Laffi G, Cinotti S, Filimberti E, Ciabattoni G, Caporale R, Marra F, Melani L, Grossi A, Carloni V, Gentilini P
Istituto di Medicina Interna, Università Degli Studi di Firenze, Rome, Italy.
J Hepatol. 1996 Apr;24(4):436-43. doi: 10.1016/s0168-8278(96)80164-4.
BACKGROUND/AIMS: Platelet function abnormalities contribute to the hemostatic defect in patients with cirrhosis. In this study we evaluated the occurrence of in vivo platelet activation as a possible mechanism of defective platelet aggregation in patients with cirrhosis.
Nine patients with severe (Child B-C) cirrhosis and defective platelet aggregation were studied in comparison with age- and sex-matched healthy controls. The presence of activated platelets in the bloodstream was evaluated by fluorescence-activated flow cytometry using antibodies directed against activation-dependent platelet proteins and by measuring plasma levels of beta-thromboglobulin and platelet factor 4. Urinary levels of 11-dehydro-TXB2 and of 2,3-dinor-TXB2 were assayed by radioimmunoassay following chromatographic separation.
In unstimulated platelets, the expression of both GMP 140 and GP 53 was not significantly different in patients with cirrhosis and in controls. After stimulation with ADP and epinephrine, expression of activation-dependent antigens was lower in platelets from patients (GMP 140: 0.64 +/- 0.09 vs 0.73 +/- 0.04, p = 0.02; GP 53: 0.41 +/- 0.13 vs 0.54 +/- 0.14). Plasma levels of beta-thromboglobulin and platelet factor 4, as indexes of in vivo platelet activation, were also comparable in the two groups of subjects. Urinary levels of 11-dehydro-TXB2 and of 2,3-dinor-TXB2, the major systemic metabolites of TXA2, were significantly higher in patients with cirrhosis (1807 +/- 518 vs 341 +/- 121 ng/pg creatinine and 693 +/- 512 vs 205 (93 ng/pg creatinine, respectively, p < 0.001). However, increased excretion of TXB2 metabolites was also observed in three patients with chronic autoimmune thrombocytopenia.
These data indicate that circulating platelets are not activated in cirrhosis, and that defective aggregation is most likely dependent on the alteration of the transmembrane signaling pathways. The increased urinary excretion of systemic TXA2 metabolites may be related to increased intrasplenic platelet destruction.
背景/目的：血小板功能异常导致肝硬化患者出现止血缺陷。在本研究中，我们评估了体内血小板活化的发生情况，其可能是肝硬化患者血小板聚集缺陷的一种机制。
研究了9例重度（Child B - C级）肝硬化且血小板聚集缺陷的患者，并与年龄和性别匹配的健康对照者进行比较。通过使用针对活化依赖性血小板蛋白的抗体的荧光激活流式细胞术以及测量血浆β-血小板球蛋白和血小板因子4水平，评估血流中活化血小板的存在情况。经色谱分离后，采用放射免疫分析法测定尿中11 - 脱氢 - TXB2和2,3 - 二去甲 - TXB2的水平。
在未受刺激的血小板中，肝硬化患者和对照者的GMP 140和GP 53的表达均无显著差异。用ADP和肾上腺素刺激后，患者血小板中活化依赖性抗原的表达较低（GMP 140：0.64±0.09对0.73±0.04，p = 0.02；GP 53：0.41±0.13对0.54±0.14）。作为体内血小板活化指标的血浆β-血小板球蛋白和血小板因子4水平，在两组受试者中也相当。肝硬化患者尿中11 - 脱氢 - TXB2和2,3 - 二去甲 - TXB2（TXA2的主要全身代谢产物）的水平显著更高（分别为1807±518对341±121 ng/pg肌酐和693±512对205（93）ng/pg肌酐，p < 0.001）。然而，在3例慢性自身免疫性血小板减少症患者中也观察到TXB2代谢产物排泄增加。
这些数据表明，肝硬化患者循环中的血小板未被激活，聚集缺陷很可能取决于跨膜信号通路的改变。全身TXA2代谢产物尿排泄增加可能与脾内血小板破坏增加有关。
