Do Aspirin and Other Antiplatelet Drugs Reduce the Mortality in Critically Ill Patients?

Abstract

Platelet activation has been implicated in microvascular thrombosis and organ failure in critically ill patients. In the first part the present paper summarises important data on the role of platelets in systemic inflammation and sepsis as well as on the beneficial effects of antiplatelet drugs in animal models of sepsis. In the second part the data of retrospective and prospective observational clinical studies on the effect of aspirin and other antiplatelet drugs in critically ill patients are reviewed. All of these studies have shown that aspirin and other antiplatelet drugs may reduce organ failure and mortality in these patients, even in case of high bleeding risk. From the data reviewed here interventional prospective trials are needed to test whether aspirin and other antiplatelet drugs might offer a novel therapeutic option to prevent organ failure in critically ill patients.

Platelet Activation by Streptococcus pyogenes Leads to Entrapment in Platelet Aggregates, from Which Bacteria Subsequently Escape

“…Furthermore, this may explain in part the genesis of thrombocytopenia during S. pyogenes sepsis, where platelets are consumed within bacteria-platelet aggregates. Interestingly, it has been reported that a low-dose antiplatelet treatment during sepsis may reduce the risk of multiorgan failure (33,34), implying that platelet activation may directly contribute to the pathogenesis of bloodstream infections. Taken together, the results of our study support the important role of platelets for the pathophysiology of invasive S. pyogenes infection.…”

The Toll-like receptor 2/1 (TLR2/1) complex initiates human platelet activation via the src/Syk/LAT/PLCγ2 signalling cascade

“…In addition, platelets are also critically involved in the pathophysiology of sepsis [49] and systemic platelet activation due to bacterial infections augments the degree of thrombocytopenia and, hence, the severity of sepsis [50]. Anti-thrombotic drugs, such as cyclooxygenase-inhibitors or P2Y12-and integrin  IIa  3 -antagonists have been shown to be beneficial under septic conditions [51], and may also, in line with previous and our observations, being considered to prevent bacteria-related thrombotic events. …”

The Role of Platelets in Viral Hemorrhagic Fevers

“…The presence of activated platelets or platelet-leucocyte aggregates has also been shown to lead to activation of the endothelium [113]. Preliminary evidence suggests that the use of aspirin, and/or clopidogrel, may reduce mortality in sepsis [114,115]. However, while anti-platelet agents preserve platelet numbers, they do so by inhibiting platelet function, which may exacerbate hemorrhagic complications in thrombocytopenic patients.…”

“…This could potentially be achieved with conventional anti-platelet agents. For instance, there is evidence that aspirin may be beneficial in sepsis [155,156], and other critically ill patients associated with SIRS [115], and this is also true for clopidogrel [157]. There is a paucity of studies of the use of anti-platelet agents in VHF, although a 1979 paper found that while the combination of aspirin and dipyridamole did not affect mortality, it did reduce the progression to DHF [158].…”