What am I supposed to do with non-LFT Lab Abnormalities?

Peter F. Bidey, DO, MSEd, FACOFPVice Chair and Assistant Professor, Department of Family Medicine

Philadelphia College of Osteopathic Medicine

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Outline – The Usual Suspects

• The CBC

• The BMP

• The UA

Keys to Remember

1. Should I even order this test?

2. What is normal?

3. Is this person’s abnormal, a possible normal?

The CBC

• Hemoglobin

• WBCs

• Platelets

The CBC – “Normal”White Male White Female A.A. Male A.A. Female

Hemoglobin (g/dL) 12.7-17 11.6-15.6 11.3-16.4 10.5-14.7

MCV (fL) 81.2-101.4 81.1-99.8 77.4-103.7 74.2-100.9

WBC (x109/L) 3.6-9.2 3.5-10.8 2.8-7.2 3.2-7.8

Platelets (xx109/L) 143-332 169-358 115-290 125-342

Bain and NHANES-II

The CBC – Hemoglobin

• Non-Applicable Normal Ranges• Athletes• Living in High Altitude• Smokers• African Americans• Presence of Chronic Disease• Older Adults• Pregnancy• Volume Depletion

The CBC – Hemoglobin - LOW• Approach

• Questions?• Is there now or previous bleeding?• Increase in destruction?• Bone marrow suppression?• Iron Deficiency?• B12 or Folate deficiency?• Urgency?

• History and Physical• Examine MCV, Abnormal RBCs and/or Peripheral Smear

• Obvious Cause – Proceed with identification and treatment

The CBC – Hemoglobin – LOW – Morphologic ApproachMicrocytic Anemia

Check Iron Studies?Lead Exposure

Low FerritinLow Fe

High TIBC

Iron Def. Anemia

Normal or Elevated FerritinLow FE

Acquired Microcytosis

Normal or Elevated Ferritin

Non-Low FE w/oSideroblasts

Consider Thalassemia

Hemoglobin Electrophoresis

The CBC – Hemoglobin – LOW – Morphologic Approach

Normocytic Anemia

Peripheral Smear

Hemolysis

LDHHaptoglobin

Indirect Bilirubin

Bone Marrow Suppression

Reticulocyte Count

Renal Insufficiency

Creatinine Level

Blood Loss

The CBC – Hemoglobin – LOW – Morphologic Approach

Macrocytic Anemia

Drug UseEtOH Abuse

B12/Folate LevelTSH

Low B12

Identify Cause and Treat

Borderline B12

MMA LevelHomocysteine

The CBC – Hemoglobin - High• Approach

• Questions?• Urgency?

• CVA, Chest Pain, etc.• True Polycythemia or Relative Polycythemia?• Do I need specialized testing?

• History and Physical

• Examine CBC and Peripheral Smear, Pulse Ox, UA and CMP.

The CBC – Hemoglobin – HighPolycythemia

Volume Depletion

Replete and Monitor

Serum Erythropoietin

Normal/Low

ConsultationJAK2 Mutation

Bone Marrow Biopsy

High

Unlikely Secondary Polycythemia Vera or other cause

Consider:Cardiopulmonary Cause

CarboxyhemoglobinRenal Conditions

Imaging for Tumor

The CBC – WBCs – Leukopenia - Neutropenia• Approach

• Questions?• Urgency?• Possible Causes?

• Benign Ethnic Neutropenia• Familial Neutropenia• Congenital Neutropenia• Infection• Medications• Nutritional• Malignancy• Rheumatologic Disease• Autoimmune Disease• Aplastic Anemia• Chronic Idiopathic Neutropenia

The CBC – WBCs – Leukopenia – Neutropenia • Approach cont.

• History and Physical

• Calculate ANC• ANC = WBC (cells/microL) x percent (PMNs + bands)

• CBC with Diff and Peripheral Smear

The CBC – WBCs – Leukopenia - Neutropenia

Leukopenia-Neutropenia

Calculate ANC

SepsisHemodynamically

Unstable

Admission

ANC < 500 with symptoms or

worrisome findings on Peripheral Smear

Urgent Eval and Consider Admission

Asymptomatic patients with ANC

≥500 to <1000 neutrophils/microL

Repeat CBC and with Diff 1-2 weeks and

evaluation if persists

Asymptomatic patients with ANC >1000 cells/microL

Repeat CBC with Diff in 2-6 weeks and

evaluation if persists

The CBC – WBCs – Leukocytosis• Approach

• Questions?• Urgency?• Abnormal Normal?

• Pregnancy• Age

• Causes?• Infection• Reactive• Chronic inflammation• Medications• Bone Marrow Stimulation• Splenectomy• Congenital

The CBC – WBCs – Leukocytosis• Approach cont.

• History and Physical

• Repeat CBC with Diff and Peripheral Smear

• Determine Cell Lines affected

The CBC – WBCs – Leukocytosis

Leukocytosis

Repeat CBC with Diff and SmearAssess H and P cause

No further Work Up No Signs of Malignancy – Determine Cell Line Cause

NeutrophiliaLymphocytosisMonocytosisEosinophilia

Signs of Malignancy:Symptoms

Additional cell lines downIncrease in blasts

DurationRisks

Consult Heme/OncFlow Cytometry, Cytogenetic testing, or

molecular testing

The CBC – Platelets - Thrombocytopenia• Approach

• Urgency• Bleeding in the setting of severe thrombocytopenia (ie, platelet count <50,000/microL)• Urgently needed invasive procedure with severe thrombocytopenia• Pregnancy with severe thrombocytopenia• Suspected heparin-induced thrombocytopenia (HIT) or post-transfusion purpura• Suspected thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), or

drug-induced thrombotic microangiopathy (DITMA)• Suspected acute leukemia, aplastic anemia, or other bone marrow failure syndrome

• Questions?• Is the thrombocytopenia real?• Is the thrombocytopenia new?• Are there other hematologic abnormalities?

• History and Physical• Consider Liver causes, HIV and/or Hep C.

The CBC – Platelets - Thrombocytopenia• Approach cont.

• Repeat CBC with Diff• For symptomatic patients (signs of bleeding) or those with severe thrombocytopenia

(<50,000/microL), such retesting should be performed immediately with referral.• For asymptomatic patients (non-bleeding, no associated comorbidities) with moderate

thrombocytopenia (50,000 to 100,000/microL), testing may be repeated in one to two weeks.• Refer if count decreases

• For outpatients with isolated mild thrombocytopenia (100,000 to 149,000/microL), testing may be repeated in 2-4 weeks.• Monitor for normalization• An exception is a patient recently started on a new medication, new clinical

findings, or other abnormalities on the CBC, because mild thrombocytopenia may be a sign of an evolving disorder.

The CBC – Platelets - Thrombocytopenia

Thrombocytopenia

Repeat CBC with Diff

Other cell lines Down

Refer to Heme/Onc

Personal or Fam Hx

CongenitalThrombocytopenia

Obtain Peripheral Smear

Physical Findings

Refer to Heme/OncObtain Peripheral Smear

Peripheral Smear

If no abnormalities found follow Cell Count

Guidelines

The CBC – Platelets - Thrombocytopenia• Other Management Guidelines

• General recommendations for activity participation have been based on historical data from patients with chronic severe thrombocytopenia. A platelet count greater than 50 × 103 per μL is adequate for hemostasis and is unlikely to be clinically recognized. • Patients with a platelet count greater than this level can engage in most activities, but

should use caution if participating in contact sports. • Patients with platelet counts less than 10 × 103 per μL should be restricted from contact

sports and other potentially traumatic activities. • Most surgical and invasive procedures can be performed safely in patients with platelet

counts greater than 50 × 103 per μL.• The American College of Obstetricians and Gynecologists recommendations state that

epidural anesthesia in pregnancy is safe in patients with platelet counts between 70-80 ×103 per μL

The CBC – Platelets - Thrombocytosis• Approach

• Urgency• Clinical Emergency• Actively clotting or bleeding

• Questions?• Is the thrombocytopenia real?• Is the thrombocytopenia new?• Are there other hematologic abnormalities?

