北京协和医院住院患者凝血四项异常原因分析
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摘要
研究背景及目的：
凝血酶原时间(prothrombin time, PT)、活化部分凝血活酶时间(activated partial thromboplastin time, APTT)、凝血酶时间(thrombin time, TT)及纤维蛋白原(fibrinogen, Fbg)水平是目前最常用的凝血功能初筛试验。临床上常见的检查目的包括抗凝药物监测、出血倾向评估及常规术前凝血功能筛查。除接受抗凝治疗的患者其APTT及PT延长外,当其他有或无临床症状者出现凝血四项结果异常时,都应进一步找出患者可能存在的先天或获得性出血性疾病。我院住院患者大多要进行此项检查,但对其中异常结果所占比例及产生原因、处于临界值范围(指APTT或/和PT超过正常值上限,但仍未达具临床意义延长的程度)的结果是否也存在着出血风险目前并未做过系统研究及统计。进行这方面的研究将有助于了解我院不同科室、不同住院原因的患者APTT、PT、TT延长及Fbg减少的检出率。
本研究以导致APTT或/和PT延长的原因为主要研究对象,进一步探求异常结果背后潜在出血性疾病,以期为临床治疗提供一定的指导。
研究方法：
统计2013年1月15日至2013年3月14日期间北京协和医院检验科所有常规送检凝血四项试验的检查例数、科室分布情况及结果异常率(异常定义仅包括APTT、PT及TT延长,Fbg减少的情况)。收集其中APTT或/和PT延长者的血样和住院病历。对原因明确者分析其原因构成比,对原因不明者,进行正常混合血浆纠正试验及相应的因子活性、vWF：Ag、狼疮抗凝物和特异因子抑制物检测。
研究结果：
1.2个月中全院常规送检凝血四项例数为3596例,异常例数为1304例。ICU异常率最高。
2.在所有异常情况中,APTT合并PT延长所占比例最高,为35.3%。
3.2个月内APTT或/和PT延长者共701人,原因明确者319人,以抗凝治疗、慢性肝病为主,不明者382人。
4. APTT独立延长组中最常见原因为FXII缺乏,占该分组的36.1%。
5.PT独立延长组中最常见原因为维生素K依赖性因子的联合缺乏,占该分组的23.0%。
6. APTT合并PT延长组中以原因仍未明确者最多,占该组的49.0%,均不能被正常混合血浆纠正,其次为狼疮抗凝物阳性者,占34.0%。
7.狼疮抗凝物的弱阳性样本APTT中位数为38.2s(范围在32.3s-56.4s之间),中阳性样本中位数为34.5s(范围在32.4s-41.3s之间)。APTT值延长程度和狼疮抗凝物阳性强弱之间没有明显相关性。
研究结论：
1.我院凝血四项检查异常结果以APTT或／和PT延长最为常见。
2.我院东院APTT独立延长最常见的原因为FXII缺乏,因此大部分APTT延长患者均无需进行血液制品补充治疗。
3.我院东院PT独立延长最常见的原因为维生素K依赖性因子的联合缺乏,因此对于临床上存在维生素K缺乏危险因素者,建议行维生素K补充治疗。
4. APTT或／和PT延长处于临界值范围内的患者也有存在出血风险的可能,临床医生应警惕。
5. APTT值延长程度和狼疮抗凝物阳性强弱之间没有明显相关性。
6.正常混合血浆可纠正的样本也可能存在狼疮抗凝物。
7.检验前误差是导致异常结果的一个重要部分,应当尽量避免。
Background and objectives:
Prothrombin time (PT), activated partial thromboplastin time(APTT), thrombin time(TT)and fibrinogen(Fbg) level are the most common coagulation tests. Their common uses include anticoagulation monitoring, bleeding tendency assessment and routine preoperative coagulation screening. Besides receiving anticoagulant therapy, when coagulation test results appear abnormal in patients without known causes like receiving anticoagulant therapy, further investigation should be needed to identify possible congenital or acquired bleeding disorders. Most patients in our hospital have received these tests. However, the proportion of abnormal results hasn' t been systematically calculated. Besides, the underlying causes and bleeding risk of patients with borderline results haven't been thoroughly studied.
Researches focus on these matters will help us to understand the incidience of abnormal coagulation test results in our hospital.
