Identifying orthopedic patients at high risk for venous thromboembolism despite thromboprophylaxis

OBJECTIVE: To evaluate risk factors for venous thromboembolism (VTE) despite thromboprophylaxis in major orthopedic surgery patients at a tertiary care hospital. METHODS: Charts from consecutive patients who underwent total hip replacement (THR), total knee replacement (TKR), or hip fracture surgery (HFS) [hip pinning or hemiarthroplasty] from August 1, 1999, to April 30, 2000, at a large Canadian teaching hospital were abstracted using standardized case report forms. Data were collected on patient characteristics, surgical characteristics, and thromboprophylaxis regimen. Results of tests performed for suspected VTE were documented. Associations between characteristics of interest and objectively confirmed VTE were examined in multivariate analysis. RESULTS: Over the study period, 310 patients underwent major orthopedic surgery and received standard thromboprophylaxis with either dalteparin or enoxaparin (mean duration of prophylaxis, 7 days). Of these, 34% underwent THR, 30% underwent TKR, and 36% underwent HFS. Of 83 suspected cases of VTE, 44 cases (7 proximal and 37 distal deep venous thrombosis [DVT]); 14% of study population) were confirmed with objective testing. Multivariate analyses revealed that knee surgery (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.3 to 10.1) and type of low molecular weight heparin (LMWH) [enoxaparin (more protective): OR, 0.39; 95% CI, 0.20 to 0.80] independently predicted VTE. No patient characteristics (including previous VTE, malignancy, hormonal therapy, postoperative complications) were associated with VTE. CONCLUSION: Despite standard thromboprophylaxis, symptomatic breakthrough VTE, primarily distal DVT, developed in 14% of patients undergoing major orthopedic surgery. Factors that independently predicted VTE in our population were TKR surgery and type of LMWH. TKR patients may warrant more aggressive postoperative physiotherapy and ambulation and adjunctive prophylactic measures such as pneumatic compression. Due to the heterogeneity of different LMWH compounds, direct comparison of the effectiveness of enoxaparin with dalteparin for orthopedic prophylaxis in prospective, randomized trials seems warranted.     

Treating venous thromboembolism in patients with cancer

Venous thromboembolism (VTE) is a major cause of morbidity and mortality among patients with cancer. Although much is known about the factors that contribute to VTE risk, pre-emptive therapy in high-risk populations is clearly indicated in only a few clinical situations. Low-molecular-weight heparin is still the recommended class of anticoagulants for cancer-associated VTE. Management of VTE in patients with renal failure, hemorrhagic brain metastases, thrombocytopenia and coagulopathy remains challenging with few safe and effective alternatives. Novel oral agents are currently being investigated and may play a role in the future in the treatment of cancer-associated VTE.     

Gastroduodenal ulcer incidence in patients with venous thromboembolism

The presence of peptic ulcer disease implies a high risk of bleeding in patients on heparin therapy. We reviewed our experience with 166 consecutive patients admitted because of venous thromboembolism. Of these 166 patients, 29 were referred for upper gastrointestinal endoscopy in order to detect the presence of any lesion that might contraindicate heparin therapy. A gastric ulcer was found in 10 patients, a duodenal ulcer in 11, and gastric erosions with signs of bleeding in 3 patients. Given the unexpectedly high frequency of ulcer in these patients, an upper gastrointestinal endoscopy was routinely performed early in the course of admission in 50 consecutive patients with venous thromboembolism. A gastric ulcer was found in 5 patients (10%), a duodenal ulcer in 7 (14%), and erosions in 2. Five of these patients had an unsuspected ulcer. A case can be made for prophylactic antiulcer therapy for all patients placed on anticoagulants for venous thromboembolism. Upper gastrointestinal endoscopy is indicated in patients with ulcer symptoms, in those with a previous history of peptic ulcer disease, and perhaps, in patients developing occult blood in the stools while on treatment with anticoagulants.     

Factor Xa inhibition in the prevention of venous thromboembolism and treatment of patients with venous thromboembolism

Venous thromboembolism (VTE) is a life-threatening complication following orthopedic surgery. Selective factor Xa inhibition is a new antithrombotic approach designed to avoid difficulties associated with heparins and other current anticoagulants. Several antifactor Xa compounds are in early investigation, but fondaparinux (Arixtra; NV Organon, Oss, The Netherlands; Sanofi-Synthelabo, Paris, France) is the first and most advanced compound in the development of a new class of synthetic antithrombotic agents--the selective factor Xa inhibitors. Fondaparinux has a highly favorable pharmacokinetic profile; four large phase 3 trials comparing subcutaneous fondaparinux 2.5 mg once daily with the low molecular weight heparin (LMWH) enoxaparin in doses approved by regulatory bodies showed that fondaparinux reduced the overall risk of VTE in major orthopedic surgery by > 50% without increasing clinically relevant bleeding. Fondaparinux also appears to be a very promising candidate for the treatment of patients with existing VTE.     

The prevalence of risk factors for venous thromboembolism among hospital patients.

