Sat. Jun 12th, 2021

What is hemophilia and the Causes of Hemophilia?

A small wound, which is insignificant to most people, can be a problem for hemophilia patients because their blood does not clot normally, and they can bleed.

Hemophilia is an inherited disease that is difficult or inability of the blood to clot. A small wound, which is insignificant for anyone in normal conditions, for a hemophiliac can be a real problem. The pathology is usually characterized by the appearance of internal and external bleeding and other symptoms derived from this situation.

This bleeding disorder is considered a rare disease, affecting a very small percentage of the population: 1 in 6,000 live newborns in hemophilia A and 1 in 30,000 in hemophilia B.

It is caused by an alteration in the genes F8 or F9 that produce factor VIII (FVIII) and factor IX (FIX) of coagulation; it is a disease produced by the deficiency of one these factors in the coagulation system.

Our blood clotting system works thanks to what is known as the coagulation cascade. There are 13 factors (From Factor I to Factor XIII) that work in a chain. Suppose one fails or does not work as it should. In that case, this cascade, responsible for generating clots in a wound or similar event, is interrupted, causing the injuries to bleed more time, thus increasing the risk of both internal and external bleeding.

When there is a congenital deficiency of factor VIII, we speak of hemophilia A, the most common among those affected. The factor IX deficiency is known as hemophilia B.

Hemophilia: the disease of kings

The first descriptions found, in Jewish writings, of cases that probably correspond to hemophilia date back to the second century BC. Certain regulations exempted from the ritual of circumcision those boys whose older brothers had suffered major hemorrhages or died during this procedure. Later, various stories appear that narrates the strange death by exsanguination of, for example, all the siblings of a family.

When talking about the history of hemophilia, one can remember the case of Queen Victoria of England (19th century), who discovered that she was a carrier of hemophilia after the birth of her eighth child. As was customary among the noble classes, there were numerous arranged marriages with members of other royal families in this family. The germ of hemophilia was spreading through the royal houses of half Europe. This is how this disease came to be known in the western world as ‘the disease of kings.’

Causes of Hemophilia

The causes of hemophilia are found in the absence, deficiency, or inadequate confirmation of specific proteins that are part of the so-called coagulation cascade. When an injury occurs, the organism gives the order to mobilize a series of components present in the blood (which are in circulation at all times, whether or not there is an injury) that will go to the injured point, forming a wall that prevents the exit of the blood. The formation of this wall (clot) occurs after the action of proteins called coagulation factors. The process by which these activate the clotting mechanism is called the coagulation cascade. Since each of them (12 in total) activates the next one, due to this cascade activation, if one of the factors is not present or is so poorly, it will cause a failure in the whole process.

Hemophilia is an inherited disease; its transmission is linked to the X chromosome (sex chromosome), and there is no equivalent allele on the Y chromosome.

The defective gene is recessive against the normal gene. This means that as long as a normal copy of the gene is present, the carrier individual will be healthy. That is why hemophilia is a disease in which women are usually only carriers, while men are the ones who suffer from the disease: In humans, chromosomes come in pairs.

Thus, in its genome, there are two copies of all genes. If one of the copies shows an error, the other remains to ensure that its functions are carried out correctly. But there is an exception: the sex chromosomes, X and Y. Women have two copies of the X chromosome, so if a girl inherits a chromosome with the defective gene from one of her parents, she will still have another copy that will ensure correct clotting (there is an extremely low probability that both carry the defective gene). Men, however, only have one X chromosome. If it has a defective gene, the disease will appear in 100% of cases.

Types of hemophilia

Two types of hemophilia can be distinguished; both are characterized by the same symptoms but differ in the coagulation cascade’s wrong factor.

  • Hemophilia A: the defect is in factor VIII. This is the most frequent type. It is the one that manifests itself in 85% of cases.
  • Hemophilia B: the defect is in factor IX.

Some individuals may have some factor, and others nevertheless have a total lack.