静脉血栓栓塞症潜在生物标志物的研究进展*

doi:10.3969/j.issn.1671-2587.2025.01.019

临床输血与检验 ›› 2025, Vol. 27 ›› Issue (1): 135-139.DOI: 10.3969/j.issn.1671-2587.2025.01.019

静脉血栓栓塞症潜在生物标志物的研究进展^*

马筱洁, 陈伟

新疆维吾尔自治区人民医院输血科,新疆乌鲁木齐 830001

收稿日期:2024-12-05 发布日期:2025-02-25
通讯作者: 陈伟,主要从事输血前相容性检测及血液免疫学方面研究,（E-mail）41821618@qq.com。
作者简介:马筱洁,主要从事临床输血及患者出凝血管理方面研究,（E-mail）611042335@qq.com。
基金资助:
*本课题受新疆维吾尔自治区人民医院院内项目（No. 20230239）资助

Potential Biomarkers Related to Venous Thromboembolism: Current Research Trends

MA Xiaojie, CHEN Wei

Blood Transfusion Department, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001

Received:2024-12-05 Published:2025-02-25

摘要/Abstract

摘要： 静脉血栓栓塞是一种病因复杂多样、症状体征不典型的临床常见血管疾病,以下肢深静脉血栓和肺血栓栓塞为主,早期诊疗对静脉血栓栓塞性疾病预后至关重要。新疆特高海拔地区较多发,受限于一线医疗条件,临床易发生漏诊或误诊。经典D-二聚体与影像学检查的联合应用有助于静脉血栓栓塞性疾病的诊断和评估。可溶性P选择素、血管性血友病因子、血管性血友病因子裂解酶、血栓调节蛋白、C型凝集素样受体2、平足蛋白、血清淀粉样蛋白A、髓样相关蛋白8/14、胞内蛋白Kindlin-3等潜在生物标志物对静脉血栓形成的早期快速诊断、高危人群监测、抗凝溶栓疗效评估有广泛的应用前景和价值。

关键词: 静脉血栓栓塞, 诊断, 生物标志物, 可溶性P选择素, 血管性血友病因子

Abstract: Venous thromboembolism (VTE) is a common vascular diso with complex and diverse etiologies, often presenting with atypical symptoms. The primary manifestations include deep vein thrombosis in the lower extremities and pulmonary thromboembolism. Early diagnosis and timely treatment are crucial for improving the prognosis of VTE. The border defense personnel in Xinjiang, stationed at high altitudes, experience a higher incidence of VTE. Due to limited access to first-line medical resources, clinical misdiagnosis or delayed diagnosis is common. The combined use of D-dimer testing and imaging techniques plays a vital role in the accurate diagnosis and evaluation of VTE. Additionally, potential biomarkers such as von Willebrand factor and soluble P-selectin hold promise for early and rapid diagnosis, monitoring high-risk populations, and assessing the effectiveness of anticoagulant and thrombolytic therapies.

Key words: Venous Thromboembolism, Diagnosis, Biomarkers, SP-selectin, Von Willebrand factor

中图分类号:

R446

马筱洁, 陈伟. 静脉血栓栓塞症潜在生物标志物的研究进展^*[J]. 临床输血与检验, 2025, 27(1): 135-139.

MA Xiaojie, CHEN Wei. Potential Biomarkers Related to Venous Thromboembolism: Current Research Trends[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2025, 27(1): 135-139.

