血栓形成与肿瘤.ppt
血栓形成与血栓形成与肿瘤瘤静脉血栓栓塞症静脉血栓栓塞症的分类的分类深静脉血栓DVT,deep venous thrombosis肺栓塞PE,pulmonary embolism弥散性血管内凝血DIC门静脉血栓PVT动脉血栓栓塞AT游走性浅表血栓性静脉炎等 其中以下肢DVT及PE最为常见。静脉血栓栓塞症静脉血栓栓塞症DVTdeep venous thrombosis血液在深静脉内不正常凝结引起的病症多发生在下肢血栓脱落可引起肺栓塞pulmonary embolism,PE静脉血栓栓塞症与肿瘤静脉血栓栓塞症与肿瘤 cancer body thrombosis静脉血栓栓塞症静脉血栓栓塞症的流行病学的流行病学静脉血栓栓塞症与肿瘤静脉血栓栓塞症与肿瘤 发生原因发生原因高凝状态血管壁损伤 静脉血液淤滞 血小板异常纤溶系统功能异常 补液量缺乏解剖因素 肿瘤细胞侵袭静脉系统静脉血栓栓塞症与肿瘤静脉血栓栓塞症与肿瘤 高凝状态高凝状态 TF和CP TNF、IL-1 凝血酵素高凝状态高凝状态高凝状态高凝状态血血小小板板的的黏黏着着和和聚聚集集单单核核 和和内内皮皮细细胞胞产产生生TF活活化化凝凝血血因因子子VIIa 和和 Xa血栓形成的原因之血栓形成的原因之血管壁损伤血管壁损伤临床显示:易引起血管壁损伤的化疗药物有顺铂、氟尿嘧啶及甲氨蝶呤等。而EPO、他莫昔芬、激素、反响停、贝伐单抗都可以导致癌症病人血栓形成。高危人群高危人群高危人群高危人群腺癌;手术;卧床腺癌;手术;卧床腺癌;手术;卧床腺癌;手术;卧床静脉导管;化疗静脉导管;化疗静脉导管;化疗静脉导管;化疗DVT 的诊断的诊断DVT 的诊断的诊断In 2006,Scarvelis and Wells overviewed a set of clinical prediction rules for DVT on the heels of a widely adopted set of clinical criteria for pulmonary embolism.Wells score or criteria:(Possible score-2 to 9)Active cancer(treatment within last 6 months or palliative)+1 point Calf swelling 3cm compared to other calf(measured 10cm below tibial tuberosity)+1 point Collateral superficial veins(non-varicose)+1 point Pitting edema(confined to symptomatic leg)+1 point Previous documented DVT+1 point.Swelling of entire leg+1 point Localized pain along distribution of deep venous system+1 point Paralysis,paresis,or recent cast immobilization of lower extremities+1 point Recently bedridden 3 days,or major surgery requiring regional or general anesthetic in past 4 weeks+1 point Alternative diagnosis at least as likely-2 pointsInterpretation:Score of 2 or higher deep vein thrombosis is likely.Consider imaging the leg veins.Score of less than 2 deep vein thrombosis is unlikely.Consider blood test such as d-dimer test to further rule out deep vein thrombosis.DVT 的治疗的治疗PE的诊断的诊断PE的诊断的诊断PE的治疗的治疗 注意DVT治疗的重点是 缓解病症使栓子局限减少肺栓塞的风险预防复发PE治疗的重点是缓解病症抗凝溶栓预防复发抗凝治疗的监测普通肝素:血小板计数50109L时停用肝素或输注血小板,抗凝血酶活性(AT:A)测定维持在80以上;LMWH:APTT、PT、抗凝血酶复合物(TAT)等试验与LMWH无明显相关性,一般无需进展监测,可监测heptest、抗因子Xa活性;华法令:维持INR在2.0-3.0,第1-3天每日监测至INR达治疗范围,应用第1周时每周应监测3次,第2周时每周监测2次,至华法令治疗第3周后,应每周监测1次,共4周,以后再改为每2周1次,共2个月,最后维持每个月监测1次即可。DVT的治疗低分子肝素LMWH推荐为长期治疗用药,但经肾代谢。戊聚糖钠用于肾功能不全者肌酐去除率小于30ml/min普通肝素与LMWH普通肝素:血小板减少(肝素诱导血小板减少症,Heparin induced thrombocytopenia,HIT),发生率约为5%,临床主要表现血小板计数减少,出血风险增加.LMWH是由普通肝素通过化学方法或酶解聚而得到的小分子片段,仅保存抗凝血因子a的作用,其抗a因子作用强,抗凝血酶作用弱,抗凝效果呈明显的剂效关系,对血小板功能影响较小,血小板减少的发生罕见,仅1%。