Adjuvant enoxaparin therapy may decrease the incidence of postoperative thrombotic events though does not increase the incidence of postoperative intracranial hemorrhage in patients with meningiomas

Patients with brain tumors including intracranial meningiomas are at increased risk for developing deep vein thrombosis (DVTs) and suffering thromboembolic events (VTEs). Many surgeons are concerned that early use of low dose enoxaparin may increase the risk of intracranial hemorrhage which outweighs the benefit of DVT/VTE reduction. We aimed to address concerns around the use of enoxaparin after meningioma resection in the development of postoperative intracranial hemorrhages and DVT/VTEs. This is a retrospective review of 86 patients with intracranial meningiomas who underwent craniectomy and surgical resection of the mass, treated by one attending surgeon at UCSF Medical Center between 2000 and 2005. Within 48 h after surgery patients treated 2003–2005 routinely received enoxaparin therapy unless there was documented intracranial hemorrhage, lumbar subarachnoid drain, enoxaparin hypersensitivity, or thrombocytopenia (n = 24). These were compared to a cohort treated 2000–2002 who did not receive the drug (n = 62). Exclusion criteria were prior VTEs or coagulopathies. The groups were similar in tumor and surgical characteristics. Enoxaparin therapy did not increase the incidence of intracranial hemorrhage following surgical meningioma resection and the incidence of DVTs/VTEs was 0% (n = 0) versus 4.8% (n = 3) in the non-enoxaparin group. Results did not reach statistical significance. In this retrospective study, postoperative administration of enoxaparin following meningioma resection does not increase the risk of intracranial hematoma though enoxaparin administration may slightly decrease the incidence of post-surgical thromboembolic events. Due to study design and power, we were not able to demonstrate DVT/VTE reduction with statistical significance.     

Risk factors for central venous catheter thrombotic complications in children and adolescents with cancer

BACKGROUND:

The use of central venous catheters (CVCs) has greatly improved the quality of care in children with cancer, yet these catheters may cause serious infectious and thrombotic complications. The aim of this prospective registry study was to assess the host and CVC‐related risk factors for CVC‐created thrombotic complications.

METHODS:

Patients undergoing CVC insertion for chemotherapy were followed prospectively for CVC complications. At the time of enrollment, demographic, clinical, and CVC‐related data, and family history of thrombosis were collected. Survival and Cox regression analyses were performed.

RESULTS:

A total of 423 CVCs were inserted into 262 patients for a total of 76,540 catheter days. The incidence of CVC‐related deep‐vein thrombosis (DVT) was 0.13 per 1000 catheter‐days (95% confidence interval [CI], 0.06‐0.24). Insertion of peripherally inserted central catheters (PICCs) and insertion in an angiography suite significantly increased the risk of symptomatic CVC‐related DVT. The incidence of CVC occlusion was 1.35 per 1000 catheter‐days (95% CI, 1.1‐1.63). Positive family history of thrombosis significantly increased the risk of CVC occlusion (hazard ratio [HR], 2.16; 95% CI, 1.2‐3.8). The CVC‐related risk factors were insertion of Hickman catheters, insertion in angiography suite, and proximal‐tip location. Patients developing at least 1 episode of both CVC occlusion and infection had an increased risk for developing symptomatic CVC‐related DVT (HR, 4.15; 95% CI, 1.2‐14.4).

CONCLUSIONS:

Both patient‐related and CVC‐related factors are associated with higher risk of symptomatic thrombotic complications. These risk factors could be used in the clinical setting and in developing future studies for CVC thromboprophylaxis. Cancer 2010. © 2010 American Cancer Society.     

Early and short-term acenocumarine or dalteparin for the prevention of central vein catheter-related thrombosis in cancer patients: a randomized controlled study based on serial venographies

