Abstract
Despite the early discovery of factor XIII (FXIII) in 1944, the diagnosis of FXIII
deficiency was not made until 1960, after all the other coagulation factor deficiencies,
most likely due to the normality of routine coagulation testing in FXIII deficiency.
Although the first case was detected by the clot solubility test and this test has
long since been used to detect FXIII deficiency, the test is no longer recommended
by experts. Over the past 60 years, knowledge about FXIII deficiency has expanded
considerably, between 1992, when the first variant was identified, and 2022, 197 mutations
have been reported. Almost all missense mutations have a similar effect on FXIII,
leading to instability and faster degradation of mutant FXIII protein. Therapeutic
options have evolved from historical fresh frozen plasma (FFP), old plasma, whole
blood, and cryoprecipitate, to plasma-derived and recombinant FXIII concentrates,
respectively available since 1993 and 2012. These concentrate products were respectively
approved by the Food and Drug Administration in 2011 and 2013. This historical review
covers various aspects of FXIII related disorders, including the discovery of the
FXIII, associated disorders, molecular basis, diagnosis, and treatment of FXIII deficiency.
Keywords
factor XIII deficiency - factor XIII - bleeding - diagnosis - management
