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

One Patient's Story: Living with and Learning from Thalassemia

August 12, 2010 - High school student Aaron Cheng shares a speech about thalassemia which he recently delivered to his classmates. We share this inspiring testimony with you below.
To My Classmates

Throughout the course of this year you all have learned little snippets about my interests: my passions for science, for music, and for learning in general; however, you do not yet know my whole story. You do not yet understand what has led to my extreme love of learning, my dedication to the sciences, and my goals for the future. And through this speech, I intend to tell you about my greatest passion of all.
My life began - well, when I was born, as lives tend to do. And for a while I lived normally, a chubby little tyke who rolled around on the floor, spending my days observing the world from eleven inches off the ground, philosophizing, getting acquainted with the floor on which I crawled; however, when I was only a few months old, a five-syllable word crudely entered my life and took control of it:
“Thalassemia.”
This seemingly Martian term isn’t as alien as it may appear. In fact, this term describes a blood disease that is carried by over sixty million people in the world. But thalassemia alone isn’t what made me genetically unique. No, doctors discovered soon after my birth that I had the worst form of thalassemia, the form that affects only a thousand people in the United States, the form that renders the victim helpless and completely dependent on blood from other people: beta-thalassemia major. My innocent, happy life came tumbling down around me with this medical discovery.
And my bright, hopeful days as an infant became the darkest days of my life. You see, thalassemia, in simple terms, is a genetic mutation that affects the blood cell and causes it to be unable to carry oxygen. While a red blood cell should be plump and red, my blood is shriveled and useless. The single change in the nucleotide sequence in my DNA that causes this monstrous disease leads to a multitude of problems. Ever since I was born, I’ve had to go to the Miller Children’s Hospital in Long Beach to receive a four- to eight-hour blood transfusion every month. And every day at home I took shots to counteract the iron deposits that have resulted from these transfusions.
Thalassemia is a daunting disease. The victim must receive blood from donors, but in doing so he receives an excess of iron through the transfusion. The very process that is saving his life is killing him. Though there are drugs that help patients excrete iron, the sad fact is that not all the iron exits the body. As a result, iron deposits form in the pituitary gland, the liver, the pancreas, and eventually, the heart. So while the victim of thalassemia usually does not die from lack of functioning blood cells, he eventually dies from heart complications caused by the iron.
My infancy was the most difficult part of my life. Doctors were unable to find suitable veins in my tiny arms, so they stabbed my feet with the needles. Needles often fell out during the course of the transfusion, so one trip to the hospital could mean up to five shots. At home I continued to take shots every day to counteract the deadly iron deposits. By the age of five I had taken more shots than most adults had taken in their lifetime.
I still remember my elementary school days. I was often ostracized because of the frequency of my doctor appointments, and I missed up to three days of school per week. And when I realized that the blood that was being pumped into my body was from other living people, I felt like a vampire. Not as shiny and awesome as Edward Cullen, but a vampire nonetheless. It was during my elementary school days that I resolved to repay all of my blood donors for their generosity, to pay back all of my doctors for all the work they had put into me.
Through middle school I immersed myself in the world of academia, motivated to help the medical community all I could. Whenever I felt exhausted of studying, it only took one more visit to the hospital, one more transfusion, to make me work at full speed once again. I was determined to make an impact on the medical community, to ensure that everybody with disease as devastating as thalassemia would be able to fulfill happy, productive lives.
Upon entering high school I joined every club associated with academics that I could, such as the Academic Decathlon, science club, and math club, with the hopes of being as prepared for my future as possible. And my internal drive to learn and to contribute to society continues even as I speak.
As I write this, I realize that within thalassemia is a hidden jewel: the treasure of dedication and passion. Thalassemia is no longer a monster to me; rather, it is part of me, and it breathes the fire of passion and inspiration throughout my body. What was once a weakness, a flaw, is now my prized gem. The darker my circumstances, the brighter its light will shine. It is because of thalassemia that the motivation to succeed runs through my veins. It is because of thalassemia that I have learned to endure pain. And it is because of thalassemia that I am able to lead a productive, albeit shortened, life today.
There is something I want you all to take away today from my experience, since I’m not just up here to say my life story. Always embrace obstacles, for obstacles are actually valuable lessons cleverly disguised. Without confronting obstacles you will never grow. Obstacles will never crush you as long as you have the resolve to overcome them.