Excess risk of cancer in patients with primary venous thromboembolism: a national, population-based cohort study

We conducted a nationwide, retrospective cohort study assessing the risk of cancer in VTE patients diagnosed in Scotland in 1982-2000. Significantly elevated risks of cancer were sustained for 2 years after VTE diagnosis, most notably for ovarian tumours and lymphomas. Younger patients were at an increased relative risk from this association.     

The risk and prognosis of cancer after hospitalisation for herpes zoster: a population-based follow-up study

We examined the risk of cancer and survival in a cohort of patients hospitalised with herpes zoster between 1977 and 1996, drawn from the Danish National Registry of Patients. Through linkage with the Danish Cancer Registry, we compared the observed number of cancers with the expected number on the basis of national age-, gender-, and site-specific incidence rates. The survival of herpes zoster patients with cancer was compared with that of non-herpes zoster patients with cancer. Among the 10 588 patients hospitalised with herpes zoster whom we identified, 1427 cancers were observed compared with 1239 expected (relative risk=1.2, 95% confidence interval 1.1-1.2). The risk was substantially elevated during the first year of follow-up, mainly for haematological cancer. Patients with cancer within 1 year of follow-up had a higher prevalence of distant metastases than controls, although the mortality was similar. For those with haematological cancer, however, the mortality was higher for herpes zoster patients than for controls. Haematological cancer following hospitalisation for herpes zoster has a poorer prognosis than in non-herpes zoster patients.     

Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients

BACKGROUND: Venous thromboembolism (VTE) contributes to morbidity and mortality in cancer patients and is a frequent complication of anticancer therapy. In the current study, the frequency, risk factors, and trends associated with VTE were examined among hospitalized cancer patients. METHODS: A retrospective cohort study was conducted using the discharge database of the University HealthSystem Consortium. This included 1,824,316 hospitalizations between 1995 and 2003 at 133 U.S. medical centers. RESULTS: Among 1,015,598 cancer patients, 34,357 (3.4%) were diagnosed with deep venous thrombosis and 11,515 with pulmonary embolism (PE) (1.1%) for an overall VTE rate of 4.1%. Subgroups of cancer patients with the highest rates included black ethnicity (5.1% per hospitalization) and those receiving chemotherapy (4.9%). Sites of cancer with the highest rates of VTE included pancreas (8.1%), kidney (5.6%), ovary (5.6%), lung (5.1%), and stomach (4.9%). Among hematologic malignancies, myeloma (5%), non-Hodgkin lymphoma (4.8%), and Hodgkin disease (4.6%) had the highest rates of VTE. The rate of VTE increased by 28%, secondary to a near-doubling of PE rates from 0.8% to 1.5% (P < .0001). Among patients receiving chemotherapy, the rates of VTE rose from 3.9% to 5.7%, an increase of 47% (P < .0001). In multivariate analysis, risk factors associated with VTE included age >or=65 years, female sex, black ethnicity, use of chemotherapy, primary site of cancer, presence of comorbidities, and year of admission. CONCLUSIONS: VTE, particularly PE, is an increasingly frequent complication of hospitalization in cancer patients. Patients with black ethnicity, specific sites of cancer, or those receiving chemotherapy are disproportionately at risk.     

宫颈癌患者合并静脉血栓栓塞症的危险因素和治疗

目的:探讨宫颈癌化疗患者合并静脉血栓栓塞症的危险因素与治疗.方法:回顾性分析2010年至2015年我院158例宫颈癌化疗患者,按是否合并静脉血栓栓塞症(VTE)分成VTE组(n=40)与无VTE组(n=118),记录分析两组的性别、年龄、既往史、病例类型、肿瘤分期、血小板计数、血黏稠度、D-二聚体以及治疗措施.结果:VET组Ⅳ期:90.00%,血黏稠度增高:67.50%,D-二聚体增高:70.00%;无VTE组Ⅳ期:70.34%,血黏稠度增高:46.61%,D-二聚体增高:49.15%(均P<0.05).Logistic回归显示:肿瘤分期、D-二聚体水平以及血黏稠度与宫颈癌化疗患者发生静脉血栓高度相关,差异均有统计学意义(均P<0.05).40例宫颈癌化疗合并VTE患者2例并发大出血死亡;其余经溶栓、抗凝治疗后19例治愈,4例好转,总有效率为57.50%.结论:宫颈癌肿瘤分期晚、D-二聚体水平高以及血黏稠度高与宫颈癌化疗患者发生静脉血栓高度相关,为宫颈癌患者并发VTE的高危因素;及时评价宫颈癌化疗患者合并VTE的高危因素,及早抗凝治疗,可预防及减少并发VTE,同时提高治疗效果.     