BackgroundWe evaluated efficacy and safety of early and short-term prophylaxis with acenocumarine or dalteparin in the prevention of non-occlusive or occlusive central vein catheter-related thrombosis (CVCrT).Patients and methodsConsecutive cancer patients scheduled for chemotherapy randomly received: acenocumarine 1 mg/day for 3 days before and 8 days after central vein catheter (CVC) insertion; dalteparin 5000 IU 2 h before and daily for 8 days after CVC insertion; no anticoagulant treatment (NT). All patients underwent venography on days 8 and 30, some of them on days 90, 150 and 210 after CVC.ResultsA total of 450 patients were randomized, 348 underwent at least two venography. Both acenocumarine and dalteparin reduced venography-detected CVCrT rate [21.9% acenocumarine versus 52.6% NT, odds ratio (OR) 0.3, P < 0.01; 40% dalteparin versus 52.6% NT, OR 0.6, P = 0.05]. Acenocumarine was more effective than dalteparin (OR 0.4, P = 0.01). The rate of occlusive CVCrT was not different in the three groups (0.9% acenocumarine, 3.3% dalteparin, 1.8% NT; P = 0.40). Most CVCrTs (95.6%) were observed on day 8 after CVC insertion and were non-occlusive.ConclusionsIn this study of early and short-term prophylaxis, acenocumarine was more effective than dalteparin on non-occlusive and asymptomatic CVCrT events. The first days following CVC insertion represent the highest risk for CVCrT.     

恶性淋巴瘤合并静脉血栓栓塞的临床特征及血液学指标检测

目的:了解恶性淋巴瘤（malignant lymphoma,ML）患者并发静脉血栓栓塞（venous thromboembolism ,VTE ）的临床特点及血液学指标变化情况,为预防和治疗ML合并VTE 提供有效依据。方法:回顾性分析2010年10月至2014年4 月江苏大学附属昆山医院收治的65例ML合并VTE 患者的临床资料,观察凝血功能和血液流变学等血栓相关血液学指标。结果:ML合并VTE 患者男女比例为2.6 1:1,主要集中于较晚期的患者,81.54% 病例为ⅢB～Ⅳ期。66.15%（43例）在ML确诊后发现。55例（84.62%）并发深静肿血栓形成（deep vein thrombosis,DVT ）,7 例（10.77%）并发肺栓塞（pulmonary embolism,PE）,仅3 例（4.62%）同时并发DVT和PE。上肢和颈部静脉为DVT 的最常见发生部位,占67.27%（37例）。 ML合并DVT 主要表现为患肢肿胀、胀痛和皮温升高,而PE患者表现为不明原因的呼吸困难、胸痛和晕厥。55例DVT 患者治疗总有效率为49.09%（27例）,而PE患者仅为14.29%（1例）。 与单独ML患者相比,ML合并VTE 患者血小板聚集、D-dimer、血液高切黏度、低切黏度、血浆黏度、红细胞比容、红细胞聚集指数和刚性指数均明显升高,而APTT、血沉、变形指数和血平均流速明显降低。结论:ML合并VTE 多为DVT ,好发于男性,且集中于晚期患者,上肢和颈部静脉为好发部位,患者血液学指标向“易栓状态”变化。      

Frequency, clinical pattern and outcome of thrombosis in cancer patients in Saudi Arabia

Objectives: Thrombotic risk is increased in patients with cancer and there are important implications forthose who suffer a venous thromboembolism (VTE). We undertook this study to determine the frequency, clinicalpatterns, and outcome of VTE in Saudi patients with cancer. Methods: Cancer (solid tumors and lymphoma)patients who developed VTE from January 2004 to January 2009 were studied retrospectively. Demographicsand clinical characteristics related to thrombosis and cancer were evaluated. Results: A total of 701 patientswith cancer were seen during the study period. VTE was diagnosed in 47 (6.7%) patients (median age 52, range18-80 years). Lower limb DVT was the most common type, seen in 47% patients, followed by PE in 19%, and19% patients had both DVT & PE. Thrombosis was symptomatic in 72% patients while it was an incidentalfinding on routine workup in 28% . Cancer and VTE were diagnosed at the same time in 38% of patients, and47% patients developed VTE during the course of disease after the cancer diagnosis. The majority of VTE postcancer diagnoses occurred during the first year (median 4 months, range 1-14). Additional risk factors for VTEwere present in 22 (47%) patients and 14 (30%) of these patients were receiving chemotherapy at the time ofthrombosis. Only 5 (10.6%) patients were receiving thrombo-prophylaxis at the time of VTE diagnosis. Mostcommon types of tumors associated with thrombosis were breast cancer, non-Hodgkin’s lymphoma and lungcancer. The majority of the affected patients (79%) had advanced stage of cancer. After a median follow-up of13 (range 0.5-60) months, 38 (81%) patients had died. There was no difference in the mortality of patients withsymptomatic or asymptomatic thrombosis (82% vs 78.6%). Conclusions: Thrombotic complications can developin a significant number of patients with cancer, and almost half of the patients have additional risk factors forVTE. Thrombosis is usually associated with advanced disease and can be asymptomatic in more than a quarterof cases. Thromboprophylaxis in cancer patients is under-utilized. Community based studies are needed toaccurately define the extent of this problem and to develop effective prophylactic strategies.     

