\u9ad8\u4e3d\u971e(\u7efc\u8ff0)\uff0c\u5434\u514b\u96c4\uff0c\u5f20\u76ca\u679d(\u5ba1\u6821)<\/p>\n
(1.\u514b\u62c9\u739b\u4f9d\u5e02\u4e2d\u5fc3\u533b\u9662\u8840\u6db2\u80bf\u7624\u79d1\uff0c\u65b0\u7586 \u514b\u62c9\u739b\u4f9d 834000\uff1b 2.\u4e2d\u56fd\u533b\u5b66\u79d1\u5b66\u9662\u5929\u6d25\u8840\u6db2\u75c5\u533b\u9662\u767d\u8840\u75c5\u4e2d\u5fc3\uff0c\u5929\u6d25 300020)<\/p>\n
\u86cb\u767dC\u548c\u86cb\u767dS\u53ca\u6d3b\u5316\u86cb\u767dC\u62b5\u6297\u5728\u6613\u6813\u75c7\u4e2d\u8054\u5408\u7f3a\u9677\u7684\u7814\u7a76\u8fdb\u5c55<\/p>\n
\u9ad8\u4e3d\u971e1\u203b(\u7efc\u8ff0)\uff0c\u5434\u514b\u96c41\uff0c\u5f20\u76ca\u679d2(\u5ba1\u6821)<\/p>\n
(1.\u514b\u62c9\u739b\u4f9d\u5e02\u4e2d\u5fc3\u533b\u9662\u8840\u6db2\u80bf\u7624\u79d1\uff0c\u65b0\u7586 \u514b\u62c9\u739b\u4f9d 834000\uff1b 2.\u4e2d\u56fd\u533b\u5b66\u79d1\u5b66\u9662\u5929\u6d25\u8840\u6db2\u75c5\u533b\u9662\u767d\u8840\u75c5\u4e2d\u5fc3\uff0c\u5929\u6d25 300020)<\/p>\n
\u6458\u8981\uff1a\u6613\u6813\u75c7\u662f\u4e34\u5e8a\u5e38\u89c1\u7684\u591a\u75c5\u56e0\u75be\u75c5\uff0c\u81f4\u6b7b\u81f4\u6b8b\u7387\u9ad8\u3002\u4ece\u9057\u4f20\u6027\u51dd\u8840\u3001\u6297\u51dd\u7ea4\u6eb6\u5f02\u5e38\u7684\u89d2\u5ea6\u53bb\u63a2\u8ba8\u5176\u75c5\u56e0\u548c\u53d1\u75c5\u673a\u5236\uff0c\u5bf9\u4e8e\u8be5\u75c5\u7684\u9884\u9632\u5341\u5206\u91cd\u8981\u3002\u9057\u4f20\u6027\u6613\u6813\u75c7\u5305\u62ec\u6d3b\u5316\u86cb\u767dC\u62b5\u6297(APCR)\u3001\u6297\u51dd\u8840\u9176\u7f3a\u9677\u75c7\u3001\u86cb\u767dC\u3001\u86cb\u767dS\u7f3a\u9677\u75c7\u3001\u51dd\u8840\u56e0\u5b50\u2164 Leiden\u548c\u51dd\u8840\u9176\u539fG20210A\u7a81\u53d8\u7b49\u3002\u90e8\u5206\u9057\u4f20\u6027\u6613\u6813\u75c7\u60a3\u8005\u53ef\u80fd\u5b58\u5728\u86cb\u767dS\u7f3a\u9677\u548cAPCR\u4e24\u79cd\u7f3a\u9677\u75c7\u5e76\u5b58\u7684\u53ef\u80fd\u5373\u8054\u5408\u7f3a\u9677\u3002\u8be5\u6587\u5bf9\u86cb\u767dC\u3001\u86cb\u767dS\u3001APCR\u5728\u6613\u6813\u75c7\u4e2d\u7684\u8054\u5408\u7f3a\u9677\u6297\u51dd\u4f53\u7cfb\u4e88\u4ee5\u7efc\u8ff0\u3002<\/p>\n
\u5173\u952e\u8bcd\uff1a\u86cb\u767dC\uff1b\u86cb\u767dS\uff1b\u6d3b\u5316\u86cb\u767dC\u62b5\u6297\uff1b\u8054\u5408\u7f3a\u9677<\/p>\n
\u6613\u6813\u75c7\u4e8e1965\u5e74\u7531Egeberg[1]\u63d0\u51fa\uff0c\u662f\u6307\u56e0\u5206\u5b50\u9057\u4f20\u7f3a\u9677\u800c\u51fa\u73b0\u7684\u51dd\u8840\u3001\u7ea4\u6eb6\u6d3b\u6027\u5931\u8861\uff0c\u6781\u6613\u53d1\u751f\u8840\u6813\u5f62\u6210\u7684\u4e00\u7c7b\u75be\u75c5\uff0c\u4e34\u5e8a\u4e3b\u8981\u8868\u73b0\u4e3a\u9759\u8109\u8840\u6813\u7684\u5f62\u6210\u3002\u6613\u6813\u75c7\u4e3b\u8981\u6709\u9057\u4f20\u6027\u53ca\u83b7\u5f97\u60272\u79cd[2]\u3002\u5176\u4e2d\uff0c\u9057\u4f20\u6027\u6613\u6813\u75c7\u6709\u6297\u51dd\u8840\u9176\u7f3a\u9677\u75c7\u3001\u86cb\u767dC\u7f3a\u9677\u75c7\u3001\u86cb\u767dS\u7f3a\u9677\u75c7\u3001\u6d3b\u5316\u86cb\u767dC\u62b5\u6297(activated protein C resistance\uff0cAPCR)\u3001\u51dd\u8840\u56e0\u5b50\u2164 Leiden\u548c\u51dd\u8840\u9176\u539fG20210A\u7a81\u53d8\u53ca\u5bb6\u5ead\u6210\u5458\u4e2d\u6709\u57fa\u56e0\u7f3a\u9677\u8005[3]\u3002\u7814\u7a76\u8bc1\u5b9e\uff0c\u90e8\u5206\u9057\u4f20\u6027\u6613\u6813\u75c7\u60a3\u8005\u53ef\u80fd\u5b58\u5728\u4e24\u79cd\u7f3a\u9677\u75c7\u5e76\u5b58\u7684\u53ef\u80fd\uff0c\u5373\u8054\u5408\u7f3a\u9677[4]\u3002\u6709\u5b66\u8005\u53d1\u73b0\uff0cAPCR\u4e0e\u86cb\u767dC\/\u86cb\u767dS\u7f3a\u9677\u5e76\u5b58\u8005\u660e\u663e\u9ad8\u4e8e\u5355\u4e00\u86cb\u767dC\u7f3a\u9677\u6