恶性肿瘤合并静脉血栓形成相关危险因素及风险评估

静脉血栓(VTE)是恶性肿瘤的常见并发症,静脉血栓可发生于肿瘤形成的任何阶段并有较高的死亡率和致残率.本文就恶性肿瘤合并静脉血栓形成的相关危险因素及风险评估等方面做一综述,利于早期识别恶性肿瘤合并静脉血栓,并作早期治疗.     

原发性肝癌术后发生静脉血栓栓塞症的危险因素及Caprini风险预测模型的应用

目的:研究原发性肝癌术后发生静脉血栓栓塞症（venous thromboembolism,VTE）的危险因素,并验证和改良Caprini模型对肝癌术后患者VTE发生的预测能力。方法:对我院收治的452例肝癌患者进行回顾性分析,根据术后1月内是否发生VTE而分为VTE组和非VTE组。采用多因素Logistic回归以用来筛选VTE发生的独立危险因素。采用受试者操作特征曲线（receiver operating characteristic,ROC）和曲线下面积（area under ROC curve,AUC）来描述和比较传统Caprini模型和改良Caprini模型对VTE发生预测的准确性。结果:共有41例原发性肝癌患者术后出现VTE,整体发生率为9.07%。单因素分析示BMI、糖尿病患病率、门静脉癌栓发生率、手术时间、二次手术率、以及Caprini评分可能与VTE的发生有关。多因素分析示BMI（OR=1.14,P=0.01）、手术时间（OR=10.91,P=0.001）、有门静脉癌栓（OR=4.98,P=0.001）、二次手术（OR=7.85,P=0.01）和Caprini评分（OR=2.63,P=0.001）是VTE发生的独立危险因素。改良后的Caprini模型和一般Caprini模型在预测VTE时的AUC分别为0.912和0.811;当取最大约登指数时,二者敏感度分别为85.37%和63.41%,特异度分别为85.64%和87.59%。结论:BMI、手术时间、门静脉癌栓、二次手术是原发性肝癌患者术后VTE发生的独立影响因素,联合上述四种指标可以显著提高Caprini模型对VTE的预测能力。     

Risk assessment models for cancer-associated venous thromboembolism

Venous thromboembolism (VTE) is common in cancer patients, and is associated with significant morbidity and mortality. Several factors, including procoagulant agents secreted by tumor cells, immobilization, surgery, indwelling catheters, and systemic treatment (including chemotherapy), contribute to an increased risk of VTE in cancer patients. There is growing interest in instituting primary prophylaxis in high-risk patients to prevent incident (first-time) VTE events. The identification of patients at sufficiently high risk of VTE to warrant primary thromboprophylaxis is essential, as anticoagulation may be associated with a higher risk of bleeding. Current guidelines recommend the use of pharmacological thromboprophylaxis in postoperative and hospitalized cancer patients, as well as ambulatory cancer patients receiving thalidomide or lenalidomide in combination with high-dose dexamethasone or chemotherapy, in the absence of contraindications to anticoagulation. However, the majority of cancer patients are ambulatory, and currently primary thromboprophylaxis is not recommended for these patients, even those considered at very high risk. In this concise review, the authors discuss risk stratification models that have been specifically developed to identify cancer patients at high risk for VTE, and thus might be useful in future studies designed to determine the potential benefit of primary thromboprophylaxis.     

Chronic lymphocytic leukaemia is a risk factor for venous thromboembolism

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in cancer patients. The literature is sparse on the incidence in the most common lymphoid malignancy, chronic lymphocytic leukaemia (CLL). We calculated the incidence rates for VTE in an unselected UK CLL clinic population at 1.45% per patient year. This represents a tenfold increase over previously published estimates of incidence in the general population and a twofold increase over that of the local hospital inpatient population. In our cohort, the risk of VTE was related to stage C disease. Clinicians should be aware that CLL patients are at risk of VTE.     