Association between Level of Tumor Markers and Development of VTE in Patients with Pancreatic,Colorectal and Ovarian Ca: Retrospective Case- Control Study in Two Community Hospitals

The risk of venous thromboembolism (VTE) is increased in patients with cancer. However, the role of tumor markers as potential indicators of increased risk of VTE is still undetermined. In this retrospective observational case control study, levels of the tumor markers CEA, CA 19–9 and CA 125 in patients with colorectal, pancreatic, and ovarian cancer respectively, who were admitted to two community hospitals between January 2001 and December 2011, were compared between patients who were VTE positive and those who were VTE negative. The primary goal of this study was to determine whether VTE positive cancer patients had higher tumor marker levels compared to VTE negative cancer patients. In our study, 66.7% (48/72) of patients who were positive for VTE had elevated tumor markers while 65.3% (66/101) of patients who were negative for VTE had low (normal) tumor markers, indicating an association of high tumor marker levels with the diagnosis of VTE. This was statistically significant with an odds ratio of 3.77 and p-value of <0.0001 (95% CI of 1.99–7.14). When the VTE group was further divided into DVT and PE groups, 70.2% (40/57) of patients in the DVT positive group had high tumor markers with a p value of <0.0001 and an odds ratio of 3.99 (95% CI of 2.02 to 7.89) while 57.9% (11/19) of patients in pulmonary embolism positive group had high tumor markers; this was, however, not statistically significant (p-value of 0.35 and a CI of 0.59 to 4.10). In this retrospective study of 173 individuals with a diagnosis of either colorectal, pancreatic, or ovarian Cancer, higher tumor marker levels (CEA, CA 19–9, and CA 125 respectively) were associated with an increased risk of VTE, either DVT or PE. However, when further divided into either DVT or PE groups, the association remained statistically significant only for DVT but not for PE.     

Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: final results of a double-blind, placebo-controlled phase III trial.

BACKGROUND: Cancer patients receiving chemotherapy experience thromboembolic complications associated with the use of long-term indwelling central venous catheters (CVCs). This prospective, double-blind, placebo-controlled, multicenter study evaluated whether prophylactic treatment with a low molecular weight heparin could prevent clinically relevant catheter-related thrombosis. PATIENTS AND METHODS: Patients with cancer undergoing chemotherapy for at least 12 weeks (n=439) were randomly assigned, in a 2:1 ratio, to receive either dalteparin (5000 IU) or placebo, by subcutaneous injection, once daily for 16 weeks. Patients underwent upper extremity evaluation with either venography or ultrasound at the time of a suspected catheter-related complication (CRC) or upon completion of study medication. The primary end point, as determined by a blinded adjudication committee, was the occurrence of a CRC, defined as the first occurrence of any one of the following: clinically relevant catheter-related thrombosis that was symptomatic or that required anticoagulant or fibrinolytic therapy; catheter-related clinically relevant pulmonary embolism; or catheter obstruction requiring catheter removal. RESULTS: There was no significant difference in the frequency of CRCs between the dalteparin arm (3.7%) and the placebo arm (3.4%; P=0.88), corresponding to a relative risk of 1.0883 (95% confidence interval 0.37-3.19). No difference in the time to CRC was observed between the two arms (P=0.83). There was no significant difference between the dalteparin and placebo groups in terms of major bleeding (1 versus 0) or overall safety. CONCLUSIONS: Dalteparin prophylaxis did not reduce the frequency of thromboembolic complications after CVC implantation in cancer patients. Dalteparin was demonstrated to be safe over 16 weeks of treatment in these patients.     

Risk factors for venous thromboembolic events in cancer patients.

