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https://www.readbyqxmd.com/read/29126301/coagulation-testing-in-the-core-laboratory
#1
William E Winter, Sherri D Flax, Neil S Harris
Primary hemostasis begins with endothelial injury. VWF, produced by endothelial cells, binds to platelets and links them to subendothelial collagen. Platelet-derived ADP and thromboxane activate non-adhered platelets via their GPIIb/IIIa receptors, allowing these platelets to participate in platelet aggregation. Secondary hemostasis is initiated with the binding of factor VII to extravascular tissue factor (TF). Factors II, VII, IX and X are vitamin K-dependent factors. The role of vitamin K is to assist in the addition of gamma carboxylate groups to glutamic acids in the "GLA" domains of these factors...
November 8, 2017: Laboratory Medicine
https://www.readbyqxmd.com/read/29117605/-new-oral-anticoagulants-noac-in-stroke-treatment
#2
Clemens Küpper, Lars Kellert, Steffen Tiedt, Frank Arne Wollenweber
Since 2011, new oral anticoagulants (NOAC) can be prescribed for prevention of cardio-embolic ischemic strokes in addition to vitamin K antagonists. NOAC are indicated in patients with non-valvular atrial fibrillation. Although its use is a matter of debate in Germany, the neurological and cardiological societies recommend the use of NOAC over and above vitamin K antagonists due to a better benefit-to-risk ratio attributed to it, especially because of the lower risk of intracranial hemorrhage in NOAC use. A specific antidote is commercially available for the direct thrombin inhibitor dabigatran only...
November 8, 2017: Fortschritte der Neurologie-Psychiatrie
https://www.readbyqxmd.com/read/29105079/direct-oral-anticoagulants-versus-warfarin-for-preventing-stroke-and-systemic-embolic-events-among-atrial-fibrillation-patients-with-chronic-kidney-disease
#3
REVIEW
Miho Kimachi, Toshi A Furukawa, Kimihiko Kimachi, Yoshihito Goto, Shingo Fukuma, Shunichi Fukuhara
BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for atrial fibrillation (AF), which is more prevalent among CKD patients than the general population. AF causes stroke or systemic embolism, leading to increased mortality. The conventional antithrombotic prophylaxis agent warfarin is often prescribed for the prevention of stroke, but risk of bleeding necessitates regular therapeutic monitoring. Recently developed direct oral anticoagulants (DOAC) are expected to be useful as alternatives to warfarin...
November 6, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29072911/the-design-of-small-molecule-active-site-inhibitors-of-the-s1a-family-proteases-as-procoagulant-and-anticoagulant-drugs
#4
Peter M Fischer
Vitamin K antagonists (VKA) have long been the default drugs for anticoagulant management in venous thrombosis. While efficacious, they are difficult to use due to interpatient dose-response variability and the risks of bleeding. The approval of fondaparinux, a heparin-derived factor Xa (fXa) inhibitor, provided validation for the development of direct oral anticoagulants (DOAC), and currently such inhibitors of thrombin and fXa are in clinical use. These agents can be used without regular coagulation monitoring but the inherent risk of bleeding complications associated with blocking the common coagulation pathway remains...
October 26, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29053656/is-it-necessary-to-alter-anticoagulation-therapy-for-tooth-extraction-in-patients-taking-direct-oral-anticoagulants
#5
M Caliskan, H-C Tükel, M-E Benlidayi, A Deniz
BACKGROUND: The number of patients using direct oral anticoagulants (DOACs) instead of vitamin K antagonists (VKA) is increasing and there is limited data on the safety of tooth extractions in patients taking DOACs. The aim of this study was to compare the amount of bleeding (AOB) and postoperative complications after tooth extractions between patients taking VKAs and patients taking DOACs without altering the anticoaguation therapy. MATERIAL AND METHODS: The study consisted of four groups: Direct thrombin inhibitor group, factor Xa inhibitor group, warfarin group and a control group...
