Modulation of platelet activation in chronic kidney disease patients on erythropoiesis-stimulating agents.

Background: Clinical trials demonstrate either no benefit or increased risk of cardiovascular events and mortality in patients with chronic kidney disease (CKD) targeted for higher hemoglobin levels, who are treated with erythropoiesis-stimulating agents (ESAs). The mechanism underlying this observation remains unexplained.

Methods And Results: We assessed platelet activation by measuring soluble P-selectin (sPsel), CD40 ligand (CD40L), and circulating microparticles (CMP) in patients with CKD.

Aspirin prophylaxis for the prevention of thrombosis: expectations and limitations.

Platelets play a very important role in the pathogenesis of acute vascular events leading to thrombosis of the coronary and cerebral arteries. Blockage of these arteries leading to regional ischemia of heart and brain tissues precipitate heart attacks and stroke. Acetyl salicylic acid (Aspirin) has been the drug of choice for over half a century for the primary and secondary prophylaxis of thrombotic events.

Structural and pharmacological profile of generic enoxaparins used in Brazil.

Generic active pharmaceutical ingredients (APIs) have been commonly used in Brazil, since 1999, but most of them are synthetic and small molecules. Recently, a large number of generic enoxaparins were introduced into the market raising concerns related to product-to-product interchangeability, efficiency, and drug counterfeiting. These drugs are produced from biological sources and their production involves complex procedures and purification processes.

Gender-based differences in hemostatic responses.

Aim: Recent reports indicate increased mortality in women owing to cardiovascular diseases necessitating more gender-based studies. It is hypothesized that women have variable hemostatic responses to anticoagulant drugs.

Materials & Methods: The hemostatic responses in healthy males (n = 10) and females (n = 10) were evaluated by performing various assays in the presence of anticoagulant drugs.

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.

Cross-reactivity of various thrombin products with anti-rabbit antibodies to bovine, human, and recombinant thrombin.

JMI-thrombin is used as topical hemostatic agent. While earlier clinically available JMI were reported to produce immunologic responses upon repeated exposure, the improved JMI, Recothrom?, and Evithrom? are claimed to be less immunogenic. Recothrom, despite its reduced immunogenic nature, upon repeated administration may result in the generation of antibodies (Abs) and that may cross react with bovine and human thrombin.

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.

Interactions of oversulfated chondroitin sulfate (OSCS) from different sources with unfractionated heparin.

In 2008, oversulfated chondroitin sulfate (OSCS) was identified as the main contaminant in recalled heparin. Oversulfated chondroitin sulfate can be prepared from bovine (B), porcine (P), shark (Sh), or skate (S) origin and may produce changes in the antithrombotic, bleeding, and hemodynamic profile of heparins. This study examines the interactions of various OSCSs on heparin in animal models of thrombosis and bleeding, as well as on the anticoagulant and antiprotease effects in in vitro assays.

A comparison of the pharmacodynamic behavior of branded and biosimilar enoxaparin in primates.

Pharmacodynamic behavior of branded and biosimilar enoxaparin was compared in a crossover study in primates. Blood samples collected at baseline and at 1, 4, 6, and 28 hours post-subcutaneous administration of Lovenox or Fibrinox were evaluated using clot-based and amidolytic assays. Anti-Xa levels following Fibrinox and Lovenox administration were not different.

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.

US Food and Drug Administration approval of generic versions of complex biologics: implications for the practicing physician using low molecular weight heparins.

Low-molecular-weight heparins (LMWHs) have shown equivalent or superior efficacy and safety to unfractionated heparin as antithrombotic therapy for patients with acute coronary syndromes. Each approved LMWH is a pleotropic biological agent with a unique chemical, biochemical, biophysical and biological profile and displays different pharmacodynamic and pharmacokinetic profiles. As a result, LMWHs are neither equipotent in preclinical assays nor equivalent in terms of their clinical efficacy and safety.

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.

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.

Defibrotide blunts the prothrombotic effect of thalidomide on endothelial cells.

Patients with multiple myeloma (MM) are at relatively high risk of developing thromboembolic events such deep venous thrombosis (DVT) where thalidomide therapy has been identified to increase this risk. Defibrotide (DF), a polydisperse oligonucleotide, showed previously to counteract the alterations in endothelial cells (ECs) induced by lipopolysaccharide. It prompts us to investigate the impact of thalidomide on ECs and whether DF modulates changes in fibrinolysis induced by thalidomide.

Prophylaxis of venous thromboembolism: low molecular weight heparin compared to the selective anticoagulants rivaroxaban, dabigatran and fondaparinux.

Newer therapeutic options available in the prevention of postoperative thromboembolism, currently focused on fondaparinux, rivaroxaban and dabigatran warrant an overall therapeutic assessment. The constitutive comparisons with enoxaparin are based on a combined outcome measure solely driven by the incidence of "asymptomatic deep vein thrombosis". Its validity as a clinically relevant endpoint is missing if antithrombotics of different classes are compared.

Immune responses associated with perioperative exposure and reexposure to topical bovine thrombin do not impair hemostasis.

Topical bovine thrombin has been associated with immune responses and anecdotal reports of coagulopathy. This open-label study assessed the impact on clinical hemostasis of human antibodies to bovine thrombin (aBT) or factor V/Va (aBV/Va) in response to topical bovine thrombin (THROMBIN-JMI) in patients both with and without preexisting anti-bovine antibodies. Noninferiority analysis assessed primary endpoint for mean shift from baseline activated partial thromboplastin time (aPTT) at 48 hours postsurgery; secondary endpoints included changes from baseline antibodies/titers and coagulation parameters through 8 weeks postsurgery.

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.

A common standard is inappropriate for determining the potency of ultra low molecular weight heparins such as semuloparin and bemiparin.

Introduction: Lower low-molecular-weight heparins are being developed to improve on the safety and efficacy of antithrombotic therapy. Semuloparin and bemiparin are two depolymerized heparins produced by distinct manufacturing processes. The objective of this investigation was to determine whether a common standard could be used to define their potency.

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.

Antiphospholipid syndrome and pre-eclampsia.

Antiphospholipid syndrome (APS) is defined as an autoimmune disorder characterized by recurrent thrombosis or obstetrical morbidity. These features are linked to the presence in blood of autoantibodies against negatively charged phospholipids or phospholipid-binding proteins. Obstetric morbidity includes recurrent abortion (early and late) and severe pre-eclampsia (P-EC)/hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and/or severe placental insufficiency.

Functionality of fondaparinux (pentasaccharide) depends on clinical antithrombin levels.

Fondaparinux (Arixtra) is an antithrombin (AT)-dependent synthetic inhibitor of factor Xa (FXa). We undertook a study to determine the ramifications of varying levels of circulating AT on the pharmacologic activity of fondaparinux. AT-deficient human plasma supplemented with 0.