Abstract
Factor XIII-A (FXIII-A) deficiency is an ultra-rare bleeding disorder characterized
by high rates of morbidity and mortality, primarily resulting from intracranial hemorrhage,
umbilical cord bleeding, and miscarriage, whereas patients with severe FXIII-B deficiency
present with a milder phenotype. Although the estimated incidence of severe FXIII-A
deficiency is one per 2 million, a high prevalence ranging from 0.8 to 3.5% has been
observed for heterozygous FXIII-A deficiency. Unlike most bleeding disorders, individuals
with heterozygous FXIII-A deficiency, particularly women, are more likely to experience
hemorrhagic complications during hemostatic challenges. About 200 Mutations have been
observed in F13A and F13B genes, with most being missense mutations, while large deletions are the rarest.
There is no correlation between genotype and phenotype and a moderate to strong correlation
between factor activity and clinical severity in FXIII-A deficiency, making it difficult
to predict bleeding patterns based on genotype and FXIII activity levels. Primary
prophylaxis is mandatory for all patients with severe FXIII-A deficiency, while those
with heterozygous deficiency are generally asymptomatic and may require on-demand
therapy during hemostatic challenges, most commonly in women. On the other hand, patients
with severe FXIII-B deficiency may only require on-demand therapy, while heterozygotes
are generally asymptomatic. Although there are general recommended therapeutic regimens
for prophylaxis or on-demand therapy in different situations, personalized pharmacokinetic-based
replacement therapy represents the optimal approach that can optimize intervention
efficacy. In such an approach, several factors may affect the effectiveness of treatment
and determine the dose and type of intervention, including the classification of FXIII
deficiency, residual plasma levels of FXIII, clinical situation requiring intervention,
age, weight, and also gender.
Keywords
FXIII deficiency - rare bleeding disorders - intracranial hemorrhage - umbilical cord
bleeding