November 1, 2017: Medicina Oral, Patología Oral y Cirugía Bucal
https://www.readbyqxmd.com/read/29050502/first-evidence-trap-induced-platelet-aggregation-is-reduced-in-patients-receiving-xabans
#6
Frantisek Nehaj, Juraj Sokol, Jela Ivankova, Michal Mokan, Frantisek Kovar, Jan Stasko, Marian Mokan
The availability of direct oral anticoagulants has caused a paradigm shift in the management of thrombosis. Rivaroxaban and apixaban are 2 direct oral anticoagulants whose target specificity is activated factor X (FXa). However, it is still not fully understood if and how xabans impact platelet function. This observational study aimed to assess the in vitro platelet function in patients with atrial fibrillation receiving xabans. This was a single-center study quantifying platelet aggregation in 41 patients treated with apixaban or rivaroxaban by light transmission aggregometry...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28979172/reversing-factor-xa-inhibitors-clinical-utility-of-andexanet-alfa
#7
REVIEW
Scott Kaatz, Hardik Bhansali, Joseph Gibbs, Robert Lavender, Charles E Mahan, David G Paje
Approximately half of patients started on an oral anticoagulant in the USA now receive one of the newer direct oral anticoagulants (DOACs). Although there is an approved reversal agent for the direct thrombin inhibitor dabigatran, a specific reversal agent for the anti-factor Xa (FXa) DOACs has yet to be licensed. Unlike the strategy to reverse the only oral direct thrombin inhibitor with idarucizumab, which is a humanized monoclonal antibody fragment, a different approach is necessary to design a single agent that can reverse multiple anti-FXa medications...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28952381/discovery-methods-of-coagulation-inhibiting-drugs
#8
Antonio Gómez-Outes, Minerva García-Fuentes, Mª Luisa Suárez-Gea
In the last decade, several direct oral anticoagulants (DOAC) targeting thrombin (dabigatran) or activated factor X (FXa) (rivaroxaban, apixaban and edoxaban) have been marketed for a number of indications related to prophylaxis and treatment of thrombotic diseases. All these drugs are effective in preventing thrombosis, but are associated with an increased bleeding risk. Areas covered: This review includes a summary of new targets for anticoagulation (e.g.: FXIa, FXIIa, protein disulfide isomerase, polyphosphates, etc...
September 27, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28930804/venous-thromboembolism-in-gynecological-malignancy
#9
Abigail Cohen, Chung Sim Lim, Alun Huw Davies
OBJECTIVE: Venous thromboembolism (VTE) is a recognized complication of gynecological malignancy and represents a leading cause of morbidity and mortality in these patients. The review aimed to discuss the incidence, risk factors, and clinical presentation of VTE before examining the literature on the diagnosis, prevention, and management in the context of uterine, cervical, ovarian, and vulval cancers. METHODS/MATERIALS: A literature search was performed using Ovid Medline and Embase with the following words: "gynecological malignancy," "pelvic tumor," "venous thromboembolism," "deep vein thrombosis" and "pulmonary embolism...
November 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28929298/chronic-kidney-disease-and-anticoagulation-from-vitamin-k-antagonists-and-heparins-to-direct-oral-anticoagulant-agents
#10
REVIEW
Savino Sciascia, Massimo Radin, Karen Schreiber, Roberta Fenoglio, Simone Baldovino, Dario Roccatello
Anticoagulation in patients with impaired kidney function can be challenging since drugs' pharmacokinetics and bioavailability are altered in this setting. Patients with chronic kidney disease (CKD) treated with conventional anticoagulant agents [vitamin K antagonist (VKA), low-molecular weight heparin (LMWH) or unfractionated heparin (UFH)] are at high risk of bleeding events (both non-major and major clinically relevant bleeding). While anticoagulation reduces the risk of thromboembolic events, the co-existing bleeding risk and the fact that the most commonly used anticoagulation agents are eliminated via the kidneys pose additional challenges...
