紫绀型先天性心脏病凝血机制异常的研究
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摘要
一、目的
在临床工作中发现,紫绀型先天性心脏病患儿手术后出血量及发生术后血栓栓塞性并发症的几率常常较其它非紫绀型先天性心脏病患儿为多,同时在对此类患儿进行术前常规凝血功能检查时也常常发现其APTT值和PT值明显高于正常范围,因此考虑此类患儿可能存在围手术期凝血机制异常,可能同低氧血症以及低氧血症导致的脏器功能不全密切相关。为进一步证实紫绀型先天性心脏病患儿术前凝血、抗凝及纤溶机制是否异常以及其同低氧血症间的相关性,此类患儿术后凝血机制变化情况以及改良超滤和选择氧合器类型对术后出血量的影响,我们设计本课题,选择了两组患者(紫绀组和非紫绀组)进行临床对照研究,主要内容如下:
1、选择紫绀型及非紫绀型先天性心脏病患儿组进行对照研究,探讨二组间在凝血系统、抗凝系统、纤溶系统功能以及血小板数量上的差异性;
2、对紫绀型先天性心脏病患儿凝血、抗凝、纤溶各指标以及血小板计数同氧分压进行数学相关性分析;
3、探讨法乐氏四联症患者围手术期凝血、抗凝、纤溶系统功能及血小板计数变化的一般规律;
4、对法乐氏四联症患者术后出血量以及术中改良超滤和选择氧合器类型此类患者术后出血量的影响进行分析。
二、方法
1、病例收集与整理
将2006年6月～2008年10月间我院收治并手术治疗的先天性心脏病患者中,将术前存在显性紫绀的先天性心脏病患者共69例纳入研究组,同时随机选择同期收治并成功接受外科手术的非紫绀型先天性心脏病患者24例纳入研究作对照组。
所有患者术前心功能Ⅰ～Ⅱ级(NYHA),入院前2周内未接受抗血小板药物(如阿司匹林,双嘧达莫等)、抗凝药物及激素治疗,术前肝、肾功能检查正常,不伴有其它系统性疾病,近期无外伤及手术史,所有患儿均经术前超声及心导管检查确诊并手术证实。
2、分析指标及数据采集
患者一般资料采集:包括姓名、性别、年龄、体重、住院病历号、诊断、手术方式、主动脉阻断时间、体外循环时间,对42例法乐氏四联症患儿还需统计所选择氧合器的类型、是否进行术中改良超滤、术后第一天出血量及体重平均出血量。
动脉血气及血常规数据采集:所有先天性心脏病患儿均在手术前于股动脉采血行血气分析及外周静脉采血行血常规检查,记录股动脉血氧分压、血红蛋白定量、红细胞压积和血小板计数;法乐氏四联症患者于术后第4、7、10天经桡动脉/外周静脉抽血进行血常规检查,记录血红蛋白定量、红细胞压积和血小板计数。
凝血、抗凝及纤溶系统功能指标采集:所有先天性心脏病患儿均在术前抽取外周静脉血测定凝血四项(包括PT、APTT、TT、纤维蛋白原定量),血浆Ⅱ、Ⅶ、Ⅷ、Ⅸ、Ⅹ因子活性,血浆抗凝血酶Ⅲ活性,蛋白C活性,纤溶酶原活性,纤维蛋白降解产物定量及D-二聚体定量并计算Ⅱ因子活性/抗凝血酶Ⅲ活性。法乐氏四联症患者于术后第4、7、10天经股/桡动脉抽血重复检测凝血四项(包括PT、APTT、TT、纤维蛋白原定量),血浆Ⅱ、Ⅶ、Ⅷ、Ⅸ、Ⅹ因子活性,血浆抗凝血酶Ⅲ活性,蛋白C活性并计算Ⅱ因子活性/抗凝血酶Ⅲ活性比值。
三、结果第一部分
1、紫绀型心脏病组的患者术前PT、APTT值均显著高于非紫绀对照组患者,TT值同对照组比较无显著性差异;Fbg定量则同对照组比较显著降低。
2、紫绀组心脏病患者术前的凝血因子Ⅱ、Ⅶ、Ⅷ、Ⅸ、Ⅹ活性均显著低于非紫绀对照组患者。
3、紫绀组心脏病患者术前的抗凝血酶Ⅲ活性显著高于对照组,而蛋白C活性同对照组比较则呈降低趋势,但无显著性差异,二者变化呈现一种分离的现象;紫绀组的凝血因子Ⅱ活性/抗凝血酶Ⅲ比值显著低于对照组。
4、紫绀组及对照组间术前纤溶酶原活性、FDP及D-二聚体定量均无显著差异。
5、紫绀组患者的血红蛋白含量、红细胞压积显著高于对照组,而血小板计数及动脉血氧分压则显著低于对照组。
6、紫绀组患者术前静脉血红蛋白浓度同动脉氧分压间以及血小板计数同血红蛋白浓度间存在数学相关性,而血小板计数同动脉血氧分压间则无明显数学相关性。
7、紫绀组患者术前APTT值,凝血因子Ⅱ、Ⅶ、Ⅷ、Ⅸ、Ⅹ活性以及抗凝血酶Ⅲ活性同动脉氧分压间存在数学相关性,而蛋白C活性及纤溶酶原活性同动脉氧分压间不存在数学相关性。第二部分
1、法乐氏四联症患者PT及APTT值在术后第4～10天间同术前值比较显著下降;TT值在术后第4～7内显著低于术前值,在术后第10天则较术前值略升高;
2、法乐氏四联症患者术后Ⅱ、Ⅶ、Ⅷ、Ⅸ、Ⅹ因子活性均较术前水平显著上升,其中Ⅱ、Ⅶ、Ⅹ因子活性在术后第4天达到峰值,此后逐渐下降;Ⅷ、Ⅸ因子活性在术后第7天达到峰值,此后逐渐下降;所有凝血因子活性在术后第10天仍显著高于术前值;
3、法乐氏四联症患者术后抗凝血酶Ⅲ较术前显著上升,术后第4天达到峰值后逐渐下降,至术后第10天同术前比较略下降,但无显著性差异;蛋白C活性在术后呈现类似抗凝血酶Ⅲ变化趋势,白术后第4天达到峰值后逐渐下降,但无显著性差异。血浆Ⅱ因子活性/AT-Ⅲ比值在术后早期同术前比较无显著性差异,此后逐渐上升,至术后第10日达到峰值并具有显著性差异。
4、法乐氏四联症患者血小板计数在术后早期显著下降,于术后1周后呈明显上升趋势,至术后第10天则显著高于术前值。血红蛋白含量和红细胞压积在术后显著低于术前值,术后变化趋势不明显:
5、法乐氏四联症患者术后第一天的平均引流量略少于对照组,而体重平均出血量则显著高于对照组;
6、法乐氏四联症矫治术选择不同类型氧合器与术后出血量有一定相关性。比较术后第1日出血量发现,国产膜肺组同进口膜肺组比较无显著性差异,而国产鼓泡肺组与进口膜肺组比较则显著增加;比较平均体重出血量,国产膜肺组与进口膜肺组比较无显著性差异,国产鼓泡肺同进口膜肺组比较明显增加,但无显著性差异;
