Peripheral Artery Disease: Overview of Diagnosis and Medical Therapy.

Peripheral artery disease (PAD) affects approximately 230 million people worldwide and is associated with an increased risk of major adverse cardiovascular and limb events. Even though this condition is considered a cardiovascular equivalent, it remains an underrecognized and undertreated entity. Antiplatelet and statin therapy, along with smoking cessation, are the foundations of therapy to reduce adverse events but are challenging to fully implement in this patient population. Race and socioeconomic status also have profound impacts on PAD outcomes.

Peripheral Artery Disease: Treatment of Claudication and Surgical Management.

Peripheral artery disease (PAD) affects approximately 230 million people worldwide and is associated with an increased risk of major adverse cardiovascular and limb events. Even though this condition is considered a cardiovascular equivalent, it remains an under-recognized and under-treated entity. Anti-platelet and statin therapy, along with smoking cessation, are the foundations of therapy to reduce adverse events but are challenging to fully implement in this patient population. Race and socioeconomic status also have profound impacts on PAD outcomes. Exercise therapy is the gold standard treatment of claudication while revascularization procedures are often reserved for patients with limb-threatening ischemia.

Apixaban Discontinuation for Invasive Or major Surgical procedures (ADIOS): A prospective cohort study.

Background: Apixaban pharmacokinetic properties and some clinical reports suggest cessation 48 hours prior to surgery is safe, but this has not been demonstrated in a naturalistic setting. We sought to measure the residual apixaban exposure in patients who had apixaban held as part of standard of care perioperative management. Methods: This was a prospective, observational study of patients in whom apixaban plasma concentration and anti-Xa activity were measured while at steady state apixaban dosing and again immediately prior to surgery. Clinical management of cessation and resumption of apixaban was at the discretion of the treating physician. Results: Paired blood samples were provided by 111 patients. Ninety-four percent (104/111) of patients had measured apixaban concentrations of ⩽ 30 ng/mL. Only one patient had a value > 50 ng/mL. The median time between the self-reported last dose and presurgery blood sampling was 76 hours (range 32-158) for those who achieved concentrations ⩽ 30 ng/mL and 59 hours (range 49-86) for those > 30 ng/mL. Measured anti-Xa activity correlated well with apixaban exposure. Clinically significant nonmajor bleeding was reported in one patient at 1 week postsurgery. There was one venous thromboembolic event and one stroke in the perioperative period. Conclusion: In a naturalistic setting with a heterogeneous patient population, apixaban discontinuation for at least 48 hours before a procedure resulted in a clinically insignificant degree of anticoagulation prior to a surgical procedure. ClinicalTrials.gov Identifier: NCT02935751.

Surgical Pulmonary Embolectomy Outcomes for Acute Pulmonary Embolism.

BACKGROUND: Acute pulmonary embolism (PE) is associated with significant mortality. Surgical embolectomy is a viable treatment option; however, it remains controversial as a result of variable outcomes. This review investigates patient outcomes after surgical embolectomy for acute PE. METHODS: An electronic search was performed to identify articles reporting surgical embolectomy for treatment of PE. 32 studies were included comprising 936 patients. Demographic, perioperative, and outcome data were extracted and pooled for systematic review. RESULTS: Mean patient age was 56.3 years (95% confidence interval [CI], 52.5, 60.1), and 50% were male (95% CI, 46, 55); 82% had right ventricular dysfunction (95% CI, 62, 93), 80% (95% CI, 67, 89) had unstable hemodynamics, and 9% (95% CI, 5, 16) experienced cardiac arrest. Massive PE and submassive PE were present in 83% (95% CI, 43, 97)] and 13% (95% CI, 2, 56) of patients, respectively. Before embolectomy, 33% of patients (95% CI, 14, 60) underwent systemic thrombolysis, and 14% (95% CI, 8, 24) underwent catheter embolectomy. Preoperatively, 47% of patients were ventilated (95% CI, 26; 70), and 36% had percutaneous cardiopulmonary support (95% CI, 11, 71). Mean operative time and mean cardiopulmonary bypass time were 170 minutes (95% CI, 101, 239) and 56 minutes (95% CI, 42, 70), respectively. Intraoperative mortality was 4% (95% CI, 2, 8). Mean hospital and intensive care unit stay were 10 days (95% CI, 6, 14) and 2 days (95% CI, 1, 3), respectively. Mean postoperative systolic pulmonary artery pressure (sPAP) was significantly decreased from the preoperative period (sPAP 57.8, mm Hg; 95% CI, 53, 62.7) to the postoperative period (sPAP, 31.3 mm Hg; 24.9, 37.8); P < .01). In-hospital mortality was 16% (95% CI, 12, 21). Overall survival at 5 years was 73% (95% CI, 64, 81). CONCLUSIONS: Surgical embolectomy is an acceptable treatment option with favorable outcomes.

