卢涛,曾毅,孙忠敏
(荆州市中心血站,湖北 荆州434000)
自上世纪60年代始,多项研究[1-3]表明ABO血型对凝血机能有重大影响,因为ABO血型是血浆血管性血友病因子(vWF)水平的主要决定因素。总体而言,约70%的vWF/FⅧ血浆水平的变化是由遗传决定的,其中约30%与个体ABO血型有关。值得注意的是,约25%的非O血型个体vWF水平偏高,许多学者进而研究这种生物学相互关系可能的临床意义,诸如ABO血型是否可能是出血或动脉/静脉血栓形成风险的影响因素等等。
一些研究者分析表明,ABO血型不同,发生静脉血栓栓塞(VTE)的风险有差别[4-5]。Wautrecht及同事回顾性分析过去14年间门诊诊断为下肢深静脉血栓栓塞患者的血型表型分布,已知血型的369例患者与49373位比利时无症状献血者比较,非O血型下肢深静脉血栓患者频次显著高于健康献血者(70.6%vs 53.9%,P<0.01)[6]。
为进一步厘清ABO血型、vWF和FⅧ因子与VTE疾病的相互关系,许多学者进行了深入研究[7-12]。Koster及同事进行了基于人群的VTE病例对照研究,301例确诊VTE患者和301例健康人配对比较。数据表明,O型血个体VTE患病率比对照组低(25%比43%),O型组凝血因子FⅧ和vWF浓度比非O型组个体低。总体而言,在不考虑FⅧ和vWF水平的情况下分组配对,非O型与O型血组个体发生VTE的比值(OR)为2.0(95%CI,1.4~2.9)。修正FⅧ和vWF水平对结果的影响后,非 O血型组患 VTE的风险仍然显著高于 O型血组(OR 1.5,95%CI,1.0~-2.2)[13]。
Tirado等进行了类似研究[14],VTE和对照组各250例,调查FⅧ、vWF和ABO血型与血栓形成风险的关系。结果发现,对照组O型的频次比VTE患者组高(44%比23%),其中,A型血患者组比对照组高(59%vs 41%)。因此,总体上看,非O型组个体血栓形成的风险高于O型血组(OR 2.6,95%CI,1.8~3.8),修正FⅧ和 VWF水平等影响因素后 OR 1.7(95%CI,1.1~2.6)。非 O型组个体凝血因子FⅧ和vWF水平明显较高,发生VTE的相对危险归因于vWF水平强烈依赖于血型,因为消除血型因素后与VTE的关联效应就消失。
2007年,Ohira及合作者进行了独立的病例对照研究[15],纵向调查血栓症病因研究。观察对象中,492人最终发展成VTE,另外1008人观察对象正常。血型基因型分析发现,非O血型基因携带者发生VTE的风险显着高于O型(年龄调整后 OR 1.64,95%CI,1.32~2.05),进一步调整修正性别、种族、体质指数、糖尿病凝血因子FⅧ水平等影响因素后,后仍具有统计学意义(OR 1.31,95%CI,1.02~-1.68)。非O 血型 FV Leiden携带者罹患 VTE 的风险也增高(OR 6.77,95%CI,3.65~12.6)。
近期,有研究组对ABO血型和血管疾病之间的关联进行了系统回顾和Mete分析[16]。其中VTE分析研究中,非O型与O型对照组VTE的合并比为1.79(95%CI,1.56~2.05),带有凝血因子FV Leiden缺陷的个体,该比值更高,合并OR达到3.88(95%CI为2.51~6.00)。三个血型基因分型研究结果表明,A1A1/A1B/BB表型的合并比值为2.44(95%CI为1.79~3.33),而A1O/BO/A2B表型的比值为2.11(95%CI为1.66~-2.68),提示VTE患病风险与O(H)抗原表达有关。
Spiezia等发表的研究报告[17]与上述观点一致。他们回顾性研究进行了大量的意大利深静脉血栓病例患者和对照(712例患者,712名对照)发现,与O型个体比较非O血型患肾部静脉栓塞(DVT)的风险增加2.2倍,当凝血因子FV Leiden、凝血酶原G20210A突变、抗凝血酶、蛋白C和蛋白S缺陷等遗传性血栓形成因素存在时,非O血型较非血栓形成O型个体患VTE的风险会大幅提升达7倍。该数据令人侧目,表明非O血型人群的患病率高,提示血型是似乎是最重要的静脉血栓形成遗传风险因素之一。与其他遗传性血栓形成因素(凝血因子FV Leiden和凝血酶原G20210A突变)类似,非O血型是导致VTE发生的有限风险因素,因此作者建议对有血栓形成倾向的个体进行ABO血型分析以评估其血栓形成的风险状况。其它许多学者对血管栓塞与血型的关系研究结果也支持上述观点[18-21]。但是否为静脉血栓栓塞患者开展血栓形成倾向检测,学界存在争议。Spiezia等建议,如果决定开展该类检查,ABO血型应被列入遗传性血栓形成的标准筛查项目[17]。
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