supportive therapies as the cornerstone of treatment.
Pregnancy Management
Therapeutic Abortion
Pregnant patients with aplastic anemia should avoid conception until the condition is in remission. For those who become pregnant during remission, therapeutic abortion in early pregnancy can be performed while ensuring readiness for blood transfusions. Termination of pregnancy in the second or third trimester poses greater risks, and efforts should focus on supportive treatment and close monitoring until term delivery.
Supportive Therapy
Adequate rest and improved nutrition are essential. Frequent, small-volume transfusions of fresh blood may be used to increase hemoglobin levels to above 60 g/L.
Bleeding Tendency
Glucocorticoid therapy, such as prednisone (10 mg, three times per day), may be administered if significant bleeding tendencies are noted, though prolonged use is not recommended. Androgens are not advised during pregnancy, but treatment with cyclosporine A may be individualized.
Infection Prevention
Broad-spectrum antibiotics that do not harm the fetus should be used for infection prophylaxis.
Delivery
Most patients are able to deliver vaginally. Efforts should focus on shortening the second stage of labor to prevent excessive exertion, which could increase the risk of critical organ hemorrhage. Assisted delivery may be considered when necessary. For patients requiring a cesarean section, surgical hemostasis techniques should be employed to minimize postpartum hemorrhage. Careful examination of the soft birth canal is crucial postpartum to identify and prevent hematoma formation.
Postpartum Period
Supportive therapy should continue during the postpartum period. Measures to promote uterine contraction, prevent postpartum hemorrhage, and reduce the risk of infection are essential.
Thrombocytopenia
A platelet count of < 100 × 109/L during pregnancy is diagnosed as pregnancy-associated thrombocytopenia. Thrombocytopenia during pregnancy is classified into primary immune thrombocytopenia (ITP) and gestational thrombocytopenia (GT), with the former being non-pregnancy-specific and the latter specific to pregnancy.
Primary Immune Thrombocytopenia
Primary immune thrombocytopenia, previously referred to as idiopathic thrombocytopenic purpura (ITP), is a common acquired autoimmune hemorrhagic disorder. The pathogenesis involves excessive platelet destruction along with insufficient platelet production.
Mutual Effects of ITP and Pregnancy
Impact of Pregnancy on ITP
The course and prognosis of ITP are not affected by pregnancy, though pregnancy may exacerbate the condition or trigger relapses, increasing the risk of bleeding.
Impact of ITP on Pregnant Women
Pregnant individuals with ITP primarily face an increased risk of bleeding. During labor, complications including hemorrhage from birth canal lacerations, hematoma formation, and postpartum hemorrhage may occur. Intracranial hemorrhage can be induced by maternal exertion and breath-holding during delivery. Rates of natural miscarriage and maternal-fetal mortality are higher in pregnant individuals with ITP compared to those without the condition.
Impact of ITP on the Fetus and Neonate
Transfer of anti-platelet antibodies across the placenta can result in platelet destruction in the fetus, causing fetal and neonatal thrombocytopenia. Severe cases may be associated with a risk of intracranial hemorrhage. Neonatal thrombocytopenia is transient, with platelet counts gradually returning to normal as the antibodies are cleared from the newborn's system.
Clinical Manifestations and Diagnosis
ITP primarily presents with asymptomatic thrombocytopenia, bleeding in the skin and mucosa, and bleeding in critical organs. Mild cases may involve petechiae, purpura, and ecchymoses on the skin of the extremities and trunk, as well as epistaxis and gum bleeding. Severe cases may present with gastrointestinal tract bleeding, reproductive tract bleeding, retinal hemorrhage, or intracranial hemorrhage. Splenomegaly is typically absent or mild. Laboratory findings include a platelet count of < 100 × 109/L, with symptoms generally appearing when the platelet count drops below 50 × 109/L. Bone marrow examination reveals normal or increased megakaryocyte numbers, with reduced mature platelets. Platelet antibody tests are frequently positive.
ITP is a diagnosis of exclusion, and other causes of thrombocytopenia, such as gestational thrombocytopenia, aplastic anemia, drug-induced thrombocytopenia, HELLP syndrome, and hereditary thrombocytopenia, must be ruled out.
Treatment
Management During Pregnancy
Management of ITP during pregnancy involves collaboration between obstetricians and hematologists. Pregnancy does not usually require termination due to ITP, except in cases of severe thrombocytopenia with bleeding symptoms that fail to respond to first-line treatments. Treatment principles for ITP during pregnancy mirror those for non-pregnant individuals, with efforts made to minimize adverse effects on the fetus. In addition to supportive care and anemia correction, treatment strategies are tailored to the severity of the condition.
Glucocorticoids
Glucocorticoids are the first-line treatment for ITP during pregnancy. Treatment is generally initiated when platelet counts fall to < 20–30 × 109/L or when bleeding symptoms are present. Prednisone is typically administered at an initial dose of 0.25–0.50 mg/kg/day, with effects observed within 4–14 days. The dose can be gradually tapered once platelet counts increase and stabilize, aiming to maintain platelet counts above 30 × 109/L.
Intravenous Immunoglobulin (IVIG)
IVIG competes with platelets for Fc receptor binding in the monocyte-macrophage system, thereby reducing platelet destruction. A standard dose of 400 mg/kg/day for 3–5 days constitutes one course of treatment. For cases requiring rapid platelet count increases or preoperative preparation, a higher dose of 1 g/kg/day may be administered for 1–2 days.
Platelet Transfusion
Platelet transfusion provides only short-term benefit and may stimulate the production of anti-platelet antibodies, accelerating platelet destruction. Transfusion is reserved for specific indications, such as platelet counts below 10 × 109/L, a tendency for bleeding, prevention of critical organ hemorrhage, or preparation for surgery or delivery. Concurrent administration of glucocorticoids or IVIG is recommended when transfusions are utilized.
Other Therapies
Immunosuppressants and androgens are generally avoided during pregnancy. Splenectomy is typically not performed during pregnancy unless absolutely necessary, with the ideal timing being during the second trimester (between 3 and 6 months of gestation).
Management During Delivery
The mode of delivery should be determined based on obstetric indications. Vaginal delivery is preferred when the maternal platelet count is above 50 × 109/L. Cesarean sections performed under spinal anesthesia require platelet counts above 70 × 109/L. Procedures that increase the risk of fetal or neonatal bleeding, such as vacuum extraction, should be avoided during vaginal delivery. Cesarean sections may be considered for individuals with a history of fetal or neonatal intracranial hemorrhage.
Postpartum Management
Individuals treated with glucocorticoids during pregnancy generally require continued treatment postpartum, complemented by regular follow-up evaluations.
Gestational Thrombocytopenia
Gestational thrombocytopenia (GT) is a common cause of thrombocytopenia during pregnancy with an unclear etiology, potentially related to increased blood volume and platelet consumption in pregnancy. Patients are usually asymptomatic, with the condition often identified during routine prenatal visits in the second or third trimester or during labor. GT does not typically affect platelet counts in the fetus or newborn.
A platelet count of < 100 × 109/L is diagnostic for GT. Platelet counts usually remain above 70 × 109/L. Counts below 70 × 109/L require differentiation from ITP, while those below 50 × 109/L are managed according to ITP treatment guidelines. Platelet counts in individuals with GT typically return to normal within 1–2 months postpartum.