What interval should blood donors wait between donations, and what are the risks involved in donating with shorter intervals than recommended?
The only known significant long-term risk of blood donation is iron deficiency. Immunity (which you asked about) is primarily mediated by white blood cells, which can be easily deployed from the lymphatic system and bone marrow to replace those lost in donation. Red blood cells, on other hand, are not stored as mature cells in large numbers outside of the bloodstream. They also contain hemoglobin, which requires iron for its production. The body has a limited supply of iron, and when red blood cells are removed via blood donation, this can be depleted. Approximately 200 - 230 mg of iron is lost during a standard blood donation (~450 mL whole blood). It has been shown that short-term iron supplementation is effective in replacing iron loss.1
The American Red Cross recommends donors wait 8 weeks between transfusions. The NHS guideline is more conservative, recommending 12 weeks for men and 16 weeks for women. The difference between the sexes in that recommendation is because women lose blood regularly through menstruation and thus tend to have lower stores of iron and can easily become anemic. The threshold hemoglobin level required for donation is also different between the US and Europe: 12.5 g/dL for both sexes in the US; 12.5 g/dL for women but 13.5 g/dL for men in the Europe.*
The optimal interval for blood donation remains a bit of an open question. (Note that for women, the NHS recommendation is twice as long as the Red Cross’s recommendation!) To investigate that, there was recently a large trial conducted within NHS centers that randomized men to 12-week, 10-week, or 8-week intervals between donation while women were randomized to 16-week versus 14-week versus 12-week intervals.2 They will report hemoglobin levels in donors, including the number of donations that have to be deferred due to hemoglobin levels below the recommended levels (NHS guidelines above). The full methodology is available online, but to my knowledge the results have not yet been published.
1. Radtke H, Mayer B, Röcker L, Salama A, Kiesewetter H. Iron supplementation and 2-unit red blood cell apheresis: a randomized, double-blind, placebo-controlled study. Transfusion. 2004 Oct;44(10):1463-7.
2. Moore C, Sambrook J, Walker M, Tolkien Z, Kaptoge S, Allen D, Mehenny S, Mant J, Di Angelantonio E, Thompson SG, Ouwehand W, Roberts DJ, Danesh J. The INTERVAL trial to determine whether intervals between blood donations can be safely and acceptably decreased to optimise blood supply: study protocol for a randomised controlled trial. Trials. 2014 Sep 17;15:363. doi: 10.1186/1745-6215-15-363.
*Note: The European guideline appears to be a practical concession to the fact that many menstruating woman have hemoglobin <13.5 g/dL. However, to my knowledge there is no physiologic reason to believe that women should tolerate an absolute hemoglobin level lower than men. Thus, the logic of it is somewhat lost on me.