New anemia paradox
Anemia is known as one of the risk factors of major bleeding in subjects treated with antithrombotic agents [5,17-19]. Our findings thus seem to be contradictory. Would the present study be “heretical”? There are 2 studies with a large number of participants that reported similar findings to ours [19,20], where subjects with anemia at baseline had a smaller hemoglobin drop following coronary or peripheral vascular interventions compared to those without. The authors did not provide any comments on this paradoxical finding, though. What is the mechanism? It is well-known that thalassemia, sickle cell disease, and other hemolytic anemias can cause thromboembolic events [21]. The same can be said for more common types of anemia. For instance, anemia was found to be an independent predictor of myocardial infarction and stroke in the RE-LY trial substudy [18]. A tight link between iron deficiency anemia and venous thrombosis or ischemic stroke has been repeatedly reported in adults and children [22-24]. The proposed mechanisms behind the hypercoagulability in anemia include (1) reactive thrombocytosis [23,25,26], (2) erythropoietin-mediated platelet hypersensitivity [26], (3) endothelial damage caused by increased blood flow to compensate for an oxygen deficiency [25.26], or (4) increased blood viscosity due to a morphological change in the erythrocytes [25,26]. Let us look at our data regarding blood tests and intraprocedural anticoagulation. The D-dimer level at baseline was higher in the anemic patients. Their procedural ACT was lower, and they had a tendency to require a longer time to achieve the target ACT, despite a similar amount of heparin given compared to non-anemic patients. These findings may indicate the potential increased coagulability in anemic subjects, and it might have been rather advantageous for reducing the blood loss.
Again, there is a consensus that anemia increases bleeding complications in antithrombotic therapy. Why did not this anemia’s aspect come to the fore in the present study? In general, anemia itself is not the cause but the effect of bleeding as long as no anticoagulants are on board. Accordingly, anemia must not increase the risk of bleeding once the anticoagulants are withdrawn. In our series, patients skipped a single dose of their DAOC prior to the ablation, and thus, their remaining anticoagulant effect was probably vanishingly small during the procedure, thanks to their short half-lives [7]. Therefore, the bleeding risk in anemic patients might have been the same as that in the non-anemic patients during the procedure. On the other hand, the potential hypercoagulable state caused by anemia must have remained, and consequently the anemia’s hypercoagulable aspect may have come to the front, instead. An alternative likely explanation is that the operators might have been more careful not to lose blood in the patients with preexisting anemia, which perhaps may not appear in any data. Consequently, this operator’s effort might have done more than just cancel out the higher bleeding risk of anemic patients.