Outpatient use of low molecular weight heparin monotherapy for first-line treatment of venous thromboembolism in advanced cancer

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.     

Extended venous thromboembolism prophylaxis for high-risk patients undergoing surgery for malignancy

Background

In surgical patients with known malignancy, the odds ratio for an episode of a venous thromboembolism is approximately 6.5 compared to a group of patients without malignancy undergoing the same procedure [Heit et al.: Arch Intern Med 2000;160:809–815].

Case Report

We present a case of a 46-year-old Caucasian male with a history of adenocarcinoma of the rectum. The patient received neoadjuvant treatment prior to low anterior resection with diverting colostomy. He received short-term prophylaxis for venous thrombosis, but unfortunately developed a blood clot in a lower extremity several weeks after surgery.

Conclusion

There is a well-defined role in carefully selected patients for the use of extended prophylaxis to prevent venous thromboembolic complications following cancer surgery.Key Words: Venous thromboembolism prophylaxis, Venous thromboembolism, Surgery, Deep vein thrombosis, Pulmonary embolism     

Treatment of venous thromboembolism with low molecular weight heparins.

The accumulating evidence indicates that certain LMW-heparins administered subcutaneously may replace classical intravenous heparin therapy. Certain of these subcutaneously administered LMW-heparins do not require monitoring. The simplified care offered by LMW-heparin therapy offers the possibility of transferring care from in the hospital to out of the hospital in uncomplicated patients with deep vein thrombosis. The advantages to the patient of avoiding in-hospital care and its associated hazards are obvious. Outpatient LMW-heparin therapy will likely prove to be highly cost-effective. It is uncertain at the present time whether the findings associated with an individual LMW-heparin preparation can be extrapolated to a different LMW-heparin. For this reason the findings of clinical trials apply only to the particular LMW-heparin evaluated and cannot be generalized to the LMW-heparins at large.     

Short-term antibiotic prophylaxis in open urologic surgery

The aim of the present study was to compare the efficacy of a single dose of ceftriaxone with a triple dose of gentamicin as prophylactic agents in patients undergoing open urologic surgery. Fifty-two patients were allocated into two groups which were well matched with respect to sex, age and surgical procedure: --24 were given single-dose ceftriaxone (2 g i.v.) at the time of anesthesia (ceftriaxone group); --28 received gentamicin (80 mg i.v.) at the time of anesthesia and two additional doses of the same antibiotic were subsequently administrated every 8 hours (gentamicin group). The incidence of urinary tract infection (UTI) was 3.5% in the gentamicin group and 0% in the ceftriaxone group (p = n.s.); postoperative fever (greater than 38 degrees C) occurred in 28.3% and 8.3% in the gentamicin and ceftriaxone groups respectively (p = n.s.). There was no clinical or hematological evidence of drug side effects in any patient. Results of the study show that short-term antibiotic regimens can improve UTI rates after open urologic surgery; moreover a single preoperative dose of ceftriaxone resulted to be as effective as three doses of gentamicin.     

低分子肝素钙在妇科肿瘤腹腔镜术后深静脉血栓预防中的效果观察

目的探讨低分子肝素钙在妇科肿瘤腹腔镜术后深静脉血栓(DVT)预防中的应用效果。方法选取2017年1月至2018年9月间上海市长征医院收治的138例行腹腔镜手术治疗的妇科肿瘤患者,采用随机数字表法分为A组和B组,每组69例。A组患者术前0. 5h单次皮下注射低分子肝素钙5000U,B组患者术后12h皮下注射低分子肝素钙5000U,连用5d。比较两组患者术前和术后5d血小板(PLT)、血红蛋白(Hb)、纤维蛋白原(FIB)和D-二聚体(D-D)水平,统计两组患者手术指标、术后DVT发生率和出血性事件发生情况。结果 A组患者围手术期DVT发生率为2. 9%(2例),B组患者为4. 3%(3例),两组比较,差异无统计学意义(P> 0. 05)。两组患者气腹压力、术中出血量、麻醉时间和手术时间比较,差异均无统计学意义(均P> 0. 05)。术前和术后5d,两组患者FIB、D-D、PLT和Hb水平比较,差异均无统计学意义(均P> 0. 05)。治疗过程中,两组患者均未出现皮下出血和过敏等并发症。结论术前单次低分子肝素钙预防妇科肿瘤腹腔镜手术患者术后DVT发生的效果和安全性与术后应用低分子肝素钙类似,但单次应用减轻了患者的经济负担和注射痛苦,值得临床推广应用。     

