Hemophilia: Causes, Types, Treatments, and Genetic Diagnosis
Understanding Hemophilia
Hemophilia is a genetic disorder linked to the X chromosome, characterized by the blood’s inability to clot properly. It leads to internal and external bleeding due to a partial deficiency of specific clotting proteins, known as antihemophilic globulin or coagulation factors.
How Blood Clotting Works
Coagulation factors are a group of proteins responsible for activating the clotting process. There are 13 identified factors (I, II, …, XIII; Factor IV has not been assigned). These clotting factors act in a cascade, meaning one activates the next. If one factor is deficient, the clotting process is either significantly delayed or does not occur effectively.
When there is a lack or deficiency of a coagulation factor, the blood takes longer to form a clot. If formed, the clot may not be consistent or strong enough to stop bleeding. Consequently, in severe hemophiliacs, even small injuries can lead to significant and potentially fatal blood loss.
Key Characteristics and Symptoms
- Platelet aggregation is not altered in hemophiliacs; the Ivy bleeding time is normal.
- Hemarthrosis (internal bleeding into the joints) is a pathognomonic symptom. This occurs because the tissue factor, which triggers the extrinsic coagulation pathway, is the only pathway functioning adequately in hemophiliacs.
Types of Hemophilia
There are three main varieties of hemophilia:
- Hemophilia A: Caused by a shortage of clotting factor VIII.
- Hemophilia B: Caused by a shortage of clotting factor IX.
- Hemophilia C: Caused by a deficiency of Factor XI.
Hemophilia Treatment Options
Currently, hemophilia is incurable, but effective treatments are available to manage and control bleeding episodes.
There are two primary types of treatments:
- On-Demand Treatment: Involves administering coagulation factors as soon as the first symptoms of bleeding appear.
- Prophylactic Treatment: Involves regular administration of coagulation factors to prevent hemorrhages.
Coagulation Factor Concentrates
Coagulation factors consist of concentrates obtained from human plasma or from other mammalian cells using recombinant technology. These concentrates have a high degree of purity and are obtained after several stages of processing.
The process typically involves:
- Introducing the human gene encoding factors VIII and IX into mammalian cells.
- Allowing these cells to multiply to produce sufficient quantities of factors VIII and IX.
Preimplantation Genetic Diagnosis (PGD) for Hemophilia
Preimplantation Genetic Diagnosis (PGD) is an assisted reproduction technique used to prevent the gene that causes hemophilia from being passed on to your children.
PGD is often performed in conjunction with In Vitro Fertilization (IVF), an assisted reproduction technique that involves placing one or more of the woman’s eggs in contact with sperm in a laboratory to facilitate fertilization. This technique is recommended as a treatment for couples with various types of infertility if there is a problem that hinders or requires such a procedure.
PGD Process Steps
The PGD process typically involves the following stages:
1. Egg Retrieval
This step requires controlled ovarian stimulation, monitored through hormonal and echographic analysis. At the moment of ovulation, follicular puncture is performed to retrieve a sufficient number of eggs directly from the ovary.
2. In Vitro Fertilization (IVF)
The retrieved eggs are then inseminated in the laboratory with sperm obtained from a semen sample from the couple or from a sperm bank (in cases of male infertility). The fertilized cells (zygotes) are grown until they reach the 8-cell pre-embryo stage.
3. Biopsy and Genetic Analysis
One cell is carefully taken from each pre-embryo (biopsy). Biochemical and genetic analyses are then performed on these cells to determine which embryos are not carriers of the defective gene and are therefore suitable for transfer.
A maximum of 3 healthy pre-embryos are typically transferred into the woman’s uterus. This transfer is usually performed 2 days after fertilization.