• History and Physical

• Examine CBC with Diff and Peripheral Smear

The CBC – Platelets - ThrombocytosisCBC and Peripheral

Smear

Pathologic Peripheral Smear

Refer to Heme/Onc

Evidence of Reactive

Thrombocytosis

YesMonitor CBC for

normalization

NoSigns of MPN?

YesRefer to Heme/Onc

NoFerritin

Normal/High Ferritin

Examine again for evidence of RT and consider Referral

Low Ferritin

Replete Iron and Monitor for

Referral

The BMP

• Calcium

• Reference Range: 8.5-10.5 ng/dL

• Low: <8.5 ng/dL

• High:• Mild – 10-12 ng/dL• Moderate – 12-14 ng/dL• Crisis – 14-16 ng/dL

The BMP – Calcium - Hypocalcemia

• Approach• Questions?

• Is this truly low Calcium?• Urgency?• Causes?

• History and Physical

• Repeat and Confirm with Calcium Level, Albumin level• Consider Ionized Calcium

The BMP – Calcium - HypocalcemiaConfirm Hypocalcemia

Serum intact PTHConsider: Magnesium, Phosphate, Vitamin D,

Creatinine

Low PTH

Hypoparathyroidism:Elevated Phos, Normal Mg,

Normal Vit D, Normal Creatinine

Normal/Low Normal PTH

Hypomagnesemia:Normal Phos, Low Mg, Normal

Vit D, Normal Creatinine

High PTH

Pseudohypoparathyroidism:Elevated Phos, Normal Mg, Normal Vitamin D, Normal

Creatinine

Vitamin D Def:Low/Normal Phos, Normal Mg, Low Vit D, Normal Creatinine

Chronic Kidney Disease:Elevated Phos, High/Normal

Mg, Normal/Low Vit D, Elevated Creatinine

The BMP – Calcium - Hypercalcemia

• Approach• Questions?

• Is this truly high Calcium?• Urgency?• Causes?

• History and Physical

• Repeat and Confirm with Calcium Level, Albumin level• Consider Ionized Calcium

The BMP – Calcium - HypercalcemiaConfirm Hypercalcemia

Serum intact PTH

Low PTH

Non-PTH related Hypercalcemia

Measure PTHrp and VitD 1,25 and 25

PTHrp Normal

See Next Slide

PTHrp elevated

Yes: Possible Malignancy

Normal/High Normal(35-65 pg/mL)

Likely Primary Hyperparathyroidism

vs. FHH

Measure 24hr Urinary Calcium Excretion

Normal to High:Likely Primary

Hyperparathyroidism

Low:Familial Hypocalciuric

Hypercalcemia

High PTH

Primary Hyperparathyroidism

The BMP – Calcium - Hypercalcemia

PTHrp Normal

Vit D 1,25 elevated:Lymphoma,

granulomatous diseaseVit D 1,25 normal

Vit D 25 elevated:Vit D intoxication

Vit D 25 normal

Measure SPEP, UPEP, and Serum Free Light

Chains

The UA

• Blood

• Protein

• Bacteria

The UA

• Reference Ranges:Dipstick Analysis Result

Color Yellow

Clarity Clear

pH 4.5-8

Specific Gravity 1.005-1.025

Glucose <130 mg/d

Blood Negative

Ketones None

Protein Negative

Urobilinogen Negative

Bilirubin Negative

Leukocyte Esterase Negative

Nitrate Negative

The UA – Blood - Hematuria• Prevalence of microscopic hematuria 0.18% to 16.1%

• Approach• Questions?

