1/8

An Important Featur...

Metadata

• Author: @WilliamAird4 on Twitter
• Full Title: 1/8
  An Important Featur...
• Category: #tweets
• URL: https://twitter.com/WilliamAird4/status/1622347756789456897

Highlights

• 1/8
  An important feature of SCD pathophysiology is the DELAY TIME, which is defined as the time between deoxygenation of blood (in capillaries) and the appearance of polymers. If the delay time is short than the TRANSIT TIME, sickling occurs, resulting in vascular occlusion.
  (View Tweet)
• 2/8
  HbS concentration (reflected by the MCHC) is a critical determinant of the delay time. Even a small decrement in sickle hemoglobin results in a large extension of the time delay between deoxygenation and sickling. (View Tweet)
• 3/8
  In 1980, a report appeared in the NEJM in which DDAVP and high fluid intake was used to reduce serum Na+ and MCHC in 3 patients with SCD. Chronic hypoNa+ reduced the frequency of painful crises, providing proof of principle for importance of intracellular [deoxy HbS].
  (View Tweet)
• 4/8
  2 recent studies appeared in BLOOD, one in August 2022, the other in January 2023 showing that iron restriction in mouse models of SSD results in hypochromia-associated amelioration of hemolysis, inflammation and vaso-occlusion, without accentuating the underlying anemia.
  (View Tweet)
• 5/8
  1. The first study employed an oral ferroportin inhibitor called vamifeport. They also tested the effect dietary iron restriction, but failed to see a similar effect.
  2. The second study used dietary iron restriction. (View Tweet)
• 6/8
  As pointed out in a commentary on the first study, iron restriction may provide a way of “buying time” for erythrocytes to escape the hypoxic microvasculature before sickling.
  That's really novel and opens up a whole new avenue for therapy. (View Tweet)
• 7/8
  But there is something that doesn't sit right. While Study 2 refers to Study 1's finding with vamifeport, they make no mention of the fact that Study 1 was unable to replicate the results with dietary iron restriction (the very method relied upon by Study 2). (View Tweet)
• 8/8
  How is that possible? The two papers were published a full 6 months apart in the same journal! How did this get by the reviewers and the editors? Am I missing something? (View Tweet)