7、法乐氏四联症矫治术中是否选择改良超滤与术后出血量有一定相关性。进行术中改良超滤组较未超滤组的术后第1日引流量显著增加;体重平均引流量仍有增加趋势,但不具有显著性差异。
四、结论
1、紫绀型先天性心脏病患者术前存在以内源性凝血功能障碍为主的凝血机制缺陷,表现在PT和APTT值显著升高,其中以APTT值升高更为显著,且多种凝血因子活性显著降低并与低氧血症间存在数学相关性。由于此类患者术前并不存在纤溶亢进的情况,故考虑凝血机制障碍可能同低氧血症导致的凝血因子合成不足有关,而同凝血因子的大量消耗无关。
2、紫绀型先天性心脏病患者的凝血/抗凝平衡向抗凝方向偏移,抗凝活性相对增强。抗凝血酶是相对广谱的循环内抗凝系统,其活性的增强是作为对血液高粘性以及缺氧性损伤所导致局部高凝状态的一种代偿,从而与凝血系统保持相对的平衡来维持正常的循环功能;而蛋白C系统则主要起局部抗凝及调节的作用,其活性的下降使局部凝血功能增强,在于减少因缺氧导致的血管壁结构损害的危险。
3、法乐氏四联症患者术后早期的凝血功能随着缺氧的改善而得到改善,而此期的抗凝活性同样增强,但凝血/抗凝平衡总体上向凝血方向偏移,此过程有利于术后早期的止血;而术后晚期抗凝活性减弱导致的凝血/抗凝平衡向凝血方向偏移则可能带来血栓栓塞性并发症,此时期需适当进行抗凝治疗以预防血栓栓塞性并发症的发生。
4、法乐氏四联症患者术前血小板计数显著低于对照组,是对高粘血症的一种自身代偿反应,但在术后晚期则迅速反跳至显著高于术前水平。这种变化同样是术后发生血栓栓塞性并发症的危险因素之一。
5、法乐氏四联症患者术后出血量显著高于对照组,与凝血机制缺陷有关。术中应用膜式氧合器及进行改良超滤可以达到减少凝血因子破坏,改善凝血机制以及减少术后出血的目的。
Objectives:
In clinical practice,we find a phenomenon that the patients with cyanotic congenital heart disease usually have more risks of blood loss and embolisms than that of acyanotic patients after open heart surgery with cardiopulmonary bapss,and the APTT and PT values of cyanotic patients are also usually higher than that of acyanotic patients in routine coagulation function test before operation.For these reasons,we have a hypothesis that the coagulation function of cyanotic patients may be abnormal for hypoxia and related organ dysfunction.To prove our hypothesis,we selected two groups of patients(cyanotic group and acyanotic group) for contrast study.The followings are what we will discuss.
1、Discuss the differences of coagulation function,anti-coagulation function, fibrinolysis function,and blood platelet count between cyanotic and acyanotic patients.
2、Making regression analysis for parameters of coagulation function, anti-coagulation function,fibrinolysis function,and blood platelet count with blood oxygen pressure for patients with cyanotic heart diseases.
3、Discuss the changes of coagulation function,anti-coagulation function, fibrinolysis function,and blood platelet count during perioperative periods.
4、Analyze the blood loss after open heart surgery with cardiopulmonary bypass for patients with Fallot of Tetralogy and the effects of modified ultrafiltration and oxygenator.
Methods
1、Cases collection
In our study,we adopted 69 cases of patients with cyanotic congenital heart diseases hospitalized in Nan Fang hospital from June,2006 to October,2008 for study group,and we also adopted 24 cases of patients with acyanotic congenital heart diseases as contrast group.