肿瘤并发血栓的机制及预防治疗

恶性肿瘤可通过多种途径导致血栓发生,影响肿瘤患者的生活质量和预后,血栓的形成又可以早期预示着肿瘤的发生,所以恶性肿瘤与血栓的相互关系越来越受到重视.恰当的预防血栓治疗不仅可减少并发症的发生,还可以改善肿瘤患者的预后.     

Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism.

PURPOSE: Experimental studies and indirect clinical evidence suggest that low molecular weight heparins may have antineoplastic effects. We investigated the influence of a low molecular weight heparin dalteparin on the survival of patients with active cancer and acute venous thromboembolism. PATIENTS AND METHODS: Survival data were examined in a posthoc analysis in patients with solid tumors and venous thromboembolism who were randomly assigned to dalteparin or a coumarin derivative for 6 months in a multicenter, open-label, randomized, controlled trial. All-cause mortality at 12 months was compared between treatment groups in patients with and without metastatic malignancy. The effect of dalteparin on survival was compared between the two patient subgroups. RESULTS: During the 12-month follow-up period, 356 of 602 patients with solid tumors and acute venous thromboembolism died. Among patients without metastatic disease, the probability of death at 12 months was 20% in the dalteparin group, as compared with 36% in the oral anticoagulant group (hazard ratio, 0.50; 95% CI, 0.27 to 0.95; P = .03). In patients with metastatic cancer, no difference in mortality between the treatment groups was observed (72% and 69%, respectively; hazard ratio, 1.1; 95% CI, 0.87 to 1.4; P = .46). The observed effects of dalteparin on survival were statistically significantly different between patients with and without metastatic disease (P = .02). CONCLUSION: The use of dalteparin relative to coumarin derivatives was associated with improved survival in patients with solid tumors who did not have metastatic disease at the time of an acute venous thromboembolic event. Additional studies are warranted to investigate these findings.     

超声监测胸外科肿瘤术后低分子肝素预防深静脉血栓的临床研究

目的探讨应用超声监测胸外科肿瘤术后给予低分子肝素预防深静脉血栓的临床效果。方法将2010年1月至2010年12月间80例行胸外科恶性肿瘤手术治疗的患者随机分为两组,每组各40例。观察组患者术后给予低分子肝素治疗,对照组患者术后未给予低分子肝素治疗,对两组患者进行超声检查,观察深静脉血栓发生的情况。结果两组患者手术时间、胸腔引流量、拔管时间比较差异无统计学意义（P〉0．05）;观察组患者静脉血栓形成率显著低于对照组,差异有统计学意义（P〈0．05）;两组患者D-二聚体、血小板计数（PLIT）和纤维蛋白原（FIB）治疗后均有不同程度的改善,差异有统计学意义（P〈0．05）。治疗1d后两组患者的观察指标比较无显著性差异（P〉0．05）,但治疗3天后,FIB和D-二聚体比较,差异有统计学意义（P〈0．05）。结论临床上胸外科肿瘤手术后给予低分子肝素能够有效预防深静脉血栓的形成,超声能够作为早期监测患者下肢深静脉血栓形成的重要方法。     

Low molecular weight heparins as extended prophylaxis against recurrent thrombosis in cancer patients

