What Is Hemophilia? Causes, Symptoms and Pregnancy

By MD, PhD, MSc (gynecologist), BSc, MSc (embryologist), BSc, MSc (embryologist) and (invitra staff).
Last Update: 01/17/2020

Hemophilia is a genetic disease that affects blood clotting. Hemophiliacs do not clot their blood well and, for this reason, they may suffer from more or less severe bleeding.

People with hemophilia are mainly men, as it is an inherited recessive disease linked to the X chromosome.

In this article we will discuss the most important aspects of hemophilia, as well as the reproductive options that exist to avoid it.

Definition of hemophilia

Hemophilia is an inherited disease that affects blood clotting and causes bleeding problems.

This blood alteration is due to the lack of coagulation factors, essential proteins to be able to block the lesions of the blood vessels next to the platelets and thus prevent bleeding.

Hemophiliacs do not bleed faster than normal, but bleed for a longer period of time.

In the US, approximately 18,000 people suffer from hemophilia. Hemophilia A, also known as factor VIII deficiency, is the most common type of hemophilia. It occurs in about 80% of people suffering from hemophilia. Hemophilia B is less common though, with only 20% of hemophiliacs presenting type B.

The great majority of those affected by hemophilia are men, because it is a recessive genetic disease linked to the X chromosome, which means that women will be carriers in most cases.

However, there is one type of hemophilia not linked to the X chromosome (hemophilia type C), so some women may be hemophiliacs.

Types

Depending on the deficient clotting factor, hemophilia is classified as follows:

Hemophilia A
occurs when there is a deficit of coagulation factor VIII. This is the most common type of hemophilia.
Hemophilia B
occurs when the coagulation factor IX is lower. It is also known as Christmas disease and is a very rare type of hemophilia.
Hemophilia B
occurs when there is a lack of clotting factor XI, which is encoded on chromosome 4. This means that this type of hemophilia is not sex-linked and affects men and women equally.

Although haemophilia is not very common, hemorrhagic conditions and their long-term clinical repercussions can be severe.

For this reason, it is especially important to detect women who carry hemophilia in order to prevent their transmission to their offspring.

How is it transmitted?

As we have already said, haemophilia is an inherited disease, that is, it is passed from parents to children through genes.

In this section, we are going to explain the type of inheritance associated with hemophilia A and B: recessive inheritance linked to the X chromosome.

The X chromosome is a sex chromosome that is present in both males and females. However, females have two copies of this (XX) chromosome, while males have one copy of the X chromosome and one copy of the Y (XY) chromosome to define their sex.

Since this is a recessive genetic disease, it will be necessary for a woman to inherit both sex chromosomes with the mutation caused by hemophilia from her parents in order to have the disease. If she receives only one X chromosome with the mutation, the woman will be a carrier with no symptoms.

Instead, it is enough for men to inherit an X chromosome with the mutation to be hemophiliacs.

This is why men manifest hemophilia in a greater proportion than women, who will be mainly carriers of the mutation. However, there are some women who carry hemophilia who have mild symptoms.

Symptoms and Diagnosis

The main symptoms of hemophilia are prolonged, unrelenting bleeding that may occur spontaneously and bleeding that is difficult to stop after trauma.

Besides, hemorrhages can be:

External
when bleeding occurs through a natural hole in the body (nose, mouth, or ears) or through a superficial wound.
Internal
are bleedings that occur inside the body, especially in muscle and joints (knees, elbows, ankles, etc.). These hemorrhages can be serious and cause injury to internal organs and also arthritis.

Diagnosis is based on family history, blood determination of clotting factors and, finally, genetic identification of mutations.

Depending on the amount of clotting factor missing in the blood, the following degrees of severity are established:

Mild hemophilia
between 5% and 40% normal clotting factor. These people do not have serious bleeding problems, they only have bleeding after surgery or serious injury.
Moderate hemophilia
between 1% and 5% normal clotting factor. These people usually bleed once a month and above all they can have serious hemorrhages after surgery, serious injury or any dental procedure.
Severe hemophilia
less than 1% normal clotting factor. These people have frequent hemorrhages in muscles and joints. In addition, these bleedings may appear spontaneously, without any cause.