Methods:
Information about all the routine coagulation test results in Peking Union Medical College Hospital between January15th,2013and March14th,2013was collected. The number, incidence and department distrubution of abnormal results (abnormal is defined as PT, APTT or TT prolongation or Fbg decrease in this study) were calculated. The clinical data and plasma samples were collected. For those with obvious causes, the incidence of each cause was caculated. For those with unknown etiology, an initial50:50correction with normal pooled plasma was done and a standard panel of tests including measurement of coagulant factor acitivity, von Willebrand factor antigen (vWF:Ag) levels and detection of lupus anticoagulant or other specific factor inhibitors was performed.
Results:
1.3596requests were performed within these two months, of which1304turned out to be abnormal. The Intensive Care Unit had the largest proportion in all the abnormal results.
2. Among all the abnormal conditions, APTT and PT prolongation made up the largest part.
3.701cases had APTT or/and PT prolongation, in which319had known causes, mainly anticoagulant therapy and chronic liver disease. Among the rest382cases, the causes were unknown.
4. FXII deficiency was the most common cause of isolated APTT prolongation, accounting for36.1%of this group.
5. Combined vitamin K-dependent coagulation factor deficiency was the most common cause of isolated PT prolongation, accounting for23.0%of this group.
6. Cases with unknown etiology was the most common cause of combined APTT and PT prolongation, accounting for49.0%of this group and couldn't be corrected by mixing study. The second common cause was lupus anticoagulant(34.0%).
7. The median APTT for weak lupus anticoagulant is38.2s (ranging from32.3s to56.4s),34.5s for the moderate lupus anticoagulant (ranging from32.4s to41.3s). There was no obvious correlation between the degree of APTT prolongation and the strength of lupus anticoagulant positivity.
Conclusions:
1. APTT or/and PT prolongation is the most common group of all the abnormal results in Peking Union Medical College Hospital.
2. The most common cause for isolated APTT prolongation is FXII deficiecy in our study. Thus FFP is not indicated for most patients with this abnormal result.
3. The most common cause for isolated PT prolongation is combined vitamin K-dependent coagulation factor deficiency. Thus we recommend vitamin K supplementary therapy for patients with isolated PT prolongation who are at high risk of vitamin K deficiency.
4. Clinicians should be aware of the possibility that even the APTT or PT prolongation is within the borderline range, patients may still have bleeding risk.
5. There is no obvious correlation between APTT prolongation and the strength of lupus anticoagulant positivity.
6. Lupus anticoagulant could exist in samples that can be corrected by normal pooled plasma.
7. Preanalytical error is an important cause of abnormal coagulation results and should be avoided.
凝血酶原时间(prothrombin time, PT)、活化部分凝血活酶时间(activated partial thromboplastin time, APTT)、凝血酶时间(thrombin time, TT)及纤维蛋白原(fibrinogen, Fbg)水平是目前最常用的凝血功能初筛试验。临床上常见的检查目的包括抗凝药物监测、出血倾向评估及常规术前凝血功能筛查。除接受抗凝治疗的患者其APTT及PT延长外,当其他有或无临床症状者出现凝血四项结果异常时,都应进一步找出患者可能存在的先天或获得性出血性疾病。我院住院患者大多要进行此项检查,但对其中异常结果所占比例及产生原因、处于临界值范围(指APTT或/和PT超过正常值上限,但仍未达具临床意义延长的程度)的结果是否也存在着出血风险目前并未做过系统研究及统计。进行这方面的研究将有助于了解我院不同科室、不同住院原因的患者APTT、PT、TT延长及Fbg减少的检出率。
本研究以导致APTT或/和PT延长的原因为主要研究对象,进一步探求异常结果背后潜在出血性疾病,以期为临床治疗提供一定的指导。
研究方法：
统计2013年1月15日至2013年3月14日期间北京协和医院检验科所有常规送检凝血四项试验的检查例数、科室分布情况及结果异常率(异常定义仅包括APTT、PT及TT延长,Fbg减少的情况)。收集其中APTT或/和PT延长者的血样和住院病历。对原因明确者分析其原因构成比,对原因不明者,进行正常混合血浆纠正试验及相应的因子活性、vWF：Ag、狼疮抗凝物和特异因子抑制物检测。
研究结果：
1.2个月中全院常规送检凝血四项例数为3596例,异常例数为1304例。ICU异常率最高。
2.在所有异常情况中,APTT合并PT延长所占比例最高,为35.3%。
3.2个月内APTT或/和PT延长者共701人,原因明确者319人,以抗凝治疗、慢性肝病为主,不明者382人。
4. APTT独立延长组中最常见原因为FXII缺乏,占该分组的36.1%。
5.PT独立延长组中最常见原因为维生素K依赖性因子的联合缺乏,占该分组的23.0%。
6. APTT合并PT延长组中以原因仍未明确者最多,占该组的49.0%,均不能被正常混合血浆纠正,其次为狼疮抗凝物阳性者,占34.0%。
7.狼疮抗凝物的弱阳性样本APTT中位数为38.2s(范围在32.3s-56.4s之间),中阳性样本中位数为34.5s(范围在32.4s-41.3s之间)。APTT值延长程度和狼疮抗凝物阳性强弱之间没有明显相关性。
研究结论：
1.我院凝血四项检查异常结果以APTT或／和PT延长最为常见。
2.我院东院APTT独立延长最常见的原因为FXII缺乏,因此大部分APTT延长患者均无需进行血液制品补充治疗。
