# Common laboratory studies

### Author Credentials

Update Author: Phillip Breslow, MD and David Richards, MD, Denver Health Medical Center Residency in Emergency Medicine

Original Author: David Richards, MD, FACEP, Denver Health Medical Center, University of Colorado School of Medicine

Update Editor: Navdeep Sekhon, Baylor College of Medicine

Original Editor: Matthew Tews, DO, MS, Medical College of Wisconsin

Update: 2023

### Case Study

It's a busy day in your Emergency Department, where you work as an attending. You have the good fortune of working with a medical student. You send the medical student to see a patient who has some hand pain after a motor vehicle collision. After an excellent patient presentation, the medical student starts out their plan: “Well, first I would like to get some basic labs, and then…” You smile as you begin your next teaching point…

### Objectives

By the end of this module, the student will be able to:

1. Identify commonly ordered tests in the Emergency Department as well as their clinical indications

2. Understand reference values for common test results as well as which abnormal values may be clinically significant

3. Identify tests prone to false positive and negative results

4. Begin to understand the limitations of various laboratory tests

5. Know the price for commonly ordered tests

### Introduction

Laboratory studies are an important component of the Emergency Medicine work-up. A thoughtful approach to their utilization, including a combination of specific tests with the patient’s pretest probability of a disease (symptoms, signs, and risk factors), can yield a post-test probability of such disease that may change the management of the patient.  While statistics, likelihood ratios and Bayesian theorem are out of the scope of this current discussion, we will focus on indications to order, interpretation of, and costs of common emergency department tests.

This module should help to form the foundation of initial appropriate laboratory test selection, allowing for consideration of a number of factors including cost, assay performance and disease epidemiology.

In the following sections, the price listed next to each test indicates the typical cost to perform the test, not the charge to the patient. In many situations the charge to the patient is many times higher. These charges will vary depending on the institution, but the cost to perform provides an idea of what laboratory resources are required to perform the test.

###### A note about reference ranges

Included ranges are for average adult patients. Normal values vary slightly among different labs and should be interpreted as institution-specific.

### Laboratory Stewardship

Judicious ordering of laboratory studies is paramount to the cost-effective practice of Emergency Medicine. Under-ordering can miss life-threatening diagnoses, while over-ordering can increase the risk of false positives, patient discomfort from laboratory draws, and cost. As health care costs soar, it is imperative that the Emergency Physician practice cost-effective medicine and order laboratory studies with care.

The challenge in ordering studies in Emergency Medicine is the “Goldilocks Principle,” to not order too many or too few laboratory studies, but just the “right” amount.

Below are some general themes you should consider when ordering laboratory studies:

• Only order studies that will change your management. If you are ordering tests whose results will not change your management, you are creating undue costs to the patient and the health system.

• Factor in the pretest probability of the disease when ordering a test. For patients with a low pretest probability of disease, the risk of false positives is increased.

• Consider the severity of a disease process when ordering laboratory tests to check for it. In Emergency Medicine, there are “can’t miss” diagnoses because missing them can be catastrophic to the patient. Hence, for these “can’t miss diagnoses,” have a lower threshold to test for them. A classic example of this is the use of the troponin for Acute Coronary Syndrome.

### Lab Tests: Indications, Interpretation, Cost

Complete Blood Count (CBC) (Cost – \$11)

• WBC – Reference level: 4.5-11 x 10(9)/L

• Highly variable among patients and disease processes, therefore necessitates clinical correlation. Neither sensitive nor specific enough to rule in or rule out specific diseases in many circumstances. A classic example is that a normal white blood cell count is not sensitive enough to rule out appendicitis.

• WBC Differential (CBC w/ diff) (Cost – \$14)

• Required to further differentiate component types of the total white blood count

• Leukocytosis
• Neutrophil predominance – may represent bacterial infection, inflammatory, or neoplastic process.

• Bandemia - immature neutrophils may be released from the bone marrow in response to significant infections. Classically called a “left shift.”

• Lymphocyte predominance – may represent viral (e.g. EBV) or bacterial infections (e.g. Pertussis). Lymphocytic leukemia is another possible etiology.

• Basophilia – autoimmune conditions (e.g. Crohn’s disease, multiple sclerosis, rheumatoid arthritis), hypothyroidism, splenectomy, neoplastic (e.g. CML, polycythemia vera)

• Monocytosis – GI disorders, sarcoidosis, recovery from marrow suppression, mononucleosis

• Eosinophilia – parasitic infections, allergic diseases, GI diseases, cutaneous diseases

• Leukopenia
• Neutropenia – overwhelming bacterial infection, AIDS, hypersplenism, anaphylactic shock, cachexia, chemotherapeutic drugs

• Lymphopenia – immunodeficiency disorders, adrenocortical hormone excess or corticosteroid treatment, impaired drainage of intestinal lymphatics, chemotherapeutic drugs, advanced lymphomas and carcinomas, infections (e.g. HIV)

• RBC – Red Blood Cell count. This is not used to determine the need for a transfusion, while the hemoglobin and hematocrit can.

• Mean Corpuscular Volume (MCV)- average size of a red blood cell. In the anemic patient:

• MCV < 80fL – microcytic anemia. Think iron deficiency, iron absorption problems, chronic disease, lead poisoning, thalassemia, and sideroblastic anemia.

• MCV >100fL – macrocytic anemia. Think alcohol use, vitamin B12 and folate deficiencies, hypothyroidism.

• Hemoglobin- concentration of the protein that carries oxygen in red blood cells.

• Hematocrit- the ratio of the volume of red blood cells to the total volume of blood. The hematocrit can be estimated by multiplying the hemoglobin by three. Reference level for hematocrit: 41-50% (M), 36-44% (F)

• Acute hemorrhage pearls

• Plasma volume needs 12-24 hours to equilibrate after acute red blood cell loss, therefore the hemoglobin and hematocrit may be falsely elevated above the true level in active bleeding. Do not delay transfusion in the patient with an acute bleed based on a single hemoglobin/hematocrit!!

• Transfusion threshold in symptomatic anemia (for majority of patients) is Hgb <7 mg/dL. Transfuse with packed red cells.

• Platelets – Reference level: 150-450 x 10(9)/L

• Thrombocytopenia – caused by disorders of production, distribution, or destruction

• 20-50 x 10(9)/L – associated with minor spontaneous bleeding and major bleeding associated with trauma

• <10-20 x 10(9)/L – associated with major spontaneous bleeding

• Consider transfusion of platelets in the setting of acute bleeding with platelets <70 x 10(9)/L or in asymptomatic patients with platelets <10 x 10(9)/L.

• Thrombocytosis – reactive (infections, inflammatory disorders, splenectomy, acute blood loss or injury) or malignancy/myeloproliferative disorder

• Reactive thrombocytosis rarely >1000 x 10(9)/L

• Platelets are an acute phase reactant

#### Basic Metabolic Panel (BMP/Chem7) (Cost – \$15)

• A panel of blood tests used to monitor kidney function, electrolytes, acid/base status and fluid balance.

• Sodium (Na+) – Reference level (135-145 mmol/L)

• Important in neurological disorders (seizures, AMS), head trauma, malnutrition/dietary issues (dehydration, water intoxication, failure to thrive)

• Hyponatremia: Below is an algorithmic approach to identify the etiology

1. Determine serum osmolality. True hyponatremia is hypotonic (<280 mOsms/kg)

• Be sure to correct serum sodium for degree of hyperglycemia. For each 100 mg/dL of glucose above the normal range then laboratory reported sodium decreases by 1.6 mmol/L.

1. Use clinical exam findings/history to determine a patient’s fluid/volume status

2. Order urine electrolytes (urine osmolality/urine Na+) to help determine an etiology.

• Hypovolemic hyponatremia

• Urine Na <20 mEq/L – vomiting, diarrhea, third spacing (pancreatitis)

• Urine Na >20 mEq/L – diuretics, Addison’s disease

• Euvolemic hyponatremia

• Urine dilute (urine Osm < 100 mOsm/kg) – beer potomania, primary polydipsia.

• Urine concentrated (urine Osm > 100 mOsm/kg) – SIADH, Hypothyroidism, ACTH deficiency

• Hypervolemic

• Urine Na <20 mEq/L – heart failure, cirrhosis, nephrotic syndrome, hypoalbuminemia

• Urine Na >20 mEq/L – renal failure

• Hyponatremia pearl- remember that rapid correction of chronic hyponatremia can cause central pontine myelinolysis, which can be neurologically devastating and cause “locked-in” syndrome.

• Hypernatremia: below are the general causes.

• Free water deficit (reduced water relative to Na+): Diarrhea, lactulose, hypertonic fluid administration.