Cancer has been shown to be an independent risk factor for the development of venous thromboembolism (VTE; deep vein thrombosis and pulmonary embolism). Thromboprophylaxis reduces the incidence of VTE in patients with cancer; however, active cancer places patients at high risk for recurrent VTE, necessitating extended prophylactic regimens. Extended prophylaxis in patients with cancer can be problematic because of increased risk for bleeding. Oral anticoagulants, such as warfarin, have been the standard of care for extended prophylaxis, but maintaining a clinically effective level of anticoagulation can be difficult because of a wide range of drug interactions, a narrow therapeutic window, and an increased risk of bleeding complications, particularly in patients with cancer. Recent evidence indicates that long-term prophylaxis with low-molecular-weight heparins (LMWHs) is an effective and safe alternative to oral anticoagulation in patients with VTE and cancer, reducing the risk for recurrent VTE by up to 52%. LMWHs can also be seen as cost-effective for long-term prophylaxis, because higher drug acquisition costs are offset by the potential for reduced hospital stays, reduced need for coagulation monitoring, and fewer bleeding complications. Some studies suggest that LMWHs may also have direct antitumor effects and improve survival rates, most notably in patients with non-metastatic disease. Further clinical research is needed to evaluate the potential survival benefits of LMWH therapy in patients with cancer.     

Low molecular weight heparin for Hickman catheter--induced thrombosis in thrombocytopenic patients undergoing bone marrow transplantation.

BACKGROUND. Patients with an indwelling central venous catheter are prone to development of thrombotic complications. Thrombocytopenia in patients undergoing bone marrow transplantation (BMT) generally is protracted. The management of thrombosis in thrombocytopenic patients is difficult because heparin and warfarin are relatively contraindicated because of the high risk of major bleeding. Low molecular weight heparin (LMWH) is a new class of antithrombotic drug. Enoxaparin (Rhone Poulenc Rorer, Antony, France) is an LMWH that has been shown to be effective in the treatment and prophylaxis of venous thrombosis. Enoxaparin, with its high antithrombotic to anticoagulant ratio, may be safer than standard heparin in patients at high risk of hemorrhagic complications. METHODS. The authors report the cases of five thrombocytopenic patients, undergoing autologous BMT, in whom venous thrombosis developed related to a Hickman catheter. RESULTS. All the patients were treated with Enoxaparin and recovered promptly without hemorrhagic complications. CONCLUSIONS. The authors suggest that Enoxaparin is an effective drug in treating thrombocytopenic patients in whom acute venous thrombosis develops.     

低分子量肝素预防胸部肿瘤开胸术后血栓性疾病的临床研究

目的观察低分子量肝素预防胸部肿瘤开胸术后血栓性疾病的效果。方法将2004年1月至2005年8月住我科的食管癌、贲门癌、肺癌患者随机分为治疗组和对照组,每组320例,治疗组于术后第1天开始皮下注射低分子量肝素,每日1次,连用5d,观察术后胸液量并统计血栓性疾病发生率。结果两组患者胸液量差异无显著性(P>0.05),治疗组血栓性疾病发生率明显低于对照组(P<0.01)。结论低分子量肝素预防胸部肿瘤开胸术后血栓性疾病有明显效果,较为安全可靠。     

Application of venous thromboembolism prophylaxis program in patients with colorectal cancer using the enhanced recovery after surgery protocol

IntroductionThe incidence of postoperative symptomatic venous thromboembolism (VTE) in western colorectal cancer is 1.1–2.5%. Anticoagulation and mechanical devices are recommended for moderate-to high-risk patients. Hospital stay and immobilization, as risk factors for VTE, are reduced by enhanced recovery after surgery (ERAS). This study aimed to evaluate short- and long-term outcomes for a VTE prophylaxis program after minimally invasive colorectal cancer surgery with ERAS protocol. In addition, predicting factors associated with VTE were investigated.Materials and methodsWe included 1043 patients diagnosed with colorectal cancer who required surgical treatment between January 2017 and December 2019 at a single institution. The patients enrolled followed the VTE prophylaxis program.ResultsFive (0.5%) patients developed symptomatic VTE, and the median follow-up period was 21 months. The Caprini score for all VTE patients was ≤8 points; thus, only mechanical prophylaxis was applied. The incidence rate of postoperative symptomatic VTE was only 0.5%. There was no association between variables considered as associated with VTE onset, such as age, perioperative complication, and length of postoperative day. TNM staging (OR 2.44, 95% CI 1.4–4.16, p = 0.001) and the Caprini score (OR 1.75, 95% CI 1.1–2.8, p = 0.001) were associated with VTE onset.ConclusionAlthough pharmacological prophylaxis was only performed for Caprini scores ≥9, the VTE incidence rate of patients with colorectal cancer undergoing VTE prophylaxis program was 0.6%; 0.7% is the incidence criterion of the moderate group recommended for pharmacological prophylaxis. Continuous follow-up is required for patients with advanced-stage colorectal cancer with high-risk Caprini scores.     

