Footstrike Hemolysis in Distance Runners: Understanding the Mechanical Destruction of Red Blood Cells

Introduction

Footstrike causes a shock to the sole of the foot, which can create enough pressure to cause the red blood cell to break down, causing hemolysis. When this process is repeated thousands and thousands of times, for example in long-distance runners, the cumulative breakdown of red blood cells can even lead to anemia. This is called footstrike anemia. In clinical work, especially with athletes or long-distance runners, it is good to keep this potential cause of anemia in mind.

Footstrike hemolysis is a fairly well-known phenomenon. It was first noted by Fleischner in 1881 and later by Kast in 1884. They noticed that soldiers returning from marches or long runs had hemoglobinuria[1]. The condition exists on a spectrum from subclinical laboratory changes to, rarely, clinically significant anemia requiring intervention.

Research cohorts to date have largely been male populations. A recent systematic scoping review analyzing 267 runners across nine studies found that 88% of study participants were male with a mean age of 37 years, reflecting that this condition has been most extensively studied in adult male endurance athletes[2]. However, the phenomenon is not gender-specific and occurs equally in women.

Mechanism of Footstrike Hemolysis

Footstrike hemolysis is most likely caused by a direct blow to the plantar surface while running. Hemolysis is more common in running than in other sports. A controlled study comparing 10 male triathletes performing one hour of running versus cycling at equivalent oxygen uptake (75% peak) revealed that plasma free hemoglobin increased fourfold more after running compared to cycling[3].

During each footstrike, vertical ground reaction forces (vGRF) typically reach 1.5-3 times body weight [7]. This is a force large enough to rupture red blood cells in capillaries. The released hemoglobin binds to haptoglobin, but if there is a lot of exertion, haptoglobin may become saturated, leading to hemoglobinemia and, as a result, hemoglobinuria.

Hematological Response in Footstrike Hemolysis: Laboratory Evidence

Intravascular hemolysis is characterized by reticulocytosis, reflecting compensatory red blood cell production by the bone marrow. Reticulocytes are larger, younger red blood cells. In contrast, haptoglobin decreases because the released hemoglobin consumes haptoglobin.

The 2024 scoping review quantified the hematological changes following marathon and ultramarathon distance running. Between pre- and post-race measurements across 267 runners, reticulocyte count demonstrated a 16% increase, though values remained within normal limits. Simultaneously, haptoglobin levels decreased by 21%, confirming intravascular hemolysis. Notably, despite these indicators of hemolysis, hemoglobin levels remained within accepted normal limits, increasing by only 1.1% from baseline[2]. This reflects the effectiveness of compensatory mechanisms in athletes.

In acute intravascular hemolysis, ferritin levels may increase, while serum iron levels often decrease. Although the increase in ferritin levels is often due to hemoconcentration and the fact that ferritin is an acute phase protein, in the long-term state, ferritin levels may decrease, which may reflect true iron loss through hemoglobinuria and hemosideruria.

This was reflected in the review, while ferritin levels increased by 45%, from 93 ng/mL to 135 ng/mL and serum iron decreased by 28%, from 103 μg/dL to 74 μg/dL. Red blood cell distribution width (RDW) showed a 3.4% increase, consistent with the size variability between mature erythrocytes and newly released reticulocytes[2].

Clinical Presentation of Footstrike Hemolysis

In my clinical practice, footstrike hemolysis is most often an incidental finding, detected during a routine check-up, and athletes are often completely asymptomatic. On the other hand, in some situations, for example after strenuous exercise, even macroscopic hemoglobinuria may occur, which can turn the urine dark. Sometimes athletes may experience fatigue or decreased performance, but these are non-specific symptoms and often cannot be directly linked to anemia caused by hemolysis, but are more often related to the overall situation.

In most cases, hemolysis does not cause actual anemia. In the majority of people who experience hemolysis, hemoglobin levels remain normal, which is compensated for by erythropoiesis. However, approximately 8% of elite athletes in studies develop anemia (<14.0 g/dL in males, <12.0 g/dL in females), though this varies by study definitions and timing of assessment[2]. However, even without actual anemia, a patient’s physical performance can decline, as I have discussed in my previous article about ferritin levels for athletes.

Footstrike anemia is primarily a cumulative phenomenon. A single athletic performance or heavy physical effort does not typically cause anemia or significant iron loss, but the cumulative effect over months and years can lead to depletion of iron stores, especially if there are other risk factors for anemia, which I have discussed in my article about iron panel interpretation for athletes.

Laboratory Evaluation of Footstrike Hemolysis

Diagnosis of footstrike hemolysis is based on patient history and typical hemolysis laboratory test such as:

Complete Blood Count: If anemia is present, it is often normocytic anemia and reticulocytosis is typically found. This differs from iron deficiency anemia in that it is not microcytic.

Haptoglobin: Haptoglobin is a molecule that binds free hemoglobin. When it binds free hemoglobin during hemolysis, its concentration usually decreases.

Lactate Dehydrogenase (LDH): LDH is found in red blood cells. Its concentration usually increases in hemolysis. On the other hand, LDH can also be released from muscle cells, making diagnosis difficult.

Bilirubin: The breakdown product of hemoglobin is bilirubin. The liver conjugates bilirubin, which is then excreted into the bile and removed from the bloodstream. When the amount of bilirubin exceeds the liver’s conjugation capacity, the bilirubin concentration in the blood increases.

