Update on diagnosis and anticoagulant therapy for venous thromboembolism

Venous thromboembolism (VTE) continues to be a common medical problem requiring the need for rapid treatment with anticoagulant therapy. Until the recent availability of the direct oral anticoagulants for treatment of VTE, the option for oral anticoagulation was limited to warfarin therapy. The addition of these new medications has been welcomed, but has led to added complexities in deciding the most appropriate agent for each patient based on individual risk factors. Furthermore, there are several circumstances where optimal duration of therapy is not well established. This article will focus on the diagnosis of VTE, the choice of anticoagulant and treatment duration.     

The worcester venous thromboembolism study

BACKGROUND: While there have been marked advances in diagnostic and therapeutic strategies for venous thromboembolism, our understanding of its clinical epidemiology is based on studies conducted more than a decade ago. OBJECTIVE: The purpose of this observational study was to describe the incidence and attack rates of venous thromboembolism in residents of the Worcester Statistical Metropolitan Area in 1999. We also describe demographic and clinical characteristics, management strategies, and associated hospital and 30-day outcomes. DESIGN AND MEASUREMENTS: The medical records of all residents from Worcester, MA (2000 census=477,800), diagnosed with International Classification of Diseases, 9th revision (ICD-9) codes consistent with possible venous thromboembolism during 1999 were independently validated, classified, and reviewed by trained abstractors. RESULTS: A total of 587 subjects were enrolled with validated venous thromboembolism. The incidence and attack rates of venous thromboembolism were 104 and 128 per 100,000 population, respectively. Three quarters of patients developed their venous thromboembolism in the outpatient setting - a substantial proportion of these patients had undergone recent surgery or had a recent prior hospitalization. Less than half of the patients received anticoagulant prophylaxis during high-risk periods before their venous thromboembolism. Thirty-day rates of venous thromboembolism recurrence, major bleeding, and mortality were 4.8%, 7.7%, and 6.6%, respectively. CONCLUSION: These data provide insights into recent incidence and attack rates, changing patient profiles, management strategies, and subsequent outcomes in patients with venous thromboembolism. The underutilization of prophylaxis before venous thromboembolism, and relatively high 30-day recurrence rates, suggest a continued need for the improvement of venous thromboembolism prophylaxis and management in the community.     

Recent air travel and venous thromboembolism resulting in hospital admission

OBJECTIVE: The objective of the study was to determine the proportion of patients admitted to hospital with a deep vein thrombosis (DVT) or pulmonary embolism (PE) in whom recent air travel was documented in the medical records. METHODS: A retrospective review of the medical records of patients with a primary or secondary discharge diagnosis of DVT or PE in four hospitals in New Zealand was undertaken. From the medical records information was collected on demographic details, documentation of the presence of risk factors and results of radiological investigations. Strict radiological criteria were applied to ensure that the diagnosis of DVT or PE was firmly established. RESULTS: In 60 of 576 (10.4%) patients with a confirmed venous thromboembolism there was documentation of recent air travel; in 31 of these 60 subjects no other risk factors were recorded. In those cases in whom details of the air travel had been recorded, it had been undertaken in the previous 1 week in 65.0%, and in 43.3% the air travel was of at least 10-h duration. CONCLUSION: Long distance air travel is an important risk factor for venous thromboembolism requiring hospital admission and represents a significant public health problem in New Zealand.     

Duration of anticoagulant therapy for venous thromboembolism: balancing benefits and harms on the long term

Venous thromboembolism (VTE) is effectively treated with anticoagulant therapy. After an initial treatment phase, extended treatment is effective to prevent recurrence after a first event but this is at the expense of a continued risk of bleeding. Ideally, patients at a high risk of recurrence and low risk of bleeding continue anticoagulant therapy, and for those at low risk of recurrence the duration of treatment can be limited. Identifying these patients, however, is difficult. Duration of treatment after a first VTE provoked by a transient risk factor should be limited to 3 months. Although guidelines suggest extended treatment for all patients after unprovoked VTE unless bleeding risk is high, we emphasize that the long-term risks of recurrent VTE off anticoagulation are uncertain whereas the risk of bleeding associated with anticoagulant therapy increases with age. In the absence of evidence of replaced mortality or improved quality of life with extended anticoagulant treatment, we suggest a limited duration for most patients after a first VTE. Extended treatment can be considered, based mainly on patient preference.     

