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Alteplase

Tissue plasminogen activator (PLAT) is a secreted serine protease which converts the proenzyme plasminogen to plasmin, a fibrinolytic enzyme. PLAT is synthesized as a single chain which is cleaved by plasmin to a two chain disulfide linked protein.This enzyme plays a role in cell migration and tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding; decreased activity leads to hypofibrinolysis which can result in thrombosis or embolism. more...

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Gene

Alternative splicing of the PLAT gene, PLAT, produces three transcripts.

Applications

Recombinant PLAT is used in diseases which feature blood clots, such as myocardial infarction and stroke. To be effective, PLAT must be administered within the first six or so hours of the attack. Because of this, only about 3% of patients qualify for this treatment. Since PLAT dissolves blood clots, there is risk of hemorrhage with its use.

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Gusto III suggests that reteplase has slight edge over alteplase
From Nursing, 3/1/98

How do reteplase and alteplase compare? In pilot studies of the two antithrombotic drugs, reteplase (recombinant plasminogen activator) produced superior angiographic results in patients with acute myocardial infarction. Subsequently, the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) trial aimed to compare the safety and efficacy of the two agents more definitively.

The GUSTO III study followed more than 15,000 patients in 807 hospitals in 20 countries, including more than 4,700 patients in the United States. Patients (average age, 63) were seen within 6 hours of symptom onset and had to have more than 30 minutes of continuous symptoms and ST-segment elevation or bundle-branch block on ECG. Two-thirds of the patients received reteplase; the rest received alteplase. The study found a statistically insignificant difference in the mortality rates for the two patient groups; rates of stroke and bleeding complications were also very similar. However, study chairman Eric J. Topol, MD, notes that reteplase (a mutant of alteplase) is easier to administer than alteplase, requiring less nursing time and carrying a lower chance of medication error. More research is needed to compare the costs of the two drugs, including the costs of administering them.

Sources: The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO III) Investigators: "A Comparison of Reteplase with Alteplase for Acute Myocardial Infarction," The New England Journal of Medicine, October 16, I997; "Major Thrombo lyrics Trial Concludes: GUSTO liU Preliminary Results Reported," The New Era of Reperfusion Nurse Edition, August 1997.

Copyright Springhouse Corporation Mar 1998
Provided by ProQuest Information and Learning Company. All rights Reserved

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