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Runner's Anemia

Runner's Anemia Abstract Macrocytic anemia occurring in patients with fatigue suggests numerous diagnoses, ranging from nutritional deficiencies to a myelodysplastic syndrome. A careful history-taking is critically important for recognition of runner's anemia, which is due to plasma volume expansion, with hemolysis from the pounding of feet on pavement, and hemoglobinuria. Gastrointestinal blood loss may also contribute to anemia in long-distance runners. Early recognition of runner's anemia in patients with a complex presentation of anemia is important in circumventing many diagnostic tests. Runner's anemia should be considered when, amidst a constellation of signs and symptoms, mild anemia is well tolerated by an avid runner. Case presentation The patient is a 41-year-old lawyer who was referred for evaluation of anemia and leukopenia of 2 years' duration. The history of the current illness reveals 8 years of chronic fatigue that culminates at the end of a normal working day. In 1995, the patient had the incidental finding of mild anemia and leukopenia. In February 1996, the patient's values from an outside laboratory were as follows: hematocrit, 33%; hemoglobin, 11 g/dL; mean corpuscular volume (MCV), 102 fL; reticulocyte count, 2.3%; white blood cell count, 3.1 × 103/µL; and platelet count, 133 × 103/µL. Evaluation of her pancytopenia performed before her visit to Johns Hopkins revealed various pertinent normal values (Table 1). The bone marrow aspirate performed at another institution was cellular with erythroid hyperplasia, stainable iron, and no ringed sideroblasts. An outside interpretation of the bone marrow specimen suggested the presence of moderate megaloblastic changes and occasional dysplastic cells. While the interpretation was not definitive, the report raised the possibility of a myelodysplastic syndrome, about which the patient was told. With heightened concern over this possibility, she sought additional evaluation at the Johns Hopkins Hospital. The patient's past medical history was remarkable for a tubal ligation that was subsequently subjected to reanastomosis. Her medications included ibuprofen and diazepam as needed. She had no known drug allergies, her diet was normal, and she had no history of toxin exposure. A review of systems revealed no excessive bleeding, weight loss, or night sweats. She did not smoke or abuse alcohol. Her appetite was normal, and she exercised regularly. There is no family history of hematologic disorders. On physical examination, she had an oral temperature of 36°C; weight, 47.3 kg; blood pressure, 104/60 mm Hg; pulse, 76/min; and respirations, 18/min. She was anicteric, her oropharynx showed no exudates or injection, and she had small bilateral, nontender mobile submandibular nodes and a small mobile right axillary node. The lung and heart sounds were normal. Her abdomen showed no splenic or hepatic enlargement, and her extremities were normal. She had normal vibratory and 2-point discrimination in the lower extremities and no other neurologic abnormalities. The patient's laboratory test results were as follows: hematocrit, 34%; hemoglobin, 11.3 g/dL; red blood cell count, 3.28 × 106/µL; MCV, 102 fL; white blood cell count, 4.3 × 103/µL; and platelet count, 190 × 103/L. The reticulocyte count was slightly elevated at 1.9%. The peripheral blood smear showed macrocytic round red blood cells and occasional fragments, with no polychromasia or stippling. The white blood cell series was slightly decreased with an occasional hyposegmented neutrophil. The platelets appeared normal. Discussion This patient's presentation, which included macrocytic anemia and history of pancytopenia, was a challenge in diagnosing what turned out to be an uncommon disorder with a common presentation. The differential diagnosis for macrocytosis or elevated MCV, which is defined as the packed cell volume divided by the red blood cell count, is listed in the BOX. Box. Differential Diagnosis of Macrocytosis Reticulocytosis Hemolysis, bleeding Megaloblastic Hematopoiesis Vitamin B12, folate deficiency Drugs interfering with DNA synthesis (such as antifolates, nucleosides, and hydroxyurea) Conditions Associated With Macrocytosis or Megaloblastic