Thrombolytic agent adverse effect

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. 

It is clear from this discussion that although there is significant potential for the use of hypothermia in combination with additional neuroprotective agents, it is premature to consider this a viable option in the near future. Moreover, there are no adequate data on the safety of such combination therapy. In fact, there is some evidence suggesting that hypothermia could result in such adverse effects as reduced thrombolytic efficacy and increased susceptibility to infectious complications. 

To bypass the potential fatal side effects of systemically applied thrombolytic therapy, thrombolytic agents have been delivered locally into the vitreous. Elman et al. (46) reported on a retrospective series of nine eyes treated with 100 pg (0.2 mL) of intravitreal tPA followed by paracentesis. At six months of follow-up there were no adverse events, and four of the nine eyes had improved by at least three lines of visual acuity. However, two eyes sustained a loss of six or more lines. None of the four cases deemed ischemic at baseline improved beyond 20/200. In a similar series, Glacet-Bernard et al. (47) reported on 15 patients with CRVO of 1 to 21-day duration (mean of eight days) treated with intravitreal tPA. Eight of 15 patients had a baseline visual acuity of 20/50 or better. Of those patients available for the eight-month follow-up, visual acuity increased in five, remained unchanged in five, and decreased in four. Six of 15 patients developed an increased amount of intraretinal hemorrhage. The results were deemed to be no better than the natural history. 

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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