Platelet activation: yet another strike against routine TRANSFUSION.

In the past, anaemia in patients with established coronary artery disease, especially acute anaemia as a result of bleeding, has been treated with a relatively liberal use of allogenic red blood cell (RBC) transfusions. RBC transfusions are believed to increase oxygen delivery by increasing haemoglobin concentration. Therefore, transfusion would seem to be a logical approach, as anaemia is associated with a number of maladaptive responses, such as increased sympathetic tone, heart rate, and myocardial contractility, which may all prove detrimental in patients with coronary artery disease. Laboratory-based studies further suggest that patients with coronary artery disease may require higher haemoglobin concentrations to maintain oxygen delivery in diseased or occluded arteries. In one of the largest cohort studies on the salutary effects of blood transfusion, Wu et al. noted that in 78 974 Medicare beneficiaries older than 65 years of age who were hospitalized for acute myocardial infarction (MI), lower admission haematocrit values were associated with increased 30-day mortality, with a rate as high as 35–39% among patients with a haematocrit of ≤27%. RBC transfusion, on the other hand, was associated with a seemingly linear reduction in 30-day mortality for patients who received at least one RBC transfusion if their admitting haematocrit was ≤33%. The age-old adage of transfusing for a haemoglobin concentration ,10 g/dL or a haematocrit ,30% (the so-called ‘10/30 rule’) is still commonly applied. More recent studies have suggested a null effect and possibly even an adverse impact of RBC transfusion on cardiovascular outcomes. Rao and colleagues examined the potential impact of RBC transfusion in 24 112 patients with acute coronary syndromes (ACS) enrolled in three large international trials. There were significantly higher 30-day all-cause mortality [adjusted hazard ratio (HR) 3.94] and 30-day death or MI (adjusted HR 2.92) rates among patients who received transfusions, as compared with those who did not. Mortality rates were particularly high when transfusions were given to patients with haematocrit values of ≥25% (as compared with those with a haematocrit ,25%). The management dilemmas arising from acute anaemia due to bleeding, and the pros and cons of blood transfusion, have been encountered with increasing frequency in the last few years with the emergence of several new antithrombotic regimens in patients with ACS. While there has been a significant improvement in reducing recurrent ischaemic episodes, this has been tempered by an increase in bleeding complications. Periprocedural bleeding has been shown to be associated with numerous adverse outcomes, including prolonged hospital stay, intraprocedural complications such as coronary perforation, dissection, ventricular fibrillation, and increased risk of MI, stroke, renal failure, and death. The reasons for the increased morbidity and mortality noted with bleeding are multifactorial. The location (intracranial) or torrential nature of the haemorrhage (gastrointestinal, retroperitoneal) may result in death. Further, patients most likely to bleed are also more likely to have a higher severity of illness such as older age, renal insufficiency, pre-existent anaemia, and presentation with acute MI. Antiplatelet therapy such as aspirin and clopidogrel are frequently stopped, which can prove catastrophic in patients with recent percutaneous coronary intervention (PCI). Additionally, cardioprotective medications such as b-blockers may be held. Thus, while bleeding can have dire consequences, RBC transfusion also seems to be associated with adverse outcomes. The mechanisms behind this are probably numerous and have not been completely delineated yet (Figure 1). General risks associated with transfusion include transfusion-transmissible infections [such as human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV)], haemolytic and non-haemolytic reactions, transfusion-related acute lung injury (TRALI), alloimmunization, citrate toxicity, iron overload, and hypothermia, and are all infrequently encountered. Prolonged storage of RBCs has also been associated with activation of several inflammatory and prothrombotic pathways. Transfusion, especially of stored blood,