Bleeding that occurs repeatedly in the same joint can also cause damage and pain.

How can hemophilia be avoided during pregnancy?

When a hemophilic man or a woman with hemophilia makes the decision to have children, it is important to be well informed about the likelihood of transmitting this disease to her offspring and to receive genetic counseling before pregnancy.

There are several diagnostic options and reproductive strategies to avoid having a child with hemophilia.

Preimplantation genetic diagnosis

Preimplantation genetic diagnosis (PGD) is the best option when parents have some genetic alteration and want to avoid transferring it to their future children.

This diagnostic technique consists of analysing the embryos genetically during in vitro fertilisation (IVF) treatment, in order to transfer to the woman's uterus only healthy embryos free from the disease, in this case hemophilia.

To perform a PGD, one should undergo IVF as the main treatment. If you are looking for a clinic to get started, we recommend that you generate your individual Fertility Report now. It is a useful, simple tool that, in just 3 steps, will give you a list of the clinics that have passed our rigorous selection process. You will receive an email in your inbox with a report that contains tips and recommendations to get started.

If you want to know more about this method, you can read more here: What is preimplantation genetic diagnosis?

Therapeutic gender selection

PGD also allows us to know the gender of the embryos before they are transferred to the uterus.

In many countries, gender selection is illegal. However, it is permitted in cases where it is intended to prevent the birth of children with serious illnesses. This is what is known as a therapeutic sex selection.

For example, a couple may select the sex of their baby to avoid hemophilia in the following cases:

Hemophilic father and healthy mother
can only have healthy sons, since all daughters would be carriers and the disease would continue in future generations.
Healthy father and hemophilic mother
can only have carrier daughters, as all sons would be sick.

In cases where future parents do not want to run the risk of having sick children or hemophilia carriers, they also have the possibility of resorting to other assisted reproduction treatments such as the donation of gametes (eggs or sperm) and the adoption of embryos.

Prenatal Diagnosis

Pregnant women who may have a child with hemophilia because of their family history and who have not had PGD may have other prenatal diagnostic tests such as the following:

Non-invasive prenatal test
is a cell-free fetal DNA test, that allows us to know the sex of the baby, but does not detect the specific mutations of hemophilia. Therefore, it will be useful in cases in which the sex of the baby is determinant for suffering or not suffering from the disease.
Invasive prenatal test
refers to corial biopsy and amniocentesis tests. In these cases, it is possible to study fetal DNA mutations and know whether the baby will be healthy, a carrier or sick.

If an unfavorable result indicates that the fetus has hemophilia, the woman can make the decision to terminate pregnancyuntil the 22nd week if she's a carrier of severe hemophilia.

FAQs from users

Can women have hemophilia or are they just carriers?

By Zaira Salvador BSc, MSc (embryologist).

Yes, cases of women with hemophilia can occur when the father is a hemophiliac and the mother carries the same mutation. However, this possibility is very unlikely and is not usually contemplated.

It is most common to find men with hemophilia and women who are carriers.

Are there cases of acquired hemophilia?

By Zaira Salvador BSc, MSc (embryologist).

Yes, but acquired hemophilia is a very rare disorder. It occurs when the affected person begins to generate antibodies that attack blood clotting factors and prevent them from doing their job.

The exact causes of this disorder are unknown, although they may be related to autoimmune diseases, certain drugs, or tumors.

What are the symptoms and clinical manifestations of hemophilia?

By Zaira Salvador BSc, MSc (embryologist).

