Tissue plasminogen activator adverse effects

For hypothermia, one major possible difficulty involves the effect of low temperature on metabolism and enzyme activity. Many pharmaceutical agents have reduced biological activity at lower temperature compared with higher temperature. The thrombolytic activity of recombinant tissue plasminogen activator (rt-PA), for example, is clearly temperature dependent, with decreased activity at lower temperature (1). Thus, the assumption that hypothermia will not have an adverse effect on other treatment agents cannot be presumed. Hypothermia is also known to reduce the activity of inflammatory and antiinfectious biological processes. This could potentially result in increased susceptibility to infection. This possibility is of particular concern because infections are a major cause of morbidity in stroke patients (2). Therefore, combination therapy with hypothermia and antiinflammatory agents could potentially worsen outcome. 

Thrombosis is one of the most common and devastating diseases. Fibrinolytic enzymes are effectively in treating thrombosis. A variety of fibrinolytic enzymes, such as UK, streptokinase (SK), recombinant tissue-type plasminogen activator (rt-PA), staphylokinase (SAK) and recombinant prourokinase (pro-UK), have been studied as thrombolytic agents [67,68]. In general, these agents are administered via intravenous injection, and their limitations include fast clearance, lack of resistance to re-occlusion, bleeding complications and other adverse effects [67]. 

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