• Evaporative water loss: excess sweating and insensible losses from skin and respiratory tract (tachypnea)

• Renal losses: osmotic and loop diuretics, Diabetes insipidus, hypercalcemia, hypokalemia

• Potassium (K+) – Reference level (3.5-5.5 mmol/L)

• Critically important to cardiac function (arrhythmias), acid/base abnormalities, muscle function. Should be evaluated in disorders that can cause electrolyte shifts (e.g. DKA, sepsis, crush injuries, renal failure etc.)

• Hyperkalemia: Strongly consider checking an EKG as dysrhythmias provoked by hyperkalemia can be catastrophic to the patient.

• Pseudohyperkalemia: Erroneous cause of elevated potassium result. This can be caused by hemolysis of the sample, prolonged tourniquet use during venipuncture, thrombocytosis, and leukocytosis.

• Reduced excretion: renal failure, oliguria & anuria, adrenal insufficiency, aldosterone deficiency

• Cellular shifts: acidosis, insulin deficiency, tissue destruction/breakdown (burns, rhabdomyolysis).

• Medications: decrease RAAS (Beta blockers, ACEI, ARBs), K+ sparing diuretics (spironolactone, triamterene, amiloride), NSAIDS, cyclosporin, pentamidine, Bactrim

• Hypokalemia: Etiologies

• GI & Skin loss: vomiting, diarrhea, laxative abuse

• Renal loss: diuresis, RTA, hypomagnesemia, hyperaldosteronism

• Cellular shifts: alkalosis, β -Adrenergic medications (albuterol, epinephrine), catecholamine excess, gluco- and mineralocorticoids

• Other medications: loop and thiazide diuretics, other drugs promoting K+ loss in distal collecting tubule (carbenicillin, ticarcillin), licorice

• Pearl: Strongly consider checking magnesium levels in hypokalemic patients as magnesium deficiency can cause hypokalemia.

• Pearl #2: Hypokalemic periodic paralysis is a disorder where low potassium levels are associated with a reversible paralysis

• Chloride (Cl-) – Reference level (96-106 mmol/L)

• Important in determining the anion gap

• Hyperchloremia – contributes to a non-anion gap metabolic acidosis (e.g. diarrhea, large volumes of NaCl, RTA)

• Hypochloremia – loss of chloride-containing body fluids (e.g. prolonged vomiting, burns, diuretics, salt-wasting nephropathy)

• Urine Cl- Useful in determining cause of metabolic alkalosis

• Low (<15mmol/L) – Chloride responsive indicating volume depletion. Treat with chloride containing fluids

• High (>15mmol/L) – Chloride resistant indicating mineralocorticoid excess, hypomagnesemia, Gitelman’s syndrome

• Bicarbonate (HCO3-/CO2) – Reference level (22-29 mmol/L)

• Indicator of the acid/base status of the serum.

• HCO3- < 22mmol/L suggests a metabolic acidosis (bicarbonate being used to buffer excess acid)

• Calculate Anion gap to determine the etiology of metabolic acidosis.

• Anion gap = Na – (Cl– + HCO3-).  Reference level (4-12 mmol/L)

• Increased gap indicates presence of unmeasured ions (e.g. lactic acid, phosphate, sulfate, ketones)

• Normal gap indicates losses of HCO3– & Cl– (e.g. diarrhea and renal losses)

• Low gap (e.g. hypoalbuminemia, CHF, multiple myeloma)

• HCO3- > 29mmol/L suggests metabolic alkalosis secondary to loss of acid (e.g. vomiting with hypovolemia)

• Blood Urea Nitrogen (BUN) – Reference level (6-24 mg/dL)

• A marker of nitrogenous products in the serum and important in determining volume status in conjunction with the creatinine, renal function, excretory ability.

• Increases in 4 scenarios (Azotemia) –

• Prerenal azotemia: intravascular hypovolemia (e.g. dehydration, CHF, cirrhosis, GI bleed). At low flow rates, renal tubules increase reabsorption of urea (relative to Cr) to increase osmolarity and retain more water.

• Renal azotemia: kidney not excreting urea properly (pyelonephritis, glomerulonephritis, renal failure)

• Post-renal: obstructive uropathy

• GI Bleed: the breakdown and absorption of the protein in blood in the GI tract causes an elevation of BUN. More common in upper GI bleeds.

• Decreases in decreased Urea synthesis (e.g severe liver disease, malnutrition) and dilutional states (e.g. SIADH, 3rd trimester pregnancy)

• Creatinine (Cr) – Reference level (0.5-1.2 mg/dL)

• A product of muscle metabolism. Level depends on muscle mass, race, age, gender, diet and is used as a marker of renal function and to determine the etiology of renal injury (along with BUN)

• Impaired renal function associated with an elevated creatinine.