Circulating tumour cells are associated with increased risk of venous thromboembolism in metastatic breast cancer patients

Background:

Cancer is a risk factor for venous thromboembolism (VTE). Circulating tumour cells (CTCs) are an independent predictor of survival in metastatic breast cancer (MBC) patients. The aim of this study was to test the hypothesis that CTCs are associated with the risk of VTE in MBC patients.

Methods:

This retrospective study included 290 MBC patients treated in the MD Anderson Cancer Center from January 2004 to December 2007. Circulating tumour cells were detected and enumerated using the CellSearch system before starting new lines of therapy.

Results:

At a median follow-up of 12.5 months, 25 patients experienced VTE and 53 patients died without experiencing thrombosis. Cumulative incidence of thrombosis at 12 months was 8.5% (95% confidence interval (CI)=5.5%, 12.4%). Patients with CTCs ⩾1 and ⩾5 had a higher incidence of VTE compared with patients with 0 and <5 CTCs (12-month estimate, 11.7 and 11.6% vs 3 and 6.6%; P=0.006 and P=0.076, respectively). In the multivariate model, patients with CTCs⩾1 had a hazard ratio of VTE of 5.29 (95% CI=1.58, 17.7, P=0.007) compared with patients with no CTCs.

Conclusion:

These results suggest that CTCs in MBC patients are associated with increased risk of VTE. These patients should be followed up more closely for the risk of VTE.     

Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients.

BACKGROUND: The aim was to investigate the outcomes associated with venous thromboembolism (VTE) among irresectable pancreatic cancer patients. METHODS: This is a follow-up study of consecutive irresectable cancer patients, treated and followed up in clinical trials between December 2001 and December 2004 in order to evaluate the prognostic impact of symptomatic VTE on clinical outcomes, such as response to treatment, progression-free survival (PFS) and overall survival (OS). RESULTS: Among 227 irresectable pancreatic cancer patients, with Eastern Cooperative Oncology Group performance status (ECOG-PS) < or = 2, 59 (26.0%) patients developed a VTE. A synchronous VTE occurred in 28 (12.3%) patients, while a VTE during chemotherapy was observed in 15 (6.6%) patients, and 16 (7.0%) patients experienced both events. Presence of synchronous VTE was associated with a higher probability of not responding to treatment (odds ratio 2.98, 95% CI 1.42-6.27, P = 0.004), but showed no effect on both PFS and OS at least at multivariate analysis. Occurrence of a VTE during chemotherapy showed a statistically significant effect on PFS (hazard ratio [HR] 2.59, 95% CI 1.69-3.97, P < 0.0001) and OS (HR 1.64, 95%CI 1.04-2.58, P = 0.032). CONCLUSIONS: Our data suggest that the occurrence of VTE may be associated with a reduced response rate and a shorter PFS and OS among patients with irresectable pancreatic cancer. In these patients the development of VTE may reflect the presence of a biologically more aggressive cancer that in turn leads to a worse prognosis.     

恶性肿瘤与静脉血栓栓塞的研究进展

静脉血栓栓塞(VTE)是恶性肿瘤患者常见并发症,是仅次于肿瘤本身引起患者死亡的第二位原因。血栓有时可作为隐匿性癌的初始表现。血栓形成参与了肿瘤的进展、血管生成和转移等机制。恶性肿瘤患者合并血栓栓塞不仅增加治疗难度,而且降低患者的生存质量并缩短生存时间。抗凝治疗不仅能有效的治疗血栓,而且具有一定的抗肿瘤作用。低分子肝素(LMWH)作为预防和治疗静脉血栓栓塞有效的和安全的首选药物,其优点包括延长生存时间和改善生活质量,减少静脉血栓栓塞的发生率。推荐在院的及接受手术治疗的肿瘤患者预防性使用LMWH。LMWH应作为已确诊的和存在再发可能的VTE的肿瘤患者的一线治疗。     

恶性肿瘤与静脉血栓栓塞的研究进展

静脉血栓栓塞（VTE）是恶性肿瘤患者常见并发症,是仅次于肿瘤本身引起患者死亡的第二位原因。血栓有时可作为隐匿性癌的初始表现。血栓形成参与了肿瘤的进展、血管生成和转移等机制。恶性肿瘤患者合并血栓栓塞不仅增加治疗难度,而且降低患者的生存质量并缩短生存时间。抗凝治疗不仅能有效的治疗血栓,而且具有一定的抗肿瘤作用。低分子肝素（LMWH）作为预防和治疗静脉血栓栓塞有效的和安全的首选药物,其优点包括延长生存时间和改善生活质量,减少静脉血栓栓塞的发生率。推荐在院的及接受手术治疗的肿瘤患者预防性使用LMWH。LMWH应作为已确诊的和存在再发可能的VTE的肿瘤患者的一线治疗。     

