abnormal cbc ohsu...•visceral larva migrans ohsu •tropical pulmonary eosinophilia eosinophilia:...
TRANSCRIPT
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Abnormal CBC
Tom DeLoughery, MD MACP FAWMOregon Health and Sciences University
OHSU
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Abnormal CBC
• What I look at in a CBC
• Approach to specific
abnormalitiesOHSU
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What I look at in a CBC
• Hct
• MCV
• MCHC
• Plts
• WBC
• Diff - # not %!
OHSU
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MCV• < 70 fl
–Either thalassemia or iron
deficiency
• > 100 fl but not anemic
–Alcohol
–Smoking
–Dysproteinemia
–Normal variant
OHSU
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Microcytosis
• Iron Deficiency
• Thalassemia
• Anemia of chronic disease
–Rarely < 70fl
• Sideroblastic
–Rare
OHSU
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Meltzer Index
• MCV/RBC
• > 13 – Iron deficiency
• < 13 – ThalasemmiaOHSU
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MCHC• Mean Corpuscular Hemoglobin
–Moves with MCV
• > 36 can be a sign of hereditary
spherocytosisOHSU
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Differential
• Absolute counts not percent that
matters.OHSU
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Anemia
• My approach
OHSU
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Work-Up: I• Reticulocyte Count
• Smear Review
• Nutritional
–Ferritin
–Methylmalonic acid
–Homocystine
–Copper
• Neutropenia
• Sensory deficits/ataxia
OHSU
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Ferritin: Bottom Line• Ignore lab reference ranges!
• < 15 ng/ml 100% specific
• > 100 ng/ml rules-out
• In older patients ferritins
< 100ng/ml consider GI work-up
• Iron supplementation to women
with ferritins < 50ng/ml improves
fatigue
OHSU
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Work-Up II
• ACD/Renal
–Erythropoietin Level
–CMP
• Hemolysis
–Reticulocyte count
–LDH
–Bilirubin – total and direct
–Direct antibody test
–Haptoglobin
OHSU
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Work-Up III
• SPEP/Serum Free Light Chains
–Older patient
–Back pain
–New onset renal disease
–Severe anemia
OHSU
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When to Do a Bone Marrow?
• Circulating immature cells
• Severe pancytopenia
• Very low reticulocyte count (<0.01%)
• Nucleated red cells
• Evidence of marrow infiltration
• Staging of malignancies
• Unexplained anemias
OHSU
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Erythrocytosis• Hemoglobin > Men: 18.5 (16.5) or
Women 16.5 (16)
• High hematocrit and other blood
counts up
• Big question – Polycythemia
vera vs other causes
OHSU
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Differential Diagnosis• Polycythemia vera
• Hypoxia
–Lung disease
–High altitude
–Sleep apnea (nocturnal
desaturation)
• Impaired oxygen delivery
–Smoking
• > 1 PPD -> Hbg by 1
OHSU
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Testosterone
• Increased sensitivty to EPO
• Onset months
–Can take several months to
resolved
• Phlebotomy with hct >54%
• Space out injections
• Transdermal
OHSU
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Other Important Causes
• Renal
–Cancer
–Big renal cysts
–Renal artery stenosis
• Hepatic
–Hepatomas
–Hepatitis
• Endocrine Tumors
OHSU
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Genetic Causes
• Abnormal Hemoglobins
– Impaired oxygen delivery
–Most common
• EPO-R mutations
• HIF pathways
OHSU
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Work-up I• Suspicion for PRV increases if
–Other counts elevated
–Splenomegaly
–Aquagenic pruritus
• JAK2 mutation assay
–Abnormal in 99% of PRV
–Diagnostic test
OHSU
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Work-Up II• Erythropoietin levels
–PRV if below normal
• Oxygen saturation
• Sleep Studies
• Carboxyhemoglobin
• Renal/Liver imaging
• Hemoglobin electrophoresis
• P50 studies (Mayo Clinic)
OHSU
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Therapy• PRV
–Phlebotomy
–Hydroxyurea
–Ruxolitinib
• Secondary
–Congenital cardiac – NO!
–Lung disease hct > 57
–Oxygen, CPAP, …
OHSU
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Neutrophilia
• Neutrophils > 10,000/ul
• Red Flags
– Immature forms (blasts)
–> 20,000/ulOHSU
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http://www.mog-eg.com/apps/photos/photo?photoid=38256199
OHSU
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Neutrophilia - DDX
• Neoplastic
–Acute myelogenous leukemia
• Blasts
–Chronic myelogenous leukemia
• Immature cells
–Chronic neutrophilic leukemia
• High neutrophils counts
OHSU
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Neutrophilia - DDX• Infections
• Rheumatic conditions
• Obesity
–Adipose cells make growth factors
• Smoking
–Doubles WBC
• Pregnancy
• Steroids
–Cushings
OHSU
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Leukemoid Reactions
• Very high blood counts (up to
100,000)
–Predominantly neutrophil
• Chronic infections
• Bad C diff
• Solid tumors
OHSU
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OHSU
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Neutrophilia - Evaluation
• History/physical
–Smoking/obestiy
• Testing – rule out neoplasm
• CML – obtain FISH for BCR-ABL
• Other counts up – JAK2
• Bone Marrow if > 20,000/ul
OHSU
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http://www.bwhct.nhs.uk/genetics-index/reglab_oncology.htm
OHSU
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Neutropenia
• Mild Neutropenia is very common!
• Concern
–ANC < 1000
• Really concerned
–ANC < 500
OHSU
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Ann Intern
Med April 3,
2007
146:486-492
OHSU
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Neutropenia• Ethnic
–800-1000
–Lack of Duffy blood group
• SSRI
–Mild neutropenia
• Copper deficiency
–Usually anemic
–Sensory neurologic defects
OHSU
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Drugs• Antiseizure medications
–Dilantin
• Nonsteroidal Anti-inflammatory
• Vancomycin
• Penicillins
• TMP-SMZ
• Anti-Thyroid
OHSU
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Neutropenia
• “Benign”
–ANC < 500
–Responds to infections
• NK/T-Suppresser cell leukemia
• Hairy cell Leukemia
• Felty’s syndrome
OHSU
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Neutropenia - Evaluation
• Sudden and sick
–Admit
–Stop new medications
–Prophylactic antibiotics
–Growth factors
OHSU
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Neutropenia - Evaluation
• History
• < 1000/ul
–Flow cytometry for abnormal
lymphocytes
–Anti-granulocyte antibodies
• Copper levels
• Evaluation for other rheumatoid
disorders
• Duffy blood group
OHSU
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Therapy
• Immune
– Immunosuppression
• Hairy cell
–Chemotherapy
• Benign - nothingOHSU
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OHSU
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Eosinophilia
• Very common issue
• Almost always secondary to
other process
• Hypereosinophilia syndrome
rare but interesting disease
OHSU
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Causes of
Hypereosinophilia
• Neoplastic
• Allergic/Asthma
• Addison
• Collagen Vascular
• Parasites
OHSU
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Neoplastic
• Hodgkin disease classic
• Solid tumors (lung, pancreas,
colon, GYN)
• Lymphoma
• Hyper Eosinophilic Syndrome
(HES)
OHSU
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What is HES?
• Eosinophil count > 1500/uL
–6 months*
• End organ damage
–Heart
–Neurological
–Skin
–GI
• No other obvious cause
OHSU
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Allergic
• Seasonal allergies
• Asthma
• Drug allergiesOHSU
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Addison
• Lack of endogenous steroids
OHSU
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Collagen Vascular
• Churg-Strauss
–Pulmonary involvement
• Any VasculitisOHSU
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Parasites
• Any tissue invasive parasite
• Toxocara – dog and cat poop
• Strongyloides – can reoccur
after many years
• Trichinella – why we need to
cook our pork!
OHSU
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DDX of Eosinophilia by Eos
Counts
OHSU
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500-1,000/uL
• Endocrine disorders
• Allergies
• Dermatologic disorders
• Solid tumors OHSU
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1,000-5,000/uL
• Asthma
• Aspirin allergies
• Parasites
• Vasculitis
• HES
OHSU
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5,000-50,000/uL
• Churg-Strauss
• Hypereosinophilic syndrome
• Visceral larva migrans
• Tropical pulmonary eosinophiliaOHSU
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Eosinophilia: Evaluation
• Detailed history
• Guided by counts
• May need stool samples,
biopsies, etc..OHSU
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Therapy
• Remove primary cause!
• HES:
– Imatinib
–Steroids
–Hydroxyurea
– IL-5 antibodies
OHSU
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Monocytosis
• The Poor Man’s Sed Rate
–Any inflammation
• > 1000 or abnormal monocytes
–Chronic myelomonocytic leukemia
–Can be subtle
–Worry about if other counts are low
OHSU
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Elevated Immature
Granulocytes• The curse of every hematologist
existence
• Essentially meaningless
–Validity for a few conditions
–Often up in inflammation
• Lab will call out blasts, etc..
• I ignore
OHSU
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Lymphocytosis
• Lymphocytes > 5000/uL
• Very common!!!
