Hematologic Concerns in the Athlete

1. Hematologic Concerns in the Athlete Emily Jones, M.D. Jan 8, 2009 Adapted from lecture by Michael Simpson, D.O.

2. OUTLINE: • Sports Anemia • Iron Deficiency Anemia • Laboratory Evaluation of Anemia • Foot Strike Hemolysis • Sickle Cell Trait • Acute Exertional Rhabdomyolysis • Hypercoaguable States

3. All hematologic problems that happen in the non-athlete, can happen in the athlete – plus a few that are unique to athletes In general the differential diagnosis is the same as well as the work-up.

4. Anemia Definition • Anemia is a condition characterized by low levels of red blood cells or hemoglobin • Measured as a percentage of red blood cells in a given volume of plasma

5. Sports Anemia • Also called “Dilutional Pseudoanemia” • Not true anemia • Increased Plasma Volume in Response to Exercise • Increase in aldosterone, renin, ANF, vasopressin • increased renal retention of water and salts • Increase in plasma proteins • Increased hydration

6. Sports Anemia • Increased Plasma Volume occurs in response to long term exercise • Stroke Volume • Thins Blood to Thrombosis • Volume Available for Perspiration and therefore heat regulation • Improves oxygen delivery to muscles

7. Sports Anemia • Plasma Volume by 8-24% • RBC no change to 20% • Labs – Hg/Hct mildly decreased • All other parameters will be normal • R/O other causes

8. Sports Anemia • Temporary and benign • Will resolve after a few days rest from training • No adverse effect on athletic performance and possible beneficial effects • No treatment needed

9. Iron Deficiency Anemia • #1 Nutritional Deficiency in U.S. • Iron Deficiency ~ 11% of women • Iron Deficiency Anemia 1-2% adults • #1 cause of Anemia in Athletes • Up to 12.5% of athletes •  Dietary intake • Menstruation •  Loss from other sources (GI, GU, hemolysis, sweating) •  Absorption

10. Iron Deficiency Anemia • Hg <12g/dL (36 Hct) Female • Hg < 14 g/dL (42 Hct) Male • MCV < 75 • (if < 60 consider hemoglobinopathy) • Ferritin <12 • Low Serum Iron w/ High TIBC

11. Iron Deficiency Anemia • Stage 1- “prelatent anemia” • Depleted Iron Stores • Ferritin NL-TIBC/Iron NL-HCT • Stage 2- “iron-deficient erythropoisesis” • above plus Ferritin TIBC IRON, Mild HCT • Normocytic to mildly microcytic, mild Hypochromic • Stage 3- overt Microcytic and Hypochromic anemia •  Ferritin TIBC IRON HCT

12. Iron Deficiency Anemia • Rule Out Underlying Medical cause • Bowel disease – Celiacs, Crohn’s, UC • Cancer • Thalasemia • Sickle cell • Other chronic disease

13. Gastrointestinal Hemorrhage in Athletes • Particularly in distance runners, triathletes • Following endurance events stool occult positive 13-85% • Overt hematochezia was reported in 6% • Increased blood loss with increased intensity • Mixed results on increased blood loss with concurrent use of NSAIDs • Blood loss can be trivial to severe

14. Gastrointestinal hemorrhage in Athletes • Visceral ischemia due to decreased splanchinc perfusion • Gastritis and espohagitis most frequently noted abnormalities on endoscopy – but also cases of small bowel and colonic ischemia • Exercising at 70% of VO2 max reduces blood flow to the gastrointestinal tract by 60-70%; more intense exercise may cause reductions in excess of 80% - worsened by dehydration • Up and down motion of running appears to be risk factor - ? Direct trauma to viscera

15. Genitourinary system losses • Exercise-induced hematuria • Typically microscopic • Usually resolves within a few days of event • Renal causes • Renal vasoconstriction • decreased renal plasma flow with damage to nephron • direct trauma to GU system • Intravascular hemolysis causing hemoglobinuria

16. Work up for Anemia • Detailed history • Symptoms of: fatigue, sob, decreasing performance, palpitations, tachycardia, pica • GI, urinary bleeding • Menstrual history • Nutritional practices • Training • Use of medications

17. Physical Exam • Resting bp, pulse, orthostatics • Skin – pallor, jaundice • Cardiopulmonary • Abdominal • Possibly rectal exam

18. Laboratory studies • Hemoglobin/Hct including MCV, MCH • Reticulocyte count • Possible smear – for abnormal cells • Serum iron, ferritin • Total iron-binding capacity/transferrin • LDH, bilirubin, haptoglobin • Possibly further GI/GU evaluation • Consider CRP, ESR, TSH, electrophoresis if ruling out other dz

