（血液）高凝状态

所有患者都应该评估。

不明原因的贫血可能与恶性肿瘤有关。[50]Trujillo-Santos J, Prandoni P, Rivron-Guillot K, et al. Clinical outcome in patients with venous thromboembolism and hidden cancer: findings from the RIETE Registry. J Thromb Haemost. 2008;6:251-255.http://www.ncbi.nlm.nih.gov/pubmed/18021305?tool=bestpractice.com

不明原因细胞压积或白细胞或血小板计数持续性升高可能表明骨髓增殖性疾病。[105]Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood. 2007;110:1092-1097.http://www.bloodjournal.org/content/110/4/1092http://www.ncbi.nlm.nih.gov/pubmed/17488875?tool=bestpractice.com

肝素治疗后 5 到 10 天血小板计数下降 30% 到 50% 可能提示肝素引起的血小板减少症。[102]Middeldorp S, van Hylckama Vlieg. Does thrombophilia testing help in the clinical management of patients? Br J Haematol. 2008;143:321-335.http://www.ncbi.nlm.nih.gov/pubmed/18710381?tool=bestpractice.com血小板减少是弥散性血管内凝血的常见特点。血小板减少是 DIC 的常见特点。[70]Levi M, Toh CH, Thachil J, et al. Guidelines for the diagnosis and management of disseminated intravascular coagulation. British Committee for Standards in Haematology. Br J Haematol. 2009;145:24-33.http://www.ncbi.nlm.nih.gov/pubmed/19222477?tool=bestpractice.com

贫血：红细胞压积 (PCV)；白细胞升高；血小板升高或减少

如果怀疑溶血性贫血或慢性DIC或者全血细胞计数提示不正常时进行。

微血管病性溶血性贫血的特点包括与血小板减少症相关的红细胞破碎。

全血细胞减少和巨红细胞可提示阵发性睡眠性血红蛋白尿症。

红细胞碎片、球形红细胞、血小板减少、全血细胞减少或巨红细胞可提示基本病理变化；在镰状细胞贫血中可见有核红细胞、镰状红细胞和 Howell-Jolly 小体。

应对疑似高凝状态的病例进行评估。

活化部分凝血活酶时间 (aPTT) 延长(使用对狼疮抗凝物敏感的凝血活酶)可能提示存在潜在的狼疮抗凝物。

停止抗凝治疗后 aPTT（活化部分凝血活酶时间）减少可能与静脉血栓栓塞反复发作风险增加 2 倍有关。[106]Legnani C, Mattarozzi S, Cini M, et al. Abnormally short activated partial thromboplastin time values are associated with increased risk of recurrence of venous thromboembolism after oral anticoagulation withdrawal. Br J Haematol. 2006;134:227-232.http://www.ncbi.nlm.nih.gov/pubmed/16846482?tool=bestpractice.com

活化部分凝血活酶时间缩短反应了因子 IX、VIII 和 XI 水平增加。

aPTT 延长结合其他临床特点可支持 DIC 的诊断。[106]Legnani C, Mattarozzi S, Cini M, et al. Abnormally short activated partial thromboplastin time values are associated with increased risk of recurrence of venous thromboembolism after oral anticoagulation withdrawal. Br J Haematol. 2006;134:227-232.http://www.ncbi.nlm.nih.gov/pubmed/16846482?tool=bestpractice.com

开始抗凝之前应该测出一个基线值。

柠檬酸盐抗凝管采血过多或不足可能导致错误的结果。

减少或延长

应对疑似高凝状态的病例进行评估。

水平下降结合其他临床特点支持 DIC 或异常纤维蛋白原血症的诊断。[22]Acharya SS, Dimichele DM. Rare inherited disorders of fibrinogen. Haemophilia. 2008;14:1151-1158.http://www.ncbi.nlm.nih.gov/pubmed/19141154?tool=bestpractice.com[107]Toh CH, Hoots WK. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview. J Thromb Haemost. 2007;5:604-606.http://www.ncbi.nlm.nih.gov/pubmed/17096704?tool=bestpractice.com

