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

Abstract

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.Key words: coagulation; arterial thrombosis; standard heparin; low-molecular weight heparins List of abbreviations ABI = axillary/...index, t-PA = tissue-type plasminogen activator, ADP = adenosin diphosphate, AG = angiography, AMI = acute myocardial infarction, APSAC = acylated plasminogen streptokinase activator complex, APTT = acti...

Effect of Aloe Vera (Aloe barbadensis) on Thrombosis in Mice

“…The present data supported by earlier reports which states that the heparin binds to enzyme inhibitor antithrombin-III and inactivates thrombin and other proteases involved in blood clotting. It is also reported by many scientists that heparin and its low molecular weight derivatives prevent thrombosis [18][19][20][21] . In the present study, it is found that the aqueous gel of aloe vera significantly enhanced the bleeding time and mean λ max in mice.…”

Review article: DOES INTRA-ARTERIAL HEPARIN FLUSHING (IAHF) CAN ACTUALLY INCREASE MANUAL MUSCLE TEST (MMT) SCORE IN CHRONIC ISCHEMIC STROKE PATIENTS?

“…Its properties can be defined as anti-inflammatory (Perretti & Page 2000, Salas et al 2000, anticoagulative, antithrombotic, pro-fibrinolytic, anti-aggregative, anti-proliferative and anti-ischemic (Lundin et al 2000, Dvorak et al 2010. Recently, a clear change in the main use of heparin, as well as lowmolecular 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 (Dvorak et al 2010).…”

“…Generally, heparin disturbs homeostasis through inhibition of coagulation enzymes. This effect is facilitated by plasma cofactors and through inhibition of platelets (Dvorak et al 2010). Heparin is thought to enhance thrombolytic by inhibiting TAFI (thrombin activatable fibrinolysis inhibitor), a carboxypeptidase that inhibits fibrinolysis.…”

Intra Arterial Heparin Flushing Increases Cereberal Blood Flow in Chronic Ischemic Stroke Patients

“…(15) Thus, heparin is commonly used to treat both arterial and venous thrombosis because of its safety-proven reason. (3,16,17) Intravascular studies showed that heparin therapy can reduce the clot size (18), suggested by its potency in brain reperfusion after ischemic. The potential of heparin a s antioxidant is well known, so that it is used in hemodialysis to suppress oxidative stress during dialysis.…”