广东省易栓症诊治多学科专家共识

doi:10.3969/j.issn.1009-976X.2023.05.001

摘要/Abstract

摘要： 易栓症（thrombophilia）,是指因各种遗传性或获得性因素导致容易发生血栓形成和血栓栓塞的病理状态,其主要临床结局为静脉血栓栓塞症（venous thromboembolism,VTE）。易栓症导致VTE可能表现为多种形式,如深静脉血栓形成（deep vein thrombosis,DVT）、肺栓塞（pulmonary embolism,PE）、颅内静脉血栓形成（cerebral venous thrombosis, CVT）、门静脉血栓形成（Portal vein thrombosis,PVT）、肠系膜静脉血栓形成（mesenteric vein thrombosis,MVT）等。除此之外,易栓症还可表现为年轻早发的急性冠脉综合征、缺血性卒中等动脉血栓事件。通常可将易栓症分成两大类：遗传性易栓症和获得性易栓症,其中遗传性易栓症为人体自身抗凝或凝血系统等的先天缺陷导致血液处于高凝状态。临床上,易栓症患者往往发病年龄早,而且一旦发病,常导致非常严重的后果。为了提高广东省临床医生对于易栓症及其继发疾病的诊治水平,指导和规范广东省地区各级医院对易栓症的诊治工作,从事血栓相关领域的专家组成多学科协作小组（Multidisciplinary team, MDT）,经过反复研讨,并广泛征求意见,制定本共识,主要针对遗传性易栓症以及特殊易栓人群的诊疗,为易栓症的临床诊疗决策提供参考。本共识将根据国内外研究进展定期修订与更新。

关键词: 易栓症, 凝血功能, 诊治, 共识

Abstract: Thrombophilia refers to a pathological condition where the risk of thrombosis is increased due to various genetic or acquired factors. The main clinical outcome of thrombophilia is venous thromboembolism （VTE）, which can manifest in various forms such as deep vein thrombosis （DVT）, pulmonary embolism （PE）, cerebral venous thrombosis （CVT）, portal vein thrombosis （PVT）, and mesenteric vein thrombosis （MVT）. Moreover, thrombophilia also can cause arterial thrombotic events like early-onset acute coronary syndrome and ischemic stroke. Thrombophilia is typically categorized into two main types,genetic and acquired type. Genetic thrombophilia results from inherent defects in the body's anticoagulation or coagulation system, leading to a hypercoagulable state. Patients with thrombophilia often develop thrombotic condition at a young age, and once it occurs, it can lead to severe consequences. In order to enhance the diagnostic and treatment capabilities of clinical doctors in Guangdong Province and provide guidance and standardization for the diagnosis and treatment of thrombophilia at various levels of hospitals, a multidisciplinary team （MDT） of experts in the field of thrombosis was formed. After extensive discussions and seeking opinions from various sources, this consensus document was developed. It primarily focuses on the diagnosis and treatment of genetic thrombophilia and special population prone to clot formation, aiming to provide guidance for clinical decision-making in the management of thrombophilia. This consensus will be regularly revised and updated based on advances in domestic and international research.

Key words: thrombophilia, coagulation function, diagnosis and treatment, consensus

中图分类号:

R654.3

广东省精准医学会血液分会出凝血青年专委会, 广东省易栓症多学科专家共识编写组. 广东省易栓症诊治多学科专家共识[J]. 岭南现代临床外科, 2023, 23(05): 367-378.

Guangdong Province Precision Medicine Association Hematology Branch Hemostasis Youth Committee, Expert Consensus Writing Group on the Diagnosis, Treatment of Thrombophilia in Guangdong Province. Expert consensus on the diagnosis and treatment of thrombophilia in Guangdong Province[J]. Lingnan Modern Clinics In Surgery, 2023, 23(05): 367-378.