水平增高同罹患静脉血栓栓塞的风险增加两倍相关。[77]Cosman F, Lindsay R. Selective estrogen receptor modulators: clinical spectrum. Endocr Rev. 1999;20:418-434.http://press.endocrine.org/doi/full/10.1210/edrv.20.3.0371http://www.ncbi.nlm.nih.gov/pubmed/10368777?tool=bestpractice.com

纤维蛋白原升高与血栓前状态有关；纤维蛋白原降低可能提示潜在的 DIC 或异常纤维蛋白原血症。

应对疑似高凝状态的病例进行评估。

有其他支持性证据（如，aPTT 延长、血小板计数低、纤维蛋白原低、D-二聚体高）和与 PT 延长相关的疾病情形存在时，凝血酶原时间延长提示 DIC。[107]Toh CH, Hoots WK. The scoring system of the Scientific and Standardisation Committee on Disseminated Intravascular Coagulation of the International Society on Thrombosis and Haemostasis: a 5-year overview. J Thromb Haemost. 2007;5:604-606.http://www.ncbi.nlm.nih.gov/pubmed/17096704?tool=bestpractice.com

存在狼疮抗凝物时很少出现延长。

开始抗凝之前应该测出一个基线值。

柠檬酸盐抗凝管采血过多或不足可能导致错误的结果。

延长

应对疑似高凝状态的病例进行评估。D-二聚体的升高与急性静脉性血栓 (VTE) 相关（且并不确定存在潜在高凝状态）。

纤维溶解蛋白的标记；升高可能表明凝血系统的激活。

水平升高与静脉血栓栓塞首发风险增加超过 2 倍有关。[108]Andreescu AC, Cushman M, Rosendaal FR. D-dimer as a risk factor for deep vein thrombosis: the Leiden Thrombophilia Study. Thromb Haemost. 2002;87:47-51.http://www.ncbi.nlm.nih.gov/pubmed/11858188?tool=bestpractice.com

抗凝治疗结束后或D-二聚体水平正常者静脉血栓栓塞复发风险低。[91]Eichinger S, Minar E, Bialonczyk C, et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA. 2003;20:1071-1074.http://www.ncbi.nlm.nih.gov/pubmed/12941680?tool=bestpractice.com[92]Palareti G, Legnani C, Cosmi B, et al. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost. 2002;87:7-12.http://www.ncbi.nlm.nih.gov/pubmed/11848459?tool=bestpractice.com抗凝血治疗后D-二聚体水平升高可以预测静脉血栓栓塞复发的高风险。[91]Eichinger S, Minar E, Bialonczyk C, et al. D-dimer levels and risk of recurrent venous thromboembolism. JAMA. 2003;20:1071-1074.http://www.ncbi.nlm.nih.gov/pubmed/12941680?tool=bestpractice.com[92]Palareti G, Legnani C, Cosmi B, et al. Risk of venous thromboembolism recurrence: high negative predictive value of D-dimer performed after oral anticoagulation is stopped. Thromb Haemost. 2002;87:7-12.http://www.ncbi.nlm.nih.gov/pubmed/11848459?tool=bestpractice.com

可作为临床风险评分的一个部分辅助鉴别那些能从延长抗凝治疗中获益的妇女，但需要进一步的临床研究。[90]Rodger MA, Kahn SR, Wells PS, et al. Identifying unprovoked thromboembolism at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ. 2008;179:417-426.http://www.cmaj.ca/content/179/5/417.fullhttp://www.ncbi.nlm.nih.gov/pubmed/18725614?tool=bestpractice.com

