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Cascade for treatment with new anticoagulants

Simone Negrini, Fabrizio Pappalardo, Giuseppe Murdaca, Francesco Indiveri, Francesco Puppo
Antiphospholipid antibody syndrome (APS) is an autoimmune acquired thrombophilia characterized by recurrent thrombosis and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). APS can be primary, if it occurs in the absence of any underlying disease, or secondary, if it is associated with another autoimmune disorder, most commonly systemic lupus erythematosus. The exact pathogenetic mechanism of APS is unknown, but different, not mutually exclusive, models have been proposed to explain how anti-PL autoantibodies might lead to thrombosis and pregnancy morbidity...
June 22, 2016: Clinical and Experimental Medicine
Youssef Bennis, Subashini Vengadessane, Sandra Bodeau, Valérie Gras, Giampiero Bricca, Saïd Kamel, Sophie Liabeuf
Despite the availability of new oral anticoagulants, vitamin K antagonists (VKA, such as fluindione, acenocoumarol or warfarin) remain currently the goal standard medicines for oral prevention or treatment of thromboembolic disorders. They inhibit the cycle of the vitamin K and its participation in the enzymatic gamma-carboxylation of many proteins. The VKA prevent the activation of the vitamin K-dependent blood clotting factors limiting thus the initiation of the coagulation cascade. But other proteins are vitamin K-dependent and also remain inactive in the presence of VKA...
September 2016: Thérapie
Ramyashree Tummala, Ana Kavtaradze, Anjan Gupta, Raktim Kumar Ghosh
The Vitamin K antagonist warfarin was the only oral anticoagulant available for decades for the treatment of thrombosis and prevention of thromboembolism until Direct Oral Anticoagulants (DOACs); a group of new oral anticoagulants got approved in the last few years. Direct thrombin inhibitor: dabigatran and factor Xa inhibitors: apixaban, rivaroxaban, and edoxaban directly inhibit the coagulation cascade. DOACs have many advantages over warfarin. However, the biggest drawback of DOACs has been the lack of specific antidotes to reverse the anticoagulant effect in emergency situations...
July 1, 2016: International Journal of Cardiology
Peter Stachon, Ingo Ahrens, Christoph Bode, Andreas Zirlik
In 10 % of patients, who suffer an acute coronary syndrome (ACS), a major cardiovascular event occurs despite optimal therapy. The occlusion of the vessel is driven by atherothrombosis, which arises from platelet activation and activation of the coagulation cascade. In the last decade the secondary prevention continuously improved by development of dual anti-platelet therapy with new P2Y12-inhibitors such as clopidogrel, prasugrel, and ticagrelor. Until recently, the coagulation cascade was not targeted in secondary prevention...
August 2016: Journal of Thrombosis and Thrombolysis
Michelle P Zeller, Khalid S Al-Habsi, Mia Golder, Geraldine M Walsh, William P Sheffield
Plasma obtained via whole blood donation processing or via apheresis technology can either be transfused directly to patients or pooled and fractionated into plasma protein products that are concentrates of 1 or more purified plasma protein. The evidence base supporting clinical efficacy in most of the indications for which plasma is transfused is weak, whereas high-quality evidence supports the efficacy of plasma protein products in at least some of the clinical settings in which they are used. Transfusable plasma utilization remains composed in part of applications that fall outside of clinical practice guidelines...
July 2015: Transfusion Medicine Reviews
Marta A Miyares, Kyle A Davis
OBJECTIVE: To review the evidence for the use of the direct-acting oral anticoagulants (DOACs) in adult patients with heparin-induced thrombocytopenia (HIT). DATA SOURCE: A PubMed search (1950-February 2015) was collected using the terms heparin-induced thrombocytopenia, with dabigatran, rivaroxaban, or apixaban, or heparin-induced thrombocytopenia and target-specific anticoagulants, or heparin-induced thrombocytopenia and direct-acting oral anticoagulants, or heparin-induced thrombocytopenia and new oral anticoagulants...
June 2015: Annals of Pharmacotherapy
Cheol Whan Lee
Platelets initiate the formation of a thrombus at the site of an arterial injury, and the clotting cascade is activated as the thrombus matures. After coronary stent placement, dual antiplatelet therapy (DAPT) with aspirin and ticlopidine dramatically reduces the risk of stent thrombosis, compared with anticoagulation therapy, and has become the standard of care for prevention of stent thrombosis. Clopidogrel is a second-generation thienopyridine that eliminates the serious side effects of ticlopidine, and new P2Y12 receptor blockers have emerged to overcome the limitations of clopidogrel...
