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INTERPRETATION OF
LABORATORY TESTS
CRP
TUMOR MARKERS
SERUM FERRITIN
Dr. Jyothi Reshma S
C-reactive protein
• Acute phase reactant - liver
• Binding to C polysaccharide of Pneumococcus
• Tillet and Francis 1930
• Pentraxin – 23kDa
• T ½ 19hours
• Raised in infections, inflammatory disorders
and malignancies
Activation of complement – classical pathway IL6, IL1, TNFα
Helps in opsonisation
Glucocorticoids ++
Insulin --
• Normal < 0.3mg/dL
• Clinically significant >1mg/dL
• <1 : increasing age, low level of physical
activity, vigorous exercise, obesity, pregnancy,
sleep deprivation, depression, insulin
resistance, DM, seizures
INFECTIONS MALIGNANCY
• High at onset: bacterial
• Rise on day 3-4:
superimposed bacterial
infection
• Elevated in systemic
fungal infection –
immunocompromised
• Marker of sepsis –
300mg/dL
• Ca lung, liver, skin, kidney,
bladder, lymphoma,
leukaemia
• Tumor necrosis and local
tissue damage ++ CRP
• Opsonization and removal
of tumor cells
Inflammatory disorders
• Evaluation- extent or severity of inflammation
• Monitoring- disease activity
• Prognostic value
• RA: 2-3 (moderate)to >10 (severe) – synovitis, erosions,
normal in 40%
• SLE: serositis, synovitis ++
• PMR, GCA: CRP > ESR, GCA with vison loss - CRP
• Still’s disease, vasculitis, ankylosing spondylitis, erosive
OA, gout, reactive arthritis, sarcoidosis, scleroderma, PsA
• Inflammatory bowel disease: CD(70-100%) UC(50-60%)
• Patients with ++ CRP respond better to biological therapy
Cardiovascular disease
• Proatherogenic- binds to LDL-C- monocyte adhesion,
transmigration, macrophage polarization
• 2013 guidelines- ACC and AHA: hs-CRP : statin therapy
• 1) 40-75yr, nonDM, without clinical ASCVD, LDL C 70-
189mg/dL, 5 year risk of ASCVD <5%: hsCRP ≥2- statin COR
IIb, LOE C
• 2) <40/>75yr, nonDM, without clinical ASCVD, LDL C 70-
189mg/dL, hsCRP ≥2- statin COR ILb, LOE C
• 3) DM without clinical ASCVD, <40/>75yr, LDL C <70mg/dL,
hsCRP ≥2- statin COR ILb, LOE C
ASCVD: atherosclerotic cardiovascular disease COR: class of recommendation LOE:level of evidence
• CRP: 0.7 – 0.9: 22 wk till delivery, 1.3: onset of
labor
• Higher levels – 1st TM, early 2nd TM: preterm
delivery
TUMOR MARKERS
Biomolecules secreted by cancer cells – diagnosis,
treatment response, early recognition of recurrence
Oncofetal antigens: AFP, CEA
Tumor associated antigen: CA125, CA 19-9, CA 15-3,
CA72-4
Hormones: beta-HCG, PSA, calcitonin
Enzymes: LDH, PAP, NSE, PLAP, TDT
Serum and tissue proteins: beta-2 microglobulin, GFAP,
ferritin, FDP
AFP (Alpha-feto protein)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Liver, germ cell cancer
of ovaries or testes
• Also elevated during
pregnancy
• Help diagnose, monitor
treatment, and
determine recurrence
• Blood
B2M (Beta-2 microglobulin)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Multiple myeloma
and lymphomas
• Crohn's disease and
hepatitis
• Determine prognosis
• Blood
CA 15-3 (Cancer antigen 15-3)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Breast cancer and lung,
ovarian
• Also elevated in benign
breast conditions
• Stage disease, monitor
treatment, and
determine recurrence
• Blood
CA 19-9 (Cancer antigen 19-9)
• CANCERS
• WHAT ELSE?