BACKGROUND: Cancer patients of the Department of Internal Medicine (Cancer Research) of the Essen University Medical School (Tumor Clinics), Germany, were examined and questioned with the aim of identifying those who run a high risk of deep vein thrombosis (DVT). PATIENTS AND METHODS: Between September 2002 and April 2003, cancer therapy and DVT risk factors of 507 cancer patients (53% males, 47% females, mean age 56+/-12 years) were documented. During a mean follow-up of 8+/-5 months, 60 patients (12%) suffered from new venous thromboembolic events (VTE): 28 at the lower limb, 25 at the upper limb and 13 pulmonary embolisms. RESULTS: The following factors were considered as predictive for an increased VTE risk: inpatient treatment (P<0.0001), prior DVT in medical history (P=0.0275), DVT in family (P=0.0598), chemotherapy (P=0.0080), fever (P=0.0093) and CRP (P<0.001). After combining factors in one variable (number of factors) the predicted VTE risk increased with the number of factors in both outpatients (OR 1.85, 95% CI 1.18-2.88, P=0.0071) and inpatients (OR 2.34, 95% CI 1.63-3.36, P相似文献   

Venous thromboembolism in high grade glioma among surgical patients: results from a single center over a 10 year period

Patients with high-grade glioma are at elevated risk of venous thromboembolism (VTE). The relationship between VTE and survival in glioma patients remains unclear, as does the optimal protocol for chemoprophylaxis. The purpose of this study was to assessthe incidence of and risk factors associated with VTE in patients with high-grade glioma, and the correlation between VTE and survival in this population. Furthermore, we sought to define a protocol for perioperative DVT prophylaxis. This was a retrospective review of patients who underwent craniotomy for resection of high-grade glioma (WHO grade III or IV) at Northwestern University between 1999 and 2010. A total of 336 patients met inclusion criteria. 53 patients developed postoperative VTE (15.7 %). Median survival was 12.0 months and was not significantly different between VTE(+) and VTE(?) patients. Demographics and surgical factors were not significantly correlated with VTE development. Prior history of VTE was highly predictive of postoperative VTE (OR 7.1, p < .01), as was seizure (OR 2.4, p = .005). Increased duration of postoperative ICU stay was also a risk factor for VTE (p = .025). 25 patients in our study received prophylactic anticoagulation(pAC) with either heparin or enoxaparin. Early initiation of pAC was associated with decreased incidence of VTE (p = .042). There were no hemorrhagic complications in patients receiving pAC. VTE is a common complication in high-grade glioma patients. Early initiation of anticoagulation is safe and may decrease the risk of VTE. We recommend initiation of chemoprophylaxis on postoperative day 1 in patients without contraindication.     

Prophylactic recombinant erythropoietin therapy and thalidomide are predictors of venous thromboembolism in patients with multiple myeloma: limited effectiveness of thromboprophylaxis

BACKGROUND:

Venous thromboembolism (VTE) is a significant but poorly understood complication in patients with newly diagnosed multiple myeloma (NDMM). As a result, most patients receive thromboprophylaxis with low molecular weight heparin (LMWH). The purpose of this retrospective study was to identify risk factors for VTE in NDMM and evaluate the effectiveness of LMWH.

METHODS:

A total of 604 patients with newly diagnosed myeloma completed 3 induction cycles with multiagent chemotherapy with up‐front randomization to thalidomide between 1998 and 2004. Prophylactic enoxaparin was given to thalidomide recipients beginning in June 2001, and 122 subjects received prophylactic epoetin alfa (EPO) as part of an exercise trial. The primary study endpoint was grades 3‐4 VTE.

RESULTS:

A total of 72 patients (11.9%) developed VTE (mostly deep venous thrombosis), with a higher incidence among EPO recipients (P = .001), although only significant for upper extremity DVT (P = .0002). The EPO‐treated patients had higher hemoglobin (Hb) levels throughout the study (P < .0005), although no relationship between higher Hb levels and increasing incidence of VTE could be shown. A history of VTE was a strong predictor of VTE on univariate analysis (P < .000005). Enoxaparin did not reduce the rate of VTE (P = .158). Logistic regression analysis identified thalidomide therapy (P = .001; odds ratio [OR], 2.428; 95% confidence interval [CI], 1.418‐4.159) and prophylactic EPO (P = .002; OR, 2.488; 95% CI, 1.432‐4.324) as risk factors for VTE. Myeloma response and survival were not negatively affected by prophylactic EPO or VTE.

CONCLUSIONS:

Prophylactic EPO, thalidomide therapy, and VTE history, but not higher Hb levels, were found to increase the risk of VTE among NDMM patients receiving multiagent chemotherapy. This risk was not found to be reduced in this population by LMWH thromboprophylaxis. Cancer 2011;. © 2011 American Cancer Society.     