September 19, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28921890/phase-iia-study-of-dabigatran-etexilate-in-children-with-venous-thrombosis-pharmacokinetics-safety-and-tolerability
#11
J M L Halton, M Albisetti, B Biss, L Bomgaars, M Brueckmann, S Gropper, R Harper, F Huang, M Luciani, H Maas, I Tartakovsky, L G Mitchell
Essentials Dabigatran etexilate may provide a new treatment option for pediatric venous thromboembolism. Children aged 1 to < 12 years were given dabigatran etexilate in an open-label, single-arm study. The pharmacokinetic-pharmacodynamic relationship was similar to that seen in adult patients. There were no serious adverse events, bleeding events or recurrent venous thromboembolism. SUMMARY: Background The current standard-of-care treatments for pediatric venous thromboembolism (VTE) have limitations...
September 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28910988/anticoagulation-after-coronary-stenting-a-systemic-review
#12
Zhe Dong, Jingang Zheng
Introduction or background: Anticoagulant therapy is mainly used to prevent patients from suffering coronary and systemic thromboembolism after stenting. Many studies have been done to formulate an optimized regimen of a post-PCI or long-time anticoagulant therapy. Recent advances in the selection and duration of anticoagulant agents will be conducive to the management of patients who are considered to need anticoagulant therapy after stenting. Sources of data: Key recent published literature, including international guidelines and relevant reviews...
September 1, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/28878572/dabigatran-reversal-with-idarucizumab-in-a-patient-undergoing-heart-transplantation-first-european-report
#13
António Tralhão, Carlos Aguiar, Jorge Ferreira, Maria José Rebocho, Emília Santos, Dinis Martins, José Pedro Neves
BACKGROUND: Dabigatran is a direct thrombin inhibitor with a favorable effectiveness and safety profile when compared to vitamin K antagonists, both in randomized trials and real world registries of atrial fibrillation patients. Yet, physicians' fear of high bleeding risk scenarios in daily clinical practice still precludes a more widespread use of oral anticoagulation. We hereby report a successful case of dabigatran reversal with the novel monoclonal antibody fragment idarucizumab in a patient undergoing heart transplantation...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28856946/spontaneous-hit-syndrome-post-knee-replacement-surgery-with-delayed-recovery-of-thrombocytopenia-a-case-report-and-literature-review
#14
Dilli Ram Poudel, Sushil Ghimire, Rashmi Dhital, Daniel A Forman, Theodore E Warkentin
Recently published reports have established a heparin-induced thrombocytopenia (HIT)-mimicking thromboembolic disorder without proximate heparin exposure, called spontaneous HIT syndrome. Although the pathophysiology remains unclear, anti-platelet factor 4 (PF4)/heparin antibodies possibly triggered by exposure to knee cartilage glycosaminoglycans or other non-heparin polyanions found on bacterial surfaces and nucleic acids have been postulated. We present a 53-year-old female receiving antithrombotic prophylaxis with aspirin following right total knee replacement surgery (without perioperative or any previous lifetime heparin exposure) who acutely presented with high-risk pulmonary embolism (PE) and right great saphenous vein thrombophlebitis on postoperative day (POD) 14; her platelet count at presentation was 13 × 10(9)/L...
September 2017: Platelets
https://www.readbyqxmd.com/read/28856671/direct-oral-anticoagulant-medications-in-calciphylaxis
#15
Brian J King, Rokea A El-Azhary, Marian T McEvoy, Raymond C Shields, Robert D McBane, James T McCarthy, Mark D P Davis
BACKGROUND: Recent studies suggest that calciphylaxis is a thrombotic condition in which arteriolar thrombosis leads to painful skin infarcts and consequent morbidity and mortality. Paradoxically, warfarin is implicated as a risk factor for calciphylaxis. Our objective is to report the use of oral direct thrombin and factor Xa inhibitors (termed direct oral anticoagulants [DOACs]) in patients with calciphylaxis. METHODS: We retrospectively reviewed records of 16 patients with calciphylaxis who received concomitant administration of novel anticoagulants...
