Coagulation Disturbances in Patients with Argininemia

Abstract

Background: Argininemia is an autosomal recessive urea cycle disorder (UCD). Unlike other UCD, hyperammonemia is rarely seen. Patients usually present in childhood with neurological symptoms. Uncommon presentations like neonatal cholestasis or cirrhosis have been reported. Although transient elevations of liver transaminases and coagulopathy have been reported during hyperammonemia episodes, a permanent coagulopathy has never been reported. Methods: In this retrospective study, coagulation disturbances are examined in 6 argininemia patients. All of the patients were routinely followed up for hepatic involvement due to argininemia. Laboratory results, including liver transaminases, albumin, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and clotting factor levels, were assessed in all of the patients. Results: All of the patients had a prolonged PT and an increased INR, while none of the patients had a prolonged aPTT. Five patients had slightly elevated liver transaminases. A liver biopsy was performed in 1 patient but neither cirrhosis nor cholestasis was documented. Five of the 6 patients had low factor VII and factor IX levels, while other clotting factors were normal. Conclusions: Argininemia patients should be investigated for coagulation disorders even if there is no apparent liver dysfunction or major bleeding symptoms.

Liver-transplantation-corrected coagulation dysfunction and neurological impairment in patients with argininemia

“…PT was prolonged and INR was increased in all patients. APTT was prolonged for > 10 s in ve patients with hyperammonemia, which is different from a previous report 5 . This maybe related to the severity of different groups of patients.…”

“…In addition to nervous system damage, the effect on liver is often manifested as mildly elevated ammonia and transaminase. Coagulation disorders with hyperammonemia episodes have been described previously, although there is no consensus on their relationship 2,5 . All the patients in our study presented with marked coagulation dysfunction, and elevated liver transaminase and plasma ammonia were found in the same blood samples.…”

“…Although the mechanism of liver injury in UCD patients is still unclear, hyperammonemia is considered to be an important cause of liver damage 5,6 . Fortunately, we got liver specimen by LT in seven patients with argininemia.…”

“…None of the nine patients had life-threatening hemorrhage, despite the serious clotting disorder, which may be related to the decrease in clotting and anticlotting factors 6,15 . Clotting factor V is considered to be a sensitive indicator of liver synthetic function, but levels are within the normal reference in patients with argininemia 5 . Measurement of coagulation factors was not included in the preoperative evaluation, so patients in this group were not further checked for coagulation factor de ciency.…”

“…Liver damage ranging from mild elevation of transaminases to liver failure have been reported in previous studies 4 . Additionally, coagulation dysfunction is the characteristic of patients with argininemia, which is not accompanied by life-threatening hemorrhagic complications, and the mechanism is still unclear 5 . Studies have suggested that elevated plasma ammonia is an important cause of clotting disorders in other UCDs 6 ; however, there is no consensus on whether coagulopathy in patients with argininemia is related to elevated plasma ammonia.…”