Thrombosis, acute arterial

Plasminogen, an inactive precursor, is activated to plasmin which as a protease is able to break down fibrin clots. The thrombolytic agents in use promote the conversion of plasminogen to plasmin at the site of a thrombus. Indications include post-myocardial infarction treatment. The thrombolytic must be administered within 6 hours for an optimal effect. Other indications are treatment of acute pulmonary thromboembolism, deep-vein thrombosis, acute arterial thrombosis and thromboembolism, as well as in the clearance of arteriovenous catheters and can-nulae. Agents are streptokinase, anistreplase, urokinase, alteplase, reteplase and tenecteplase. 

In contrast to unfractionated heparin, the factor Xa inhibitor tick anticoagulant peptide (TAP) effectively inhibited coronary arterial thrombosis in a canine electrolytic injury model (57). TAP was also effective in inhibition of the procoagulant properties of whole blood clots in vitro however, it was stated that TAP might be not optimal due to its slow binding kinetics (54). Meanwhile, several low molecular weight direct factor Xa inhibitors are in clinical development (Table I), some of them specifically for the treatment and secondary prevention of ACS. DX-9065a, ZK-807834 and otamixaban have been intensively characterized in vitro and in vivo and are in clinical investigations for the treatment of acute arterial thrombosis. 

A ferret model of acute arterial thrombosis was developed by Schumacher et al. (1996a,b). A 10-min anodal electrical stimulation of 1 mA was delivered to the external surface of the carotid artery while measuring carotid blood flow. This produced an occlusive thrombus in all vehicle treated ferrets within 41 3 min with an average weight of 8 1 mg. Thrombus weight was reduced by aspirin or a thromboxan receptor antagonist. 

Erickson LA, Fici GJ, Lund JE et al. (1990) Development of venous occlusions in mice transgenic for the plasminogen activator inhibitor-1 gene. Nature 346 74—76 Kawasaki T, Dewerchin M, Lijnen HR et al. (2000) Vascular release of plasminogen activator inhibitor-1 impairs fibrinolysis during acute arterial thrombosis in mice. Blood 96 153-160... 

Conti JA, Scher HI. Acute arterial thrombosis after escalated-dose methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy with recombinant granulocyte colony-stimulating factor. A possible new recombinant granulocyte colony-stimulating factor toxicity. Cancer 1992 70(ll) 2699-702. 

Randall, M. J., Wilding, R. I. R., 1983 Acute arterial thrombosis in rabbits reduced platelet accumulation after treatment with thromboxane synthetase inhibitor dizoxyben hydrochloride (UK-37,428-00). Br. J. Clin. Pharmacol. 15, 495-555. 

Junghans U, Seitz RJ, Wittsack HJ, Aulich A, Siebler M. Treatment of acute basilar artery thrombosis with a combination of systemic alteplase and tirofiban, a nonpeptide platelet glycoprotein Ilb/HIa inhibitor report of four cases. Radiology 2001 221 795-801. 

Acute MI (myocardial infarction), 5 107 antianginal agents for, 5 110t and coronary arterial thrombosis, 5 170 Acute myelogenous leukemia (AML), and benzene exposure, 3 616 Acute oral toxicity... 

It is indicated in acute myocardial infarction, pulmonary embolism, deep vein thrombosis, arterial thrombosis, acute thrombosis of central retinal vessels, extensive coronary emboli and severe iliofemoral thrombophlebitis. 

Tissue plasminogen activator has been used successfully to treat acute myocardial infarction, and the benefits of this treatment are well documented.102,116 This drug, however, does not seem to be superior to other thrombolytics when treating coronary artery thrombosis, and streptokinase may be a more cost-effective method of treating myocardial infarction. Alternatively, t-PA may be more effective than other thrombolytics in its ability to initially reopen cerebral vessels this drug is often used preferentially during ischemic stroke.4,44 Hence, the added cost of t-PA may be justified in this situation. 