All patients' heart function gradeⅠ～Ⅱ(NYHA),without antiplatelet agents(aspirin,et al),anticoagulation agents and hormone therapy two weeks before hospitalization.Normal liver and kidney function,without any system diseases,no history of trauma and operation.All patients were diagnosed with echocardiography or cardioangiography and proved by operation.
2、Parameters collected and analyzed
General parameters:every patients' name,sex,age,weight,ID number,dianosis, procedure,clamp time were recorded,and oxygenator,ultrafiltration,blood loss of first day postoperation and weight averaged blood loss were recorded for patients with Fallot of tetralogy.
Blood gas parameters and blood cell counting:all patients were collected artery blood for blood gas analysis and peripheral blood for routine blood test,blood gas pressure,hemoglobulin,HCT,and platelet counting were recorded.The same parameters were recorded for patients with Fallot of tetralogy on the 4~(th),7~(th),and 10~(th) day postoperation.
Parameters of coagulation,anticoagulation,and fibrinolysis function:all patients received routine coagulation function,coagulation factor activities,antithrombin activity,protein C activity,fibrinogen activity,FDP,D-dimer test and coagulationⅡactivity/ATⅢration was calculated.The same parameters were recorded for patients with Fallot of tetralogy on the 4~(th),7~(th),and 10~(th) day postoperation except parameters of fibrinolysis system.
Results
PartsⅠ
1、APTT and PT values of patients with cyanotic congenital heart diseases are significantly higher than that of patients in contrast group;no significant differences of TT values between two groups are not showed;Fbg content of patients with cyanotic heart diseases showed significantly lower than that of patients in contrast group.
2、Coagulation factorⅡ,Ⅶ,Ⅷ,Ⅸ,Ⅹactivities are significantly lower of patients with cyanotic heart diseases than that of patients in contrast group.
3、ATⅢactivities of patients with cyanotic heart diseases are significantly higher than that of patients in contrast group,well protein C activities of patients with cyanotic heart diseases are lower than that of patients in contrast group without statistics difference,coagulationⅡactivity/ATⅢration are significantly lower of patients with cyanotic heart diseases than that of patients in contrast group.
