Effects of Marathon Running on Platelet Activation Markers

Direct Evidence for In Vivo Platelet Activation

Alexander Kratz, MD, PhD, MPH; Malissa J. Wood, MD; Arthur J. Siegel, MD; Jennifer R. Hiers, MT; Elizabeth M. Van Cott, MD


Am J Clin Pathol. 2006;125(2):1-5. 

In This Article


We report the effects of participation in a marathon race on all basic hematologic parameters routinely reported by a clinical hematology laboratory and on markers of platelet activation and RBC fragmentation. Our findings confirm earlier reports, including a previous study by our group, that have shown increases in WBC count after a marathon.[23,24,25,26] This leukocytosis after a race is generally assumed to be due to demargination of WBCs induced by increased blood flow or by an inflammatory response caused by tissue injury, for example, rhabdomyolysis. The increases in RBC count, hemoglobin, and hematocrit are most likely due to dehydration caused by the race. In our previous study of 37 participants of the 2001 Boston Marathon, we observed a drop in hematocrit (from 44.0% [0.44] to 43.0% [0.43]; P = .01, 2-tailed t test),[26] as opposed to the increase seen in the present study. This difference could be due to a change in fluid replacement guidelines: In 2003 the International Marathon Medical Directors Association and USA Track and Field issued recommendations advising runners to drink ad libitum between 400 and 800 mL/h, as opposed to the previous "as much as possible" recommendations.[27,28] Alternatively, the difference between the findings in the 2 marathons may be due to differences in the timing of the phlebotomy after the race (<30 minutes in this study vs < 2 hours in the group examined in 2001, allowing more time for postrace fluid intake). Like the RBC changes, the (statistically nonsignificant) elevation of platelet counts also could be due to dehydration, or it could be part of the acute phase response to tissue injury; our group has described an increase in C-reactive protein after a marathon.[6]

Exercise-induced hemolysis is especially associated with running and is thought to be due to mechanical trauma to RBCs during footstrike.[29] Our finding of an increased number of RBC fragments after the marathon is a reflection of this phenomenon (Table 3) and shows that an automated cell counter can be used to quantify the degree of RBC destruction caused by long-distance running. The increase in RDW and the decrease in MCV after the race also may reflect RBC fragmentation.

Vigorous exercise is associated with a significant increase in the risk of acute myocardial infarction.[4] It is estimated that 6% to 17% of all sudden deaths are associated with exertion.[30] Platelet activation can have an important role in the acute coronary syndrome; several groups, therefore, have probed the activation status of platelets after physical exertion. These investigators generally have used in vitro platelet aggregation assays or measurements of soluble factors associated with platelet activation.

Among investigators using aggregation studies, a group studying participants in the Athens marathon found that although in vitro platelet aggregation induced by adenosine diphosphate (ADP) and by collagen increased in participants in a marathon run in extreme heat, it remained unaltered when the event took place in more moderate weather.[12,13] Rock and colleagues[15] reported that 24 hours after participation in a marathon, platelet aggregation in response to epinephrine, ADP, and collagen was decreased, indicating activation during the period of exercise. Similarly, Knudsen and coworkers[14] reported decreases in ADP-induced platelet "aggregability" and decreased serotonin release induced by ADP and collagen after long-distance running, consistent with exhaustion of platelet aggregation capacity. Limitations of these investigations include the possibility that changes in platelet counts in some patients may have influenced the results of the in vitro platelet aggregation studies.

Some groups have used soluble plasma factors to study exercise-induced platelet activation, focusing mainly on β-thromboglobulin, platelet factor 4 (PF4), and glycoprotein Ib.[31] Schernthaner et al[32] found a 2- to 3-fold increase in β-thromboglobulin and PF4 levels after exercise. Placanica and colleagues[33] reported that patients with ischemic heart disease had high basal concentrations of PF4 and that these levels increased with exercise. In the study by Knudsen and coworkers,[14] PF4 levels were increased immediately following a long-distance run.

The ADVIA 2120 Hematology System determines platelet parameters with 2-angle light-scatter analysis. The 2 scattering signals obtained from each platelet are converted into a cell volume measure and a refractive index measure; the refractive index measure is used to calculate the MPC, a measure that indicates the amount of platelet granulation.[17,19] A decrease in the MPC has been demonstrated to correlate with anticoagulant-induced and thrombin-stimulated platelet activation.[17,18] A decrease in MPC also was shown to correlate with CD62 expression on the platelet membrane and electron microscopic changes associated with platelet activation.[17,20] Kennon and colleagues[21] found that the MPC is lower in acute myocardial infarction than in unstable angina, confirming the central role of platelet activation in the pathogenesis of the acute coronary syndrome. Similarly, Bae and coworkers[22] found that the MPC was lower in patients with diabetic retinopathy, implying a role for platelet activation in the pathogenesis of this disease.

Our finding of a decrease in MPC after running a marathon indicates that platelet activation (degranulation) occurs in vivo during the race (Table 3). The decrease in mean MPC in our study (27.3 to 26.0 g/dL; P < .0001) was similar in magnitude to the differences reported by Kennon and colleagues[21] (25.9 vs 24.7 g/dL; P = .0001) for unstable angina vs acute myocardial infarction but less than the difference reported by Bae and coworkers[22] for patients with diabetic retinopathy vs control subjects (22.5 vs 26.9 g/dL; P < .05). The increase in the number of platelet clumps also is indicative of platelet activation (Table 3). Our results are consistent with the findings of earlier studies that showed evidence for platelet activation by vigorous exercise as measured by in vitro platelet aggregation studies and by the measurement of plasma factors released by activated platelets. In addition, our studies confirm the use of the MPC as a measure of platelet activation. The availability of the MPC on an automated platform in the routine hematology laboratory with no additional labor requirements is a clear advantage over other methods to measure platelet activation.

We used a modern cell counter to study the effects of a marathon on platelets and on RBC integrity and obtained evidence for in vivo platelet activation and for RBC fragmentation. Our findings indicate that further study is warranted to investigate the use of automated hematology systems to rapidly identify patients who may benefit from specific therapeutic interventions directed at counteracting platelet activation.


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