华法林与低分子肝素华法林的作用机制华法林的作用机制竞争性对抗维生素K的作用抑制肝细胞中凝血因子的合成降低凝血酶诱导的血小板聚集反响,因而具有抗凝和抗血小板聚集功能。低分子肝素的作用机制低分子肝素的作用机制通过形成Xa-TFPI复合物或直接与TF结合抑制外源性凝血途径内皮调节作用,释放纤溶激活因子和抗血小板物质,抑制白细胞的促凝血作用抑制平滑肌细胞增殖华法林与低分子肝素Hull et al 对200例恶性肿瘤合并近端静脉血栓的患者分别采用LMWH治疗和常规华法林治疗,结果发现,LMWH组的血栓再发率为7%,而常规华法林治疗组的血栓再发率为16%,两组间的出血发生率却无明显差异P大于0.05。小结肿瘤与血栓是相互促进的关系肿瘤患者血栓形成的原因高危患者的预防静脉血栓栓塞的诊治DVT与PE血栓形成的原因之其它肿瘤细胞静脉血液淤滞静脉特有解剖结构静脉血栓形成VTE血小板异常纤溶系统功能异常侵犯静脉系统1.原发性血小板聚集2.主动性血小板增多3.凝血酶原成分增加纤溶系统活性降低以及PAI水平增高补液量缺乏长期卧床血流速慢易受压变形静脉血栓栓塞症临床表现静脉血栓栓塞症临床表现在癌症病人中VTE的预防 静脉血栓栓塞症与肿瘤静脉血栓栓塞症与肿瘤静脉血栓性栓塞症静脉血栓性栓塞症(venous thromboembolism)肿瘤患者的VTE发生率较正常人增加了4到6倍25%的病例与癌症有关:急性VTE:20%已查出肿瘤 特发性VTE:10%患者12个月之内查出肿瘤 cancer body thrombosis VTE静脉血栓性栓塞症静脉血栓性栓塞症(venous thromboembolism)肿瘤患者的VTE发生率较正常人增加了4到6倍25%的病例与癌症有关:急性VTE:20%已查出肿瘤 特发性VTE:10%患者12个月之内查出肿瘤According to Virchows triad,venous thrombosis occurs via three mechanisms:decreased flow rate of the blood,damage to the blood vessel wall and an increased tendency of the blood to clot(hypercoagulability).Several medical conditions can lead to DVT,such as compression of the veins,physical trauma,cancer,infections,certain inflammatory diseases and specific conditions such as stroke,heart failure or nephrotic syndrome.There are several factors which can increase a persons risk for DVT,including surgery,hospitalization,immobilization(such as when orthopedic casts are used,or during long-haul flights,leading to travellers thrombosis),smoking,obesity,age,certain drugs(such as estrogen,or erythropoietin)and inborn tendencies to form clots known as thrombophilia(for example,in carriers of factor V Leiden).Women have an increased risk during pregnancy,if they are on oral contraceptives,and in the postnatal period,due to increased estrogen levels.DVT病理生理学DVT临床表现诊断治疗肺栓塞的诊疗预后肿瘤与血栓形成的关系Blood testsedit D-dimerIn a low-probability situation,current practice is to commence investigations by testing for D-dimer levels.This cross-linked fibrin degradation product is an indication that thrombosis is occurring,and that the blood clot is being dissolved by plasmin.A low D-dimer level should prompt other possible diagnoses(such as a ruptured Bakers cyst,if the patient is at sufficiently low clinical probability of DVT).3233edit Other blood testsOther blood tests usually performed at this point arecitation needed: