Comparative Efficacy and Safety of Dabigatran, Enoxaparin, and Rivaroxaban for Prophylaxis of Cancer-associated Venous Thromboembolism: A Single-center Randomized Trial.

Heart failure (HF) represents a major and growing public health problem because of its prevalence, incidence, morbidity, mortality, and economic costs. The prevalence of HF is 2% to 3% of the general population.1 Five million Americans are affected, with >550 000 cases diagnosed each year.2 The mortality rate from severe HF remains >60% within 5 years of diagnosis, and 50% of hospitalized patients with HF require readmission within 6 months of discharge. In the US estimated costs amount to > $35 billion per year.3 Although several therapies (eg, β-blockers, angiotensin-converting enzyme [ACE] inhibitors, and cardiac resynchronization therapy) have been proven effective in improving HF outcomes, many unanswered questions about optimal treatment remain. One area of ongoing uncertainty is the appropriate role for antithrombotic therapy in patients with HF. Observational data suggest that patients with HF have an increased venous thromboembolism (VTE) risk (deep venous thromboembolism [DVT], pulmonary embolism [PE], peripheral arterial thromboembolism, and stroke).4 These epidemiological findings are supported by multiple mechanisms that can contribute to a hypercoagulable state in patients with HF. Despite this increased risk of VTE, the role of antithrombotic therapy remains unclear. In this article, we provide an overview of epidemiology, pathophysiology, clinical trial data, and therapeutic recommendations for prevention of thromboembolism in HF. We searched PubMed for articles published between 1958 and 2010 using the following search terms: epidemiology of heart failure , thromboembolism and heart failure , thrombogenesis and heart failure , anticoagulation in heart failure , antiplatelet agent and heart failure , aspirin and heart failure , bleeding risk and anticoagulation , and aspirin and angiotensin-converting enzyme inhibitors . We also studied abstracts from national and international cardiovascular meetings to identify unpublished studies using the key words anticoagulation and dilated cardiomyopathy . Data from published observational studies and secondary …

This is a recommended evaluation and management algorithm from the Western Trauma Association (WTA) Algorithms Committee focused on the management of pharmacologic prophylaxis for venous thromboembolism (VTE) prevention in trauma patients. Because there are few related published prospective, randomized clinical trials that have generated class I data on this topic in the trauma population, these recommendations are based primarily on published prospective and retrospective cohort studies, and expert opinion of the WTA members. The final algorithm is the result of an iterative process including an initial internal review and revision by the WTA Algorithm Committee members, and then final revisions based on input during and after presentation of the algorithm to the full WTA membership. Goals The algorithm (Fig. 1) and accompanying comments represent a safe and sensible approach to reducing VTE in trauma patients. The aim for this approach was to provide updated guidelines that apply to most patients, most of the time. We recognize that there will be multiple factors that may warrant or require deviation from any single recommended algorithm and that no algorithm can completely replace expert bedside clinical judgment. We encourage institutions and clinicians to use this algorithm as a general framework in the approach to trauma patients and to customize and adapt it to better suit the specifics of that program or location.Figure 1: The WTA algorithm for VTE prophylaxis after trauma. Circled letters correspond to sections in the associated article. Algorithm circle-bubbles represent patient criteria; algorithm square-bubbles represent expert recommendations. CrCl, creatinine clearance; Hb, hemoglobin; LMWH, enoxaparin; q8h, every 8 hours; q12h, every 12 hours; UFH, unfractionated heparin.Burden of Disease Venous thromboembolism, including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a potentially preventable complication after trauma. The focus of this algorithm is on optimizing the delivery of pharmacologic prophylaxis to prevent VTE and minimize any associated complications. For those trauma patients diagnosed with a DVT or PE, including distal upper extremity or calf thrombosis, specific treatments are addressed in other guidelines and will not be covered in this algorithm.1,2 Without pharmacologic prophylaxis, a 1994 study determined that the DVT rate was 58% in severely injured trauma patients who undergo serial impedance plethysmography with lower extremity contrast venography.3 In a landmark, 1996 New England Journal of Medicine publication 30 mg of subcutaneous enoxaparin twice daily performed better than 5,000 U of subcutaneous heparin twice daily at reducing DVT in moderate to severely injured trauma patients (31% vs. 44%, p = 0.04).4 The risk of major bleeding was low regardless of therapy, and importantly, the first dose of pharmacologic prophylaxis was initiated within 36 hours of the injury and continued through all surgical procedures except spinal fixation