19. LAB VALUE ETIOLOGIES EVALUATION

20. Iron Deficiency Anemia Treatment • Discuss Dietary consumption • Males require 10mg/day, female 15mg/day • Heme iron (meats) more bioavailable (10-35%) vs non-heme iron (2-5%) • Handouts/Websites - www.fwhc.org/health/iron.htm • Consider Iron Replacement • Stage 1&2?, Stage 3 yes

21. Ferrous vs Ferric Ferrous is absorbed better sulfate 325mg(65mg) gluconate 325mg(36mg) Replace w/ palatable forms Increased absorption w/ Vitamin C (Ascorbic Acid) GI side effects Take w/ food (but can absorption up to 65%) Do not use enteric coated forms (do not dissolve in stomach) Drug Interactions (H2 blockers, PPI, tea and coffee tannates, Caffeinated drinks) Iron Replacementneed 150-200mg/day

22. Iron Deficiency Treatment • Re-evaluate • CBC in 1 month • Reticulocytes and MCV increase first • If HCT not up despite therapy – consider further evaluation • Replaced Iron stores complete when Ferritin = 50 • Can take 4-6 months to treat then maintenance therapy

23. Iron Deficiency Anemia - Impact on Performance • Reduction in aerobic capacity, endurance and energetic efficiency due to decreased oxygen delivery • Correction of anemia with iron supplementation improves performance • ? No improvement in performance shown with iron supplementation in nonanemic, iron-deficient athletes

24. Intravascular Hemolysis • Also called “Foot Strike Hemolysis” • Caused by RBC destruction from repeated trauma • Elevated temperature in muscle, turbulence and acidosis may also be involved

25. Foot Strike HemolysisDiagnosis •  Bilirubin •  Haptoglobin •  Schistocytes • Slight  MCV & Reticulocytes • Preferential breakdown of older rbcs • Hemoglobinuria • Anemia resolves w/ d/c exercise

26. Foot Strike HemolysisTreatment • Change Shoes • Change Running Surfaces • Modification of Training Program • Search for other causes of Hemolysis • - Drugs (ABX, INH) • - Acute Illnesses (Mycoplasma, Mono, Sepsis, Viral) • - Chronic Illnesses (Autoimmune) • - Heredity (G6PD, Thalassemia, Sickle Cell)

27. Intravascular hemolysis in non-foot strike sports • Swimmers • Compression from contracting muscles • Cyclists, other sports - ? Increase in body temperature may increase red cell turnover - oxidative and osmotic stress

28. Sickle Cell • Inherited disease of abnormal hemoglobin S • Polymerizes under physiologic stress = destruction of rbcs • Sickle disease – usually incompatible with participation in intense physical activity • Sickle Trait - Heterozygous state where Hgb S is present with Normal Hgb A in RBC • < 50% Hgb is Hgb S • Usually Asymptomatic w/ no anemia • Up to 8% of African Americans • 1/10,000 Whites

29. Sickle Cell Risks • Gross hematuria • Splenic infarction • Exertional heat illness • Rhabdomyolysis • heat stroke • renal failure • Idiopathic sudden death • Physiologic changes associated with exercise – (regional hypoxemia, acidosis, dehydration, hyperthermia) – all increase risk of sickling

30. Sickle Cell Trait HEMATURIA • Sickle Cell trait carries 2-fold increase at rest • Papillary Necrosis • Due to sickling and decreased blood flow Rest until hematuria clears • Hyposthenuria • inability to concentrate urine in tubules = Secretion of low specific gravity urine = Dehydration = more at risk for EHI

31. Sickle Cell Trait SPLENIC INFARCTION • Rare in sickle cell trait – 47 reported cases • Due to microvascular occlusion • Severe Hypoxia - Elevations > 10,000 feet • Descend to lower height, O2, hydration

32. Sickle Cell Trait EXERTIONAL SICKLING/ EXERTIONAL RHABDOMYOLISIS • Dehydration • Elevated Temperatures • Hypoxia, High Altitude • Acidosis

33. Sickle Trait in Military Recruits • Estimated to be 20 fold increased risk factor for sudden death compared to non-sickle trait recruits • Causes of death – rhabdomyolysis, exertional heat stroke, sudden cardiac arrhythmia • Risk factors – dehydration, extreme heat, high altitude. Avoidance of these proved protective. • Possibility that athletics carries similar risk

34. Sickle Cell and Exercise • Study done in Senegal no difference in max performance or recovery (despite theoretical decrease in O2 delivery) • ? D/t adaptations • endurance, severe heat, altitude not tested • Exercise-Induced cardiac dysfunction due to anemia • Abnormal EF, wall motion, filling • With more severe disease and anemia

35. Sickle Cell • Train Wisely • Stay Hydrated • Avoid heat and elevation • Rest when Sick • Report Hematuria • Respect pain – abdominal, muscles, cardiac