–Up to 4-5% of the population will
have clonal lymphocytes
–Monoclonal B-lymphocytosis
(MBL)
OHSU
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Lymphocytosis - DDX
• Clonal
–CLL
–MBL
• Reactive
• Post-splenectomy
OHSU
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CLL vs MBL• Old criteria for CLL was
lymphocytes > 15,000/ul
• With new lab techniques lowered
to 5,000/ul
• MBL – clonal lymphocytes but
less than 5000/ul
OHSU
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CLL vs MBL
• Risk of progression higher with
counts > 10,000/uL
• BUT – can progress at any count
(~ 1-2%/yr)OHSU
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Rarer Causes of
Lymphocytosis
• T-cell CLL
• Hairy cell leukemia
• LymphomaOHSU
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Work-Up
• Work-up if > 5,000/uL
• Flow Cytometry
–Detects cell surface proteins
–Looks for clonal populations
• Lymph node examOHSU
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Prognosis: MBL and
Stage O CLL
• Overall good but moving target
• Unclear if more elaborate testing
will helpOHSU
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Thrombocytosis
• > 450,000/uL
• Primary
–Myeloproliferative
• Secondary
• Idiopathic?OHSU
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Thrombocytosis
• Myeloproliferative
–Essential thrombocytosis
–Polycythemia rubra vera
–Chronic myelogenous leukemiaOHSU
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Secondary
• Can be > 1,000,000/ul
• Inflammation
• Iron deficiency
• Post-splenectomy
• “Rebound”
OHSU
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Clues to ET
• Splenomegaly
• Erythromelalgia
• Thrombosis
–Visceral vein thrombosis
• Bleeding
OHSU
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Work-up
• Myeloproliferative
–JAK2/CALR/MPL
–BCR-ABL
–Splenic ultrasound
• Secondary
–Ferritin
–CRP
OHSU
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“Idiopathic”• Patients with mild increases in
platelets and no positive tests
–Essential thrombocytosis
–Congenital
–?
• Avoid labeling
• Treat with aspirin
• Follow closely
OHSU
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The Paradox of Essential
Thrombocytosis
• The higher the platelet count, the
greater the risk of bleeding!OHSU
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Essential
Thrombocytosis• Very prolonged natural history
• Therapy
–Aspirin if not bleeding
–Cytoreduction if
• > age 60
• Vascular risk factors
• Previous thrombosis
OHSU
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Thrombocytopenia
• Classic definition
–< 150,000
• DBM definition
–< 100,000OHSU
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Thrombocytopenia
• Production defects
• Sequestration
• Destruction
–Immune destruction
–Non-immune destruction
OHSU
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Thrombocytopenia1. Production defects
– Rare cause of isolated
thrombocytopenia
2. Sequestration
– “Hypersplenism”
3. Immune destruction
– Immune thrombocytopenia
4. Non-immune destruction
– Thrombotic thrombocytopenia
purpura
OHSU
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< 10,000/ul Platelets
• Immune thrombocytopenia
• Drug induced thrombocytopeniaOHSU
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Thrombocytopenia• 10-50,000/uL
– DIC
– TTP
– ITP
– Congenital
• 50,-100,000/uL
– Liver disease
– ITP
– TTP
– Myelodysplasia
– Congenital
OHSU
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Basic Question #1
• Is the patient sick?
–Yes: TTP, HIT, DIC, Sepsis, etc…
–Pregnant and sick: TTP, HELLP,
fatty liverOHSU
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Basic Question #2
• Other cell lines affected?
–Yes – myelodysplasia, bone
marrow issues, liver disease
–No – ITP or congenital
thrombocytopeniaOHSU
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Liver Disease
• Leukopenia common
–~ 1,000/ul
• Thrombocytopenia
–~ 50,-90,000/uL
• Hypersplenism
• Lack of platelet growth factor
OHSU
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Immune Thrombocytopenia
• 1:50,000
• Autoimmune destruction of
platelets
• Patients present with very low
platelet counts (<1,000/uL)
• Clinical history is diagnostic test
–No other cause of thrombocytopenia
–Normal blood smear
OHSU
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Drug Induced Thrombocytopenia
• Most common autoimmune
heme complication of medicine
• Implicated drugs:
–Vancomycin
–TMP/SMZ
–NSAID
OHSU
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Congenital
Thrombocytopenia• Counts 10-150,000/uL
• Long history of abnormal counts
• Family history
• “Giant Platelets”
–Missed by automatic CBC
machines
OHSU
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http://www.hscj.ufl.edu/pathology/cases/case1.asp
OHSU
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Work-Up• Guided by counts
–Sick -> admit
– <20,000 -> admit
• Review smear
–Giant platelets
– Schistocytes (TTP, HELLP)
• Splenic ultrasound
• Liver panel
OHSU
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The Abnormal CBC
• Find old CBC
• Sudden changes most worrisome
• Is the patient sick?OHSU