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anticoagulants are withdrawn.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.