Clinical laboratory and special studies

I. Laboratory diagnosis of musculoskeletal conditions

A. Paget’s disease of bone – osteitis deformans

1. first described by Sir James Paget in 1877
2. bony deformities
3. serum alkaline phosphatase usually increased (normal in 6%)
4. serum calcium normal, rarely increased (unless concurrent generalized inactivity, hyperparathyroidism, hyperthyroidism, malignancy)
5. serum phosphorus normal
6. urine calcium may be increased due to immobilization
7. increased 24-hour urinary excretion of total peptide hydroxyproline (normal in 5%)
8. urine pyridinoline corsslinks is now the most sensitive test (associated with extent of disease)
9. localized and asymptomatic disease requires no treatment
10. approximately 1% of patients develop osteosarcoma (Paget’s sarcoma), resulting in about 20% survival in 5 years (increased pain, increased ALP)

B. Multiple myeloma

1. monoclonal tumor plasma cell proliferation that usually reveals monoclonal protein in the serum or urine of more than 90% of patients
2. progressive neoplastic disease characterized by marrow plasma cell tumors and overproduction of intact monoclonal immunoglobulin or Bence Jones protein (half of antibody)
3. often associated with multiple osteolytic lesions, hypercalcemia, anemia, renal damage and increased susceptibility to bacterial infections
4. cancer of the bone marrow
5. cause unknown
6. 1% of malignancies, 10% of hematological malignancies
7. persons over the age of 40 are most commonly affect with the peak at 60-65 years (2-3/100,000)
8. approximately 13,000 new cases per year
9. renal failure or renal insufficiency
10. recurrent bacterial infections in 10-52% of cases; usually encapsulated bacteria such as pneumococcal
11. anemia with weakness and fatigue
12. bleeding (purpura or epistaxis) if thrombocytopenia
13. back pain, renal failure, bacterial infections
14. serum total protein elevated due to increased globulin
15. serum protein electrophoresis reveals abnormal proteins in 75-80% of patients
16. reverse A:G
17. monoclonal M spike
18. urine electrophoresis positive about 70% of the time for light chains
19. Bence-Jones proteinuria in 70% of patients
    • 50% detectable with the heat test
    • 70-80% detectable using urine ELP
    • not picked up on dipstick which is only sensitive to albumin
20. normochromic, normocytic anemia in 60-80% of patients at the time of diagnosis; nearly all patients will develop anemia as disease progresses
21. peripheral blood smear: rouleaux formation in 60-85% of cases)
22. increased ESR in over 90% of patients
23. 20% plasma cells in bone marrow
24. normal WBC and platelet count
25. lymphocytosis
26. serum calcium increased in 20-50% of patients due to OAF
27. serum phosphorous normal
28. serum ALP normal or slightly increased
29. serum BUN (50-55% of patients), creatinine (50% of patients) and uric acid increased
30. increased urinary albumin (60-90%) and casts
31. peripheral blood plasmacytosis in 1-2% of patients with greater than 5% plasma cells
32. X-ray: punched-out lesions; diffuse osteopenia

C. Bone tumors

1. often non-specific, but routine studies should be obtained in any patient with suspected tumor
2. patients 5-30 years of age
   • CBC with differential
   • ESR
3. patients more than 40 years of age
   • CBC with differential
   • ESR
   • serum calcium and phosphate
   • serum or urin protein ELP
   • urinalysis
4. osteolytic metastasis
   • urine calcium increased
   • serum calcium and phosphorus normal (calcium will increase at some time)
   • serum ALP normal to slight increase
   • serum ACP slightly increase if prostate cancer
   • X-ray: pathological fractures; no periosteal reaction or sclerosis; kidney, lung, breast and thyroid are most common (kidney and thyroid cause blow-out lesions)
5. osteoblastic metastasis
   • serum ALP increased
   • serum ACP increased
   • serum calcium normal
   • urine calcium decreased
   • serum phosphorus variable
   • X-ray: sclerosis; normal architecture is lost; usually breast or prostate
6. primary malignant bone tumors – osteogenic sarcoma
   • serum ALP increased (50% of patients)