• False elevation of Cr with certain medications (e.g. H2-blockers, fibrates)

• When assessing a patient, always want to consider their baseline.

• Glucose – Reference level (70-99 mg/dL)

• Hypoglycemia: <70 mg/dL. Below is a list of possible etioligies:

• Fasting hypoglycemia, particularly in malnourished (e.g. alcohol abuse)

• Excess insulin or sulfonylurea administration, insulinoma

• Hepatic, adrenal, or renal insufficiency

• Sepsis

• Hyperglycemia: Fasting glucose >126 mg/dL

• Typically seen in the setting of diabetes mellitus, medication non-adherence, DKA, HHS

• Calcium (Ca2+) – Reference level (8.5-10.5 mg/dL)

• Important in cardiac dysrhythmias and often associated with other electrolyte abnormalities.

• Total calcium = Protein-bound (albumin) calcium (40-50%) + Free (Ionized) calcium (50%).

• Hypercalcemia: > 90% due to hyperparathyroidism or malignancy

• Order PTH and 24-hour urinary Ca2+ to assist in etiology

• Hypocalcemia most commonly associated with:

• Hypoalbuminemia and hypomagnesemia

• Other etiologies:

• CKD, Vit D deficiency, hypoparathyroidism, pseudohypoparathyroidism

• Decreased ionized Ca2+ (Citrate transfusion, acute pancreatitis, rhabdomyolysis, acute hypocarbia)

• Because calcium is bound to albumin, in patients with hypoalbuminemia (e.g. cirrhosis, nephrotic syndrome, malnutrition) correct for missing albumin by either:

• Order an ionized Ca2+ level (4.8-5.6 mg/dL)

• Correct Ca2+ for albumin:

C Ca2+ = Measured calcium + .8 x (4 - Albumin)

#### Magnesium (Mg2+/Mag) (Cost \$12)

• Often ordered when evaluating for cardiac dysrhythmias, neuromuscular irritability, and in patients taking medications causing electrolyte abnormalities (loop and thiazide diuretics, digitalis, aminoglycosides, pentamidine, cyclosporin, cisplatin). Should be evaluated in the setting of hypokalemia, QT prolongation/polymorphic ventricular tachycardia, protracted vomiting and diarrhea.

• Reference level (1.7-2.2 mg/dL)

• Hypermagnesemia:

• Excess intake in patient with CKD

• Iatrogenic (magnesium containing enemas/laxatives, overtreatment in preeclampsia).

• Rhabdomyolysis, tumor lysis syndrome

• Not symptomatic until 4-6 mg/dL

• Hypomagnesemia:

• Reduced intestinal absorption – malnutrition/malabsorption, chronic diarrhea

• Increased urinary losses – renal tubular disorders, ketoacidosis

• Intracellular shifts – hypokalemia, hypocalcemia

• Obtain Spot urine fractional excretion of Mg2+: >2% suggests renal losses

Phosphorus inorganic (Phosphate/Phos) (Cost – \$9)

• Should be included in evaluation of renal insufficiency (over 70% of dialysis-dependent patients will be hyperphosphatemic) or in any condition involving massive cell death (e.g. crush injury, hemolysis, tumor lysis, etc). Consider in patients with risk of hypoparathyroidism (history of neck/thyroid surgery), or excess Vitamin D intake.

• Reference level (2.5-4.5 mg/dL)

• Hyperphosphatemia:

• Most common cause: Renal insufficiency or decreased renal secretion in hypoparathyroidism

• Less common: increased cellular turnover/metabolism (e.g. crush injuries, rhabdomyolysis, tumor lysis syndrome), DKA (though total body phosphate depleted)

• Generally accompanies hypocalcemia and symptoms of such

• Hypophosphatemia (clinically significant < 1.5 mg/dL)

• Clinically significant in few settings, generally accompanying high phosphate turnover states (refeeding syndrome, TPN, recovery from DKA)

• Chronic in hyperparathyroidism, hypothyroidism, vitamin D deficiency, chronic diuretic use, chronic starvation/malabsorption, chronic antacid use (due to aluminum binding)

#### Liver Function Tests (LFTs) (Cost – \$14)

• Evaluates for and/or helps monitor hepatic/biliary disease, injury, inflammation, and obstruction.

