Patozone

Laboratory Calculations

 

Reticulocyte Proliferation Index (RPI)

 

RPI = reticulocytes (%) x Hct/45 x 1/ MI

 

- Hct = Hematocrit; MI = Maturation Index

 

International Normalized Ratio (INR)

 

INR = (PT:pt / PT:normal)^ISI

 

- PT:pt = pt's measured pt

- PT:normal = mean normal PT of the lab

- ISI = international standardization index given in the package insert

 

Corrected (platelet) count increment (CCI)

 

CCI = OI x BSA / P

 

OI = PsPC - PrPC

 

- OI = Observed Increment; BSA = Body Surface Area; P = Platelets Transfused; PsPC = PoSt-transfusion Platelet Count; PrPC = PRetransfusion Plt Count

- P (Platelets transfused) is the number of plts in the products if multiplied by 10^11; ie 4 random donor plts have ~2 x 10^11, so would use 2.0; an apheresis unit has ~3 x 10^11, so you would use 3

- CCI > 10,000/uL considered adequate, while 5000 is considered refractoriness

 

Anion gap

 

anion gap = [Na+] - ( [Cl-] +[HCO3-] )

 

Normal anion gap = 12 +- 4 (or 8 to 16)

 

Osmolal gap (OG)

 

OG = O:measured - O:calculated

- O = Osmolarity

 

OG = O:measured - ( 2x[Na] + glu / 18 + [BUN] / 2.8 )

 

Friedwald equation

 

IDL = Total cholesterol - HDL - (TG / 5)

 

- total cholesterol, HDL (high dens lipoprotein), and Triglyceride (TG) measured directly

 

Creatinine Clearance (Cl:Cr)

 

Cl:Cr = vol:urine x urine:Cr / plasma:Cr

 

- Cl:Cr is roughly = GFR

 

Fractional Excretion of Sodium (FENa)

 

FENa = (U:Na x P:Cr) / (U:Cr x P:Na)

 

FENa of 1% indicative of primary glomerular dz and hepatorenal syndrome (HRS), while FENa > 1% found in acute tubular necrosis (ATN), prerenal azotemiia, and postrenal azotemia

 

Henderson-Hasselbach equation

 

pH = pK + log(base / acid)

 

Corrected serum sodium in hyperglycemia

- Na inc by 1.6 mmol/L per 100 mg/dL serum glucose

 

Corrected serum sodium in hyperlipidemia

Na inc by 1 mmol/L for each 500 mg/dL of plasma lipid (triglyceride + cholesterol)

 

Corrected serum sodium in hyperproteinemia

- Na inc by 1 mmol / L for each 4 G/dL of plasma protein

 

Body Surface Area (BSA)

 

BSA (m^2) = (height [cm[ x weight [kg] / 3600)^1/2

 

- various other formulas are used

General management

 

Productivity = # products produced divided by resources used to produce the product

- in the lab, the product is billable lab result, the resource is the technical FTEs to make the result

- only billable tests count toward productivity

 

Break-even analysis = sales needed to cover costs so that there is zero profit or loss

- clinical needs and physician and patient satisfaction can override a break-even analysis

 

Breakeven point

number of tests that must be performed to reach the point where total revenue = total cost; ie the point where the net income is zero

- commonly necessary to determine the breakeven point when deciding whether to offer a test or sent it out

- in addition to the costs, must know the charge of the test (to see the revenue expected)

 

Net income = R - FC - VC

R = Revenue, FC = Fixed Costs, VC = Variable Costs

 

to find where net income = 0:

0 = R - FC - VC

 

if Z is the number of tests performed:

0 = R x Z - FC - VC x Z

 

Can rearrange:

FC = R x Z - VC x Z

to

FC = (R-VC) x Z

and finally:

Z = FC / (R-VC)

 

- can be tricky to predict bc in reality rarely are paid what you charge (allowances) and sometimes you are not paid at all (bad debt)

 

thus, R = total charges - (allowances + bad debt)

R = Revenue

 

The total cost of performing a lab test includes labor costs, material costs (reagents and other supplies), indirect costs (overhead) and fixed costs

 

Direct costs are costs assoc c directly producing a product (assoc c # tests performed)