4、Fibrinogen activity and FDP,D-dimer content analysis showed no statistics differences with two groups.
5、Hemoglobulin and HCT are significantly higher of patients with cyanotic heart diseases than that of patients in contrast group,well platelet counting and artery blood oxygen pressure are significantly lower of patients with cyanotic heart diseases than that of patients in contrast group.
6、Hemoglobulin contents are related with blood oxygen pressure and platelet counting are related with hemoglobulin for patients with cyanotic heart diseases,but platelet counting are not related with blood oxygen pressure.
7、APTT values and coagulation factorⅡ,Ⅶ,Ⅷ,Ⅸ,Ⅹactivities are related with blood oxygen pressure for patients with cyanotic heart diseases,but protein C activities and fibrinogen activities are not related with blood oxygen pressure.
PartⅡ
1、The PT and APTT values of patients with Fallot of Tetralogy are significantly lower during postoperative periods than that before operation;the TT values are significantly lower during early postoperative periods than that before operation,well higher after 10~(th) day postoperation.
2、The coagulation factorⅡ,Ⅶ,Ⅷ,Ⅸ,Ⅹactivities of patients with Fallot of Tetralogy are significantly higher during early postoperative periods than that before operation and decreased after one week postoperation,but still remained significantly higher than that before operation.
3、The ATⅢactivities of patients with Fallot of Tetralogy are significantly higher during early postoperative periods than that before operation and decreased after 10~(th) day postoperation without statistics differences.Protein C activities changed similarly to that of ATⅢ.CoagulationⅡactivity/ATⅢration increased after operation and was significantly higher than that before operation.
4、The platelet counting of patients with Fallot of Tetralogy decreased early after operation and increased one week later after operation;hemoglobulin and HCT are significantly lower after operation than that before operation.
5、The blood losses during 1~(st) day after operation of patients with Fallot of Tetralogy are less than that of contrast group,but the weight averaged blood losses are significantly more than that of contrast group.
6、The type of oxygenator for CPB are related with blood losses after operation, the blood losses during 1~(st) day and weight averaged blood losses after operation showed no significantly differences for patients using domestic membrane oxygenators and imported membrane oxygenators.For patients using bubble oxygenators,the blood losses during 1~(st) day after operation are significantly more than that of the patients using imported membrane oxygenators,but weight averaged blood losses after operation increase without significantly differences for patients of the contrast group.
7、The blood losses during 1~(st) day after operation for patients with Fallot of Tetralogy are related wih ultrafiltration.For the patients accepted ultrafiltration,the blood losses are more than that of patients without ultrafiltration,but weight blood losses increased without no significant differences.
Conclusions
1、For patients with cyanotic congenital heart diseases,there are some coagulation function anomalies mainly about the intrinsic coagulation pathway. Usually the PT and APTT values increase significantly,but the APTT values increased more significantly.For there are no evidences of hyper fibrinlysis activities and the coagulation factors activities decreased significantly related to hypoxia,we conclude that the coagulation function anomalies are related to less coagulation factor synthesis due to hypoxia well not related to consumption of coagulation factors.
2、The balance between coagulation and anticoagulation system moved to hyper anticoagulation activities for patients with cyanotic heart diseases.ATⅢis a broad-spectrum circulationary factors,whose function is to compensate the local hyper coagulation activity due to hypoxia and thicker blood.Protein C activities mainly acts as a local anticoagulation factor,whose function is to enhance the local hyper coagulation activities to ensure the complete of blood vessels.
3、For patients with Fallot of Tetralogy,the coagulation function recovered after operation due to the enhanced blood oxygen pressure.During early postoperation periods,the coagulation function play more important roles than anticoagulation function does to ensure normal hemostasis procedure.But during late postopration periods,the hyper coagulation activities may cause embolisms and the patients man accept anticoagulation therapy.
4、For patients with Fallot of Tetralogy,the platelet counting are less due to the higher HCT and hemoglobulin,and increased significantly higher late postoperation.This may also increase the risk of embolisms and may need some antiplatelet agents.
5、The blood losses for patients with Fallot of Tetralogy are more than that of the contrast group due to coagulation function anomalies,and the selection of membrane oxygenators and modified ultrafiltration can reduce the consumption of coagulation factors,enhance the coagulation function and reduce the blood losses after operation.
