Combined deficiency of vitamin K-dependent coagulation factors and extensive hemorrhage

Factor (F) II, FVII, FIX, and FX are known as vitamin K-dependent coagulation factors, as ?-carboxylation of the glutamine (Glu) residues is a critical step for their coagulant activities [1–3]. Gamma-carboxylation of the Glu residues which is mediated by ?-glutamyl carboxylase (GGCX) and reduced vitamin K (KH2) as its cofactor, is necessary for binding of calcium ions which then allows binding to phospholipid membranes. Another enzyme playing an important role in this cycle is called vitamin K epoxide reductase (VKOR). The VKOR catalyzes reconversion of vitamin K epoxide (KO), which is produced during the last reaction, to KH2 [2, 4]. Some natural anticoagulants including protein C, protein S, and protein Z also requires Glu residues to be modified into ?-carboxyglutamate (Gla) residues and therefore there are low levels of protein C and protein S in the deficiencies of GGCX or VKOR. The deficiency of vitamin K-dependent coagulation factors can be an inherited or acquired disorder. In inherited form of disease, the disorder is usually manifest in infancy period, although it may also remain latent for a short time. Clinical manifestations are depending on the level of reduced coagulation factors [2, 6, 7]. Acquired vitamin K-dependent coagulation factors are more common than congenital deficiency of these factors and only a few congenital form of disorders were reported up to now. Acquired deficiency can results in different conditions including liver disease and malabsorption [8, 9]. In the present study, we reported a woman with acquired vitamin K-dependent coagulation factors with extensive menorrhagia. We described a 43-year-old female with simultaneous decrease in vitamin K-dependent coagulation factors. She was born from an Iranian mother and a Russian father. Three years later, patient was referred with extensive menorrhagia and was hospitalized for management of her severe bleeding as well as diagnosis of disorder. In routine coagulation tests, prothrombin time (PT, normal range: 11.7–14.2 s) and activated partial thromboplastin time (APTT, normal range: 29–40 s) that was performed by STA compact automated coagulometer (Stago, Paris, France) both were prolonged while bleeding time (BT) (Ivy method) and platelet count (Sysmex kx21 hematology analyzer) were normal. In the mixing study, PT and APTT were corrected that indicating factor deficiency rather than inhibitor formation against deficient coagulation factors. Factor activity for all coagulation factors were performed (STA, compact automatic coagulometer, Diagnostica, Stago) except on factor XIII (FXIII) that was screened by clot solubility test as described by Dorgalaleh et al. [7]. Vitamin K dependent coagulation factors level were abnormal (Table 1).