- direct costs: 1) integral part of making the product (not benefiting >1 product); 2) easily traceable; 3) economically traceable (tracing the cost does not cost an unreasonable amt)

- ie technologist salaries, instrument supplies and reagents, equipment maintenance

 

Indirect costs = costs that benefit more than one product or project

- ie overhead, custodial services, building maintenance, telephone service, building rent, transport, general administration, depreciation

- indirect costs are usually difficult to trace and assign a specific product

 

Fixed costs do not vary over time and do not change with sample volume

- can vary, but in stepwise fashion

- ex: rent, taxes, insurance, maintenance, purchase of equipment

 

Variable costs expenses that change with the volume of tests performed

- ie regent rental, volume of reagents, cuvetes

 

In general, one can control direct and variable costs the best, while indirect and fixed costs are the hardest to control

- lab test are thus variable direct costs

- lab space rental is fixed indirect

- supervisor and tech costs are fixed direct

 

Semi-variable costs (or "step variable costs") are expenses that vary c test volume but not in direct proportion to the volume

- ie salaries of the staff to perform the tests (supervisory staffing)

 

Unit cost

- cost incurred in performing 1 test (cost per reportable)

- determined, generally, by adding the fixed and variable costs involved in performing the test

-- note that variable costs, per unit, are the same regardless of the number of tests performed, whereas fixed costs , per unit decrease as the number of tests performed increases

 

Budgeting

Usually done for periods of 1 year, and planned at least 6 mo in advance

 

Capital budget

- for big ticket items whose cost and return on investment can be mapped over several budget years (at least 3 usually)

- when capital is restricted, a lease (reagent rental agreement) should be considered, though reagents usually more expensive under these arrangements

 

Personnel budget

projection of personnel needs, usually expressed in full time equivalents (FTEs)

 

Operating budget

considers the costs of day to day operations, including reagents and other consumables, the cost of reference lab tests, blood transfusion service, professional fees, depreciation, maintenance and nonconsumable equipment (small item stuff like computer monitors)

- educational budget also falls under operating budget

 

Allocation budget

labs allocated share of the hospitals fixed costs (electricity, admin, marketing)

 

Diagnosis-Related Groups (DRG) - each DRG assigned a weight based on severity of dx, the types of procedures performed, and presence of comorbid conditions or considerations

- hospitals reimbursed fir each DRG by rate determined by reference to type of hospital, hospital setting, and hospital location

- in DRG-based system hospitals get lump sum to tx each pt, and no more money pain for more lab tests on that pt

 

Employee turnover = number of separations or terminations divided by the total number of employees on staff at the end of a given time period

- salary expenses account for 60-80% of the lab expenses

 

Laboratory Instrument Purchasing

Reagent rentals ("reagent leases") - labs usually do not have the capital to buy instruments, so they can be billed for reagents used and the price of reagents includes the price of the instruments

- the price the lab pays for reagents decreases as the price of the machine depreciates

 

Considerations for whether to perform tests in house or not include quality / reliability of assays, TATs, ability to interface c labs LIS, and price

 

Total Turnaround Time (TAT)  includes everything form order-to-physician notification time and thus preanalytical, analytical, and post-analytical intervals

- preanalytical - time from ordering test to beginning of sample analysis

-- includes order to collection, collection to receipt in lab, receipt to accessioning, accessioning to completion of preanalytic tests (centrifuging and aliquotting)

- analytical interval - time needed for analysis

- postanalyical interval - time from completion of analysis to notification of ordering clinician

 

Serum Separator Tube (SST) contains a gel that, during centrifugation, localizes bwt packed cells and the top serum layer

- mainly used in clin chem for routine assays

 

Hospitalized pts have lower albumin levels than ambulatory pts, and thus drugs, hormones and other ions are less protein bound

 

Prolonged application of tourniquet causes hemoconcentration which increases the serum and plasma levels of total protein, iron, lipid and cholesterol

- anaerobic glycolysis causes inc in plasma lactate and decrease in pH

- repeated fist clenching during phlebotomy can cause 1-2 mEq/L inc in serum potassium levels

 