216APCR\u8005(\u8840\u6813\u4e8b\u4ef6\u7684\u53d1\u751f\u7387\u5206\u522b\u4e3a73%\u300131%\u548c13%)[5]\u3002\u5bf9\u4e8e\u5df2\u77e5\u5b58\u5728\u9057\u4f20\u6027\u6613\u6813\u75c7\u7684\u9759\u8109\u8840\u6813\u60a3\u8005\u7684\u4e00\u7ea7\u4eb2\u5c5e\u5728\u53d1\u751f\u83b7\u5f97\u6027\u6613\u6813\u75be\u75c5\u6216\u5b58\u5728\u83b7\u5f97\u6027\u6613\u6813\u56e0\u7d20\u65f6\uff0c\u5efa\u8bae\u8fdb\u884c\u76f8\u5e94\u9057\u4f20\u6027\u7f3a\u9677\u7684\u68c0\u6d4b\u3002\u73b0\u5c31\u86cb\u767dC\u3001\u86cb\u767dS\u3001APCR\u5728\u6613\u6813\u75c7\u4e2d\u7684\u8054\u5408\u7f3a\u9677\u6297\u51dd\u4f53\u7cfb\u4e88\u4ee5\u7efc\u8ff0\u3002<\/p>\n
1\u86cb\u767dC\u548c\u86cb\u767dS\u7cfb\u7edf<\/p>\n
\u86cb\u767dC\u3001\u86cb\u767dS\u7cfb\u7edf\u5305\u62ec\u86cb\u767dC\u3001\u86cb\u767dS\u3001\u6d3b\u5316\u86cb\u767dC(activated protein C,APC)\u6291\u5236\u7269\u548c\u8840\u6813\u8c03\u8282\u7d20\u3002\u5728\u76f8\u5e94\u7684\u6761\u4ef6\u4e0b,\u86cb\u767dC\u6fc0\u6d3b\u5f62\u6210APC\uff0c\u5176\u4f5c\u7528\u4e8e\u51dd\u8840\u3001\u7ea4\u6eb6\u7b49\u7cfb\u7edf\u53d1\u6325\u6297\u51dd\u4f5c\u7528[6]\u3002\u86cb\u767dC\u548c\u86cb\u767dS\u662fAPC\u5f62\u6210\u7684\u91cd\u8981\u6d3b\u6027\u6210\u5206\uff0c\u5176\u9057\u4f20\u7f3a\u9677\u6216\u529f\u80fd\u5f02\u5e38\u5747\u53ef\u4ee5\u5bfc\u81f4APC\u4e0b\u964d\u4ea7\u751fAPCR\u3002\u4e34\u5e8a\u7814\u7a76\u53d1\u73b0\uff0c\u9759\u8109\u8840\u6813\u5f62\u6210\u7684\u4e3b\u8981\u539f\u56e040%\uff5e60%\u7531\u51dd\u8840\u56e0\u5b50\u2164\u7f3a\u9677\u6240\u81f4\u7684APCR\u73b0\u8c61\u5f15\u8d77\uff0c5%\uff5e10%\u662f\u56e0\u86cb\u767dC\u3001\u86cb\u767dS\u7b49\u9057\u4f20\u7f3a\u9677\u5bfc\u81f4[7]\u3002\u86cb\u767dC\u662f\u4e00\u79cd\u7ef4\u751f\u7d20K\u4f9d\u8d56\u6027\u86cb\u767d\u8d28\uff0c\u4ee5\u9176\u539f\u5f62\u5f0f\u5b58\u5728\uff0c85%\uff5e95%\u7684\u86cb\u767dC\u4ee5\u53cc\u94fe\u5f62\u5f0f\u5b58\u5728\u4e8e\u8840\u6db2\u4e2d\uff0c\u5728\u56e0\u5b50\u2161a-\u8840\u6813\u8c03\u8282\u7d20\u590d\u5408\u7269\u7684\u4f5c\u7528\u4e0b\uff0c\u86cb\u767dC\u88ab\u6fc0\u6d3b\u4e3aAPC[8]\u3002\u86cb\u767dS\u5728\u4eba\u7684\u8840\u6d46\u4e2d40%\u5448\u6e38\u79bb\u6001\uff0c60%\u4e3a\u7ed3\u5408\u6001\u7684\u590d\u5408\u7269\uff0c\u7ed3\u5408\u6001\u7684\u86cb\u767dS\u8f85\u52a9\u6d3b\u6027\u5f88\u4f4e[9]\u3002\u86cb\u767dC\u3001\u86cb\u767dS\u5728\u8840\u6d46\u4e2d\u4f5c\u4e3aAPC\u7684\u8f85\u52a9\u56e0\u5b50\uff0c\u53c2\u4e0e\u5bf9\u51dd\u8840\u56e0\u5b50\u2164\u548c\u2167a\u7684\u964d\u89e3[10]\u3002\u86cb\u767dC\u3001\u86cb\u767dS\u5206\u5b50\u7f3a\u9677\u5747\u80fd\u964d\u4f4e\u4f53\u5185\u51dd\u8840\u6297\u51dd\u5e73\u8861\uff0c\u51dd\u8840\u4ea2\u8fdb\u5bb9\u6613\u5f62\u6210\u8840\u6813\u3002\u9057\u4f20\u6027\u86cb\u767dS\u7f3a\u9677\u60a3\u8005\u7684\u5206\u5b50\u7f3a\u9677\u9633\u6027\u68c0\u51fa\u7387\u663e\u8457\u9ad8\u4e8e\u6b63\u5e38\u4eba(7%\u548c0.15%)[11]\uff0c\u6545\u5bb9\u6613\u5bfc\u81f4\u9057\u4f20\u6027\u6613\u6813\u75c7\u3002<\/p>\n
2\u6d3b\u5316\u86cb\u767dC\u7684\u751f\u7269\u5b66\u529f\u80fd<\/p>\n