when a single preoperative dose was held.4 This study established that early, uninterrupted enoxaparin was superior to heparin at reducing VTE after trauma. In the last decade, a number of reviews and societal recommendations focused on improving the guidelines to reduce the rate of VTE and related complications after trauma.1,2,5–11 Despite this progress, debate persists regarding optimal dosing and timing of enoxaparin, including when to initiate, hold, and resume it before and after surgery or epidural placement. Trauma patients frequently receive a delayed, suboptimal dose of enoxaparin, which is then held for any potential surgical procedure despite substantial evidence that encourages early, uninterrupted pharmacologic prophylaxis. An updated algorithm on the appropriate management of VTE prophylaxis is therefore indicated. ALGORITHM The following lettered sections correspond to the letters identifying specific sections of the algorithm shown in Figure 1. In each section, we provide a brief summary of the important aspects and options that should be considered at that point in the evaluation and management process. A This algorithm is designed for adult trauma patients 18 years and older. Importantly, although younger children have a significantly lower VTE risk, older children and adolescents have a VTE risk that approaches their adult counterparts.12 Guidance for VTE prophylaxis in children can be found in the joint practice management guideline from the Pediatric Trauma Society and the Eastern Association for the Surgery of Trauma, which recommends, "pharmacologic prophylaxis be considered for children older than 15 years old and in younger postpubertal children with Injury Severity Score (ISS) greater than 25."11 B Assessment of VTE risk will assist in determining which patients require pharmacologic prophylaxis. In general, an ISS of 10 or more suggests that pharmacologic prophylaxis should be initiated as soon as possible, whereas patients with an ISS of less than 10 are at lower VTE risk and may not require pharmacologic prophylaxis.13–15 Because ISS is not calculated in real time, the Greenfield Risk Assessment Profile or the Trauma Embolic Scoring System can assist with calculating VTE risk.13–15 Patients with spine or pelvic fractures, repair of venous injury, a history of VTE, or inherited clotting disorders have increased VTE risk and should be considered for pharmacologic prophylaxis.2,13,14 Among trauma patients with minor injuries, independent predictors of increased VTE risk are increased age, obesity, and lower extremity fractures; any combination of these three characteristics should encourage initiation of pharmacologic prophylaxis.13 C Patients with minor trauma may not require pharmacologic prophylaxis. Given the related pain with injection, potential for hematoma at the injection site, cost for the medication, and nursing costs for administration, avoiding pharmacologic prophylaxis may be indicated for select low-risk patients after minor trauma. The Trauma Embolic Scoring System can be used to assess VTE risk, as patients with a low score require no pharmacologic prophylaxis because of their low VTE rate.13 Ambulatory patients with minor injuries and short hospital stays may not require pharmacologic prophylaxis. Trauma patients capable of ambulation but confined to bed because of intoxication, restraints, or other reasons should receive pharmacologic prophylaxis. In general, trauma patients who require hospital admission for more than 24 hours require pharmacologic prophylaxis, whereas those hospitalized for less than 24 hours do not. For the patients who do not receive pharmacologic prophylaxis, mechanical prophylaxis and/or aspirin are low cost and low morbidity options, although their benefit is uncertain given the low VTE rate.13–16 D Appropriate delays in pharmacologic prophylaxis may occur for those patients with an active bleed, coagulopathy, hemodynamic instability, solid organ injury, traumatic brain injury (TBI), or spinal trauma. Quantifying the risk and benefit of initiating pharmacologic prophylaxis for each patient is a challenge that is best determined by the trauma team at bedside. Detailing every indication where a delay may be indicated is outside the scope of these guidelines; several are described below. However, it is important to note that the guidance in both the literature and clinical practice supports very short delays to the initiation of pharmacologic prophylaxis, even among these cohorts. Active Bleeding, Coagulopathy, or Hemodynamic Instability Control of active bleeding is necessary before starting pharmacologic prophylaxis. In the presence of hemodynamic instability, a hemoglobin drop of greater than 2 g/dL in under 12 hours or ongoing blood transfusion is an appropriate indication to delay the initiation of pharmacologic prophylaxis.2,4 Systemic coagulopathy was previously proposed as a reason to delay pharmacologic prophylaxis with one study holding pharmacologic prophylaxis for an elevated prothrombin time of more than 3 seconds above control or a platelet count of less than 50,000 per cubic millimeter.4 More recent studies indicate that prothrombin time and platelet count are not as reliable at predicting systemic coagulopathy as viscoelastic