Shibagaki Yugo, Fujita Toshiro
Department of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hypertens Res. 2005 Jan;28(1):89-95. doi: 10.1291/hypres.28.89.
Patients with malignant hypertension sometimes exhibit microangiopathic hemolytic anemia/thrombocytopenia known as thrombotic microangiopathy (TMA). On the other hand, severe hypertension is sometimes associated with hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP). Because the clinical features of the two entities overlap significantly, it is sometimes difficult to distinguish one from the other. However, such differentiation is indispensable, since early performance of plasmapheresis is critical in HUS/TTP. It has been suggested that severe thrombocytopenia is one of the most useful differential points in diagnosing HUS/TTP from malignant hypertension caused by other etiologies. Early performance of plasmapheresis can be justified in the presence of both TMA and thrombocytopenia. However, thrombocytopenia can be seen in the cases with malignant hypertension from etiologies other than HUS/TTP, and in these particular cases, plasmapheresis is useless and can be harmful. Recently, the plasma level of ADAMTS13 (a disintegrin and metalloprotease domain, with thrombospondin type 1 motif 13), which is a von Willebrand Factor cleaving protease, has been shown to be very low in familial or some of the sporadic cases of TTP, and a low level of ADAMTS13 is very specific to TTP. Some reports have shown that patients with a very low plasma level of ADAMTS13 respond very well to plasmapheresis. We recently experienced two cases with TMA. Although both of our patients had severe hypertension with TMA, different therapeutic strategies ameliorated their illness: symptomatic treatment was effective in case 1, which showed normal ADAMTS13 activity, whereas plasma infusion was necessary to save case 2, which showed low ADAMTS13 activity. Thus, patients with a low level of ADAMTS13 activity might respond well to plasmapheresis or plasma infusion. When presented with patients with severe hypertension and thrombotic microangiopathy, ADAMTS13 activity may prove to be a promising adjunctive tool in differentiating TTP from TMA due to other etiologies, but in the meantime, we should make the choice of whether or not to perform plasmapheresis based on the degree of thrombocytopenia.
恶性高血压患者有时会出现微血管病性溶血性贫血/血小板减少症，即血栓性微血管病（TMA）。另一方面，重度高血压有时与溶血尿毒综合征（HUS）/血栓性血小板减少性紫癜（TTP）相关。由于这两种疾病的临床特征有显著重叠，有时很难将它们区分开来。然而，这种区分是必不可少的，因为早期进行血浆置换对HUS/TTP至关重要。有人提出，严重血小板减少是将HUS/TTP与其他病因引起的恶性高血压进行鉴别诊断时最有用的鉴别点之一。在同时存在TMA和血小板减少的情况下，早期进行血浆置换是合理的。然而，在非HUS/TTP病因引起的恶性高血压病例中也可出现血小板减少，在这些特殊情况下，血浆置换无用且可能有害。最近研究表明，在家族性或部分散发性TTP病例中，血管性血友病因子裂解蛋白酶ADAMTS13（一种去整合素和金属蛋白酶结构域，含血小板反应蛋白1型基序13）的血浆水平非常低，且ADAMTS13水平低对TTP具有高度特异性。一些报告显示，ADAMTS13血浆水平极低的患者对血浆置换反应良好。我们最近遇到了两例TMA患者。尽管我们的两名患者都患有伴有TMA的重度高血压，但不同的治疗策略改善了他们的病情：病例1的ADAMTS13活性正常，对症治疗有效，而病例2的ADAMTS13活性低，需要进行血浆输注来挽救生命。因此，ADAMTS13活性低的患者可能对血浆置换或血浆输注反应良好。当遇到重度高血压和血栓性微血管病患者时，ADAMTS13活性可能是将TTP与其他病因引起的TMA进行鉴别的一个有前景的辅助工具，但与此同时，我们应根据血小板减少的程度来决定是否进行血浆置换。