Outcomes of extracorporeal life support for the treatment of acute massive pulmonary embolism: A systematic review.

BACKGROUND: Massive pulmonary embolism (PE) can cause hemodynamic instability leading to high mortality. Extracorporeal life support (ECLS) has been increasingly used as a bridge to definitive therapy. This systematic review investigates the outcomes of ECLS for the treatment of massive PE. METHODS: Electronic search was performed to identify all relevant studies published on ECLS use in patients with PE. 50 case series or reports were selected comprising 128 patients with acute massive PE who required ECLS. Patient-level data were extracted for statistical analysis. RESULTS: Median patient age was 50 [36, 63] years and 41.3% (50/121) were male. 67.2% (86/128) of patients presented with cardiac arrest. Median heart rate was 126 [118, 135] and median systolic pulmonary artery pressure (sPAP) was 55 [48, 69] mmHg. The majority of ECLS included veno-arterial ECLS [97.1% (99/102)]. Median ECLS time was 3 [2, 6] days. 43.0% (55/128) patients received systemic thrombolysis, 22.7% (29/128), received catheter-guided thrombolysis, and 37.5% (48/128) underwent surgical embolectomy. 85.1% (97/114) were weaned off ECLS. Post-ECLS complications included bleeding in 23.4% (30/128), acute renal failure in 8.6% (11/128), dialysis in 6.3% (8/128), heparin-induced thrombocytopenia in 3.1 (4/128), and extremity hypoperfusion in 2.3% (3/128). The most common cause of death was shock at 30.3% (10/33). The median length of hospital stay was 22 [11, 39] days including 8 [5, 13] intensive care unit (ICU) days. The 30-day mortality rate was 22% (20/91). CONCLUSIONS: ECLS is safe and effective therapy in unstable patients with acute massive pulmonary embolism and offers acceptable outcomes.

Pylephlebitis treated with apixaban.

Pylephlebitis is a rare condition that is characterized by an infected thrombus of the portal vein system and was traditionally associated with a high mortality rate prior to the introduction of antibiotics. This report details a 77-year-old Chinese male found to have a splenic vein thrombosis, Parvimonas micra bacteremia, and a polymicrobial splenic abscess. The patient was treated with abscess drainage and a 6 week course of intravenous antibiotics, and a direct oral anticoagulant, apixaban 2.5 mg twice daily. To our knowledge, this is the second documented case of pylephlebitis treated with apixaban. Here, we summarize our experience treating this case of pylephlebitis and briefly report on the existing body of literature.

Cost of Purchased Versus Produced Plasma from Donor Recruitment Through Transfusion.

BACKGROUND: Plasma is used to treat acquired coagulopathy or thrombotic thrombocytopenic purpura, or to reverse warfarin effect. Scant data are available, however, about its costs. OBJECTIVE: To estimate total costs of plasma from production through administration, from the perspective of a US hospital blood donor center (BDC). STUDY DESIGN AND METHODS: Six sequential decision analytic models were constructed and informed by primary and secondary data on time, tasks, personnel, and supplies for donation, processing, and administration. Expected values of the models were summed to yield the BDC's total cost of producing, preparing, and transfusing plasma. Costs ($US 2015) are reported for a typical patient using three units of plasma. Models assume plasma was obtained from whole blood donation and transfused in an inpatient setting. Univariate sensitivity analyses were performed to test the impact of changing inputs for personnel costs and adverse event (AE) rates and costs. RESULTS: BDC production cost of plasma was $91.24/patient ($30.41/unit), a $30.16/patient savings versus purchased plasma. Administration and monitoring costs totaled $194.64/patient. Sensitivity analyses indicated that modifying BDC personnel costs during donation and processing has little impact on total plasma costs. However, the probability and cost of transfusion-associated circulatory overload (TACO) have a significant impact on costs. CONCLUSION: Plasma produced by our BDC may be less costly than purchased plasma. Though plasma processes have multiple tasks involving staff time, these are not the largest cost driver. Major plasma-related AEs are uncommon, but are the biggest driver of total plasma costs.

