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中华卫生应急电子杂志 ›› 2023, Vol. 09 ›› Issue (06) : 321 -332. doi: 10.3877/cma.j.issn.2095-9133.2023.06.001

专家共识

脓毒症相关的血小板减少症临床诊疗中国专家共识
脓毒症相关的血小板减少症临床诊疗中国专家共识专家组   
  • 收稿日期:2023-07-19 出版日期:2023-12-18

Chinese expert consensus on the clinical diagnosis and treatment of sepsis induced thrombocytopenia

Task Force on Chinese expert consensus on the clinical diagnosis and treatment of sepsis induced thrombocytopenia   

  • Received:2023-07-19 Published:2023-12-18
引用本文:

脓毒症相关的血小板减少症临床诊疗中国专家共识专家组. 脓毒症相关的血小板减少症临床诊疗中国专家共识[J]. 中华卫生应急电子杂志, 2023, 09(06): 321-332.

Task Force on Chinese expert consensus on the clinical diagnosis and treatment of sepsis induced thrombocytopenia. Chinese expert consensus on the clinical diagnosis and treatment of sepsis induced thrombocytopenia[J]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2023, 09(06): 321-332.

血小板减少症是指外周血中血小板计数(platelet,PLT)<100×109/L而引起的临床综合征。据报道有13.0%~44.1%的重症患者可能发生血小板减少症,且血小板减少的程度是重症患者预后的重要预测指标之一[1,2]。重症患者发生血小板减少症的原因众多,其中脓毒症相关血小板减少症(sepsis induced thrombocytopenia,SIT)最为常见,约占50%。SIT的发生不仅延长重症患者ICU住院时间、机械通气时间及血管活性药物使用时间,还可导致出血相关性不良事件及全因病死率增加。目前,尚缺乏SIT的监测、诊断及治疗规范。因此,中华医学会重症医学分会组织专家制订《脓毒症相关的血小板减少症临床诊疗中国专家共识》,以期对此疾病进行规范化管理。

