Overview 

Glanzmann thrombasthenia (GT) is a rare inherited, genetic disorder whereby a patient has a platelet deficiency. More specifically, patients have a genetic mutation which prevents platelets in their body from aggregating.¹ There are multiple challenges throughout the life of a GT patient, and in this article, we will cover the challenges of GT in pregnant patients. Pregnant GT patients are particularly important because it makes women more vulnerable to bleeding complications before and during birth.² The purpose of this article is first to outline what GT is, then move into how pregnant individuals are particularly at risk and how this can be managed and treated.

Glanzmann thrombasthenia

Genetic pathophysiology

Pathophysiology is the study of abnormal physiological changes from the normal function of bodily processes that further enhance the development of pathogens and diseases.³ In cells in the body, genetic information is stored in DNA (deoxyribonucleic acid), fragments of DNA  are called genes, which code for proteins that perform and assist with different bodily functions. 

With these two pieces of information in mind GT’s pathophysiology can be understood more easily. Since GT is a genetically inherited condition, particular genes are passed down each generation, which triggers GT in patients. The genes are mutated and no longer form the proteins to aggregate platelets, thus triggering symptoms of GT. The GT mutated genes are: ITGA2B or ITGB3.^4,5

These genetic mutations trigger the main characteristic of GT: dysfunctional platelet aggregation. This is where blood is unable to clot due to the mutation preventing the formation of glycoprotein IIb/IIIa. This protein is normally present on platelets in blood and assists in their clotting and aggregation when needed, however, due to the mutation, glycoprotein IIb/IIIa is not made, so platelets do not aggregate effectively.^4,6

Symptoms

Symptoms arise in patients as young as babies one week post-birth. Generally, as a patient ages, the symptoms tend to improve and decrease in severity, however, in those patients and infants who do have severe GT, here are some common symptoms that are expected

• Bruising easily
• Epistaxis (nosebleeds)
• Gingival (gum bleeding)
• Purpura (red, brown, and purple markings on the skin, occurring in patches)
• spontaneous bleeding
• Menorrhagia (abnormally heavy periods in women
• Hematuria (bleeding during urination)
• Prolonged bleeding in minor injuries

Diagnosis

Diagnosis mainly involves doing laboratory testing of blood. Scientists who conduct these tests look for particular characteristics that are used to identify GT. Blood test types include:

• Platelet aggregation tests involve conducting a complete blood count (via a blood smear) to assess the number of platelets present in blood. Counting the number of platelets present in blood can provide insight into how severe GT is per patient
• Flow cytometry - similar to platelet aggregation tests, this assists in providing numerical data about patients' platelet levels and the quality of the platelets, hence providing more information about GT severity⁷
• Prothrombin time (PT) and Thromboplastin time (PTT) tests are used to evaluate how well blood can clot. Platelets are responsible for blood clots, so by evaluating how effectively blood can clot, more information about the disorder per patient is gathered⁸
• Genetic testing is an easy method to assess whether an individual has the necessary mutation in ITGA2B or ITGB3 genes to develop GT⁹

Pregnancy with glanzmann thrombasthenia

As previously established, GT is a disorder where, upon physical trauma, blood is unable to clot in the damaged area. Therefore, being pregnant with GT is a very risky circumstance where a large number of necessary precautions need to be taken to reduce risk to the mother and the baby. In this part of the article, the homeostatic challenges of pregnancy will be explained and outlined in detail.

Pregnancy as a hemostatic challenge

To first clarify, homeostatic challenges are challenges posed in the body which make it difficult to sustain a stable internal environment.¹⁰

Being able to maintain homeostasis is particularly important during pregnancy since the mother now must be able to maintain a healthy internal environment for, not only herself but for the development of a baby.

Physiological changes during pregnancy that impact blood clotting and platelet function.

• How pregnancy may exacerbate bleeding risks in GT patients
• Bleeding Risks
  • Increased risk of haemorrhage during pregnancy, labour, and postpartum
  • Specific complications such as miscarriage, antepartum haemorrhage, and postpartum haemorrhage

Management of pregnancy in glanzmann thrombasthenia

Despite GT posing a large risk during pregnancy, there are management techniques and strategies that can be put in place which can minimise the risk to the mother and the developing baby. Some strategies include:

Preconception planning

Before conceiving a baby, it is important to plan how to cope with complications that can be introduced during the pregnancy since patients with GT will be affected. Some methods of planning involve genetic counselling, where patients will be briefed and made aware of the fact that GT is a hereditary condition, meaning that it can be inherited by their child.⁴

Furthermore, prenatal testing options are offered to individuals, these tests aim to conclude whether the developing foetus (post-conception) or foetus that is going to be conceived will have the disorder, and how likely it is for the foetus to develop it. These tests include DNA analysis, polymorphic markers (to search for mutated GT genes), and platelet analysis (to find out whether they are missing the glycoprotein).