晚期肺癌化疗患者伴静脉血栓栓塞症的相关因素分析

目的：分析晚期肺癌化疗患者伴静脉血栓栓塞症的相关因素。方法回顾性分析晚期肺癌化疗伴静脉血栓栓塞症的53例患者（栓塞组）和晚期肺癌化疗未伴有静脉血栓栓塞症的60例患者（对照组）的临床资料,并对晚期肺癌化疗患者伴静脉血栓栓塞症发生的影响因素进行Logistic回归分析。结果单因素分析表明两组患者的性别、病理分型、高脂血症、高血压、肥胖、糖尿病及血小板计数上升比较,差异均无统计学意义（P﹥0.05）;两组患者的年龄、临床分期、吸烟史、D-二聚体上升及血黏稠度升高比较,差异均有统计学意义（P﹤0.05）。通过对筛选出的影响因素予以多因素Logistic回归分析发现,年龄≥60岁、吸烟史、临床分期为Ⅳ期、D-二聚体上升及血黏稠度升高属于晚期肺癌化疗患者伴有静脉血栓栓塞症的危险因素。结论年龄≥60岁、吸烟史、临床分期为Ⅳ期、D-二聚体上升及血黏稠度升高作为晚期肺癌化疗患者伴有静脉血栓栓塞症的危险因素,在临床中,应加以重视。     

Incidence and risk factors for venous thromboembolism,bleeding, and death in colorectal cancer (Cancer‐VTE Registry)

The impact of venous thromboembolism in Japanese colorectal cancer patients has not been elucidated. This prespecified subanalysis of the Cancer‐VTE Registry aimed to report venous thromboembolism and event data after 1 year of follow‐up in 2477 patients with colorectal cancer and investigate risk factors of venous thromboembolism. Of 2477 patients, 158 (6.4%) had venous thromboembolism in venous thromboembolism screening at enrollment. Asymptomatic distal deep‐vein thrombosis accounted for 123/158 (77.8%) of venous thromboembolism cases. During the follow‐up period, symptomatic, incidental events requiring treatment and composite venous thromboembolism incidences were 0.3%, 0.8%, and 1.0%, respectively. The incidence of bleeding events, cerebral infarction/transient ischemic attack/systemic embolic event, and all‐cause death were 1.0%, 0.3%, and 4.8%, respectively. These results were consistent with the main study results. In multivariable analysis, venous thromboembolism at baseline was a risk factor of composite venous thromboembolism during the follow‐up period. Japanese patients with colorectal cancer and advancing cancer stage before treatment had more frequent venous thromboembolism complications at baseline, higher incidence of venous thromboembolism events during cancer treatment, and higher mortality.     

Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer: a systematic review

BACKGROUND.

The authors compared the relative efficacy and safety of low‐ molecular‐weight heparin (LMWH) and unfractionated heparin (UFH) for the initial treatment of venous thromboembolism (VTE) between patients with and without cancer.

METHODS.

By using Cochrane methodology for systematic reviews, separate meta‐analyses were conducted for subgroups of patients with and without cancer, and relative risks (RRs) were compared for statistical significance. The methodologic quality for each outcome was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.

RESULTS.

LMWH reduced mortality significantly compared with UFH in patients with cancer (RR of 0.71; 95% confidence interval [95% CI], 0.52‐0.98 [moderate‐quality evidence]) but not in patients without cancer (RR of 0.97; 95% CI, 0.65‐1.46 [low‐quality evidence]). However, the difference in the RR for the 2 subgroups did not reach statistical significance (P = .113). The difference between LMWH and UFH in the effect on recurrent VTE was not statistically significant in the subgroup with cancer (RR of 0.78; 95% CI, 0.29‐2.08 [low‐quality evidence]), in the subgroup without cancer (RR of 0.94; 95% CI, 0.60‐1.46 [low‐quality evidence]), or between the 2 subgroups (P = .367). No data were available for bleeding outcomes, thrombocytopenia, or postphlebitic syndrome.

CONCLUSIONS.

The current results indicated that LMWH most likely is superior to UFH in reducing mortality in the initial treatment of VTE for patients with cancer. There is a need for more and better designed trials to confirm these findings. Cancer 2008. © 2008 American Cancer Society.     