在临床工作中发现,紫绀型先天性心脏病患儿手术后出血量及发生术后血栓栓塞性并发症的几率常常较其它非紫绀型先天性心脏病患儿为多,同时在对此类患儿进行术前常规凝血功能检查时也常常发现其APTT值和PT值明显高于正常范围,因此考虑此类患儿可能存在围手术期凝血机制异常,可能同低氧血症以及低氧血症导致的脏器功能不全密切相关。为进一步证实紫绀型先天性心脏病患儿术前凝血、抗凝及纤溶机制是否异常以及其同低氧血症间的相关性,此类患儿术后凝血机制变化情况以及改良超滤和选择氧合器类型对术后出血量的影响,我们设计本课题,选择了两组患者(紫绀组和非紫绀组)进行临床对照研究,主要内容如下:
1、选择紫绀型及非紫绀型先天性心脏病患儿组进行对照研究,探讨二组间在凝血系统、抗凝系统、纤溶系统功能以及血小板数量上的差异性;
2、对紫绀型先天性心脏病患儿凝血、抗凝、纤溶各指标以及血小板计数同氧分压进行数学相关性分析;
3、探讨法乐氏四联症患者围手术期凝血、抗凝、纤溶系统功能及血小板计数变化的一般规律;
4、对法乐氏四联症患者术后出血量以及术中改良超滤和选择氧合器类型此类患者术后出血量的影响进行分析。
二、方法
1、病例收集与整理
将2006年6月～2008年10月间我院收治并手术治疗的先天性心脏病患者中,将术前存在显性紫绀的先天性心脏病患者共69例纳入研究组,同时随机选择同期收治并成功接受外科手术的非紫绀型先天性心脏病患者24例纳入研究作对照组。
所有患者术前心功能Ⅰ～Ⅱ级(NYHA),入院前2周内未接受抗血小板药物(如阿司匹林,双嘧达莫等)、抗凝药物及激素治疗,术前肝、肾功能检查正常,不伴有其它系统性疾病,近期无外伤及手术史,所有患儿均经术前超声及心导管检查确诊并手术证实。
2、分析指标及数据采集
患者一般资料采集:包括姓名、性别、年龄、体重、住院病历号、诊断、手术方式、主动脉阻断时间、体外循环时间,对42例法乐氏四联症患儿还需统计所选择氧合器的类型、是否进行术中改良超滤、术后第一天出血量及体重平均出血量。
动脉血气及血常规数据采集:所有先天性心脏病患儿均在手术前于股动脉采血行血气分析及外周静脉采血行血常规检查,记录股动脉血氧分压、血红蛋白定量、红细胞压积和血小板计数;法乐氏四联症患者于术后第4、7、10天经桡动脉/外周静脉抽血进行血常规检查,记录血红蛋白定量、红细胞压积和血小板计数。
凝血、抗凝及纤溶系统功能指标采集:所有先天性心脏病患儿均在术前抽取外周静脉血测定凝血四项(包括PT、APTT、TT、纤维蛋白原定量),血浆Ⅱ、Ⅶ、Ⅷ、Ⅸ、Ⅹ因子活性,血浆抗凝血酶Ⅲ活性,蛋白C活性,纤溶酶原活性,纤维蛋白降解产物定量及D-二聚体定量并计算Ⅱ因子活性/抗凝血酶Ⅲ活性。法乐氏四联症患者于术后第4、7、10天经股/桡动脉抽血重复检测凝血四项(包括PT、APTT、TT、纤维蛋白原定量),血浆Ⅱ、Ⅶ、Ⅷ、Ⅸ、Ⅹ因子活性,血浆抗凝血酶Ⅲ活性,蛋白C活性并计算Ⅱ因子活性/抗凝血酶Ⅲ活性比值。
三、结果第一部分
1、紫绀型心脏病组的患者术前PT、APTT值均显著高于非紫绀对照组患者,TT值同对照组比较无显著性差异;Fbg定量则同对照组比较显著降低。
2、紫绀组心脏病患者术前的凝血因子Ⅱ、Ⅶ、Ⅷ、Ⅸ、Ⅹ活性均显著低于非紫绀对照组患者。
3、紫绀组心脏病患者术前的抗凝血酶Ⅲ活性显著高于对照组,而蛋白C活性同对照组比较则呈降低趋势,但无显著性差异,二者变化呈现一种分离的现象;紫绀组的凝血因子Ⅱ活性/抗凝血酶Ⅲ比值显著低于对照组。
4、紫绀组及对照组间术前纤溶酶原活性、FDP及D-二聚体定量均无显著差异。
5、紫绀组患者的血红蛋白含量、红细胞压积显著高于对照组,而血小板计数及动脉血氧分压则显著低于对照组。
6、紫绀组患者术前静脉血红蛋白浓度同动脉氧分压间以及血小板计数同血红蛋白浓度间存在数学相关性,而血小板计数同动脉血氧分压间则无明显数学相关性。
7、紫绀组患者术前APTT值,凝血因子Ⅱ、Ⅶ、Ⅷ、Ⅸ、Ⅹ活性以及抗凝血酶Ⅲ活性同动脉氧分压间存在数学相关性,而蛋白C活性及纤溶酶原活性同动脉氧分压间不存在数学相关性。第二部分
1、法乐氏四联症患者PT及APTT值在术后第4～10天间同术前值比较显著下降;TT值在术后第4～7内显著低于术前值,在术后第10天则较术前值略升高;
2、法乐氏四联症患者术后Ⅱ、Ⅶ、Ⅷ、Ⅸ、Ⅹ因子活性均较术前水平显著上升,其中Ⅱ、Ⅶ、Ⅹ因子活性在术后第4天达到峰值,此后逐渐下降;Ⅷ、Ⅸ因子活性在术后第7天达到峰值,此后逐渐下降;所有凝血因子活性在术后第10天仍显著高于术前值;
3、法乐氏四联症患者术后抗凝血酶Ⅲ较术前显著上升,术后第4天达到峰值后逐渐下降,至术后第10天同术前比较略下降,但无显著性差异;蛋白C活性在术后呈现类似抗凝血酶Ⅲ变化趋势,白术后第4天达到峰值后逐渐下降,但无显著性差异。血浆Ⅱ因子活性/AT-Ⅲ比值在术后早期同术前比较无显著性差异,此后逐渐上升,至术后第10日达到峰值并具有显著性差异。
4、法乐氏四联症患者血小板计数在术后早期显著下降,于术后1周后呈明显上升趋势,至术后第10天则显著高于术前值。血红蛋白含量和红细胞压积在术后显著低于术前值,术后变化趋势不明显:
5、法乐氏四联症患者术后第一天的平均引流量略少于对照组,而体重平均出血量则显著高于对照组;
6、法乐氏四联症矫治术选择不同类型氧合器与术后出血量有一定相关性。比较术后第1日出血量发现,国产膜肺组同进口膜肺组比较无显著性差异,而国产鼓泡肺组与进口膜肺组比较则显著增加;比较平均体重出血量,国产膜肺组与进口膜肺组比较无显著性差异,国产鼓泡肺同进口膜肺组比较明显增加,但无显著性差异;