BACKGROUND--This study provides an estimate of the prevalence of risk factors for venous thromboembolism among hospital patients. METHODS--The presence of risk factors for venous thromboembolism was determined from a retrospective review of the medical records of 1,000 randomly selected patients in 16 acute care hospitals in central Massachusetts. RESULTS--The most common risk factors for venous thromboembolism were age 40 years (59%) or more, obesity (28%), and major surgery (23%). The average number of risk factors increased with increasing age. One or more risk factors for venous thromboembolism were present in 78% of hospital patients, two or more in 48%, three or more in 19%, four or more in 6%, and five or more in 1%. CONCLUSION--Risk factors for venous thromboembolism are common among hospital patients, suggesting that prophylaxis should be widely employed. The cost-effectiveness and risk benefit of prophylaxis is well established in patients undergoing major surgery. Further studies are needed to confirm the benefit of prophylaxis in patients with nonsurgical risk factors for venous thromboembolism.     

Graduated compression stockings to prevent venous thromboembolism in hospital: evidence from patients with acute stroke

Pulmonary embolism is the most common preventable cause of death in hospital patients and prevention of venous thromboembolism (VTE) is cost-saving in high-risk patients. Low-dose anticoagulation is very effective at preventing VTE but increases bleeding. Graduated compression stockings and intermittent pneumatic compression devices are also used to prevent VTE and do not increase bleeding, which makes their use appealing in patients who cannot tolerate bleeding, such as patients with acute stroke. Studies that evaluated mechanical methods of preventing VTE were small and mainly used asymptomatic deep vein thrombosis (DVT), detected using screening tests, as the study outcome. The recently published CLOTS Trial 1 (Clots in Legs Or sTockings after Stroke) compared thigh-level compression stockings with no stockings in about 2500 patients with stroke and immobility, and found that thigh-level stockings were not effective. Indirectly, the findings of this study question the ability of stockings to prevent VTE in other patient groups, including those after surgery. CLOTS 1 compared thigh-level and below-knee stockings in about 3000 patients with acute stroke. Given that thigh-level stockings were ineffective in CLOTS 1, it is surprising that they were more effective than below-knee stockings in CLOTS Trial 2. A possible explanation is that below-knee stockings increase DVT, although this seems unlikely. CLOTS 1 and CLOTS 2 question whether graduated compression stockings prevent VTE and suggest the need for further trials evaluating their efficacy in medical and surgical patients.     

Retrospective survey of unselected hospital patients with and without cancer comparing outcomes following venous thromboembolism

Background: Cancer patients are at risk of venous thromboembolism (VTE). Currently, management of these patients is based on studies performed in the general population. Aims: To determine whether the natural history of VTE in cancer patients differs sufficiently from patients in general such that a specific management approach is required. Methods: A retrospective survey was conducted using case records from three tertiary referral hospitals (1993?2001). One hundred and forty‐seven VTE patients with cancer and 82 control patients matched for age and gender were followed for a median of 24 months (0?104 months). Results: The overall prevalence of cancer among patients with VTE was 19.3% (vs 4% in patients with arterial thromboembolic events). In the follow‐up groups, cancer conferred a significantly worse functional status, although other risk factors for VTE were similar. Proximal sites of VTE were twice as common in cancer as in non‐cancer patients. The majority of patients in both groups were treated with oral anti­coagulants. Complications were more common in cancer patients (40%vs 23%) and occurred more frequently despite apparently adequate anticoagulation. Following VTE, cancer patient survival (median 4.1 months, 127 deaths) was markedly worse than non‐cancer patients (median not reached, eight deaths). Thirty‐five cancer deaths occurred within 5 weeks of VTE. Eleven deaths in cancer patients were directly related to VTE compared to three in patients without cancer. Conclusions: Cancer patients with VTE fare extremely poorly compared to the general hospital population. Prospective treatment studies, specifically in cancer patients with VTE, are needed. (Intern Med J 2002; 32: 437?444)     

How I treat venous thromboembolism in patients with cancer

Venous thromboembolism (VTE) is a frequent complication in cancer patients and represents an important cause of morbidity and mortality. Especially in patients who have a poor life expectancy, preventing death from pulmonary embolism is the mainstay of treatment. Critically ill patients should promptly be administered thrombolytic drugs. Except for selected patients requiring aggressive therapy, the initial VTE treatment should be conducted with either adjusted-dose unfractionated heparin or fixed-dose low-molecular-weight heparin (LMWH). LMWHs have the potential to greatly simplify the initial treatment of VTE, making the treatment of suitable patients feasible in an outpatient setting. During anticoagulant therapy, cancer patients have a 2- to 4-fold higher risk of recurrent VTE and major bleeding complications when compared with noncancer patients. The long-term administration of LMWH should be considered as an alternative to anti-vitamin K drugs in patients with advanced disease and in those with conditions limiting the use of oral anticoagulants. Prolongation of anticoagulation should be considered for as long as the malignant disorder is active. The evidence of lowered cancer mortality in patients on LMWH has stimulated renewed interest in these agents as antineoplastic drugs and raises the distinct possibility that cancer and thrombosis share common mechanisms.     

