Prevention of venous thromboembolism in the cancer surgery patient

Cancer patients, especially those undergoing surgery for cancer, are at extremely high risk for developing venous thromboembolism (VTE), even with appropriate thromboprophylaxis. Anticoagulant prophylaxis in cancer surgery patients has reduced the incidence of VTE events by approximately one-half in placebo-controlled trials, and extended prophylaxis (for up to 1 month) has also significantly reduced out-of-hospital VTE events in clinical trials in this population. Clinical trials show no difference between low-molecular-weight heparin (LMWH) and unfractionated heparin in VTE prophylaxis efficacy or bleeding risk in this population, although the incidence of heparin-induced thrombocytopenia is lower with LMWH. The risk-benefit profile of low-dose anticoagulant prophylaxis appears to be favorable even in many cancer patients undergoing neurosurgery, for whom pharmacologic VTE prophylaxis has been controversial because of bleeding risks.     

Evaluation of a thromboprophylaxis quality improvement project in a palliative care unit

ContextThe benefits of anticoagulation treatment for primary prophylaxis in patients with advanced progressive diseases are unclear. Moreover, there are no empirically based guidelines on thromboprophylaxis for palliative care patients.ObjectivesTo prospectively evaluate a quality improvement protocol on the use of thromboprophylaxis on a 36-bed palliative care unit (PCU).MethodsA protocol was developed to guide and standardize practice related to venous thromboembolic events (VTE) and anticoagulation medication use on the PCU in patients with a life expectancy of less than six months. Through a prospective audit, data were collected for consecutively admitted patients over a period of four months.ResultsOf the 127 patients admitted to the PCU, 41 (32.3%) were on thromboprophylaxis on admission. All but one of these patients had come from an acute care hospital. Thromboprophylaxis was discontinued in 36 (87.8%) of these patients; one patient went on to develop a VTE. Of the 71 patients admitted without thromboprophylaxis, none of the patients were started on thromboprophylaxis and six went on to develop a VTE.ConclusionIn this quality improvement study of patients admitted to a PCU largely for end-of-life care, thromboprophylaxis was discontinued in most patients without a significant increase in the incidence of symptomatic VTE. The validity of recommendations extrapolated from the general hospitalized cancer population supporting routine thromboprophylaxis and applied to these patients can be challenged. A policy that requires thromboprophylaxis in all hospitalized cancer patients may run the risk of indiscriminately including patients who are in the terminal phase of their lives.     

Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study

BACKGROUND: Patients undergoing major abdominal surgery carry a high risk of venous thromboembolism (VTE), but the optimal duration of postoperative thromboprophylaxis is unknown. OBJECTIVES: To evaluate the efficacy and safety of thromboprophylaxis with the low molecular weight heparin (dalteparin), administered for 28 days after major abdominal surgery compared to 7 days' treatment. PATIENTS/METHODS: A multicenter, prospective, assessor-blinded, open-label, randomized trial was performed in order to evaluate prolonged thromboprophylaxis after major abdominal surgery. In total, 590 patients were recruited, of whom 427 were randomized and received at least 1 day of study medication, and 343 reached an evaluable endpoint. The primary efficacy endpoint was objectively verified VTE occurring between 7 and 28 days after surgery. All patients underwent bilateral venography at day 28. RESULTS: The cumulative incidence of VTE was reduced from 16.3% with short-term thromboprophylaxis (29/178 patients) to 7.3% after prolonged thromboprophylaxis (12/165) (relative risk reduction 55%; 95% confidence interval 15-76; P=0.012). The number that needed to be treated to prevent one case of VTE was 12 (95% confidence interval 7-44). Bleeding events were not increased with prolonged compared with short-term thromboprophylaxis. CONCLUSIONS: Four-week administration of dalteparin, 5000 IU once daily, after major abdominal surgery significantly reduces the rate of VTE, without increasing the risk of bleeding, compared with 1 week of thromboprophylaxis.     

Low-molecular-weight heparin thromboprophylaxis in medical-surgical critically ill patients: A systematic review

Purpose

The study aimed to systematically review the effect of low-molecular-weight heparin (LMWH) thromboprophylaxis in medical-surgical critically ill patients in the intensive care unit.

Methods

In duplicate and independently, we searched for relevant articles using MEDLINE and EMBASE; we also contacted experts and reviewed reference lists. For included studies, we abstracted data on study and patient characteristics, LMWH use, clinical outcomes (venous thromboembolism [VTE], bleeding, and mortality), laboratory outcomes (anti-Xa levels and thrombocytopenia), and methodological quality.

Results

We included 8 prospective cohort studies and 1 randomized trial, with a total of 629 patients. Eight studies (n = 406 patients) reported anti-Xa levels and only 3 studies (n = 240 patients) reported on at least one clinical outcome. Low-molecular-weight heparin does not appear to bioaccumulate based on repeated measurements of trough anti-Xa levels. Thrombocytopenia occurred in 9.3% of patients receiving LMWH; heparin-induced thrombocytopenia was not reported. In studies reporting clinical outcomes, the frequency of VTE in patients receiving LMWH ranged from 5.1% to 15.5%, bleeding complications ranged from 7.2% to 23.1%, and mortality ranged from 1.4% to 7.4%.

Conclusions

Low-molecular-weight heparin may be effective for thromboprophylaxis in medical-surgical critically ill patients, but no trials have compared LMWH against an alternative active strategy; thus, LMWH cannot be recommended routinely. Trials testing LMWH thromboprophylaxis are required, which examine patient-important end points such as the incidence and clinical consequences of VTE, bleeding, heparin-induced thrombocytopenia, and mortality.     

Epidemiology of venous thromboembolism in Asian patients undergoing major orthopedic surgery without thromboprophylaxis. The SMART Study

Summary.  Background:  In Asian patients undergoing surgery, the incidence of venous thromboembolism (VTE) is thought to be low relative to Western patients, and the routine use of thromboprophylaxis is controversial. Objectives:  The aim of this work was to study the epidemiology of VTE in Asian patients undergoing orthopedic surgery without thromboprophylaxis. Patients and methods:  We performed a prospective observational study of a cohort of consecutive Asian patients hospitalized for total hip or knee replacement or hip fracture surgery without thromboprophylaxis. The primary study outcome was the incidence of the composite of symptomatic VTE or sudden death at hospital discharge. This outcome was also assessed at 1 month's follow-up. Results:  Between April 2001 and July 2002, 2420 patients were enrolled. Median age was 68 years and the median duration of hospital stay was 13 days. The rate of symptomatic VTE or sudden death as notified by investigators was 2.3%[55 patients, 99% confidence interval (CI) 1.6, 3.2] and 1.2% (28 patients, 99% CI 0.7, 1.8) after adjudication by an independent committee. Chronic heart failure, varicose veins and a history of VTE were independent risk factors ( P <  0.05) for the occurrence of the primary endpoint. At 1 month's follow-up, the incidence of adjudicated symptomatic VTE or sudden death was 1.5% (35/2264 patients). Conclusion:  In Asian patients, the incidence of symptomatic VTE after major orthopedic surgery is not low, consistent with the rates observed in Western countries. The use of thromboprophylaxis should be considered in Asian patients undergoing such high-risk surgical procedures.     

Retrospective database analysis of the prevention of venous thromboembolism with low-molecular-weight heparin in acutely III medical inpatients in community practice

BACKGROUND: Clinical trials have demonstrated that prophylaxis with low-molecular-weight heparin reduces the occurrence of venous thromboembolism (VTE) among acutely ill medical inpatients in the experimental setting. OBJECTIVE: The goal of this retrospective database analysis was to examine the outcomes of low-molecular-weight heparin thromboprophylaxis among acutely ill medical inpatients in community practice. METHODS: Using a large, geographically diverse, multihospital US database, we identified persons aged > or =40 years who had a hospital stay > or =6 days for an acute medical condition (including selected circulatory disorders, respiratory disorders, infectious diseases, or neoplasms) during calendar-year 2000. From these patients, those who received either enoxaparin thromboprophylaxis or no thromboprophylaxis were identified. Surgical patients, patients with nonthrombotic conditions requiring anticoagulant therapy, those transferred from or discharged to another acute care facility, and those medically ineligible for anticoagulation therapy were excluded. We compared the incidence of deep-vein thrombosis (DVT), pulmonary embolism (PE), all VTE (ie, DVT and/or PE), and death during the hospital stay in the 2 cohorts. RESULTS: A total of 162 patients receiving enoxaparin thromboprophylaxis and 3557 receiving no thromboprophylaxis were identified. The risk of VTE over the course of hospitalization was 1.9% with enoxaparin thromboprophylaxis versus 6.2% with no thromboprophylaxis (relative risk = 0.30; P=0.023 ); mortality was similar in the 2 groups (8.0% vs 7.3; P=NS ). CONCLUSIONS: Using hospital administrative data, we observed a 70% lower risk of VTE for hospitalized acutely ill medical patients receiving low-molecular-weight heparin thromboprophylaxis verus those receiving no thromboprophylaxis; these results are consistent with findings from clinical trials of low-molecular-weight heparin versus placebo. We conclude that the low-molecular-weight heparin enoxaparin is effective in reducing the risk of VTE in acutely ill medical inpatients in community practice.     

Prévention de la maladie veineuse thromboembolique en réanimation : Quand ? Pourquoi ? Comment ?

The occurrence of venous thromboembolism(VTE) in critically ill patients represents an important cause of increased morbidity and mortality. Because the incidence of VTE in the intensive care unit (ICU) is about 30% without thromboprophylaxis, patients hospitalized in these units should be considered at high risk for thrombosis and should receive a prophylactic treatment. Besides conventional risk factors for VTE (age, cancer, surgery, obesity…), specific factors present in ICU patients may also contribute to VTE, including mechanical ventilation, vasopressors, and central venous lines. Despite these observations, there are few rigorous studies evaluating thromboprophylaxis specifically in the ICU. Low-molecular weight heparins and unfractionated heparin appear effective in preventing VTE. However, the impact of certain clinical characteristics of critically ill patients (oedema, renal insufficiency, or vasopressor) on the risk/benefit of these drugs needs to be clarified. Mechanical devices, elastic stockings, and intermittent pneumatic compression are recommended for critical care patients who are at high risk for bleeding; however, they have never been evaluated in any clinical trial in ICU patients. Further studies are needed to better understand the reasons of VTE occurrence in ICU patients in order to improve management of their thromboprophylaxis.     

Recurrent pregnancy loss and thrombophilia

In the last decades we found many data concerning the association between a hypercoagulable state and its causes and adverse pregnancy outcome, in particular recurrent pregnancy loss (RPL). Although first studies were focused only on the association between thrombophilia and RPL, subsequent studies underlined also a potential role of antithrombotic treatment to prevent vascular complication such as venous thromboembolism (VTE) during pregnancy. Now, emerging data seem to be available also on the role of active thromboprophylaxis with heparin and pregnancy outcome. This review will be focused on the recent knowledge between thrombophilia, hypercoagulable state, RPL, VTE and future perspectives.     

Universal pharmacological thromboprophylaxis for total knee arthroplasty may not be necessary in low‐risk populations: a nationwide study in Taiwan

Summary. Background: Thromboprophylaxis should be universally administered in major orthopedic surgery. However, epidemiology of venous thromboembolism (VTE) following major knee surgery in Asia is scarce. Objective: To describe the use of thromboprophylaxis and calculate the incidence and risk factors of symptomatic VTE following major knee surgery in Taiwan. Methods: We used Taiwan’s National Health Insurance Research Database to retrospectively identify patients (≧45 years) who underwent major knee surgery from 1998 to 2007 and collected the medical records within 3 months after the discharge. Logistic regression analysis was used to determine the risk factors of symptomatic VTE after the surgery. Results: We identified 113 844 patients (mean age, 69.0 ± 7.7 years; female, 75.2%) receiving major knee arthroplasties. The mean length of stay was 9.1 ± 3.3 days. The overall pharmacological thromboprophylaxis rate was 2.2%. The 3‐month cumulative incidence of procedure‐related symptomatic VTE was 0.46% (95% CI, 0.42–0.50%). The median time to the first post‐operation VTE was 7 days, with 85.4% occurring within 2 weeks after the discharge. Logistic regression analysis showed that previous VTE, malignancy, heart failure and neurologic disorder with extremity paralysis or pararesis were independent risk factors (P < 0.05) for symptomatic VTE following major knee arthroplasties. Conclusions: The thromboprophylaxis rate is low, which may be due to the very low incidence of symptomatic VTE after the surgery in Taiwan. Most symptomatic VTE occurred within 2 weeks after the surgery. Universal thromboprophylaxis for knee arthroplasties may not be necessary in Taiwan, but it should be considered in some high‐risk populations.     

Extended thromboprophylaxis with low-molecular-weight heparins after hospital discharge in high-risk surgical and medical patients: A review

Background: Prophylaxis against venous thromboembolism (VTE) is routinely administered during the hospital stay in at-risk surgical and medical patients. However, in high-risk groups, the risk of deep-vein thrombosis or pulmonary embolism may persist for several weeks after discharge. The standard duration of thromboprophylaxis (6–14 days) may not provide adequate protection against such events.Objective: This article reviews published data on the efficacy and safety profile of extended-duration thromboprophylaxis in patients at high risk for VTE, the potential cost-effectiveness of such treatment, and practical aspects of ensuring an effective transition from the inpatient to the outpatient setting.Methods: MEDLINE and the Cochrane Database of Systematic Reviews were searched through January 2009 for relevant English-language reports of clinical trials, abstracts, and case reports. The search terms included, but were not limited to, venous thromboembolism, pulmonary embolism, anticoagulation, thromboprophylaxis, prolonged duration, and extended duration. The reference lists of the identified articles were reviewed for additional relevant publications. Congress Web sites were also consulted. The principal criteria for inclusion of a study were that it have a prospective, randomized design and include a control group. Case series and retrospective analyses were excluded.Results: Studies have found that extended-duration thromboprophylaxis (28–45 days) with low-molecular-weight heparins (LMWHs) can reduce the risk of VTE in high-risk patients. In separate meta-analyses, extended-duration thromboprophylaxis with LMWH was associated with significant reductions in the likelihood of symptomatic VTE compared with standard-duration thromboprophylaxis in patients undergoing major orthopedic surgery (odds ratio [OR] = 0.38; 95% CI, 0.24–0.61) or major abdominal or pelvic surgery (Peto OR = 0.22; 95% CI, 0.06–0.80). There was large heterogeneity in the reported rates of major and minor bleeding. The occurrence of clinically relevant bleeding events was generally low (<1%), particularly during extended prophylaxis. Extended-duration thromboprophylaxis was cost-effective compared with standard-duration thromboprophylaxis, with increased pharmacy costs offset by reductions in VTE and the associated costs of hospitalization.Conclusions: In high-risk surgical and medical patients, the risk of VTE may extend beyond the period of hospitalization. Such patients may benefit from extended-duration thromboprophylaxis to reduce the risk of late VTE events. LMWHs were efficacious, were associated with low rates of clinically relevant bleeding complications, and were cost-effective in patients at high risk for VTE.     

Antithrombotic therapy for secondary prevention of unprovoked venous thromboembolism: a systematic review and network meta-analysis of randomized controlled trials

BackgroundExtended antithrombotic treatment is recommended for secondary prevention of unprovoked venous thromboembolism (VTE), however, there is no consensus on which antithrombotic strategy is preferable.AimTo compare the efficacy and safety of different antithrombotic strategies for secondary prevention unprovoked VTE.MethodsCochrane Central Register of Controlled Trials, Embase, and MEDLINE were systematically searched from inception to 22 July 2020 for randomized controlled trials (RCTs) that compared the efficacy and/or safety of extended antithrombotic strategies including aspirin, warfarin and direct oral anticoagulants (DOACs) for secondary prevention of unprovoked VTE. The primary outcome was risk of major bleeding and the secondary outcomes were risks of recurrent VTE and all-cause death. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using pairwise and network meta-analysis with random effect. Possible ranking of extended antithrombotic strategies was plotted using the surface under the cumulative ranking curve and mean ranks.ResultsSeventeen RCTs met the inclusion criteria, and meta-analysis results showed that warfarin was associated with significantly higher risk of major bleeding than placebo/observation (OR 2.71, 95% CI 1.32–5.55) or apixaban (OR 10.65, 95% CI 1.06–107.13). Apixaban and low-apixaban were the top two strategies according to the ranking of major bleeding. Warfarin (OR 0.25, 95%CI 0.13–0.49), rivaroxaban (OR 0.18, 95%CI 0.03–0.90), apixaban (OR 0.18, 95%CI 0.04–0.85) and low-apixaban (OR 0.18, 95%CI 0.04–0.82) were related to significantly lower risk than placebo/observation; edoxaban was non-inferior to warfarin on the risk of recurrent VTE. Furthermore, apixaban was linked with significantly lower risk of all-cause death than placebo/observation (OR 0.29, 95% CI 0.09–0.88).ConclusionApixaban showed superiority to other antithrombotic strategies on major bleeding and all-cause death for secondary prevention of unprovoked VTE. Further studies are warranted owing to the limited number of studies and positive cases.

Key messages

1. All antithrombotic strategies including warfarin, DOACs and aspirin were superior to placebo/observation on recurrent VTE for secondary prevention of unprovoked VTE.
2. Apixaban demonstrated lower risk of major bleeding than warfarin, and lower risk of all-cause death than placebo/observation.
3. Further research about the efficacy and safety of antithrombotic treatments for secondary prevention of unprovoked VTE is warranted.

     

Venous thromboembolism and its prevention in critical care

BACKGROUND: Evidence-based guidelines for the prevention of venous thromboembolism (VTE) are available for most major surgical and medical patient groups. Such guidelines have not been established for critically ill patients. OBJECTIVE: To perform a systematic review of the prevalence of deep vein thrombosis (DVT), the efficacy of thromboprophylaxis, and the rates of thromboprophylaxis use in critically ill patients. METHODS: Computerized literature search for relevant studies meeting prespecified criteria. RESULTS: The rates of objectively confirmed DVT in 4 prospective studies ranged from 13% to 31%. We identified only 3 randomized trials (1 in abstract form) of thromboprophylaxis in critical care unit patients. These studies show the efficacy of low-dose heparin and low molecular weight heparin compared with no prophylaxis; however, we found no trials comparing these 2 interventions. Eleven compliance studies reported that some form of thromboprophylaxis was used in 33% to 100% of critically ill patients, although only 1 study addressed the issue of appropriate prophylaxis use. CONCLUSIONS: Data on the epidemiology of VTE and its prevention in critically ill patients are very limited. Further research is needed to better define patient risk factors for VTE, optimal methods of thromboprophylaxis, and strategies to improve compliance with prophylaxis recommendations. In the meantime, prevention strategies, shown to be effective in other related patient groups, and general principles of individual pharmacotherapy should guide the routine use of prophylaxis during critical illness.     

From Trousseau to targeted therapy: new insights and innovations in thrombosis and cancer

Summary.  Venous thromboembolism (VTE) commonly occurs in patients with malignant disease. At the 1997 ISTH meeting, cancer and thrombosis was discussed in a state-of-the-art symposium. Since then, there have been many new developments on this topic. Tumors, through expression of tissue factor can activate coagulation. Furthermore, local peritumor activation of coagulation may have important effects on the biology of cancer. A randomized trial has been conducted which evaluated extensive screening to detect underlying malignancy vs. no screening in patients presenting with idiopathic VTE. No statistically significant difference was detected in cancer-related mortality between the two groups. A trial has evaluated extended prophylaxis in patients undergoing surgery for abdominal malignancy. There was a statistically significant reduction in venographically detected deep vein thrombosis in favor of 4 weeks of treatment. In contrast, there is clearly a need for more information on the use of thromboprophylaxis in medical cancer patients. Low molecular weight heparin (LMWH) has replaced unfractionated heparin as the first line treatment in the majority of patients with acute VTE. Many cancer patients with acute VTE can be treated safely at home with subcutaneous LMWH without admission to hospital. The results of a recent trial demonstrated that long-term low molecular weight heparin administered over a 6-month period substantially reduced the rate of recurrent VTE compared with oral anticoagulant therapy with no increase in bleeding. Finally, the first trial specifically designed to evaluate the anticancer effect of long-term LMWH in cancer patients has been conducted and will no doubt stimulate future research.     

Extended pharmacologic thromboprophylaxis in oncologic liver surgery is safe and effective

Essentials

• The risk for venous thromboembolism after liver surgery remains high in the modern era.
• We evaluated the safety/efficacy of extended anticoagulation in liver surgery.
• This protocol reports zero venous thromboembolism events in 124 liver surgery patients.
• Extended anticoagulation after oncologic liver surgery is safe and effective.

Summary

Background

The incidence of venous thromboembolism (VTE) after liver surgery remains high.

Objective

To evaluate the safety and efficacy of extended pharmacologic thromboprophylaxis after liver surgery for the prevention of VTE.

Patient/Methods

From August 2013 to April 2015, 124 patients who underwent liver resection for malignancy were placed on an extended pharmacologic thromboprophylaxis protocol. Intraoperative VTE prophylaxis included thromboembolic deterrent hoses and sequential compression devices. Once hemostasis had been ensured following hepatectomy, daily anticoagulant VTE prophylaxis was initiated for the duration of hospitalization. After hospital discharge, the large majority of patients (114, 91.9%) continued to receive anticoagulant thromboprophylaxis (enoxaparin) to complete a total course of 14 days after minor/minimally invasive hepatectomy or 28 days after major hepatectomy or a history of VTE.

Results

The cohort included 39 (31.2%) major hepatectomies and 38 (31.5%) minor/minimally invasive approaches. The intraoperative, postoperative and overall transfusion rates were 5.6%, 8.1%, and 10.5%, respectively. Pharmacologic thromboprophylaxis was started on postoperative day (POD) 0 for 40 (32.3%) patients and on POD 1 for 84 (67.7%) patients. During 90 days of follow‐up, no postoperative symptomatic deep vein thrombosis or pulmonary embolic events were diagnosed. Standard‐protocol computed tomography scans of the chest, abdomen and pelvis that were obtained for 112 (90.3%) study patients showed no pulmonary emboli, or other thoracic, splanchnic or ileofemoral vein thromboses. Two (1.6%) patients had minor bleeding events that resolved after discontinuation of enoxaparin, requiring neither blood transfusion nor reoperation. The severe complication rate was 5.6%, with no 90‐day mortalities.

Conclusions

These preliminary data suggest that extended pharmacologic thromboprophylaxis for liver surgery patients is safe and effective.     

Prevention of venous thromboembolism after acute ischemic stroke

Venous thromboembolism (VTE) is a common complication after acute ischemic stroke. When screened by 125I fibrinogen scanning or venography, the incidence of deep-vein thrombosis (DVT) in stroke patients is comparable with that seen in patients undergoing hip or knee replacement. Most stroke patients have multiple risk factors for VTE, like advanced age, low Barthel Index severity score or hemiplegia. As pulmonary embolism is a major cause of death after acute stroke, the prevention of this complication is of crucial importance. Prospective trials have shown that both unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are effective in reducing DVT and pulmonary embolism in stroke patients. Current guidelines recommend the use of these agents in stroke patients with risk factors for VTE. Some clinicians are concerned that the rate of intracranial bleeding associated with thromboprophylaxis may outweigh the benefit of prevention of VTE. Low-dose LMWH and UFH seem, however, safe in stroke patients. Higher doses clearly increase the risk of cerebral bleeding and should be avoided for prophylactic use. Both aspirin and mechanical prophylaxis are suboptimal to prevent VTE. Graduated compression stockings should be reserved to patients with a clear contraindication to antithrombotic agents.     

PRODIGE: a randomized placebo‐controlled trial of dalteparin low‐molecular‐weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma

Summary. Background and objectives: Venous thromboembolism (VTE) occurs in 20–30% of patients with malignant glioma per year of survival. We tested the efficacy of long‐term dalteparin low‐molecular‐weight heparin (LMWH) for prevention of VTE in these patients. Patients/methods: Adults with newly diagnosed malignant glioma were randomized to receive dalteparin 5000 anti‐Xa units or placebo, both subcutaneously once daily for 6 months starting within 4 weeks of surgery. Treatment continued for up to 12 months. The primary outcome was the cumulative risk of VTE over 6 months. The target sample size was 512 patients. Events were adjudicated by a committee unaware of treatment. Results: The trial began in 2002 and closed in May 2006 because of expiration of study medication. Ninety‐nine patients were randomized to LMWH and 87 to placebo. Twenty‐two patients developed VTE in the first 6 months: nine in the LMWH group and 13 in the placebo group [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.19–1.4, P = 0.29]. At 6 months, there were three major bleeds on LMWH and none on placebo; at 12 months, 5 (5.1%) major bleeds on LMWH and 1 (1.2%) on placebo occurred (HR = 4.2, 95% CI: 0.48–36, P = 0.22). All major bleeds were intracranial and occurred while on study medication. The 12‐month mortality rates were 47.8% for LMWH and 45.4% for placebo (HR = 1.2, 95% CI: 0.73–2.0, P = 0.48). Conclusions: Trends suggesting reduced VTE and increased intracranial bleeding were seen in the LMWH thromboprophylaxis group. The role of long‐term anticoagulant thromboprophylaxis in patients with brain tumors remains uncertain.     

Factors influencing hospice thromboprophylaxis policy: a qualitative study

Despite level 1 evidence supporting the use of low-molecular weight heparin thromboprophylaxis in hospitalised cancer patients, only 7% of specialist palliative care units (SCPU) have thromboprophylaxis guidelines. The reasons for this are unclear. To explore specialist palliative care units (SPCU) directors' views on thromboprophylaxis in the inpatient unit, audiotaped semi-structured interviews were conducted with SCPU medical directors to explore factors influencing thromboprophylaxis practice. Purposive sampling of units known not to have thromboprophylaxis guidelines was conducted (as identified from previous research). The hospice directory was used to sample from units in each region of Great Britain and Ireland to ensure representation across the specialty. Interviews were transcribed and analysed using interpretative phenomenological analysis (IPA). Four major and four sub themes were identified. Participants were progressive in their attitudes to palliative care and comfortable with instigating active interventions for patient benefit. Symptomatic venous thromboembolism (VTE) was rarely seen and therefore not considered important enough to warrant guidelines. There was concern that evidence informing thromboprophylaxis guidelines in the general population was not transferable to the advanced cancer population and that the outcome measures from these studies were less meaningful to a palliative care patient. Thromboprophylaxis was considered a life prolonging intervention which may result in a poorer death than one because of VTE. Nevertheless, participants were receptive to change if presented with convincing evidence derived from a representative population. Until the true prevalence and symptomatic burden of VTE is known, the role of thromboprophylaxis in the SPCU setting will remain controversial. There is a need for a well-designed study to explore the utility of thromboprophylaxis in the palliative care inpatient setting. However, this will require meaningful outcome measures to be used within a clinically applicable population.     

Anticoagulant therapy for venous thromboembolism during pregnancy: a systematic review and a meta‐analysis of the literature

Summary. Venous thromboembolism (VTE) is one of the most relevant causes of maternal death in industrialized countries. Low molecular weight heparin (LMWH), continued throughout the entire pregnancy and puerperium, is currently the preferred treatment for patients with acute VTE occurring during pregnancy. However, information on the efficacy and safety of anticoagulant drugs in this setting is extremely limited. We carried out a systematic review and a meta‐analysis of the literature to provide an estimate of the risk of bleeding complications and VTE recurrence in patients with acute VTE during pregnancy treated with antithrombotic therapy. The weight mean incidence (WMI) of bleeding and thromboembolic events and the corresponding 95% confidence interval (CI) were calculated. Eighteen studies, giving a total of 981 pregnant patients with acute VTE, were included. LMWH was prescribed to 822 patients; the remainder were treated with unfractionated heparin. Anticoagulant therapy was associated with WMIs of major bleeding of 1.41% (95% CI 0.60–2.41%; I) antenatally and 1.90% (95% CI 0.80–3.60%) during the first 24 h after delivery. The estimated WMI of recurrent VTE during pregnancy was 1.97% (95% CI 0.88–3.49%; I² 39.5%). Anticoagulant therapy appears to be safe and effective for the treatment of pregnancy‐related VTE, but the optimal dosing regimens remain uncertain.     

Preventing venous thromboembolism in acute medical patients

BACKGROUND: While extensive data support the clinical benefit and cost-effectiveness of routine thromboprophylaxis in surgical patients, the use of this approach in medical patients has been controversial. However, recent data, mainly from the MEDENOX trial, support routine thromboprophylaxis in acutely ill medical patients. AIM: To determine attitudes towards VTE prevention in such patients, in departments of internal medicine in Israel. DESIGN: Questionnaire-based survey. METHODS: A questionnaire regarding aspects of VTE prophylaxis was mailed to all heads of internal medicine departments in Israel (n = 90). The questionnaire also included data concerning VTE prevention measures in specific acute medical illnesses, based on the MEDENOX study population. RESULTS: Fifty-eight (64%) departments returned the questionnaire. Forty-seven (81%) of them considered VTE a clinical problem in their departments, but only 37 (63%) had a routine VTE prevention policy. The most frequently used modality for VTE prophylaxis was low-molecular-weight heparin. There was little agreement concerning the exact indications or risk factors in which VTE prophylaxis measures should be used, except the combination of acute medical disabling illness and previous VTE. DISCUSSION: The results emphasize the need for detailed guidelines and risk assessment models for VTE prevention treatments in acutely ill medical patients, as well as better education for physicians.