van Oosterom A T, Mattie H, Hermens W T, Veltkamp J J
Thromb Haemost. 1976 Jun 30;35(3):607-19.
The influence of the thyroid function on the metabolic rate of prothrombin, factor VII, and X was studied in the rat. Disappearance rates of the three coagulation factors were measured after synthesis had been blocked with appropriate doses of warfarin, and reappearance rates were assessed upon induction of synthesis by high doses of vitamin K1 injected into rats displaying coumarin induced hypocoagulability. No statistically significant difference in the disappearance and production rates of any of the factors could be found between normal euthyroid rats and thyroxin-treated hypothyroid rats proven to be euthyroid. The differences between the two euthyroid groups and the hypothyroid group were highly significant, however: hypothyroidism results in an approximately 50% decrease of the metabolic rates of the three coagulation factors under study. The reappearance of the three factors, under euthyroid as well as hypothyroid conditions, showed a biphasic pattern: in the first two hours after vitamin K1 administration to warfarin treated rats, a rapid reappearance was observed, to the same extent for all three factors, in hypo- as well as euthyroid rats. This finding suggests that in vitamin K1 deficiency an intracellular accumulation of precursor proteins (PIVKAs) occurs, which after rapid conversion into biologically active coagulation factors by vitamin K1 are shed into circulation. The subsequent phase of reappearance is much slower and reflects the synthesis rate of coagulation enzymes. It is characteristic for each factor and clearly slower in hypothyroid rats than in euthyroid rats. From this an influence of thyroid function on the synthesis rate of the protein moiety of coagulation factors can be inferred. An apparent difference between disappearance and reappearance rate of the coagulation factors in the plasma, particularly pronounced for factors VII and X in euthyroid rats, could theoretically be explained as the consequence of the model used for derivation of these rates.
在大鼠中研究了甲状腺功能对凝血酶原、因子VII和因子X代谢率的影响。在用适当剂量的华法林阻断合成后，测量这三种凝血因子的消失率，并在向显示香豆素诱导的低凝性的大鼠注射高剂量维生素K1诱导合成后评估再出现率。在正常甲状腺功能正常的大鼠和经甲状腺素治疗的甲状腺功能减退大鼠（已证明甲状腺功能正常）之间，未发现任何一种因子的消失率和产生率有统计学上的显著差异。然而，两个甲状腺功能正常组与甲状腺功能减退组之间的差异非常显著：甲状腺功能减退导致所研究的三种凝血因子的代谢率降低约50%。在甲状腺功能正常和甲状腺功能减退的情况下，这三种因子的再出现呈现双相模式：在对华法林处理的大鼠给予维生素K1后的头两个小时内，观察到快速再出现，在甲状腺功能减退和甲状腺功能正常的大鼠中，所有三种因子的再出现程度相同。这一发现表明，在维生素K1缺乏时，会发生前体蛋白（PIVKAs）的细胞内积累，这些前体蛋白在被维生素K1快速转化为生物活性凝血因子后释放到循环中。随后的再出现阶段要慢得多，反映了凝血酶的合成速率。这是每种因子的特征，在甲状腺功能减退的大鼠中明显比甲状腺功能正常的大鼠慢。由此可以推断甲状腺功能对凝血因子蛋白质部分的合成速率有影响。血浆中凝血因子消失率和再出现率之间的明显差异，在甲状腺功能正常的大鼠中尤其明显，对于因子VII和因子X来说，从理论上可以解释为用于推导这些速率的模型的结果。