正常或升高

怀疑有高凝状态的人应进行评估以检查是否有肾病综合征的可能性。

水平减少提示肾病综合征。

肾病综合征中水平降低

怀疑有高凝状态的人应进行评估以检查是否有肾病综合征的可能性。

升高提示肾病综合征。

肾病综合征中升高

怀疑有高凝状态的人应进行评估以检查是否有肾病综合征的可能性。

升高提示肾病综合征。

肾病综合征中升高

怀疑有高凝状态的人应进行评估以检查是否有肾病综合征的可能性。

升高提示肾病综合征。

肾病综合征中升高

静脉血栓栓塞首次发病年龄＜ 50岁，无诱因（特发性）或复发性静脉血栓栓塞，少见部位血栓形成，新生儿暴发性紫癜，华法林诱发的皮肤坏死。[110]Grody WW, Griffin JH, Taylor AK, et al. American College of Medical Genetics Consensus Statement on factor V Leiden mutation testing. Genet Med. 2001;3:139-148.http://www.ncbi.nlm.nih.gov/pubmed/11280951?tool=bestpractice.com[111]Press RD, Bauer KA, Kujovich JL, et al. Clinical utility of factor V Leiden (R506Q) testing for diagnosis and management of thromboembolic disorders. Arch Pathol Lab Med. 2002;126:1304-1318.http://www.ncbi.nlm.nih.gov/pubmed/12421138?tool=bestpractice.com

对于有静脉血栓栓塞家族史的患者，尤其是一级亲属年轻发病史的也应该考虑。

基本的测试包括蛋白 C，抗凝血酶活性，游离蛋白 S，活化蛋白 C 抵抗和 PCR 检测凝血酶原基因突变 (G-20210-A)。

活化蛋白 C 抵抗可以用作凝血因子 V Leiden 的筛查试验，如果检测到，应该积极检测基因型。[103]Heit JA. Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007;127-135.http://asheducationbook.hematologylibrary.org/cgi/content/full/2007/1/127http://www.ncbi.nlm.nih.gov/pubmed/18024620?tool=bestpractice.com获得性活化蛋白C抵抗可能与妊娠，雌激素治疗，和凝血因子 VIII 水平升高有关。[116]Clark P, Walker ID. The phenomenon known as acquired activated protein C resistance. Br J Haematol. 2001;115:767-773.http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2141.2001.03203.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/11843807?tool=bestpractice.com

没有很强的临床指征，儿童检测更应该避免。[3]Baglin T, Gray E, Greaves M, et al; British Committee for Standards in Haematology. Clinical guidelines for testing for heritable thrombophilia. Br J Haematol. 2010;149:209-220.http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2009.08022.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/20128794?tool=bestpractice.com

最好推迟到抗凝治疗完成后 4-6 周。

遗传性易栓症阳性

易栓症试验显示样本活化的蛋白 C 抵抗减少或有凝血因子 V Leiden 突变家族史时应该检测基因型。[103]Heit JA. Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007;127-135.http://asheducationbook.hematologylibrary.org/cgi/content/full/2007/1/127http://www.ncbi.nlm.nih.gov/pubmed/18024620?tool=bestpractice.com

阳性

当考虑系统性红斑狼疮或抗磷脂综合征或检测显示活化部分凝血活酶时间 (aPTT) 延长时评估。

狼疮抗凝剂试验应该包括敏感的活化部分凝血酶原时间和稀释印度蝰蛇毒时间两个试验。稀释印度蝰蛇毒时间延长应该进一步评估磷脂的存在证实狼疮抗凝物的存在。其他试验不再推荐。[117]Pengo V, Tripodi A, Reber G, et al; Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost. 2009;7:1737-1740.http://onlinelibrary.wiley.com/doi/10.1111/j.1538-7836.2009.03555.x/fullhttp://www.ncbi.nlm.nih.gov/pubmed/19624461?tool=bestpractice.com

发现多达 20% 的静脉血栓栓塞患者在发生之前就有抗心磷脂抗体水平增高。[60]Ginsburg KS, Liang MH, Newcomer L, et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med. 1992;117:997-1002.http://www.ncbi.nlm.nih.gov/pubmed/1443986?tool=bestpractice.com

应该检测狼疮抗凝剂，抗心磷脂抗体，β-2 糖蛋白 1 抗体。

除了临床标准外，还需要间隔至少12周的2次重复的阳性结果才能确诊抗磷脂综合征。[112]Cornuz J, Pearson SD, Creager MA, et al. Importance of findings on the initial evaluation for cancer in patients with symptomatic idiopathic deep venous thrombosis. Ann Intern Med. 1996;125:785-793.http://www.ncbi.nlm.nih.gov/pubmed/8928984?tool=bestpractice.com