7、法乐氏四联症矫治术中是否选择改良超滤与术后出血量有一定相关性。进行术中改良超滤组较未超滤组的术后第1日引流量显著增加;体重平均引流量仍有增加趋势,但不具有显著性差异。
四、结论
1、紫绀型先天性心脏病患者术前存在以内源性凝血功能障碍为主的凝血机制缺陷,表现在PT和APTT值显著升高,其中以APTT值升高更为显著,且多种凝血因子活性显著降低并与低氧血症间存在数学相关性。由于此类患者术前并不存在纤溶亢进的情况,故考虑凝血机制障碍可能同低氧血症导致的凝血因子合成不足有关,而同凝血因子的大量消耗无关。
2、紫绀型先天性心脏病患者的凝血/抗凝平衡向抗凝方向偏移,抗凝活性相对增强。抗凝血酶是相对广谱的循环内抗凝系统,其活性的增强是作为对血液高粘性以及缺氧性损伤所导致局部高凝状态的一种代偿,从而与凝血系统保持相对的平衡来维持正常的循环功能;而蛋白C系统则主要起局部抗凝及调节的作用,其活性的下降使局部凝血功能增强,在于减少因缺氧导致的血管壁结构损害的危险。
3、法乐氏四联症患者术后早期的凝血功能随着缺氧的改善而得到改善,而此期的抗凝活性同样增强,但凝血/抗凝平衡总体上向凝血方向偏移,此过程有利于术后早期的止血;而术后晚期抗凝活性减弱导致的凝血/抗凝平衡向凝血方向偏移则可能带来血栓栓塞性并发症,此时期需适当进行抗凝治疗以预防血栓栓塞性并发症的发生。
4、法乐氏四联症患者术前血小板计数显著低于对照组,是对高粘血症的一种自身代偿反应,但在术后晚期则迅速反跳至显著高于术前水平。这种变化同样是术后发生血栓栓塞性并发症的危险因素之一。
5、法乐氏四联症患者术后出血量显著高于对照组,与凝血机制缺陷有关。术中应用膜式氧合器及进行改良超滤可以达到减少凝血因子破坏,改善凝血机制以及减少术后出血的目的。
Objectives:
In clinical practice,we find a phenomenon that the patients with cyanotic congenital heart disease usually have more risks of blood loss and embolisms than that of acyanotic patients after open heart surgery with cardiopulmonary bapss,and the APTT and PT values of cyanotic patients are also usually higher than that of acyanotic patients in routine coagulation function test before operation.For these reasons,we have a hypothesis that the coagulation function of cyanotic patients may be abnormal for hypoxia and related organ dysfunction.To prove our hypothesis,we selected two groups of patients(cyanotic group and acyanotic group) for contrast study.The followings are what we will discuss.
1、Discuss the differences of coagulation function,anti-coagulation function, fibrinolysis function,and blood platelet count between cyanotic and acyanotic patients.
2、Making regression analysis for parameters of coagulation function, anti-coagulation function,fibrinolysis function,and blood platelet count with blood oxygen pressure for patients with cyanotic heart diseases.
3、Discuss the changes of coagulation function,anti-coagulation function, fibrinolysis function,and blood platelet count during perioperative periods.
4、Analyze the blood loss after open heart surgery with cardiopulmonary bypass for patients with Fallot of Tetralogy and the effects of modified ultrafiltration and oxygenator.
Methods
1、Cases collection
In our study,we adopted 69 cases of patients with cyanotic congenital heart diseases hospitalized in Nan Fang hospital from June,2006 to October,2008 for study group,and we also adopted 24 cases of patients with acyanotic congenital heart diseases as contrast group.