恶性肿瘤并发静脉血栓栓塞症的临床分析

目的分析并发静脉血栓栓塞症(VTE)恶性肿瘤患者的原发肿瘤种类、分期、分化程度等,以识别高危患者,提高防治意识,减少VTE的发生。方法回顾性分析北京医院2003年1月至2013年1月期间并发静脉血栓栓塞症的恶性肿瘤患者的年龄、性别、基础疾病、原发肿瘤种类、病理类型、分化程度、TNM分期、化疗方案及预后等临床信息。结果在所有18 531例恶性肿瘤患者中,280例并发VTE,其中男性157例,女性123例,年龄(66.60±12.60)岁。包括单纯肺栓塞(PTE)41例,单纯下肢深静脉血栓形成(DVT)189例,PTE合并DVT 50例。肺癌82例,消化道肿瘤78例,泌尿系肿瘤32例,妇科肿瘤27例,血液科肿瘤27例,乳腺癌12例,其他部位肿瘤22例。相比未并发VTE肿瘤患者,并发VTE多见于肺癌、妇科肿瘤和其他肿瘤患者,差异有统计学意义(P0.05)。151例(53.9%)并发VTE肿瘤患者病理类型为腺癌;206例(73.6%)患者发生VTE时,肿瘤处于进展期;247例有明确TNM分期患者中Ⅲ~Ⅳ期患者187例(66.8%);144例有明确病理组织分化程度报告,中、低度分化程度者120例(85.4%)。至随访结束,共有130例患者死亡,中位生存时间为(24.0±7.8)个月,明确诊断VTE后3,6,9,12个月的累积死亡率分别为46.9%、69.2%、80.0%和82.3%。导致死亡的主要原因是肿瘤本身、肺栓塞和感染。结论肿瘤与VTE密切相关,腺癌、进展期肿瘤、分化程度低的肿瘤患者和化疗方案中含铂类药物者更易发生VTE,临床医师应注意对这部分患者进行VTE风险评估,采取必要的预防措施,减少VTE的发生。     

Prolonged seated immobility at work is a common risk factor for venous thromboembolism leading to hospital admission

The role of seated immobility at work in the pathogenesis of venous thromboembolism (VTE) is uncertain. In this case series, 61 patients aged <65 years with a recent admission for deep venous thrombosis and/or pulmonary embolism completed an interviewer-administered questionnaire to obtain information regarding risk factors. Prolonged seated immobility at work in the 4 weeks before the VTE event was defined as being seated at least 8 h in a 24-h period and at least 3 h at a time without getting up, at least 10 h in a 24-h period and at least 2 h at a time without getting up or at least 12 h in a 24-h period and at least 1 h at a time without getting up. The most commonly identified risk factors were family history of VTE (21 of 61, 34%), seated immobility at work (21 of 61, 34%) and a thrombophilic state (19 of 61, 31%). We conclude that prolonged seated immobility at work may represent a common and important risk factor for VTE.     

Venous thromboembolism and ethnicity

Venous thromboembolism (VTE) has long been considered a disease that affects predominantly white populations, a misconception resulting from a paucity of epidemiological data from non-Western countries, and the low incidence of hereditary thrombophilia in those of non-Caucasian background. Over the last decade, interest has grown in this area with the emergence of evidence that VTE is as prevalent, if not more so, in the black population and is also common in Asian groups. Much is still to be learned, as our current knowledge of hereditary thrombophilia and acquired risk factors do not fully explain the risk of VTE in non-Caucasian groups. This review summarises the current understanding of ethnic variation in VTE and highlights the need for further research in this area.     

Evaluation of an automated latex D‐dimer immunoassay in the clinical assessment of suspected venous thromboembolism

Because the reliability of clinical signs in venous thromboembolism (VTE) is poor, a highly sensitive, non‐invasive test may improve the selection of patients requiring further investigation. We assessed the sensitivity and negative predictive value of an automated D ‐dimer latex immunoassay (IL‐Test?) in 68 patients presenting with suspected VTE. The plasma D ‐dimer concentration was estimated and an appropriate diagnostic radiological investigation performed. Control values were obtained from healthy young and elderly volunteers. Using a cut‐off value of 330 ng/ml, the assay had a sensitivity of 100% and negative predictive value of 100% for VTE. We conclude that the IL‐Test^TM. automated D ‐dimer assay has a suitably high sensitivity and adequate negative predictive value to be included in a pre‐test clinical probability protocol for the evaluation of patients with suspected VTE.     

肺癌合并肺血栓栓塞症和深静脉血栓形成的比较研究

目的比较肺癌合并肺血栓栓塞症(PTE)和深静脉血栓形成(DVT)的临床特点及预后。方法对2003年1月至2013年4月北京医院肺癌合并PTE和DVT的患者进行回顾性临床分析,记录年龄、性别、临床表现、病理类型、TNM分期、PS评分、化疗方案及预后等临床信息。结果 PTE组35例,年龄(67.31±9.38)岁,DVT组45例,年龄(64.62±12.48)岁。PTE组肺部基础疾病的发生率高于DVT组(9 vs 4例,P=0.043);而DVT组留置深静脉导管的患者显著多于DVT组(11 vs 1例,P=0.007)。PTE组HCT和Hb较DVT组增高(分别为36.9±4.01 vs 33.44±5.57,P=0.003;125.4±14.43 vs 113.48±21.28,P=0.006)。PTE组中有14例PTE患者为无意中发现。在两组病人中,以NSCLC为主,病理类型多为腺癌,TNM分期Ⅲ~Ⅳ期居多。肺癌合并PTE组3月、6月、9月和12个月累积发生率分别为71.4%、77.1%、82.9%和85.7%;DVT组3月、6月、9月和12个月累积发生率分别为75.6%、77.8%、82.2%和84.4%。生存分析显示,PET组和DVT组,中位生存时间无显著差异(5.0±2.1月vs 15.6±6.59月,P=0.12)。结论肺癌合并PTE和DVT患者具有相同的危险因素,但PTE组较多合并肺部疾病,而DVT组较多留置深静脉导管。两组患者中腺癌是最常见的病理类型,TNM分期多为Ⅲ~Ⅳ期。PTE或DVT多发于肺癌诊断3~6月内,并导致患者预后不佳。     

