Landolfi R, Ciabattoni G, Patrignani P, Castellana M A, Pogliani E, Bizzi B, Patrono C
Department of Medicine, Catholic University School of Medicine, Rome, Italy.
Blood. 1992 Oct 15;80(8):1965-71.
Increased thromboxane (TX) production and modified aspirin sensitivity has been detected in vitro in platelets isolated from patients with polycythemia vera. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo and its suppression by oral aspirin, we have investigated the urinary excretion of major enzymatic metabolites of TXB2 in 17 patients with polycythemia vera and 23 gender- and age-matched controls. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. In addition, urinary immunoreactive leukotriene (LT) E4 was measured to explore the 5-lipoxygenase pathway of arachidonate metabolism. Polycythemic patients had significantly (P < .001) higher excretion rates of both 11-dehydro-TXB2 (1,033 +/- 1,050 v 117 +/- 45 pmol/mmol creatinine; mean +/- SD) and 2,3-dinor-TXB2 (725 +/- 676 v 82 +/- 43 pmol/mmol creatinine) than controls. In contrast, urinary LTE4 was not significantly different. Enhanced metabolite excretion did not correlate with the platelet count or with the hematocrit value, and was not related to the current treatment or to a clinical history of thrombotic complications. Platelet TX receptor studies did not show any significant changes in the binding characteristics of two different ligands. A platelet-selective regimen of aspirin therapy (50 mg/d for 7 to 14 days) was associated with greater than 80% suppression in metabolite excretion in nine patients. These results are consistent with abnormal stimuli operating in polycythemia vera to induce a selective enhancement in the platelet biosynthesis of TXA2 without changes in receptor binding. This in vivo abnormality in platelet biochemistry can be largely suppressed by low doses of aspirin.
在真性红细胞增多症患者分离出的血小板中，已在体外检测到血栓素（TX）生成增加和阿司匹林敏感性改变。为了验证这些与能力相关的测量结果与体内TXA2生物合成的实际速率及其被口服阿司匹林抑制之间的相关性，我们研究了17例真性红细胞增多症患者和23例性别及年龄匹配的对照者尿中TXB2主要酶促代谢产物的排泄情况。通过先前验证的放射免疫分析法测量尿中11-脱氢-TXB2和2,3-二去甲-TXB2。此外，测量尿中免疫反应性白三烯（LT）E4以探索花生四烯酸代谢的5-脂氧合酶途径。真性红细胞增多症患者的11-脱氢-TXB2（1,033±1,050对117±45 pmol/mmol肌酐；平均值±标准差）和2,3-二去甲-TXB2（725±676对82±43 pmol/mmol肌酐）排泄率均显著高于对照组（P <.001）。相比之下，尿LTE4无显著差异。代谢产物排泄增加与血小板计数或血细胞比容值无关，也与当前治疗或血栓形成并发症的临床病史无关。血小板TX受体研究未显示两种不同配体的结合特性有任何显著变化。9例患者采用血小板选择性阿司匹林治疗方案（50 mg/d，持续7至14天）后，代谢产物排泄抑制率超过80%。这些结果与真性红细胞增多症中存在异常刺激导致血小板TXA2生物合成选择性增强而受体结合无变化一致。低剂量阿司匹林可在很大程度上抑制血小板生物化学的这种体内异常。
