A Quick Review of Lab Options - PowerPoint Presentation

Slide1

A Quick Review of Lab Options

Slide2

Be thoughtful

This is not meant to be “Thou shalt not….” but a gentle nudge. There is a science to medicine, but there is also an art. Sometimes you should “break the rules.”

Please also have a discussion with your supervising provider about their thoughts if appropriate.

Slide3

Topic 1: D-dimer

D-dimer, a degradation product of cross-linked fibrin, is elevated in nearly all patients with acute DVT (

ie

, it is highly sensitive).

However, it is nonspecific since elevated levels are found in many other conditions (

eg

, malignancy, sepsis, recent surgery or trauma, pregnancy, renal failure)

Slide4

Problems from

over-use

of the D-dimer test include:

Unnecessary cost of D-dimer test

Unnecessary delays in investigation, management or disposition

Unnecessary further imaging (if PERC rule would have prevented a false-positive D-dimer result from being obtained)

Radiation exposure from CTPA or CT venographyRisk of contrast nephropathyDiversion of focus away from other more likely causes

Problems from

under-use

of the D-dimer test include:

Unnecessary further imaging (if negative D-dimer would have precluded further investigation)

Radiation exposure from CTPA or CT venography

Risk of contrast nephropathy

Missed diagnosis of venous thromboembolism resulting in morbidity and mortality

Slide5

D-dimer

Durieux

et al (2001). Single center prospective study of 168 patients to analyze D-dimer usage after an educational intervention to implement guidelines for the diagnosis of PE. Despite the intervention

20% of the D-dimer requests were inappropriate and 45% of those with a positive D-dimer test had no imaging procedures performed.

Whether it is being used appropriately or not,

over half of D-dimer positive tests are false positives. This number is higher in primary care.

Slide6

DVT: Wells Criteria

Low probability

Check

D-dimer

(unless it will be high for other reasons)

Normal

Done.

High or you know it will be high.

Order US to r/o

DVT

Moderate Probability

High Probability

Do

not

order

D-dimer

. Even if negative, you need an ultrasound

Ultrasound

Slide7

PE: Wells Criteria

For patients in whom the risk of PE is thought to be

low

, a normal D-dimer effectively excludes PE, and typically no further testing is required. If it is elevated, further testing is needed

For

most patients

in whom the risk of PE is thought to be

intermediate

, a normal D-dimer also effectively excludes PE, and typically no further testing is required. However, some experts believe that a subset of patients in the intermediate risk category (

eg

, those in the upper zone of the intermediate range [

eg

, Wells score 4 to 6 or Modified Geneva sore 8 to 10] or patients with limited cardiopulmonary reserve) should undergo imaging based upon the higher probability of PE in these patients so the sensitivity of D-dimer is not as good.

For patients in whom the risk of PE is thought to be

high

, don’t check a D-dimer. If the result is positive or negative, you will need further testing.

Slide8

PERC (Pulmonarly

Embolism Rule out Criteria)

The eight-factor PERC rule was developed in 2004

A clinical decision rule that gives a

99% clinical probability of no PE

, allowing the physician to avoid workup (e.g., D-dimer test, CT) The PERC rule has

better sensitivity than the Wells Criteria for ruling out PE.

Slide9

PERC (Pulmonarly

Embolism Rule out Criteria)

Is the patient > 49 years?

Is the pulse rate > 99 beats per minute?

Is pulse oximetry < 95% on room air? Does the patient have current hemoptysis? Is the patient taking exogenous estrogen? Does the patient have a history of venous thromboembolism?

Has the patient had surgery or trauma requiring hospitalization in the past four weeks?

Does the patient have unilateral leg swelling?If all

negative

no

D-dimer, no CT

Slide10

Topic 2: Syphilis is an Increasing Problem in NC

NC was ranked

#8

in STDs in 2016 (most recent data): 1,082 cases at a rate of 10.8 per 100,000 population

The majority of cases occurred among men who have sex with men. There was also a 36 percent increase in rates of syphilis among women.

Durham ranks

2nd

in NC syphilis cases (2016). Charlotte was 1

st

.

Slide11

Who should be tested? Symptomatic

Those with symptoms: a painless genital ulcer or rash on palms, soles (primary syphilis); a diffuse, symmetric macular or

papular

eruption involving the entire trunk and extremities (secondary syphilis); general paresis; or

tabes

dorsalis (weakness, diminished reflexes, change in gait).