Changes Alcohol abuse, liver disease Myelodysplastic syndromes Hypothyroidism Bone Marrow Failure States Congenital dyserythropoiesis Pure red blood cell aplasia of infancy Aplastic anemia Given the wide spectrum of possible diagnoses, the patient's evaluation focused on the identification of reversible causes and prognostic indicators. Evaluation of a Patient With Macrocytic Anemia With a slightly elevated reticulocyte count, hemolysis was suspected. The patient's haptoglobin level as determined at the Johns Hopkins Hospital was 29 mg/dL (the normal range at Johns Hopkins laboratory is 60-270 mg/dL). The decrease in haptoglobin level, which can result from its clearance after binding globin that is released from red blood cells, suggested a hemolytic process. However, bluish ribosome-rich red cells or polychromasia, a marker of newly released red blood cells in the peripheral blood smear, was noted to be absent. Because concomitant iron deficiency, which commonly occurs in menstruating women, could cause an inappropriate low hematopoietic response, iron studies were performed. The iron studies revealed normal serum iron levels and iron saturation percentage. The ferritin level was 62 ng/mL (normal range, 10-110 ng/mL). Results of the direct Coombs test, which detects antibodies directed at and attached to red blood cells, were negative. The differential diagnosis for a macrocytic anemia associated with a decrease in platelet or white blood cell count includes disordered hematopoiesis, known as the myelodysplastic syndromes or "preleukemia." About 40% of myelodysplastic cases are associated with abnormal bone marrow karyotype, so a bone marrow examination was performed. The bone marrow aspirate showed a cellular specimen with increased erythroid precursors and absent iron stores. The bone marrow biopsy was cellular with normal-appearing hematopoiesis. The bone marrow karyotype was 46XX. These findings are nondiagnostic for a myelodysplastic syndrome; however, the presence of a myelodysplastic syndrome could not be excluded on the basis of these findings. This uncertainty directed the evaluation toward an explanation for a hemolytic anemia confounded by limited iron stores. The previous bone marrow biopsy sample had residual stainable iron, perhaps destined to be completely diminished with continued loss of iron. While the single previous iron study is compatible with normal iron availability, it should be noted that levels of serum iron are highly labile and not a reliable indicator of iron stores. The constellation of findings of hemolytic anemia with a history of mild pancytopenia and absent iron stores suggested the possibility of paroxysmal nocturnal hemoglobinuria, which is an uncommon disorder resulting from defective posttranslational (glycosylphosphatidyl-inositol [GPI] linkage) modification of membrane proteins. This defect culminates in hemolysis and is associated with pancytopenia and iron deficiency. A test for this disorder is the detection of a GPI-linked cell surface marker CD59, which was normal for this patient. The previously used, less sensitive sucrose hemolysis test for paroxysmal nocturnal hemoglobinuria was also notably negative. Because of the lack of bone marrow iron stores, the patient received iron supplements as a therapeutic trial. This trial did not improve her hemoglobin level, which remained at 11.5 g/dL after 2 months of full oral iron therapy. Although hemoglobinuria was suspected, the urinalysis and urine hemosiderin values were negative. A lack of a definitive diagnosis at this point prompted us to review her history, clinical presentation, and laboratory test results. A careful history of the patient revealed that her usual exercise consisted of a 8-km run every other day. It was then hypothesized that the patient's presentation was most consistent with the uncommon diagnosis of runner's anemia. Runner's anemia is a mechanically induced hemolytic anemia resulting from the pounding of feet on pavement, also known as "footstriking." A manifestation of this syndrome is plasma volume expansion in the presence of mild hemolysis. As such, red blood cell mass and plasma volume were measured through the use of radiolabeled red blood cells and radio-iodinated albumin, respectively. In this assay, known