阳性

认为患者有静脉血栓栓塞风险时偶有测量。

它对高凝固性的作用是有争议的；可能不会增加 VTE 易感性。[36]Den Heijer M, Lewington S, Clarke R. Homocysteine, MTHFR and risk of venous thrombosis: a meta-analysis of published epidemiological studies. J Thromb Haemost. 2005;3:292-299.http://www.ncbi.nlm.nih.gov/pubmed/15670035?tool=bestpractice.com[37]Bezemer ID, Doggen CJM, Vos HL, et al. No association between the common MTHFR 677C->T polymorphism and venous thrombosis: results from the MEGA Study. Arch Intern Med. 2007;167:497-501.http://archinte.jamanetwork.com/article.aspx?articleid=769649http://www.ncbi.nlm.nih.gov/pubmed/17353498?tool=bestpractice.com

异常结果应该重复检测确定。[103]Heit JA. Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007;127-135.http://asheducationbook.hematologylibrary.org/cgi/content/full/2007/1/127http://www.ncbi.nlm.nih.gov/pubmed/18024620?tool=bestpractice.com

升高

偶尔检测。

是黑人中血栓形成风险最重要的实验室检测指标。[15]Patel RK, Ford E, Thumpston J, et al. Risk factors for venous thrombosis in the black population. Thromb Haemost. 2003;90:835-838.http://www.ncbi.nlm.nih.gov/pubmed/14597978?tool=bestpractice.com

水平高于150U/升，静脉血栓栓塞的首发风险高达 10 倍，复发风险高达 6 倍。[31]Koster T, Blann AD, Briet E, et al. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet. 1995;345:152-155.http://www.ncbi.nlm.nih.gov/pubmed/7823669?tool=bestpractice.com[32]Kraaijenhagen RA, in't Anker PS, Koopman MM, et al. High plasma concentration of factor VIIIc is a major risk factor for venous thromboembolism. Thromb Haemost. 2000;83:5-9.http://www.ncbi.nlm.nih.gov/pubmed/10669145?tool=bestpractice.com[33]Kyrle PA, Minar E, Hirschl M, et al. High plasma levels of factor VIII and the risk of recurrent venous thromboembolism. N Engl J Med. 2000;343:457-462.http://www.ncbi.nlm.nih.gov/pubmed/10950667?tool=bestpractice.com

[103]Heit JA. Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007;127-135.http://asheducationbook.hematologylibrary.org/cgi/content/full/2007/1/127http://www.ncbi.nlm.nih.gov/pubmed/18024620?tool=bestpractice.com急性血栓形成时应避免检测。

升高

考虑红细胞增多，原因不明血小板减少，内脏静脉血栓形成时可进行该检查。

95% 的真性红细胞增多症的患者和高达 60% 的原发性血小板增多症患者中发现。[64]Campbell PJ, Green AR. The myeloproliferative disorders. N Engl J Med. 2006;355:2452-2466.http://www.ncbi.nlm.nih.gov/pubmed/17151367?tool=bestpractice.com

隐匿性骨髓增生异常可表现为内脏静脉血栓形成，高达 59% 的患者存在 JAK2 突变。[63]Hexner EO. JAK2 V617F: implications for thrombosis in myeloproliferative diseases. Curr Opin Hematol. 2007;14:450-454.http://www.ncbi.nlm.nih.gov/pubmed/17934351?tool=bestpractice.com[114]Patel RK, Lea NC, Heneghan MA, et al. Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari Syndrome. Gastroenterology. 2006;130:2031-2038.http://www.ncbi.nlm.nih.gov/pubmed/16762626?tool=bestpractice.com

目前

伴有全血细胞减少和或溶血性贫血的患者可以考虑。

诊断PNH并检测其克隆比例的理想检查。[72]Hill A, Richards SJ, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2007;137:181-192.http://www.ncbi.nlm.nih.gov/pubmed/17408457?tool=bestpractice.com

多色分析可以发现低至0.01%的小克隆。[113]Richards SJ, Hill A, Hillmen P. Recent advances in the diagnosis, monitoring, and management of patients with paroxysmal nocturnal hemoglobinuria. Cytometry B Clin Cytom. 2007;72:291-298.http://onlinelibrary.wiley.com/doi/10.1002/cyto.b.20358/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17549742?tool=bestpractice.com