D. Fat embolism syndrome

1. usually after trauma, especially after fractures (2% insertion of femoral prostheses)
2. fat globules appear in the veins and act as emboli to the lungs and other tissues
3. embolism appears rather slowly and attains a maximum in about 48 hours
4. source of fat droplets is in dispute
5. open fractures furnish less emboli than closed fractures
6. long bones, pelvis and ribs furnish more emboli
7. petechiae (upper chest and face)
8. fat droplets in urine or cerebrospinal fluid (floats on top)
9. thrombocytopenia and anemia (unexplained)
10. hypocalceumia
11. elevated serum lipase
12. lipuria
13. increased ESR
14. increased serum triglycerides
15. fat globules in blood
16. oxygen therapy
17. mortality is 20-30%

E. Osteomyelitis (medical emergency)

1. leukocytosis in the acute cases but not in the chronic cases; not a reliable indicator of infection
2. ESR is a non-specific acute-phase reactant that is elevated in more than 90% of patients and is a reliable indication of infection; it begins to elevate at 2-3 days and returns to normal after 2-3 weeks if the infection has resolved (both children and adults)
3. elevated level of CRP; more reliable in assessing infection because it not only peaks earlier (50 hours versus 3-5 days) but also returns to normal earlier (7 days)
4. blood cultures are positive in 40-50% of younger patients with hematogenous disease
5. definitive diagnosis is made by needle aspiration or bone biopsy and demonstration of the microorganism by culture or histology
6. X-ray: 10 days in the extremities and 21 days in the spine before X-ray changes are seen in acute infection
7. MRI excellent but more expensive

F. Osteoarthritis

1. DIPs, Heberdeen’s nodes
2. no specific laboratory features
3. ESR normal to moderate increase
4. anemia and leukocytosis are absent
5. negative RF
6. synovial fluid analysis normal (Rope’s test: add glacid (?) acetic acid to synovial fluid; should clot)
7. normal serum uric acid, calcium, phosphorus, alkaline phosphatase and negative VDRL

G. Rheumatoid arthritis

1. B/L, PIPs and MCPs, extensor surfaces (subcutaneous nodules)
2. ulnar drift, skin shiny, atrophy, smooth
3. atrophy of thenar eminence, indicates surgery
4. swan neck
5. Boutinnierre’s
6. anemia of chronic disease is found in 80% of cases due to chronic inflammation; Hb>10; normochromic, normocytic or hypochromic, microcytic
7. ESR is elevated in 90% of cases; positive CRP
8. positive serologic tests for RF
   • >1:80 in 70-80% of patients with RA, 20% negative despite other signs of RA
   • RF is a poor screening tool for RA with a PPV of only 20% in asymptomatic person; in patients with rheumatologic symptoms, its PPV is 80%
   • not useful to monitor course of the illness
   • RF is immunoglobulin IgG, IgM or IgA with specificity of IgG that has been altered in certain ways (usually IgM against IgG)
   • most important RF is IgM macroglobulin
   • RF combines with IgG and is accompanied by complement fixation
   • RF has 76% sensitivity in well-established clinical cases of adult TA
   • it may take up to 6 months before TA serological test results become abnormal
   • 75% of typical cases; 90% of cases with subcutaneous nodules; 5-6% of the normal population
   • high titers of RF indicate a poor prognosis (associated with progressive disease, nodules)
   • not specific for RA: false positive in Sjogren’s syndrome (75-96%), SBE (50%), collagen disease, sarcoidosis, syphilis, chronic hepatitis, cirrhosis, bacterial infections, old age, mixed cryoglobulinemia, parasitic infections, acute viral infections
   • latex fixation tube dilution titer of 1:160 is considered the lowest positive value for a diagnosis of RA
   • titer often falls as inflammatory joint activity decreases
9. synovial fluid analysis: cloudy, sterile, reduced viscosity, poor mucin clot, increased WBCs, predominately polymorphonuclear cells, decrease complement
10. decreased serum iron and TIBC
11. 25% of patients with RA have occasional leukocytosis usually not exceeding 15,000/ul
12. mild polyclonal hypergammaglobulinemia
13. ANA factors resent (20-30%)
14. normal serum calcium, phosphorus, ALP uric acid, and ASOT
15. increased frequency of HLA-DR4 in 70% of Caucasian seropositive patients

