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Fibrinolytic Enzymes for Thrombolytic Therapy
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Swaroop S. Kumar, Sabu Abdulhameed
Several thrombin inhibitors have been developed during the past couple of decades and proved their efficacy as anticoagulants. Hirudin is one of the most important, naturally occurring thrombin inhibitor molecule isolated from leach. Administration of hirudin has been associated with increased risk of bleeding as well as formation of non-neutralizing antibodies in patients (Hoppensteadt et al., 2008). Later, many thrombin inhibitors with better efficacy and therapeutic potential have been developed such as argatroban, bivalirudin, lepirudin, and dabigatran etexilate. The first used thrombin inhibitor is argatroban and it is now widely used in Japan. It was recommended as an alternate anticoagulant for patients suffering from HIT and its clinical use significantly reduced bleeding complications in comparison to heparin (Lewis et al., 2001, 2003). Bivalirudin is a bivalent reversible inhibitor and when compared to heparin and LMWHs, they declined the bleeding complications by almost 50%, whereas the efficacy remained same for all of them (Carswell and Plosker, 2002; Ahrens et al., 2007). Another thrombin inhibitor lepirudin was found to be marginally superior to heparin and more suitable for patients with previously reported HIT though continuous monitoring is required here also (Lubenow et al., 2004). Dabigatran etexilate is an oral prodrug that would get converted into active dabigatran, a direct thrombin inhibitor, upon intestinal absorption (Lee and Ansell, 2011). All those thrombin inhibitors described here are FDA approved for preventing various cardiovascular diseases.
Clinical Effects of Pollution
Published in William J. Rea, Kalpana D. Patel, Reversibility of Chronic Disease and Hypersensitivity, Volume 5, 2017
William J. Rea, Kalpana D. Patel
However, the use of anticoagulation in a patient with an underlying coagulopathy is inherently problematic if an agent that is monitored by the activated partial thromboplastin time (APTT) is used. This is because the systematic administration of an inappropriately reduced dose of anticoagulant therapy, called APTT confounding, can result when a standard APTT-adjusted treatment nomogram is applied to a patient whose baseline (pretreatment) APTT is already elevated.501 Such an effect can occur if unfractionated heparin is used to treat cancer-associated hypercoagulability or if argatroban is given for thrombosis complicating severe HIT with associated DIC.501,502 Warfarin also prolongs the APTT, further contributing to less effective administration of heparin or argatroban.501,503 This problem can be avoided by the use of LMWH or monitoring of unfractionated heparin by measuring levels of antifactor Xa (for treating cancer-associated hypercoagulability) or the use of an anticoagulant that does not require APTT monitoring (e.g., danaparoid or fondaparinux for treating HIT).
Drug-induced bronchospasm
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
K Suresh Babu, Jaymin Morjaria
Heparin, a mucopolysaccharide with a molecular weight of 6–20 kDa, can elicit several types of immunologically mediated reactions, such as asthma and anaphylaxis.39 Skin-testing does not appear to be useful in elucidating immediate-type hypersensitivity responses to heparin, and cross-reactivity has been demonstrated between heparin, the low-molecular-weight heparins and donaporoid sodium. It is therefore recommended that the new direct thrombin inhibitors (argatroban and lepirudin) be used in patients allergic to heparin.40
Device profile of the Impella 5.0 and 5.5 system for mechanical circulatory support for patients with cardiogenic shock: overview of its safety and efficacy
Published in Expert Review of Medical Devices, 2022
Mohit Pahuja, Jaime Hernandez-Montfort, Evan H. Whitehead, Masashi Kawabori, Navin K. Kapur
Impella device involves blood to flow continuously into the catheter, hence, a purge solution flows runs retrograde to the blood flow that creates a pressure barrier and prevents blood entry into the motor. It also requires heparin which helps to maintain adequate purge pressure by preventing thrombotic complications. Currently the manufacturer recommends titrating heparin to maintain the goal activated clotting time (ACT) of 160–180. Many patients require non-purge systemic heparin to maintain this target but, in some patients, purge heparin solution may be sufficient to maintain the therapeutic targets. If the patients is running higher targets with only the purge solution, it is recommended to reducing the heparin to half concentration. In patients with heparin-induced thrombocytopenia, a direct thrombin inhibitor such as bivalirudin or argatroban can by given separately outside the purge solution [45].
Pediatric ventricular assist devices: what are the key considerations and requirements?
Published in Expert Review of Medical Devices, 2020
Roland Hetzer, Mariano Francisco del Maria Javier, Eva Maria Javier Delmo
After 2000 and onwards, the standard institutional anticoagulation protocol strictly adhered to [20,29] (1) no postoperative anticoagulation is given for the first 8–24 hours. The effect is monitored two to four times daily, if necessary. (2) For the next 48 hours, continuous unfractionated heparin infusion is administered to keep the activated partial thromboplastin time between 60 and 80 seconds and activated clotting times of 140–160 seconds. Vitamin K antagonists, such as Warfarin or Coumadin, were not used. (3) TEF, performed twice a week after VAD implantation, helps to identify the coagulation status and efficacy of heparin. It is very useful to evaluate hypo- or hyper-coagulation and to adjust the target value of activated partial thromboplastin time. (4) Antithrombin III is substituted if activated partial thromboplastin time falls below 70% of the target level. This approach however led to frequent bleeding complications. (5) When oral feeding has been started and chest tubes have been removed, platelet inhibitor treatment with acetylsalicylic acid combined with dipyridamole (assuming a normal platelet number and function) in a weight-adjusted dose is started one week after implantation. The modified current anticoagulation practice is that the older children receive Vitamin K antagonist with a target international normalized ratio (INR) level of 2.5–3.5. (6) Platelet aggregation tests are performed at least weekly, with target activation of 30%. TEF (Haemonetics Corporation, Braintree, MA, U.S.A.) monitors the efficacy of antithrombotic treatment. L-hirudin or Argatroban is used in patients with heparin-induced thrombocytopenia type II. This is monitored by the platelet aggregation test with arachidonic acid [23].
Immobilizing argatroban and mPEG-NH2 on a polyethersulfone membrane surface to prepare an effective nonthrombogenic biointerface
Published in Journal of Biomaterials Science, Polymer Edition, 2019
Yanling Dai, Siyuan Dai, Xiaohui Xie, Jianping Ning
Argatroban (AG), a synthetic direct thrombin inhibitor that does not require a co-factor to impart activity, has been developed to provide superior nonthrombotic efficacy to heparin [7, 34–36]. First, AG can not only reversibly and selectively inhibit plasma-free and clot-bound thrombin but can also inhibit protein C, several procoagulant factors and platelet aggregation [37–39]. Second, as a homogeneous synthetic molecule, AG does not generate heparin/PF4 complex antibodies; thus, it cannot lead to heparin-induced thrombocytopenia, and it is a suggested treatment for patients with acute HIT who are undergoing hemodialysis [40–41].