A study on the subclinical hepatic dysfunction as a causative factor of infantile vitamin K deficiency hemorrhage

婴儿维生素K缺乏性出血是一种严重的疾病，主要见于婴儿期早期的母乳喂养婴儿，通常没有任何明显的原因。我们怀疑肝功能与本病的发生发展有一定的关系，并研究其作为本病的致病因素的作用。在三周时显示低正常值的9名婴儿中，有8名随后出现肝功能障碍。患者以及正常水平较低的婴儿血清中快速转化蛋白（如青蓝蛋白）水平升高。这些结果表明，维生素K缺乏的婴儿没有产生蛋白质的损害，但存在胆汁淤积。用气相色谱法测定了8例维生素K缺乏症患儿的血清胆汁酸。所有患儿血清总胆汁酸均明显升高，C/CDC比值较高，提示存在胆汁淤积。对194例5日龄正常新生儿口服维生素K，测定血清维生素K和血清PIVKA-II水平。其中，7名婴儿在给予维生素K 3小时后血清维生素K没有升高，其中6名婴儿在3周时出现PIVKA- II阳性，提示存在维生素K缺乏症。本研究结果清楚地表明，婴儿早期“生理性”胆汁淤积导致的维生素K吸收不良在特发性婴儿维生素K缺乏性出血的发展中起重要作用。

Infantile vitamin K deficiency hemmorrhage is a serious disease, mainly seen in breast-fed infants during early infancy, usually without any apparent causes. We suspected the liver function somehow related to the development of this desease, and studied to elucidate its role as a causative factor of this disease.1. Eight out of nine infants, who showed low normotest at the age of three weeks, developed hepatic dysfunction later.2. Serum levels of rapid turnover proteins, such as ceruloplasmin, were elevated in the patients, as well as in the infants who showed low normotest. These results suggested that there was no impairment in the production of the proteins, but there existed bile stasis in the infants with vitamin K deficiency.3. Serum bile acids were determined in eight infants with vitamin K deficiency with gas-chromatography. All the infants showed markedly elevated serum total bile acid and high C/CDC ratio, which strongly suggested the existense of bile stasis.4. Vitamin K was administered p.o. to 194 normal newborn infants at the age of 5 days, and serum level of vitamin K and serum PIVKA-II were determined. Among them, seven infants showed no elevation of serum vitamin K after 3 hours post vitamin K adminstration, of whom six became positive for PIVKA- II at the age of 3 weeks, suggesting the presence of vitamin K deficiency.The results of the present study clearly indicate that malabsorption of vitamin K due to "physiologic" cholestasis in early infancy plays an important role in the development of idiopathic infantile vitamin K deficiency hemorrhage.