Bleeding diseases or blood clotting disorders are a group of conditions that affect the body’s ability to stop blood loss. The mechanism by which blood loss is normally stopped is known as hemostasis and involves several phases. One of these phases is the blood clotting or coagulation phase. Here a number of chemicals known as clotting factors mediate a series of reactions (coagulation cascade) to help with the formation of a blood clot. The blood clot then strengthens the already formed platelet plug. A blood clot stops further blood loss until a more permanent repair mechanism can remove the threat. With blood clotting disorders, this mechanism of hemostasis is compromised.
What is Hemophilia?
Hemophilia is a blood clotting disease that arises due to the deficiency of one of the clotting factors. It is the most common of the bleeding/clotting disorders. About 85% of hemophilics have a deficiency of Factor VIII while the other 15% have a deficiency of Factor IX. A very rare type of hemophilia involves Factor XI.
These clotting factors play crucial roles in creating a series of chemicals known as prothrombin activator which then converts prothrombin in the blood into thrombin. This newly activated thrombin in turn converts fibrinogen in to fibrin. These long protein stands form the mesh network necessary for a blood clot. Without fibrin, a blood clot cannot be formed at a rate that is fast enough for rapid clotting. This is a crucial phase of hemostasis and can jeopardize the life of a person especially when there is severe bleeding (hemorrhage).
Types of Hemophilia
There are two types of hemophilia :
- Hemophilia A – deficiency in Factor VII (more common)
- Hemophilia B – deficiency in Factor IX
- Hemophilia C – deficiency in Factor XI (rare)
Both these clotting factors are used in the intrinsic pathway to activate Factor X which is one of the components of prothrombin activator. The intrinsic pathway is explained in detail under blood coagulation cascade.
In this type of hemophilia, there is a deficiency in Factor VIII. This clotting factor is manufactured in the liver and the endothelial cells lining the blood vessel, circulates in the blood by binding to von Willebrand factor (vWF) and is activated by thrombin. Once activated Factor VIIIa then works with Factor IX, calcium and phospholipids to activate Factor X.
This type of hemophilia is due to a deficiency in Factor IX. It is also known as Christmas Disease. Factor IX circulates in the blood stream in an inactive form and depends on Factor XI to activate it (IXa). Once activated it works with Factor VIII, calcium and phospholipids to activate Factor X.
A third type of hemophilia known as hemophilia C is a mild form of hemophilia. It is not as common as other blood clotting disorders and is mainly seen in certain ethnic groups. This type of hemophilia is due to a deficiency of Factor XI and prevents the activation of sufficient quantities of Factor IX.
Causes of Hemophilia
Hemophlia is due to genetic abnormalities. The gene for Factor VIII (hemophilia A) is located on chromosome X and is one of the largest genes in the body. Hemophilia arises when there is a large, even complete, deletion of the gene or small mutations. The gene for Factor IX (hemophilia B) is also located on chromosome X but is not as large as the Factor VIII gene. It may also be affected by gene deletions or mutations.
Genes are the blueprint for the formation of different proteins, in this case clotting factors. These genetic abnormalities affect the liver’s ability to produce Factor VIII or Factor IX either completely or only partially. In some cases the correct amount of the protein is manufactured but it is an abnormal protein.
An important point to note with hemophilia is that due to the location of the causative clotting factors genes, on chromosome X, it is strongly associated with gender. Chromosome X, or the female chromosome, means that hemophilia is transmitted by way of the mother (carrier) and almost only affects male children because males have only one X chromosome. Female children of a carrier are unlikely to be affected because females have two X chromosomes and one chromosome should have the appropriate “normal” gene. Nevertheless females can be affected if there is inactivation of the normal gene. This may lead to reduced levels of the clotting factor.
The gene for Factor XI (hemophilia C) is on chromosome 4. This means that it can occur in both males and females.