免疫介导性血小板减少性血栓性紫癜患者的皮肤微血管低反应性可逆。

Reversible skin microvascular hyporeactivity in patients with immune-mediated thrombocytopenic thrombotic purpura.

机构信息

Intensive Care Unit, Saint-Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France.

Centre de Recherche Saint-Antoine Inserm UMR-S 938, Sorbonne University, 75012, Paris, France.

出版信息

Crit Care. 2023 Mar 21;27(1):116. doi: 10.1186/s13054-023-04405-w.

DOI:10.1186/s13054-023-04405-w

PMID:36944989

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10028781/

Abstract

BACKGROUND

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by arteriolar and capillary microthrombosis precipitating organ failure. However, the contribution of endothelial dysfunction on impaired microvascular blood flow in iTTP patients has been poorly explored. This pilot observational study aimed to explore endothelial-mediated vasoreactivity in iTTP patients at admission and its changes after plasma exchange therapy (PE).

METHODS

We conducted a prospective observational study in patients (> 18-year old) admitted in ICU for iTTP. Using laser Doppler flowmetry and acetylcholine (Ach) iontophoresis in the forearm, we recorded the skin microvascular blood flow and the endothelium-mediated vasoreactivity at admission and after PE. Demographics, biological, clinical courses, and outcomes were also collected. As a control group, we used a previously published cohort of young diabetic patients after correction of ketoacidosis.

RESULTS

Eighteen confirmed iTTP patients and 34 controls were included in the study, mainly female (72%) aged 43 ± 16-year-old. At admission, 55% had neurological abnormalities, 50% cardiac issues and 27.8% an acute kidney injury. Median platelet count was 19 G/mL [10-37]. Baseline microvascular blood flow was decreased in iTTP patients when compared to controls (5.97 ± 4.5 vs. 10.1 ± 6.3 PU, P = 0.03), associated with markedly impaired endothelial-mediated skin microvascular reactivity (AUC: 9627 ± 8122 vs. 16,475 ± 11,738, P = 0.03). Microvascular reactivity improved after the first PE session (AUC: 9627 ± 8122 vs 16,558 ± 10,699, P = 0.007, respectively, baseline and post-PE1) and much more after the second session (26,431 ± 23,181, P = 0.04 post-PE1 vs post-PE2). Hemolysis biomarkers (LDH and bilirubin) negatively correlated with skin microvascular flow and vasoreactivity.

CONCLUSION

We highlighted a marked yet reversible skin endothelium-mediated microvascular hyporeactivity in iTTP patients that could participate in organ injury pathophysiology.

摘要

背景

免疫介导性血栓性血小板减少性紫癜（iTTP）是一种罕见的疾病，其特征为微动脉和毛细血管微血栓形成导致器官衰竭。然而，内皮功能障碍对 iTTP 患者微血管血流受损的贡献仍未得到充分探索。本前瞻性观察性研究旨在探讨 iTTP 患者入院时的内皮介导血管反应性及其在血浆置换治疗（PE）后的变化。

方法

我们对因 iTTP 入住 ICU 的患者（>18 岁）进行了一项前瞻性观察性研究。我们在前臂使用激光多普勒血流仪和乙酰胆碱（Ach）离子电渗法记录皮肤微血管血流和内皮介导的血管反应性，分别在入院时和 PE 后进行。还收集了人口统计学、生物学、临床过程和结局数据。作为对照组，我们使用了以前发表的年轻糖尿病患者在纠正酮症酸中毒后的队列。

结果

本研究共纳入 18 例确诊的 iTTP 患者和 34 例对照，主要为女性（72%），年龄为 43±16 岁。入院时，55%的患者有神经异常，50%有心脏问题，27.8%有急性肾损伤。中位血小板计数为 19 G/mL[10-37]。与对照组相比，iTTP 患者的微血管血流在基线时降低（5.97±4.5 对 10.1±6.3 PU，P=0.03），内皮介导的皮肤微血管反应性明显受损（AUC：9627±8122 对 16475±11738，P=0.03）。第一次 PE 后，微血管反应性改善（AUC：9627±8122 对 16558±10699，P=0.007，分别为基线和第一次 PE 后），第二次 PE 后改善更为明显（26431±23181，P=0.04，第一次 PE 后与第二次 PE 后）。溶血生物标志物（LDH 和胆红素）与皮肤微血管流量和血管反应性呈负相关。