血浆D-二聚体水平与恶性肿瘤患者发生静脉血栓的相关性

目的:观察血浆D-二聚体（D-dimer,D-D）水平对恶性肿瘤患者相关静脉血栓栓塞症（venous thromboembolism,VTE）发生的风险评估效果。方法:回顾性分析2016年1月至2017年1月本院新收住并经病理组织学证实的171例恶性肿瘤患者的临床资料,以初诊3个月内是否发生静脉血栓栓塞症（VTE）分为VTE组（32例）和非VTE组（139例）,比较两组患者、不同临床分期患者、不同治疗方式患者、不同静脉血栓风险分层患者的血浆D-D值水平,采用Logistic多因素回归分析血浆D-D水平对恶性肿瘤患者相关VTE发生的风险评估效果。结果:VTE组的血浆D-D值水平显著高于非VTE组（P＜0.05）,且随着恶性肿瘤临床分期的增加和静脉血栓风险分层的增高,该现象更加显著。Logistic多因素回归分析结果表明,化疗、手术、静脉血栓风险评估和血浆D-D水平是患者发生VTE的独立危险因素（P＜0.05）。结论:恶性肿瘤患者血浆D-D值水平明显升高,且与恶性肿瘤的临床分期和血栓风险分层相关;对恶性肿瘤患者进行血浆D-D值水平的检测,对预防恶性肿瘤患者初诊3个月内VTE的发生具有十分重要的参考意义。     

The pathogenesis of venous thromboembolism in cancer: emerging links with tumour biology

Venous thromboembolism (VTE) is a frequent complication in individuals with cancer and is considered to be a cause of substantial mortality. Epidemiological studies identify malignancy as an independent VTE risk factor and show that cancer patients are at increased risk of both initial and recurrent VTE events. The risk due to cancer is compounded by the effects of chemotherapy and other treatments. The pathogenesis of cancer-associated VTE is complex involving multiple interactions between tumours and various components of haemostasis. The development of a systemic hypercoagulable state is considered a key pathogenetic feature and is attributed to tumour expression of tissue factor and other procoagulants, activation of vascular cells by tumour-derived cytokines and adhesive interactions between tumour cells and host cells. An increasing body of evidence indicates that the activation of haemostasis in malignant disease contributes to tumour growth and progression by stimulation of intracellular signalling pathways. The interaction of tissue factor, thrombin and other coagulation factors with protease activated receptor (PAR) proteins expressed by tumour cells and host vascular cells leads to the induction of genes related to the processes of angiogenesis, cell survival and cell adhesion and migration.     

Biomarkers predictive of venous thromboembolism in patients with newly diagnosed high-grade gliomas

Background

High-grade gliomas (HGGs) are among the most prothrombotic of malignancies.

Methods

We performed a prospective study to investigate 11 potential biomarkers for prediction of venous thromboembolism (VTE) in newly diagnosed HGG patients who had undergone a neurosurgical intervention. In addition, we tested 2 VTE risk assessment models (RAMs). The strongest predictors of VTE, which were identified by statistical forward selection, were used for the first RAM. The parameters used for the second RAM were both predictive of VTE and available in routine clinical practice.

Results

One hundred forty-one HGG patients were included in this study, and 24 (17%) of them developed VTE during follow-up. An association with the risk of future VTE was found for the following parameters: leukocyte count, platelet count, sP-selectin, prothrombin-fragment 1 + 2, FVIII activity, and D-dimer. The first RAM included low platelet count (<25th percentile of the study population) and elevated sP-selectin (≥75th percentile). The cumulative VTE probability after 12 months was 9.7% for score 0 (n = 76), 18.9% for score 1 (n = 59), and 83.3% for score 2 (n = 6). The second RAM included low platelet count (<25th percentile), elevated leukocyte count, and elevated D-dimer (≥75th percentile). The probability of VTE was 3.3% for score 0 (n = 63), 23.0% for score 1 (n = 53), and 37.7% for score 2 (n = 22) or score 3 (n = 3).

Conclusions

We identified biomarkers suitable for assessing the VTE risk in newly diagnosed HGG patients. The application of 2 RAMs allowed identification of patients at high risk of developing VTE. We could also define patients at low risk of VTE, who would most probably not benefit from extended primary thromboprophylaxis.