Anemia and Thrombocytopenia in Pregnancy

Author: Diana Curran, MD, FACOG, Assistant Professor, Residency Program Director, Department of Obstetrics and Gynecology, University of Michigan Health Systems

Thrombocytopenia

Thrombocytopenia in pregnancy is common and is diagnosed in approximately 7% of pregnancies. It is typically defined as a platelet count of less than 150,000/µL. The most common cause of thrombocytopenia during pregnancy is gestational thrombocytopenia, which is a mild thrombocytopenia with platelet levels remaining greater than 70,000/µL.

Patients who are affected usually are asymptomatic and have no history of thrombocytopenia prior to 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 thrombocytopenia purpura
Acute ITP is a disorder occurring in childhood with little implication 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. 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. 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. 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.
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.

Anemia

With normal pregnancy, blood volume increases, which results in a concomitant hemodilution. Although red blood cell 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 red blood cell (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 less 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.
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/d of elemental iron. 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 is additional supplementation with oral iron sulfate (320 mg, 1-3 times daily). Iron is preferable once daily 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.1
Folate and vitamin B-12 deficiency
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.
Infectious causes of anemia
Although rare, anemia can be caused by infections such as parvovirus B-19, CMV, HIV, hepatitis viruses, 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

This is a rare (7 per 1 million) autosomal dominant disorder of pure red cell aplasia requiring 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.1