Blood, Vol. 93 No. 3 (February 1), 1999:
pp. 909-917
Autoimmune Antibody in a Hemorrhagic Patient Interacts With
Thrombin-Activated Factor XIII in a Unique Manner
Laszlo Lorand,
Pauline T. Velasco,
S.N. Prasanna Murthy,
Phil Lefebvre, and
David Green
From the Department of Cell and Molecular Biology and the Feinberg
Cardiovascular Research Institute, and the Department of Medicine,
Northwestern University Medical School, Chicago, IL.
Without a prior history of hemorrhagic disease, a 62-year-old man
suffered recurrent episodes of bleeding. Solubility of the patient's
clot in 5 mol/L urea indicated a problem with fibrin stabilization. The
transamidase activity potential of factor XIII, measured by the
incorporation of radioactive putrescine into N,N-dimethylcasein as test
substrate, was 62% of control, close to the normal range of values.
Examination of the patient's clot from recalcified plasma by sodium
dodecyl sulfate-polyacrylamide gel electrophoresis showed that
essentially none of the 
chains and only about two thirds of the 
chains of fibrin became cross-linked under conditions where both were
fully cross-linked in the controls. An antibody to factor XIII was
isolated which, although recognizing the recombinant rA2
subunits, as well as the virgin A2B2 plasma
ensemble, showed a 100-fold greater affinity for the thrombin-activated
rA2' and A2'B2 forms of
the zymogen, suggesting that the latter would be its main target during
coagulation. Furthermore, the patient's IgG has an ability, never seen
before, for inducing an enzymatically active configuration in the
thrombin-activated zymogen in the absence of Ca2+.