H. Felty’s syndrome

1. consists of RA, splenomegaly, neutropenia
2. positive serologic tests for RF
3. leukopenia, neutropenia, anemia, thrombocytopenia

I. Psoriatic arthritis

1. DIPs
2. 90% nails; 15% skin
3. increased serum uric acid in 30% of cases due to cell turnover
4. HLA-B27 antigen present in patients with spondylitis-type psoriatic arthropathy (35% of cases)
5. negative serology for RF
6. ESR elevated in acute phase
7. may have anemia of chronic disease

J. Gouty arthritis

1. podagra: gout of MTP of great toe
2. increased serum uric acid levels although 7-8% of patients have uric acid levels within reference limits at the time of the first attack; not diagnostic (cardinal biochemical abnormality; ASA and vitamin C may lower uric acid to below reference values)
3. leukocytosis with left shift (acute attack)
4. increased ESR
5. joint fluid and tophi contain crystals of monosodium urate with are strongly negative birefringent on polarizing exam (crystals point N, W, E, S, blue or yellow)
6. uric acid crystals and amorphous urates in urinary sediment
7. uric acid stones in 15% of patients
8. low grade proteinuria in 20-80% of patients

K. Chondrocalcinosis; calcium pyrophosphate dihydrate (CPPD) crystal deposition disease; pseudogout

1. synovial fluid analysis: consistent with an inflammatory effusion; will reveal CPPD crystals engulfed in leukocytes or floating free; leukocytosis with predominantly neutrophils (80-90%); crystals are weakly positive birefringent
2. elevated ESR
3. leukocytosis with left shift
4. blood and urine findings can be normal
5. metabolic studies should always be obtained in patients under 50 and considered in the elderly to exclude an underlying cause (e.g., calcium, phosphorous, ALP, TSH, TT4, serum iron studies)

L. Septic arthritis

1. osteomyelitis of joint
2. aspiration of synovial fluid and search for organism by Gram stain and culture
3. leukocytosis with left shift (50-98% of patients)
4. increased ESR, but normal in 20%
5. positive joint fluid culture possibly
6. synovial fluid analysis: cloudy; >50,000/ul WBC/hpf; 90% PMNs; poor mucin clot; blood glucose less than 0.5; absence of crystals

M. Ankylosing spondylitis

1. often nocturnal recurrent back pain (get up to “walk off” back pain)
2. anemia of chronic disease in 30% of cases
3. increased ESR in 80% of patients (mild increase in most patients with active disease; correlates poorly with disease activity and prognosis)
4. increased CSF protein
5. negative RF and antinuclear antibodies
6. increased incidence of HLA-B27 antigen in 90-95% of whites and 50% in American blacks (not specific)

N. Lyme disease

1. erythema chronicum migrans (ECM) within couple days of being bit
2. ELISA is the best diagnostic test; determines titers of specific IgM and specific IgG antibodies to the I. dammini spirochete; levels of IgM antibody peak during 3-6 weeks after disease onset and then gradually decline
3. titers of specific IgG antibodies are generally low during the first several weeks of illness, reach maximal levels months later during arthritis, and often remain elevated for years; in the absence of ECM lesions, a single titer of specific IgM antibody may suggest the correct diagnosis; later in the illness, determination of specific IgG antibodies can separate Lyme disease from aseptic meningitis or unexplained cranial or peripheral nerve palsies
4. specific anti-spirochetal (Borrelia burgdorferi) antibodies in significant titer–first IgM, then IgG–appear within weeks of ECM; a titer of >1:80 is considered positive; if positive, it should be followed up by a Western blot test (very specific)
5. IgG titers are higher later in the illness when arthritis is present
6. ESR may be elevated
7. WBC is 25,000 to 90,000 and may include up to 95% PMNs
8. AST and LDH level may be slightly abnormal when ECM is present

O. Reactive arthritis

1. increased ESR
2. leukocytosis (10,000 to 20,000, increased PMNs)
3. hypergammaglobulinemia
4. nonbacterial cystitis, prostatitis, or seminal vesiculitis
5. 60-85% of white persons with reactive arthritis have HLA-B27
6. hematuria and pyuria
7. normochromic anemia (moderate)
8. cultures or serology positive for Chlamydia, or stools positive for salmonella, shigella, yersinia, or Campylobacter

