Three problems of hemophilia B : a study of abnormal factor IX molecules with an inhibitor neutralization assay

Briët, E. (1977)

Doctoral Thesis

Hemophilia is a sex linked, recessive, hereditary disorder characterized
by excessive bleeding. This bleeding tendency manifests
itself in spontaneous hemorrhages in the joint cavities and muscles,
and in excessive bleeding after trauma or surgical procedures.
The first written references to the disease can be found in the
Babylonian Talmud, in which it can be read that Rabbi Judah the
Patriarch exempted the third son from circumcision if his mother
had already lost two sons because they had bled to death after
this operation ( 1 ) . Rabbi Simon hen Gamaliel even forbade a boy
to be circumcised whien sons of his mother's three elder sisters had
died from bleeding after circumcision ( 2).
In the 19th century Wardrop discovered the prolonged clotting
time of hemophilic blood. For a long time lack of prothrombin was
held responsible for the clotting defect until in 1935 Quick found
that the prothrombin time of hemophilic plasma was normal ( 2) .
Patek and Taylor reported in 1937 that the prolonged clotting
time of hemophilic plasma could be normalized by the addition of
a globulin fraction of normal blood. For this reason the lacking
clotting component was called antihemophilic globulin; later, by
international agreement, it was named clotting factor VIII (2).
In 1944 Pavlovsky observed that a mixture of the blood of two
hemophiliacs known to him had a normal clotting time ( 3, 4). The
right interpretation of this finding was given only in 1952 and not
by Pavlovsky himself. In that year reports from New York, San
Francisco, and Oxford described a disease which was clinically and
genetically undistinguishable from hemophilia, but the lacking
clotting component was not factor VIII ( 5-7). The missing factor
in this new disorder, PTC-deficiency, Christmas disease or hemophilia
B, was later called factor IX.

• Hemophilia B
• Genetic heterogeneity
• Carrier detection

• All authors: Briët, E.
• Supervisor: Veltkamp, J.J.
• Committee: Hijmans, W.; Sixma, J.J.
• Qualification: Doctor (dr.)
• Awarding Institution: Medicine / Leiden University Medical Center (LUMC), Leiden University
• Date: 1977-06-16
• Publisher: Leiden: Drukkerij "Luctor et emergo"
• Sponsorship: Financial support was obtained from the "Hippocrates Studiefonds"