凝血收敛模型下肝素和疫苗诱导血小板减少症的发病机制与临床特征

doi:10.3969/j.issn.1006-5725.2025.18.007

Abstract

Abstract:

The coagulopathy convergence model， by integrating the complex interplay among coagulation， inflammation， and innate immunity， offers novel insights into the intricate pathophysiology of heparin-induced thrombocytopenia （HIT） and vaccine-induced immune thrombotic thrombocytopenia （VITT）， thereby facilitating their differential diagnosis and clinical management. This review systematically outlines the core pathophysiological differences between these two conditions within the framework of the model. Although both disorders involve a platelet factor 4 （PF4）-dependent thrombotic pathway， they demonstrate notable differences in antibody profiles and mechanisms of immune amplification. Recent advances in diagnosis include the rapid diagnostic algorithm TORADI-HIT for HIT and the emerging clinical utility of neutrophil extracellular traps （NETs） as biomarkers for VITT. For refractory and severe cases， in addition to conventional anticoagulant and immunomodulatory therapies， model-guided targeted therapeutic strategies have become a focal point of research， including inhibition of NET formation （NETosis）， blockade of the complement cascade， and modulation of FcγRⅡa signaling. The translational potential of these strategies merits further investigation. Moreover， monitoring NET degradation products and complement activation fragments may aid in optimizing treatment and stratifying prognoses. This review proposes and visually illustrates an integrated "diagnosis-treatment-monitoring" clinical pathway for HIT and VITT， providing a standardized approach for clinical application. The model highlights a key damage-associated molecular patterns （DAMPs）-NETs-immunothrombosis axis， which serves as a crucial framework for understanding and implementing stratified， precision-based interventions in these complex immune-mediated thrombotic disorders.

Key words: convergent coagulation model, heparin-induced thrombocytopenia, vaccine-induced immune thrombotic thrombocytopenia, neutrophil extracellular traps, diagnostic optimization, targeted therapy, clinical pathway?

CLC Number:

R552

Yang ZHOU,Min XIE. Accurate diagnosis and treatment of HIT and VITT under coagulopathy convergence model and clinical pathway transformation[J]. The Journal of Practical Medicine, 2025, 41(18): 2828-2838.

Figures/Tables 4

Fig.1

Tab.1

Tab.2

Fig.2

References 59

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对比维度	HIT	VITT
抗体特性	肝素-PF4构象表位^［12］，多克隆IgG^［1，13］，中等亲和力（Kd ≈ 10^-7 M）^［14］	PF4的线性表位（C端为主），单/寡克隆IgG^{［11-12，15］}，高亲和力（Kd ≈ 10^-9 M）^［14］
免疫复合物	肝素与PF4形成四聚体复合物^［12］，肝素为“分子桥” 稳定结构^［1］	PF4与腺病毒疫苗载体组分（外壳蛋白/游离DNA）组分直接结合^{［12，15］}
血小板活化	需中高浓度PF4，通过FcγRⅡa受体激活血小板，释放PF4/ADP等促凝^{［1，13，16}^-^17］	低PF4浓度高效活化，通过FcγRⅡa受体直接激活血小板， C5a协同增强^{［1，13，15］}
补体激活	局部C3a/C5a激活，增强血栓部位炎症^［1，13］	全身性C5a风暴，加剧微血管损伤^［13］
NETs释放	局部少量，TLR4介导炎症^［1，13］	全身风暴，且瓜氨酸化组蛋白H3（citH3）是HIT约3.9倍（中位数：VITT 4.7 ng/mL vs. HIT 1.2 ng/mL）^［10］
抗体存续	抗体通常在3个月内消退^{［14，18］}	抗体可能持续> 6个月^{［14，18］}

评估项目	2分	1分	0分
血小板减少程度	同时具备下列两者： ?血小板减少> 50% ?最低值≥ 20 × 10⁹/L	具备下列两者之一： ?血小板减少30% ~ 50% ?最低值处于（10 ~ 19）×10⁹/L间	具备下列两者之一： ?血小板减少≤ 30% ?最低值< 10 × 10⁹/L
血小板减少时间	具备下列两者之一： ?使用肝素5 ~ 10 d ?再次接触肝素≤ 1 d（在过去30 d内曾接触肝素）	具备下列两者之一： ?使用肝素> 10 d ?使用肝素≤ 1 d（在过去30 ~ 100 d曾接触肝素）	?使用肝素< 5 d （近期未接触肝素）
血栓形成	?新发的静/动脉血栓 ?皮肤坏死 ?肝素负荷后的急性全身反应	?进展性/复发性血栓形成 ?皮肤红斑 ?疑似血栓（未证实）	无
其他原因的排除	无其他原因	可能存在其他原因	明确存在其他原因

Accurate diagnosis and treatment of HIT and VITT under coagulopathy convergence model and clinical pathway transformation

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