P. Osteoporosis

1. CBC, multi-panel chemistry tests usually normal
2. ALP may be transiently elevated following fractures
3. normal serum calcium, phosphorus, ALP, protein ELP, ESR, urinary calcium
4. abnormal biochemical findings suggesting secondary osteoporosis

Q. Osteomalacia and rickets

1. serum calcium may be normal or decreased (never high)
2. hypophosphatemia
3. ALP is increased
4. decreased serum vitamin D and its metabolites
5. increased serum parathormone
6. urinary calcium is low in all forms of the disease except those associated with acidosis

II. Anemias

A. Beta thalassemia minor: Mild anemia; Slightly elevated RBC count; Elevated reticulocyte count (>3%); Mentzer index (MCV/RBC count) <13; Hemoglobin electrophoresis: elevated Hb A2, decreased Hb A and slightly increased Hb; Peripheral blood smear: hypochromic, microcytic RBCs, few target cells

B. Iron deficiency anemia: Decreased RBC, Hg, Hct; Decreased RBC indices; Increased RDW; Low serum ferritin; Decreased serum iron, % saturation; Increased transferrin; Peripheral blood smear: hypochromic, microcytic anemia; Mentzer index (MCV/RBC count) >13

C. Anemia of renal disease: Normochromic, normocytic anemia; Peripheral blood smear: burr cells

D. Iron­ reutilization anemia (anemia of chronic disease): Peripheral blood smear: hypochromic, microcytic anemia; Normal RDW; Decreased serum iron, transferrin; Transferrin saturation > 10%; Normal to slightly increased serum ferritin

E. Myelophthisic anemia: Peripheral blood smear: normochromic, normocytic anemia; Nucleated RBCs; Immature WBC’s; Polychromatophilia and reticulocytosis

F. Anemia due to vitamin B12 deficiency: Peripheral blood smear: macrocytic anemia, hypersegmentation of granular leukocytes; Leukopenia; Thrombocytopenia; Autoantibodies to gastric parietal cells and intrinsic factor; Elevated serum bilirubin; Decreased levels of serum vitamin B12

G. Beta thalassemia major: Severe anemia; Elevated RBC count; Increased serum bilirubin; Elevated serum iron and ferritin levels; Hemoglobin electrophoresis: elevated Hb F (>50%) and Hb A2, reduced or absent HbA; Peripheral blood smear: hypochromic, microcytic RBCs, prominent target cells

H. Hemolytic anemias: Reticulocyte count more than 5%; Lactate dehydrogenase (LDH­1) increased; Decreased serum haptoglobin; Positive Direct Coomb’s test; Elevated serum unconjugated bilirubin

I. Sickle cell anemia: Moderate to severe anemia; Serum bilirubin mildly elevated; Serum LDH elevated; Haptoglobin absent or very low; Reticulocytosis; Decreased ESR; “Sickledex” test positive; Hb electrophoresis: Sickle cell anemia: 80–100% Hb S, variable amounts of Hb F and no Hb A. Sickle cell trait: 20–40% Hb S, 60–80% Hb A1, minimal Hb F; Peripheral blood smear: sickled cells

J. Iron utilization anemia [sideroblastic anemia (SA)]: High RDW; Peripheral blood smear: hypochromic, microcytic anemia, siderocytes; Low reticulocyte count; Increased ferritin; Increased serum iron; Increased transferrin saturation; increased Ringed sideroblasts in BM

K. Glucose­6­phosphate dehydrogenase defect: Moderate anemia; Increased bilirubin; Peripheral blood smear:”bite” cells

L. Anemia due to hypothyroidism: Peripheral blood smear: normochromic, normocytic anemia; Peripheral blood smear: hypochromic, microcytic anemia; Peripheral blood smear: macrocytic anemia

M. Anemia due to folic acid deficiency: Peripheral blood smear: macrocytic anemia, hypersegmentation of granular leukocytes; Serum folic acid levels <5 ng/ml; Low RBC folate levels; Normal B12 levels

N. Hereditary spherocytosis: Mild to moderate anemia; Elevated reticulocyte counts; Increased MCHC; Increased osmotic fragility of RBCs; Increased serum bilirubin; Peripheral blood: spherocytes

