Biomedical Engineering Reference
In-Depth Information
Hemophilia
13
A (FVIII deficiency)
The disease is caused by a defective gene located on the X chromosome. Females
have two copies of the X chromosome and the disease does not manifest if one of
the chromosomes is normal. It is the most common coagulation disorder.
Hemophilia B (FIX deficiency)
It is also known as Christmas disease, because it was identified (Oxford, 1952) and
distinguished from Hemophilia A in a boy whose name was Stephen Christmas (he
died in 1993, a victim of HIV contracted by blood transfusions). The defective gene
is also located on the X chromosome.
Hemophilia C (FXI deficiency)
Also known as Rosenthal's Disease. The fourth most common coagulation disorder,
after the preceding two forms and vWD (see below). It is a much milder disease,
also discovered in the 1950's.
Remark 3.
FVIII, FIX, FXI are also called
Antihemophilic Factors A, B, C,
respec-
tively. FIX is sometimes called
Christmas Factor
. For a detailed description of
Hemophilia A and B see [30]. According to the cell based model, FXIa is the only
activator of FIX, thus one may wonder why hemophilia C is milder than hemophilia
B. An explanation can be the ability of platelets to produce FXI even in individuals
defective of plasma born FXI [28, 66].
Parahemophilia (FV deficiency)
A rare disease. Here we also mention ([8]) that there are mutations of FV that make
FVa resistant to APC, thus prolonging Thrombin release: the so called
Leiden
mu-
tation of FV is believed to be the most common genetic cause of thrombosis.
von Willebrand Disease (vWD: vWF deficiency)
In a small village in the
˚
Aland Islands von Willebrand studied an inherited and se-
vere bleeding disorder hitting consanguineous families. It was 1924. He recognized
that the disease was not one among the known congenital bleeding diseases, though
he could not identify the cause. vWF deficiency affects both primary and secondary
hemostasis. vWD comes in different types (1: partial deficiency, 2: partially defec-
tive vWF, 3: total deficiency). It may induce a deficiency of FVIII, of which vWF
is a carrier in blood, as we have seen. A form of vWD-2 is hyperactivity of vWF
leading to excessive platelet adhesion. Hyperactivity is caused by deficiency of the
enzymes that shorten the vWF multimer, leaving only the larger, more active species.
A study performed on pigs affected by vWD ([69]) showed that platelets failed to
undergo significant morphological changes, thus proving that vWF has a key role
13
Abbreviation of the term haemorrhaphilia, coined by the German physician Friedrich Hopff
(1828).
