Abstract
Vitamin K–dependent coagulation factors deficiency (VKCFD) is a rare autosomal recessive
genetic disease characterized by impaired levels of multiple coagulation factors (II,
VII, IX, and X) and natural anticoagulants (proteins C and S). VKCFD is part of familial
multiple coagulation factor deficiencies, reporting overall 50 affected families thus
far. Disease manifestations are quite heterogeneous, bleeding symptoms may vary, and
even, although generally mild, some patients may succumb to fatal outcomes. VKCFD
diagnosis may be delayed because the disease phenotype simulates the most frequently
acquired deficiencies of vitamin K. First-line coagulation assays, prothrombin time/international
normalized ratio (PT/INR) and activated partial thromboplastin time (aPTT), are both
prolonged; mixing test typically normalizes the clotting times; and vitamin K–dependent
coagulation factors will be variably decreased. Molecularly, VKCFD is associated with
mutations in γ-glutamyl-carboxylase (GGCX) or vitamin K epoxide reductase complex subunit 1 (VKORC1) genes. Vitamin K is involved not only in the biosynthesis of coagulation proteins
but also in bone metabolism and cell proliferation. Therapeutic options are based
on vitamin K supplementation, coagulation factors (prothrombin complex), and fresh
frozen plasma, in case of severe bleeding episodes. Two case studies here illustrate
the diagnostic challenges of VKCFD: case 1 depicts a woman with a history of bleeding
episodes, diagnosed, only in her third decade of life with inherited homozygous GGCX gene mutation. Case 2 shows a man with an acquired vitamin K deficiency caused by
Crohn's disease. Better understanding of GGCX and VKORC1 mutations aids in prognosis and treatment planning, with emerging insights suggesting
potential limitations in the effectiveness of vitamin K supplementation in certain
mutations.
Keywords
VKCFD - γ-Glutamyl carboxylase - VKORC1 - rare bleeding disorders - familial multiple
factor deficiencies - vitamin K antagonists