\u8840\u6d46\u4e2d\u7684\u86cb\u767dC\u7ecf\u4f53\u5185\u5916\u5404\u79cd\u56e0\u7d20\u6fc0\u6d3b\u540e\u5f62\u6210APC[12]\u3002\u86cb\u767dS\u662f\u8840\u7ba1\u5185\u76ae\u7ec6\u80de\u6216\u8840\u5c0f\u677f\u819c\u4e0a\u7684\u4e00\u79cd\u542by-\u7fa7\u57fa\u8c37\u6c28\u9178\u7684\u86cb\u767d\u8d28\uff0c\u5316\u5b66\u672c\u8d28\u662f\u5355\u94fe\u7cd6\u86cb\u767d\uff0c\u4f5c\u4e3a\u8f85\u52a9\u56e0\u5b50\u534f\u52a9APC\u6e05\u9664\u2169a\u7b49\uff0c\u4e0e\u86cb\u767dC\u5f62\u6210\u819c\u7ed3\u5408\u578b\u201cAPC-\u86cb\u767dS\u201d\u590d\u5408\u7269\uff0c\u4fc3\u8fdbAPC\u5bf9\u2164a\u548c\u2167a\u7684\u964d\u89e3[13]\u3002\u7531\u4e8e\u86cb\u767dC\u3001\u86cb\u767dS\u6c34\u5e73\u53ca\u6d3b\u6027\u964d\u4f4e\uff0c\u86cb\u767dC\u7cfb\u7edf\u706d\u6d3b\u51dd\u8840\u56e0\u5b50\u2164a\u3001\u51dd\u8840\u56e0\u5b50\u2167a\u548c\u6291\u5236\u51dd\u8840\u56e0\u5b50\u2169a\u4f5c\u7528\u51cf\u5f31\uff0c\u4f7f\u51dd\u8840\u9176\u4f5c\u7528\u589e\u5f3a\u4ece\u800c\u5bfc\u81f4\u8840\u6813\u5f62\u6210[14]\u3002APC\u6d3b\u6027\u4e2d\u5fc3\u5177\u6709\u7684\u751f\u7269\u5b66\u529f\u80fd\uff1a\u2460APC\u901a\u8fc7\u86cb\u767d\u6c34\u89e3\u4f5c\u7528\u706d\u6d3b\u56e0\u5b50\u2164\u548c\u2167\u7684\u5f62\u6210\uff0c\u5f71\u54cd\u56e0\u5b50\u2161\u7684\u5f62\u6210\uff0c\u4ece\u800c\u963b\u6b62\u51dd\u8840\u8fc7\u7a0b\u7684\u53d1\u5c55\uff0c\u53d1\u6325\u6297\u51dd\u6d3b\u6027\uff1b\u2461APC\u901a\u8fc7\u81ea\u8eab\u6d3b\u6027\u7834\u574f\u8840\u5c0f\u677f\u6d3b\u6027\uff0c\u51cf\u6162\u5185\u6e90\u6027\u8840\u51dd\u901f\u5ea6\uff1b\u2462APC\u53d1\u6325\u5176\u86cb\u767d\u6c34\u89e3\u9176\u4f5c\u7528\uff0c\u6c34\u89e3\u2167\u91cd\u94fe\uff0c\u4ece\u800c\u706d\u6d3b\u56e0\u5b50\u2167[15]\u3002<\/p>\n
3APCR<\/p>\n
APCR\u662f\u8840\u6813\u6027\u75be\u75c5\u91cd\u8981\u98ce\u9669\u56e0\u7d20\uff0c\u6700\u65e9\u7531Svensson\u548cDahlb\u00e4ck[16]\u63d0\u51fa\uff0c\u8377\u5170\u5b66\u8005Leiden\u6700\u65e9\u53d1\u73b0APCR\u662f\u56e0\u5b50\u2164a(\u51dd\u8840\u56e0\u5b50\u2164)\u57fa\u56e0\u7a81\u53d8\u5bfc\u81f4\uff0c\u5e76\u5c06\u51dd\u8840\u56e0\u5b50\u2164\u79f0\u4e3aF\u2164 Leiden\uff0c\u5c06\u6b64\u73b0\u8c61\u79f0\u4e3aAPCR\u3002F\u2164 Leiden\u5728\u6b27\u6d32\u6b63\u5e38\u4eba\u7fa4\u4e2d\u68c0\u51fa\u7387\u9ad8\uff0c\u4e3a2%[17]\u3002\u6211\u56fd\u9759\u8109\u8840\u6813\u4e2dLeiden\u7a81\u53d8\u53d1\u751f\u7387\u4f4e\uff0c\u5728\u90e8\u5206\u5c11\u6570\u6c11\u65cf\u4e2d\u53d1\u73b0Leiden\u6742\u5408\u5b50\u57fa\u56e0[18]\u3002APCR\u662f\u8fd1\u5e74\u6765\u53d1\u73b0\u7684\u53d1\u751f\u7387\u8f83\u9ad8\u7684\u4e00\u79cd\u9057\u4f20\u6027\u8840\u6813\u98ce\u9669\u56e0\u7d20,\u5b58\u5728APCR\u7684\u60a3\u8005\u53ca\u5bb6\u7cfb\u5f62\u6210\u8840\u6813\u98ce\u9669\u9ad8\uff0c\u5927\u591a\u6570APCR\u60a3\u8005\u662f\u9057\u4f20\u6027APCR\uff0c\u7531Leiden\u7a81\u53d8\u5f15\u8d77\uff0c\u53e6\u4e00\u90e8\u5206APCR\u60a3\u8005\u4e3a\u65e0F\u2164\u57fa\u56e0\u7a81\u53d8\u7684\u83b7\u5f97\u6027APCR\u3002APCR\u4e0d\u4ec5\u662f\u4e0b\u80a2\u6df1\u9759\u8109\u8840\u6813\u5f62\u6210\u7684\u9ad8\u5371\u56e0\u7d20\uff0c\u4e5f\u4e0e\u89c6\u7f51\u819c\u4e2d\u592e\u9759\u8109\u3001\u80ba\u9759\u8109\u3001\u8111\u9759\u8109\u7b49\u9759\u8109\u8840\u6813\u5f62\u6210\u5bc6\u5207\u76f8\u5173[19]\u3002\u56e0\u6b64\uff0c\u53ef\u901a\u8fc7\u68c0\u6d4bAPCR\u6765\u7b5b\u67e5\u8840\u6813\u6027\u75be\u75c5\u7684\u9ad8\u5371\u4eba\u7fa4(\u5982\u91c7\u7528\u53e3\u670d\u907f\u5b55\u836f\u3001\u6fc0\u7d20\u66ff\u4ee3\u6cbb\u7597\u3001\u5916\u79d1\u624b\u672f\u548c\u80bf\u7624\u5316\u7597\u7b49)\uff0c\u56e0\u4e3a\u4e0d\u7ba1\u662fF\u2164\u3001\u86cb\u767dS\u3001\u86cb\u767dC\u6216\u8005\u8840\u6813\u8c03\u8282\u7d20\u7684\u7a81\u53d8\u6700\u7ec8\u90fd\u4ee5APCR\u73b0\u8c61\u8868\u73b0\u51fa\u6765\u3002<\/p>\n
4FV Leiden\u7a81\u53d8<\/p>\n