quantities of labeled red blood cells or iodinated albumin are injected, and the dilution of the tracers are determined at different time intervals as shown in Table 2. Red blood cell and plasma volumes are then derived from the extent of dilution of the tracers. It is expected that the values would plateau with time as the tracers equilibrate with the unlabeled circulating components. The red blood cell mass was normal, and the plasma volume was significantly expanded (Table 2). These findings indicate that the patient's anemia was, in fact, a dilutional anemia, since the red blood cell mass was normal. The results are consistent with the suspected diagnosis of runner's anemia. To further confirm the diagnosis, the patient was advised to stop running for 4 weeks, when her hematocrit value rose from 34% to 38%. Since this change was of no physiological or symptomatic consequence, she resumed running with the comfort of a definitive diagnosis for her persistent pseudoanemia. She still had baseline chronic fatigue that is unlikely due to her hematologic status. History and Pathophysiology Runner's anemia is also known as footstrike hemolysis, March hemoglobinuria, runner's hemoglobinuria, or pseudoanemia in runners.1 This syndrome was probably first noted in 1881 in a German soldier who passed dark urine after prolonged strenuous field marches.2 In 1943, runner's hemoglobinuria was documented through studies of long-distance runners.3 It was not until 1964 that an explanation for the anemia was provided.4 It was suspected that forceful striking of the feet destroyed red blood cells in 2 track runners. Although padded insoles appeared to alleviate the hemolysis, a later study did not confirm this observation. Rather, this latter study demonstrated that running mileage correlated with hemolysis as measured by haptoglobin levels and reticulocyte count.5 It is notable that the MCV increased as a function of running mileage. The very mild reticulocyte count elevation, however, does not appear to fully explain the increase in MCV. Therefore, it is hypothesized that older, smaller red blood cells are more susceptible to footstrike hemolysis, which spares younger and larger red blood cells. In addition to hemolysis from footstrikes, gastrointestinal bleeding, which is thought to result from ischemia during long-distance running, has been documented in up to 20% of runners.6 Although hemoglobinuria, hemolysis, and blood loss were the suspected causes for the anemia, it only became clear later that expanded plasma volume significantly contributes to the "pseudoanemia."1,7 The expansion of plasma volume was documented in a study of the effect of exercise on blood volume.7 Fourteen sedentary middle-aged men were enrolled in a 4-month exercise program. At the end of the study, a 5% decrease in hemoglobin concentration and a 10% increase in plasma volume were observed. Other studies have since confirmed these observations. The increased plasma volume and associated decrease in whole blood viscosity are thought to be beneficial for effective oxygen delivery. In fact, a controlled study suggests that acute artificial plasma volume expansion improves cardiac function through increases in cardiac stroke volume and cardiac output with a decrease in heart rate.8 The hormonal regulation of plasma volume expansion during exercise is not well understood. In one study, the circulating levels of atrial naturietic factor and norepinephrine were unaltered, whereas aldosterone and epinephrine levels were reduced.9 Whether these humoral factors regulate plasma volume in runners is unknown. Conclusion Runner's anemia is largely due to plasma volume expansion with elements of hemolysis, hemoglobinuria, and in long-distance runners, gastrointestinal blood loss. The recognition of these symptoms is extremely important in patients—such as the one reported here—with a complex presentation of anemia and chronic fatigue. In particular, reaching this diagnosis at an earlier stage would have circumvented many of the diagnostic tests discussed above. Furthermore, recognition of this syndrome is important in patient management, which should include reassurance and avoidance of unnecessary therapies. Nevertheless, it was the methodical evaluation of the differential diagnoses that led to the correct diagnosis. Amidst the constellation of signs and symptoms, mild anemia that is tolerated by an avid, devoted runner should raise the possibility of a diagnosis of runner's anemia. References 1. Erslev AJ. March hemoglobinuria and sports anemia. In: Williams WJ, Beutler E, Erslev AJ, Lichtman MA. Hematology. 