3.我院东院PT独立延长最常见的原因为维生素K依赖性因子的联合缺乏,因此对于临床上存在维生素K缺乏危险因素者,建议行维生素K补充治疗。
4. APTT或／和PT延长处于临界值范围内的患者也有存在出血风险的可能,临床医生应警惕。
5. APTT值延长程度和狼疮抗凝物阳性强弱之间没有明显相关性。
6.正常混合血浆可纠正的样本也可能存在狼疮抗凝物。
7.检验前误差是导致异常结果的一个重要部分,应当尽量避免。
Background and objectives:
Prothrombin time (PT), activated partial thromboplastin time(APTT), thrombin time(TT)and fibrinogen(Fbg) level are the most common coagulation tests. Their common uses include anticoagulation monitoring, bleeding tendency assessment and routine preoperative coagulation screening. Besides receiving anticoagulant therapy, when coagulation test results appear abnormal in patients without known causes like receiving anticoagulant therapy, further investigation should be needed to identify possible congenital or acquired bleeding disorders. Most patients in our hospital have received these tests. However, the proportion of abnormal results hasn' t been systematically calculated. Besides, the underlying causes and bleeding risk of patients with borderline results haven't been thoroughly studied.
Researches focus on these matters will help us to understand the incidience of abnormal coagulation test results in our hospital.
Methods:
Information about all the routine coagulation test results in Peking Union Medical College Hospital between January15th,2013and March14th,2013was collected. The number, incidence and department distrubution of abnormal results (abnormal is defined as PT, APTT or TT prolongation or Fbg decrease in this study) were calculated. The clinical data and plasma samples were collected. For those with obvious causes, the incidence of each cause was caculated. For those with unknown etiology, an initial50:50correction with normal pooled plasma was done and a standard panel of tests including measurement of coagulant factor acitivity, von Willebrand factor antigen (vWF:Ag) levels and detection of lupus anticoagulant or other specific factor inhibitors was performed.
Results:
1.3596requests were performed within these two months, of which1304turned out to be abnormal. The Intensive Care Unit had the largest proportion in all the abnormal results.
2. Among all the abnormal conditions, APTT and PT prolongation made up the largest part.
3.701cases had APTT or/and PT prolongation, in which319had known causes, mainly anticoagulant therapy and chronic liver disease. Among the rest382cases, the causes were unknown.
4. FXII deficiency was the most common cause of isolated APTT prolongation, accounting for36.1%of this group.
5. Combined vitamin K-dependent coagulation factor deficiency was the most common cause of isolated PT prolongation, accounting for23.0%of this group.
6. Cases with unknown etiology was the most common cause of combined APTT and PT prolongation, accounting for49.0%of this group and couldn't be corrected by mixing study. The second common cause was lupus anticoagulant(34.0%).
7. The median APTT for weak lupus anticoagulant is38.2s (ranging from32.3s to56.4s),34.5s for the moderate lupus anticoagulant (ranging from32.4s to41.3s). There was no obvious correlation between the degree of APTT prolongation and the strength of lupus anticoagulant positivity.
Conclusions:
1. APTT or/and PT prolongation is the most common group of all the abnormal results in Peking Union Medical College Hospital.
2. The most common cause for isolated APTT prolongation is FXII deficiecy in our study. Thus FFP is not indicated for most patients with this abnormal result.
3. The most common cause for isolated PT prolongation is combined vitamin K-dependent coagulation factor deficiency. Thus we recommend vitamin K supplementary therapy for patients with isolated PT prolongation who are at high risk of vitamin K deficiency.
4. Clinicians should be aware of the possibility that even the APTT or PT prolongation is within the borderline range, patients may still have bleeding risk.
5. There is no obvious correlation between APTT prolongation and the strength of lupus anticoagulant positivity.
6. Lupus anticoagulant could exist in samples that can be corrected by normal pooled plasma.
7. Preanalytical error is an important cause of abnormal coagulation results and should be avoided.
引文
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