• Is this cancer - Smoking History?• Causes

• Glomerular Causes• Metabolic Causes• Renal Causes• Urologic Causes• Other Causes

• History and Physical• Consider repeat unless history of smoking

The UA – Blood - HematuriaAsymptomatic Hematuria

Possible causes that can be corrected – Non-

Smoker

Repeat and monitor for correction

Smoker orNon-corrected possible

causes

Renal Function TestingCystoscopy

CT Urography

Negative:Follow up UA annually x

2 years

If still positive consider referrals, monitor annual UA, and consider repeat

imaging 3-5 years.

Positive:Treat Accordingly

The UA – Protein• Approach

• Questions?• How much protein is actually present?• What types of proteins are actually present?

• Causes• Transient Proteinuria• Persistent Proteinuria

• Glomerular• Tubular• Overflow

• History and Physical

The UA – Protein• Proteinuria is defined as excretion of >150mg of protein per day (10-20mg / dL) and is the

hallmark of renal disease

• The reagent on most dipsticks tests is sensitive to albumin but may not detect low concentrations of some of other proteins (Bence Jones etc.)

• Thresholds:• +1 – 30mg of protein per dL• +2 – 100mg of protein per dL• +3 – 300 mg of protein per dL• +4 – 1000mg of protein per dL

• Asymptomatic proteinuria is associated with significant renal disease in less than 1.5% of patients.

• Patients with dipstick results of 3+ or greater may have significant proteinuria. Follow up with spot urinary protein-creatinine ratio, microscopic examination of sediment, and urinary protein electrophoresis with renal function assessment may be warranted.

The UA – Asymptomatic Bacteriuria• Approach

• Questions?• Any symptoms?

• Causes• Catheterization?

• Data• 605 consecutive weekly urine specimens in 20 patients showed 98%

contained bacterial in prolonged catheter patients• 1413 urine cultures in 407 patients undergoing clean intermittent

catheterizations found 50.6% contained bacteria.• History and Physical• The Infectious Disease Society of America recommends against treatment of

asymptomatic bacteriuria in non-pregnant patients with spinal chord injury with catheters.

The UA – Asymptomatic Bacteriuria• Therefore, in the absence of symptoms of UTI or nephrolithiasis:

• There is no need to culture urine• Use antibiotics• Refer to urology• Perform imaging of abdomen and pelvis

References

• Bain, B. J. (1996). Ethnic and sex differences in the total and differential white cell count and platelet count. Journal of clinical pathology, 49(8), 664-666.

• Berliner, N. (2020). Approach to the adult with unexplained neutropenia. Uptodate (Internet).• Gauer, R., & Braun, M. M. (2012). Thrombocytopenia. American family physician, 85(6), 612-622.• Goltzman, D. (2019) Etiology of hypocalcemia in adults. Uptodate (Internet).• Riley, L. K., & Rupert, J. (2015). Evaluation of patients with leukocytosis. American family physician, 92(11),

1004-1011.• Shane, E., Rosen, C. J., & Mulder, J. E. (2018). Diagnostic approach to hypercalcemia. Uptodate (Internet).• Sharp, V. J., Lee, D. K., & Askeland, E. J. (2014). Urinalysis: case presentations for the primary care

physician. American Family Physician, 90(8), 542-547.• Simerville, J. A., Maxted, W. C., & Pahira, J. J. (2005). Urinalysis: a comprehensive review. American family

physician, 71(6), 1153-1162.• Tefferi, A. (2019). Diagnostic approach to the patient with polycythemia. Uptodate (Internet).• Tefferi, A., Hanson, C. A., & Inwards, D. J. (2005, July). How to interpret and pursue an abnormal complete

blood cell count in adults. In Mayo Clinic Proceedings (Vol. 80, No. 7, pp. 923-936). Elsevier.