WHEN/HOW USED
USUAL SAMPLE
• Pancreatic, sometimes
colorectal and bileducts
• Pancreatitis and
inflammatory bowel
disease
• Stage disease, monitor
treatment, and
determine recurrence
• Blood
CA-125 (Cancer antigen 125)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Ovarian
• endometriosis, some
other benign diseases
• Help diagnose, monitor
treatment, and
determine recurrence
• Blood
Calcitonin
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Thyroid medullary
carcinoma
• pernicious anemia and
thyroiditis
• Help diagnose, monitor
treatment, and
determine recurrence
• Blood
CEA (Carcino-embryonic antigen
• CANCERS
WHAT ELSE?
WHEN/HOW USED
• USUAL SAMPLE
• Colorectal, lung,
breast, thyroid,
pancreatic, liver, cervix,
and bladder
• hepatitis, COPD, colitis,
pancreatitis, and in
cigarette smokers
• Monitor treatment and
determine recurrence
• Blood
Chromogranin A (CgA)
• CANCERS
WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Neuroendocrine tumors
(carcinoid tumors,
neuroblastoma)
• May be most sensitive
tumor marker for
carcinoid tumors
• To help diagnose and
monitor
• Blood
Estrogen receptors
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Breast
• Increased in hormone-
dependent cancer
• Determine prognosis
and guide treatment
• tissue
hCG (Human chorionic
gonadotropin)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Testicular and
trophoblastic disease
• Elevated in pregnancy,
testicular failure
• Help diagnose, monitor
treatment, and
determine recurrence
• Blood, urine
Her-2/neu
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Breast
• Oncogene that is
present in multiple
copies in 20-30% of
invasive breast cancer
• Determine prognosis
and guide treatment
• Tissue
Monoclonal immunoglobulins
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Multiple myeloma and
Waldenstrom’s
macroglobulinemia
• Overproduction of an
immunoglobulin or
antibody, usually
detected by protein
electrophoresis
• Help diagnose,
monitor treatment, and
determine recurrence
• Blood, urine
Progesterone receptors
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Breast
• Increased in hormone-
dependent cancer
• Determine prognosis
and guide treatment
• Tissue
PSA (Prostate specific antigen), total
and free
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Prostate
• benign prostatic
hyperplasia, prostatitis
and with age
• Screen for and help
diagnose, monitor
treatment, and
determine recurrence
• Blood
Thyroglobulin
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Thyroid
• Used after thyroid is
removed to evaluate
treatment
• Determine recurrence
• Blood
BTA (Bladder tumor antigen)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Bladder
• Not widely available,
but gaining acceptance
• Help diagnose and
determine recurrence
• Urine
CA 72-4 (Cancer antigen 72-4)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Ovarian
• No evidence that it is
better than CA-125 but
may be useful when
combined with it; still
being studied
• Help diagnose
• Blood
Des-gamma-carboxy prothrombin
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Hepatocellular
carcinoma (HCC)
• New test; often used
along with an imaging
study plus AFP and/or
AFP-L3% to evaluate if
someone with
• To evaluate risk of
developing HCC; to
evaluate treatment; to
• Blood
NMP22 (nuclear matrix protein)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Bladder
• Not widely used
• Help diagnose and
determine recurrence
• Urine
Prostate-specific membrane antigen
(PSMA)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Prostate
• Not widely used; levels
increase normally with
age
• Help diagnose
• Blood
Prostatic acid phosphatase (PAP)
• CANCERS
• WHAT ELSE?