参考文献

[1] ZHANG Z,LEI J P,SHAO X,et al.Trends in hospitalization and in-hospital mortality from VTE,2007 to 2016,in China[J].Chest,2019,155(2):342-353.
[2] VIRANI S S,ALONSO A,BENJAMIN E J,et al.Heart disease and stroke statistics-2020 update:a report from the American heart association[J].Circulation,2020,141(9):e139-e596.
[3] 谢玉海,王学军.高原地区患者术前凝血功能特征及血栓弹力图评估凝血功能的价值研究[J].中国现代医学杂志,2017,27(17):80-83.
[4] 田茂生,张珊珊,丁国良,等. 冰冻血小板收缩功能与P-选择素的相关性研究[J]. 临床输血与检验,2013,15(4):351-352.
[5] RIVA N,VELLA K,HICKEY K,et al.Biomarkers for the diagnosis of venous thromboembolism:d-dimer,thrombin generation,procoagulant phospholipid and soluble P-selectin[J].J Clin Pathol,2018,71(11):1015-1022.
[6] SÁNCHEZ-LÓPEZ V,GAO L,FERRER-GALVÁN M,et al.Differential biomarker profiles between unprovoked venous thromboembolism and cancer[J].Ann Med,2020,52(6):310-320.
[7] SWAMY S,UELAND T,HANSEN J B,et al.Plasma levels of P-selectin and future risk of incident venous thromboembolism[J].J Thromb Haemost,2023,21(9):2451-2460.
[8] CASTELLÓN RUBIO V E,SEGURA P P,MUÑOZ A,et al.High plasma levels of soluble P-Selectin and Factor VIII predict venous thromboembolism in non-small cell lung cancer patients:The Thrombo-Nsclc risk score[J].Thromb Res,2020,196:349-354.
[9] VAN ES N,LOUZADA M,CARRIER M,et al.Predicting the risk of recurrent venous thromboembolism in patients with cancer:a prospective cohort study[J].Thromb Res,2018,163:41-46.
[10] VANDY F C,STABLER C,ELIASSEN A M,et al.Soluble P-selectin for the diagnosis of lower extremity deep venous thrombosis[J].J Vasc Surg Venous Lymphat Disord,2013,1(2):117-1125.
[11] 马焕林,郑毅勇,邱开封,等.血清P选择素、AKP、APCR联合检测对下肢创伤骨折术后深静脉血栓的临床价值研究[J].中国骨与关节杂志,2023,12(6):429-432.
[12] EDVARDSEN M S,HINDBERG K,HANSEN E S,et al.Plasma levels of von Willebrand factor and future risk of incident venous thromboembolism[J].Blood Adv,2021,5(1):224-232.
[13] VAN LOON J,DEHGHAN A,TANG W H,et al.Genome-wide association studies identify genetic loci for low von Willebrand factor levels[J].Eur J Hum Genet,2016,24(7):1096.
[14] IBRAHIM-KOSTA M,BAILLY P,SILVY M,et al.ABO blood group,glycosyltransferase activity and risk of venous thromboembolism[J].Thromb Res,2020,193:31-35.
[15] FRANCHINI M,MARANO G,VAGLIO S,et al.The role of ABO blood type in thrombosis scoring systems[J].Semin Thromb Hemost,2017,43(5):525-529.
[16] JAGAU H,BEHRENS I K,LAHME K,et al.Von willebrand factor mediates pneumococcal aggregation and adhesion in blood flow[J].Front Microbiol,2019,10:511.
[17] GOH C Y,PATMORE S,SMOLENSKI A,et al.The role of von Willebrand factor in breast cancer metastasis[J].Transl Oncol,2021,14(4):101033.
[18] SHETH R A,NIEKAMP A,QUENCER K B,et al.Thrombosis in cancer patients:etiology,incidence,and management[J].Cardiovasc Diagn Ther,2017,7(Suppl 3):S178-S185.
[19] PÉPIN M,KLEINJAN A,HAJAGE D,et al.ADAMTS-13 and von Willebrand factor predict venous thromboembolism in patients with cancer[J].J Thromb Haemost,2016,14(2):306-315.
[20] MIKUŁA T,KOZŁOWSKA J,STAŃCZAK W,et al.Serum ADAMTS-13 levels as an indicator of portal vein thrombosis[J].Gastroenterol Res Pract,2018,2018:3287491.
[21] SINGH K,KWONG A C,MADARATI H,et al.Characterization of ADAMTS13 and von Willebrand factor levels in septic and non-septic ICU patients[J].PLoS One,2021,16(2):e0247017.
[22] TAN Y,LUAN Z Q,HAO J B,et al.Plasma ADAMTS-13 activity in proliferative lupus nephritis:a large cohort study from China[J].Lupus,2018,27(3):389-398.
[23] PAGLIARI M T,BOSCARINO M,CAIRO A,et al.ADAMTS13 activity,high VWF and FVIII levels in the pathogenesis of deep vein thrombosis[J].Thromb Res,2021,197:132-137.
[24] SUZUKI J,NAMISAKI T,TAKYA H,et al.ADAMTS-13:a prognostic biomarker for portal vein thrombosis in Japanese patients with liver cirrhosis[J].Int J Mol Sci,2024,25(5):2678.
[25] SUGIYAMA S,HIROTA H,KIMURA R,et al.Haplotype of thrombomodulin gene associated with plasma thrombomodulin level and deep vein thrombosis in the Japanese population[J].Thromb Res,2007,119(1):35-43.
[26] TANG L,WANG H F,LU X,et al.Common genetic risk factors for venous thrombosis in the Chinese population[J].Am J Hum Genet,2013,92(2):177-187.
