Metabolic differences of current thienopyridine antiplatelet agents.

Introduction: Antithrombotics are one of the most commonly prescribed classes of medication around the world. The thienopyridines are an integral part of antithrombotic therapy and are prescribed for various indications including acute coronary syndrome, peripheral vascular disease and cerebrovascular disease. These drugs have distinct metabolic pathways, which lead to the formation of active metabolites that produce both observed clinical differences as well as pharmacokinetic and pharmacodynamic differences in response.

Nonhemostatic adverse effects of anticoagulants and antiplatelet agents.

The topic of adverse effects of drugs is now receiving due attention in both the lay and medical communities. For drugs of the coagulation disorder class, such as anticoagulants and antiplatelet agents, the obvious adverse effects are bleeding from a dose too high and thrombosis from a dose too low. However, these drugs have other potential adverse effects that are not directly related to blood coagulation, yet cannot be dismissed due to their medical importance.

Assessment of HIT antibody complex in hip fracture patients receiving enoxaparin or unfractionated heparin.

Thromboembolic disease is a common complication of hip fracture in the elderly. Anticoagulants represent a standard of care in preventing postoperative thrombotic complications following surgical fixation. We asked whether levels of antibody to heparin-platelet factor 4 (PF4) complex were differentially present in unfractionated heparin (UFH) versus Enoxaparin, following hip fracture and whether one particular subtype of antibodies was more prevalent.

Assessment of levels of vascular endothelial growth factor in patients with ESRD and its possible role in cardiovascular morbidity and mortality.

Patients with end-stage renal disease (ESRD) are known to have an elevation of a variety of abnormal thrombotic and inflammatory markers associated with high cardiovascular mortality. Vascular endothelial growth factor (VEGF) is also dysregulated in ESRD but not much is known about the serum levels of VEGF in patients with ESRD. Published reports suggest that elevated levels of VEGF may be protective to the kidney during periods of acute injury and may maintain local glomerular function.

Oral factor Xa and direct thrombin inhibitors: a clinical perspective.

Oral anticoagulation used to be synonymous with warfarin until the recent approval of oral direct thrombin inhibitors and factor Xa inhibitors in United States and other countries across the world. Thrombosis prevention and treatment continue to be the main objective and goal for surgical and medical patients. Regulatory agencies continue to revise their guidelines to treat these patients with appropriate medication and for optimal duration.

Ischemic stroke in the setting of chronic immune thrombocytopenia in an elderly patient--a therapeutic dilemma.

Chronic immune thrombocytopenia (ITP) carries a poor prognosis in the elderly patients. Increasing evidence proposes that a subgroup of patients with chronic ITP may be more susceptible to ischemic stroke. An 84-year-old Caucasian man with multiple ischemic stroke risk factors presented with acute onset of slurred speech, confusion, and unsteady gait.

Generic versus branded enoxaparin in the prevention of venous thromboembolism following major abdominal surgery: report of an exploratory clinical trial.

Introduction: Several generic low-molecular-weight heparins (LMWHs) have recently become available worldwide, including the United States. Companies have filed for regulatory approval of generic versions in many countries, based only on compound biochemical characteristics or its immunogenicity.

Methods: Prospective study to evaluate the comparative effect of 2 enoxaparins (Sanofi-Aventis branded enoxaparin [SAe] vs eurofarma-enoxaparin [Ee], a generic version) as prophylaxis for venous thromboembolism (VTE) following major abdominal surgery.

Upregulation of inflammatory mediators in end-stage renal disease as measured using biochip array technology.

Systemic vascular changes contribute to both the pathogenesis and thrombotic comorbidities of end-stage renal disease (ESRD). This study aims to profile various biomarkers and better understand their role in the pathogenesis of ESRD. Plasma samples from 49 patients with ESRD and 56 control individuals were analyzed for markers for inflammation, specifically C-reactive protein (CRP), tumor necrosis factor receptor 1 (TNFR1), neutrophil gelatinase-associated lipocalin (NGAL); thrombomodulin (TM); neuron-specific enolase (NSE), and thrombosis-D-dimer (DD).

