Kodama J, Uchida K, Kushiro H, Murakami N, Yutani C
Institute for Medical Care and Health Maintenance, Health Insurance Association, Sanyo Electric Group, Osaka.
Intern Med. 1998 May;37(5):440-3. doi: 10.2169/internalmedicine.37.440.
Localized edema of the larynx and pharynx leading to death from asphyxia has long been recognized as a characteristic symptom of hereditary angioneurotic edema (HANE). Long-term follow-up of younger HANE patients has revealed that transient localized acute attacks of edema affect tissues where the microcirculation maintains the blood supply. However, with aging, HANE attacks precipitate disseminated intravascular coagulation (DIC) or multiple organ failure (MOF). Substitution with a C1-inhibitor (C1-INH) has resulted in a fulminant lethal end with a rapid and profound decrease in antithrombin-III (AT-III) activity. A possible mechanism is as follows: Exogenous stimuli activate plasma proteinase systems with the generation of plasma kallikrein that activates the tissue factor pathway (TF) and liberates bradykinin (BK). In younger patients, BK enhances vascular permeability. In the elderly, activated TF is controlled by tissue factor pathway inhibitor (TFPI) and generates thrombin, which is the target enzyme of AT-III and precipitates DIC or MOF. In elderly patients, the characteristic symptom of HANE is hypercoagulation by age-related changes in the biosynthesis of AT-III or TFPI.
喉部和咽部的局部水肿导致窒息死亡，长期以来一直被认为是遗传性血管性水肿（HANE）的特征性症状。对年轻HANE患者的长期随访表明，水肿的短暂局部急性发作会影响微循环维持血液供应的组织。然而，随着年龄增长，HANE发作会引发弥散性血管内凝血（DIC）或多器官功能衰竭（MOF）。用C1抑制剂（C1-INH）替代会导致暴发性致命结局，抗凝血酶III（AT-III）活性迅速且显著降低。一种可能的机制如下：外源性刺激激活血浆蛋白酶系统，产生血浆激肽释放酶，后者激活组织因子途径（TF）并释放缓激肽（BK）。在年轻患者中，BK增强血管通透性。在老年人中，活化的TF由组织因子途径抑制剂（TFPI）控制并产生凝血酶，凝血酶是AT-III的靶酶，会引发DIC或MOF。在老年患者中，HANE的特征性症状是由于AT-III或TFPI生物合成的年龄相关变化导致的高凝状态。