阳性

临床特征未提示该诊断时应避免检测。

应使用” 4T 评分“对验前概率进行评估，包括肝素使用后血小板计数下降的时间，血小板计数从基线降到最低点变化的百分比，有无血栓形成，缺乏血小板减少症的替代诊断。[74]Linkins LA, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(suppl 2):e495S-e530S.http://journal.publications.chestnet.org/article.aspx?articleID=1159542http://www.ncbi.nlm.nih.gov/pubmed/18574270?tool=bestpractice.com

血小板活化分析的灵敏度为 85%，经验丰富的实验室可通过使用洗涤后的血小板提高检测的灵敏度。

ELISA（酶联免疫吸附试验）检测 IgG 灵敏度高（80% 到 100%），但是特异度低。

结果应结合所选试验方法和验前概率进行解释。[115]Watson H, Davidson S, Keeling D; Haemostasis and Thrombosis Task Force of the British Committee for Standards in Haematology. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol. 2012;159:528-540.http://onlinelibrary.wiley.com/doi/10.1111/bjh.12059/fullhttp://www.ncbi.nlm.nih.gov/pubmed/23043677?tool=bestpractice.com

抗体发病率

不明原因出现的（特发性）静脉血栓栓塞都应该进行以排除恶性肿瘤。[112]Cornuz J, Pearson SD, Creager MA, et al. Importance of findings on the initial evaluation for cancer in patients with symptomatic idiopathic deep venous thrombosis. Ann Intern Med. 1996;125:785-793.http://www.ncbi.nlm.nih.gov/pubmed/8928984?tool=bestpractice.com

存在肺结节，胸腔积液或纵隔异常可能提示潜在的恶性肿瘤

疑似恶性肿瘤患者。

显著增加恶性肿瘤的检出率。[52]Carrier M, Le Gal G, Wells PS, et al. Systematic review: the Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism? Ann Intern Med. 2008;149:323-333.http://www.ncbi.nlm.nih.gov/pubmed/18765702?tool=bestpractice.com

对潜伏性恶性肿瘤的检出优于腹部超声和肿瘤标志物检测。但是，早期检出的生存获益尚未阐明。[52]Carrier M, Le Gal G, Wells PS, et al. Systematic review: the Trousseau syndrome revisited: should we screen extensively for cancer in patients with venous thromboembolism? Ann Intern Med. 2008;149:323-333.http://www.ncbi.nlm.nih.gov/pubmed/18765702?tool=bestpractice.com

隐匿性恶性肿瘤

无法使用CT检测隐匿性恶性肿瘤时使用。

隐匿性恶性肿瘤

可以作为一个广泛的筛选策略的一部分用于发现无明显原因(特发性)发生静脉血栓栓塞患者的隐匿性恶性肿瘤。但是，肿瘤标志物是非特异性的而且对大多数 VTE 相关的肿瘤并不敏感。[112]Cornuz J, Pearson SD, Creager MA, et al. Importance of findings on the initial evaluation for cancer in patients with symptomatic idiopathic deep venous thrombosis. Ann Intern Med. 1996;125:785-793.http://www.ncbi.nlm.nih.gov/pubmed/8928984?tool=bestpractice.com

这些包括前列腺特异性抗原，针对结直肠癌的癌胚抗原，针对卵巢上皮癌的 CA 125。

发现隐匿性恶性肿瘤

怀疑肾病综合征的病例应该考虑。

诊断肾病综合征时必须满足蛋白尿＞3.5 g/dL。[65]Mahmoodi BK, ten Kate MK, Waanders F, et al. High absolute risks and predictors of venous and arterial thromboembolic events in patients with nephrotic syndrome: results from a large retrospective cohort study. Circulation. 2008;117:224-230.http://circ.ahajournals.org/content/117/2/224.fullhttp://www.ncbi.nlm.nih.gov/pubmed/18158362?tool=bestpractice.com

肾病综合征中蛋白尿升高