F\u2164 Leiden\u7a81\u53d8(G1691A)Gln\u4ee3\u66ffArg506\uff0c\u4f7fF\u2164\u5bf9APC\u7684\u88c2\u89e3\u53d1\u751f\u62b5\u6297\uff0cF\u2164\u662f\u4f53\u5185\u51dd\u8840\u9176\u539f\u6700\u4e3b\u8981\u7684\u6fc0\u6d3b\u7269\uff0cF\u2164 Leiden\u7a81\u53d8\u4e3b\u8981\u89c1\u4e8e\u767d\u79cd\u4eba\uff0c\u4e14\u5728\u4eba\u7fa4\u4e2d\u5177\u6709\u5730\u57df\u5dee\uff0c\u662f\u897f\u65b9\u4eba\u7fa4\u4e2d\u6613\u6813\u75c7\u72ec\u7acb\u7684\u9057\u4f20\u6027\u5371\u9669\u56e0\u7d20[20]\u3002F\u2164 Leiden\u8fd9\u79cd\u9057\u4f20\u6027\u6613\u6813\u7f3a\u9677\u5728\u9ad8\u52a0\u7d22\u4eba\u7fa4\u4e2d\u68c0\u51fa\u7387\u9ad8\u8fbe5%[21]\uff0c\u5728\u9759\u8109\u8840\u6813\u60a3\u8005\u4e2d\u7684\u68c0\u51fa\u7387\u5e73\u5747\u4e3a20%\uff1b\u5728\u8377\u5170\u4eba\u7fa4\u4e2d\u4e3a2%\uff5e4%\uff1b\u5728\u58a8\u897f\u54e5\u53ca\u4eba\u7f8e\u56fd\u767d\u4eba\u4eba\u7fa4\u76f8\u8fd1\u4e3a\uff0c1.89%[22]\uff1b\u5728\u4e9a\u6d32\u4eba\u7fa4\u4e0e\u975e\u6d32\u9ed1\u4eba\u4eba\u7fa4\u4e2d\u6781\u4e3a\u7f55\u89c1\u3002F\u2164 Leiden\u5728\u4e2d\u56fd\u6c49\u65cf\u4eba\u7fa4\u4e2d\u5341\u5206\u7f55\u89c1[23]\u3002\u90ed\u8fb0\u8679\u7b49[24]\u548c\u674e\u51e4\u82b9\u7b49[25]\u7684\u7814\u7a76\u672a\u53d1\u73b0F\u2164 Leiden\u57fa\u56e0\u7a81\u53d8\uff1b\u4f46\u5728\u7ef4\u543e\u5c14\u65cf\u4eba\u7fa4\u7684\u7814\u7a76\u4e2d\u53d1\u73b0F\u2164 Lejden \u57fa\u56e0\u7a81\u53d8[23]\uff0c\u8868\u660eF\u2164 Leide\u7a81\u53d8\u7684\u5206\u5e03\u6709\u5730\u57df\u53ca\u79cd\u65cf\u5dee\u5f02\u3002\u6545\u5728\u4e0d\u540c\u5730\u57df\u4e0e\u79cd\u65cf\u4eba\u7fa4\u4e2d\u7814\u7a76\uff0c\u6709\u5229\u4e8e\u4e86\u89e3\u8840\u6813\u6027\u75be\u75c5\u5728\u4e0d\u540c\u79cd\u65cf\u4e2d\u7684\u53d1\u75c5\u673a\u5236\u3002<\/p>\n
5\u51dd\u8840\u9176\u539fG20210A<\/p>\n
1996\u5e74\uff0cPoort\u7b49[26]\u7814\u7a76\u53d1\u73b0\uff0c\u9996\u6b21\u53d1\u751f\u8840\u6813\u7684\u60a3\u8005\u4e2d\uff0c20 210\u4f4d\u6838\u82f7\u9178G\u2192A\u7684\u53d8\u5f02\u53d1\u751f\u7387(6.2%)\u660e\u663e\u9ad8\u4e8e(\u5065\u5eb7\u4eba2.3%)\uff0c\u6709G20210A\u53d8\u5f02\u60a3\u8005\u7684\u9759\u8109\u8840\u6813\u5f62\u6210\u5371\u9669\u8f83\u6b63\u5e38\u4eba\u589e\u52a02.8\u500d\u3002Simioni\u7b49[27]\u7814\u7a76\u53d1\u73b0\uff0c\u5728\u9759\u8109\u8840\u6813\u60a3\u8005\u4e2d\uff0cG20210A\u7a81\u53d8\u7684\u53d1\u751f\u7387\u66f4\u9ad8(8.0%)\u3002\u53e6\u5916\uff0c\u6709\u5b66\u8005\u5728\u5bf9\u6211\u56fd\u4eba\u7fa4\u7814\u7a76\u4e2d\u672a\u53d1\u73b0\u51dd\u8840\u9176\u539f\u57fa\u56e0G20210A\u7a81\u53d8[28-29]\u30022003\u5e74\uff0c\u91d1\u56fd\u680b\u7b49[30]\u7814\u7a76\u53d1\u73b0\u4e86\u9996\u4f8bG20210A\u7a81\u53d8\u3002F\u2164 Leiden \u7a81\u53d8\u4e0eG20201A\u7a81\u53d8\u4e3a\u6b27\u7f8e\u4eba\u4e3b\u8981\u7684\u9057\u4f20\u6027\u6613\u6813\u56e0\u7d20[31]\uff0c\u6211\u56fd\u6c49\u65cf\u4eba\u7fa4F\u2164 Leiden\u7a81\u53d8\u4e0eG20201A\u53d8\u5f02\u4e0d\u662f\u5176\u4e3b\u8981\u5371\u9669\u56e0\u7d20[32]\u3002<\/p>\n
6APCR\u3001\u86cb\u767dC\u548c\u86cb\u767dS\u7684\u8054\u5408\u7f3a\u9677<\/p>\n
APCR\u662f\u9057\u4f20\u6027\u8840\u6813\u6027\u75be\u75c5\u7684\u98ce\u9669\u56e0\u7d20\uff0c\u86cb\u767dS\u7f3a\u9677\u60a3\u8005(\u76f8\u5bf9\u4e8e\u6b63\u5e38\u4eba)\u53d1\u751f\u6df1\u9759\u8109\u8840\u6813\u7684\u5371\u9669\u589e\u52a08\u500d\uff0c\u7eaf\u5408\u5b50\u578b\u86cb\u767dC\u7f3a\u9677\u60a3\u8005\u5e38\u5728\u65b0\u751f\u513f\u671f\u5c31\u4f1a\u51fa\u73b0\u5e7f\u6cdb\u6027\u8840\u7ba1\u5185\u51dd\u8840[33]\uff0c\u8be5\u79cd\u75c7\u72b6\u662f\u81f4\u547d\u7684\uff0c\u9057\u4f20\u6027\u86cb\u767dC\u7f3a\u9677\u662f\u4e00\u79cd\u5e38\u67d3\u8272\u4f53\u9690\u5f62\u9057\u4f20\u75be\u75c5[34]\u3002\u86cb\u767dC\u548c\u86cb\u767dS\u7684\u8054\u5408\u7f3