All patients' heart function gradeⅠ～Ⅱ(NYHA),without antiplatelet agents(aspirin,et al),anticoagulation agents and hormone therapy two weeks before hospitalization.Normal liver and kidney function,without any system diseases,no history of trauma and operation.All patients were diagnosed with echocardiography or cardioangiography and proved by operation.
2、Parameters collected and analyzed
General parameters:every patients' name,sex,age,weight,ID number,dianosis, procedure,clamp time were recorded,and oxygenator,ultrafiltration,blood loss of first day postoperation and weight averaged blood loss were recorded for patients with Fallot of tetralogy.
Blood gas parameters and blood cell counting:all patients were collected artery blood for blood gas analysis and peripheral blood for routine blood test,blood gas pressure,hemoglobulin,HCT,and platelet counting were recorded.The same parameters were recorded for patients with Fallot of tetralogy on the 4~(th),7~(th),and 10~(th) day postoperation.
Parameters of coagulation,anticoagulation,and fibrinolysis function:all patients received routine coagulation function,coagulation factor activities,antithrombin activity,protein C activity,fibrinogen activity,FDP,D-dimer test and coagulationⅡactivity/ATⅢration was calculated.The same parameters were recorded for patients with Fallot of tetralogy on the 4~(th),7~(th),and 10~(th) day postoperation except parameters of fibrinolysis system.
Results
PartsⅠ
1、APTT and PT values of patients with cyanotic congenital heart diseases are significantly higher than that of patients in contrast group;no significant differences of TT values between two groups are not showed;Fbg content of patients with cyanotic heart diseases showed significantly lower than that of patients in contrast group.
2、Coagulation factorⅡ,Ⅶ,Ⅷ,Ⅸ,Ⅹactivities are significantly lower of patients with cyanotic heart diseases than that of patients in contrast group.
3、ATⅢactivities of patients with cyanotic heart diseases are significantly higher than that of patients in contrast group,well protein C activities of patients with cyanotic heart diseases are lower than that of patients in contrast group without statistics difference,coagulationⅡactivity/ATⅢration are significantly lower of patients with cyanotic heart diseases than that of patients in contrast group.
