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Tuesday, May 03, 2022

Hemolysis is part of strenuous exercise - it is not a disease

 The intravascular destruction of red blood cells (rbcs) is a normal part of strenuous exercise.It is a feature not a bug of strenuous exercise.A recent review by Lippi and Sanchis-Gomar describes hemolysis as being common place in running and characterizes the intravascular hemolysis as "paraphysiological"  and is "typically mild" with average variations of hemolysis  biomarkers( serum free hemoglobin and haptoglobin) perturbated    between 1.2 and 1.8 times and "self limiting"resolving within 24 to 8 hours.

All types of repeated  strenuous exercise are associated with hemolysis but  more notably so with running usually attributed to foot strike but non contact activities including rowing,swimming and cycling are all known to cause hemolysis.

Foot strike is thought to be a major contributor in running related hemolysis as was demonstrated in an excellent cross over study of hemolysis  in  running and cycling by Telford in 2003. Tri athletes ran and  cycled at 75% of their measured 02 max and serum free hemoglobin was elevated during both activities but  there was significant drop in haptoglobin only after the running session. Methemoglobin , an indicator of oxidative stress, was elevated to the same degree after each exercise.

Red blood cell survival is significantly shorter in runners versus sedentary controls. Chromium labelled RBCs survival is 74 days in runners  versus 115  days in a sedentary control group..

This shortened life span increases need for  RBC production with an associated increase in iron utilization. The 1 to 2 mg of iron absorption per day  normally is balanced against the normal 1-2 mg of iron loss. Endurance athletes will need a larger iron intake.Iron deficiency and iron deficiency anemia have been described not only in runners but cyclists,swimmers and rowers as well is in rugby,tennis and soccer players.

A possible mechanism for increased iron loss secondary to strenuous  exercise induced hemolysis (SEIH) is the following.Hepcidin is stimulated by the increased iron in the blood.Hepcidin decreases the release of iron from duodenal cells into the blood, trapping iron in the enterocytes. These cells live only about 3 days and then shed off which is probably one mechanism by which there increased GI blood loss in runners. Hepcidin also limits iron egress from macrophages and liver cells limiting the supply of iron to the bone marrow at a time when more iron is needed. The more running,the more hepcidin release ,the more iron tapped in the duodenal enterocytes the more iron loss in the stool. So runners and other endurance athletes  loose more iron and need more iron to increase RBC production and need a higher iron intake than a sedentary person.

Arguing against the role of hepcidin  in runner's anemia is the following: Although hepcidin is definitely elevated acutely several studies have demonstrated that after a period  of time ( 1-2 weeks) the hepcidin levels return to their baseline values.So hepcidin is only transiently elevated  and other studies have demonstrated that hepcidin levels are only elevated in those persons whose ferritin levels are above 30 suggesting that the red blood cell production imperative overrides the hemolysis induced hepcidin increase and any significant exercise related cytokine increase, 

Add to that metabolic supply chain issue a vegan diet in some athletes and menstrual  blood and there is no surprise that there is  iron deficiency and iron deficiency anemia is athletes who take part in repetitive strenuous exercise 

Hemoglobinemia and hemoglobinuria were first described medically in the early 1940s with studies of cross country runners and marathoners describing march hemoglobinuria  although observation of dark urine associated with strenuous exercise was described in the 1880s.

Iron deficiency in athletes is now so well recognized that athletes themselves and coaches and sport Medine doctors all utilize the measurement of blood ferritin levels to monitor iron levels. The 2019 Olympia Committe on Physical examination for athletes including measurement of iron status .One recent study reported that 70% of professional cyclists and competitive rowers had iron deficiency by the end of their seasons. 

"Runners anemia" is the prototype  of an iron deficiency anemia brought about by  the hemolysis associated with  multiple bouts of  strenuous exercise in an individual whose iron intake does not match the increased iron needed for the increased red blood cell production needed to compensate for the shortened average life span  and GI iron loss. Runner's anemia might be more  accurately described as the anemia of repeated strenuous exercise induced hemolysis in the face of inadequate iron intake to compensate for the associated increased iron needs. Or much simply-exertional hemolysis in a person with an iron poor diet. 


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