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ADAMTS13 unbound to larger von Willebrand factor multimers in cryosupernatant: implications for selection of plasma preparations for thrombotic thrombocytopenic purpura treatment

发布于：2013年4月22日    文字：【大】【中】【小】

Transfusion. 2013 Apr 8.doi: 10.1111/trf.12182. [Epub ahead of print]

ADAMTS13 unbound to larger von Willebrand factor multimers in cryosupernatant: implications for selection of plasma preparations for thrombotic thrombocytopenic purpura treatment.

Hori Y, Hayakawa M, Isonishi A, Soejima K, Matsumoto M, Fujimura Y.

Source

Department of Blood Transfusion Medicine, Nara Medical University, Kashihara, Nara, Japan; The Chemo-Sero-Therapeutic Research Institute, Kikuchi, Kumamoto, Japan.

Abstract

BACKGROUND:

Thrombotic thrombocytopenic purpura (TTP) is characterized by deficient ADAMTS13 activity. Treatment involves plasma exchange (PE). Both fresh-frozen plasma (FFP) and cryosupernatant (CSP) are used, but it remains to be determined which is more effective.

STUDY DESIGN AND METHODS:

To analyze the interaction between von Willebrand factor (VWF) and ADAMTS13, we used large-pore isoelectric focusing (IEF) analysis followed by detection with anti-ADAMTS13 monoclonal antibody. FFP, CSP, cryoprecipitate (CP), and purified ADAMTS13 were analyzed for their effects on high shear stress-induced platelet aggregation (H-SIPA).

RESULTS:

IEF analysis of normal plasma revealed three groups of ADAMTS13 bands with pI of 4.9 to 5.6, 5.8 to 6.7, and 7.0 or 7.5. Two band groups (pI 4.9-5.6 and 5.8-6.7) were found in plasma of a patient with Type 3 von Willebrand disease, in which VWF is absent, whereas no bands were found in plasma of a patient with congenital ADAMTS13 deficiency.Mixing these plasmas generated the bands at pI 7.0 or 7.5, representing the VWF-ADAMTS13 complex; these bands were absent in CSP. FFP and purified ADAMTS13 down regulated H-SIPA in a dose-dependent manner. However, CP did not inhibit H-SIPA in the initial phase, and the degree of inhibition at the endpoint was almost indistinguishable from those of the other two plasma products.

CONCLUSION:

Both plasma products (FFP and CSP) are effective for PE in TTP patients. However, CSP may be more favorable, because it has lower levels of VWF and almost normal ADAMTS13 activity, but lower levels of ADAMTS13 incomplex with larger VWF multimers.

背景：血栓性血小板减少性紫癜(TTP)是一种以ADAMTS13缺陷为特点的疾病。其治疗主要为血浆置换，新鲜冰冻血浆(FFP)和冷上清(CSP)均可使用，但何种方法更为有效目前尚有待证实。

实验设计和方法：应用大孔径等电点聚焦法和抗ADAMTS13抗体检测，本实验研究了血管性假性血友病因子(vWF)和ADAMTS13的相互作用。检测了鲜冰冻血浆(FFP)、冷上清(CSP)、冷沉淀(CP)以及纯化的ADAMTS13在高血流剪切力下血小板聚集中的作用。

结果：等电点聚焦法检测到正常血浆中存在三种ADAMTS13条带，分别为等电点4.9至5.6、5.8 至 6.7以及 7.0 或7.5的条带。3型血管性血友病患者血浆中缺乏vWF，存在两种ADAMTS13条带，等电点分别为4.9至5.6 和 5.8至6.7。在先天性ADAMTS13缺乏的患者血浆中，没有出现ADAMTS13条带。将这些血浆混合后，出现等电点7.0 或7.5的条带：代表vWF–ADAMTS13复合物。在冷上清中这些条带均缺失。新鲜冷冻血浆和纯化的ADAMTS13可降低高血流剪切力下的血小板聚集，呈剂量依赖效应。冷沉淀在初始阶段不能抑制高血流剪切力下的血小板聚集，但在剂量终点时效应与前两者并无差别。

结论：TTP患者血浆置换使用新鲜冰冻血浆和冷上清均有效，但冷上清可能疗效更好，原因是其含有更低的vWF和正常的ADAMTS13活性，但vWF–ADAMTS13复合物含量更少。