4、Fibrinogen activity and FDP,D-dimer content analysis showed no statistics differences with two groups.
5、Hemoglobulin and HCT are significantly higher of patients with cyanotic heart diseases than that of patients in contrast group,well platelet counting and artery blood oxygen pressure are significantly lower of patients with cyanotic heart diseases than that of patients in contrast group.
6、Hemoglobulin contents are related with blood oxygen pressure and platelet counting are related with hemoglobulin for patients with cyanotic heart diseases,but platelet counting are not related with blood oxygen pressure.
7、APTT values and coagulation factorⅡ,Ⅶ,Ⅷ,Ⅸ,Ⅹactivities are related with blood oxygen pressure for patients with cyanotic heart diseases,but protein C activities and fibrinogen activities are not related with blood oxygen pressure.
PartⅡ
1、The PT and APTT values of patients with Fallot of Tetralogy are significantly lower during postoperative periods than that before operation;the TT values are significantly lower during early postoperative periods than that before operation,well higher after 10~(th) day postoperation.
2、The coagulation factorⅡ,Ⅶ,Ⅷ,Ⅸ,Ⅹactivities of patients with Fallot of Tetralogy are significantly higher during early postoperative periods than that before operation and decreased after one week postoperation,but still remained significantly higher than that before operation.
3、The ATⅢactivities of patients with Fallot of Tetralogy are significantly higher during early postoperative periods than that before operation and decreased after 10~(th) day postoperation without statistics differences.Protein C activities changed similarly to that of ATⅢ.CoagulationⅡactivity/ATⅢration increased after operation and was significantly higher than that before operation.
4、The platelet counting of patients with Fallot of Tetralogy decreased early after operation and increased one week later after operation;hemoglobulin and HCT are significantly lower after operation than that before operation.
5、The blood losses during 1~(st) day after operation of patients with Fallot of Tetralogy are less than that of contrast group,but the weight averaged blood losses are significantly more than that of contrast group.
6、The type of oxygenator for CPB are related with blood losses after operation, the blood losses during 1~(st) day and weight averaged blood losses after operation showed no significantly differences for patients using domestic membrane oxygenators and imported membrane oxygenators.For patients using bubble oxygenators,the blood losses during 1~(st) day after operation are significantly more than that of the patients using imported membrane oxygenators,but weight averaged blood losses after operation increase without significantly differences for patients of the contrast group.
7、The blood losses during 1~(st) day after operation for patients with Fallot of Tetralogy are related wih ultrafiltration.For the patients accepted ultrafiltration,the blood losses are more than that of patients without ultrafiltration,but weight blood losses increased without no significant differences.
Conclusions
1、For patients with cyanotic congenital heart diseases,there are some coagulation function anomalies mainly about the intrinsic coagulation pathway. Usually the PT and APTT values increase significantly,but the APTT values increased more significantly.For there are no evidences of hyper fibrinlysis activities and the coagulation factors activities decreased significantly related to hypoxia,we conclude that the coagulation function anomalies are related to less coagulation factor synthesis due to hypoxia well not related to consumption of coagulation factors.
2、The balance between coagulation and anticoagulation system moved to hyper anticoagulation activities for patients with cyanotic heart diseases.ATⅢis a broad-spectrum circulationary factors,whose function is to compensate the local hyper coagulation activity due to hypoxia and thicker blood.Protein C activities mainly acts as a local anticoagulation factor,whose function is to enhance the local hyper coagulation activities to ensure the complete of blood vessels.
3、For patients with Fallot of Tetralogy,the coagulation function recovered after operation due to the enhanced blood oxygen pressure.During early postoperation periods,the coagulation function play more important roles than anticoagulation function does to ensure normal hemostasis procedure.But during late postopration periods,the hyper coagulation activities may cause embolisms and the patients man accept anticoagulation therapy.
4、For patients with Fallot of Tetralogy,the platelet counting are less due to the higher HCT and hemoglobulin,and increased significantly higher late postoperation.This may also increase the risk of embolisms and may need some antiplatelet agents.
5、The blood losses for patients with Fallot of Tetralogy are more than that of the contrast group due to coagulation function anomalies,and the selection of membrane oxygenators and modified ultrafiltration can reduce the consumption of coagulation factors,enhance the coagulation function and reduce the blood losses after operation.
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