Associations between post-PCI bleeding, transfusion and mortality may require multipronged solutions

The relationships between major bleeding after percutaneous coronary intervention, subsequent blood transfusion and increased mortality risk presents physicians with a multifaceted set of challenges, according to a state-of-the-art paper published in the Journal of the American College of Cardiology.

Recent data has suggested associations between post-PCI major bleeding, blood transfusion and increased mortality. According to the paper’s authors, the need to clarify the nature of the relationship is important not only for academic interest, but also because of the potential implications for clinical practice.

“In current practice, the risk for major bleeding is dependent not only on patient characteristics, but also to a large extent on choice of vascular access strategy (radial or femoral), and to a lesser extent on choice of an antithrombotic regimen,” the authors wrote. “Physician preference in these matters may be heavily influenced by the perception of bleeding as a nuisance complication, rather than a life-threatening one.”

Major bleeding, blood transfusion

The authors cited results from eight clinical trials suggesting a robust link between major post-PCI bleeding, blood transfusion and an increased risk for mortality, but also said that no causal link has yet been established. The association between blood transfusions and increased mortality is multifaceted, according to the authors, but several mechanisms may play a role in increasing the risk. Interactions between activated platelets and the clotting cascade may break down, leading to less control over the magnitude of the clotting response, putting the patient in a hypercoagulated state. Other experimental data suggested in increased synthesis and release of erythropoietin could be in part responsible for a prolonged prothrombotic state.

“Although it is impossible to randomly allocate patients to bleeding, a randomized comparison of transradial vs. transfemoral PCI with mortality as a primary end point may be a clinically relevant way to address the issue,” the authors wrote.

The mechanisms linking blood transfusion with excess mortality are related the functional and chemical changes that red blood cells may undergo, particularly depending upon their during storage. Red blood cells may lose their deformity, change their shape, increase their mean hemoglobin concentrations or have altered intracellular viscosity. These changes, according of the authors, can predispose the transfused cells to plugging of the microvasculature, leading to tissue ischemia. Another potential adverse effect is transfusion-related immunomodulation and prothrombotic protective responses induced by alterations in the endogenous cytokine and microparticle levels.

“The specific effects of this phenomenon on plaque biology, thrombosis and microvascular function are as yet undefined, but given the inflammatory nature of atherosclerosis, the potential for such interplay is of obvious concern,” the authors wrote.

The authors said that the concerns highlighted in the paper should not lead clinicians to withhold blood transfusion in patients in whom it is indicated.

“Efforts to reduce the impact of bleeding complications on the PCI population should rather focus on identification of measures to decrease the incidence of bleeding complications without increasing risk for ischemic events, and on the development of strategies for more targeted and safer use of blood transfusion,” they wrote.

Strategies for further evaluation

The authors’ proposed framework for reduction of bleeding complications included greater care in the selection of periprocedural antithrombotic therapy. The authors also suggested that preemptively targeting patients with anemia could reduce the transfusion requirements following PCI, and that arbitrary cutoffs to trigger transfusion after PCI should be avoided in most circumstances.

“Accumulating clinical and experimental data establish a strong association between major bleeding, blood transfusion and the risk of death after PCI, but it remains to be proven that strategies to reduce bleeding and/or blood transfusion will consistently lower all-cause mortality,” they concluded. “These issues need to be addressed as a priority by adequately powered studies.”

Doyle B. J Am Coll Cardiol. 2009;53:2019-2027.