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Development and clinical applications of novel oral anticoagulants. Part I. Clinically approved drugs.

Discov Med. 2012 Jun;13(73):433-43

Authors: Ahrens I, Peter K, Lip GY, Bode C

Abstract
Two new classes of orally available anticoagulant drugs, the direct thrombin inhibitor (dabigatran etexilate) and direct factor Xa inhibitors (the -xabans), have been approved for various clinical indications, as alternatives to the vitamin K antagonists (e.g., warfarin). These include the prevention of venous thromboembolism after major orthopedic surgery, the prevention of stroke and systemic embolism in non-valvular atrial fibrillation, and the secondary prevention and treatment of venous thromboembolism including pulmonary embolism. Other clinical indications including the add-on therapy to dual antiplatelet therapy in patients with acute coronary syndrome and extended prophylaxis of venous thromboembolism in acute medically ill patients are currently under clinical investigation. The clinical phase III development and indications of the currently clinically approved novel oral anticoagulants dabigatran etexilate, rivaroxaban, apixaban, and edoxaban are summarized and discussed.

PMID: 22742649 [PubMed - in process]

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Perioperative Pulmonary Embolism: Detection, Treatment, and Outcomes.

Am J Ther. 2012 Jun 22;

Authors: Hall D

Abstract
Acute pulmonary embolism (PE) is a relatively rare but potentially fatal complication during the perioperative period. Its diagnosis is particularly challenging in the anesthetized patient, yet early diagnosis and treatment are essential in preventing morbidity and mortality. Preventative measures including anticoagulant treatment are well-established modalities in the management of venous thromboses and PE in the nonsurgical patient. However, a patient undergoing surgery suffering a new PE presents a unique challenge. Conventional treatment is often not an option in the perioperative period, as surgical bleeding may be equally life threatening as a PE. Therefore, techniques that target the embolism directly and avoid systemic anticoagulation seem to promise safer and more efficient treatment of the patient with PE in the perioperative period. Fast detection, correct diagnosis, and appropriate treatment are all essential in improving the outcome of this severe complication.

PMID: 22743348 [PubMed - as supplied by publisher]

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Pulmonary Embolism Without Deep Venous Thrombosis.

Ann Vasc Surg. 2012 Jun 28;

Authors: Schwartz T, Hingorani A, Ascher E, Marks N, Shiferson A, Jung D, Jimenez R, Jacob T

Abstract
BACKGROUND: To identify patients with pulmonary embolism (PE) without deep venous thrombosis (DVT), and to compare them with those with an identifiable source on upper (UED) and lower-extremity venous duplex scans (LED). METHODS: We performed a retrospective review of 2700 computed tomography angiograms of the chest between January 2008 and September 2010 and identified 230 patients with PE. We then evaluated the results of UED and LED and divided the patients into four groups based on the results of their duplex studies. We compared patients with PE and DVT with those with PE and no DVT in terms of age, gender, size and location of PE, critical illness, malignancy, and in-hospital mortality. RESULTS: We identified 152 women and 78 men (mean age, 68 years) with PE. One hundred thirty-one patients had a documented source of PE (group 1). Fifty-three patients had negative LED results, but did not undergo UED (group 2). Thirty-one patients did not undergo either LED or UED (group 3). Seven men and eight women had no documented source of PE on UED and LED (group 4). Ten of 15 patients in group 4 had a documented malignancy listed as one of their diagnoses. Because patients in groups 2 and 3 did not undergo complete duplex studies, we excluded them from our analysis. We then reviewed the discharge summaries of patients in groups 1 and 4. There was no statistically significant difference in age and gender distribution, size and location of PE, critical illness, smoking status, cardiovascular disease, trauma, and in-hospital mortality between patients in group 1 and 4. Patients in group 4 had a statistically significant increased prevalence of malignancy (67% vs. 40%, P = 0.046). Patients in group 4 also had a higher percentage of active cancer than those in group 1 (47% vs. 24%, P = 0.084), although not statistically significant. We defined active cancer as either a metastatic disease or a malignancy diagnosed shortly before or after the diagnosis of PE. Patients who were undergoing treatment for cancer at the time of diagnosis of PE were also considered to have active cancer. CONCLUSION: We demonstrated a statistically significant increased prevalence of malignancy in patients with PE without DVT. However, pathophysiology and clinical significance are the aspects that remain to be understood after accrual of more patients and further research. Possibilities such as de novo thrombosis of pulmonary arteries, complete dislodgement of thrombi from peripheral veins, or false-negative venous duplex need to be explored.

PMID: 22749324 [PubMed - as supplied by publisher]

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Low Incidence of Pulmonary Embolism Associated With Upper-Extremity Deep Venous Thrombosis.

Ann Vasc Surg. 2012 Jun 29;

Authors: Levy MM, Albuquerque F, Pfeifer JD

Abstract
BACKGROUND: Most recent Chest 2008 guidelines counsel at least 3 months of anticoagulation for acute upper-extremity deep venous thrombosis (UEDVT). These guidelines are inconsistently followed, perhaps owing to relatively limited information regarding clinical outcomes among patients with UEDVT. Our institution maintains an UEDVT registry of consecutively encountered patients with sonographically confirmed UEDVT. We analyzed patient characteristics, treatment, and outcomes among these patients. METHODS: Between April 2005 and November 2008, 300 consecutively encountered peripheral vascular laboratory patients with UEDVTs were identified. Data on UEDVT sonographic characteristics, patient demographics, anticoagulation treatment, pulmonary embolism (PE) incidence and diagnostic modality, hemorrhagic complications, and mortality were then extracted. RESULTS: Among the 300 patients, there was deep venous obstruction in the distal innominate (n = 69), internal jugular (n = 146), subclavian (n = 161), axillary (n = 107), and brachial (n = 91) veins. Two hundred forty-six patients (82%) had UEDVTs identified as clearly acute or acute on chronic, based on sonographic appearance. Most patients with UEDVTs were symptomatic (n = 265, 88%). One hundred six patients had documented malignancy (35%), 92 were postoperative or trauma patients (31%), and 76 patients were obese (body mass index: >30, 25%). Additionally, 240 patients had associated or previous indwelling central venous lines or leads (80%). One hundred twenty-eight patients (43%) were initially anticoagulated with heparin, whereas 121 of these patients were converted to warfarin therapy (40%) for variable lengths of time. One hundred sixty-seven patients were not treated with anticoagulation (56%), of whom 16 had documented contraindication to anticoagulation. Although the anticoagulated subset of patients tended to be younger, the decision to anticoagulate patients correlated significantly with the sonographically documented acute nature of the deep venous thrombosis, and its extent. Six patients (2%) suffered PE in association with their UEDVT diagnosis. There was no PE-related mortality. However, among anticoagulated UEDVT patients, there were four patients who suffered intracranial hemorrhage resulting in three deaths, and an additional three patients who required rehospitalization for upper gastrointestinal (n = 2) or stomal (n = 1) hemorrhage. CONCLUSIONS: Anticoagulation therapy is inconsistently used to treat UEDVT and most often used for patients with multiple vein segments involved and with sonographically acute UEDVT components. However, regardless of the decision to anticoagulate, the incidence of PE attributable to UEDVT is small (2%), regardless of treatment with anticoagulation. Given the observed mortality associated with anticoagulation in this fragile patient cohort, the risk-benefit analysis for anticoagulation does not favor routine anticoagulation among these patients.

PMID: 22749742 [PubMed - as supplied by publisher]