In the Clinic. Deep venous thrombosis.

This issue provides a clinical overview of deep venous thrombosis, focusing on prevention, diagnosis, treatment, and patient information. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including ACP Smart Medicine and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of science writers and physician writers. Editorial consultants from ACP Smart Medicine and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://smartmedicine.acponline.org, http://mksap.acponline.org, and other resources referenced in each issue of In the Clinic.

Contemporary treatment of venous thromboembolic disease.

Venous thromboembolism (VTE) is a potentially fatal condition and includes deep vein thrombosis and pulmonary embolism. The novel oral anticoagulants, which include the direct thrombin and factor Xa inhibitors, have been shown to be safe and effective for the treatment of VTE. Additional interventions include thrombolysis and the use of inferior vena cava filters. The purpose of this article is to provide a contemporary review of the treatment of VTE.

Facilitating anticoagulation for safer transitions: preliminary outcomes from an emergency department deep vein thrombosis discharge program.

INTRODUCTION: Patients presenting to the emergency department (ED) with an acute uncomplicated deep vein thrombosis (DVT) may be eligible for outpatient treatment. This study aims to establish a transition of care program in the ED for patients with DVT presenting with an acute uncomplicated DVT. METHODS: This article specifies the transition of care program for DVT patients in the ED. Data was collected on patients admitted and discharged from the ED who had an acute DVT both prior to the initiation of facilitating anticoagulation for safer transitions (FAST) and after initiation of FAST. Follow-up phone calls were made to patients discharged from the ED after the initiation of FAST, and data were collected on follow-up appointments, anticoagulation adherence, readmission rates, and patient satisfaction. RESULTS: The FAST program has been successfully implemented. By the 30-day follow-up phone call, 100% of patients had attended a follow-up appointment. The average time to the follow-up appointment post-discharge was 4.4 days (range, 1-7 days). None of the patients at the 3- to 5-day follow-up phone call and 30-day phone call had any issues taking their anticoagulant, and none reported side effects of significant bleeding. One patient was re-admitted after discharge with a pulmonary embolism. Patient satisfaction has also been very high with the program, with all patients indicating at the 30-day phone call that they would recommend the program to a friend or family member. The educational components of this program also improved the discharge process for this population compared with patients discharged prior to the initiation of FAST. CONCLUSION: The FAST program is an example of a successful transition-of-care program for discharging DVT patients from the ED. Reassessment and improvements to the program are underway to ensure it remains current, sustainable, and provider friendly.

Venous thromboembolism in cancer patients.