Therapy Insight: venous-catheter-related thrombosis in cancer patients

Central venous catheters (CVCs) have improved the management of patients with cancer substantially, by facilitating chemotherapy and supportive therapy. The use of CVCs is associated with complications such as infection and upper-limb deep vein thrombosis (UL-DVT). The incidence of clinically overt UL-DVT related to the use of CVCs ranges between 2% and 4%. In the most recent study, the incidence of CVC-related thrombosis, as screened by venography, was approximately 18% in the absence of prophylaxis. In cancer patients with CVC-related UL-DVT, the incidence of clinically overt pulmonary embolism was between 15% and 25%, and the incidence of autopsy-proven pulmonary embolism was up to 50%. Pathogenic factors for CVC-related thrombosis include vessel injury caused by the CVC insertion procedure, venous stasis because of the indwelling CVC, and hypercoagulability associated with cancer. Recent studies have not confirmed a benefit for prophylaxis with antithrombotic agents for CVC-related thrombosis. The recommended treatment for CVC-related thrombosis is based on long-term anticoagulant therapy, with or without catheter removal.     

Inferior vena cava filters in the management of cancer-associated venous thromboembolism: a systematic review

This study systematically reviews outcomes after inferior vena cava (IVC) filtration in cancer-associated venous thromboembolism (VTE). A comprehensive review of the English language literature was performed using MEDLINE, COCHRANE library, Embase and CINAHL on outcomes (i.e., pulmonary embolism, recurrent DVT, post-phlebitic syndrome and survival) following IVC filtration in cancer-associated VTE. Fourteen studies with 2,154 cancer patients receiving IVC filters post-VTE were included. All were observational studies. The mean duration of follow-up was 0.7–38 months and mean patient age was 56.8–68 years. Among study participants, 47–87% had stage 3 or 4 cancers. Of the 47–93% of filters inserted for contraindications to anticoagulation (AC), 10–33% were placed for relative contraindications. Recurrent PE was seen in 0–6%, fatal PE in 0–4.5%, recurrent DVT in 0–18.2%, post-phlebitic syndrome (PPS) in 0–2.7%, and IVC thrombosis (ICVT) in 3% of cancer patients. Median survival post-filter insertion was 2–10 months. Evidence supporting the utility of IVC filter insertion in cancer-associated VTE is limited to observational studies only. Preliminary data demonstrate similar safety and efficacy of filters in cancer and non-cancer populations. The combination of filters and anticoagulation is no more effective than either modality alone. Retrievable filters are an attractive option for prevention of VTE in the presence of temporary risk factors or temporary contraindications to anticoagulation in patients who have a reasonable life expectancy, but there is no evidence to support their preferential use in patients with advanced malignancy.     

Venous thromboembolism in colorectal cancer patients with central venous catheters for 5-FU infusion-based pharmacokinetic modulating chemotherapy

Colorectal cancer patients with central venous catheters (CVC) for pharmacokinetic modulating chemotherapy (PMC) have a substantial risk of venous thromboembolism (VTE). PMC, designed as a hybrid of lower metronomic and higher shorter plasma 5-FU concentrations, has been clinically successful. To determine the effectiveness and safety of D-dimer tests and multidetector-row CT (MDCT) for diagnosis in cancer patients with suspected VTE, we carried out a clinical outcome study on PMC outpatients. Patients received a D-dimer test before and after commencing the PMC regimen. MDCT was performed additionally if the D-dimer test appeared positive or showed signs of VTE. When CT results were positive for thromboembolism, anticoagulation was started. The overall prevalence of VTE in PMC patients was 2.0% (7 of 350 patients). In this study, 34 out of 102 colorectal cancer patients gave a positive D-dimer test (33.3%). CT identified venous thrombi in 2 of the 102 patients (2.0%), mural thrombosis on catheterized veins in another 3 patients (2.9%), and endothelial hyperplasia on catheterized veins in 8 patients (7.8%). The catheters of these patients did not show any significant abnormalities. Patients with negative D-dimer tests showed no signs or symptoms of VTE. In colorectal cancer patients receiving continuous 5-FU infusion via CVC, a D-dimer test can be safely used as the primary diagnostic test for ruling out VTE. We suggest 7.0 microg/ml as the D-dimer cut-off value. Thromboprophylaxis should be considered in the patients showing values >7.0 microg/ml.     