hemostatic assays, which may demonstrate hypocoagulability and hypercoagulability after trauma.2,17–19 The hypocoagulability due to trauma largely resolves within 24 hours, after which hypercoagulability becomes prevalent. In this setting, pharmacologic prophylaxis may be considered after the initial resuscitation is complete.17,20 Deferring the initiation of pharmacologic prophylaxis during trauma-induced coagulopathy is associated with an increased VTE rate such that the initiation of pharmacologic prophylaxis is encouraged if the hypocoagulable state is expected to resolve and there are no signs of ongoing bleeding.17 Solid Organ Injury Delays occur in the initiation of pharmacologic prophylaxis for patients with solid organ injury. Several studies indicate that patients with solid organ injury who received early pharmacologic prophylaxis had lower DVT and PE rates without increased risk of failure of nonoperative management, bleeding complications, or mortality; these risks did not increase when pharmacologic prophylaxis was started within 24 hours compared with within 48 hours.20–23 Early pharmacologic prophylaxis within 12 to 24 hours appeared to be safe across moderate American Association for the Surgery of Trauma injury grade and type of solid organ injury (liver, spleen, and/or kidney), without an increased risk of bleeding that necessitated intervention or blood transfusion.21 Although those with grade IV and V injuries should be approached with caution, pharmacologic prophylaxis may be initiated within 24 hours for most patients with solid organ injury.21–23 Traumatic Brain Injury Concern for progression of TBI is a common reason for the delay in initiation of pharmacologic prophylaxis. This delay is dependent on the type of TBI; those with "cerebral contusion, localized petechial hemorrhages, or diffuse axonal damage" may safely receive pharmacologic prophylaxis without delay.4 When pharmacologic prophylaxis is appropriately delayed, the follow-up computed tomography (CT) after TBI diagnosis is an important indicator for when to initiate pharmacologic prophylaxis.24 For patients with TBI progression on the follow-up CT, exposure to pharmacologic prophylaxis is a predictor for further progression, and it should be held until a follow-up CT demonstrates no progression.24 In contrast, if the follow-up CT demonstrates no TBI progression, then pharmacologic prophylaxis should be initiated.24 Importantly, progression of TBI occurs in about 10% of patients with a stable follow-up CT, regardless of whether pharmacologic prophylaxis is provided or not.24 Those trauma centers that provide pharmacologic prophylaxis within 24 hours after TBI have significantly lower rates of VTE with no difference in rates of late neurosurgical intervention.23,25–30 Even in the setting of combat related penetrating TBI, initiating pharmacologic prophylaxis 24 hours after injury for those patients with a stable CT was safe, with similar progression rates regardless of pharmacologic prophylaxis.29 The majority of TBI patients with a stable CT may be initiated on enoxaparin within 24 hours, and nearly all TBI patients should receive pharmacologic prophylaxis within 72 hours of the time of injury.23,28,31 Spinal Trauma In the absence of pharmacologic prophylaxis, patients who undergo spine surgery or those with spine trauma, fracture, or cord injury have a high incidence of VTE,2 and delays longer than 72 hours lead to a substantial increase in the VTE rate.32 Pharmacologic prophylaxis must be initiated as soon as possible after spine surgery or any spine injury.32,33 Regimens that provide pharmacologic prophylaxis preoperatively34 or immediately after operative fixation are considered safe.4,34 When a departmental protocol was implemented that required pharmacologic prophylaxis preoperatively or the same day of spine surgery, the VTE rate decreased and the rate of spinal hematoma was unchanged.34 Similarly, pharmacologic prophylaxis initiated within 48 hours of operative fixation of traumatic spine fractures did not increase the risk of bleeding, progression of neurological injury, or postoperative complications including spinal hematoma.23,33 E Mechanical prophylaxis for moderate to high VTE risk patients is encouraged regardless of concurrent pharmacologic prophylaxis. For patients who are not started immediately on pharmacologic prophylaxis, mechanical prophylaxis with intermittent pneumatic compression and mobilization, when possible, should be encouraged. Intermittent pneumatic compression lowers the DVT incidence if no pharmacologic prophylaxis is initiated and therefore is recommended for patients with a contraindication to pharmacologic prophylaxis.2,35,36 In contrast, the addition of intermittent pneumatic compression in critically ill patients who received pharmacologic prophylaxis did not lead to a reduction in the DVT rate, although the study had a low DVT rate and only 8% of the population were trauma patients.16 Combining mechanical prophylaxis with pharmacologic prophylaxis is therefore encouraged for moderate to high VTE risk patients in part because those who received the combination had a lower incidence of symptomatic PE.35 Compression stockings do not appear to reduce the VTE rate in the presence of pharmacologic