Miljic Dragana, Miljic Predrag, Doknic Mirjana, Pekic Sandra, Djurovic Marina, Colovic Milica, Popovic Vera
Institute of Endocrinology, University Clinical Center, Belgrade, Yugoslavia.
Hormones (Athens). 2006 Jul-Sep;5(3):187-91. doi: 10.14310/horm.2002.11183.
In rodents, Growth Hormone (GH) has been shown to stimulate coagulation parameters, including Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT) and vitamin K dependent coagulation factors. However, there are no reports on the influence of GH replacement therapy on global coagulation tests in Growth Hormone Deficiency (GHD).
The aim of this study was to investigate the effects of GH administration on basic coagulation parameters: PT, aPTT and fibrinogen concentrations in adult GHD patients before and during one year of GH replacement.
Twenty-one adult patients with severe GHD (mean age +/- SE: 38.6 +/- 2.8 years) were included in this hospital based, prospective, interventional study. All patients were treated with rhGH for 12 months (GH dose: 0.4 mg/day for male and 0.6 mg/day for female patients). IGF-1 concentrations were determined using RIA-INEP kits. Basic coagulation tests, i.e. aPTT and fibrinogen concentrations, were measured before and after 3, 6 and 12 months of treatment with rhGH. Control values were obtained from fourteen "healthy" subjects matched by age, sex and body mass index (BMI).
At baseline, we observed no significant differences in PT, aPTT and fibrinogen values between GHD and healthy subjects. IGF-1 concentrations increased significantly within 3 months of GH therapy (8.2 +/- 1.5 vs. 24.2 +/- 2.9 nmol/l, p <0.05) and remained stable thereafter. A significant increase in PT values, which was more pronounced in female subjects, was noted after 6 and 12 months of treatment with GH. aPTT values increased significantly after 12 months of treatment only in male patients (28.8 +/- 4.6 vs. 39.7 +/- 2.1 s.; p <0.05). No significant changes in fibrinogen concentrations were found during the study.
Twelve months of GH replacement therapy led to a significant increase in PT and aPTT values in adult GHD patients, while fibrinogen concentrations did not change. Changes in PT were more pronounced in female GHD patients, while an increase in aPTT values was observed only in male patients with GHD. The clinical significance of these changes needs further evaluation.
在啮齿动物中，生长激素（GH）已被证明可刺激凝血参数，包括凝血酶原时间（PT）、活化部分凝血活酶时间（aPTT）和维生素K依赖的凝血因子。然而，尚无关于生长激素替代疗法对生长激素缺乏症（GHD）患者整体凝血试验影响的报道。
本研究旨在调查生长激素给药对成年GHD患者在生长激素替代治疗1年之前及期间的基本凝血参数（PT、aPTT和纤维蛋白原浓度）的影响。
本项基于医院的前瞻性干预性研究纳入了21例严重GHD成年患者（平均年龄±标准误：38.6±2.8岁）。所有患者接受重组人生长激素（rhGH）治疗12个月（男性患者生长激素剂量：0.4mg/天，女性患者0.6mg/天）。使用RIA-INEP试剂盒测定胰岛素样生长因子-1（IGF-1）浓度。在rhGH治疗3、6和12个月之前及之后测量基本凝血试验，即aPTT和纤维蛋白原浓度。对照值取自14名年龄、性别和体重指数（BMI）相匹配的“健康”受试者。
在基线时，我们观察到GHD患者与健康受试者之间在PT、aPTT和纤维蛋白原值方面无显著差异。生长激素治疗3个月内IGF-1浓度显著升高（8.2±1.5对24.2±2.9nmol/l，p<0.05），此后保持稳定。生长激素治疗6个月和12个月后，PT值显著升高，在女性受试者中更为明显。仅在男性患者中，治疗12个月后aPTT值显著升高（28.8±4.6对39.7±2.1秒；p<0.05）。在研究期间未发现纤维蛋白原浓度有显著变化。
12个月的生长激素替代治疗导致成年GHD患者PT和aPTT值显著升高，而纤维蛋白原浓度未改变。PT的变化在女性GHD患者中更为明显，而仅在男性GHD患者中观察到aPTT值升高。这些变化的临床意义需要进一步评估。
