Michiels Jan Jacques, Berneman Zwi, Schroyens Wilfried, Koudstaal Peter J, Lindemans Jan, Neumann H A Martino, van Vliet Huub H D M
Department of Hematology, University Hospital Antwerp, Hemostasis Thrombosis Research, Antwerp, Belgium.
Platelets. 2006 Dec;17(8):528-44. doi: 10.1080/09537100600758677.
Microvascular circulation disturbances including erythromelalgia, its microvascular ischemic complications, and migraine-like atypical or typical transient ischemic cerebral, ocular, and coronary ischemic attacks are specific clinical manifestations in patients with essential thrombocythemia (ET), and polycythemia vera (PV) associated with thrombocythemia. Thrombocythemia (ET and PV) patients with microvascular disturbances have shortened platelet survival, increased beta-thromboglobulin (beta-tg), platelet factor 4 (PF4), and thrombomoduline (TM) levels, and increased urinary thromboxane B2 (TxB2) excretion indicating platelet-mediated processes in vivo. Inhibition of platelet cyclooxygenase (COX 1) by aspirin is followed by relief of microvascular disturbances, correction of shortened platelet survival, and return of plasma levels of beta-tg, PF4, TM levels and TxB2 excretion to normal. The transient ischemic attacks and thrombotic complications in thrombocythemia are very likely caused by hypersensitive platelets produced by spontaneously proliferating enlarged megakaryocytes in the bone marrow of ET and PV patients. In contrast to normal platelets in healthy individuals the circulating hypersensitive thrombocythemic platelets spontaneously activate and secrete their products, thus forming aggregates that transiently plug the microcirculation, or result in occlusive platelet thrombi in arterioles or small arteries. Clear evidence is presented that the microvascular transient ischemic and occlusive thrombotic complications in thrombocythemia patients are relieved by treatment with aspirin and by reduction of platelet counts to normal (<400 x 109/l), but not by coumadin. In patients with thrombocythemia associated with PV, increased hematocrit and whole blood viscosity aggravate the platelet-mediated microvascular ischemic and thrombotic syndrome of thrombocythemia to major arterial and venous thrombotic complications. Correction of hematocrit and blood viscosity by phlebotomy significantly reduces the major arterial and venous thrombotic complications, but fails to prevent the platelet-mediated microvascular circulation disturbances in PV patients because thrombocythemia persists. Complete relief and prevention of microvascular and major thrombosis in PV patients are obtained by treatment with low-dose aspirin on top of phlebotomy or by treatment with the platelet lowering agents, anagrelide, interferon or hydroxyurea.
微血管循环障碍，包括红斑性肢痛症、其微血管缺血性并发症，以及偏头痛样非典型或典型短暂性脑缺血、眼部缺血和冠状动脉缺血发作，是原发性血小板增多症（ET）以及与血小板增多症相关的真性红细胞增多症（PV）患者的特定临床表现。伴有微血管障碍的血小板增多症（ET和PV）患者血小板生存期缩短，β-血小板球蛋白（β-tg）、血小板因子4（PF4）和血栓调节蛋白（TM）水平升高，尿血栓素B2（TxB2）排泄增加，表明体内存在血小板介导的过程。阿司匹林抑制血小板环氧化酶（COX 1）后，微血管障碍得到缓解，血小板生存期缩短得以纠正，血浆β-tg、PF4、TM水平以及TxB2排泄恢复正常。血小板增多症中的短暂性缺血发作和血栓形成并发症很可能是由ET和PV患者骨髓中自发增殖的肿大巨核细胞产生的超敏血小板引起的。与健康个体的正常血小板不同，循环中的超敏血小板增多症血小板会自发激活并分泌其产物，从而形成聚集物，短暂阻塞微循环，或在小动脉或小动脉中形成闭塞性血小板血栓。有明确证据表明，血小板增多症患者的微血管短暂性缺血和闭塞性血栓形成并发症可通过阿司匹林治疗以及将血小板计数降至正常水平（<400×10⁹/L）得到缓解，但华法林无效。在与PV相关的血小板增多症患者中，血细胞比容增加和全血粘度升高会使血小板介导的血小板增多症微血管缺血和血栓形成综合征加重，导致主要的动脉和静脉血栓形成并发症。通过放血纠正血细胞比容和血液粘度可显著降低主要的动脉和静脉血栓形成并发症，但由于血小板增多症持续存在，无法预防PV患者中血小板介导的微血管循环障碍。通过在放血基础上加用小剂量阿司匹林治疗，或使用降低血小板的药物阿那格雷、干扰素或羟基脲进行治疗，可使PV患者的微血管和主要血栓形成得到完全缓解和预防。