If a patient has symptoms, do not wait for the test results to treat. Treat them before they walk out the door. UpToDate also lists: Patients who present with signs and symptoms that are less specific for syphilis (

eg

, cranial nerve dysfunction, chronic headache, aortic insufficiency, meningitis, other signs of

meningovascular

disease, including cerebrovascular accidents), particularly if no alternative etiology is identified.

Slide12

Who should be tested? Asymptomatic

Pregnant women. All women in first trimester and women at high risk of infection: repeat screening at 28 to 32 weeks and at delivery.*

Sexually active men who have sex with men (MSM). CDC says annually, but q3

mo

also has data.

Those with HIV at baseline and then annually if sexually active

Patients currently engaging in high-risk sexual behaviors (eg, patients diagnosed with a sexually transmitted disease, people who exchange sex for drugs or money, individuals having

condomless

sex with multiple partners

Individuals with a history of incarceration or commercial sex work

USPTF Grade

A

: The USPSTF recommends screening for syphilis infection in persons who are at increased risk for infection.

Slide13

Who else should we keep in mind? Infants

Congenital syphilis rates rose 229% between 2014 and 2018 in NC

Nearly two-thirds of the women who delivered congenital syphilis infants in 2017 were negative for syphilis at the time of their first prenatal screen, meaning they acquired syphilis later in pregnancy.

North Carolina Public Health Law

requires all pregnant women be screened for syphilis at the first prenatal visit, between 28-30 weeks gestation, AND at delivery.

Screening should occur three times during pregnancy.

Slide14

The tests you can order:

“RPR, Syphilis Response to Therapy Only”

“Syphilis Screen -

Treponemoa

Pallidum AB with Reflex to RPR”

“Syphilis Antibody by TP-PA, Serum (MAYO)”

“VDRL, CSF (aka Syphilis)”

Slide15

The tests you can order:

“RPR, Syphilis Response to Therapy Only”

This test is based upon the reactivity of serum from infected patients to a

cardiolipin

-cholesterol-lecithin antigen

These screening tests are nonspecific, and therefore not definitive, they have traditionally been used for initial syphilis screening due to their relatively low cost, ease of performance, and ability to be quantified for the purpose of following response to therapy

The test is manual and not high through put

May take 3-6 weeks to become positive

Slide16

The tests you can order:

“RPR, Syphilis

Response to Therapy

Only”

A fourfold decline in the non-

treponemal

titer, equivalent to a change of two dilutions (

eg

, from 1:16 to 1:4 or from 1:32 to 1:8), is considered to be an acceptable response to syphilis therapy.

Over time, most patients successfully treated for syphilis experience

seroreversion

; however, some remain

serofast

.

Slide17

The tests you can order:

“Syphilis Screen -

Treponemoa

Pallidum AB with

Reflex to RPR”

“Syphilis Antibody by TP-PA, Serum (MAYO)”

Complex test. The test looks for antibodies directed against specific

treponemal

. It is more specific than non-

treponemal

tests.

Treponemal

tests are qualitative only and are reported as "reactive" or "nonreactive“

High through put and higher cost than RPR

ONCE POSITIVE, ALWAYS POSITIVE

But also note, there is a potential for FALSE POSITIVES. Positive Predictive Value can be from 12%-90%, depending upon the population.* However, negative predictive value is >98%.

*With high pretest probability in NC, the PPV will be higher.

Slide18

Reverse Algorithm: Advantages

Non-

treponemal

test (e.g., RPR)

Reactive

Non-reactive

Negative for syphilis

Treponemal

test (e.g., FTA)

Reactive

Non-reactive

Syphilis

Second

Treponemal

Test (e.g., TP-PA)

Reactive

Non-reactive

Negative for syphilis

Evaluation Required*

Automated, high through put

Objective

Better detection of patients with early syphilis

With a lesion, RPR was negative 3.2% of the time.

Slide19

Reverse Algorithm: Disadvantages

Non-

treponemal

test (e.g., RPR)

Reactive

Non-reactive

Negative for syphilis

Treponemal

test (e.g., FTA)

Reactive

Non-reactive

Syphilis

Second

Treponemal

Test (e.g., TP-PA)

Reactive

Non-reactive

Negative for syphilis

Evaluation Required*

Higher cost per sample (but we perhaps decrease transmission)

Higher assay complexity

Results can be more complicated to interpret

Slide20

Interpretation can be tricky

Slide21

Topic 3: FIT testing

This test reacts to a protein component of human hemoglobin (globin); guaiac tests are less sensitive as they react to the

heme

portion

No

dietary or medication restrictions

. Keep taking ASA,

Eliquis

, etc.