Interference

Bilirubin interferes in spectrophotometric assays by its high light absorbance (bwt 340 and 500 nm)

- hemoglobin interferes c spectrophotometric  assays 2/2 high light absorbance esp surrounding the Soret band at 412 nm

- lipids interfere by scattering light and blocking light transmission

- Atkins diet (high-protein, low carb) increases urine ketones and increases serum levels of BUN

- age affects many analytes, esp alk phos (5x higher in adolescents)

- recent exercise can inc vals of LDH, CK, and AST

- proteins and Ca2+ levels can inc from 3-15% if pt sitting upright vs supine

- tourniquets can cause artifically hemoconcentrated and anaerobic part of the body in 1-3 mins, which is made worse by fist clenching (esp avoid for lactate)

- serum can have higher Ca, Mg, LDH and K vs plasma, if plasma converted to serum in clotting process, and clotting also uses serum proteins up (and is thus higher in plasma)

- paraproteinemia can alter many lab vals (ie Ca)

- pts c high leukemic cell counts (ALL, AML) can have factitious hyperkalemia, which is more pronounced in serum than plasma (CML also causes high B12 levels)

 

Tube types

Cultures always have first priority in order of draw, and serum separator tubes and finally additive tubes (green then lavender then gray) have last priority

*** to remember, think of tube tops as rainbow: Red, Yellow, Green, Blue, Purple, then superimpose *** NO CHoiCE *** for NOne, Citrate with dextrose, Heparin, Citrate, EDTA ***

 

Red - no additive in glass; plastic has silica clot activator

- used for serum chemistry and serology

- should NOT be used in coag bc clots before tests are run! (not good for plasma chemistry, but ok for serum chemistry, can also be used in blood bank for ab work ups and for "serology")

-- remember: serum is what is left behind when blood clots

 

Green - has heparin;

- used for plasma chemistry

- heparin would also affect coag assay, but since it does not clot, the plasma can be assayed

- G (green) and H (heraprin) next to each other in alphabet

 

Blue - contains citrate

- used for coagulation tests

- "Sea blue" (C(itrate) blue (top))

 

Black - has citrate (calcium chelation)

- used for ESR (very specific purpose)

 

Lavender (purple top) - EDTA (calcium chelation)

- used for cell counts

- EDTA inhibits enzymatic assays, preventing clotting and proteolysis

 

Yellow - has citrate and dextrose (ACD)

- used in blood bank tests and HLA typing

- adding adenine to citrate and dextrose gives one of the MC blood preservatives

 

Gray-top tubes - has sodium fluoride (inhibits glycolysis)

- used to collect samples for glucose or lactate measurements, esp if there is reason to expect delay bwt sample collection and analysis

- when running a gray-top tube, must collect another tube (gold or red-t top) to run a BMP

*** if you don't brush the glucose off your teeth c fluorinated toothpaste, they will turn gray!!! ***

 

 

 

 

 

Regulations

 

CDC Biosafety Levels (see figures)

BSL-1

agents not known to cause disease

Least amount of risk

BSL-2

agents associated with human disease which are easily treatable or prevented by vaccination

BSL-3

indigenous/exotic agents associated with human disease and with potential for aerosol transmission

BSL-4

dangerous/exotic agents of life threatening nature

Greatest amount of risk

 

Three-day Stay Rule of 1990

A hospital must include in its charges for inpt hospital stay the charges from all lab services performed in the 3-day period prior to hospital admission

 

Clinical Laboratory Improvement Amendments (CLIA) '88

Establishes that all clinical labs must be certified by the fed govt c programs to ensure quality, appropriate personnel training, and regular proficiency assessment

- prior to this, there wasn't any federal regulation of diagnostic lab testing

 

Code of Federal Regulations, Title 42, Section 353

Applies to all labs that do testing on "materials derived from the human body"

- executive authority given to CMS, a part of the DHHS

- the FDA, also part of the DHHS, classifies testing into 3 levels of complexity

 

Code of Federal Regulations, Title 42, section 493.1105 Standard: Retention Reqs

Labs must keep:

- peripheral blood smears / body fluids for 7 days

- stained slides from microbiology (Grams stains) for 7 days

- clinical path test / QC records for 2 years

- cytology slides for 5 years

- blood bank QC records kept for at least 5 years

- histology slides must be kept for 10 years

- flow cytometry plots and histograms for 10 years

- pathology reports retained for 10 years

 

A CLIA-approved lab is one that is inspected by an organization approved by the CMS

- CMS oversees the enforcement of CLIA regulations

- CAP offers a lab accreditation program where the lab is inspected once every 2 years

- other lab-accrediting orgs can inspect a lab in lieu of the CMS

- the certificate holder is the medical director, who can hold no more than 5 certificates

 

CMS-approved accreditation agencies:

- AABB

- American Osteopathic Association

- American Society for Histocompatibility and Immunogenetics

- COLA
- CAP

- the Joint Commission

 

CLIA certificate of accreditation

Issued to labs accredited by orgs other than CLIA, such as CAP

 

CLIA certificate for provider-performed microscopy procedures - issued to a physician, midlevel practitioner, or dentist does specific microscopy procedures for a pt

- 2nd MC certificate issued (after the CLIA waiver)

- ie Urine sediment examination, Fecal leukocyte examination, the fern test, Pinworm examination, semen analysis for presence and/or mobility of sperm, nasal smear for eosinophils

 

CLIA certificate of Registration - needed if lab does moderate- or high-complexity testing (non-waived tests) before the lab is surveyed by the state dept of Health or an accredited agency to determine compliance c CLIA regulations

- only needed for labs applying for certificate of compliance or certificate of accreditation

- labs can perform testing after getting a certificate of registration (before accreditation / compliance certificates) if there are no other state regulations

 

CLIA certificate of Waiver - issued if lab only does waived tests (not needed if lab does more high complexity testing)

- MC type of CLIA certificate issued; is effective for 2 years after date of issue

- waived tests are those simple tests that have an insignificant risk of an erraneous result

- ie FOBT, pregnancy test, blood glucose test

 

Per CLIA 88' regulations, new moderate-complexity assays approved by the FDA must be checked for:

1) accuracy

2) precision

3) reportable range

4) confirmation of the manufacturers reference range

- a full reference range study requires 120 individuals in each demographic subset, while reference range confirmation needs 20-40 healthy pts

 

CLIA requires QC samples to be run every 24 hours (??? see below...?), or more frequently as recommended by manufacturer

- QC samples should be run after maintenance or calibration of an instrument

- blood gas has stricter QC reqs, and must be done q 8 hours

 

For all non-waived tests, CLIA requires a minimum of 2 levels of controls to be run on each day that pt testing is performed

 

Labs performing high-complexity testing needs to be staffed by personnel that can fulfill qualifications and responsibilities of a technical and general supervisor, testing personnel and a clinical consultant

- if lab does mod- and high-complex testing, only employees in the high-complexity area need the above reqs

- the positions can be filled in by one person (such as the lab director) as long as he/she meets the qualifications and can meet the established responsibilities  from Subsection M of CLIA

- lab directors must ensure that appropriate personnel are working in the lab

- the personnel reqs of a lab determined by the level of complexity of assays run in the lab

 

For waived and non-waived testing, the competency of all operators must be tested before the operator performs the testing, semiannually during the first year, and annually thereafter

-competency can be checked by:

1. direct obs of routine pt test performance, such as pt id and prep, specimen collection, handling, processing, and testing

2. monitoring the recording and reporting of test results, inc critical results

3. Review of intermed test results, QC records, proficiency test results,

4. direct obs of performance of instrument maintenance and function tests

5. assessment of test performance through testing previously analyzed samples, or external proficiency

6. eval of problem solving skills

 

Citations

Phase II citations: Most serious; req documented corrective action within 30 days

 

Phase I citations - Less serious; must be corrected before the next internal inspection

 

Phase 0 citations - not officially graded and usually are items under development (may become mandatory)

 

Advanced Beneficiary Notice of Noncoverage

- formerly the Advance Beneficiary Notice

Legal notice given to outpt Medicare fee-for-service participants defining services expected to not be covered under their Medicare insurance plan

- provider notifies a beneficiary in advance if the service will probably be denied as "not reasonable and necessary"