O. Aplastic anemia: Severe pancytopenia; Peripheral blood smear: normochromic, normocytic anemia; Leukopenia; Thrombocytopenia; Decreased reticulocytes

Urinalysis 

• Physical Examination / PE: 
  • Color: 
    • Normal: Yellow
    • Abnormal: 
      • Reddish Amber: Urobilinogen 
      • Milky: Pus, Bacteria, Fat 
      • Green/Brownish-Yellow: Bile 
      • Coke Colored/Red-Brown: AGN 
      • Yellow Foam: Bilirubin 
      • White Foam: Albumin 
  • Clarity: 
    • Normal: Clear 
    • Abnormal: Turbid
  • Odor: 
    • Normal: Aromatic 
    • Abnormal: 
      • Ammoniacal: Old
      • Fruity: Diabetes
      • Stale Water: Acute Tubular Injury Foul: UTI 
• Dipstick Reagent Strip: 
  • Specific Gravity: 
    • Measure of dissolved Subst. in urine 
    • Normal: 1.003 – 1.030 
    • Fixed: 1.010 
  • pH: Normal: 4.5 – 8
  • The rest: Should be Negative except Urobilinogen is “normal”
  • Protein: Mostly indicative of Renal Disease
    • Functional Proteinuria: No systemic/renal damage—Exercise, Prego, Cold, Diet
    • Organic Proteinuria: Systemic/renal damage: 
      • Prerenal: Fever, Myxedema, Hypertension
      • Renal: Glomerulonephritis, Nephrotic Syndrome
      • Postrenal: Ureter infection, Cystitis, Urethritis, Prostatitis 
  • Glucose: 
    • Never should be in urine…Glucosuria=DM! 
    • Renal Threshold=180mg/100ml serum glucose 
  • Ketone: 
    • Seen w/ Inc Fat Metabolism—Indicates DM! 
    • Also: Starvation, Alcoholic, Prego 
  • Blood: Bleeding in Urinary tract
  • Leukocyte Esterase: Inflammation
  • Nitrite: Gram-Negative Bacteria 
  • Bilirubin: Liver Disease or Biliary Tract Obstruction
  • Urobilinogen: Usually there is a SM amount…LG amount=Liver Dysfunction or Anemia
• Microscopic Exam: 
  • RBC: Normal: 0-2
    • High=AGN 
  • WBC: Normal: 0-5
    • Renal Origin seen w/ Proteinuria 
    • UTI seen w/ Bacteriuria 
  • Epithelial Cells: Contamination 
  • Hyaline Cast: Normal: 0-2 (occasional) 
  • Waxy Cast: Endstage Kidney Disease 
  • RBC Cast: AGN 
  • WBC Cast: Acute Pyelonephritis 
  • Fatty Cast: Nephrotic Syndrome 
  • RBC, WBC, & Fatty Casts Always Significant!! 
  • Crystals: 
    • Non-pathologic: Uric Acid, Calcium Oxalate, Amorphous Urate, Phosphates 
    • Pathologic: Sulfonamides, Cystine, Leucine, Tyrosine, Cholesterol 