Burden of venous thromboembolism in patients with pancreatic cancer

Pancreatic cancer (PC) is a devastating malignancy with fewer than 10% of patients being alive at 5 years after diagnosis. Venous thromboembolism (VTE) occurs in approximatively 20% of patients with PC, resulting in increased morbidity, mortality and significant health care costs. The management of VTE is particularly challenging in these frail patients. Adequate selection of the most appropriate anticoagulant for each individual patient according to the current international guidelines is warranted for overcoming treatment challenges. The International Initiative on Thrombosis and Cancer multi-language web-based mobile application (downloadable for free at www.itaccme.com) has been developed to help clinicians in decision making in the most complex situations. In this narrative review, we will discuss the contemporary epidemiology and burden of VTE in PC patients, the performances and limitations of current risk assessment models to predict the risk of VTE, as well as evidence from recent clinical trials for the primary prophylaxis and treatment of cancer-associated VTE that support up-dated clinical practice guidelines.     

Incidence of venous thromboembolism in patients hospitalized with cancer

Background

There are sparse data on the frequency of venous thromboembolism in patients with various types of cancer. We sought to determine the incidence and relative risk of venous thromboembolism, pulmonary embolism, and deep venous thrombosis in patients with malignancies.

Subjects and methods

The number of patients discharged with a diagnostic code for 19 types of malignancies, pulmonary embolism or deep venous thrombosis from 1979 through 1999 was obtained from the National Hospital Discharge Survey. Patients studied were men and women of all ages and races.

Results

In patients with any of the 19 malignancies studied, 827 000 of 40 787 000 (2.0%) had venous thromboembolism, which was twice the incidence in patients without these malignancies, 6 854 000 of 662 309 000 (1.0 %). The highest incidence of venous thromboembolism was in patients with carcinoma of the pancreas, 51 000 of 1 176 000 (4.3%), and the lowest incidences were in patients with carcinoma of the bladder and carcinoma of the lip, oral cavity or pharynx. The overall incidences of pulmonary embolism and deep venous thrombosis were also twice the rates in noncancer patients. Incidences with cancer were not age dependent. The incidence of venous thromboembolism in patients with cancer began to increase in the late 1980s.

Conclusion

Patients with cancer had twice the incidence of venous thromboembolism, pulmonary embolism and deep venous thrombosis as patients without cancer. The incidence of venous thromboembolism, pulmonary embolism and deep venous thrombosis associated with cancer differed according to the type of cancer, was comparable in elderly and younger patients, and increased in the late 1980s and 1990s.     

Screening for venous thromboembolism in patients with COVID-19

Journal of Thrombosis and Thrombolysis - Infection with the SARS-COV2 virus (COVID-19) may be complicated by thrombotic diathesis. This complication often involves the pulmonary microcirculation....     

The treatment of venous thromboembolism in patients with cancer

Advances in neuroimaging have modified our knowledge on cerebral vein thrombosis (CVT). This disease is now diagnosed more frequently, and increasing evidence as to what are the most common risk factors and on the natural history of the disease is becoming available. Most patients with CVT have a benign prognosis: only a minority of patients die during the acute phase or in the following months. Most patients surviving CVT recover completely, or have only mild functional or cognitive deficits. Unfractionated or low-molecular weight heparin is widely used as a first-line therapy of CVT, despite the absence of conclusive evidence about the safety and efficacy in this setting. Vitamin K antagonists are usually prescribed for secondary prevention, but the optimal duration of treatment remains unknown. Because most patients with CVT have partial or complete recanalization of the vessels within the first few months after the index event, and because recurrences of CVT after a first episode appear to be uncommon, routine use of long-term therapy or event life-long secondary prevention seem to be unnecessary.     

Congenital thrombophilia among patients with venous thromboembolism.

During a 3-year period we studied 393 adult patients (382 of whom were unrelated) with a history of acute venous thromboembolism. A congenital deficiency state known to predispose to thrombosis was found in 27.2%. Of these, most were due to deficiencies of protein C (9.2%), protein S (7.6%), antithrombin III (5%) or to increased plasma PAI-1 concentration (3.1%) which, in the absence of any known factor that predisposes towards thrombosis, results in a diminished fibrinolytic activity. There was a characteristic pattern between the age of onset (mean 34 years) of thrombosis and individual protein deficiency. Thrombosis appeared spontaneously in 73% of cases with recurrence in 80%. In contrast, in the remaining unrelated patients, 138 (35.1%) in whom venous thromboembolism was secondary and occurred at a mean age of 43 years, and in the other 140 (35.6%) who suffered thromboembolism spontaneously at a later age (mean age 55), there was no permanent protein deficiency state or alteration in fibrinolytic activity and thrombosis recurrence was lower (53.6% and 20.7% respectively). Of the 393 patients, deep vein thrombosis was the most common manifestation; however, in congenital thrombophilia, thrombosis of visceral vessels and Raynaud's syndrome (6%) were also detected.     

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。