Multidisciplinary care team

It is also important to have a team of haematologists, obstetricians, anesthesiologists, and paediatricians to ensure the pregnancy continues risk-free, as specialists in the field of GT will understand what symptoms and signs of damage or risk to look out for.¹¹

Monitoring throughout pregnancy

Monitoring through pregnancy is one of the most important management tactics, it allows medical professionals to ensure the foetus and the mother are safe and not at any risk of harm from GT-triggered issues. 

Doctors can search for any signs of bleeding, or anaemia (iron deficiencies), and will also assess the clotting status (blood tests which evaluate how effectively the blood can clot throughout the pregnancy.) These tests can be done by regularly going to medical checkups.¹²

Additionally, there are non-invasive strategies that allow doctors to assess and evaluate foetal development and its well-being. These strategies can include:¹² 

• Ultrasound to visualise the anatomical development of the foetus
• Blood test of the mother where traces of foetal DNA can be found. From this DNA, doctors can search for any abnormalities or genetic disorders, such as a mutation in the ITGA2B or ITGB3 genes 

Prophylactic treatments

Prophylactic treatments are methods put in place to decrease the spread and development of pathogens or diseases and stabilise as well as enhance remaining health. In the context of GT in pregnant women, it is aimed to reduce blood clots and enhance the ability of platelet function in patients. Two very effective examples of these treatments include:

1. Platelet transfusions - where patients receive platelets that can prevent excessive bleeding¹³
   • The timing and frequency are particularly important since labour and delivery are where most bleeding occurs 
   • Transfusions that are too early mean that the platelets don't function on time with delivery
   • Too late means that they are useless in preventing excessive bleeding 
   • Incorrect timing of transfusion might even result in haemorrhaging. 
2. Using recombinant factor VIIa (rFVIIa) for controlling and preventing excessive bleeding¹⁴
   • This is a synthetic version of a factor found in platelets that assist with blood clots. It helps to prevent excessive bleeding specifically with GT in patients 
   • This is helpful during pregnancy because during labour and delivery, there is a very high likelihood of postpartum haemorrhage (PPH) which is one of the leading causes of maternal death during pregnancy. GT in particular increases the likelihood of pregnant women experiencing PPH¹⁵
   • rFVIIa is a drug that is used to treat PPH by preventing haemorrhaging and enhancing blood clotting

Labour and delivery in women with glanzmann thrombasthenia

Labour and delivery and the most risk-ridden times in patients with GT. Therefore, they need to be prepared as much as possible. Methods of preparation can include:

Delivery plan 

• Establishing a preferred delivery plan that is the least harmful to the foetus and the delivering mother is imperative 
• This means that pregnant women must have a clear understanding of vaginal and caesarean section delivery and how they both affect bleeding risks
• With these delivery options in mind, women are then able to make an informed decision regarding their preferred method of delivery based on risks of bleeding and PPH

Haemorrhage prevention (as covered previously) 

• Pre-delivery administration of platelets or rFVIIa can be pivotal in preventing the likelihood of PPH from occurring, especially since GT patients are at a higher risk of experiencing PPH¹⁶
• These haemorrhaging management techniques are often accompanied by close monitoring by healthcare professionals and having emergency blood transfusion products at hand during labour¹⁶

Postpartum care 

• Equally as important as labour and delivery precautions, postpartum care is critical.
• PPH is a risk post-delivery too, therefore, strategies should be put in place that manage and prevent any risks of excess bleeding¹⁷
• Strategies include: continuing transfusions of platelets or rFVIIa during recovery to minimise the likelihood of haemorrhaging at all¹⁷

Summary

Pregnancy is severely affected by Glanzmann thrombasthenia (GT) since it affects platelets’ ability to aggregate. This causes difficulties in blood clotting, which is harmful to pregnant women as they are vulnerable to many circumstances of bleeding during pregnancy and delivery. GT is caused by a mutation in the ITGA2B or ITGB3 gene, which makes the glycoprotein IIb/IIIa dysfunctional. This glycoprotein is essential for platelet aggregation and blood clotting. Some main symptoms include: excessive bleeding from small minor injuries or menstrual periods, and bruising. GT is diagnosed with genetic testing and blood platelet evaluation tests furthermore, during pregnancy GT increases the risks of PPH and decreases maternal and foetal survival rates. To combat this, management tactics such as delivery plans, haemorrhage prevention, and postpartum care, as well as prophylactic treatments have been developed to make pregnancy and delivery as risk-free as possible.