• Aspartate Transaminase/Alanine Transaminase (AST/ALT) – Reference level (8-48 IU/L / 7-55 IU/L)

• Hepatocellular labs; markers of cellular injury.

• ALT more specific to the liver. AST is also found in the heart, kidneys, skeletal muscle, RBCs.

• General trends:

• Marked elevation >15x upper limits of normal is seen with significant necrosis (i.e. acute viral/drug-induced hepatitis, acute biliary obstruction)

• AST>ALT 2:1 is EtOH. AST rarely >300 IU/L

• ALT>AST more likely related to chronic liver disease (e.g. chronic viral hepatitis, fatty liver, chronic hepatotoxic meds—thionamides)

• Isolated elevation of AST should prompt consideration of extrahepatic etiologies (e.g. myocardial or skeletal muscle abnormalities).

• Alkaline phosphatase – Reference level (44-147 IU/L)

• Found in liver, bone, intestine, and placenta

• Marker of cholestasis (biliary obstruction) given high concentration within biliary canaliculi

• Bilirubin – Reference level (total 0.1-1.2 mg/dL; direct < .3 mg/dL)

• Marker of cholestasis (direct) and hepatic function (indirect to direct ratio) as bilirubin is the end result of heme catabolism.

• Direct = Conjugated, Indirect = Unconjugated

• Direct + Indirect = Total

• Most common etiology of unconjugated hyperbilirubinemia – Gilbert’s (5%), hemolysis, recent hematoma, ineffective erythropoiesis.

• Most common etiology of conjugated hyperbilirubinemia are exocrine hepatic excretion defects – extrahepatic obstruction (e.g. stone), intrahepatic cholestasis, hepatitis, cirrhosis, toxins

• Albumin – Reference level (3.4-5.4 g/dL)

• Marker of hepatic synthetic function (along with PT/INR).

• Major protein found within serum, with 10 g/day produced by liver.

• A decrease in albumin and concurrent additional LFT abnormalities is an indicator of liver dysfunction. Low albumin without LFT abnormalities is reflective of malnourishment vs protein loss (e.g. nephrotic syndrome)

#### Amylase/Lipase (Cost – \$10)

• Used to evaluate suspected pancreatitis.

• Reference levels (Lipase 0-160 U/L; Amylase 40-140 U/L)

• Amylase may begin rising sooner (2-4 hours) than lipase (4-8 hours) in pancreatic injury, however returns to baseline sooner (3-5 days) than lipse (8-14 days), limiting its diagnostic window.

• Amylase also found in salivary glands, and is less specific than lipase

• Highly specific for pancreatitis when levels are >3x ULN

• Non-pancreatic etiologies of elevation:

• Both: Renal failure (20% renal excretion)

• Lipase: Cholecystitis, perforated peptic ulcer

• Amylase (inflammatory marker): Intestinal perforation, ischemia, obstruction, DKA, ruptured ectopic pregnancy

• Pearl: Lipase is both more sensitive and specific than amylase. This has caused most Emergency Departments to use ONLY lipase for the evaluation of pancreatitis. Amylase is rarely ordered in the modern Emergency Department.

Complete Metabolic Panel (CMP) (Cost – \$18)

• Is the BMP plus tests that monitor liver function but generally does not fractionate the bilirubin into direct and indirect components (See Liver Function Tests [LFT’s] above).

### Cardiopulmonary Tests

#### Troponin (Cost – \$22)

• Can be useful in the evaluation of patients where there is concern for myocardial cellular damage. Troponin I is specific to the myocardium and is the latest generation of biomarkers for myocardial cellular damage (earlier tests included CK-MB, LDH, and AST).

• Troponin I is released into the bloodstream within hours of myocardial infarction or ischemic damage. Troponin concentrations can be detected 2-4 hours following onset of chest pain, peaking at 12-24 hours, remaining elevated for 5-9 days

• Reference level (≤ 0.03 ng/mL, representing the 99th percentile for Troponin level compared to a reference control group)

• High Sensitivity Troponins (hs-cTn) –

• Almost universal adoption of high sensitivity troponin with higher analytic precision, greater clinical sensitivity, within a shorter time frame has recently occurred.

• Institution-specific algorithms exist for their utilization including the ability to effectively rule out ACS with a single troponin test when certain timing criteria and test values are met.

• Positive troponin result is not synonymous with myocardial infarction therefore should be interpreted in the context of patient presentation, ECG findings, vital signs.