4th ed. New York, NY: McGraw-Hill; 1990:653-654. 2. Fleischer R. Uber eine neue Form von Hamoglobinurie beim Menschen. Berlin Klin Wochenschr.1881;18:691-695.Google Scholar 3. Gilligan DR, Altschule MD, Katersky EM. Psychologic intravascular hemolysis of exercise: hemoglobinemia and hemoglobinuria following cross-country runs. J Clin Invest.1943;22:859-869.Google Scholar 4. Davidson RJL. Exertional hemoglobinuria: a report on three cases with studies on the haemolytic mechanism. J Clin Pathol.1964;17:536-540.Google Scholar 5. Eichner ER. Runner's macrocytosis: a clue to footstrike hemolysis: runner's anemia as a benefit versus runner's hemolysis as a detriment. Am J Med.1985;78:321-325.Google Scholar 6. Stewart JG, Ahlquist DA, McGill DB, Ilstrup DM, Schwartz S, Owen RA. Gastrointestinal blood loss and anemia in runners. Ann Intern Med.1984;100:843-845.Google Scholar 7. Oscai LB, Williams BT, Hertig BA. Effect of exercise on blood volume. J Appl Physiol.1968;24:622-624.Google Scholar 8. Roy BD, Green HJ, Grant SM, Tarnopolsky MA. Acute plasma volume expansion alters cardiovascular but not thermal function during moderate intensity prolonged exercise. Can J Physiol Pharmacol.2000;78:244-250.Google Scholar 9. Shoemaker JK, Green HJ, Ball-Burnett M, Grant S. Relationship between fluid and electrolyte hormones and plasma volume during exercise with training and detraining. Med Sci Sports Exerc.1998;30:497-505.Google Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA American Medical Association

Runner's Anemia

JAMA , Volume 286 (6) – Aug 8, 2001

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American Medical Association
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Copyright © 2001 American Medical Association. All Rights Reserved.
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0098-7484
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1538-3598
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10.1001/jama.286.6.714
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Abstract

Abstract Macrocytic anemia occurring in patients with fatigue suggests numerous diagnoses, ranging from nutritional deficiencies to a myelodysplastic syndrome. A careful history-taking is critically important for recognition of runner's anemia, which is due to plasma volume expansion, with hemolysis from the pounding of feet on pavement, and hemoglobinuria. Gastrointestinal blood loss may also contribute to anemia in long-distance runners. Early recognition of runner's anemia in patients with a complex presentation of anemia is important in circumventing many diagnostic tests. Runner's anemia should be considered when, amidst a constellation of signs and symptoms, mild anemia is well tolerated by an avid runner. Case presentation The patient is a 41-year-old lawyer who was referred for evaluation of anemia and leukopenia of 2 years' duration. The history of the current illness reveals 8 years of chronic fatigue that culminates at the end of a normal working day. In 1995, the patient had the incidental finding of mild anemia and leukopenia. In February 1996, the patient's values from an outside laboratory were as follows: hematocrit, 33%; hemoglobin, 11 g/dL; mean corpuscular volume (MCV), 102 fL; reticulocyte count, 2.3%; white blood cell count, 3.1 × 103/µL; and platelet count, 133 × 103/µL. Evaluation of her pancytopenia performed before her visit to Johns Hopkins revealed various pertinent normal values (Table 1). The bone marrow aspirate performed at another institution was cellular with erythroid hyperplasia, stainable iron, and no ringed sideroblasts. An outside interpretation of the bone marrow specimen suggested the presence of moderate megaloblastic changes and occasional dysplastic cells. While the interpretation was not definitive, the report raised the possibility of a myelodysplastic syndrome, about which the patient was told. With heightened concern over this possibility, she sought additional