Genetic Disorders that Affect Blood Clotting Factors

When bleeding occurs (internally or externally), the body relies on a chain reaction of events known as the clotting cascade to signal the appropriate key players to stop that bleeding.  It is a very specific game of dominoes, with each protein signaling the next on the chain and no other.  However, because this chain reaction is dependent on so many different proteins doing their job, there is also a lot of opportunity for genetics to make mistakes.  Each protein, theoretically, could have a disease associated with its genetic absence or dysfunction, and a slightly different pathology to each disease.  While there has not been a diseased discovered for every factor, many genetic bleeding disorders have been discovered.

By far, the most common of these is hemophilia.  Of the three types of hemophilia, hemophilia A is the most common.  Hemophilia A is caused by low levels of Factor VIII, one of the clotting factors.  Generally, those with hemophilia A experience prolonged clotting times.  Contrary to popular belief, hemophiliacs do not die from a paper cuts, and in fact, external bleeding rarely pose serious problems (unless it is a deep or large enough cut to be dangerous for anyone).  Internal bleeding, especially in the joints, is the main concern for a hemophiliac. Membrane bleeds in the mouth and nose can also be problematic, because wet environments impede the clotting process.

Hemophilia B, hemophilia A’s close cousin, is the next most common hemophilia. Hemophilia B is caused by low levels of Factor IX.  Because Factor IX and Factor VIII both activate Factor X, they have very similar functions.  As such, hemophilia A and hemophilia B are almost indistinguishable in terms of symptoms and complications.  

Both of these two hemophilias also have the same inheritance pattern—they are both x-linked recessive. In X-linked recessive traits, generally the gene is carried by women, but the disease generally affects men. This is because women have two X chromosomes, whereas men only have one; in short, women have to get doubly unlucky and get two dysfunctional copies.  It is possible for a woman to have hemophilia, but significantly more unlikely.  It is also possible for a woman with only one affected chromosome to exhibit hemophilia through Barr body inactivation or Lyonization.

The last hemophilia, hemophilia C, is quickly losing the name hemophilia and starting to be called Factor XI deficiency.  The major reason for the name shift is that it does not share exact symptoms like hemophilias A and B do.  Also, Factor XI deficiency doesn’t show the same inheritance pattern.  Rather, it exhibits an autosomal inheritance pattern, or a pattern not linked to gender.  The symptoms associated with Factor XI deficiency are similar, but not identical. Hemophilia C is also extremely rare, except in Ashkenazi Jews.

The next most common bleeding disorder is von Willebrand’s Disease (vWD). Like hemophilia C, vWD is inherited in an autosomal fashion.  There are several different subtypes of vWD, but all tend to show more membrane-bleeding and less joint-bleeding when compared to hemophilia.  

Other bleeding disorders are also present.  Seven other deficiencies   have been discovered to date, but each is extremely rare.

Because so many proteins are involved in this process, there are many different diseases that can result from genetic mistakes.  Each of these is a disease which can really change the way that lives are lived, but many of them have effective comprehensive available.