Wu K K, Minkoff I M, Rossi E C, Chen Y C
Br J Haematol. 1981 Feb;47(2):241-9. doi: 10.1111/j.1365-2141.1981.tb02785.x.
A large family with a hereditary bleeding disorder was investigated. Easy bruising, epistaxis and menorrhagia were noted in seven members of three generations and at least one member in each generation was affected. Platelet function abnormalities were characterized by reduced 14C-serotonin release, absent second wave aggregation in response to ADP or epinephrine and reduced aggregation in response to collagen. Bleeding time was prolonged in three individuals and platelet factor 3 availability was abnormal in four. Platelet count, morphology, adhesiveness and clot retraction were normal in all. Platelet ADP and ATP as well as ATP to ADP ratio were normal. This family probably represents the first documented instance of hereditary platelet primary release disorder. To elucidate the pathogenetic mechanism, further functional studies were performed. No appreciable shape change, 14C-serotonin release of aggregation was observed when the propositus' platelets were stimulated with sodium arachidonate or a PGH2 analogue. By contrast, platelets responded normally to ionophore A23187, thrombin and ristocetin. The findings indicate that the hereditary primary release disorder is probably due to a reduced thromboxane A2 production secondary to thromboxane synthetase deficiency. Alternatively, it may be due to platelet membrane abnormalities which render platelets unresponsive to thromboxane A2.
对一个患有遗传性出血性疾病的大家族进行了调查。三代家族中的7名成员出现了易瘀伤、鼻出血和月经过多的症状，且每一代至少有一名成员受到影响。血小板功能异常的特征为14C - 5 -羟色胺释放减少、对ADP或肾上腺素无第二波聚集反应以及对胶原的聚集反应减弱。3名个体的出血时间延长，4名个体的血小板因子3有效性异常。所有个体的血小板计数、形态、黏附性和血块收缩均正常。血小板ADP和ATP以及ATP与ADP的比值均正常。这个家族可能代表了遗传性血小板原发性释放障碍的首个有记录的病例。为阐明发病机制，进行了进一步的功能研究。当用花生四烯酸钠或PGH2类似物刺激先证者的血小板时，未观察到明显的形状变化、14C - 5 -羟色胺释放或聚集。相比之下，血小板对离子载体A23187、凝血酶和瑞斯托霉素反应正常。研究结果表明，遗传性原发性释放障碍可能是由于血栓素合成酶缺乏继发血栓素A2生成减少所致。或者，也可能是由于血小板膜异常，使血小板对血栓素A2无反应。