Iron Markers: In hemolysis, ferritin may increase acutely, while serum iron often decreases. Ferritin is an acute phase protein, so it may increase in the acute phase, but may decrease in the long term, indicating true iron deficiency. The decrease in serum iron in the acute phase is often more hepcidin-mediated than true iron loss.

Urine sample: A urine chemical screen may show hemoglobin. However, a cell count may not show red blood cells. Hemosiderin in the urine may indicate prolonged or recurrent hemolysis.

The timing of the tests matters depending on what is being measured. A possible drop in haptoglobin and an increase in LDH usually occur immediately after the exercise, while diagnostic changes in iron markers occur with a delay. Measuring iron markers may only be meaningful 2-3 days after the exercise, as the acute phase increase in ferritin has usually subsided, as has the hepcidin response, making the serum iron value more accurate[2].

Factors Modifying Hemolytic Response

Footwear and Running Surface Hardness

I cannot give any reliable guidance on the type of shoe to use, as research data on shoe sole material is mixed. One study found that a soft sole would increase hemolysis compared to a firm sole, up to a point. The study comparing soft versus firm insoles during one hour of running at 60-70% maximum heart rate demonstrated that firm insoles effectively reduced unconjugated bilirubin elevation and LDH increases compared to soft insoles. However, the same study noted that excessively hard surfaces without adequate cushioning also increase hemolysis, suggesting an optimal intermediate firmness maximizes shock absorption[5].

In contrast, a second contradictory study of runners performing 430 km over 17 days found that reticulocyte counts were 29% higher in runners wearing firm-soled shoes compared to soft-soled shoes, indicating greater erythropoietic stimulus from increased hemolysis in the hard-sole group[6]. Of course, these studies examined different biomechanical phenomena on different time scales, so the results are not directly comparable. Thus, the final effect remains unclear.

In addition, based on current research evidence, there is no high-quality, direct research evidence on the effect of surface hardness on footstrike hemolysis.

Length of Running Journey

Not surprisingly, the length of the journey affects the amount of hemolysis. The 2024 scoping review revealed that hemoglobin changes varied by race distance, with marathon distance (42.2 km) showing a 0.30 g/dL increase, while six-day ultramarathons demonstrated a 1.50 g/dL decrease[2]. In the shorter marathon distance, the effect was probably just due to the effect of hemoconcentration, and in the longer ultra-running distance, the effect probably reflected true hemolysis.

Individual Variability

The study found that there is significant individual variation in the hematological response to footstrike hemolysis. Not all athletes show a typical hemolytic response despite exertion[2]. This indicates that individual factors influence the response, although these were not specified in the study.

Differential Diagnosis Considerations

Ultimately, however, footstrike hemolysis is a diagnosis of exclusion and is often a relatively benign phenomenon that most often does not require specific therapeutic measures. Therefore, before attributing hematological abnormalities to footstrike hemolysis, it is necessary to do careful evaluation of differential diagnostic possibilities[2].

Gastrointestinal Blood Loss is quite common in endurance athletes. During prolonged exertion, blood flow is diverted to working muscles and the skin for thermoregulation. This can cause splanchnic hypoperfusion, which in turn can cause gastrointestinal ischemia, which can lead to gastrointestinal bleeding, which can be anemic[8].

Hematuria: Long distance running can cause hematuria, mainly through a traumatic mechanism. It is usually microscopic hematuria, rarely macroscopic hematuria[9].

Inflammatory Anemia: Physical exercise causes an acute inflammatory response that activates hepcidin, which in turn inhibits iron absorption. The hepcidin response may, in the long term, contribute to anemia, particularly through inhibition of iron absorption[10].

Nutritional Deficiencies: In addition to iron deficiency, folate and B12 deficiency can also cause megaloblastic anemia. Megaloblastic anemia is a macrocytic anemia[11], meaning the red blood cells are larger, while iron deficiency anemia is a microcytic anemia[12], meaning the red blood cells are smaller..

True Pathology: When diagnosing anemia, it is also important to determine possible underlying diseases, such as hemolytic diseases, hereditary red blood cell structural or hemoglobin defects, and bone marrow diseases.

Sports anemia: This often occurs at the same time as footstrike hemolysis. It is not true anemia, but pseudoanemia caused by exercise-induced hemodilution, i.e. when the volume of blood plasma increases but the actual total hemoglobin mass remains the same or increases[4].

Conclusion

Footstrike hemolysis is a phenomenon in which repeated foot strikes cause intravascular red blood cell breakdown, or hemolysis. The hemolysis is often subtle, mild, and in athletes, compensatory processes usually minimize its impact.

It is rare for footstrike hemolysis to cause clinically significant anemia and very rarely does anything need to be done about it. And anyway, based on current knowledge and my experience, there is not much that can be done about the phenomenon, other than avoiding running, which is often out of the question for athletes. There is also no clear broad research consensus on shoe choice, as the evidence is mixed. There is also no direct high-quality research data on the effect of running surface hardness.

In footstrike hemolysis, hemoglobin levels usually remain normal because of compensatory erythropoiesis. Clinically significant anemia is very rare. The greatest impact may be on reduced iron levels, which often do not yet cause anemia. Usually, it does does not cause symptoms and is found incidentally along with other investigations.

Footstrike hemolysis is most often a diagnosis of exclusion. The diagnosis is often made only after other causes of anemia and hemolysis have been ruled out. Overall, footstrike hemolysis is also mostly benign and is often clinically relevant only as a contributing factor to other anemic and iron deficiency causes.