prophylaxis,16 but thigh high compression stockings may provide a benefit to those trauma patients who cannot be started on pharmacologic prophylaxis.2 Mobility is also an important component for VTE prevention, as early mobility leads to a reduction in VTE.37 A mobility protocol is safe in trauma patients and may reduce patient deconditioning besides decreasing the rate of VTE.37 Prolonged maintenance of spinal precautions is associated with an increased DVT rate and should be avoided to allow early mobility.38 F Weekly venous compression duplex should be considered in patients at high VTE risk who cannot be started or maintained on pharmacologic prophylaxis. Although debate persists, routine surveillance with venous compression duplex is not indicated or feasible for all trauma patients.2 Routine surveillance duplex after trauma does not decrease the risk of PE or fatal PE, and false-positive results lead to unnecessary therapeutic anticoagulation.2 In trauma patients at low VTE risk, the high cost and low yield of acute, clinically relevant findings suggest that the practice may be avoided. Some institutions advocate for routine surveillance in low-risk trauma patients to identify both acute and preexisting DVT, which may help identify and treat the related complications such as venous insufficiency, venous stasis ulcers, or pain with ambulation.39 For trauma patients at high VTE risk, routine surveillance duplex is associated with a reduced PE rate.39 The Greenfield Risk Assessment Profile can identify which trauma patients may benefit from routine surveillance.14,39 Weekly duplex scanning may be particularly beneficial in high VTE risk patients who cannot be started or maintained on pharmacologic prophylaxis. Whatever the institutional guidelines, identification of DVT should not be a hospital-reported outcome. Institutions that routinely screen all trauma patients have higher rates of DVT, and those centers with comprehensive quality improvement efforts that do not routinely screen will also have higher DVT rates because of a lower threshold for ordering a venous compression duplex. G Pharmacologic prophylaxis must be initiated as soon as possible and for most trauma patients may be initiated within 24 hours. When high VTE risk trauma patients who receive enoxaparin within 24 hours of admission are compared with those who receive only mechanical prophylaxis, minor and major bleeding events do not differ.40 As detailed in section E, appropriate delays may occur in the initiation of pharmacologic prophylaxis because of active bleeding, coagulopathy, hemodynamic instability, solid organ injury, TBI, or spinal trauma. In most cases, pharmacologic prophylaxis may be started in less than 24 hours, and in almost every case, pharmacologic prophylaxis may be started in less than 72 hours. Pharmacologic prophylaxis is often held because of pending surgery despite the evidence that it may be initiated before most surgical procedures.4,41–43 Trauma patients who require an operation are unique in that their first operation may occur within minutes of arrival or days into the hospitalization. Increasingly, pharmacologic prophylaxis is delayed or skipped for pending surgery, which leads to an increased VTE rate.40 Preoperative dosing of pharmacologic prophylaxis is not unique to trauma. In other patient populations at high risk for VTE, the use of preoperative pharmacologic prophylaxis decreased the DVT rate without increasing the complication rate.41,42 Guidelines for perioperative care in gynecologic/oncology recommend, "Prophylaxis should be initiated pre-operatively and continued post-operatively."44 Patients who underwent elective hip surgery who received low molecular weight heparin approximately 6 hours before surgery had a lower rate of proximal DVT without increasing major, minor, or trivial bleeding rates.43 This benefit was not observed when low molecular weight heparin was provided 12 hours or more preoperatively.43 We believe that the common and somewhat reflexive process of withholding pharmacologic prophylaxis for 12 to 24 hours before planned surgical procedures is almost always unnecessary and will result in an increased VTE risk without an accompanying decrease in the risk of bleeding events. H After deciding to start pharmacologic prophylaxis, the specific anticoagulant and initial dose should be determined for each patient. Enoxaparin is the recommended choice for most trauma patients with higher doses considered the of The for pharmacologic prophylaxis is the low molecular weight heparin enoxaparin because of increased longer and more and compared with unfractionated Enoxaparin less with which may reduce bleeding complications compared with unfractionated a lower incidence of and does not have the associated observed with heparin When the initial mg of enoxaparin twice daily should be considered the for most trauma patients, as 30 mg twice daily frequently results in pharmacologic patients 18 to years with weight of more than and a creatinine of more than should be started on mg of enoxaparin twice as this dose is safe and the VTE Patients who are older than less than or who have a creatinine of 30 to should to receive initial dosing at 30 mg of enoxaparin twice The initial enoxaparin dose for