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多发性骨髓瘤和意义未明的单克隆丙种球蛋白病患者的血栓前异常。

Prothrombotic abnormalities in patients with multiple myeloma and monoclonal gammopathy of undetermined significance.

作者信息

Nielsen Thøger, Kristensen Søren Risom, Gregersen Henrik, Teodorescu Elena Manuela, Pedersen Shona

机构信息

Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.

Department of Hematology, Aalborg University Hospital, Denmark.

出版信息

Thromb Res. 2021 Jun;202:108-118. doi: 10.1016/j.thromres.2021.03.015. Epub 2021 Mar 21.

Abstract

BACKGROUND

Multiple myeloma (MM) and its precursor condition, monoclonal gammopathy of undetermined significance (MGUS) have an increased risk of thrombotic events, especially during anti-myeloma treatment. Many different underlying causes for this hypercoagulability have been suggested, but current techniques to identify abnormalities in these patients are sparse and inefficient. The aim of this study was to assess the hypercoagulability in MGUS and MM patients through various coagulation analyses and identify changes in the MM patients throughout their treatment regimen.

MATERIALS AND METHODS

Platelet-free plasma from 38 MM patients, 19 MGUS patients and 34 healthy controls were tested for hypercoagulability using calibrated automated thrombogram, a procoagulant phospholipid assay, a microvesicle-associated (MV) tissue factor (TF) assay, and a cell-free deoxyribonucleic acid (cf-DNA) assay as a surrogate measurement for neutrophil extracellular traps (NETs).

RESULTS

MGUS and MM patients both had elevated thrombin generation and procoagulant phospholipid activity in comparison to the control subjects. MM, and partly MGUS, showed increased MV-TF activity, however, only MM had increased levels of the cf-DNA.

CONCLUSIONS

Here we demonstrated that hypercoagulability was present in patients with MGUS and MM through increased thrombin generation, possibly due to higher TF and procoagulant phospholipids (PPL) activity. This may be associated to MVs and, for MM patients, be attributed to procoagulant NETs activity; however, this remains to be determined.

摘要

背景

多发性骨髓瘤(MM)及其前驱疾病意义未明的单克隆丙种球蛋白病(MGUS)发生血栓事件的风险增加,尤其是在抗骨髓瘤治疗期间。对于这种高凝状态,已提出许多不同的潜在原因,但目前用于识别这些患者异常情况的技术稀少且效率低下。本研究的目的是通过各种凝血分析评估MGUS和MM患者的高凝状态,并确定MM患者在整个治疗过程中的变化。

材料与方法

使用校准自动血栓图、促凝磷脂测定、微泡相关(MV)组织因子(TF)测定以及作为中性粒细胞胞外诱捕网(NETs)替代测量的游离脱氧核糖核酸(cf-DNA)测定,对38例MM患者、19例MGUS患者和34例健康对照者的无血小板血浆进行高凝状态检测。

结果

与对照受试者相比,MGUS和MM患者的凝血酶生成和促凝磷脂活性均升高。MM患者以及部分MGUS患者的MV-TF活性增加,然而,只有MM患者的cf-DNA水平升高。

结论

我们在此证明,MGUS和MM患者存在高凝状态,其凝血酶生成增加,可能是由于TF和促凝磷脂(PPL)活性较高。这可能与微泡有关,对于MM患者,可能归因于促凝NETs活性;然而,这仍有待确定。

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