a\u9677\u662f\u8840\u6813\u5f62\u6210\u7684\u5371\u9669\u56e0\u7d20\uff0c\u53d1\u751f\u8840\u6813\u7684\u5e74\u8f7b\u60a3\u8005(40\u5c81\u524d)\u670910%\uff5e15%\u662f\u7531\u4e8e\u86cb\u767dC\u3001\u86cb\u767dS\u8054\u5408\u7f3a\u9677\u5f15\u8d77\u7684\uff0c\u5176\u5bb6\u5ead\u6210\u5458\u4e2d\u6709\u57fa\u56e0\u7f3a\u9677\u8005\u53d1\u751f\u8840\u6813\u7684\u98ce\u9669\u9ad8\u8fbe50%[35]\u3002\u7814\u7a76\u53d1\u73b0\uff0cAPCR\u4e0e\u86cb\u767dS\u7f3a\u9677\u3001APCR\u4e0e\u86cb\u767dC\u7f3a\u9677\u53ef\u80fd\u76f8\u4e92\u5b58\u5728\u5173\u8054\uff0c\u5bfc\u81f4\u8840\u6813\u6027\u75be\u75c5\u7684\u53d1\u751f\u3001\u53d1\u5c55[36]\u3002\u5404\u79cd\u539f\u56e0\u5bfc\u81f4\u51dd\u8840\u9176\u539f\u3001\u86cb\u767dC\u3001\u86cb\u767dS\u6297\u51dd\u86cb\u767d\u5206\u5b50\u6d3b\u6027\u964d\u4f4e\uff0c\u8fdb\u800c\u5f71\u54cd\u51dd\u8840\u548c\u6297\u51dd\u7684\u751f\u7406\u5e73\u8861\uff0c\u5bfc\u81f4\u51dd\u8840\u4ea2\u8fdb\u8840\u6813\u5f62\u6210\u3002\u56e0\u6b64\uff0c\u6297\u51dd\u86cb\u767d\u964d\u4f4e\u662f\u8840\u6813\u6027\u75be\u75c5\u7684\u6709\u6548\u8bca\u65ad\u6307\u6807\u30021995\u5e74\uff0c\u7f8e\u56fd\u8840\u6db2\u75c5\u5b66\u4f1a\u5bf9\u86cb\u767dS\u4e0eAPCR\u7684\u8054\u5408\u7f3a\u9677\u7684\u7814\u7a76\uff0c\u7ed3\u679c\u53d1\u73b0\uff0c\u5728\u60a3\u6709\u86cb\u767dS\u7f3a\u9677\u53ca\u4e0d\u60a3\u6709\u7684\u5bb6\u65cf\u6210\u5458\u53d1\u751f\u8840\u6813\u4e8b\u4ef6\u7684\u6bd4\u4f8b\u4e3a47%\u6bd47%\uff1b\u7b5b\u67e518\u4e2a\u5bb6\u65cf\u6240\u6709\u6210\u5458APCR\uff0c7\u4e2a\u5bb6\u65cf\u4e2d\u53d1\u73b0APCR\uff0c13\u4f8b\u60a3\u6709\u86cb\u767dS\u3001APCR\u8054\u5408\u7f3a\u9677\u7684\u5bb6\u65cf\u6210\u5458\uff0c\u5176\u8840\u6813\u60a3\u75c5\u7387\u4e3a72%\uff0c\u53ea\u60a3\u6709\u86cb\u767dS\u7f3a\u9677\u6216\u53ea\u60a3\u6709APCR\u7684\u5bb6\u65cf\u6210\u5458\u8840\u6813\u75be\u75c5\u7684\u60a3\u75c5\u7387\u5747\u4e3a19%\uff1b\u53e6\u5916\uff0c\u5bf9\u86cb\u767dC\u4e0eAPCR\u7684\u8054\u5408\u7f3a\u9677\u4e5f\u4f5c\u4e86\u7c7b\u4f3c\u7684\u7814\u7a76\uff0c\u7ed3\u679c\u76f8\u4f3c[37]\u3002\u4ece\u800c\u63a8\u65ad\u8054\u5408\u7f3a\u9677\u60a3\u8005\u66f4\u5bb9\u6613\u53d1\u751f\u8840\u6813\u6027\u75be\u75c5\u3002<\/p>\n
7\u5c0f\u7ed3<\/p>\n
\u5bf9\u6613\u6813\u75c7\u60a3\u8005\u5c3d\u65e9\u5f00\u5c55\u8054\u5408\u7f3a\u9677\u7b5b\u67e5\uff0c\u53ca\u65f6\u8bc4\u4f30\u8840\u6813\u5f62\u6210\u98ce\u9669\u6307\u6807\uff0c\u66f4\u91cd\u8981\u7684\u662f\u5bf9\u4e8e\u4e34\u5e8a\u6d89\u53ca\u5230\u8bb8\u591a\u7cfb\u7edf\u7684\u6613\u81f4\u8840\u6813\u524d\u72b6\u6001\u7684\u75be\u75c5(\u5982\u9aa8\u9ad3\u589e\u6b96\u6027\u75be\u75c5\u3001\u6076\u6027\u80bf\u7624\u3001\u598a\u5a20\u9ad8\u8840\u538b\u7efc\u5408\u5f81\u3001\u5468\u56f4\u8840\u7ba1\u6813\u585e\u75c7\u3001\u624b\u672f\u521b\u4f24\u3001\u80ba\u6813\u585e\u7b49)\u63d0\u4f9b\u4e00\u4e2a\u8f83\u53ef\u9760\u7684\u9884\u6d4b\u8840\u6813\u98ce\u9669\u5f62\u6210\u7684\u6307\u6807\uff0c\u6307\u5bfc\u4e34\u5e8a\u533b\u5e08\u5c3d\u65e9\u8fdb\u884c\u5e72\u9884\u3002\u603b\u4e4b\uff0c\u86cb\u767dC\u3001\u86cb\u767dS\u7f3a\u9677\u53caAPCR\u662f\u9057\u4f20\u6027\u6613\u6813\u75c7\u91cd\u8981\u7684\u7ec4\u6210\u90e8\u5206\u53ca\u5e38\u89c1\u98ce\u9669\u56e0\u7d20\uff0c\u8054\u5408\u7f3a\u9677\u5728\u51dd\u8840\u3001\u6297\u51dd\u7684\u673a\u5236\u4ecd\u9700\u8fdb\u4e00\u6b65\u7814\u7a76\u3002<\/p>\n
\u53c2\u8003\u6587\u732e<\/p>\n
[1]Egeberg O.Inherited antithrombin deficiency causing thrombop-hilia[J].Thromb Diath Haemorrh\uff0c1965\uff0c13:516-530.<\/p>\n