CBC 

• Hb: detects Anemia (Dec.) or Erythrocytosis (Inc.) 
  • Normal: 
    • Women = 14 +/-2 g/dl 
    • Men = 16 +/-2 g/dl 
  • Anemic: 
    • Women = <11 g/dl 
    • Men = <13 g/dl 
• Total RBC: Dec. in Anemia, Inc. inErythrocytosis, Polycythemia Vera(PV), & Dehydration 
  • Normal: 
    • Women = 3.5 – 5.5 million/ul 
    • Men = 4.3 – 5.9 million/ul 
• Hct: Ratio of spun RBCs to Plasma. (Hb x 3 = Hct ) 
  • Dec=Anemia, Inc=Erythrocytosis 
  • Normal: Women = 37 – 47% 
  • Men = 40 – 54% 
• WBC Count:
  • Dec WBC=Leukopenia = viral infection. 
  • Inc WBC=Leukocytosis = bacterial infection. 
  • Normal: 4,500 – 11,000 / ul 
• Platelets: 
  • Dec=Thrombocytopenia <70,000 = Evident Bleeding Tendency.
  • Inc=Thrombocythemia = Malignancy. 
  • Normal: 150,000 – 400,000 /cu mm 
• RBC Indices: 
  • MCV: RBC Volume/Size 
    • 2nd thing that goes wrong is the MCV
    • Normal: 80 – 100 fl 
    • Macrocytosis: 
      • Folate/B12 Def. 
      • Chronic Liver Dis. 
      • Chronic Alcoholism 
      • Reticulocytosis 
      • Myxedema 
    • Microcytosis: 
      • Chronic Iron Def. 
      • Alpha or Beta Thalassemia 
      • Anemia of Chronic Disease 
      • Sideroblastic Anemia 
  • MCH: Weight 
    • Inc.= Macrocytic anemias 
    • Dec.= Microcytic anemias
    • Normal: 27 – 33 pg 
  • MPV: Platelet Size 
    • Normal: 7.8-11.0 fL 
  • MCHC: Color 
    • Normal: 32 – 36 g/dl 
    • Hyperchromasia: 
      • Spherocytosis 
      • Severe Plasma Lipidemia 
      • Heavy Smoking 
    • Hypochromasia: 
      • Chronic Iron Def. 
      • Anemia of Chronic Disease 
      • Sideroblastic Anemia 
    • RDW: Size (can only INCREASE) 
      • Says RBC’s are the wrong size
      • 1st thing that goes wrong 
      • Normal: 11 – 15% 

ESR 

• Not a good screening test, due to low sensitivity
• Children: 3 – 13 mm/hr
• Women: 
  • Up to 40 y/o: 1 – 20 mm/hr 
  • Maximum Normal= (Age + 10) / 2
• Men: 
  • Up to 40 y/o: 1 – 15 mm/hr 
  • Maximum Normal= Age / 2
• 0-50 mm/hr=NBD 
• 50-100 mm/hr=Do Follow-up Tests 
• >100mm/hr=Significant! 

CRP 

• C-Reactive Protein Test
• Most Sensitive test for Acute Inflammation! (better than ESR) 

Peripheral Blood Smear & WBC Differential 

• Anisocytosis: Variation in Size ie: Macrocytes vs Microcytes
• Poikilocytosis: Variation in Shape ie: Spherocytes, Schistocytes, Acanthocytes, Sickle cells 
  • Rouleaux= Multiple Myeloma
  • Zeta Potential= RBC’s have –charge so they repel e/o 
• Neutrophils: 50 – 70% 
  • Neutrophilic Leukocytosis / Neutrophilia = bacterial infection. 
  • Neutrophilic Leukopenia = viral infection
• Lymphocytes: 20 – 40% 
  • Lymphocytosis = viral infection 
  • Lymphocytopenia = immunodeficiency / immunosuppressive syndromes (ie; AIDS) 
• Monocytes: 2 – 10% 
  • Monocytosis = recovering from infection 
• Eosinophils: 1 – 5% 
  • Eosinophilia = Allergies or Parasites 
• Basophils: 0 – 1% 
  • Basophilia = PV, Leukemia, Myxedema 
• Reticulocytes: .5 – 1.5% 
  • Immature RBCs w/o nuclei (marrow is working hard to crank out RBCs) 
  • Reticulocytosis=Inc Reticulocyts—3 most common causes: 
    • Post- B12 / Folate / Iron Deficiency Treatment (inc RBC prod)
    • Hemolytic anemia
    • Acute bleeding (where loads of RBCs are being destroyed) 
• Plasma Cells: Marrow cells that make antibodies
  • Should never be in blood!!! 
  • Multiple Myeloma!!!!!!! 

