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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.
Evolution of Hemodialysis Technology
Published in Sirshendu De, Anirban Roy, Hemodialysis Membranes, 2017
However, the first human dialysis was performed by George Haas (1886–1971) in 1924.6,7 His technology was developed independently of Abel–Rowntree–Turner because the First World War did not allow exchange of literature between the Allied and Axis powers. His equipment was very similar to that of the Johns Hopkins group and he prepared 1.2 m long tubes, all put together to yield a surface area of 1.5–2.1 m.2,7 An important note has to be made at this juncture about the preparation of the anticoagulant. Heparin was not available in those days and hence the success of dialysis pivoted around the availability of an effective blood anticoagulant. The group at Johns Hopkins used hirudin.4 Hirudin was extracted in a solution from the crushed heads of leeches.4 In fact, the First World War inhibited John Abel’s research since leeches were imported from Europe (Hungary), and the war prohibited the import of “foreign objects.” Hence, the leeches ordered by John Abel were left to die in Copenhagen.4 Later, George Haas discovered an effective method to extract hirudin, and by employing his device, he carried out the first dialysis in autumn 1924. The dialysis lasted only 15 minutes with no reports of complications. Thereafter, a terminal uremia patient was dialyzed (the second hemodialysis in a human being) in February 18, 1925. It lasted 35 minutes. Four more dialyses were also performed later in 1926, with a duration of 30–60 minutes.8,9 Finally, on January 13, 1928, for the first time George Haas performed a dialysis on a 55 kg man using a dialyzer with an area of 1.5 m2 and with highly purified heparin as the anticoagulant.10
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].