Falling to Pieces: Hemolysis of the Hemoglobin Hypothesis

A paramount goal of this blog is to understand the evidence as it applies to the epistemology of medical knowledge, hypothesis testing, and overarching themes in the so-called evidence based medicine movement.  Swedberg et al report the results of a large[Amgen funded] randomized controlled trial of darbepoetin [to normalize hemoglobin values] in congestive heart failure (published online ahead of print this weekend) which affords us the opportunity to explore these themes afresh in the context of new and prior data.

The normalization heuristic, simply restated, is the tendency for all healthcare providers including nurses, respiratory therapists, nutritionists, physicians, and pharmacists among others, to believe intuitively or explicitly that values and variables that can be measured should be normalized if interventions to this avail are at their disposal.  As an extension, modifiable variables should be measured so that they can be normalized.  This general heuristic is deeply flawed, and indeed practically useless as a guide for clinical care.

Hemoglobin In Limbo: How Low Can [should] It Go?

In this post about transfusion thresholds in elderly patients undergoing surgery for hip fracture, I indulged in a rant about the irresistible but dodgy lure of transfusing hospitalized patients with anemia (which I attributed to the normalization heuristic) and the wastefullness and potential harms it entails.  But I also hedged my bets, stating that I could get by with transfusing only one unit of blood a month in non-acutely bleeding patients, while noting in a comment that a Cochrane review of this population was equivocal and the authors suggested an RCT of transfusion in acute upper gastrointestinal hemorrhage.  Little did I know at the time that just such a trial was nearing completion, and that 12 units of PRBCs could probably get me by for a year in just about all the patients I see.

In this article by Villanueva in the January 3, 2013 issue of the NEJM, Spanish investigators report the results of a trial of transfusion thresholds in patients with acute upper gastrointestinal hemorrhage.  After receiving one unit of PRBCs for initial stabalization, such patients were randomized to receive transfusions at a hemoglobin threshold of 7 versus 9 mg/dL.  And lo! - the probability of transfusion was reduced 35%, survival increased by 4%, rebleeding decreased by 4%, and adverse events decreased by 8% in the lower threshold group - all significant!  So it is becoming increasingly clear that the data belie the sophomoric logic of transfusion.