[27] D'APOLITO M,ARIANO A,D’ANDREA G,et al.Identification of the novel G250R variant indicates a role for thrombomodulin in modulating the risk for venous thromboembolism[J].Thromb Haemost,2022,122(10):1827-1832.
[28] VIJAY A,JHA P K,PARVEEN S,et al.Aberrant promoter hypermethylation regulates thrombomodulin in high altitude induced deep vein thrombosis[J].Thromb Res,2022,215:5-13.
[29] SUZUKI-INOUE K,OSADA M,OZAKI Y.Physiologic and pathophysiologic roles of interaction between C-type lectin-like receptor 2 and podoplanin:partners from in utero to adulthood[J].J Thromb Haemost,2017,15(2):219-229.
[30] NAGAE M,MORITA-MATSUMOTO K,KATO M,et al.A platform of C-type lectin-like receptor CLEC-2 for binding O-glycosylated podoplanin and nonglycosylated rhodocytin[J].Structure,2014,22(12):1711-1721.
[31] ASTARITA J L,ACTON S E,TURLEY S J.Podoplanin:emerging functions in development,the immune system,and cancer[J].Front Immunol,2012,3:283.
[32] PAYNE H,PONOMARYOV T,WATSON S P,et al.Mice with a deficiency in CLEC-2 are protected against deep vein thrombosis[J].Blood,2017,129(14):2013-2020.
[33] HITCHCOCK J R,COOK C N,BOBAT S,et al.Inflammation drives thrombosis after Salmonella infection via CLEC-2 on platelets[J].J Clin Invest,2015,125(12):4429-4446.
[34] RIEDL J,PREUSSER M,NAZARI P M S,et al.Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism[J].Blood,2017,129(13):1831-1839.
[35] TSUKIJI N,OSADA M,SASAKI T,et al.Cobalt hematoporphyrin inhibits CLEC-2-podoplanin interaction,tumor metastasis,and arterial/venous thrombosis in mice[J].Blood Adv,2018,2(17):2214-2225.
[36] SONG C J,SHEN Y,YAMEN E,et al.Serum amyloid A may potentiate prothrombotic and proinflammatory events in acute coronary syndromes[J].Atherosclerosis,2009,202(2):596-604.
[37] PAGE M J,THOMSON G J A,NUNES J M,et al.Serum amyloid A binds to fibrin(ogen),promoting fibrin amyloid formation[J].Sci Rep,2019,9(1):3102.
[38] DEGUCHI H,ELIAS D J,NAVARRO S,et al.Elevated serum amyloid A is associated with venous thromboembolism[J].Thromb Haemost,2013,109(2):358-359.
[39] 关羽茜,孔妍,胡亚欣,等.血清Hcy、SAA对脑卒中患者深静脉血栓形成的早期预测价值[J].脑与神经疾病杂志,2023,31(7):434-438.
[40] CROCE K,GAO H Y,WANG Y M,et al.Myeloid-related protein-8/14 is critical for the biological response to vascular injury[J].Circulation,2009,120(5):427-436.
[41] MARTA-ENGUITA J,NAVARRO-OVIEDO M,RUBIO-BAINES I,et al.Association of calprotectin with other inflammatory parameters in the prediction of mortality for ischemic stroke[J].J Neuroinflammation,2021,18(1):3.
[42] KAWANO T,SHIMAMURA M,NAKAGAMI H,et al.Therapeutic vaccine against S100A9(S100 calcium-binding protein A9)inhibits thrombosis without increasing the risk of bleeding in ischemic stroke in mice[J].Hypertension,2018,72(6):1355-1364.
[43] WANG Y M,GAO H Y,KESSINGER C W,et al.Myeloid-related protein-14 regulates deep vein thrombosis[J].JCI Insight,2017,2(11):e91356.
[44] JOO S J.Mechanisms of platelet activation and integrin αIIβ3[J].Korean Circ J,2012,42(5):295-301.
[45] MOSER M,NIESWANDT B,USSAR S,et al.Kindlin-3 is essential for integrin activation and platelet aggregation[J].Nat Med,2008,14(3):325-330.
[46] KUIJPERS T W,VAN DE VIJVER E,WETERMAN M A J,et al.LAD-1/variant syndrome is caused by mutations in FERMT3[J].Blood,2009,113(19):4740-4746.
[47] KRAEMER B F,GEIMER M,FRANZ-WACHTEL M,et al.Extracellular matrix-specific platelet activation leads to a differential translational response and protein de novo synthesis in human platelets[J].Int J Mol Sci,2020,21(21):8155.
[48] YAN Y Y,YANG H Q,HU X,et al.Kindlin-3 in platelets and myeloid cells differentially regulates deep vein thrombosis in mice[J].Aging(Albany NY),2019,11(17):6951-6959.
[49] 尤来委,程勇,郭建荣.ABO血型对癌症患者静脉血栓栓塞症影响的研究进展[J].临床输血与检验,2023,25(6):857-861.
[50] ANGELINI D E,RADIVOYEVITCH T,MCCRAE K R,et al.Bleeding incidence and risk factors among cancer patients treated with anticoagulation[J].Am J Hematol,2019,94(7):780-785.
[51] 周敏,胡大春.血小板模式识别受体在固有免疫应答与血栓形成中的作用研究进展[J].临床输血与检验,2022,24(1):126-131.

静脉血栓栓塞症潜在生物标志物的研究进展^*

Potential Biomarkers Related to Venous Thromboembolism: Current Research Trends

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