[2]\u95fa\u632f\u5b87\uff0c\u534e\u5b9d\u6765\uff0c\u9a6c\u897f\u864e\uff0c\u7b49\uff0e672\u4f8b\u9759\u8109\u8840\u6813\u6813\u585e\u75c7\u76f8\u5173\u5371\u9669\u56e0\u7d20\u5206\u6790[J]\uff0e\u4e2d\u56fd\u8840\u6db2\u5b66\u6742\u5fd7\uff0c2007\uff0c28(9)\uff1a579-581\uff0e<\/p>\n
[3]\u4e2d\u534e\u533b\u5b66\u4f1a\u8840\u6db2\u5b66\u5206\u4f1a\u6b62\u8840\u4e0e\u8840\u6813\u7ec4.\u6210\u4eba\u539f\u53d1\u514d\u75ab\u6027\u8840\u5c0f\u677f\u51cf\u5c11\u75c7\u8bca\u65ad\u4e0e\u6cbb\u7597\u4e2d\u56fd\u4e13\u5bb6\u5171\u8bc6(2012\u5e74\u7248)[J]\uff0e\u4e2d\u534e\u8840\u6db2\u5b66\u6742\u5fd7\uff0c2012\uff0c33(11)\uff1a975-977.<\/p>\n
[4]\u8d75\u6c38\u5f3a\uff0e\u6613\u6813\u75c7\u7814\u7a76\u6982\u51b5[J]\uff0e\u4e2d\u56fd\u5b9e\u7528\u5185\u79d1\u6742\u5fd7\uff0c2007\uff0c27(1)\uff1a49-52.<\/p>\n
[5]Cramer TJ,Griffin JH,Gale AJ.Factor V is an anticoagulant cofactor for activated protein C during inactivation of factor Va[J].Pathophysiol Haemost Thromb\uff0c2010\uff0c37(1):17-23.<\/p>\n
[6]Tormene D,Fortuna S,Tognin G,etal.The incidence of venous thromboembolism in carriers of antithrombin,protein C or protein S deficiency associated with the HR2 haplotype of factor V:a family cohort study[J].J Thromb Haemost\uff0c2005\uff0c3 (7):1414-1420.<\/p>\n
[7]De Kort EH,Vrancken SL,van Heijst AF,etal.Long-term subcutaneous protein C replacement in neonatal severe protein C deficiency[J].Pediatrics\uff0c2011\uff0c127(5):1338-1342.<\/p>\n
[8]\u8d56\u7ffc\uff0c\u5218\u9633\uff0c\u6797\u65b9\u662d.\u51dd\u8840\u9176\u7814\u7a76\u6982\u8bba[J].\u8840\u6813\u4e0e\u6b62\u8840\u5b66\uff0c2009\uff0c15(3)\uff1a142-144.<\/p>\n
[9]Nogami K,Shinozawa K,Ogiwara K,etal.Novel FV mutation (W1920R,FVNara) associated with serious deep vein thrombosis and more potent APC resistance relative to FVLeiden[J].Blood\uff0c2014\uff0c123(15):2420-2428.<\/p>\n
[10]Kafkas S,Kalkan U,Bolaman Z,etal.Evaluation of smoking as a risk factor for activated protein C resistance during pregnancy[J].Gynecol Obstet Invest\uff0c2007,64(2):89-94.<\/p>\n
[11]Emmerich J,Rosendaal FR,Cattaneo M,etal.Combined effect of factor V Leiden and prothrombin 20210A on the risk of venous thromboembolism–pooled analysis of 8 case-control studies including 2310 cases and 3204 controls.Study Group for Pooled-Analysis in Venous Thromboembolism[J].Thromb Haemost\uff0c2001\uff0c86 (3):809-816.<\/p>\n
[12]Bucciarelli P,Rosendaal FR,Tripodi A,etal.Risk of venous thromboembolism and clinical manifestations in carriers of antithrombin,protein C,protein S deficiency or activated protein C resistance\uff1aa multicenter collaborative family study[J].Arterioscler Thromb Vasc Biol,1999\uff0c19(4)\uff1a1026-1033.<\/p>\n
[13]Sierko E,Wojtukiewicz MZ,Zawadzki R\uff0cetal.Expression of protein C(PC),protein S(PS) and thrombomodulin(TM)in human colorectal cancer[J].Thromb Res\uff0c 2010,125(3):71-75.<\/p>\n
[14]\u6c88\u8389\uff0c\u674e\u5efa\u6c11\uff0c\u6881\u5c0f\u864e\uff0c\u7b49.\u4e9a\u7532\u84dd\/\u5149\u5316\u5b66\u75c5\u6bd2\u706d\u6d3b\u6cd5\u5bf9\u8840\u6d46\u86cb\u767d\u6d53\u5ea6\u53ca\u51dd\u8840\u56e0\u5b50\u6d3b\u6027\u7684\u5f71\u54cd[J].\u4e2d\u56fd\u8f93\u8840\u6742\u5fd7,2006\uff0c19(6)\uff1a111-112.<\/p>\n
[15]Lensen RP,Rosendaal FR,Koster T\uff0cetal.Apparent different thrombotic tendency in patients with factor V Leiden and protein C deficiency due to selection of patients[J].Blood,1996\uff0c88(11)\uff1a4205-4208.<\/p>\n