36. Acute Exertional Rhabdomyolysis Definition • Acute Exertional Rhabdomyolysis (AER): • Rhabdomyolysis syndrome resulting from damage to skeletal muscle leaking myoglobin into circulation • Rhabdomyolysis arising from exercise or exertion (non-traumatic) • Usually precipitated by running or extreme muscle overload activities • A spectrum illness ranging from insignificant asymptomatic muscle injury with minor laboratory alterations to fulminant, and life threatening syndrome

37. Epidemiology of AER • In the United States, 26,000 cases are reported annually from all causes. • Elevation of CK to the 1000s can be normal after intense exercise • Exertional rhabdomyolysis in the military is reported in .3 to 3% in military trainees, and .2% of law and fire department trainees. Brown TP: Exertional Rhabdomyolysis: Early Recognition is Key. Physician and Sports Medicine 2004.

38. Exercise Factors Experience and fitness level Intensity Duration Type Nonexercise Factors Hydration/nutrition status Metabolic myopathies Illness Sickle Cell Trait High Ambient Temperature Drugs Muscle injury / prolonged immobile state Factors in the Development of Exertional Rhabdomyolysis

39. Pathophysiology of AER • Mechanical muscle fiber injury due to eccentric contraction, trauma • Muscle necrosis resulting from ATP depletion leading to disturbance in muscle cell homeostasis • Influx of calcium, free radical formation = cell death and release of myoglobin

40. Other common presenting symptoms: Tenderness Stiffness Swelling Bruising Contractures (less common) Large muscles of the thighs, calves, and lower back involved in 50% of patients with rhabdomyolysis. Presentation of AER Gabow et al,, Medicine 1982

41. Testing AER • Urine • Myoglobinuria • Dark color • Blood by benzidine reaction, but < 5 rbc per hpf • Acidic pH • Sediment of pigmented brown granular casts and renal tubular epithelial cells • FENa > 1%

42. Testing AER • Blood tests • CK often > 10,000 (CK-MM) • Elevated aldolase, LDH, transaminases • BUN:Cr – Cr up initially, later BUN up due to increased urea production • High Anion Gap • High phosphate, causing Hypocalcemia • Hypoalbuminemia, Anemia (capillary leak) • Hyperkalemia

43. Complications • Early • Hyperkalemia • Hypocalcemia • Hepatic inflammation • Cardiac arrhythmia • Cardiac arrest • Late • ARF • DIC • Early or Late • Compartment syndrome

44. Late Complications Acute Renal Failure • Large amounts of circulating myoglobin obstructs tubules • volume depletion and renal vasoconstriction = decreased perfusion • chelatable iron toxic to tubules • Occurs in up to 15% of patients • CK levels above 16K being more likely associated with ARF

45. Algorithm for Treatment of Acute Exertional Rhabdomyolysis Service member presents with severe muscle pain Screening labs: CK and UA. Screen for Compartment synd. CK > 5 X normal or positive urine dipstick for blood Yes No Acute Exertional Rhabdomyolysis - Urine myoglobin, serum calcium, phosphate - IV hydration with NS to keep urine output > 200 mL/hr. IV rate at 1.5L/hr - Foley catheter Limited indoor duty for remainder of day. Medical re-evaluation on following day. Home oral re-hydration.

46. Algorithm for Treatment of Acute Exertional Rhabdomyolysis Acute Exertional Rhabdomyolysis Phos > 7 mg/dL or Sympt. Hypocalcemia or Severe ARF or Refract. hyperkalemia Positive urine myoglobin or metabolic acidosis Hyperkalemia: - D50 - Insulin - Inhaled B-agonist Urine output <200 cc/hr or Hypercalcemia Alkalinize urine: Moderate - 1 amp bicarb to 1 bag 1/2 NS Severe - 2 amps of bicarb to 1 bag of 1/4 NS D/C when myoglobin or acidosis resolves Increase IV fluids Consider mannitol 10g/L (controversial) Consult nephrologist for possible dialysis

47. Hypoxic stress Drug use Carbon monoxide exposure Excess erythropoietin production Training at altitude (Live High Train Low) Plasma volume contraction Hyperplastic marrow response Erythrocythemia

48. Polycythemia Vera • Myeloproliferative disorder • RBC mass increase with leukocytosis and thrombocytosis • Erythropoietin is low with markedly high Hct • Require regular phlebotomy to prevent hyperviscosity

49. Blood Doping • Increasing the number of red blood cells in the body to increase the oxygen carried to muscle • Administration of blood, red blood cells, or related blood products • Erythropoietin (EPO) or rHuEPO • Stimulates bone marrow to produce red blood cells

50. Blood Doping • Claims • Increases RBC and Hct levels for more oxygen carrying capacity and increase in endurance • Thermoregulatory advantage