Comparative Antithrombotic Potencies of Direct Thrombin Inhibitors and Low-Molecular-Weight Heparins in an Ex Vivo Human Experimental Thrombosis Model

2002 ◽  
Vol 28 (4) ◽  
pp. 379-382
Author(s):  
Job Harenberg ◽  
Kawei Zokai ◽  
Lukas Piazolo ◽  
Tavidar Fenyvesi ◽  
Ingrid Jörg
Keyword(s):  
Molecular Weight ◽  
Ex Vivo ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Experimental Thrombosis ◽  
Thrombosis Model

Parenteral anticoagulants in heart disease: Current status and perspectives (Section II)

2013 ◽  
Vol 109 (05) ◽  
pp. 769-786 ◽  
Author(s):  
Steen Husted ◽  
Lars Wallentin ◽  
Felicita Andreotti ◽  
Harald Arnesen ◽  
Fedor Bachmann ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Heart Disease ◽  
Unfractionated Heparin ◽  
Heart Diseases ◽  
Thrombin Inhibitors ◽  
Current Status ◽  
Direct Thrombin Inhibitors ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Ongoing Research

SummaryAnticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.

The Future of Anticoagulation

2004 ◽  
Vol 17 (5) ◽  
pp. 370-384 ◽  
Author(s):  
Paul P. Dobesh ◽  
Karissa Kim ◽  
Zachary Stacy
Keyword(s):  
Molecular Weight ◽  
Patient Outcomes ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
New Agents ◽  
The Past ◽  
Anticoagulant Agents ◽  
Improve Patient

Anticoagulant agents, such as unfractionated heparin and warfarin, have been in use for roughly 50 years. Over the past decade, injectable agents such as low-molecular-weight heparins, pentasaccharide, and direct thrombin inhibitors have been major advances in preventing and treating thrombosis. Despite these somewhat recent additions, there is still enormous potential to improve on the pharmacokinetic and pharmacodynamic properties of these agents, as well as improve patient outcomes. There are currently a large number of anticoagulant agents (injectable and oral) that could be available for use in the next several years. Many of these new agents have unique mechanisms that may provide practitioners with anticoagulant alternatives. This review gives a detailed analysis of the anticoagulant agents that may add to our armamentarium in the management of thrombosis.

scholarly journals  Heparin and its derivatives in the treatment of arterial thrombosis: a review 

2010 ◽  
Vol 55 (No. 11) ◽  
pp. 523-546 ◽  
Author(s):  
M. Dvorak ◽  
M. Vlasin ◽  
M. Dvorakova ◽  
P. Rauser ◽  
L. Lexmaulova ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Arterial Thrombosis ◽  
Abdominal Cavity ◽  
Arterial Occlusion ◽  
Thrombin Inhibitors ◽  
Coagulation Cascade ◽  
Adjunctive Treatment ◽  
Direct Thrombin Inhibitors ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins

Arterial occlusion due to thrombosis caused by ruptured atherosclerotic plaques (Baba et al., 1975) has been recognized as a major cause of morbidity and mortality in western populations. Thrombosis may occur in various sections of arterial circulation, peripheral arteries of the limbs, coronary arteries, brain arteries, or both major and minor vessels within the abdominal cavity. The ultimate consequence is varying degrees of organ failure, mostly of ischemic origin. Arterial thrombosis represents a continuous problem, debilitating patients and decreasing their quality of life. Moreover, along with chronic heart failure, it can significantly decrease patient life expectancy. Arterial thrombosis results in ischemia, with serious systemic consequences, such as metabolic breakdown. The major goal of treatment remains fast and efficient recanalization – surgical, interventional or thrombolytic. To be able to prevent acute reocclusion with severe consequences (rhabdomyolysis, compartment syndrome, excessive tissue necrosis leading to limb amputation, etc.), several adjunctive treatment regimens have been advocated. Among others, thrombin inhibitors and platelet inhibitors have been widely used for both prophylaxis and adjunctive treatment. Direct thrombin inhibitors and antithrombin stimulators have been recognized as typical antithrombotic drugs. Direct (antithrombin-independent) thrombin inhibitors can be divided into two main categories: monovalent, active site inhibitors (argatroban, efegatran, inovastan, melagatran) and bivalent (hirudin, hirugen, hirulog, bivalirudin), while antithrombin stimulators represent standard (unfractionated) heparin (UFH) and its depolymerizing products – low molecular weight heparins (LMWH's). Recently, a clear change in the main use of heparin, as well as low-molecular weight heparins has been advocated representing a shift from treatment and prophylaxis of deep vein thrombosis to prophylaxis of thromboembolic disease following vascular, cardiovascular or orthopedic surgery, treatment of unstable angina and prevention of acute myocardial infarction. The main effect of heparins lies in their anticoagulant activity. Heparins are involved in different pathways of the coagulation cascade with anticoagulant, antithrombotic, profibrinolytic, anti-aggregative, as well as anti-inflammatory effects. Moreover, there is a little doubt about their anti-proliferative and anti-ischemic activity (Penka and Bulikova, 2006). Unlike standard heparin, low-molecular weight heparins do not affect the patient's general coagulation profile. Obviously, the difference in molecular weight results in different pharmacokinetic and pharmacodynamic properties of the agents.

Antithrombotic Effect of Two Low Molecular Weight Thrombin Inhibitors and a Low-Molecular Weight Heparin in a Caval Vein Thrombosis Model in the Rat

1997 ◽  
Vol 78 (05) ◽  
pp. 1404-1407 ◽  
Author(s):  
B I Eriksson ◽  
S Carlsson ◽  
M Halvarsson ◽  
B Risberg ◽  
C Mattsson
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Clinical Situation ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Low Molecular Weight ◽  
Surgical Trauma ◽  
Antithrombotic Effect ◽  
Caval Vein ◽  
Thrombosis Model

SummaryA sensitive thrombosis model with a high reproducibility was developed in the rat, utilizing stasis of the caval vein and a standardized surgical trauma as the only thrombogenic stimuli. Since no procoagulant substances were used, the results of the present study might be relevant in a clinical situation. The antithrombotic effect of two recently synthesized low-molecular-weight thrombin inhibitors have been compared to dalteparin, (Fragmin) a low-molecular-weight heparin fragment. Each compound was studied at 8 different doses with 10 rats in each group. On a gravimetric basis, the thrombin inhibitor melagatran was twice as potent as dalteparin (ED50 16 and 33 µ/kg per h, respectively). The second thrombin inhibitor, inogatran, had an intermediate effect, with an ED50 of 24 µLg/kg per h. No differences in antithrombotic effect were, however, found when the compounds were compared at anticoagulant equivalent doses (same APTT prolongation). A 50% reduction in the mean thrombus weight was obtained when APTT was prolonged to 1.2 to 1.3 times the pretreatment value.

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