参考文献

[1] Campello E, Spiezia L, Adamo A, Simioni P.Thrombophilia, risk factors and prevention[J]. Expert Rev Hematol, 2019, 12(3): 147-158.
[2] 中华医学会血液学分会血栓与止血学组. 易栓症诊断与防治中国指南(2021年版)[J].中华血液学杂志, 2021, 42(11): 881-888.
[3] Patel RK, Ford E, Thumpston J, Arya R.Risk factors for venous thrombosis in the black population[J]. Thromb Haemost, 2003, 90(5): 835-838.
[4] Bates SM, Middeldorp S, Rodger M, et al.Guidance for the treatment and prevention of obstetric-associated venous thromboembolism[J]. J Thromb Thrombolysis, 2016, 41(1): 92-128.
[5] Franchini M, Veneri D, Salvagno GL, et al.Inherited thrombophilia[J]. Crit Rev Clin Lab Sci, 2006, 43(3): 249-290.
[6] Hotoleanu C.Genetic Risk Factors in Venous Thromboembolism[J]. Adv Exp Med Biol, 2017, 906: 253-272.
[7] Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group. Recommendations from the EGAPP Working Group: routine testing for Factor V Leiden (R506Q) and prothrombin (20210G>A) mutations in adults with a history of idiopathic venous thromboembolism and their adult family members[J]. Genet Med, 2011, 13(1): 67-76.
[8] Pernod G, Biron-Andreani C, Morange PE, et al.Recommendations on testing for thrombophilia in venous thromboembolic disease: a French consensus guideline[J]. J Mal Vasc, 2009, 34(3): 156-203.
[9] Baglin T, Gray E, Greaves M, et al.Clinical guidelines for testing for heritable thrombophilia[J]. Br J Haematol, 2010, 149(2): 209-220.
[10] Ridker PM, Hennekens CH, Lindpaintner K, et al.Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men[J]. N Engl J Med, 1995, 332(14): 912-917.
[11] Poort SR, Rosendaal FR, Reitsma PH, Bertina RM.A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis[J]. Blood, 1996, 88(10): 3698-3703.
[12] Franco RF, Reitsma PH.Genetic risk factors of venous thrombosis[J]. Hum Genet, 2001, 109(4): 369-384.
[13] Rees DC, Cox M, Clegg JB.World distribution of factor V Leiden[J]. Lancet, 1995, 346(8983): 1133-1134.
[14] 朱铁楠, 赵永强, 丁秋兰, 等. 汉族人群蛋白C、蛋白S和抗凝血酶活性水平及活性缺乏发生率的研究[J].中华血液学杂志, 2012, 33(2): 127-130.
[15] Chiasakul T, De Jesus E, Tong J, et al.Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis[J]. J Am Heart Assoc, 2019, 8(19): e012877.
[16] Howard LS, Hughes RJ.NICE guideline: management of venous thromboembolic diseases and role of thrombophilia testing[J]. Thorax, 2013, 68(4): 391-393.
[17] Connors JM.Thrombophilia Testing and Venous Thrombosis[J]. N Engl J Med, 2017, 377(12): 1177-1187.
[18] Graham N, Rashiq H, Hunt BJ.Testing for thrombophilia: clinical update[J]. Br J Gen Pract, 2014, 64(619): e120-122.
[19] Tientadakul P, Chinthammitr Y, Sanpakit K, et al.Inappropriate use of protein C, protein S, and antithrombin testing for hereditary thrombophilia screening: an experience from a large university hospital[J]. Int J Lab Hematol, 2011, 33(6): 593-600.
[20] 丁秋兰, 王学锋. 遗传性易栓症的表型和基因诊断流程[J].诊断学理论与实践, 2019, 18(2): 127-132.
[21] Rothberg JM, Hinz W, Rearick TM, et al.An integrated semiconductor device enabling non-optical genome sequencing[J]. Nature, 2011, 475(7356): 348-352.
[22] 李蕾, 吴希, 许冠群, 等. 基于新一代测序技术的易栓症基因检测Panel的建立及其在中国静脉血栓患者遗传背景研究中的临床应用[J].诊断学理论与实践, 2019, 18(4): 394-401.
[23] Lee EJ, Dykas DJ, Leavitt AD, et al.Whole-exome sequencing in evaluation of patients with venous thromboembolism[J]. Blood Adv, 2017, 1(16): 1224-1237.
[24] 国际血管联盟中国分部护理专业委员会. 住院患者静脉血栓栓塞症预防护理与管理专家共识[J].解放军护理杂志, 2021, 38(6): 17-21.
[25] 陆清声, 张伟, 王筱慧, 等. 上海长海医院院内静脉血栓栓塞症预防指南[J].解放军医院管理杂志, 2018, 25(11): 1032-1037.
[26] Falck-Ytter Y, Francis CW, Johanson NA, et al.Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines[J]. Chest, 2012, 141(2 Suppl): e278S-e325S.
[27] 林小娟, 张进华. 静脉血栓防治相关出血风险评估模型研究进展[J].中国实用外科杂志, 2019, 39(10): 1111-1113.
[28] Skeik N, Westergard E.Recommendations for VTE Prophylaxis in Medically Ill Patients[J]. Ann Vasc Dis, 2020, 13(1): 38-44.
[29] Schulman S, Kakkar AK, Goldhaber SZ, et al.Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis[J]. Circulation, 2014, 129(7): 764-772.