• WHEN/HOW USED
• USUAL SAMPLE
• Metastatic prostate
cancer, myeloma, lung
cancer
• Not widely used
anymore; elevated in
prostatitis and other
conditions
• Help diagnose
• Blood
SERUM FERRITIN
• Ferritin – iron storage protein
• Iron sequestration – ferroxidase- Fe2+ to Fe3+
• Ferritin captures and buffers intracellular iron
pool
• Normal – 50-200µg/L
• Low- <12 – iron depletion
• Elevated : iron overload, acute inflammatory
conditions, liver disease, alcohol excess
• Iron overload: primary: hemochromatosis,
wilson’s disease ; secondary: transfusion
overload, excess dietary iron, PCT, ineffective
erythropoiesis
High serum ferritin without iron
overload
Liver disease (NASH), viral hepatitis
Alcohol excess, chronic inflammatory conditions
(RA/IBD)
Bacterial infections, malignancy
Thyrotoxicosis
Familial hyperferritinemia and cataract
syndrome
• Acute phase reactant : inflammatory
conditions
• ++ : increaded risk of MI and CAD
• Prognostic marker : allogenic stem cell implant
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Interpretation of lab tests - CRP, TUMOR MARKERS, SERUM FERRITIN

  • 1. INTERPRETATION OF LABORATORY TESTS CRP TUMOR MARKERS SERUM FERRITIN Dr. Jyothi Reshma S
  • 2. C-reactive protein • Acute phase reactant - liver • Binding to C polysaccharide of Pneumococcus • Tillet and Francis 1930 • Pentraxin – 23kDa • T ½ 19hours • Raised in infections, inflammatory disorders and malignancies
  • 3. Activation of complement – classical pathway IL6, IL1, TNFα Helps in opsonisation Glucocorticoids ++ Insulin --
  • 4. • Normal < 0.3mg/dL • Clinically significant >1mg/dL • <1 : increasing age, low level of physical activity, vigorous exercise, obesity, pregnancy, sleep deprivation, depression, insulin resistance, DM, seizures
  • 5. INFECTIONS MALIGNANCY • High at onset: bacterial • Rise on day 3-4: superimposed bacterial infection • Elevated in systemic fungal infection – immunocompromised • Marker of sepsis – 300mg/dL • Ca lung, liver, skin, kidney, bladder, lymphoma, leukaemia • Tumor necrosis and local tissue damage ++ CRP • Opsonization and removal of tumor cells
  • 6. Inflammatory disorders • Evaluation- extent or severity of inflammation • Monitoring- disease activity • Prognostic value • RA: 2-3 (moderate)to >10 (severe) – synovitis, erosions, normal in 40% • SLE: serositis, synovitis ++ • PMR, GCA: CRP > ESR, GCA with vison loss - CRP • Still’s disease, vasculitis, ankylosing spondylitis, erosive OA, gout, reactive arthritis, sarcoidosis, scleroderma, PsA • Inflammatory bowel disease: CD(70-100%) UC(50-60%) • Patients with ++ CRP respond better to biological therapy
  • 7. Cardiovascular disease • Proatherogenic- binds to LDL-C- monocyte adhesion, transmigration, macrophage polarization • 2013 guidelines- ACC and AHA: hs-CRP : statin therapy • 1) 40-75yr, nonDM, without clinical ASCVD, LDL C 70- 189mg/dL, 5 year risk of ASCVD <5%: hsCRP ≥2- statin COR IIb, LOE C • 2) <40/>75yr, nonDM, without clinical ASCVD, LDL C 70- 189mg/dL, hsCRP ≥2- statin COR ILb, LOE C • 3) DM without clinical ASCVD, <40/>75yr, LDL C <70mg/dL, hsCRP ≥2- statin COR ILb, LOE C ASCVD: atherosclerotic cardiovascular disease COR: class of recommendation LOE:level of evidence
  • 8. • CRP: 0.7 – 0.9: 22 wk till delivery, 1.3: onset of labor • Higher levels – 1st TM, early 2nd TM: preterm delivery
  • 9. TUMOR MARKERS Biomolecules secreted by cancer cells – diagnosis, treatment response, early recognition of recurrence Oncofetal antigens: AFP, CEA Tumor associated antigen: CA125, CA 19-9, CA 15-3, CA72-4 Hormones: beta-HCG, PSA, calcitonin Enzymes: LDH, PAP, NSE, PLAP, TDT Serum and tissue proteins: beta-2 microglobulin, GFAP, ferritin, FDP
  • 10. AFP (Alpha-feto protein) • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Liver, germ cell cancer of ovaries or testes • Also elevated during pregnancy • Help diagnose, monitor treatment, and determine recurrence • Blood
  • 11. B2M (Beta-2 microglobulin) • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Multiple myeloma and lymphomas • Crohn's disease and hepatitis • Determine prognosis • Blood
  • 12. CA 15-3 (Cancer antigen 15-3) • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Breast cancer and lung, ovarian • Also elevated in benign breast conditions • Stage disease, monitor treatment, and determine recurrence • Blood
  • 13. CA 19-9 (Cancer antigen 19-9) • CANCERS • WHAT ELSE? WHEN/HOW USED USUAL SAMPLE • Pancreatic, sometimes colorectal and bileducts • Pancreatitis and inflammatory bowel disease • Stage disease, monitor treatment, and determine recurrence • Blood