trauma patients with a may also be based on twice twice or 30 mg for to patients, mg for to patients, and mg for patients greater than Patients who are initiated on higher doses of enoxaparin based weight should be by because of the in creatinine after trauma that lead to in the enoxaparin Although enoxaparin is to heparin for pharmacologic prophylaxis, institutions to dose unfractionated heparin at 5,000 U three daily based in part on a randomized that that this be and compared with 30 mg of enoxaparin twice This practice should be as the was because of an DVT rate of for unfractionated heparin for enoxaparin, and a 10% for the The difference in the VTE rate was which enoxaparin without vs. enoxaparin, p = In the study was not to a difference in the rate of PE or both of which the complication rate and care More 30 mg of enoxaparin twice daily was established as superior to U of unfractionated heparin three daily at the prevention of VTE and for Quantifying the risk and benefit of the type and initial dose of pharmacologic prophylaxis for each patient is a challenge best determined by the trauma team at bedside. As mg of enoxaparin twice daily is the recommended initial pharmacologic prophylaxis for most trauma patients. Detailing every indication where an therapeutic or dose may be indicated is outside the scope of these guidelines; several are described below. In the presence of or a creatinine of subcutaneous unfractionated heparin at U every 8 hours may be Because enoxaparin is by the to patients with failure may lead to increased bleeding complications and should be Enoxaparin not and for use in patients. lower enoxaparin doses in the setting of a creatinine of may be possible in the but is necessary before this can be In most other enoxaparin is to unfractionated as enoxaparin leads to lower VTE rates without increased bleeding Brain and Trauma For TBI patients, enoxaparin is associated with less VTE and higher than unfractionated heparin with no difference in the progression of brain regardless if the dose was in less than 24 hours after 24 to 48 hours, or after 48 Similarly, those patients with spine trauma should receive early Patients with brain and spine trauma should be initiated on 30 mg of enoxaparin twice daily and considered for dose by Patients patients require specific dose recommendations for pharmacologic prophylaxis after trauma because of the as as the increase in and weight that occur the of require higher enoxaparin doses with more unfractionated heparin enoxaparin the and both are considered safe to use in As during an admission for trauma, patients should receive 30 mg of enoxaparin twice daily by a of to or a of to For patients who more than initiating mg of enoxaparin twice daily is recommended with similar and Pharmacologic prophylaxis with or aspirin should not be a choice for pharmacologic prophylaxis for most trauma patients because of the of related clinical The use of or aspirin may be considered in the setting of injuries, but only if the patient injection with enoxaparin or unfractionated are for pharmacologic prophylaxis after elective surgery, 10 mg of and mg of twice both which are trials that or to enoxaparin demonstrate that have to better VTE rates with similar to higher bleeding In contrast, other that enoxaparin a lower VTE and a lower bleeding Because only retrospective have the use of for pharmacologic prophylaxis after trauma, randomized trials are necessary before a for trauma The use of low dose aspirin may also be considered for pharmacologic prophylaxis in trauma patients with injuries who For those trauma patients started on a for pharmacologic prophylaxis, aspirin may replace the after days with similar prevention of I trauma patients require dose after initiating Because of the in and enoxaparin by is In one of trauma patients required doses of mg or and required doses of mg or enoxaparin by or to lower the VTE rate without increasing bleeding complications in moderate to severely injured patients, trauma patients who require injuries, and surgical Although debate on the appropriate for suggests to for or to for should also be considered for those patients who receive Although not for pharmacologic prophylaxis, with platelet may assist with platelet A randomized that used as an to identify enoxaparin doses did not lower rates of VTE with the enoxaparin In contrast, with platelet may help if a hypercoagulability is due to platelet which encourages the addition of aspirin to the pharmacologic prophylaxis aspirin is the initial recommended dose is mg daily with the of increasing the dose to mg daily on with platelet The uninterrupted dosing of pharmacologic prophylaxis should be the for most trauma patients their hospital Although the and benefit of uninterrupted pharmacologic prophylaxis were established more than of trauma patients A is observed the number of doses and DVT risk such that patients who to doses have higher DVT risk compared with those with no For TBI patients who are started on pharmacologic prophylaxis, dosing an approximately increase in the VTE The following are common reasons for pharmacologic pending procedure patient was from the for bleeding epidural and When holding pharmacologic prophylaxis, the rate of bleeding with pharmacologic