Hemoglobinopathies in pregnancy: Clinical sciences

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Introduction0:00–0:55

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.

Universal Screening0:55–2:15

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.

Normal hemoglobin electrophoresis2:15–3:47

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.

Hemoglobin electrophoresis consistent with alpha thalassemias3:47–6:28

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.

Hemoglobin electrophoresis consistent with beta thalassemias6:28–8:31

Again, follow up with targeted genetic testing to determine the number of nonfunctional beta chain genes. If testing reveals deletion of one beta chain gene, diagnose beta thalassemia trait, or minor.
These patients typically have mild anemia. Perform genetic counseling and avoid supplemental iron unless there is a coexisting iron deficiency.
Intrapartum and postpartum care are routine. Now, genetic testing may reveal a scenario where both beta chain genes are present but mutated, or where one beta chain gene is deleted and the other is mutated.
This is called beta thalassemia intermedia. Again, obtain genetic counseling.
Some patients have mild anemia, while others with more severe anemia may require blood transfusions. If frequent transfusions are needed, perform chelation therapy to prevent iron overload and obtain a maternal echocardiogram to exclude cardiomyopathy.
Individualize antenatal fetal surveillance based on disease phenotype. In terms of intrapartum care, timing of delivery depends on disease severity and once postpartum consider VTE chemoprophylaxis.The final genetic testing result involves the deletion of both beta chain genes, with the diagnosis being beta thalassemia major or Cooley anemia.
Treatment is similar to alpha thalassemia major including genetic counseling if not already completed; blood transfusions to maintain hemoglobin above 10 g/dL; as well as chelation therapy and maternal echocardiogram for iron overload if present.
Antenatal fetal surveillance is recommended due to the increased risk of fetal growth restriction. Timing of delivery is individualized depending on the pregnancy course, and once postpartum, consider VTE chemoprophylaxis.Moving on, let’s talk about sickle cell disease.

Hemoglobin electrophoresis consistent with sickle cell disease8:31–12:13

As a quick reminder, patients with sickle cell disease have mutations in their beta globin genes resulting in an abnormal beta globin, called hemoglobin S.
If one beta globin gene is mutated, the diagnosis is sickle cell trait. These patients need genetic counseling and possibly serial urine cultures as sickle trait patients may have an increased risk of asymptomatic bacteriuria.
Intrapartum and postpartum care are routine.On the flip side, if both beta globin genes are mutated, you can diagnose sickle cell disease.
These patients are at an increased risk of preterm labor, premature rupture of membranes, growth restriction, stillbirth, antepartum hospitalization, and postpartum infection.
Here’s a high-yield fact! Sickle cell disease encompasses both sickle cell anemia, or hemoglobin SS, and another hemoglobin variant, called hemoglobin SC or hemoglobin sickle-C disease.
Hemoglobin SC disease is generally less severe than sickle cell anemia. However, in pregnancy, patients are at risk for similar complications, and management mirrors that of sickle cell anemia.
Speaking of management, as before, perform maternal genetic counseling if not already completed. Now, sickled red blood cells are easily destroyed, so to compensate, the cell production is increased, which leads to the depletion of folic acid stores.
Therefore, high-dose folic acid supplementation is needed. Next, since these patients are functionally asplenic, there’s a higher risk of complications from asymptomatic bacteriuria.
Because of this, you should obtain serial urine cultures. There’s also increased risk of preeclampsia, so consider prescribing daily low-dose aspirin.
Additionally, they’re at risk of pulmonary hypertension, which is why you should obtain a maternal echocardiogram. Another thing to keep in mind is that sickled red blood cells pose a risk of blood clots, so discuss outpatient VTE chemoprophylaxis.
Administer chemoprophylaxis if they have a history of VTE or are admitted in the antepartum period. Additionally, though safe when not pregnant, their regular sickle cell treatment could also be risky during pregnancy.
For example, hydroxyurea, which is used to decrease vasoocclusive crisis, can lead to teratogenicity and pregnancy loss.
Be sure to discuss these risks versus benefits with the patient, and consider stopping the medication. Be vigilant about pain management, especially during a sickle cell crisis, which is more common in pregnancy.
Consider exchange transfusion, or removing sickled cells and replacing them with morphologically normal ones. Also, perform antenatal fetal surveillance.
Delivery timing is individualized depending on the patient's pregnancy course. In labor, be sure to optimize hydration, oxygenation, and analgesia, as periods of stress can prompt sickle cell crises.
Lastly, consider VTE chemoprophylaxis postpartum due to the increased risk of clot; and for the same reason, avoid estrogen-containing contraceptives.Alright, as a quick recap… All pregnant patients should be assessed for hemoglobinopathies with universal screening like hemoglobin electrophoresis or genetic testing.

Review12:13–13:26

Keep in mind that patients with more severe types typically already know about their diagnosis. Patients with alpha or beta thalassemia minor should avoid iron supplementation if possible; while those with alpha and beta intermedia might also need blood transfusions.
Individuals with alpha and beta thalassemia major definitely need blood transfusions, plus chelation therapy and maternal echocardiogram due to the possibility of iron overload.
You should also consider VTE chemoprophylaxis in the postpartum period. Now, patients with sickle trait might need urine cultures to look out for asymptomatic bacteriuria.
Finally, patients with sickle cell disease require high-dose folic acid, and possibly low-dose aspirin, VTE chemoprophylaxis, a discussion surrounding use of hydroxyurea, and possibly exchange transfusions.
During the postpartum period, consider VTE chemoprophylaxis and remind them to avoid estrogen-containing contraception.
Hemoglobinopathies in pregnancy: Video and Causes | Osmosis