  • 14. CA-125 (Cancer antigen 125) • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Ovarian • endometriosis, some other benign diseases • Help diagnose, monitor treatment, and determine recurrence • Blood
  • 15. Calcitonin • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Thyroid medullary carcinoma • pernicious anemia and thyroiditis • Help diagnose, monitor treatment, and determine recurrence • Blood
  • 16. CEA (Carcino-embryonic antigen • CANCERS WHAT ELSE? WHEN/HOW USED • USUAL SAMPLE • Colorectal, lung, breast, thyroid, pancreatic, liver, cervix, and bladder • hepatitis, COPD, colitis, pancreatitis, and in cigarette smokers • Monitor treatment and determine recurrence • Blood
  • 17. Chromogranin A (CgA) • CANCERS WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Neuroendocrine tumors (carcinoid tumors, neuroblastoma) • May be most sensitive tumor marker for carcinoid tumors • To help diagnose and monitor • Blood
  • 18. Estrogen receptors • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Breast • Increased in hormone- dependent cancer • Determine prognosis and guide treatment • tissue
  • 19. hCG (Human chorionic gonadotropin) • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Testicular and trophoblastic disease • Elevated in pregnancy, testicular failure • Help diagnose, monitor treatment, and determine recurrence • Blood, urine
  • 20. Her-2/neu • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Breast • Oncogene that is present in multiple copies in 20-30% of invasive breast cancer • Determine prognosis and guide treatment • Tissue
  • 21. Monoclonal immunoglobulins • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Multiple myeloma and Waldenstrom’s macroglobulinemia • Overproduction of an immunoglobulin or antibody, usually detected by protein electrophoresis • Help diagnose, monitor treatment, and determine recurrence • Blood, urine
  • 22. Progesterone receptors • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Breast • Increased in hormone- dependent cancer • Determine prognosis and guide treatment • Tissue
  • 23. PSA (Prostate specific antigen), total and free • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Prostate • benign prostatic hyperplasia, prostatitis and with age • Screen for and help diagnose, monitor treatment, and determine recurrence • Blood
  • 24. Thyroglobulin • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Thyroid • Used after thyroid is removed to evaluate treatment • Determine recurrence • Blood
  • 25. BTA (Bladder tumor antigen) • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Bladder • Not widely available, but gaining acceptance • Help diagnose and determine recurrence • Urine
  • 26. CA 72-4 (Cancer antigen 72-4) • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Ovarian • No evidence that it is better than CA-125 but may be useful when combined with it; still being studied • Help diagnose • Blood
  • 27. Des-gamma-carboxy prothrombin • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Hepatocellular carcinoma (HCC) • New test; often used along with an imaging study plus AFP and/or AFP-L3% to evaluate if someone with • To evaluate risk of developing HCC; to evaluate treatment; to • Blood
  • 28. NMP22 (nuclear matrix protein) • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Bladder • Not widely used • Help diagnose and determine recurrence • Urine
  • 29. Prostate-specific membrane antigen (PSMA) • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Prostate • Not widely used; levels increase normally with age • Help diagnose • Blood
  • 30. Prostatic acid phosphatase (PAP) • CANCERS • WHAT ELSE? • WHEN/HOW USED • USUAL SAMPLE • Metastatic prostate cancer, myeloma, lung cancer • Not widely used anymore; elevated in prostatitis and other conditions • Help diagnose • Blood
  • 31. SERUM FERRITIN • Ferritin – iron storage protein • Iron sequestration – ferroxidase- Fe2+ to Fe3+ • Ferritin captures and buffers intracellular iron pool • Normal – 50-200µg/L
  • 32. • Low- <12 – iron depletion • Elevated : iron overload, acute inflammatory conditions, liver disease, alcohol excess • Iron overload: primary: hemochromatosis, wilson’s disease ; secondary: transfusion overload, excess dietary iron, PCT, ineffective erythropoiesis
  • 33. High serum ferritin without iron overload Liver disease (NASH), viral hepatitis Alcohol excess, chronic inflammatory conditions (RA/IBD) Bacterial infections, malignancy Thyrotoxicosis Familial hyperferritinemia and cataract syndrome
  • 34. • Acute phase reactant : inflammatory conditions • ++ : increaded risk of MI and CAD • Prognostic marker : allogenic stem cell implant