OBJECTIVE: Venous thromboembolism (VTE) is a common complication in cancer patients. This review summarizes some of the most current knowledge of the epidemiology, risk factors, risk models, prophylaxis, and treatment of VTE in cancer patients. METHODS: A literature search was conducted using PubMed; the search terms were venous thromboembolism, anticoagulation, and cancer. The bibliographies of pertinent studies and review articles were reviewed for additional references. RESULTS: Venous thromboembolism is the second leading cause of death in patients with cancer. Cancer patients with VTE have poorer outcomes compared with noncancer patients with VTE. Many risk factors have been identified for VTE in patients with cancer that are patient-related, cancer-related, or treatment-related. Several biomarkers have been identified as potentially predictive of VTE risk. Risk assessment models such as the Khorana Risk Score stratify cancer patients with low, intermediate, and high risk of developing VTE based on baseline clinical and laboratory variables. Currently, enoxaparin is the preferred anticoagulant for initial VTE treatment in cancer patients. Low molecular weight heparin (LMWH) is recommended for both initial and long-term management of cancer-related VTE. Because the optimal duration of anticoagulation in cancer patients with VTE is unknown, the decision to extend anticoagulation requires weighing the risk of recurrent thrombosis against the risk of major bleeding. Patients with recurrent VTE can be bridged with LMWH, transitioned to full-dose LMWH or treated with LMWH dose escalation. While there is insufficient data to determine whether anticoagulation should be held in the setting of thrombocytopenia, full-dose anticoagulation is typically considered unsafe when platelets are < 50 000/µL. Inferior vena cava filters are currently recommended only for patients with acute VTE and contraindications to anticoagulation. Although management of catheter-associated thrombosis has not been well studied in cancer patients, it is recommended that cancer patients with catheter-associated thrombosis be treated with therapeutic anticoagulation for ≥ 3 months. Venous thromboembolism prophylaxis with UFH, LMWH, or fondaparinux is recommended in all hospitalized nonsurgical cancer patients and cancer patients undergoing major cancer surgery. Primary thromboprophylaxis is only currently recommended in high-risk ambulatory cancer patients such as multiple myeloma patients receiving thalidomide- or lenalidomide- based therapy. CONCLUSION: Cancer-associated thrombosis is a common problem. As we begin to better understand the risk factors and biomarkers for cancer-associated VTE, we can further refine and develop risk-assessment models to determine those patients who would most likely benefit from anticoagulation. While LMWH products are generally preferred in cancer-related VTE, more research will continue to evolve our understanding of treatment and thrombopprophylaxis in cancer-associated VTE.

The new oral anticoagulants for the treatment of venous thromboembolism: a new paradigm shift in antithrombotic therapy.

BACKGROUND: Several novel oral anticoagulants have been studied for the prevention and treatment of venous thromboembolism (VTE) in different patient populations. Clinicians will increasingly encounter scenarios in which they must choose among these and conventional anticoagulants for the treatment of this potentially fatal condition. OBJECTIVE: To review the results of Phase III clinical trials that investigated the novel oral anticoagulants for the treatment of deep vein thrombosis and pulmonary embolism. Potential advantages and disadvantages of these anticoagulant agents with respect to each other and conventional therapy will also be explored through a case-based approach. METHODS: A literature search in PubMed was conducted that identified Phase III clinical trials investigating the novel oral anticoagulant agents for the treatment of VTE. RESULTS: The new oral anticoagulant agents have been shown to be as safe and effective for the treatment of VTE as conventional therapies. CONCLUSIONS: These novel, oral anticoagulant agents are legitimate options for the treatment of VTE. A careful assessment of a patient׳s comorbidities, medication use, and laboratory results should be undertaken before prescribing the new oral anticoagulant agents for patients with VTE.

New oral anticoagulants: prevention of VTE in phase III studies in total joint replacement surgery and the hospitalized medically-ill patients.

Effective venous thromboembolism prophylaxis in hospitalized medically-ill patients and those undergoing orthopaedic surgery remains a challenge for clinicians in the United States. Several new oral anticoagulants, which either directly inhibit the activity of thrombin or factor Xa have been developed and studied for venous thromboembolism (VTE) prevention in phase III trials in these patient populations. These new medications demonstrate several advantages over traditional anticoagulants, including their administration at fixed doses with no requirement for routine coagulation monitoring. Such advantages may potentially be offset by the lack of well-studied methods to reverse their anticoagulant effects and the potential need for standardized testing to monitor their activity in certain situations. This review will provide an overview of the clinical trial results of dabigatran, apixaban and rivaroxaban for VTE prevention in the orthopaedic and medically-ill hospitalized patients.

Direct thrombin and factor Xa inhibition for stroke prevention in patients with atrial fibrillation.