• Other conditions can lead to elevated troponin levels (e.g. arrhythmia, myocarditis, cardiac surgery, angina, congestive heart failure, renal failure, shock, pulmonary embolism)

• The kinetics of troponin in Myocardial Infarction (MI) as well as presence of increased troponin levels in other conditions is why obtaining serial troponin levels for change is more clinically useful in the evaluation of acutely evolving cardiac injury (i.e. MI).

• Earlier, less sensitive, and less precise troponin assays required an average of 6 hours before repeat testing could detect a conclusive increase in troponin.

• hs-cTn tests can detect changes in troponin levels after as early as 2-3 hours.

#### Brain Natriuretic Peptide (BNP) (Cost \$35)

• Is a chemical released by the atria when sufficient stretch occurs (e.g. conditions of volume overload). Most commonly used to distinguish primary pulmonary from cardiac etiologies of dyspnea (e.g. heart failure from COPD/pneumonia).

• Reference level (<100 pg/mL; NT-Pro BNP <300 pg/mL)

• BNP >400 pg/mL suggestive of congestive heart failure. Increased BNP values predictive of death or increased risk of adverse cardiovascular events

• Other conditions that increase BNP: Myocardial infarction, atrial fibrillation, pulmonary embolism, pulmonary hypertension, chronic kidney disease, age, and hyperthyroidism.

• May have falsely low levels in obese patients and in flash pulmonary edema.

#### D-dimer (Cost – \$119)

• Can be used to rule-out DVT or PE in low risk (by Well’s criteria) or intermediate risk (by Geneva criteria) patients. The PERC criteria can be used to identify “no risk” patients that should not have D-dimer testing.

• D-dimer is the physiological by-product of fibrin degradation. When found in the blood it can indicate the presence of a large clot or bleeding dyscrasia. It can also be elevated in Disseminated Intravascular Coagulopathy (DIC).

• Reference level –

• Historically < .5 mg/L utilized to “rule-out” thrombus

• Age adjusted if greater than 50 yo: Age x .01 mg/L provides cutoff

• YEARS criteria – Hemodynamically stable patients >18 yo without clinical evidence of DVT or hemoptysis and PE not most likely diagnosis: cutoff of 1 mg/L.

• False positive: Inflammatory processes, pregnancy, malignancy, trauma, liver disease, post-surgical, covid-19.

#### Lactate (Cost – \$55)

• Typically ordered as a surrogate marker for end-organ hypoperfusion and trended as a marker of resuscitation efforts for a patient with an anion gap metabolic acidosis. Lactate is metabolized by the liver. The serum concentration depends both on the rate of production by body tissues and the rate of liver clearance.

• Initial lactate > 4 mmol/L is associated with 28% in-hospital mortality rate)

• Common indications to order a serum lactate:

• Conditions of end organ hypoperfusion (e.g. arrest, sepsis, shock, hypovolemia, multisystem trauma, heart failure, pulmonary insufficiency)

• Metabolic disorders (e.g., undifferentiated anion gap metabolic acidosis, diabetic ketoacidosis, malignancies)

• Toxin exposures (e.g. ethylene glycol, methanol, salicylates, metformin overdose, etc).

• Two types of lactic acidosis

• Type A: Lactate elevation in the presence of cellular hypoxia

• Type B: Lactate elevation in the absence of cellular hypoxia (e.g. from medications such as albuterol, epinephrine, etc.)

#### Coagulation studies (PT/INR, PTT) (Cost – \$26, \$28)

• Prothrombin Time (PT) – evaluates how long it takes for a blood clot to form as a surrogate marker for the presence and effectiveness of various liver-produced clotting factors involved in the extrinsic pathway.

• Reference level (11-13.5 seconds)

• Often ordered as screening for coagulopathies and pre-surgical screening

• Evaluate for anticoagulation effectiveness

• Evaluate for  severity of liver disease (helps to assess the synthetic function of liver)

• Will be prolonged in vitamin K deficiency (e.g. Coumadin use, fat malabsorption syndromes, recent broad spectrum antibiotics, premature infants)

• International Normalized Ratio (INR) – standardized comparator of clotting ability calculated based on PT that can be utilized across laboratories.

• Reference level (.8 - 1.1)

• Evaluates for therapeutic level of Warfarin (INR 2-3)

• Partial Thromboplastin Time (PTT/aPTT) – evaluates clot formation time specifically related to clotting factors of the intrinsic pathway.

• Reference level (30-50 seconds; on heparin 1.5-2.5x ULN)

• