Prevention of venous thromboembolism in immobilized neurological patients: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET)

Neurological disorders are often associated with immobilization, thus placing patients at increased risk for venous thromboembolism (VTE). This risk is very high in patients with acute ischemic stroke and spinal cord injuries, and it remains poorly defined in patients with peripheral nervous disorders or degenerative disorders of the central nervous system. The benefit of prophylactic strategies remains often unclear. The Italian Society for Studies on Haemostasis and Thrombosis promoted the development of evidence- and consensus-based guidelines to help physicians involved in the management of neurological patients. After a comprehensive and systematic review of the literature, a panel of experts formulated recommendations for the prevention of VTE in adolescent or adult patients presenting with different neurological disorders. Patients with acute ischemic stroke should routinely receive pharmacological prophylaxis to be started within 48 hours and continued for approximately 14 days; patients with acute hemorrhagic stroke should routinely receive mechanical prophylaxis, pharmacological prophylaxis should be considered once the patient is stable; patients with neuro-muscular degenerative diseases and with other major risk factors for venous thrombosis should be considered for the administration of pharmacological or mechanical prophylaxis; patients with peripheral nerve diseases should receive mechanical prophylaxis while immobilized and in the presence of additional risk factors for VTE, patients with Guillain Barrè should be considered for pharmacological prophylaxis with low molecular weight heparin; patients with spinal cord injury should receive combined mechanical and pharmacological prophylaxis; patients with non traumatic spinal cord diseases should be considered for pharmacological prophylaxis.     

Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada

BACKGROUND: Venous thromboembolism (VTE) prophylaxis in acutely ill medical patients has been shown to be safe and effective. Underutilization of this patient safety practice may result in avoidable mortality and morbidity. OBJECTIVES: We aimed to determine the proportion of hospitalized, acutely ill medical patients across Canada who were eligible to receive thromboprophylaxis and to evaluate the frequency, determinants and appropriateness of its use. PATIENTS/METHODS: CURVE is a national, multicenter chart audit of 29 Canadian hospitals. Data were collected on consecutive patients admitted to hospital for an acute medical illness during a defined 3-week study period. Information on demographic and clinical characteristics, risk factors for VTE and bleeding and use of VTE prophylaxis were recorded. The indications for and appropriateness of VTE prophylaxis were assessed using pre-specified criteria based on international consensus guidelines. Multivariable analyses were performed to identify determinants of prophylaxis use. RESULTS: Of the 4124 medical admissions screened over the study period, 1894 patients (46%) were eligible for study inclusion. The most common specified admitting diagnoses were severe infection (28%), COPD exacerbation or respiratory failure (12%), malignancy (9%) and congestive heart failure (8%). Thromboprophylaxis was indicated in 1702 (90%) study patients. Overall, some form of prophylaxis was administered to 23% of all patients. However, only 16% received appropriate thromboprophylaxis. Factors independently associated with greater use of prophylaxis included internist (vs. other specialty) as attending physician (OR 1.33, 95% confidence interval (CI) [1.03, 1.71]), university-associated (vs. community) hospital (OR 1.46, 95% CI [1.03, 2.07]), immobilization (per day) (OR 1.60, 95% CI [1.45, 1.77]), presence of >or=1 VTE risk factors (OR=1.78, 95% CI [1.35, 2.34]) and duration of hospitalization (per day of stay) (OR 1.05, 95% CI [1.03, 1.07]), however, use of prophylaxis was unacceptably low in all groups. Patients with cancer had a significantly reduced likelihood of receiving prophylaxis (OR=0.40, 95% CI [0.24, 0.68]). Presence of risk factors for bleeding did not influence the use or choice of prophylaxis. CONCLUSION: Most patients hospitalized for medical illness had indications for thromboprophylaxis, yet only 16% received appropriate prophylaxis. Efforts should be made to elucidate the reasons that underlie the very low rate of thromboprophylaxis in medical patients and to develop and test strategies to improve implementation of this patient safety practice.     

Gastrointestinal Prophylaxis in Neurocritical Care

The aim of this study is to review and summarize the relevant literature regarding pharmacologic and non-pharmacologic methods of prophylaxis against gastrointestinal (GI) stress ulceration, and upper gastrointestinal bleeding in critically ill patients. Stress ulcers are a known complication of a variety of critical illnesses. The literature regarding epidemiology and management of stress ulcers and complications thereof, is vast and mostly encompasses patients in medical and surgical intensive care units. This article aims to extrapolate meaningful data for use with a population of critically ill neurologic and neurosurgical patients in the neurological intensive care unit setting. Studies were identified from the cochrane central register of controlled trials and NLM PUBMED for english articles dealing with an adult population. We also scanned bibliographies of relevant studies. The results show that H₂A, sucralfate, and PPI all reduce the incidence of UGIB in neurocritically ill patients, but H₂A blockers may cause encephalopathy and interact with anticonvulsant drugs, and have been associated with higher rates of nosocomial pneumonias, but causation remains unproven and controversial. For these reasons, we advocate against routine use of H₂A for GI prophylaxis in neurocritical patients. There is a paucity of high-level evidence studies that apply to the neurocritical care population. From this study, it is concluded that stress ulcer prophylaxis among critically ill neurologic and neurosurgical patients is important in preventing ulcer-related GI hemorrhage that contributes to both morbidity and mortality. Further, prospective trials are needed to elucidate which methods of prophylaxis are most appropriate and efficacious for specific illnesses in this population.     

Thromboprophylaxis in Acutely Ill Medical Patients: Results of A Survey Among Italian Physicians

Aims

acutely ill medical patients are at increased risk of venous thromboembolism (VTE) and often require thromboprophylaxis, but patient selection and adequate therapeutic decisions may be difficult due to the heterogeneity and the complexity of this population. We conducted a survey among a large cohort of Italian physicians to assess their approach to some important “grey” areas of VTE prevention in this setting.

Methods

a questionnaire was distributed during the meeting of a national society of Internal Medicine (FADOI), held in May 2013. Four clinical scenarios describing areas of clinical uncertainty were administered to participants: the first on a patient with acute ischemic stroke; the second on a patient with severe renal insufficiency; the third on the duration of prophylaxis in the post-acute setting; and the last on a patient at high risk of VTE and at moderate risk of bleeding with preserved mobility.

Results

453 questionnaires were returned (participants mean age 48.5 years). About 70% of participants systematically assess VTE and bleeding risk in their clinical practice, but a minority of them use risk assessment models. Prolonged prophylaxis in the post-acute setting was voted by more than eighty percent of participants; replies to the other three clinical scenarios were more heterogeneous with none of the options selected by more than 60% of participant.

Conclusion

physicians approach to “grey” areas of antithrombotic prophylaxis in the medical setting is quite heterogeneous and sometimes partially in contrast to recent guidelines, reinforcing the need for educational programs and high quality studies in this setting.     

Venous thromboembolism prophylaxis in medical patients: future perspectives

Venous thromboembolism is a common potentially life-threatening complication in acutely ill medical patients. Actually, over 70% fatal episodes of pulmonary embolism during hospitalization occur in non-surgical patients. In the absence of thromboprophylaxis, the incidence of venographically detected deep vein thrombosis is about 15% in medical patients and several trials and meta-analyses have clearly demonstrated the prophylactic role of unfractioned heparin and low-molecular-weight heparins. Although over the last years the knowledge of epidemiology, clinical features and prophylaxis in medical patients has significantly improved, there are still several relevant issues to investigate thoroughly. Scarce data are available on a simple way to stratify patients in order to identify those who should undergo prophylaxis and several studies clearly show that thromboprophylaxis in medical conditions is underused. Moreover, in comparison to surgical settings, very few randomized clinical trials on the efficacy of pharmacologic prophylaxis have been performed and no data at all have been published concerning mechanical prophylaxis in medical conditions. According to previous studies and results of very recently published trials, new data are available to tailor low molecular weight heparin optimal dose, whereas the optimal duration of prophylaxis in medical patients is still a matter of debate. Moreover, the possible role of the new antithrombotic drugs in the venous thromboembolism prevention in medical conditions and the optimal management of thromboprophylaxis in patients with ischaemic stroke have not been fully investigated. Although new evidence represents a significant improvement both in stratification of VTE risk and in decisions about the appropriate type and duration of prophylactic strategies in medical patients, additional data are still needed.     

Changing aspects of care in critically ill neurologic patients

The care of critically ill neurologic patients is not a simple combination of critical care and neurological assessment, but an amalgamated treatment plan that is specific to the cause of injury. Many of the intensive care principles apply to acutely ill neurologic patients, but some specific interventions are available for this category of patients. There is now a better understanding of medical and neurosurgical care of critically ill neurologic patients, and several of the new clinical parameters that impact on our day-to-day care are discussed here.     

Thromboprophylaxis patterns,risk factors,and outcomes of care in the medically ill patient population

Introduction

Medically ill, hospitalized patients are at increased risk for venous thromboembolism (VTE) after discharge. This study aimed to examine thromboprophylaxis patterns, risk factors, and post-discharge outcomes.

Methods

This was a retrospective claims analysis involving administrative claims data and in-patient data abstracted from a sample of hospital charts. Patients aged ≥ 40 years hospitalized for ≥ 2 days for nonsurgical reasons between 2005 and 2009 were included. Hospital chart data were abstracted for a random sample of patients without evidence of anticoagulant use at 30 days post-discharge. The combined data determined whether in-patient thromboprophylaxis (anticoagulant or mechanical prophylaxis) reduces risk of VTE at 90 days post-discharge. Hazard ratios (HR) and odds ratios (OR) were calculated using Cox proportional hazard models and logistic regression.

Results

Of 141,628 patients in the claims analysis, 3.9% received anticoagulants (3.6% warfarin). VTE, rehospitalization, and mortality rates were 1.9%, 17.2%, and 6.2%, respectively. The strongest predictors of post-discharge VTE were history of VTE (HR = 4.0, 95% confidence interval [CI]: 3.3-4.8), and rehospitalization (HR = 3.9, 95% CI: 3.6-4.3). Of 504 medical charts, 209 (41.5%) reported in-patient thromboprophylaxis. There was no statistically significant difference in post-discharge VTE rates between patients who did and did not receive in-patient thromboprophylaxis. All-cause mortality was greater among patients without use of VTE prophylaxis.

Conclusion

Utilization rates of in-hospital and post-discharge VTE prophylaxis were low. In-hospital VTE prophylaxis did not reduce the risk of post-discharge VTE in the absence of post-discharge anticoagulation. Combined in-patient and post-discharge thromboprophylaxis lowered the odds of short-term, all-cause post-discharge mortality.     

Risk factors for inpatient venous thromboembolism despite thromboprophylaxis

Introduction

Venous thromboembolism (VTE) is the most common preventable cause of morbidity and mortality in the hospital. Adequate thromboprophylaxis has reduced the rate of hospital-acquired VTE substantially; however, some inpatients still develop VTE even when they are prescribed thromboprophylaxis. Predictors associated with thromboprophylaxis failure are unclear. In this study, we aimed to identify risk factors for inpatient VTE despite thromboprophylaxis.

Materials and methods

We conducted a case–control study to identify independent predictors for inpatient VTE. Among patients discharged from the BJC HealthCare system between January 2010 and May 2011, we matched 94 cases who developed in-hospital VTE while taking thromboprophylaxis to 272 controls who did not develop VTE. Matching was done by hospital, patient age, month and year of discharge. We used multivariate conditional logistic regression to develop a VTE prediction model.

Results

We identified five independent risk factors for in-hospital VTE despite thromboprophylaxis: hospitalization for cranial surgery, intensive care unit admission, admission leukocyte count > 13,000/mm³, presence of an indwelling central venous catheter, and admission from a long-term care facility.

Conclusions

We identified five risk factors associated with the development of VTE despite thromboprophylaxis in the hospital setting. By recognizing these high-risk patients, clinicians can prescribe aggressive VTE prophylaxis judiciously and remain vigilant for signs or symptoms of VTE.     

Therapeutic strategy of erythropoietin in neurological disorders

Erythropoietin (EPO) was first identified as a hematopoietic cytokine that stimulates proliferation and differentiation of erythroid progenitor cells and was approved by the Food and Drug Administration as a treatment for chronic renal disease patients with anemia. In neural tissues, EPO is working via EPO receptors and induces non-hematopoietic effects. Recent studies have demonstrated that EPO exerts therapeutic potentials on neurological disorders such as ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury, and Parkinson's disease. EPO treatment has been shown to reduce the ischemic infarct and hemorrhage volume, decrease neuronal death including apoptosis, and improve survival rates in animal models. The mechanism of EPO action in neurological disorders involves neuroprotection and promotion of neurogenesis and angiogenesis. Clinical trials of EPO treatments in neurological diseases have accumulated positive results. In stroke patients, EPO treatment may reduce infarct volume and improve functional outcomes. EPO administration has proven safe in animal studies and adult human patients, although safety and efficacy data in neonates and infants are incomplete and long-term multi-center patient evaluations are necessary. Available information suggests that EPO is a promising therapeutic drug for the treatment of neurological diseases.     

Intensive care management of ischemic stroke

The practice of neurointensive care was initially developed to manage postoperative neurosurgical patients and expanded thereafter to the management of patients with primary head trauma, intracranial hemorrhage, vasospasm after subarachnoid hemorrhage, elevated intracranial pressure, and unstable pulmonary or cardiovascular medical conditions in neurologic patients. Can neurointensive care with its advanced medical and neurologic resources improve the outcome of the ischemic stroke patient? This review discusses selection of patients appropriate for admission to the neurologic intensive care unit (NICU) and current options for the intensive care management of severe ischemic stroke and its attendant complications. We propose that the NICU team is well suited to acute stroke management if they apply their advanced skills and technologic resources to manage the severe stroke patient from the time of presentation to the emergency ward. Study is needed to determine the effect that a critical care level of service has on functional outcome.     

Impact of a Neurointensivist on Outcomes in Critically Ill Stroke Patients

Background  

Current guidelines for management of critically ill stroke patients suggest that treatment in a neurocritical care unit (NCCU) and/or by a neurointensivist (NI) may be beneficial, but the contribution of each to outcome is unknown. The relative impact of a NCCU versus NI on short- and long-term outcomes in patients with acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and aneurysmal subarachnoid hemorrhage (SAH) was assessed.     

Missed cerebrovascular events during prolonged sedation for COVID-19 pneumonia

Cerebrovascular complications among critically ill patients with COVID-19 have yet to be fully characterized. In this retrospective case series from a single academic tertiary care referral center in New York City, we present 12 patients with ischemic or hemorrhagic strokes that were found on imaging after a period of prolonged sedation in the setting of COVID-19 pneumonia. This series demonstrates a pattern of cerebrovascular events clinically masked by deep sedation required for management of COVID-19 related acute respiratory distress syndrome (ARDS). Of the 12 patients included, 10 had ischemic stroke, 4 of which had hemorrhagic conversion, and 2 had primary intracerebral hemorrhage. Ten patients were on therapeutic anticoagulation prior to discovery of their stroke, and the remainder received intermediate dose anticoagulation (in a range between prophylactic and therapeutic levels). Additional studies are needed to further characterize the counterbalancing risks of ischemic and hemorrhagic stroke, as well as the optimal management of this patient population.     

Venous thromboembolism in medical outpatients - a cross-sectional survey of risk assessment and prophylaxis

The degree of thromboprophylaxis in medical outpatients is low despite a substantial risk for venous thromboembolism (VTE). This may be attributable to difficulties in assessing risk. Assessment tools like the Haas' scorecard aid in determining the need for thromboprophylaxis. We aimed at evaluating how the use of this tool may aid physicians in appropriately using anticoagulants. This was an epidemiological, cross-sectional survey of acute medically ill patients with limited mobility treated by general practitioners and internists. Risk assessment for VTE by the treating physician was compared to calculated risk. Of 8,123 patients evaluated between August 2006 and April 2008, 7,271 fulfilled the in- and exclusion criteria. Mean age was 69.4 ± 13.6 years, and 45.2% were male. Of these 82.8% were high risk based on their acute medical condition, 37.9% based on their underlying chronic condition. Immobilisation, heart failure, pneumonia, age, obesity, and major varicosis were the most frequently encountered risk factors. The agreement between the Haas' scorecard and physician indicated risk was high. At least 94.1% of patients with high risk received adequate anticoagulation mostly as low molecular weight heparins for a mean duration of 15.1 ± 30.5 days. There is a substantial risk for VTE in medical outpatients. Using a simple structured scorecard resulted in an overall appropriate risk assessment and high degree of anticoagulation. The scorecard may provide a tool to improve the overall awareness for VTE risk in medical outpatients, substantially improving the degree of prophylaxis in a patient population with largely underestimated risk.     

Increased platelet activation in the chronic phase after cerebral ischemia and intracerebral hemorrhage

BACKGROUND AND PURPOSE: Enhanced thromboxane (TX) biosynthesis has previously been reported in the acute phase after ischemic stroke. We investigated whether enhanced urinary excretion of 11-dehydro-TXB2, a noninvasive index of platelet activation, was present in the chronic phase after a transient ischemic attack (TIA) or stroke, including intracerebral hemorrhage. METHODS: We obtained a single urinary sample from 92 patients between 3 and 9 months after onset of stroke or TIA. The urinary excretion of the major enzymatic metabolite of TXA2, 11-dehydro-TXB2, was measured by a previously validated radioimmunoassay. The excretion rates were compared with those of 20 control patients with nonvascular neurological diseases. RESULTS: Urinary 11-dehydro-TXB2 averaged 294+/-139, 413+/-419, and 557+/-432 pmol/mmol creatinine for patients with TIA, ischemic stroke, and intracerebral hemorrhage, respectively; the values were higher in all subgroups (P<0.01) than that in control patients (119+/-66 pmol/mmol). Increased 11-dehydro-TXB2 excretion was present in 59% of all patients, in 60% (P<0.001) of patients with TIA, in 56% (P<0.001) of patients with ischemic stroke, and in 73% (P<0.001) of patients with intracerebral hemorrhage. Atrial fibrillation, no aspirin use, and severity of symptoms at follow-up contributed independently to the level of 11-dehydro-TXB2 excretion in a multiple linear regression analysis. CONCLUSIONS: Platelet activation is often present in patients in the chronic phase after stroke, including those with intracerebral hemorrhage. Persistent platelet activation, which is associated with atrial fibrillation and poor stroke outcome, can be substantially suppressed by aspirin treatment.     

Clinical presentation and time-course of postoperative venous thromboembolism: Results from the RIETE Registry

There is little literature about the clinical presentation and time-course of postoperative venous thromboembolism (VTE) in different surgical procedures. RIETE is an ongoing, prospective registry of consecutive patients with objectively confirmed, symptomatic acute VTE. In this analysis, we analysed the baseline characteristics, thromboprophylaxis and therapeutic patterns, time-course, and three-month outcome of all patients with postoperative VTE. As of January 2006, there were 1,602 patients with postoperative VTE in RIETE: 393 (25%) after major orthopaedic surgery (145 elective hip arthroplasty, 126 knee arthroplasty, 122 hip fracture); 207 (13%) after cancer surgery; 1,002 (63%) after other procedures. The percentage of patients presenting with clinically overt pulmonary embolism (PE) (48%, 48%, and 50% respectively), the average time elapsed from surgery to VTE (22 +/- 16, 24 +/- 16, and 21 +/- 15 days, respectively), and the three-month incidence of fatal PE (1.3%, 1.4%, and 0.8%, respectively), fatal bleeding (0.8%, 1.0%, and 0.2%, respectively), or major bleeding (2.3%, 2.9%, and 2.8%, respectively) were similar in the three groups. However, the percentage of patients who had received thromboprophylaxis (96%, 76% and 52%, respectively), the duration of prophylaxis (17 +/- 9.6, 13 +/- 8.9, and 12 +/- 11 days, respectively) and the mean daily doses of low-molecular-weight heparin (4,252 +/- 1,016, 3,260 +/- 1,141, and 3,769 +/- 1,650 IU, respectively), were significantly lower in those undergoing cancer surgery or other procedures. In conclusion, the clinical presentation, time-course, and three-month outcome of VTE was similar among the different subgroups of patients, but the use of prophylaxis in patients undergoing cancer surgery or other procedures was suboptimal.     

Bedside Xenon-CT Shows Lower CBF in SAH Patients with Impaired CBF Pressure Autoregulation as Defined by Pressure Reactivity Index (PRx)

The risk of death from venous thromboembolism (VTE) is high in intensive care unit patients with neurological diagnoses. This is due to an increased risk of venous stasis secondary to paralysis as well as an increased prevalence of underlying pathologies that cause endothelial activation and create an increased risk of embolus formation. In many of these diseases, there is an associated risk from bleeding because of standard VTE prophylaxis. There is a paucity of prospective studies examining different VTE prophylaxis strategies in the neurologically ill. The lack of a solid evidentiary base has posed challenges for the establishment of consistent and evidence-based clinical practice standards. In response to this need for guidance, the Neurocritical Care Society set out to develop and evidence-based guideline using GRADE to safely reduce VTE and its associated complications.     

Sticker reminders improve thromboprophylaxis appropriateness in hospitalized patients

Background

Venous thromboembolism (VTE) is a major health problem. Even though effective thromboprophylaxis measures exist to prevent VTE, close adherence to guidelines is missing. We assessed the effects of pasting VTE prophylaxis sticker reminders, on the appropriateness of thromboprophylaxis and prophylaxis underutilization.

Methods

Thromboprophylaxis reception was sought prospectively in two time points before and two time points after pasting sticker reminders in hospitalized patients of Masih Daneshvari Medical Center, Tehran, Iran. Thromboprophylaxis reception appropriateness was evaluated by the eighth American College of Chest Physicians (ACCP) guidelines on antithrombotic and thrombolytic therapy. Co-morbidities and conditions considered to affect the risk of venous thromboembolism were also recorded.

Results

Prophylaxis reception and appropriateness were studied in 298 patients before and 306 patients after the intervention. Based on the ACCP guidelines, overall thromboprophylaxis appropriateness was improved after the intervention (70.4% before, and 78.1% after the intervention, P = 0.03). Prophylaxis underutilization, and prophylaxis initiation delay in those who needed thromboprophylaxis, were also reduced (P = 0.03, and P = 0.011 respectively). The intervention did not result in an increased rate of overprophylaxis (P = 0.45).

Conclusion

Sticker reminders could be safely and effectively incorporated into strategies to improve VTE prophylaxis and prophylaxis appropriateness, particularly in healthcare settings where electronic alert systems are not available.     

Role of new anticoagulants for the prevention of venous thromboembolism after major orthopaedic surgery and in hospitalised acutely ill medical patients

Anticoagulation therapy for the prevention of venous thromboembolic events is indicated in patients after major orthopaedic surgery and in hospitalised acutely ill medical patients, who have a high or moderate risk of venous thromboembolism (VTE), respectively. Clinical trials have clearly demonstrated that short-term anticoagulation reduces the risk of VTE in these patient groups and that longer-term anticoagulation is beneficial for some indications. Evidence-based guidelines for thromboprophylaxis have been developed based on these studies. However, despite these guidelines, thromboprophylaxis is still underused, or used suboptimally, in many patients. This is, in part, because of the limitations of traditional anticoagulants such as unfractionated heparin, low- molecular-weight heparin, synthetic pentasaccharides, and vitamin K antagonists. Newer oral anticoagulants, such as rivaroxaban, apixaban, and dabigatran etexilate, have certain advantages over traditional agents. They can be administered orally at a fixed dose without routine coagulation monitoring and have minimal food and drug interactions. These characteristics may result in better adherence to guidelines and improved patient outcomes. This review provides an overview of phase III clinical trial data for these newer anticoagulants in major orthopaedic surgery and in hospitalised acutely ill medical patients, and discusses their potential for extended use in the post-hospital discharge setting. All three newer oral anticoagulants are approved in many countries for the prevention of VTE after hip replacement or knee replacement surgery in adult patients, and it is likely that these drugs will contribute considerably towards reducing the substantial healthcare burden associated with VTE.