Laine Outi, Joutsi-Korhonen Lotta, Lassila Riitta, Huhtala Heini, Vaheri Antti, Mäkelä Satu, Mustonen Jukka
Department of Internal Medicine, Tampere University Hospital School of Medicine, University of Tampere, Tampere Coagulation Disorders Unit, Clinical Chemistry, HUSLAB Laboratory Services, Helsinki University Hospital Coagulation Disorders Unit, Department of Hematology, Comprehensive Cancer Center, Helsinki University, and Helsinki University Hospital, Helsinki School of Health Sciences, University of Tampere, Tampere Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki.
Medicine (Baltimore). 2016 Dec;95(52):e5689. doi: 10.1097/MD.0000000000005689.
We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease.Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus-induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods. The results were related to data on platelet indices and functions, coagulation variables, and clinical disease.Serum TPO was nearly 4-fold higher acutely compared with the control (median 207 pg/mL, range 56-1258 pg/mL vs. median 58 pg/mL, range 11-241 pg/mL, P < 0.001) and coincided with high mean platelet volume (MPV) and immature platelet fraction (IPF%). Prothrombin fragments and D-dimer were high acutely compared with the control (F1 + 2 median 704 pmol/L, range 284-1875 pmol/L vs. median 249 pmol/L, range 118-556 pmol/L, P < 0.001; D-dimer median 2.8 mg/L, range 0.6-34.0 mg/L vs. median 0.4 mg/L, range 0.2-1.1 mg/L, P < 0.001), and associated with low platelet count and severe acute kidney injury (AKI). MPs' procoagulant activity was high acutely only among patients with mild AKI (plasma creatinine below the median at the time of the measurement).Upregulated TPO together with high MPV and IPF% confirm active thrombopoiesis, but do not predict severity of HFRS. Simultaneously, elevated prothrombin fragments and D-dimer suggest increased consumption of platelets in patients with severe AKI. Activity of platelet-derived MPs in HFRS should be studied with flow cytometry in a larger cohort of patients.
我们评估了一组急性汉坦病毒病患者血小板减少和促凝变化与临床变量相关的机制。前瞻性招募了33例连续住院的急性普马拉病毒引起的肾综合征出血热（HFRS）患者，在急性期和康复期就诊时（对照）采集血样。采用基于酶联免疫吸附测定的方法检测血清血小板生成素（TPO）和来自各种细胞来源的血浆微粒（MPs）活性。结果与血小板指标和功能、凝血变量及临床疾病数据相关。急性期血清TPO比对照高近4倍（中位数207 pg/mL，范围56 - 1258 pg/mL，对照中位数58 pg/mL，范围11 - 241 pg/mL，P < 0.001），且与高平均血小板体积（MPV）和未成熟血小板分数（IPF%）一致。与对照相比，急性期凝血酶原片段和D - 二聚体较高（F1 + 2中位数704 pmol/L，范围284 - 1875 pmol/L，对照中位数249 pmol/L，范围118 - 556 pmol/L，P < 0.001；D - 二聚体中位数2.8 mg/L，范围0.6 - 34.0 mg/L，对照中位数0.4 mg/L，范围0.2 - 1.1 mg/L，P < 0.001），并与低血小板计数和严重急性肾损伤（AKI）相关。MPs的促凝活性仅在轻度AKI患者急性期较高（测量时血浆肌酐低于中位数）。TPO上调以及高MPV和IPF%证实了活跃的血小板生成，但不能预测HFRS的严重程度。同时，凝血酶原片段和D - 二聚体升高表明严重AKI患者血小板消耗增加。应在更大的患者队列中采用流式细胞术研究HFRS中血小板衍生MPs的活性。