-- if Advance Beneficiary Notice of Noncoverage not given then providers cannot bill Medicare or the individual pts for these services

- importantly, pts cannot be billed for inpt services not covered by Medicare

 

Age Discrimination in Employment Act of 1967

Protects ppl >40 yo from age discrimination

- makes it illegal to retaliate against discimination charge / complaint / investigation

 

Agency for Healthcare Research and Quality (AHRQ)

Mission is to improve efficiency, safety and quality of pt care

- one way is to compare the effectiveness of new tx's

- it also compares the use of HIT in pt safety and determines the cost effectiveness of HC

- AHRQ is 1 of 12 agencies directed by the Department of Health and Human Services (DHHS)

 

Americans with Disabilities Act

- 3 ways to be considered disabled:

1) physical or mental condition that greatly limits a major life activity

2) has hx of disability

3) if believed to have a disability that is not transient or minor

- Title I of the ADA of 1990 says you can't discriminate against a person with a disability

- also you cannot retaliate against a person that has complained or filed a charge concerning discrimination

 

Civil Rights Law of 1964, Title VII

Makes it illegal to retaliate against someone for discrimination charges / lawsuits / investigations

- also requires that employers reasonably accommodate applicants and employee' religious practices

 

Department of Health and Human Services (DHHS)

Federal agency that oversees the CMS, FDA and OIG

 

Family Medical Leave Act (FMLA)

Gives employees up to 12 weeks of unpaid, job-protected leave per year for qualifying reasons

- qualifying reasons include: birth of newborn child, placement of child for adoption or foster care, care of immediate family member c serious health condition, employee medical leave if unable to work 2/2 serious health condition

- employees eligible if have been working at company for >12 months

- health insurance must be provided during the leave if the employee had health insurance before the leave was taken

- applies to all public agencies, elementary and secondary schools and companies c >50 employees

- FMLA is enforced by the US Dept of Labor's Employment Standards Administration, Wage and Hour division

 

Food and Drug Administration (FDA)
Part of the DHHS

- regulates manufacture of biologics, medical devices, and test kits

Oversees the regulations and compliance of blood banks, as blood products are regulated by the federal govt as a pharmaceutical (biologic)

- testing instruments and reagents are considered medical devices

 

Medical devices (testing instruments)

- must be reviewed by FDA before ready for market

- classifies medical devices from Class I - III depending on the risk assoc c its use

- 2 echelons of review: clearance and approval

 

FDA clearance

- premarket notification or 501(k) must be filed by manufacturer to document that the device is substantially equivalent to another FDA approved device

 

FDA approval

formal validation must be undertaken by the manufacturer and filed in the form of a premarked application (PMA)

 

Some devices do not need FDA review [501(k) exempt medical devices] but req the fikkiwubg as c FDA cleared and approved devices:

- proper labeling, which has statement that the device is not FDA cleared or approved

- listing

- reporting, which refers to the duty of users and or manufacturers to report device malfunction; labs are subject to this mandate

- good manufacturing practices

 

Analyte Specific Reagents (ASR)

- defined as "abs, both mono and polyclonal, spefic receptor proteins, ligans, nucleic acid swq, and similar reagents which through specific binding or chemical reactions with substances in  a specimen are intended for sue in a diagnostic application for id and quant of ind chemical substance or ligand in biological specimens

- in contrast, general purpose reagents (GPRs) are non-specific

 

Laboratory Developed Tests (LDT) are considered medical devices by the FDA, and labs that make LDTs are thus manufacturers of medical devices

- LDTs are tests designed in a lab for specific use only in that laboratory

- FDA uses enforcement discretion on LDTs which allow implementation of new lab tests in labs in a meaningful time period

- though the FDA does not actively enforce LDT regulation, CLIA does set strict performance criteria for them

 

Biologics

blood falls in FDAs Center for Biologics Eval and Research (CBER), that regs blood and blood components, cell separation devices, blood collection containers and HIV screening tests that are used in prep of blood production

- FDA inspects all blood facilities at least annually, and participation is mandatory

 

Genetic Information Nondiscrimination Act of 2009

Illegal to discriminate against employees or applicants bc of genetic info

- includes that individuals, or that persons family's genetic tests results, or a family member's dz