[30] Streiff MB, Holmstrom B, Angelini D, et al.NCCN Guidelines Insights: Cancer-Associated Venous Thromboembolic Disease, Version 2.2018[J]. J Natl Compr Canc Netw, 2018, 16(11): 1289-1303.
[31] 吴丹明, 周玉斌, 汤海涛. 下肢深静脉血栓形成的抗凝治疗及其疗程的探讨[J].中国血管外科杂志(电子版), 2014, (1): 4-6,22.
[32] Garcia D, Erkan D.Diagnosis and Management of the Antiphospholipid Syndrome[J]. N Engl J Med, 2018, 378(21): 2010-2021.
[33] Lijfering WM, Veeger NJ, Middeldorp S, et al.A lower risk of recurrent venous thrombosis in women compared with men is explained by sex-specific risk factors at time of first venous thrombosis in thrombophilic families[J]. Blood, 2009, 114(10): 2031-2036.
[34] Kearon C.Influence of hereditary or acquired thrombophilias on the treatment of venous thromboembolism[J]. Curr Opin Hematol, 2012, 19(5): 363-370.
[35] 中华医学会外科学分会血管外科学组. 深静脉血栓形成的诊断和治疗指南(第三版)[J]. 中国血管外科杂志(电子版), 2017, 9(4): 250-257.
[36] Bates SM, Greer IA, Middeldorp S, et al.VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines[J]. Chest, 2012, 141(2 Suppl): e691S-e736S.
[37] 中华医学会妇产科学分会产科学组. 妊娠期及产褥期静脉血栓栓塞症预防和诊治专家共识[J].中华妇产科杂志, 2021, 56(4): 236-243.
[38] 中华医学会内科学分会, 王建祥, 张奉春, 等. 中国成人血小板减少症诊疗专家共识[J].中华内科杂志, 2020, 59(7): 498-510.
[39] Elsebaie MAT, van Es N, Langston A, et al. Direct oral anticoagulants in patients with venous thromboembolism and thrombophilia: a systematic review and meta-analysis[J]. J Thromb Haemost, 2019, 17(4): 645-656.
[40] Bauersachs RM, Herold J.Oral Anticoagulation in the Elderly and Frail[J]. Hamostaseologie, 2020, 40(1): 74-83.
[41] Papazoglou AS, Moysidis DV, Kartas A, et al.Oral anticoagulation challenges and therapeutic dilemmas in the very elderly: to treat and how to treat octogenarians and nonagenarians?[J]. Pol Arch Intern Med, 2023, 133(6).
[42] 中国老年医学学会重症医学分会, 浙江省重症医学临床医学研究中心. 老年重症患者静脉血栓栓塞症预防中国专家共识(2023)[J].中华危重病急救医学, 2023, 35(6): 561-572.
[43] 王乔宇, 武明芬, 柳鑫, 等. 2021中国静脉血栓栓塞症防治抗凝药物的选用与药学监护指南[J].中国临床药理学杂志, 2021, 37(21): 2999-3016.
[44] Monagle P, Cuello CA, Augustine C, et al.American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism[J]. Blood Adv, 2018, 2(22): 3292-3316.
[45] 戴婷婷, 黄建华, 尹桃,等. 儿童静脉血栓栓塞症的治疗——2018美国血液病学会静脉血栓栓塞管理指南解读[J].中国普通外科杂志,2019, 28(6): 649-653.
[46] 王稳, 胡群. 儿童静脉血栓栓塞的危险因素及抗凝治疗进展[J].中国小儿血液与肿瘤杂志, 2022, 27(5): 340-343.
[47] Male C, Lensing AWA, Palumbo JS, et al.Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial[J]. Lancet Haematol, 2020, 7(1): e18-e27.
[48] 《中国血栓性疾病防治指南》专家委员会. 中国血栓性疾病防治指南[J].中华医学杂志, 2018, 98(36): 2861-2888.
[49] Qamar A, Vaduganathan M, Greenberger NJ, Giugliano RP.Oral Anticoagulation in Patients With Liver Disease[J]. J Am Coll Cardiol, 2018, 71(19): 2162-2175.
[50] Coutinho JM, Ferro JM, Canhão P, et al.Cerebral venous and sinus thrombosis in women[J]. Stroke, 2009, 40(7): 2356-2361.
[51] Farge D, Bounameaux H, Brenner B, et al.International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer[J]. Lancet Oncol, 2016, 17(10): e452-e466.
[52] Lyman GH, Bohlke K, Khorana AA, et al.Venous thromboembolism prophylaxis and treatment in patients with cancer: american society of clinical oncology clinical practice guideline update 2014[J]. J Clin Oncol, 2015, 33(6): 654-656.
[53] Kearon C, Akl EA, Comerota AJ, et al.Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines[J]. Chest, 2012, 141(2 Suppl): e419S-e496S.
[54] Brighton TA, Eikelboom JW, Mann K, et al.Low-dose aspirin for preventing recurrent venous thromboembolism[J]. N Engl J Med, 2012, 367(21): 1979-1987.
[55] Milan M, Noventa F, Ghirarduzzi A, et al.Aspirin and recurrent venous thromboembolism in patients with symptomatic atherosclerosis: retrospective cohort study[J]. J Thromb Haemost, 2012, 10(10): 2205-2206.
[56] Stevens SM, Woller SC, Kreuziger LB, et al.Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report[J]. Chest, 2021, 160(6): e545-e608.
[57] Tektonidou MG, Andreoli L, Limper M, et al.EULAR recommendations for the management of antiphospholipid syndrome in adults[J]. Ann Rheum Dis, 2019, 78(10): 1296-1304.
[58] Legault K, Schunemann H, Hillis C, et al.McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome[J]. J Thromb Haemost, 2018, 16(8): 1656-1664.