Old versus new oral anticoagulants: focus on pharmacology.

Since the discovery of heparin nearly a century ago, there have been large gaps in the development of anticoagulants. The discovery of warfarin was the first step toward using oral anticoagulants, but warfarin use has been associated with its own challenges from the perspectives of the prescribing physician and the patient. Warfarin, along with other coumarins, has a narrow therapeutic index, requires frequent monitoring, exhibits interindividual response variations, and is associated with several adverse effects.

Vascular disease: obesity and excess weight as modulators of risk.

Coronary artery diseases leading to heart attacks and cerebral artery disease leading to stroke rank number one and two respectively, in causing acute vascular events. Thrombosis of the veins and pulmonary embolism are major causes of hospital-associated acute vascular events. Increased bodyweight at all stages of life, from the very beginning of life (intrauterine growth), to adulthood, promote risks that are associated with vascular disease.

Differentiation of parenteral anticoagulants in the prevention and treatment of venous thromboembolism.

Background: The prevention of venous thromboembolism has been identified as a leading priority in hospital safety. Recommended parenteral anticoagulant agents with different indications for the prevention and treatment of venous thromboembolism include unfractionated heparin, low-molecular-weight heparins and fondaparinux. Prescribing decisions in venous thromboembolism management may seem complex due to the large range of clinical indications and patient types, and the range of anticoagulants available.

Upregulation of microparticles in DIC and its impact on inflammatory processes.

Disseminated intravascular coagulation (DIC) results in the catastrophic simultaneous activation of thrombotic and hemorrhagic processes. Its pathophysiology and the role of inflammation and microparticles (MPs) are not fully understood. Microparticles represent small phospholipid-expressing procoagulant vesicular fragments, released with cellular disruption and apoptosis.

Review: contaminants in heparin: review of the literature, molecular profiling, and clinical implications.

Background: The contaminant isolated from contaminated heparin was oversulfated chondroitin sulfate (OSCS). Other possible contaminants should be evaluated.

Methods: Contaminants were isolated from recalled contaminated heparin and were compared to OSCS from animal sources and to heparin by-products synthetically persulfated.

An open label, non-randomized, prospective clinical trial evaluating the immunogenicity of branded enoxaparin versus biosimilars in healthy volunteers.

Introduction: Compositional variations among biosimilar enoxaparin could lead to a differential immunogenic response between these preparations.

Methods: Enoxaparin (Clexane, n = 110) and a biosimilar version (Cutenox, n = 110) were administered to healthy volunteers in Brazil, 40 mg subcutaneous (SQ), daily, for 10 days. Blood was collected at baseline, days 1 and 10, and analyzed for antiheparin/PF4 antibody (AHPF4 antibodies) titers and subtypes by enzyme-linked-immunosorbent serologic assay (ELISA).

Upregulation of surrogate markers of inflammation and thrombogenesis in patients with ESRD: pathophysiologic and therapeutic implications.

Patients with end-stage renal disease (ESRD) undergoing regular hemodialysis have high annual mortality rate of around 15%. The most predominant cause of death is cardiovascular, which is not entirely explainable with conventional cardiac risk factors present in these patients. It has been postulated that ESRD is a chronic inflammatory and hypercoagulable condition with marked elevation of several markers that may explain this high mortality.

Simple scoring system for early management of heparin-induced thrombocytopenia.

This study was performed to develop a simple scoring system to aid in the early clinical management of patients suspected of heparin-induced thrombocytopenia (HIT) with regard to decisions for continued heparin therapy. The system was designed to arrive at low (0) or possible (1) probability scores without knowledge of laboratory test results (except platelet counts) to avoid delays. As the safest clinical approach is to discontinue heparin, intermediate and high scores were combined.