2015: Circulation Journal: Official Journal of the Japanese Circulation Society
Arturo J Martí-Carvajal, Vidhu Anand, Andrés Felipe Cardona, Ivan Solà
BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, not malignant, disease of the hematopoietic stem cells, associated with significant morbidity and mortality. It is a rare disease with an estimated incidence of 1.3 new cases per one million individuals per year. The treatment of PNH has been largely empirical and symptomatic, with blood transfusions, anticoagulation, and supplementation with folic acid or iron. Eculizumab, a biological agent that inhibits complement cascade, was developed for preventing hemolytic anemia and severe thrombotic episodes...
2014: Cochrane Database of Systematic Reviews
Zhi-Hao Shi, Nian-Guang Li, Yu-Ping Tang, Jin-Ao Duan
INTRODUCTION: Thrombotic disorders can lead to deep vein thrombosis, myocardial infarction and stroke. Thrombin plays a vital role in cascade reaction of blood coagulation, inhibition of the activity of thrombin can block the formation of thrombus and direct thrombin inhibitor has a prospect to overcome the limitations in application of the traditional anticoagulant drugs. AREAS COVERED: The current patent US2013296245 describes a series of prolinamide derivatives with formula (I) as thrombin inhibitors...
October 2014: Expert Opinion on Therapeutic Patents
C B Chighizola, M Moia, P L Meroni
A main goal in clinical management of patients with antiphospholipid syndrome (APS) is to prevent thrombotic recurrences and/or miscarriages. For many decades, the only available oral anticoagulant drugs have been vitamin K antagonists (VKA), which are still the cornerstone of long-term treatment of thromboembolism. However, the limits of VKA treatment are well known: narrow therapeutic window and high patient-to-patient variability of response. Moreover, in some patients with APS a higher international normalized ratio (INR) therapeutic target was suggested, and INR inaccuracy due to antiphospholipid antibodies was reported...
October 2014: Lupus
Lisa M Baumann Kreuziger, Joseph C Keenan, Colleen T Morton, David J Dries
Ease of dosing and simplicity of monitoring make new oral anticoagulants an attractive therapy in a growing range of clinical conditions. However, newer oral anticoagulants interact with the coagulation cascade in different ways than traditional warfarin therapy. Replacement of clotting factors will not reverse the effects of dabigatran, rivaroxaban, or apixaban. Currently, antidotes for these drugs are not widely available. Fortunately, withholding the anticoagulant and dialysis are freqnently effective treatments, particularly with rivaroxaban and dabigatran...
2014: BioMed Research International
Tatsufumi Nakamura, Katsuya Satoh, Taku Fukuda, Ikuo Kinoshita, Yoshihiro Nishiura, Kunihiko Nagasato, Atsushi Yamauchi, Yasufumi Kataoka, Tadahiro Nakamura, Hitoshi Sasaki, Kenji Kumagai, Masami Niwa, Mitsuru Noguchi, Hideki Nakamura, Noriyuki Nishida, Atsushi Kawakami
The main therapeutic strategy against human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) characterized by lower extremity motor dysfunction is immunomodulatory treatment, with drugs such as corticosteroid hormone and interferon-α, at present. However, there are many issues in long-term treatment with these drugs, such as insufficient effects and various side effects. We now urgently need to develop other therapeutic strategies. The heparinoid, pentosan polysulfate sodium (PPS), has been safely used in Europe for the past 50 years as a thrombosis prophylaxis and for the treatment of phlebitis...
June 2014: Journal of Neurovirology
Yiming Xu, Tian-Quan Cai, Gino Castriota, Yuchen Zhou, Lizbeth Hoos, Nina Jochnowitz, Christopher Loewrigkeit, John A Cook, Alexandra Wickham, Joseph M Metzger, Martin L Ogletree, Dietmar A Seiffert, Zhu Chen
Coagulation factor XII (FXII) plays a central role in initiating the intrinsic cascade of blood coagulation. Purified recombinant Human Albumin-tagged Infestin-4 (rHA-Infestin-4) is a recently described FXIIa inhibitor that displayed strong anticoagulant activity without compromising haemostasis in several animal models. We pursued detailed in vitro characterisation of rHA-Infestin-4 and demonstrated that it is a competitive inhibitor of FXIIa with slow on and off rate constants for binding (kon=5x10⁵ M⁻¹s⁻¹, koff=6x10⁻⁴ s⁻¹), it can block FXIIa activation of its physiological substrates (plasma prekallikrein and FXI), and it can inhibit ellagic acid-triggered thrombin generation in plasma...
