惡性腫瘤與血栓栓塞疾病關(guān)系的研究最早見于一個(gè)多世紀(jì)前，1865年Armand Trousseau報(bào)道癌癥患者發(fā)生血栓是血液系統(tǒng)繼發(fā)的特殊改變,，表現(xiàn)為自發(fā)性血管內(nèi)凝血,。1878年Billroth發(fā)現(xiàn)在這類血栓中存在腫瘤細(xì)胞，從而認(rèn)為與腫瘤轉(zhuǎn)移有關(guān),。在尸檢時(shí)一半以上的腫瘤病人可見到血栓栓塞的證據(jù),。但并不是所有的惡性腫瘤都伴發(fā)血栓，以腺癌最為突出,，肺,、胰、胃腸腫瘤較乳腺,、腎腫瘤更易出現(xiàn)高凝,。
華法林為雙香豆素類抗凝藥，能阻礙已形成血栓的擴(kuò)展,，但無溶栓作用,。臨床上能用華法林防治血栓栓塞性疾病，可防止血栓形成與發(fā)展,，另外華法林也能用于治療癌癥病人伴發(fā)的血栓癥狀,。
與華法林相似的另一抗凝藥--低分子量肝素（Low Molecular Weight Heparin，LMWH）注射劑作為改善腫瘤病人血栓癥狀的一線藥物在臨床上已被大量使用,，但LMWH注射劑的使用頻率相對(duì)于另一常用治療藥物華法林來說仍較少,。
近來,，一項(xiàng)刊登在The Oncologist雜志上的研究表明：在2000年到2007年期間，以LMWH注射劑治療晚期癌癥患者血栓并發(fā)癥的治療方式占所有治療方式中正逐年提高,。
該項(xiàng)研究調(diào)查分析了從2000年1月至2008年12月之間,，四個(gè)癌癥研究網(wǎng)絡(luò)中心關(guān)于健康計(jì)劃的電子記錄。發(fā)現(xiàn)25%的腫瘤病人接受了LMWH第一治療藥物選擇,，而74%的患者選擇華法林作為治療治療,。雖然2003年7月，一個(gè)隨機(jī)對(duì)照研究表明：在預(yù)防腫瘤患者出現(xiàn)血栓復(fù)發(fā)方面,，LMWH注射劑比華法林更有效,，但LMWH注射劑的使用率仍沒有超過華法林。
但這項(xiàng)研究的缺陷在于沒有說明華法林為什么能繼續(xù)作為治療晚期癌癥患者血栓首選藥物的原因,。研究人員猜測(cè)可能是因?yàn)榕R床醫(yī)生在治療腫瘤患者更傾向于使用華法林,。其他還有一些其他原因如華法林不用注射劑，癌癥患者們更傾向選擇華法林,。
研究人員下一步的研究將針對(duì)為什么LMWH的使用率會(huì)比華法林低,，LMWH注射劑和華法林在治療晚期癌癥病人血栓上療效有何差異性。（生物谷Bioon.com）
doi:10.1634/theoncologist.2011-0323
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Outpatient Use of Low Molecular Weight Heparin Monotherapy for First-Line Treatment of Venous Thromboembolism in Advanced Cancer
Thomas Delatea, Daniel M. Witta, Debra Ritzwollerb, Jane C. Weeksc, Lawrence Kushid, Mark C. Hornbrooke, Erin J. Aiello Bowlesf and Deborah Schragc
Abstract Background. Evidence-based treatment guidelines recommend low molecular weight heparin (LMWH) monotherapy for cancer-associated venous thromboembolism (VTE). This analysis assessed the first-line treatment strategies for VTE in patients with advanced solid tumors.
Methods. Using administrative data from advanced lung, prostate, colon, or breast cancer patients diagnosed between January 2000 and December 2007 at four HMOs with integrated delivery systems, patients with an inpatient or outpatient VTE diagnosed within 2 years after cancer diagnosis and an outpatient purchase of warfarin,LMWH, and/or fondaparinux anticoagulant within 7 days of the VTE diagnosis were identified. First-line outpatient VTE pharmacological treatment and factors independently associated with receipt/non-receipt of LMWH monotherapy were assessed.
Results. Overall, 25% of the 1,089 eligible patients received LMWH monotherapy as primary VTE treatment. The percentage increased steadily over time from 18% among patients diagnosed in 2000 to 31% among those diagnosed in 2007. Factors associated with LMWH monotherapy included VTE diagnosis year, chemotherapy within 60 days prior to VTE diagnosis, history of VTE prior to cancer diagnosis, and invasive surgery in the 90 days following VTE diagnosis. Colorectal and prostate cancer patients versus lung cancer patients and stage III versus stage IV patients were less likely to be treated with LMWH monotherapy.
Conclusions. Adoption of LMWH monotherapy as initial treatment for cancer-associated VTE was low but increased steadily over the study period. Future studies should explore reasons underlying the underutilization of this preferred evidence-based treatment as well as the comparative effectiveness of LMWH versus warfarin-based anticoagulation in real-world cancer patients with VTE.