Risk of Thrombosis in Adult Philadelphia-Positive ALL Treated with an Asparaginase-Free ALL Regimen

Background: venous thromboembolism (VTE) is a well-known complication in adults with acute lymphoblastic leukemia (ALL), especially in patients treated with asparaginase (ASNase)-including regiments. However, VTE risk in adult Philadelphia-positive ALL (Ph+ve ALL) patients treated with non-hyperCVAD chemotherapy is unclear. In this study, we examined VTE incidence in adult Ph+ve ALL patients treated with imatinib plus a pediatric-inspired asparaginase (ASNase)-free regimen modified from the Dana Farber Cancer Institute (DFCI) ALL protocol. Methods: a single centre retrospective review of Ph+ve ALL patients treated at Princess Margaret Cancer Center (PMCC) from 2008–2019 with imatinib plus modified DFCI protocol was conducted. Results: of the 123 patients included, 30 (24.3%) had at least 1 radiology confirmed VTE event from diagnosis to the end of maintenance therapy. 86.7% (26/30) of the VTE events occurred during active treatment. Of all VTE events, the majority (53.3%) were DVT and/or PE while another significant portion were catheter-related (40.0%). Major bleeding was observed in 1 patient on VTE treatment with low molecular weight heparin (LMWH). Conclusion: a high VTE incidence (24.3%) was observed in adults Ph+ve ALL patients treated with imatinib plus an ASNase-free modified DFCI pediatric ALL protocol, suggesting prophylactic anticoagulation should be considered for all adult Ph+ve ALL patients including those treated with ASNase-free regimens.     

肿瘤并发静脉血栓形成196例临床分析

背景与目的：静脉血栓形成(venous thromboembolism,VTE)是恶性肿瘤患者的第二常见死亡原因。通过了解复旦大学附属肿瘤医院5年间收治的患者VTE的发病情况,分析VTE的相关特点,以提高肿瘤合并VTE的诊断和防治意识,改善患者预后。方法：对复旦大学附属肿瘤医院2009年7月-2014年6月收治的196例肿瘤并发VTE的患者的临床资料进行回顾性分析。分析肿瘤并发VTE的临床特点及发病情况,了解相关因素对VTE发病的影响,了解VTE首发情况。结果：复旦大学附属肿瘤医院5年间共收治肿瘤患者207 514例,其中VTE患者196例,肿瘤并发VTE发生率为0.94‰。腺癌在妇科肿瘤(56.5%)、胃肠道肿瘤(91.7%)、肺癌(71.4%)和胰腺癌(80%)中所占比例较高。单变量Logistic回归分析显示,腺癌为肿瘤患者并发肺栓塞(pulmonary embolism,PE)的高危险因素(OR=0.36,95%CI：0.146~0.885,P=0.026)。化疗大于2次者明显比化疗小于等于2次者VTE的发生率更高(χ²=10.976,P=0.001)。手术组VTE发生率高于非手术组。妇科肿瘤中有大量腹水者的非手术患者并发VTE者(>2 000 mL)更多(34.1% vs 10.7%,P=0.015)。术后和放化疗期间78%~88%的患者因出现深静脉血栓(deep vein thrombosis,DVT)症状发现VTE,而术前检查期间主要是在下肢静脉加压超声(compression venous ultrasonography,CUS)检查发现(59.1%)。复旦大学附属肿瘤医院术后进行物理性预防血栓措施者为15例(13.9%)。结论：复旦大学附属肿瘤医院的肿瘤相关性VTE发生率较其他流行病学调查发生率低。肿瘤患者术后并发VTE的风险明显高于非手术者。腺癌更易并发PE。对于临床无VTE症状的肿瘤患者和大量腹水的妇科肿瘤患者应积极进行VTE的相关检查,术后应更积极采取物理抗栓措施。     

Incidence and Clinical Characteristic of Venous Thromboembolism in Gynecologic Oncology Patients attending King Chulalongkorn Memorial Hospital over a 10 Year Period