April 1, 2014: Thrombosis and Haemostasis
Gentian Denas, Vittorio Pengo
INTRODUCTION: The introduction of novel anticoagulants has had contrasting effects on the agents in the pipeline, fueling the development of some and sinking the others. The complexity of the coagulation cascade offers interesting inhibition choices that might become valid treatment options. AREAS COVERED: This review will highlight some of the anticoagulants in the pipeline. Following the success of the direct thrombin and FXa inhibitors already in the market, new agents are being tested...
October 2013: Expert Opinion on Investigational Drugs
Pilar Gallego, Vanessa Roldan, Gregory Y H Lip
Oral anticoagulants block the coagulation cascade either by an indirect mechanism (e.g., vitamin K antagonists) or by a direct one (e.g., the novel oral anticoagulants). Vitamin K antagonists are widely used as treatment of venous thromboembolism and for stroke prevention in patients with atrial fibrillation. Although low molecular weight heparin remains the first line in venous thromboembolism prophylaxis, more recently the novel oral anticoagulants such as dabigatran (initial dose of 110 mg within 1-4 h after surgery, followed by the full dose of 220 mg once daily), rivaroxaban (dose of 10 mg once daily, with the first dose administered 6-10 h after the surgery), and apixaban (dose of 2...
August 15, 2013: American Journal of Respiratory and Critical Care Medicine
Anne J Schmitt, Anna K Wallner, Shahrzad Afazel, Monika Killer-Oberpfalzer
INTRODUCTION: The purpose of this study was to monitor and to optimize heparinization during endovascular procedures in the New Zealand White Rabbit (NZWR) model. METHODS: Right common carotid artery aneurysms were surgically created in 43 NZWR, with an average weight of 4,330 g (range 3,500-5,430 g). The activated partial thromboplastin time (aPTT) was measured during different stages of the interventional procedures. Blood samples were taken before and 10 min after administration of heparin and at the end of each endovascular procedure...
July 2013: Neuroradiology
P Prandoni, F Dalla Valle, C Piovella, D Tormene, R Pesavento
In recent years, the significant limitations associated with the use of vitamin K antagonists (VKA) have encouraged the development of new agents. Based upon the central roles played by the serine proteases thrombin and Factor Xa in the blood coagulation cascade, direct thrombin inhibitors and direct Factor Xa inhibitors have been developed. These agents, which include the direct thrombin inhibitor dabigatran etexilate and the Factor Xa inhibitors rivaroxaban and idrabiotaparinux are free from many of the limitations of VKAs...
April 2013: Minerva Medica
P Gavornik, L Gašpar, A Dukát
Parenteral heparin and oral coumarin preparations represent the standard antithrombotics widely used in the prevention and treatment of venous thromboembolism (VTE). Unfractionated heparin, low molecular weight heparins, and fondaparinux have been shown to be effective and safe in reducing VTE risk. Despite high efficacy these medicaments have limitations which become to be more apparent with current widening of the indications for either primary thromboprophylaxis (PTP) or indefinite and even lifelong secondary thromboprophylaxis (STP)...
November 2012: Vnitr̆ní Lékar̆ství
Carla M Caramella, Giuseppina Sandri, Silvia Rossi, Michela Mori, Maria Cristina Bonferoni, Franca Ferrari, Claudia Del Fante, Cesare Perotti
There are still so-called unmet needs in the treatment of epithelial and cutaneous lesions. Mucositis, ocular lesions, chronic skin wounds represent typical examples. These pathologies do not yet afford a satisfactory treatment. In particular chronic wounds represent a major health care burden, likely to increase as the population ages. Healing of epithelial and cutaneous lesions progresses through a complex cascade of events starting with the secretion in the local environment of a pool of growth factors, cytokines and proteins from the serum and degranulating platelets...
February 2013: Current Drug Delivery
Karna Shah, Riad Bayoumi, Yajnavalka Banerjee
Anticoagulants are pivotal for the treatment of debilitating thromboembolic and associated disorders. Current anticoagulants such as heparin and warfarin are non-specific and have a narrow therapeutic window. These limitations have provided the impetus to develop new anticoagulant therapies/strategies that target specific factors in the blood coagulation cascade, ideally those located upstream in the clotting process. Factor VIIa (FVIIa) presents an attractive target as it, in complex with tissue factor (TF), acts as the prima ballerina for the formation of blood clot...
January 2013: Hematology (Amsterdam, Netherlands)
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