evaluation at the Johns Hopkins Hospital. The patient's past medical history was remarkable for a tubal ligation that was subsequently subjected to reanastomosis. Her medications included ibuprofen and diazepam as needed. She had no known drug allergies, her diet was normal, and she had no history of toxin exposure. A review of systems revealed no excessive bleeding, weight loss, or night sweats. She did not smoke or abuse alcohol. Her appetite was normal, and she exercised regularly. There is no family history of hematologic disorders. On physical examination, she had an oral temperature of 36°C; weight, 47.3 kg; blood pressure, 104/60 mm Hg; pulse, 76/min; and respirations, 18/min. She was anicteric, her oropharynx showed no exudates or injection, and she had small bilateral, nontender mobile submandibular nodes and a small mobile right axillary node. The lung and heart sounds were normal. Her abdomen showed no splenic or hepatic enlargement, and her extremities were normal. She had normal vibratory and 2-point discrimination in the lower extremities and no other neurologic abnormalities. The patient's laboratory test results were as follows: hematocrit, 34%; hemoglobin, 11.3 g/dL; red blood cell count, 3.28 × 106/µL; MCV, 102 fL; white blood cell count, 4.3 × 103/µL; and platelet count, 190 × 103/L. The reticulocyte count was slightly elevated at 1.9%. The peripheral blood smear showed macrocytic round red blood cells and occasional fragments, with no polychromasia or stippling. The white blood cell series was slightly decreased with an occasional hyposegmented neutrophil. The platelets appeared normal. Discussion This patient's presentation, which included macrocytic anemia and history of pancytopenia, was a challenge in diagnosing what turned out to be an uncommon disorder with a common presentation. The differential diagnosis for macrocytosis or elevated MCV, which is defined as the packed cell volume divided by the red blood cell count, is listed in the BOX. Box. Differential Diagnosis of Macrocytosis Reticulocytosis Hemolysis, bleeding Megaloblastic Hematopoiesis Vitamin B12, folate deficiency Drugs interfering with DNA synthesis (such as antifolates, nucleosides, and hydroxyurea) Conditions Associated With Macrocytosis or Megaloblastic Changes Alcohol abuse, liver disease Myelodysplastic syndromes Hypothyroidism Bone Marrow Failure States Congenital dyserythropoiesis Pure red blood cell aplasia of infancy Aplastic anemia Given the wide spectrum of possible diagnoses, the patient's evaluation focused on the identification of reversible causes and prognostic indicators. Evaluation of a Patient With Macrocytic Anemia With a slightly elevated reticulocyte count, hemolysis was suspected. The patient's haptoglobin level as determined at the Johns Hopkins Hospital was 29 mg/dL (the normal range at Johns Hopkins laboratory is 60-270 mg/dL). The decrease in haptoglobin level, which can result from its clearance after binding globin that is released from red blood cells, suggested a hemolytic process. However, bluish ribosome-rich red cells or polychromasia, a marker of newly released red blood cells in the peripheral blood smear, was noted to be absent. Because concomitant iron deficiency, which commonly occurs in menstruating women, could cause an inappropriate low hematopoietic response, iron studies were performed. The iron studies revealed normal serum iron levels and iron saturation percentage. The ferritin level was 62 ng/mL (normal range, 10-110 ng/mL). Results of the direct Coombs test, which detects antibodies directed at and attached to red blood cells, were negative. The differential diagnosis for a macrocytic anemia associated with a decrease in platelet or white blood cell count includes disordered hematopoiesis, known as the myelodysplastic syndromes or "preleukemia." About 40% of myelodysplastic cases are associated with abnormal bone marrow karyotype, so a bone marrow examination was performed. The bone marrow aspirate showed a cellular specimen with increased erythroid precursors and absent iron stores. The bone marrow biopsy was cellular with normal-appearing hematopoiesis. The bone marrow karyotype was 46XX. These findings are nondiagnostic for a myelodysplastic syndrome; however, the presence of a myelodysplastic syndrome