prophylaxis is no than without VTE events are compared with bleeding complications, the pharmacologic should focus on pharmacologic prophylaxis without The appropriate for holding or pharmacologic prophylaxis acute spinal surgery, epidural or and these are below. Although routine VTE surveillance is not indicated for all trauma duplex scanning may be in those at high VTE venous compression duplex should be performed for symptomatic evidence of DVT such as or For those trauma patients with injuries and in pharmacologic prophylaxis, venous compression duplex may be a DVT or PE is then therapeutic is necessary per guidelines, and if it is then an should be considered as detailed in section Surgery As in section routinely holding pharmacologic prophylaxis because of pending surgery is only with few for brain or spine Given the delays and of that may occur during trauma patient holding pharmacologic prophylaxis preoperatively can days of pharmacologic prophylaxis. Preoperative pharmacologic prophylaxis is safe for trauma and leads to a lower VTE The preoperative of pharmacologic prophylaxis is also encouraged for surgical patients in other who have a high VTE risk and leads to a lower DVT rate without increasing the complication The lower VTE rate is if pharmacologic prophylaxis is provided more than 12 hours preoperatively.43 reduce morbidity and in trauma patients injuries and are often a component of pain Patients who require an epidural have in pharmacologic such that epidural is associated with an increased VTE whereas previously this was not the Guidelines a enoxaparin dose and epidural by a to before enoxaparin is at 10 and 10 the dose may be held for 10 epidural to allow for the necessary without prophylaxis. 10 the enoxaparin dosing may only one dose is higher doses of enoxaparin are required for pharmacologic prophylaxis, Guidelines a for therapeutic enoxaparin before epidural by a to before at doses of enoxaparin should be for any enoxaparin enoxaparin doses are encouraged with to the higher VTE rate associated with epidural For unfractionated a to is recommended before epidural by a before unfractionated heparin is which for uninterrupted platelet should be considered for those trauma patients who receive pharmacologic prophylaxis because of the risk of is recommended for patients who are considered high risk for approximately every 3 days from day to day or until pharmacologic prophylaxis is Trauma patients who are only to enoxaparin may be considered low risk for and may not require routine platelet as the rate of clinical was with heparin compared with with The clinical diagnosis of may be by that thrombosis, and the heparin must be with such as the which can for trauma patients for because of the of these and the with dosing and their therapeutic may be considered in the setting of proximal DVT or PE when there is a contraindication to appropriate therapeutic The use of is among trauma centers although their is decreasing without a in PE is not In a randomized of high VTE risk trauma patients who were to receive pharmacologic prophylaxis during the first 72 hours of a did not lower the incidence of PE or which established the of of early of an in this The of an does not regardless of whether a DVT is or guidelines provide recommendations and most studies have among patients diagnosed with an acute proximal DVT or PE who cannot receive therapeutic an should be considered to reduce the rate of PE without the Trauma patients with TBI, or spine injuries, and those who undergo major surgery are at VTE risk and should be considered for pharmacologic prophylaxis. Pharmacologic prophylaxis after for high VTE risk trauma patients is by evidence that demonstrates the practice is safe, and and may be considered for patients with TBI, or spine injuries, and those who undergo major The VTE risk occurs during the first 3 after injury with approximately required until the VTE rate to that of the general Venous for of trauma at a cost of pharmacologic prophylaxis with enoxaparin is associated with a low rate of clinically relevant bleeding complications, and is in patients at high VTE The of pharmacologic prophylaxis following or pelvic surgery for or was associated with a decrease in VTE Because the optimal dose and of enoxaparin after trauma are not doses more than 30 mg twice daily should be and the of pharmacologic prophylaxis may be considered for to after the of For those who undergo major surgery, pharmacologic prophylaxis may be to days from the of may be initiated for pharmacologic prophylaxis for high VTE risk trauma patients, as it shown to be as as enoxaparin with less bleeding complications and better and is not by the of may also be considered for pharmacologic prophylaxis after This algorithm was designed to provide comprehensive and guidance at reducing the VTE rate after trauma. Although there are multiple factors that will lead to from the most trauma patients should be initiated on early and higher doses of enoxaparin that often should be by For most trauma patients, pharmacologic prophylaxis should uninterrupted the hospital and at after preventable and delays to the initiation and doses of pharmacologic prophylaxis should be a focus of all trauma and it associated with decreased rates of VTE events.