低分子肝素钠与常规华法林维持治疗恶性肿瘤合并深静脉血栓患者的疗效比较

目的比较低分子肝素钠与常规华法林维持治疗恶性肿瘤合并深静脉血栓患者的疗效。方法选取2012年1月至2012年12月间收治的84例恶性肿瘤合并深静脉血栓患者,按照随机数字表法分为观察组和对照组,每组42例。观察组患者采用低分子肝素钠治疗,对照组患者采用常规华法林治疗。观察两组患者临床疗效、症状改善情况和深静脉血栓复发率。结果观察组患者总有效率为73.8%,对照组为52.4%,差异有统计学意义(P<0.05)。治疗后两组患者活化部分凝血活酶时间(APTT)及血浆凝血酶原时间(PT)均明显延长,但观察组患者延长时间明显优于对照组,组间差异有统计学意义(P<0.05)。观察组患者临床症状大多在2周内明显者改善,优于对照组,组间差异有统计学意义(P<0.05)。随访1年后,观察组患者深静脉血栓复发率为6.5%,显著低于对照组的22.7%,组间差异有统计学意义(P<0.05)。结论与华法林相比,低分子肝素钠维持治疗恶性肿瘤合并深静脉血栓患者疗效显著,用药方便、安全。     

低分子肝素钙在妇科肿瘤腹腔镜术后预防深静脉血栓中的临床效果

目的：探讨低分子肝素钙抗凝方案应用于妇科肿瘤腹腔镜术后预防深静脉血栓的临床效果以及安全性。方法：选择2011年1月-2014年12月120例实施妇科肿瘤腹腔镜术患者,按数字表法随机分为对照组与观察组,对照组54例患者不使用其他抗凝剂和影响凝血功能的药物;观察组66例患者实施低分子肝素钙皮下注射抗凝,持续10d,对比两组患者血清学指标、活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）、下肢周径、血流指标、并发症发生率。结果：观察组术后5d 纤维蛋白原、D -二聚体分别为（2.77±0.73）g/ L、（0.63±0.18）μg/ ml,均低于对照组,对比差异有统计学意义（P =0.019,P =0.029）;观察组术后3d、术后5d PT 分别为（13.85±3.93）s、（13.95±3.14）s,优于对照组,对比差异有统计学意义（P =0.042,P =0.034）;观察组下肢周径、血流速度分别为（20.33±3.52）cm、（0.95±0.18）m/ s,优于对照组,对比差异有统计学意义（P =0.021,P =0.019）;并发症发生率观察组3.03%（2/66）与对照组9.26%（5/54）对比差异有统计学意义（P =0.004）。结论：低分子肝素钙抗凝方案应用于妇科肿瘤腹腔镜术后可以有效改善患者血流状态,预防深静脉血栓形成。     

Low-molecular-weight heparin and calcium heparin in thrombosis prophylaxis in patients with percutaneous arterial and venous ports for colorectal liver metastases