could not be excluded on the basis of these findings. This uncertainty directed the evaluation toward an explanation for a hemolytic anemia confounded by limited iron stores. The previous bone marrow biopsy sample had residual stainable iron, perhaps destined to be completely diminished with continued loss of iron. While the single previous iron study is compatible with normal iron availability, it should be noted that levels of serum iron are highly labile and not a reliable indicator of iron stores. The constellation of findings of hemolytic anemia with a history of mild pancytopenia and absent iron stores suggested the possibility of paroxysmal nocturnal hemoglobinuria, which is an uncommon disorder resulting from defective posttranslational (glycosylphosphatidyl-inositol [GPI] linkage) modification of membrane proteins. This defect culminates in hemolysis and is associated with pancytopenia and iron deficiency. A test for this disorder is the detection of a GPI-linked cell surface marker CD59, which was normal for this patient. The previously used, less sensitive sucrose hemolysis test for paroxysmal nocturnal hemoglobinuria was also notably negative. Because of the lack of bone marrow iron stores, the patient received iron supplements as a therapeutic trial. This trial did not improve her hemoglobin level, which remained at 11.5 g/dL after 2 months of full oral iron therapy. Although hemoglobinuria was suspected, the urinalysis and urine hemosiderin values were negative. A lack of a definitive diagnosis at this point prompted us to review her history, clinical presentation, and laboratory test results. A careful history of the patient revealed that her usual exercise consisted of a 8-km run every other day. It was then hypothesized that the patient's presentation was most consistent with the uncommon diagnosis of runner's anemia. Runner's anemia is a mechanically induced hemolytic anemia resulting from the pounding of feet on pavement, also known as "footstriking." A manifestation of this syndrome is plasma volume expansion in the presence of mild hemolysis. As such, red blood cell mass and plasma volume were measured through the use of radiolabeled red blood cells and radio-iodinated albumin, respectively. In this assay, known quantities of labeled red blood cells or iodinated albumin are injected, and the dilution of the tracers are determined at different time intervals as shown in Table 2. Red blood cell and plasma volumes are then derived from the extent of dilution of the tracers. It is expected that the values would plateau with time as the tracers equilibrate with the unlabeled circulating components. The red blood cell mass was normal, and the plasma volume was significantly expanded (Table 2). These findings indicate that the patient's anemia was, in fact, a dilutional anemia, since the red blood cell mass was normal. The results are consistent with the suspected diagnosis of runner's anemia. To further confirm the diagnosis, the patient was advised to stop running for 4 weeks, when her hematocrit value rose from 34% to 38%. Since this change was of no physiological or symptomatic consequence, she resumed running with the comfort of a definitive diagnosis for her persistent pseudoanemia. She still had baseline chronic fatigue that is unlikely due to her hematologic status. History and Pathophysiology Runner's anemia is also known as footstrike hemolysis, March hemoglobinuria, runner's hemoglobinuria, or pseudoanemia in runners.1 This syndrome was probably first noted in 1881 in a German soldier who passed dark urine after prolonged strenuous field marches.2 In 1943, runner's hemoglobinuria was documented through studies of long-distance runners.3 It was not until 1964 that an explanation for the anemia was provided.4 It was suspected that forceful striking of the feet destroyed red blood cells in 2 track runners. Although padded insoles appeared to alleviate the hemolysis, a later study did not confirm this observation. Rather, this latter study demonstrated that running mileage correlated with hemolysis as measured by haptoglobin levels and reticulocyte count.5 It is notable that the MCV increased as a function of running mileage. The very mild reticulocyte count elevation, however, does not appear to fully explain