Hemostatic rebalance in neonatal intrahepatic cholestasis with citrin deficiency

Neonatal intrahepatic cholestasis with citrin deficiency (NICCD) results in coagulopathy due to decreased levels of vitamin (V)K-dependent clotting factors, similar to biliary atresia (BA). However, the involvement of VK-independent coagulant and anticoagulant factor(s) remains unknown. We examined relationships between coagulant and anticoagulant potential before and after nutritional treatment in NICCD.

Three cases (aged 12, 21, and 45 days) with NICCD-associated coagulopathy were evaluated with standard coagulation/anticoagulation tests and comprehensive coagulation assays, rotational thromboelastometry, and protein C/protein S (PC/PS) pathway function assay (ThromboPath^® ), before and after nutritional treatment.

In all cases, activated partial thromboplastin time and prothrombin time were significantly prolonged, which is associated with very low levels of VK-independent fibrinogen and antithrombin. The initiation of nutritional treatment of medium-chain triglycerides oil improved these levels within the normal range, although low levels of other clotting factors were modestly increased. Whole blood- rotational thromboelastometry analysis revealed near-normal coagulation potential, even before treatment, comparable to healthy adults, and supportive of their non-bleeding symptoms. The introduction of nutritional treatment had further improved comprehensive coagulation potential. The global PC/PS-pathway function assay demonstrated the absence of the features of this function associated with the pathogenesis of NICCD. Compared to BA, the plasma levels of fibrinogen and antithrombin in all cases were markedly low, whilst those after treatment improved, especially to similar level of BA.

Neonatal intrahepatic cholestasis with citrin deficiency has the characteristic of rebalancing hemostatic mechanisms associated with coagulant and anticoagulant potential involving low levels of fibrinogen and antithrombin, suggesting a pathophysiological coagulopathy distinct from BA.