Hemoglobinopathies in pregnancy: Clinical sciences

Hemoglobinopathies are genetic disorders that cause abnormal hemoglobin production, most commonly affecting hemoglobin A, which is composed of two alpha and two beta chains. Using electrophoresis or genetic testing, we can detect abnormalities that indicate a deletion in genes coding for the alpha chain, called alpha thalassemias; or beta chain, called beta thalassemias; as well as a mutation in genes coding for the beta chain, called sickle cell disease.

Hemoglobinopathies have variable clinical presentations. Some cause mild anemia, while others lead to severe anemia requiring transfusions. Depending on the type and severity of hemoglobinopathy in pregnancy, complications range from anemia to increased risk of venous thromboembolism and even fetal demise.

Your first step is to screen your pregnant patient at their first prenatal visit; however keep in mind that some patients may not have received their prenatal care, so they may present with a chief concern suggesting hemoglobinopathies in pregnancy. Start by obtaining a focused history and physical exam. Now, most patients with hemoglobinopathies in pregnancy are asymptomatic, but in some cases, history might reveal a positive family history of hemoglobinopathy or mild anemia on an antepartum screening CBC. Additionally, patients may report fatigue or weakness, but keep in mind that both of these symptoms are very nonspecific in pregnancy!

Physical exam could reveal pallor, as well as jaundice, or hepatosplenomegaly due to extramedullary hematopoiesis.

Alright, since these patients are usually asymptomatic, universal screening is really important to make a diagnosis. Universal screening involves either hemoglobin electrophoresis or molecular genetic tests, both of which will give you a better idea than CBC alone. As your next step, you should obtain hemoglobin electrophoresis unless they’ve had one completed before, in which case you can use those results.

Let’s first look at normal hemoglobin electrophoresis.

Some carrier forms of alpha thalassemia will result in a normal electrophoresis, so your first step is to assess a patient’s ancestry. Alpha thalassemia minima and trait are more common in individuals of Southeast Asian, African, West Indian, or Mediterranean descent. In these patients, perform targeted genetic testing.

If testing shows a deletion of one alpha globin gene, alpha thalassemia minima is diagnosed. If two genes are deleted, that’s alpha thalassemia trait, also called alpha thalassemia minor. Patients with minima are asymptomatic, whereas those with trait may have mild anemia. Genetic counseling is recommended to assess the risk of passing on a clinically significant hemoglobinopathy to a fetus. Additionally, avoid supplemental iron to prevent iron overload, unless there’s a coexistent iron deficiency.

Intrapartum, and postpartum care are routine.

Okay, back to genetic testing. If it shows no alpha globin gene deletions, continue routine pregnancy care.

Similarly, if a patient is not of high-risk descent, there’s no need for additional testing, so continue routine pregnancy care.

Ok, let’s go back and talk about hemoglobin electrophoresis results that are consistent with alpha thalassemia.

First, perform targeted genetic testing to determine the number of alpha genes deleted. If two genes are deleted, that’s alpha thalassemia trait or minor. As before, obtain genetic counseling, avoid supplemental iron unless there’s a coexisting iron deficiency, and continue routine intrapartum and postpartum care.

If genetic testing demonstrates deletion of three alpha globin genes, the diagnosis is alpha thalassemia intermedia, commonly called hemoglobin H disease. Once again, perform genetic counseling and avoid supplemental iron unless there is a coexisting iron deficiency. Now, most of these patients only have mild anemia, however, pregnancy can cause more significant disease that may require a blood transfusion. Depending on the severity of their condition, consider antenatal fetal surveillance.

Intrapartum and postpartum care are routine.

Alright, if genetic testing demonstrates deletion of all four alpha globin genes, the diagnosis is alpha thalassemia major, also called Barts disease. Keep in mind that patients with alpha thalassemia major have severe anemia so it is more likely that they are diagnosed in infancy, meaning that they will already know about their diagnosis before pregnancy.

They probably already had genetic counseling completed, but be sure to ask and obtain it now if it wasn’t done. During the antepartum period, these patients require blood transfusion with a goal hemoglobin of at least 10 g/dL. Frequent transfusions lead to iron overload, which is managed with chelation therapy. Additionally, iron overload may cause cardiomyopathy so maternal echocardiograms are needed. Antenatal fetal surveillance is also recommended.

Regarding intrapartum care, the timing of delivery is individualized depending on the pregnancy course. Once postpartum consider venous thromboembolism, or VTE, chemoprophylaxis due to raised clot risk.

Here’s a clinical pearl! A fetus with alpha thalassemia major has a high risk of developing hydrops fetalis and intrauterine demise. The patient may develop mirror syndrome, a condition that causes similar symptoms to their hydropic fetus like vomiting, hypertension, peripheral edema, and pulmonary edema. If this happens, they require emergent delivery!

Next, let’s look at when hemoglobin electrophoresis is consistent with beta thalassemia.