Case Presentation : A 29-year-old woman presented to the emergency department with complaints of pleuritic chest pain, fever, and left ankle swelling and tenderness. Cardiac examination was normal except for tachycardia. A chest computed tomography scan with contrast demonstrated extensive bilateral pulmonary emboli. Thirteen days previously, an intoxicated driver with multiple prior convictions for driving under the influence of alcohol crashed head-on into her car at a high speed. She was 8 months’ pregnant and suffered the loss of the child. She spent 7 days in the hospital and underwent cesarean section, exploratory laparotomy, and splenectomy. No preoperative pharmacological prophylaxis against venous thromboembolism (VTE) was administered. VTE, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important and common complication of general surgery. A new era in the postoperative management of surgical patients began in 1975 when the effectiveness of low-dose heparin in preventing postoperative DVT and PE was established by the pivotal International Multicenter Trial.1 The dose was 5000 U subcutaneously every 8 hours, with the first injection administered 2 hours before the skin incision. Compared with control, the incidence of DVT in patients receiving heparin decreased from 24.6% to 7.7%. Similarly, the incidence of autopsy-proven PE was reduced 8-fold. The results of this trial introduced and validated the concept of using low-dose heparin to prevent postoperative VTE. This trial revolutionized surgical practice. By 1994, 90% of North American general surgeons reported the routine use of thromboprophylaxis.2 Most postoperative DVT originates in the deep calf veins, primarily within the valve cusps. Most thrombi remain confined to the calf. Propagation into the proximal veins increases the risk of PE. Symptoms and signs of postoperative VTE such as mild hypoxia or low-grade fever are frequently nonspecific. Moreover, clinical manifestations of postoperative VTE may not occur until …

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Heparins for preventing venous thromboembolism in general medical wards: evidence and guidelines.

Patients with multiple myeloma have an increased incidence of venous thromboembolism. The risk for venous thromboembolism further increases when these patients are placed on immunomodulatory drug therapy. This study aims to determine the incidence of venous thromboembolism in patients with multiple myeloma receiving immunomodulatory drug therapy in the ambulatory setting at UC Health and to investigate adherence with guidelines developed by The National Comprehensive Cancer Network for venous thromboembolism prevention in this patient population. A retrospective chart review of patients with multiple myeloma initiated on immunomodulatory drug therapy between January 2000 and January 2014 was conducted. Sixty-two cases met inclusion criteria and were included for analysis. The National Comprehensive Cancer Network guidelines were followed in 33.9% of cases. The rate of venous thromboembolism was 4.8% in guideline adherent cases and 12.2% in guideline nonadherent cases (p = 0.65). The overall incidence of venous thromboembolism was 9.7%. No patients on a low-molecular-weight-heparin agent or warfarin developed a venous thromboembolism, 7.9% patients on aspirin therapy developed a venous thromboembolism, and 23.1% patients on no pharmacologic thromboprophylaxis developed a venous thromboembolism (p = 0.26). Ambulatory patients with multiple myeloma who are considered for immunomodulatory drug therapy should be placed on pharmacologic thromboprophylaxis based on individual venous thromboembolism and bleeding risk factors. This study identified the need for increased adherence to national guidelines for venous thromboembolism prevention in patients with multiple myeloma receiving immunomodulatory drug therapy so as to increase the quality of care provided at UC Health.