the increase in MCV. Therefore, it is hypothesized that older, smaller red blood cells are more susceptible to footstrike hemolysis, which spares younger and larger red blood cells. In addition to hemolysis from footstrikes, gastrointestinal bleeding, which is thought to result from ischemia during long-distance running, has been documented in up to 20% of runners.6 Although hemoglobinuria, hemolysis, and blood loss were the suspected causes for the anemia, it only became clear later that expanded plasma volume significantly contributes to the "pseudoanemia."1,7 The expansion of plasma volume was documented in a study of the effect of exercise on blood volume.7 Fourteen sedentary middle-aged men were enrolled in a 4-month exercise program. At the end of the study, a 5% decrease in hemoglobin concentration and a 10% increase in plasma volume were observed. Other studies have since confirmed these observations. The increased plasma volume and associated decrease in whole blood viscosity are thought to be beneficial for effective oxygen delivery. In fact, a controlled study suggests that acute artificial plasma volume expansion improves cardiac function through increases in cardiac stroke volume and cardiac output with a decrease in heart rate.8 The hormonal regulation of plasma volume expansion during exercise is not well understood. In one study, the circulating levels of atrial naturietic factor and norepinephrine were unaltered, whereas aldosterone and epinephrine levels were reduced.9 Whether these humoral factors regulate plasma volume in runners is unknown. Conclusion Runner's anemia is largely due to plasma volume expansion with elements of hemolysis, hemoglobinuria, and in long-distance runners, gastrointestinal blood loss. The recognition of these symptoms is extremely important in patients—such as the one reported here—with a complex presentation of anemia and chronic fatigue. In particular, reaching this diagnosis at an earlier stage would have circumvented many of the diagnostic tests discussed above. Furthermore, recognition of this syndrome is important in patient management, which should include reassurance and avoidance of unnecessary therapies. Nevertheless, it was the methodical evaluation of the differential diagnoses that led to the correct diagnosis. Amidst the constellation of signs and symptoms, mild anemia that is tolerated by an avid, devoted runner should raise the possibility of a diagnosis of runner's anemia. References 1. Erslev AJ. March hemoglobinuria and sports anemia. In: Williams WJ, Beutler E, Erslev AJ, Lichtman MA. Hematology. 4th ed. New York, NY: McGraw-Hill; 1990:653-654. 2. Fleischer R. Uber eine neue Form von Hamoglobinurie beim Menschen. Berlin Klin Wochenschr.1881;18:691-695.Google Scholar 3. Gilligan DR, Altschule MD, Katersky EM. Psychologic intravascular hemolysis of exercise: hemoglobinemia and hemoglobinuria following cross-country runs. J Clin Invest.1943;22:859-869.Google Scholar 4. Davidson RJL. Exertional hemoglobinuria: a report on three cases with studies on the haemolytic mechanism. J Clin Pathol.1964;17:536-540.Google Scholar 5. Eichner ER. Runner's macrocytosis: a clue to footstrike hemolysis: runner's anemia as a benefit versus runner's hemolysis as a detriment. Am J Med.1985;78:321-325.Google Scholar 6. Stewart JG, Ahlquist DA, McGill DB, Ilstrup DM, Schwartz S, Owen RA. Gastrointestinal blood loss and anemia in runners. Ann Intern Med.1984;100:843-845.Google Scholar 7. Oscai LB, Williams BT, Hertig BA. Effect of exercise on blood volume. J Appl Physiol.1968;24:622-624.Google Scholar 8. Roy BD, Green HJ, Grant SM, Tarnopolsky MA. Acute plasma volume expansion alters cardiovascular but not thermal function during moderate intensity prolonged exercise. Can J Physiol Pharmacol.2000;78:244-250.Google Scholar 9. Shoemaker JK, Green HJ, Ball-Burnett M, Grant S. Relationship between fluid and electrolyte hormones and plasma volume during exercise with training and detraining. Med Sci Sports Exerc.1998;30:497-505.Google Scholar

Journal

JAMAAmerican Medical Association

Published: Aug 8, 2001

Keywords: anemia,anemia, macrocytic,hemolysis,myelodysplastic syndrome,hemoglobinuria,gastrointestinal bleeding,medical history taking,fatigue,malnutrition,blood plasma volume,foot

References