- also makes it illegal to retaliate against discrimination charges / lawsuits

 

Health Insurance Portability and Accountability Act (HIPAA)

 

The Privacy Act of 1994

- protects records c personal identifiers and prohibits disclosure w/o written consent unless specified exception applies

 

The Privacy Rule (1996)

- aka Standards for Privacy of Individually Identifieable Health Infrmation

- applies to all HC entities; issued by DHHS to implement HIPAA, and is enforced by the Office of Civil Rights (OCR) within the DHHS

- PHI refers to individually identifiable health information

- PHI can be shared for treatment, payment or lab purposes or if requested by DHHS for legal reasons

- covered entities have obligation to secure information from unauthorized access

 

International Standards for Organizations (ISO)

- non-govt org that develops stands for disciplines in business, govt and society

- 163-country network of ntl standards institutes

- adherence to ISO standards is voluntary, and it has no legal authority

- ISO 15189:2007 ("Medical laboratories - Particular reqs for quality and competence") designed for clinical and medical labs and includes quality management standards, technical competence standards and test reliability standards

 

Medicare and Medicaid

- est by Social Security Act of 1965

 

Medicaid

Jointly funded by state and federal govts

- to participate in Medicaid, states req;d to offer health insurance coverage to certain population groups

- states can expand the health insurance coverage to additional population groups if they deem appropriate

- states receive federal matching funds to provide the benefits

 

Medicare

federal program administered by CMS

- benefits 3 grps of pts: >65 yo, permanently disabled, end stage renal dz

- care reimbursed under parts A and B

-- Part A covers inpt care (in addition to hospice, SNFs, and home health care), aside from physician services

-- Part B covers outpt services and inpt physician services according to a fee schedule (fee for service), importantly, private insurers refer to Medicare part B fee schedule to benchmark reimbursement rates

 

Medicare part B covers payment for physician services (PC payments), which is determined but the Physician Fee Schedule (PFS), in turn determined by the Resource Based Relative Value Scale (RBRVS)

 

Some test panels must be billed as a panel and not as individual tests (which is called "unbundling")

 

National Institute of Standards and Technology (NIST)

Branch of the US Dept of Commerce

- develops and distributes standardized calibration materials for a finite list of analytes

 

Occupational Safety and Health Act (OSHA) of 1970

Passed by congress, requires employers to provide a safe workplace

- enforced by the OSHA, which is part of the US Dept of Labor

- the standards limit hazardous chemical exposure, req safety practices and equipment, req monitoring hazards, and keeping track of workplace injuries

- all employers req'd to have poster prepared by Dep of Labor informing employees of their protections under OSHA

- employees should be trained in location and use of MSDS

- labs must have exposure control plan, including provision of PPE, and use of universal precautions

 

Office of Inspector General (OIG) compliance guidelines

Helps labs make programs that promote highly ethical and lawful conduct, esp for billing

 

Reimbursement

Both ICS codes and HCPS codes must be given to get paid

2 systems:

1) International Coding of Disease (ICD) system

- describes pts med problem

- developed by WHO for epidemiology purposes

- Clinical Modification - the ICD-CM - was designed for billing

 

2) Health Care Procedural Coding System (HCPCS)

- describes services rended

- 2 levels:

-- Level I - described by CPT codes (5 numbers)

-- Level II - letter and 4 digits - published yearly by CMS and addresses services not covered by CPT (level I) codes

 

CMS needs doc of medical necessity to reimburse for pathology services rendered, thus an appropriate ICD code from physicians must accompany a claim

- for inpt sevices, typical scenario is that after discharge pts DRG and HCPCS codes sent to CMS, which gives a hospital a rate based on geographic location, and hospital type

-- billing for Professional Services (PC) coded separately from the lab fee schedule

-- Technical Component (TC) work done in the clin or anatomic path lab cannot be billed separately to Medicare, it is covered under the one time DRG related hospital payment

 

The Stark Act (Stark Law) of 1989

- aka Section 1877 of the Social Security Act (42 U.S.C. 1395)

Physician self-referral ban; prevents physicians from referring Medicare pts to self-owned labs

- the Stark Law is distinct from the anti-kickback law