October 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28808918/idarucizumab-in-dabigatran-treated-patients-with-acute-ischemic-stroke-receiving-alteplase-a-systematic-review-of-the-available-evidence
#16
REVIEW
Slaven Pikija, Laszlo K Sztriha, J Sebastian Mutzenbach, Stefan M Golaszewski, Johann Sellner
BACKGROUND AND PURPOSE: Current guidelines do not recommend the use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who receive direct oral anticoagulants. While the humanized monoclonal antibody idarucizumab can quickly reverse the anticoagulant effects of the thrombin inhibitor dabigatran, safety data for subsequent tissue plasminogen activator treatment are sparse. Here, we review current knowledge about dabigatran reversal prior to systemic reperfusion treatment in acute ischemic stroke...
September 2017: CNS Drugs
https://www.readbyqxmd.com/read/28808596/the-severity-of-intracranial-hemorrhages-measured-by-free-hemoglobin-in-the-brain-depends-on-the-anticoagulant-class-experimental-data
#17
Kyle M Ware, Douglas L Feinstein, Israel Rubinstein, Prudhvi Battula, Jose Otero, Lee Hebert, Tzu-Fei Wang, Alexandra Ivanova, Shweta Chaudhary, Jessica Hemminger, Sergey V Brodsky
Background and Purpose. Anticoagulant therapy is broadly used to prevent thromboembolic events. Intracranial hemorrhages are serious complications of anticoagulation, especially with warfarin. Direct oral anticoagulants reduce but do not eliminate the risk of intracranial hemorrhages. The aim of this study is to determine the degree of intracranial hemorrhage after application of anticoagulants without additional triggers. Methods. Rats were treated with different anticoagulant classes (vitamin K antagonists, heparin, direct thrombin inhibitor, and factor Xa inhibitor)...
2017: Stroke Research and Treatment
https://www.readbyqxmd.com/read/28805310/use-of-direct-oral-anticoagulants-for-stroke-prevention-in-elderly-patients-with-nonvalvular-atrial-fibrillation
#18
REVIEW
Lynn B Oertel, Annemarie E Fogerty
BACKGROUND AND PURPOSE: Four direct oral anticoagulants (DOACs) are available for the prevention of stroke in nonvalvular atrial fibrillation (NVAF): dabigatran (a direct thrombin inhibitor); and rivaroxaban, apixaban, and edoxaban (factor Xa inhibitors). This article summarizes the safety and efficacy of DOACs for the prevention of stroke in elderly NVAF patients. METHODS: PubMed was searched to identify published results of randomized, controlled trials evaluating DOACs for stroke prevention in elderly NVAF patients...
September 2017: Journal of the American Association of Nurse Practitioners
https://www.readbyqxmd.com/read/28805299/dissociation-between-the-pharmacokinetics-and-pharmacodynamics-of-once-daily-rivaroxaban-and-twice-daily-apixaban-a-randomized-crossover-study
#19
R Kreutz, P B Persson, D Kubitza, K Thelen, S Heitmeier, S Schwers, M Becka, M Hemmrich
Essentials In this crossover study the anticoagulant effects of rivaroxaban and apixaban were compared. Healthy volunteers received rivaroxaban 20 mg once daily or apixaban 5 mg twice daily. Rivaroxaban was associated with more prolonged inhibition of thrombin generation than apixaban. Rivaroxaban induced a clear prolongation of prothrombin time and activated partial thromboplastin time. SUMMARY: Background The anticoagulant actions of the oral direct activated factor Xa inhibitors, rivaroxaban and apixaban, have not previously been directly compared...
August 14, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28804832/measuring-direct-oral-anticoagulants
#20
Robert C Gosselin, Jonathan Douxfils
Direct oral anticoagulants (DOACs) can be quantified using methods that can be performed in any clinical or research laboratory using manual or automated instrument platforms. Dabigatran etexilate, the oral direct thrombin inhibitor, can be quantified by drug-calibrated clot or chromogenic-based assays using either thrombin or ecarin as substrates. Oral direct anti-Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban, can be quantified with drug-calibrated anti-Xa kits or reagents as typically used for measuring heparins (unfractionated, low molecular weight, or pentasaccharides)...
2017: Methods in Molecular Biology
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