Many patients who experience a venous thromboembolic event have cancer, and thrombosis is much more prevalent in patients with cancer than in those without it. Thrombosis is the second most common cause of death in cancer patients and cancer is associated with a high rate of recurrence of venous thromboembolism (VTE), bleeding, requirement for long-term anticoagulation and poorer quality of life. A literature review was conducted to identify guidelines and evidence pertaining to anticoagulation prophylaxis and treatment for patients with cancer, with the goal of identifying opportunities for pharmacists to advocate for and become more involved in the care of this population. Many clinical trials and several guidelines providing guidance to clinicians in the treatment and prevention of VTE in patients with cancer were identified. Current clinical evidence and guidelines suggest that cancer patients receiving care in hospital with no contraindications should receive VTE prophylaxis with unfractionated heparin (UFH), a low-molecular-weight heparin (LMWH) or fondaparinux. Patients who require surgery for their cancer should receive prophylaxis with UFH, LMWH or fondaparinux. Cancer patients who have experienced a VTE event should receive prolonged anticoagulant therapy with LMWH (at least 3 months to 6 months). No routine prophylaxis is required for the majority of ambulatory patients with cancer who have not experienced a VTE event. Most publicly funded drug plans in Canada have developed criteria for funding of LMWH therapy for patients with cancer. Evidence suggests that LMWH for 3 to 6 months is the preferred strategy for most cancer patients who have experienced a thromboembolic event and for hospital inpatients, but this is often not implemented in practice. Concerns about adherence with injectable therapy should not prevent use of these agents. Pharmacists should assess cancer patients for their risk of VTE and should advocate for optimal VTE pharmacotherapy as appropriate. If LMWH is the preferred agent, on the basis of the evidence, the pharmacist should educate the patients appropriately and work with the prescriber to ensure best care.

Background: Low-molecular-weight heparin (LMWH) thromboprophylaxis is widely used for reducing the risk of thrombosis after major orthopaedic surgery. However, the effect and safety on knee arthroscopic surgery are still controversial. Purpose: To assess the efficacy and safety of LMWH for the prevention of symptomatic venous thromboembolism (VTE) after knee arthroscopic surgery and anterior cruciate ligament reconstruction (ACLR) by conducting a meta-analysis of randomized controlled trials (RCTs). Study Design: Meta-analysis. Methods: The authors searched the electronic databases of MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and Web of Science for all studies from inception to June 30, 2017. All selected studies were categorized into 2 subgroups: simple knee arthroscopic surgery and ACLR. The primary effect and safety endpoint were the incidence of major VTE and major bleeding events (BEs), respectively. The secondary effect and safety endpoint were the incidence of all VTE and all BEs, respectively. Relative risks (RRs) with 95% CIs were calculated using Review Manager 5.3. Results: Eight RCTs with 4113 patients were included. For patients undergoing simple knee arthroscopic surgery, LMWH prophylaxis did not bring a significant reduction in the risk of major VTE (RR, 1.00 [95% CI, 0.37-2.67]; P > .99) and all VTE (RR, 0.63 [95% CI, 0.31-1.29]; P = .21) and did not increase the risk of major BEs (RR, 0.98 [95% CI, 0.06-15.72]; P = .99) but did have a higher risk of all BEs (RR, 1.64 [95% CI, 1.18-2.28]; P = .003) in comparison with non-LMWH prophylaxis. For patients undergoing ACLR, LMWH prophylaxis was associated with a significantly lower rate of major VTE (RR, 0.23 [95% CI, 0.12-0.43]; P < .001) and all VTE (RR, 0.22 [95% CI, 0.06-0.73]; P = .01) but no increase in major BEs (RR, 1.80 [95% CI, 0.19-17.25]; P = .61) and all BEs (RR, 1.12 [95% CI, 0.72-1.74]; P = .61) in comparison with non-LMWH prophylaxis. Conclusion: Compared with non-LMWH treatment, LMWH had no significant efficacy in preventing VTE in patients undergoing simple knee arthroscopic surgery but increased the risk of BEs. However, LMWH had significant efficacy in preventing VTE for patients mainly undergoing ACLR and did not increase the risk of BEs.