Background: Venous thromboembolisms (VTEs) constitute a group of diseases including deep vein thrombosis(DVT) and pulmonary embolism (PE). They regarded as the second leading cause of death in cancer patients andseveral studies have confirmed that VTEs have a negative impact on survival and recurrent rate in both ovarianand endometrial cancer cases. The incidence of VTEs differs worldwide and depends on several risk factorsincluding race, underlying disease, lifestyle, body weight, BMI and genetic risk factors. There is heterogeneityof DVT rates between Asian and Western countries. This study was conducted in order to evaluate the characterand incidence of VTEs in gynecologic oncology patients in King Chulalongkorn Memorial Hospital over a 10year period. Materials and Methods: A retrospective chart review was performed with VTEs defined as objectivediagnosis of acute DVT or PE with typical symptoms and signs. Diagnoses were approved byan internist and/or confirmed with imaging studies. Data from both outpatient and inpatient sessions of the affected cases fromJanuary 2004 to December 2013 were extracted. General characteristics of the patients were collected with detailsof the diseases, types of cancer, stage, date of diagnosis of cancer, operative data, treatment outcome, progressionfree survival and overall survival. Results: Thirty cases of VTEs were identified in a total 2,316 gynecologiconcology cases. The incidence of symptomatic VTEs in total gynecologic oncology patients in our institutionis 1.295%. The incidence of VTEs in ovarian cancer patients in our institution was 5.9%. Duration for VTEdetection ranged from 13 months before diagnosis of cancer to 33 months after diagnosis of cancer. Most of theVTE cases were detected in ovarian cancer patients (60%). The most common cell type was adenocarcinoma(moderately to poorly differentiated) which accounted for 26.7% of the cases. The second most common celltype was clear cell carcinoma with 23.3% of the cases. Thirty percent of VTE cases developed before cancer wasdiagnosed, 20% were diagnosed at the same time as cancer detection and fifty percent developed after cancerwas diagnosed. Median disease free survival of the gynecologic oncology patients with VTE was 7.5 months.Median overall survival (OS) was 12 months. Median progession free survivals of DVT and PE groups were11.5 and 5.5 months, respectively. OS of DVT and PE was 12.0 and 11.5 months respectively. Conclusions: Theincidence of VTE in Asian countries is believed to be lower than in European or Western countries. From ourretrospective review, the incidence of VTEs in all types of gynecologic oncology was 1.295%, much lower thanreported in the West. The reason for the lower incidence may genetic differences. Another factor is that VTEin this review was symptomatic, which is less than asymptomatic VTE. More than half of VTEs in this studydeveloped in ovarian cancer patients. The results are compatible with earlier reports that among gynecologicmalignancies, the incidence of VTE is highest in ovarian cancer.     

Catheter-related thrombosis: risks, diagnosis, and management

Symptomatic thromboembolic complications of central venous catheters (CVCs) occur in 5% or less of general oncology patients. Asymptomatic CVC-related thrombi are more common, but their clinical significance is unclear. Thrombotic risk may be increased by primary thrombophilic disorders, especially the factor V G1691A (Leiden) mutation, thrombogenic catheter material, larger catheter diameter and greater number of lumens, catheter tip malposition, left-sided placement, percutaneous or multiple insertion attempts, a previous CVC or preexisting venous obstruction, prothrombotic therapeutic agents, catheter-associated infections, and fibrinous catheter lumen occlusion. Three recent randomized, prospective, placebo-controlled trials observed no benefit of routine low-dose warfarin or low-molecular-weight heparin in preventing catheter-associated thrombosis. Nevertheless, thromboprophylaxis may be appropriate and safe for selected high-risk patients. Duplex ultrasound can accurately detect CVC-related thrombi involving the jugular, axillary, distal subclavian, and arm veins. Contrast venographic imaging is required for indeterminate duplex findings and to evaluate the deep central veins and pulmonary arteries. Therapeutic anticoagulation, with or without catheter removal, is indicated for patients with acute deep vein thrombosis (DVT) or pulmonary embolism who have no contraindications. Catheter removal alone, with close follow-up, may be sufficient when bleeding risk precludes safe anticoagulation. Approaches to managing catheter-associated thrombosis, including the use of thrombolytic agents, are guided by limited published experience and extrapolation from practices used for lower-extremity DVT. Prospective, randomized, controlled trials are needed to identify the safest and most effective anticoagulant agents, treatment durations, and alternative venous access strategies for cancer patients who develop catheter-associated thrombosis.     

