CHRISTMAS DISEASE - A CONDITION PREVIOUSLY MISTAKEN FOR HAEMOPHILIA
CHRISTMAS DISEASE - A CONDITION PREVIOUSLY MISTAKEN FOR HAEMOPHILIA
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DOI：
10.1136/bmj.2.4799.1378
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发表时间：
1952-01-01
影响因子：
--
通讯作者：
OBRIEN, JR
中科院分区：
文献类型：
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作者：
BIGGS, R;DOUGLAS, AS;OBRIEN, JR
圣诞病是一种主要影响男性的出血性疾病，直到 1952 年才与血友病区分开来，当时 Aggeler、White、Glendening、Page、Leake 和 Bates（1952 年）以及 Biggs、Douglas、Macfarlane、Dacie、Pitney、Merskey 和 O'Brien（1952 年）表明，这两种疾病是由于凝血机制中根本不同的缺陷所致。为了理解这种区别的重要性，有必要了解正常凝血所依赖的血液凝血酶原转化系统的性质。在正常血液中，大部分凝血酶原在凝血过程中消失，因为它转化为凝血酶，随后被抗凝血酶灭活。因此，正常血液在玻璃管中凝固一小时后检查的血清中含有很少的凝血酶原。在血友病和圣诞节病中，通过“凝血酶原消耗试验”以这种方式检查的血清中发现含有大量凝血酶原，这表明凝血酶原转化机制的失败。无论哪种情况，在严重的情况下，玻璃管中的凝固时间也会延长。到目前为止，这两种情况的缺陷是相同的，只有通过更详细地揭示凝血酶原转化系统的测试才能实现区分。这些结果表明，这两种疾病是由于血液中缺乏形成凝血酶原激活剂所需的两种不同成分引起的（Biggs，Douglas 和 Macfarlane，I953）。构成现代治疗基础的这两种成分的准确诊断和特定测定程序的开发取决于对该系统的理解。与凝血酶原激活剂正常形成有关的因素可以通过Biggs和Douglas(I953)设计的“凝血活酶生成试验”来研究。人们发现（Biggs、Douglas 和 Macfarlane，I953）用 AI（OH）3、正常血清、血小板和 CaCl2 处理的正常血浆的混合物会产生一种物质，该物质在 CaCl2 存在的情况下会大大加速血浆（底物）的凝固。 Al(OH) 3 处理的血浆不含有凝血酶原，因为它通过Al(OH) 3 处理而被去除。正常血清中也不存在明显量的凝血酶原。因此，底物的大大加速的凝固不可能是由于凝血酶，而一定是由于其所含的凝血酶原的快速转化。该测试现在通常用某种形式的磷脂代替血小板进行，可以直接记录形成凝血酶原转化物质的能力。结果发现，如果用来自血友病患者的经 Al(OH)3 处理的血浆代替正常处理的血浆，则得到的结果较差（由长底物凝血时间表示），而经 Al(OH)3 处理的圣诞病患者血浆在该测试中表现正常。相反，如果血清成分来自患有圣诞病的患者，则会获得异常结果，而来自血友病患者的血清则表现正常。说明这种差异的结果给出在
CHRISTMAS disease is a hamorrhagic state mainly affecting males, which was not distinguished from hemophilia until I952, when it was shown by Aggeler, White, Glendening, Page, Leake and Bates (1952) and Biggs, Douglas, Macfarlane, Dacie, Pitney, Merskey and O'Brien (I952) that the two conditions were due to fundamentally different defects in the blood-clotting mechanism. To appreciate the significance of the distinction it is necessary to understand the nature of the prothrombin-converting system of the blood, on which normal coagulation depends. In normal blood most of the prothrombin disappears during clotting because it is converted to thrombin, which is subsequently inactivated by antithrombin. Consequently serum, examinedone hour after normal blood has clotted in a glass tube, contains very little prothrombin. In both hamophilia and Christmas' disease serum examined in this way by the'prothrombin consumption test'is found to contain large amounts of prothrombin, demonstrating a failure of the prothrombin-converting mechanism. Insevere cases' of either condition the coagulation time in glass tubes is also pro-longed. The defects in the two conditions are thus far the same, and distinction can only be achieved by tests which reveal theprothrombinconverting system in greater detail. These have shown that the two diseases are caused by the lack of two different components required for the for-mation of a prothrombin activator in the blood (Biggs, Douglas and Macfarlane, I953). Accurate diagnosis and the development of specific assay procedures for these two components which form the basis of modern therapy depend on an under-standing of this system. The factors concerned in the normal formation of prothrombin activator can be studied by the'thromboplastin generation test'devised by Biggs and Douglas (I953). It was found (Biggs, Douglas and Macfarlane, I953) that a mixture of normal plasma treated with AI (OH) 3, normal serum, platelets and CaCl2 produces a substance which will greatly accelerate the clotting of plasma (sub-strate) in the presence of CaCl2. The AI (OH) 3-treated plasma does not contain prothrombin because this is removed by the Al (OH) 3 treatment. Neither is there any appreciable amount of pro-thrombin in the normal serum. Thus the greatly accelerated clotting of the substrate cannot be due to thrombin, and must be due to rapid conversion of the prothrombin which it contains. The test, which is now usually carried out replacing platelets by some form of phospholipid, gives a direct record of ability to form a prothrombinconverting substance. It is found that if Al (OH) 3-treated plasma from a hmemophilic patient is used to replace the normal treated plasma poor results (indicated by long substrate clotting times) are obtained, whereas the Al (OH) 3-treated plasma of a Christmas disease patient behaves normally in this test. Reversely, if the serum component is derived from a patientwith Christmas disease abnormal resultsare obtained, whereas serum from a haemophilic patient behaves normally. Results illustrating this difference are given in