[16]Svensson PJ,Dahlb\u00e4ck B.Resistance to activated protein C as a basis for venous thrombosis[J].N Engl J Med\uff0c1994\uff0c330(8):517-522.<\/p>\n
[17]Mannucci PM,Asselta R,Duga S,etal.The association of factor V Leiden with myocardial infarction is replicated in 1880 patients with premature disease[J].J Thromb Haemost\uff0c2010,8(10):2116-2121.<\/p>\n
[18]van Langevelde K,Flinterman LE,van Hylckama Vlieg A,etal.Broadening the factor V Leiden paradox:pulmonary embolism and deep-vein thrombosis as 2 sides of the spectrum[J].Blood\uff0c2012,120(5):933-946.<\/p>\n
[19]\u90b1\u8d35\u5174.\u4e2d\u56fd\u9aa8\u79d1\u5927\u624b\u672f\u9759\u8109\u8840\u6813\u6813\u585e\u75c7\u9884\u9632\u6307\u5357[J].\u4e2d\u534e\u5173\u8282\u5916\u79d1\uff0c2009\uff0c3(3)\uff1a70-73.<\/p>\n
[20]\u80e1\u71d5\u9752\uff0c\u9648\u65b9\u5e73\uff0c\u89e3\u52e4\u4e4b\uff0c\u7b49.\u51dd\u8840\u56e0\u5b50VR2\u7b49\u4f4d\u57fa\u56e0\u591a\u6001\u6027\u8840\u6813\u76f8\u5173\u6027\u75be\u75c5\u60a3\u8005\u4e2d\u7684\u5206\u5e03[J].\u4e34\u5e8a\u8840\u6db2\u5b66\u6742\u5fd7\uff0c2002\uff0c15(4)\uff1a159-160.<\/p>\n
[21]Segers O,Simioni P,Tormene D,etal.Genetic modulation of the FV(Leiden)\/normal FV ratio and risk of venous thrombosis in factor V Leiden heterozygotes[J].J Thromb Haemost\uff0c2012\uff0c10(1):73-80.<\/p>\n
[22]Lijfering WM,Middeldorp S,Veeger NJ,etal.Risk of recurrent venous thrombosis in homozygous carriers and double heterozygous carriers of factor V Leiden and prothrombin G20210A[J].Circulation\uff0c2010,121(15):1706-1712.<\/p>\n
[23]\u6768\u5fe0\u4f1f\uff0c\u51af\u79c0\u4e3d\uff0c\u8096\u767d\uff0c\u7b49\uff0e\u65b0\u7586\u8499\u53e4\u65cf\u51a0\u5fc3\u75c5\u4eba\u7fa4\u4e2dFV Leiden\u57fa\u56e0\u7a81\u53d8\u7684\u7814\u7a76-\u96444l\u4f8b\u62a5\u544a[J]\uff0e\u65b0\u533b\u5b66\uff0c2009\uff0c7(40)\uff1a445-447.<\/p>\n
[24]\u90ed\u8fb0\u8679\uff0c\u90ed\u743c\u884c\uff0c\u9f9a\u7476\u7434\uff0c\u7b49\uff0e\u51dd\u8840\u56e0\u5b50V\u57fa\u56e0Leiden\u7a81\u53d8\u548c\u51dd\u8840\u9176\u539f\u57fa\u56e0G20210A\u7a81\u53d8\u4e0e\u4e0b\u80a2\u6df1\u9759\u8109\u8840\u6813\u5f62\u6210\u5173\u7cfb\u7684\u63a2\u8ba8[J].\u5c71\u4e1c\u5927\u5b66\u5b66\u62a5\uff1a\u533b\u5b66\u7248\uff0c2002\uff0c40(3)\uff1a235-237\uff0e<\/p>\n
[25]\u674e\u51e4\u82b9\uff0c\u6768\u5fd7\u521a\uff0c\u5218\u56fd\u52cb\uff0c\u7b49\uff0e\u7ca4\u897f\u7c4d\u4eba\u7fa4FV Leiden\u57fa\u56e0\u7a81\u53d8\u7684\u521d\u6b65\u8c03\u67e5[J]\uff0e\u5e7f\u4e1c\u533b\u5b66\u9662\u5b66\u62a5\uff0c2000\uff0c6(2)\uff1a122-124\uff0e<\/p>\n
[26]Poort SR,Rosendaal FR,Reitsma PH\uff0cetal.A common genetic variation in the 3-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an incrense in venous thrombosis[J].Blood\uff0c1996\uff0c88(10)\uff1a3698-3703.<\/p>\n
[27]Simioni P,Prandoni P,Lensing AW,etal.Risk for subsequent venous thromboembolic complications in carriers of the prothrombin or the factor V gene mutation with a first episode of deep-vein thrombosis[J].Blood\uff0c2000,96(10):3329-3333.<\/p>\n
[28]\u8d3a\u9896.\u9057\u4f20\u6027\u9ad8\u5371\u56e0\u5b50\u57fa\u56e0\u591a\u6001\u6027\u53ca\u6297\u5fc3\u78f7\u8102\u6297\u4f53\u4e0e\u6df1\u9759\u8109\u8840\u6813\u5f62\u6210\u7684\u5173\u7cfb[D].\u90d1\u5dde\uff1a\u90d1\u5dde\u5927\u5b66\uff0c2002.<\/p>\n
[29]\u5e38\u5efa\u534e\uff0c\u9a6c\u8d8a\uff0c\u5f20\u5e7f\u68ee\uff0c\u7b49.\u4e2d\u56fd\u58ee\u65cf\u4eba\u7fa4\u51dd\u8840\u9176\u539f\u57fa\u56e0G20210A\u7a81\u53d8\u9891\u7387\u7814\u7a76[J].\u4e2d\u534e\u533b\u5b66\u9057\u4f20\u5b66\u6742\u5fd7\uff0c2005,6(22)\uff1a341-342.<\/p>\n