Activation of platelets is considered an essential process for arterial thrombosis. Thus, treatment with platelet-inhibiting drugs such as aspirin and ticlopidine or clopidogrel is indicated in patients with transient ischemic attacks and strokes or unstable angina and acute myocardial infarction. In angina and infarction, these drugs are often used in conjunction with -blockers, calcium channel blockers, and fibrinolytic drugs. 

Whether inhibition of TF will prevent acute arterial disease-associated thrombosis, where a lower possibility of bleeding can be expected, is a point that deserves to be investigated. 

Sarich TC, Osende Jl, Eriksson UG, et al, Acute antithrombotic effects of ximelagatran, an oral direct thrombin inhibitor, and r-hirudin in a human ex vivo model of arterial thrombosis, J Thromb Haemost 2003 1 999— 1004. 

The scope of the medical problems which require the use of anticoagulant drugs cannot be overstated. Arterial thrombosis is a major contributor to the number one (acute myocardial infarction), number three (stroke) and number four (renal) causes of death in the United States (1J. Venous thromboembolism is the most common non-surgical cause of death in patients hospitalized for major orthopedic procedures, the most frequent non-obstetrical cause of postpartum death, and a major cause of death in patients with chronic cardiac and pulmonary disease (1 ). Venous thrombosis is estimated to lead to the hospitalization of approximately... 

Therapeutic uses Originally used for the treatment of deep-vein thrombosis and serious pulmonary embolism, thrombolytic drugs are now being used with increasing frequency to treat acute myocardial infarction and peripheral arterial thrombosis and emboli, and for unclotting catheters and shunts. 

Therapeutic uses Streptokinase is approved for use in acute pulmonary embolism, deep venous thrombosis, acute myocardial infarction, arterial thrombosis, and occluded access shunts. 

In order to study new drugs for their antithrombotic potential in coronary arteries, Folts and Rowe (1974) developed the model of periodic acute platelet thrombosis and cyclic flow reductions (CFRs) in stenosed... 

Transient ischemic attack. An acute loss of focal brain or monocular function with symptoms lasting less than 24-hours and which is thought to be caused by inadequate cerebral or ocular blood supply as a result of arterial thrombosis, low flow or embolism associated with arterial, cardiac or hematological disease (Hatano 1976). 

About 1.5 million individuals in the USA will have an acute myocardial infarction per year 50% will be fetal and 50 will be a premature event. Thus, there are about 750,000 deaths from coronary artery thrombosis per year. Of these coronary fiurombotic events, 67% of patients harbor a coagulation blood protein or platelet defect leading to thrombosis. Fifty percent of these coagulation protein or platelet defects will be hereditary, thus Figure... 

Trade names Abbokinase (Abbott) Ukidan Indications Acute myocardial infarction, coronary artery thrombosis, pulmonary embolism Category Fibrinolytic Plasminogen activator Half-life 10-20 minutes... 

A large percentage of patients develop asymptomatic VTE. PE occurs in 25% of patients with thrombotic complications and contributes significantly to mortality. Arterial thrombosis occurs less commonly. Limb artery occlusion, stroke, and myocardial infarction are the most commonly reported arterial events. Heparin-induced skin lesions occur in 10% to 20% of patients with HIT. Lesions range from painful, localized erythematous plaques to widespread dermal necrosis. Amputation in such cases frequently is required. Mortality from HIT may be as high as 36% in patients with acute thrombosis. The relatively high frequency of thrombotic complications and poor outcomes... 

Plasmin is a proteolytic enzyme with specific affinity for fibrin of clots. The indications for Streptokinase are acute cardiac infarction, venous and arterial thrombosis, lung and arterial emboli. 

Streptokinase (1,500,000 lU within 60 minutes by fV infusion) is indicated in lysis of coronary artery thrombosis after acute myocardial infarction streptokinase (250,000 lU by IV infusion pump into each occluded limb of the cannula over 25 to 35 minutes) is indicated in arteriovenous cannula occlusion and streptokinase (250,000 lU IV infusion over 30 minutes) is indicated in the treatment of venous thrombosis, pulmonary embolism, and arterial thrombosis and embolism. 

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