表1 根据GRADE方法提出的共识推荐建议
表2 血小板减少数量与严重程度分级
表3 SIT发生的主要机制
机制类型 病理生理过程
血小板生成减少 血小板由骨髓中的巨核细胞产生,受肝脏所产生的TPO调节。脓毒症导致单核细胞和巨噬细胞对巨核细胞和其他造血细胞的主动吞噬作用,导致血小板生成减少
血小板消耗和破坏增加 脓毒症的病原微生物及其产物通过介导释放多种炎症因子损伤血管内皮、激活血小板。血小板附着在血管内皮细胞上,进而激活凝血系统,刺激纤溶酶原激活物抑制物释放,抑制纤溶系统,造成DIC,进而导致血小板的大量消耗[1]。细菌及代谢产物通过免疫途径激活补体、破坏血小板,在部分患者体内可出现抗血小板自身抗体,导致血小板与抗体结合,进而免疫识别,使得消耗增加
血小板丢失增加 脓毒症患者发生各种原因的活动性出血,包括手术、消化道应激性溃疡出血,以及女性患者月经期的出血,均可导致血小板减少。体外循环、体外膜肺氧合、血液净化治疗(全血灌流、血液滤过等)治疗过程中损失血液成分,是造成血小板减少的重要因素
血小板在脾脏的集聚 脾脏内储存的血小板占血液中的1/3,输注血小板后,也会有约30%的血小板储存于脾脏中。脓毒症患者的血小板可因通过脾索的速度减慢致使血小板接触脾巨噬细胞的时间延长,加上淤血等因素造成血小板形态改变,脾脏还分泌抑制血小板从骨髓释放的因子,综合造成脾脏对血小板的集聚、扣押和隔离,使得外周血中血小板减少。脓毒症引发的全身炎症状态下,血小板可向肺毛细血管和肝血窦迁移并被扣押和聚集,进一步导致血小板减少
表4 SIT相关的风险因素
表5 脓毒症诱导的凝血功能障碍诊断评分
表6 SIT患者出血风险因素评分表
表7 ICU血小板减少症发生的主要机制和临床诊断思路
血小板减少症发生机制 病史/临床诊断思路
假性血小板减少  
EDTA抗凝血中血小板聚集;接受GPⅡbⅢ a拮抗剂治疗 非预计或无法解释的血小板减少且无出血症状;既往使用过GP Ⅱ b Ⅲ a受体拮抗剂
血液稀释  
输注液体和(或)血浆 大量输液/输血
血小板耗竭  
失血 出血或凝血因子丢失
严重创伤 病史、体格检查及放射学检查
DIC 各种原因的休克、严重感染、产科并发症或其他的潜在因素表现为凝血时间延长,纤维蛋白分解产物增多,识别出有核红细胞
脓毒症 脓毒症相关标准及病原学指标
体外血管通路 治疗需要使用体外血管通路
血小板滞留(扣押)  
肝脾肿大 病史、特有的伴随疾病(如肝硬化或骨髓纤维瘤),以及超声或放射学诊断
血小板生成减少  
中毒 滥用或服用药物史;可进行毒物鉴定
病毒感染(EBV、CMV、COVID-19) 病毒感染的相关依据
骨髓浸润(白血病、肿瘤) 骨髓检查、血涂片发现相应疾病改变
辐射 相应病史
化疗 相应病史
血小板破坏  
ITP 血清或血小板表面有IgG抗体,脾脏无明显肿大,骨髓中巨核细胞正常或增加;糖皮质激素治疗有效
药物依赖性血小板减少性紫癜 药物史(发病前7~14 d使用过新的药物)、PLT<20×109/L、停用可疑或检测到的药物后PLT增加、确认存在药物依赖性证据
肝素诱导性血小板减少 使用肝素治疗后5~14 d PLT减少50%(最低可达20×109/L~80×109/L),PF4抗体/肝素抗体阳性
血栓性微血管病(TTP、HUS、HELLP综合征) 溶血且直接抗球蛋白试验阴性、血涂片可见碎裂红细胞、通常PLT低至10×109/L~30×109/L、血栓事件伴随神经(TTP)或肾(HUS)症状、妊娠(HELLP综合征)、乳酸脱氢酶升高
输血后紫癜 输血史、PLT低至<10×109/L、出血症状、高滴度HPA-1a抗体
被动同种免疫性血小板减少 输入(尤其是经产献血者的)含血制品后(被动传递同种血小板抗体)血小板突然、迅速下降
表8 与SIT最需要鉴别的常见重症疾病
疾病名称 引起血小板减少的机制 诊断与鉴别要点
TTP 主要以终末小动脉与毛细血管形成透明血栓为发病机制,血小板消耗性减少 好发年龄为10~40岁,临床上表现为三联征(微血管病溶血性贫血、血小板减少、神经精神异常)或五联征(三联征+发热、肾脏损害)
自身免疫性疾病    
系统性红斑狼疮 主要因血清中存在抗血小板抗体以及抗磷脂抗体和骨髓巨核细胞成熟障碍有关 好发于青年女性,临床主要表现为面部蝶形红斑,可伴发热、关节痛、肾脏及心血管系统损害,也可表现为间质性肺炎。血清学检查、皮肤及肾活检有助于诊断
抗磷脂综合征 反复动脉或者静脉血栓形成引起血小板消耗性减少 女性发病多见,主要临床表现为反复动脉、静脉血栓形成、习惯性流产及血小板减少;抗心磷脂或狼疮抗凝物实验持续阳性。依据临床表现及实验室检查可诊断
自身免疫性甲亢 甲亢代谢旺盛,能量物消耗过多,铁、维生素、叶酸产生不足,使血小板生成减少;亦可因过多的甲状腺素损伤干细胞,影响血小板生成 好发年龄为20~40岁,常伴弥漫性、对称性甲状腺肿大;有心慌、多汗、眼球突出、舌手震颤等表现,依据临床表现、甲状腺功能检测及TSAb检测可明确诊断
HIT 抗体-肝素-PF4形成的免疫复合物激活血小板,产生促凝物质,血小板消耗性减少 有应用肝素的药物史,停用肝素后数日血小板及凝血变化可得到纠正;肝素依赖性抗血小板抗体检测阳性。结合病史及实验室检查可诊断
HELLP综合征 血管内皮细胞受损,激活血小板,使血小板消耗性减少;PGⅠ2合成减少与血小板激活释放TXA2,使血管进一步痉挛和血小板聚集消耗 为妊娠期高血压疾病的严重并发症,临床上以溶血、肝酶升高和血小板减少为特点;早期应用糖皮质激素及配合应用血制品为主要治疗手段。可依据病史及临床表现诊断
嗜血综合征 感染、肿瘤、免疫介导性疾病等引起嗜血细胞增多,加速血细胞破坏,使血小板破坏性减少 该病的特征为:发热、肝脾肿大伴全血细胞减少、骨髓及脾脏或者淋巴结可见嗜血细胞但无恶性表现、NK细胞活性降低或缺乏、高铁蛋白血症、可溶性白介素受体水平升高
成人原发免疫性血小板减少症 患者对自身抗原的免疫失耐受,导致免疫介导的血小板破坏增多和免疫介导的巨核细胞产生血小板不足 60岁以上人群为高发群体,临床表现为皮肤黏膜出血,严重者有内脏出血甚至颅内出血。诊断为排除性诊断,血小板抗体及TPO检测有助于鉴别诊断
表9 引起血小板减少的常见药物
表10 WHO出血分级标准
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