The signs and symptoms of hemophilia will always be the bleeding from the lack of blood clotting. In particular, we will highlight the following:

  • Internal hemorrhages in the joints, especially in the knees, elbows and ankles. As a result, the joint swells, feels warm to the touch and hurts when bent.
  • Hemorrhages under the skin causing bruises and hematomas.
  • Excessive bleeding after a dental intervention or when a tooth falls out.
  • Hemorrhage after circumcision.
  • Blood in the urine or feces.
  • Frequent nosebleeds that are difficult to stop.
  • Excessive bleeding after a trauma, cut or surgery.

Suggested for you

If you are interested, you can learn more about genetic diseases and types of inheritance in the following post: What genetic or chromosomal diseases can PGD test for?

We have talked about sex selection to avoid transmitting genetic diseases to offspring. If you want to continue reading on this subject, we recommend you to read the following article: What are the methods for sex selection in babies?

Our editors have made great efforts to create this content for you. By sharing this post, you are helping us to keep ourselves motivated to work even harder.

References

Chen M, Chang SP, Ma GC, Lin WH, Chen HF, Chen SU, Tsai HD, Tsai FP, Shen MC. Preimplantation genetic diagnosis of hemophilia A. Thromb J. 2016 Oct 4;14(Suppl 1):33.

Fernández RM, Peciña A, Sánchez B, Lozano-Arana MD, García-Lozano JC, Pérez-Garrido R, Núñez R, Borrego S, Antiñolo G. Experience of Preimplantation Genetic Diagnosis for Hemophilia at the University Hospital Virgen Del Rocío in Spain: Technical and Clinical Overview. Biomed Res Int. 2015;2015:406096.

Fernández-Arias I, Kim HK. Factor VIII delivery devices in haemophilia A. Barriers and drivers for treatment adherence. Farm Hosp. 2016 Nov 1;40(n06):579-603.

Mingot-Castellano ME, Núñez R, Rodríguez-Martorell FJ. Hemofilia adquirida: epidemiología, clínica, diagnóstico y tratamiento. Medicina Clínica 2017;148(7): 314-322

Morales-Machín A, Borjas-Fajardo L, Zabala W, Alvarez F, Fernández E, Zambrano M, Delgado W, Hernández ML, Solis-Añez E, Chacín JA. Indirect prenatal molecular diagnostic of haemophilia A and B. Invest Clin. 2008 Sep;49(3):289-97.

FAQs from users: 'Can women have hemophilia or are they just carriers?', 'Are there cases of acquired hemophilia?' and 'What are the symptoms and clinical manifestations of hemophilia?'.

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Authors and contributors

 Carmen Ochoa Marieta
Carmen Ochoa Marieta
MD, PhD, MSc
Gynecologist
Bachelor's Degree in Medicine from the Basque Country University. PhD in Medicine & Surgery from the University of Murcia. Currently, she is the director of the Assisted Reproduction Unit of Centro de Estudios para la Reproducción (CER SANTANDER) in Santander, Spain, as well as the director of the Diagnostic Unit of Human Assisted Reproduction in Bilbao. More information about Carmen Ochoa Marieta
License: 484805626
 Sarai Arrones
Sarai Arrones
BSc, MSc
Embryologist
Bachelor's Degree in Biomedicine and Biomedical Sciences from the University of Valencia (UV). Master's Degree in Biotechnology of Human Assisted Reproduction from the UV and the Valencian Infertility Institute (IVI). Specialist Training Course of gamete, embryo, and animal tissue cryopreservation. Embryologist specializing in the field of Assisted Procreation. More information about Sarai Arrones
 Zaira Salvador
Zaira Salvador
BSc, MSc
Embryologist
Bachelor's Degree in Biotechnology from the Technical University of Valencia (UPV). Biotechnology Degree from the National University of Ireland en Galway (NUIG) and embryologist specializing in Assisted Reproduction, with a Master's Degree in Biotechnology of Human Reproduction from the University of Valencia (UV) and the Valencian Infertility Institute (IVI) More information about Zaira Salvador
License: 3185-CV
Adapted into english by:
 Romina Packan
Romina Packan
inviTRA Staff
Editor and translator for the English and German edition of inviTRA. More information about Romina Packan

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