Leukemia, Lymphomas, & Myeloproliferative Syndromes Pathognomonic Differentials 

• Hodgkin Lymphoma = “Bad cervical nodes, weird fever” 
  • Reed Sternberg cells (binucleated) 
  • Men get it 4:1
  • Age=bimodal—15-34 y/o & over 54 y/o 
  • Alcohol induced Px 
  • Pel-Ebstein fever (Alternating temps for several days) —Ebstein Barr Virus= risk factor 
  • Night sweats & weight loss
  • Triad: 
    • Fever of unknown origin
    • Pruritis (the desire to itch)
    • Lymphadenopathy (cervical region) 
• Erythrocytosis: Primary, Secondary, & Relative 
  • Primary= Polycythemia Vera = Stem cell cancer / “many cells in the bl” 
    • Increase in ALL CELLS (RBCs, WBCs, Platelets)
    • Decreased Erythropoietin
    • Erythromelalgia (Burning px in hands & feet)–Rule out DM 1^st
    • Facial Plethora 
    • Splenomegaly, Hepatomegaly (Organomagaly)
    • Risk: Men>Women, 60y/o, Jewish Ancestry
    • Chem Panel: Hyperuricemia & Hypercholesterolemia
  • Secondary Erythrocytosis: Oxygen levels drop 
    • ONLY RBC’s Increase—Not WBC’s & Platelets!!! 
    • Causes: High Altitude, Smoking, & Hormones 
  • Relative Erythrocytosis: 
    • Normal RBC’s, but appears increased due to a Decreased Plasma Volume 
    • Dehydration 
• Acute Lymphoblastic Leukemia = Most common CHILDHOOD cancer 
  • Blast Cells 
  • Increase in Lymphoblasts
  • Decrease RBCs, platelets
  • Bleeding! & Easy Bruising! (petechia, bruising, etc) 
  • Bone & joint Px 
• Acute Myeloid Leukemia (AML) = 2nd most common in ADULTS 
  • Blast Cells 
  • Increased myeloblasts w/ Auer Rods
  • Decreased RBCs, Neutrophils, and Platelets
  • Elevated ESR
  • History of Fatigue, Bleeding, & Difficulty clearing Infections 
• Chronic Lymphocytic Leukemia (CLL) = Most common in ELDERLY 
  • Mature Cells 
  • B-Cell Absolute Lymphocytosis (>5,000)
  • Smudge Cells (Ruptured Lymphocytes) 
• Chronic Myelogenous Leukemia (CML) = Most common in 50-60 y/o 
  • Mature Cells 
  • Increased Granulocytes in all developmental stages 
  • Increased WBCs, basophils, eosinophils (Giant WBC count!)
  • Philadelphia Chromosomes
  • Hepatomegaly and MASSIVE Splenomegaly 
• Infectious Mononucleosis (IM): 
  • MC= 10-19 y/o 
  • Spread by Oral-Respiratory Route 
  • 80% due to Epstein-Barr Virus (EBV) 
  • 20% due to Cytomegalovirus (CMV)
  • Worst Sore Throat in patient’s life!
  • SSX: Lymphadenopathy, Pharyngitis, Fever, and Splenomegaly
  • CBC: 
    • WBC Inc. (Exception to Virus rule) 
    • Lymphocytosis 
    • Monocytosis
  • Special Tests: Heterophil antibody test & EBV titer (IgM & IgG antibodies at 3-4 Wks) 
• Acute Rheumatic Fever (ARF): 
  • MC=Children 5-15 y/o 
  • Autoimmune Disease 
  • Requires Group A Streptococcus Infection 1st
  • Clinical Findings: 
    • Arthritis 
    • Carditis 
    • Erythema Marginatum 
    • Subcutaneous Nodules 
    • Chorea
  • Lab Findings: 
    • Antistreptolysin O (ASO)- Shows evidence of Group A Strep Infection 
    • Anemia 
    • Leukocytosis (12,000-20,000 uL) 
• Systemic Lupus Erythematosus (SLE): 
  • MC=Female 30-50 y/o 
  • Autoimmune Disease 
  • Clinical Findings: 
    • Malar “Butterfly” Erythema 
    • Alopecia(Balding) 
    • Photosensitivity 
  • Lab Findings: 
    • Immunological Tests: 
      • Positive Antinuclear Antibody (ANA) –15% false positives
      • Positive Anti-Double Stranded DNA (dsDNA)—Clarifies false positives of ANA
    • Non- Immunological Tests: 
      • CBC: 
        • Normocytic Anemia 
        • Leukopenia 
        • Thrombocytopenia (Decreased RBC’s, WBC’s, and Platelets) 

If RBC’s, WBC’s, & Platelets all go Down…Think Autoimmune Disease!!! 

Source of these notes are attributed to Dr. Linda Bowers, DC, DABCI, DABCO, DACAN, DACBN.