[30]\u91d1\u56fd\u680b,\u5f90\u8015,\u5085\u56fd\u80dc,\u7b49.\u51dd\u8840\u9176\u539f\u57fa\u56e0G20210A\u548c\u51dd\u8840\u56e0\u5b50\u2164Leiden\u7a81\u53d8\u4e0e\u51a0\u5fc3\u75c5\u7684\u76f8\u5173\u6027\u63a2\u8ba8[J].\u4e2d\u56fd\u75c5\u7406\u751f\u7406\u6742\u5fd7\uff0c2003\uff0c19(7):969-970.<\/p>\n
[31]Meyer G,Emmerich J,Helley D,etal.Factors V leiden and \u2161 20210A in patients with symptomatic pulmonary embolism and deep vein thrombosis[J].Am J Med\uff0c2001,110(1):12-15.<\/p>\n
[32]\u738b\u79c9\u6797,\u6208\u5c0f\u864e.F\u2164Leiden\u4e0eF\u2161G20210A\u7a81\u53d8\u5728\u4e0d\u540c\u79cd\u65cf\u4eba\u7fa4\u6613\u6813\u75c7\u4e2d\u8868\u8fbe\u7684\u7814\u7a76\u73b0\u72b6[J].\u4e2d\u56fd\u666e\u5916\u57fa\u7840\u4e0e\u4e34\u5e8a\u6742\u5fd7\uff0c2012,19(7)\uff1a793-795.<\/p>\n
[33]Wu J\uff0cGu J\uff0cXu J\uff0cetal.Factor V Leiden mutation in one family of Chinese origin[J]\uff0eChin Med J (Engl)\uff0c2001\uff0c114(4):379-381.<\/p>\n
[34]M\u00e4kelburg AB,Veeger NJ,Middeldorp S,etal.Different risk of deep vein thrombosis and pulmonary embolism in carriers with factor V Leiden compared with non-carriers,but not in other thrombophilic defects.Results from a large retrospective family cohort study[J].Haematologica\uff0c2010\uff0c95 (6):1030-1033.<\/p>\n
[35]\u5468\u5efa\u519b\uff0c\u80e1\u5a05\u8389.\u6613\u6813\u75c7\u7684\u53d1\u751f\u673a\u5236\u548c\u9632\u6cbb[J].\u4e2d\u56fd\u5b9e\u7528\u5987\u79d1\u4e0e\u4ea7\u79d1\u6742\u5fd7\uff0c2009\uff0c3(5):332-335.<\/p>\n
[36]\u6731\u950b\uff0c\u6208\u5c0f\u864e.\u65b0\u7586\u54c8\u8428\u514b\u65cf\u9057\u4f20\u6027\u6613\u6813\u75c7\u4eba\u7fa4\u4e2d\u6d3b\u5316C\u86cb\u767d\u62b5\u6297\u3001\u86cb\u767dC\u548c\u86cb\u767dS\u7684\u8054\u5408\u7f3a\u9677[J].\u519c\u57a6\u533b\u5b66\uff0c2012,34(6):484-487.<\/p>\n
[37]\u5f20\u5efa\u5e73,\u5434\u6653\u971e.\u8840\u6813\u524d\u72b6\u6001\u4e8e\u590d\u53d1\u884c\u6d41\u4ea7[J].\u4e2d\u56fd\u5b9e\u7528\u5987\u79d1\u4e0e\u4ea7\u79d1\u6742\u5fd7,2007,12(23):917-920.<\/p>\n
Research Progress on Joint Defects of Protein C\uff0cProtein S and Activated Protein Resistance in ThrombophiliaGAOLi-xia1,WUKe-xiong1,ZHANGYi-zhi2.(1.DepartmentofHematologyandOncology,KaramayCentralHospital,Karamay834000\uff0cChina; 2.TheCenterofLeukemia,TianjinBloodDiseasesHospital,ChineseAcademyofMedicalSciences,Tianjin300020\uff0cChina)<\/p>\n
Abstract\uff1aThrombophilia is a common clinical disease of multiple etiology,with high disability rate and mortality.From the perspectives of hereditary coagulation,anticoagulation and fibrinolysis abnormalities to investigate the etiology and pathogenesis of thrombophilia is very important to the prevention of the disease.Hereditary thrombophilia includes activated protein C resistance(APCR),antithrombin deficiency(AT.\u2162),protein C and protein S deficiencies,Factor V Leiden and prothrombin G20210A mutations and so on.There may be joint defects of APCR and protein S deficiency in some cases of hereditary thrombophilia.Here is to make a review of the anticoagulation system of joint defects of protein C,protein S,APCR in thrombophilia.<\/p>\n
Key words\uff1aProtein C\uff1b Protein S\uff1b Activated protein C resistance\uff1b Joint defects<\/p>\n","protected":false},"excerpt":{"rendered":"
\u9ad8\u4e3d\u971e(\u7efc\u8ff0)\uff0c\u5434\u514b\u96c4\uff0c\u5f20\u76ca\u679d(\u5ba1\u6821) (1.\u514b\u62c9\u739b\u4f9d\u5e02\u4e2d\u5fc3\u533b\u9662\u8840\u6db2\u80bf\u7624\u79d1\uff0c\u65b0\u7586 … \u7ee7\u7eed\u9605\u8bfb