Do not collect sample 3 days before, during, or up to 3 days after your period. Do not collect while you have bleeding hemorrhoids, blood in your urine, or cuts on your hands/fingers. Do not collect if you have strained during bowel movement.

These are home kits. They should NOT be done in the office.

Sample stability is listed as 14 days. Quicker is better. Samples degrade faster in heat. Don’t mail if >86 degrees out.

Slide22

Cost Effectiveness

FIT cards are a cost effective way to screen for colon cancer

Markov model found FIT and colonoscopy to be more effective and less costly than

Multitarget

stool DNA (1)

In general, non-invasive strategies (FOBT, FIT) tended to be cost saving and outperformed invasive strategies (colonoscopy, sigmoidoscopy) for both Medicare and private insurance.

No large head to head trials

Cologuard

false positive rate: 10%. This is due t the fact that DNA normally undergoes methylation as we age

Man insurances do NOT pay for

Cologuard

1. (

Ladabaum

U,

MannalitharaA

. Comparative

Effectivenss

and Cost Effectiveness of a

Multitarget Stool DNA Test to Screen for Colorectal Neoplasia. Gastroenterology. 2016 Sep; 151(3):427-439 e6.)

Slide23

FIT saves more lives than Cologuard

Colorectal Cancer Screening for the Average-Risk Adults: 2018 Guideline Update From the American Cancer Society

, they have a figure that shows that

mt-sDNA

only save 93% of the lives that FIT saves.

Slide24

Who should you not offer FIT to?

Those with genetic predisposition for colon cancers (FAP, HPNCC)

Those who have inflammatory bowel disease (UC,

Chron’s

)

Those with a personal history of colon cancers, serrated polyps, or high risk adenomas

Those with a first degree relative with colon cancer

Slide25

Topic 4: H. pylori testing

Option 1: Upper endoscopy is the Gold Standard

Option 2: Urea Breath Test ($492)–

UBT is based upon the hydrolysis of urea by

H. pylori

to produce CO

2 and ammonia. Urea with a labeled carbon isotope (non-radioactive 13C or radioactive 14C) is given by mouth; H. pylori

liberate labeled CO

2

that can be detected in breath samples. The dose of radiation in the 14C test is approximately 1

microCi

which is equivalent to one day of background radiation exposure. Even though this dose of radiation is small, the non-radioactive 13C test is preferred in young children and pregnant women.

They should be off of PPIs, bismuth, antibiotics x 2 weeks. Must be off H2 blockers (Pepcid,

zantac

) x 2 days.

They are not accurate with a bleeding peptic ulcerThey should be NPO x 1 hours. They breathe into a bag, then drink a liquid, and wait 15 minutes. Then they breathe into another bag.

You can do pediatrics down to 3 yo, but will need to calculate (see website)

The bags MUST BE MARKED AS PEDS – they will be processed differently

Slide26

H. Pylori testing options

Option 2: Stool Antigen ($106) –

Monoclonal enzyme immunoassay.

Patients should be

off antibiotics for four weeks, and PPIs for one to two weeks

This test is not accurate with a bleeding peptic ulcer

Slide27

H. Pylori testing options

Option 3: Serology ($90) (some insurances won’t pay for)–

IgG antibodies. Inexpensive, but should not be used in low prevalence populations as the low accuracy of serology would result in inappropriate treatment in significant numbers of patients.

In areas where the prevalence of

H. pylori

is less than 20 percent, as in much of the United States, a positive serologic test is more likely to be a false positive.

Serology does not reliably distinguish between active and past infection

In our area, prevalence in Caucasian patients is about 7%. Prevalence in African-American patients is close to 30%.

Slide28

H. Pylori, one last note

Confirmation of eradication should be performed in

all

patients treated for

H. pylori

because of increasing antibiotic resistance.

Wait at least 4 weeks after treatment to re-test. Do not use serology testing.