STUDY OBJECTIVE: The evaluation of low-molecular-weight heparin use to prevent arterial and venous thrombosis in patients with indwelling arterial Port-a-Cath implants. METHODS: From 1996 to March 2003 we placed 370 indwelling hepatic arterial catheters with a minimally invasive approach. The left distal subclavian artery was approached from beneath the left clavicle, then an angiographic study of the tumoral vascular district was performed and the gastroduodenal artery was occluded by an embolus. A polyurethane catheter was introduced distally into the hepatic artery and connected to a reservoir through a 3-4 cm long subcutaneous tunnel. In 90 patients a venous Port-a-Cath was placed for concurrent systemic chemotherapy. All 370 patients received regional chemotherapy and were treated with calcium heparin at a dose of 5000 IU twice a day and with low-molecular-weight heparin at prophylactic doses (dalteparin 2500 IU or nadroparin 3000 IU) during catheter permanence to prevent hepatic artery thrombosis. Intra-arterial trans-port radionuclide scans using technetium-99m-labeled micro-aggregated albumin were performed monthly to check the infusion distribution and hepatic artery patency. In the presence of anomalous patterns, thrombosis, pulmonary embolism or other complications, angiography and/or other diagnostic studies were performed to determine the cause of the vascular event and the local or systemic symptoms. The mean arterial and venous Port-a-Cath permanence times were 6 and 8 months, respectively. RESULTS: We observed episodes of hepatic artery thrombosis in 4.3% of patients. Three of these 17 patients were successfully treated by intra-arterial thrombolysis using urokinase. No venous thrombosis occurred as a consequence of regional and/or systemic chemotherapy, no episodes of arterial thrombosis were registered during arterial catheter permanence, nor did any hemorrhagic complications related to anti-coagulant therapy occur. Five patients treated with low-molecular-weight heparin required treatment suspension due to a platelet count of < 40,000/dL. CONCLUSION: Our experience suggests that low-molecular-weight heparin and/or calcium heparin at prophylactic doses could be useful in the prevention of arterial and venous thrombosis in patients with indwelling arterial catheters or venous Port-a-Cath treated with regional or systemic chemotherapy for hepatic metastases from colorectal cancer. The homogeneity of the patient group and the use of analogous chemotherapeutic drugs (fluoropyrimidines) avoided statistical contamination related to differences between kinds of cancer and between the chemotherapeutic agents used.     

妇科肿瘤深静脉置管患者低分子肝素治疗对静脉血栓栓塞的预防价值

目的探讨妇科肿瘤深静脉置管(PICC)患者应用低分子肝素治疗对静脉血栓栓塞(VTE)的预防价值。方法选取2015年4月至2019年6月间上海复旦大学附属中山医院青浦分院收治的因妇科肿瘤而需要进行PICC置管的124例患者。采用随机数表法分为研究组和常规组,每组62例。研究组患者在置管后3d内给予患者低分子肝素治疗,常规组患者置管后采用常规护理及治疗。观察两组患者的静脉血栓栓塞(VTE)发生率和治疗前后的凝血功能,比较两组患者治疗前后的血小板(PLT)、血红蛋白(Hb)、D-二聚体(D-D)和纤维蛋白原(FIB)水平,并比较两组患者治疗前后的下肢周径与血流速度。结果与治疗前相比,常规组患者治疗后凝血功能指标均降低,而研究组患者治疗后均升高,差异均有统计学意义(均P <0. 05)。研究组患者治疗后凝血功能指标均高于常规组患者,差异均有统计学意义(均P <0. 05)。治疗前,两组患者PLT、Hb、D-D和FIB水平比较,差异无统计学意义(P>0. 05)。治疗后,两组患者血清指标水平PLT、Hb和FIB比较,差异无统计学意义(P>0. 05);研究组患者D-D水平低于对照组患者,差异有统计学意义(P <0. 05)。常规组患者治疗后血流速度明显低于治疗前,下肢周径显著高于治疗前,差异均有统计学意义(均P <0. 05)。研究组患者治疗后血流速度和下肢周径与治疗前相比,差异无统计学意义(P>0. 05)。治疗后,研究组患者血流速度显著高于常规组患者,下肢周径显著低于常规组,差异均有统计学意义(均P <0. 05)。治疗后常规组患者VTE发生例数为9例,发生率为14. 5%,高于研究组患者的3. 2%,差异有统计学意义(P <0. 05)。结论妇科肿瘤深静脉置管患者应用低分子肝素能够显著降低VTE的发生,可有效提高患者的抗凝功能,改善血流速度。