The Epidemiology of Venous Thromboembolism in the Community: Implications for Prevention and Management

The epidemiology of venous thromboembolism (VTE) in the community has important implications for VTE prevention and management. This review describes the incidence, survival, recurrence, complications and risk factors for deep vein thrombosis and pulmonary embolism occurring in the community. VTE incidence among whites of European origin exceeds 1 per 1000; the incidence among persons of African and Asian origin may be higher and lower, respectively. VTE incidence over recent time remains unchanged. Survival after VTE is worse than expected, especially for pulmonary embolism where one-quarter of patients present as sudden death. Of those patients who survive, 30% develop VTE recurrence and venous stasis syndrome within 10 and 20 years, respectively. Common independent VTE risk factors include surgery, hospitalization for acute medical illness, nursing home confinement, trauma, active cancer, neurologic disease with extremity paresis, superficial vein thrombosis, central venous catheter/transvenous pacemaker, and among women, oral contraceptives, pregnancy and the puerperium, and hormone and SERM therapy. Exposures can identify populations at risk but have a low predictive value for the individual person. An acquired or familial thrombophilia may predict the subset of exposed persons who actually develop symptomatic VTE. In conclusion, VTE is a common, lethal disease that recurs frequently and causes serious long-term complications. To improve survival and prevent complications, VTE occurrence must be reduced. Better individual risk stratification is needed in order to modify exposures and target primary and secondary prophylaxis to the person who would benefit most. Funded, in part, by grants from the National Institutes of Health (HL-60279, HL-66216, AR-30582) and Centers for Disease Control and Prevention (TS-326), U.S. Public Health Service; and by Mayo Foundation     

Heparin-induced thrombocytopenia from venous thromboembolism treatment

OBJECTIVES: We aimed to characterize the clinical experiences of patients in whom heparin-induced thrombocytopenia (HIT) complicated heparin therapy for venous thromboembolism (VTE) and who switched to argatroban. DESIGN: A retrospective analysis of previously reported prospective, multicentre, historical-controlled Argatroban-911 and Argatroban-915 studies of argatroban therapy in HIT. SETTING: Inpatient. SUBJECTS: Patients (n = 145) administered heparin for VTE and who developed HIT were identified. INTERVENTIONS: Patients were treated with argatroban 2 mcg kg(-1) min(-1) for up to 14 days, adjusted to maintain activated partial thromboplastin times 1.5 to three times baseline. Patient characteristics, anticoagulation and outcomes were summarized. The primary end-point was a composite of death, amputation, or new thrombosis within 37 days of argatroban initiation. RESULTS: During heparin therapy, platelet counts decreased (mean +/- SD nadir: 78 +/- 67 x 10(9) L(-1)), and 75 (52%) patients developed thrombosis. After heparin was discontinued, patients received argatroban (mean dose 2.1 +/- 1.2 mcg kg(-1) min(-1)) for 6.8 +/- 4.3 days. By day 6 of argatroban therapy, the mean platelet count rose to >150 x 10(9) L(-1). The primary end-point occurred in 41 (28.3%) patients (values of 26-44% are reported for argatroban therapy of HIT from any heparin indication). Seventeen (11.7%) patients, including 12 who had also experienced thrombosis whilst on heparin, developed new thrombosis after argatroban initiation, typically on the day argatroban was discontinued or later (n = 10). Seven (4.8%) patients experienced major bleeding. CONCLUSIONS: For VTE patients with HIT, argatroban provides effective anticoagulation, with outcomes comparable with those reported for other argatroban-treated HIT patients. New thrombosis in this setting occurred most often in patients with existing HIT-associated thrombosis, before HIT recognition or either at/after argatroban discontinuation.     

Links between arterial and venous disease

An increasing body of evidence suggests the likelihood of a link between arterial and venous disease. According to the results of recent studies, atherosclerosis and venous thromboembolism (VTE) share common risk factors, including age, obesity, diabetes mellitus and metabolic syndrome. Atherosclerosis has the potential to promote the development of thrombotic disorders in the venous system. Another scenario assumes that the two clinical conditions are simultaneously triggered by biological stimuli responsible for activating coagulation and inflammatory pathways in both the arterial and the venous system. Several recent studies have consistently shown that patients with VTE of unknown origin are at a higher risk of cardiovascular diseases, including atherosclerotic complications, than patients with secondary VTE and matched control individuals. Future studies are needed to clarify the nature of this association, to assess its extent and to evaluate its implications for clinical practice.