Slide29

Labs for physicals, >18 yo

Unless you have a specific reason,

Do not order a UA

Do not order a CBC

Do not order a BMET, CMET

Slide30

Labs for physicals, >18 yo

Screen for HIV at least once

Chlamdyia

and Gonorrhea if sexually active for females age 24 and younger and in older women at risk for infection(grade B)

Slide31

Labs for physicals, >18 yo

Screening glucose (not A1c):

Adults 40 to 70 years of age who are overweight or obese, and repeating testing every three years if results are normal.

Individuals at higher risk should be considered for earlier and more frequent screening. The American Diabetes Association recommends screening for type 2 diabetes annually in patients 45 years and older, or in patients younger than 45 years with major risk factors.

*USPTF is revising their statement

Slide32

Labs for physicals, >18 yo

Screening lipids:

Screening men: The U.S. Preventive Services Task Force (USPSTF) strongly recommends screening men 35 years and older for lipid disorders.

A recommendation

.

The USPSTF recommends screening men 20 to 35 years of age for lipid disorders if they are at increased risk of coronary heart disease (CHD).

B recommendation

.

Screening women at increased risk: The USPSTF strongly recommends screening women 45 years and older for lipid disorders if they are at increased risk of CHD.

A recommendation

.

The USPSTF recommends screening women 20 to 45 years of age for lipid disorders if they are at increased risk of CHD.

B recommendation

.

Screening young men and all women not at increased risk: The USPSTF makes no recommendation for or against routine screening for lipid disorders in men 20 to 35 years of age, or in women 20 years and older who are not at increased risk of CHD. C recommendation

.

Slide33

Labs for wcc

Unless you have a specific reason, do not order:

UA – false positive rate is 84%.

Choosing Wisely Campaign, “With consideration of the currently available evidence, we recommend limiting screening UA in patients who are at high risk for chronic kidney disease (CKD), including but not necessarily limited to patients with a personal history of CKD, acute kidney injury (AKI), congenital anomalies of the urinary tract, acute nephritis, hypertension (HTN), active systemic disease, prematurity, intrauterine growth retardation, or a family history of genetic renal disease, to improve the cost-benefit ratio.

Slide34

Labs for wcc

You should order

Lead: 12

mo

, 24

mo

“All children enrolled in Medicaid, regardless of whether coverage is funded through title XIX or XXI, are required

to receive blood lead screening tests at ages

12 months and 24 months

. In addition,

any child between 24 and 72 months with no record of a previous blood lead screening test must receive one.

Completion of a risk assessment questionnaire does not meet the Medicaid requirement. The Medicaid requirement is met only when the two blood lead screening tests identified above (or a catch-up blood lead screening test) are conducted.” -

Medicaid.gov accessed 8/30/19

Slide35

Labs for wcc

You should order

POC

Hgb

: Iron deficiency is the most common nutritional deficiency and is seen most frequently in young children and pregnant women

The Centers for Disease Control and Prevention recommends screening for iron deficiency anemia at 9 to 12 months of age, again at 15 to 18 months, and then yearly until 5 years of age.

Likewise, the Institute of Medicine recommends screening infants at 9 months of age who are breastfed or not receiving iron-fortified formula.

Medicaid requires screening at

12

mo

and risk assessment at other

wccs

USPSTF Recommendation Statement concludes that “the current evidence is insufficient to assess the balance of benefits and harms of screening for iron deficiency anemia in children ages 6–24 months.”

Slide36

Labs for wcc

You should order

POC

Hgb

if

Adolescent Males:

Screen only those with known risk factors (e.g., low iron intake, special health care needs, previous diagnosis of iron-deficiency anemia).

Adolescent Females:

Screen annually those with known risk factors (e.g., extensive menstrual or other blood loss, low iron intake, a previous diagnosis of iron-deficiency anemia). Screen every 5 to 10 years during routine health examinations.

Slide37

Labs for wcc

You should order

Chlamydia females:

We suggest chlamydia screening for all sexually active women <25 years and sexually active women ≥25 years with risk factors (

eg

, a history of prior chlamydial or other sexually transmitted infection, new or multiple sex partners, sex partner with concurrent partners, sex partner with a sexually transmitted infection, or exchanging sex for drugs or money).

Chlamydia males

: high-risk populations (men attending clinics for sexually transmitted infections, men who have sex with men or men in correctional facilities).

Slide38

Labs for wcc

You should order

HIV:

The USPSTF recommends that clinicians screen for HIV infection in adolescents and adults aged 15 to 65 years. Younger adolescents and older adults who are at increased risk should also be screened.

Grade A