Randomized phase III trial of low-molecular-weight heparin enoxaparin in addition to standard treatment in small-cell lung cancer: the RASTEN trial

BackgroundCoagulation activation and venous thromboembolism (VTE) are hallmarks of malignant disease and represent a major cause of morbidity and mortality in cancer. Coagulation inhibition with low-molecular-weight heparin (LMWH) may improve survival specifically in small-cell lung cancer (SCLC) patients by preventing VTE and tumor progression; however, randomized trials with well-defined patient populations are needed to obtain conclusive data. The aim of RASTEN was to investigate the survival effect of LMWH enoxaparin in a homogenous population of SCLC patients.Patients and methodsWe carried out a randomized, multicenter, open-label trial to investigate the addition of enoxaparin at a supraprophylactic dose (1 mg/kg) to standard treatment in patients with newly diagnosed SCLC. The primary outcome was overall survival (OS), and secondary outcomes were progression-free survival (PFS), incidence of VTE and hemorrhagic events.ResultsIn RASTEN, 390 patients were randomized over an 8-year period (2008–2016), of whom 186 and 191 were included in the final analysis in the LMWH and control arm, respectively. We found no evidence of a difference in OS or PFS by the addition of enoxaparin [hazard ratio (HR), 1.11; 95% confidence interval (CI) 0.89–1.38; P = 0.36 and HR, 1.18; 95% CI 0.95–1.46; P = 0.14, respectively]. Subgroup analysis of patients with limited and extensive disease did not show reduced mortality by enoxaparin. The incidence of VTE was significantly reduced in the LMWH arm (HR, 0.31; 95% CI 0.11–0.84; P = 0.02). Hemorrhagic events were more frequent in the LMWH-treated group but fatal bleedings occurred in both arms.ConclusionLMWH enoxaparin in addition to standard therapy did not improve OS in SCLC patients despite being administered at a supraprophylactic dose and despite resulting in a significant reduction in VTE incidence. Addition of LMWH cannot be generally recommended in the management of SCLC patients, and predictive biomarkers of VTE and LMWH-associated bleeding in cancer patients are warranted.     

Central venous catheter placement by an interventional radiology unit: An Australian experience

The aim of this retrospective study was to analyse the outcomes of central venous catheter (CVC) placement carried out by an interventional radiology unit. A review of our hospital records identified 331 consecutive patients who underwent insertion of a tunnelled or non‐tunnelled CVC between January 2000 and December 2004. Key outcome measures included the technical success rate of CVC insertion and the percentage of immediate (<24 h), early (24 h–30 days) and late (>30 days) complications. A total of 462 CVCs were placed under radiological guidance, with an overall success rate of 98.9%. Immediate complications included one pneumothorax, which was diagnosed 7 days after subclavian CVC insertion, and eight episodes of significant haematoma or bleeding within 24 h of CVC insertion. No cases were complicated by arterial puncture or air embolus. Catheter‐related sepsis occurred in 2% of non‐tunnelled CVC and 8.9% of tunnelled CVC. The overall incidence of catheter‐related sepsis was 0.17 per 100 catheter days. As the demand for chemotherapy and haemodialysis grows with our ageing population, interventional radiology suites are well placed to provide a safe and reliable service for the placement of central venous access devices.     

Venous thromboembolism associated with long-term use of central venous catheters in cancer patients.

Long-term central venous catheters (CVCs) have considerably improved the management of cancer patients because they facilitate chemotherapy, transfusions, parenteral nutrition, and blood sampling. However, the use of long-term CVCs, especially for chemotherapy, has been associated with the occurrence of upper-limb deep venous thrombosis (UL-DVT). The incidence of clinically overt UL-DVT related to CVCs has been reported to vary between 0.3% and 28.3%. The incidence of CVC-related UL-DVT screened by venography reportedly varies between 27% and 66%. The incidence of clinically overt pulmonary embolism (PE) in patients with CVC-related UL-DVT ranges from 15% to 25%, but an autopsy-proven PE rate of up to 50% has been reported. Vessel injury caused by the procedure of CVC insertion, venous stasis caused by the indwelling CVC, and cancer-related hypercoagulability are the main pathogenetic factors for CVC-related venous thromboembolism (VTE). Several studies have assessed the benefit of the prophylaxis of UL-DVT after CVC insertion in cancer patients. According to the results of these studies, prophylaxis with low molecular weight heparin or a low fixed dose of warfarin has been recently proposed. However, the limitations of the experimental design of the prophylactic studies do not allow definitive recommendations. The recommended therapy for UL-DVT associated with CVC is based on anticoagulant therapy with or without catheter removal. This review focuses on the epidemiology, pathogenesis, diagnosis, prevention, and treatment of VTE in cancer patients with long-term CVC.