Abstract
Factor (F) XIII deficiency is a congenital rare bleeding disorder (RBD), with an estimated
prevalence of 1 in 1 to 2 million individuals, and more than 1,200 patients have been
diagnosed to date. In newborns, umbilical cord bleeding is typical, and later in life
during trauma, surgery and even spontaneously prolonged bleeds, reproduction, and
delivery complications occur frequently without appropriate replacement therapy. Also,
an acquired form of FXIII deficiency may occur via massive bleeds or neutralizing
antibodies. In the inherited form of FXIII deficiency, prophylaxis with FXIII concentrate
is administered to prevent the very high risk of intracranial bleeds, the incidence
being close to 30%. Laboratory diagnosis of FXIII deficiency is based on measuring
plasma FXIII antigen and activity, and it is claimed that FXIII activity of around
5 IU/dL would suffice to protect from bleeds. However, at the low levels of detection,
most FXIII methods are inaccurate, and quality controls and collaboration with reference
laboratories are important to improve the accuracy of low-level FXIII measurements.
The trough target for prophylaxis should be set to 10 to 20 IU/dL, which is achievable
by administration of 25 to 35 IU/kg every 4 to 6 weeks. However, general risk factors
influencing hemostasis should be carefully evaluated, including anemia and hypertension.
Fibrin cross-linking by FXIII is of major importance and red cells bind to fibrin
partially via platelets and FXIII to promote clot strength. Physiologically, platelets
and macrophages contain FXIII providing cellular support; thus, the patients may benefit
from platelet transfusion during problematic bleeds. Plasma-derived and recently a
recombinant FXIII concentrate are available; however, the latter has mainly anecdotal
data regarding management of bleeds and surgery, and its access is limited due to
the high cost. The international registry RBD database, (RBDD) continues to gain cumulative
knowledge, and registration of all FXIII deficient patients, both inherited and acquired,
is highly recommended.
Keywords factor XIII - FXIII - bleeding disorders - coagulation