Nonvalvular atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia occurring in patients in the United States. The primary clinical consequence of AF is an increase in the risk and severity of strokes. Treatment guidelines recommend anticoagulation therapy for most patients with AF. One risk-stratification scheme, the CHADS2 index, is simple and widely used to determine the management of patients with AF in regard to stroke prevention. However, new schemes, such as CHA2DS2-VASc, further refine risk stratification to identify patients who would obtain a net clinical benefit from a particular management strategy, thus improving the quality of management. For patients with AF for whom oral anticoagulation (OAC) is advisable, vitamin K antagonist (VKA) therapy is well established and effective. However, OAC with VKAs presents challenges to prescribers and patients in maintaining therapeutic efficacy. Novel OACs may offer alternatives to VKAs. Dabigatran etexilate, a direct thrombin inhibitor, was approved by the US Food and Drug Administration (FDA) in 2010 for reducing the risk of stroke and systemic embolism in patients with nonvalvular AF. The activated factor X (factor Xa) inhibitor rivaroxaban was recently approved by the FDA both for prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism in patients undergoing knee or hip arthroplasty, and for reducing the risk of stroke and systemic embolism in patients with nonvalvular AF. Apixaban, another factor Xa inhibitor, was recently shown to be effective for stroke prevention in patients with nonvalvular AF. This article reviews clinical considerations regarding new agents that may offer alternatives to VKA therapy for the prevention of stroke in patients with AF.

Segmental arterial mediolysis: report of 2 cases and review of the literature.

Segmental arterial mediolysis (SAM) is an idiopathic noninflammatory vasculopathy involving small to medium arteries, usually in the abdomen, although arteries in the cerebral and coronary circulations also may be affected. Some cases present as abdominal apoplexy due to aneurysmal rupture, but ischemia and infarction also occur. Not uncommonly, SAM may be misdiagnosed as a systemic necrotizing vasculitis. We present 2 patients with bilateral renal infarctions, cerebral arterial dissections, and visceral artery microaneurysms. Both were diagnosed initially as polyarteritis nodosa. The diagnosis was changed to SAM, in one case based on clinical and radiologic features, and in the other, on an open wedge kidney biopsy. We discuss the differential diagnosis and review the literature on SAM.

The incidence of deep vein thrombosis detected by routine surveillance ultrasound in neurosurgery patients receiving dual modality prophylaxis.

The optimal method of thromboprophylaxis and the value of screening ultrasonography for detection of deep venous thrombosis (DVT) in neurosurgery patients remains unclear. The goal of this study was to determine the incidence of DVT in neurosurgical patients who, by hospital protocol, receive surveillance ultrasonography of the lower extremities twice weekly, in addition to prophylaxis with unfractionated heparin and external pneumatic compression sleeves. A retrospective review of 7,298 ultrasound studies carried out on 2,593 patients over 4 years at a university neurosurgical hospital was conducted. There was a 7.4% incidence of proximal lower extremity DVT and a 9.7% total incidence including distal DVT. A greater number of distal DVTs were detected with the implementation of whole-leg ultrasonography in the last 2 years of observation. Chart review of 237 patients diagnosed with DVT demonstrated an admitting diagnosis of subarachnoid hemorrhage in nearly half of the patients. The median hospital length of stay for DVT patients was 18 days. Institutional control data demonstrated non-ruptured aneurysm and cerebrovascular anomalies to be the leading reason for admission, followed closely by subarachnoid hemorrhage. The hospital protocol of biweekly screening ultrasound and dual modality prophylaxis for neurosurgery patients resulted in a proximal DVT incidence consistent with that demonstrated by previous studies of standardized dual modality prophylaxis, and higher than that demonstrated in previous studies that employed ultrasound screening protocols.

New oral anticoagulants.

The new oral anticoagulants may prove to be one of the most significant innovations in clinical practice in the past 60 years. Apixaban and rivaroxaban are specific inhibitors of Factor Xa while dabigatran inhibits Factor IIa. The predictable pharmacological profile of these new agents will allow physicians to use these drugs without the need for routine coagulation monitoring which is the mainstay of warfarin therapy. In addition, these new agents have not been shown to have any food interactions and limited drug-drug interactions due to their minimal metabolism through the CYP450 system. This unique pharmacokinetic profile may usher in for clinicians a new era of managing thromboembolic disorders. In this paper, the pharmacology of these new oral anticoagulants are reviewed along with the major clinical trials in venous thromboembolism prevention in total hip and knee replacement orthopedic surgery, the treatment of venous thromboembolic disorders and stroke prevention in atrial fibrillation.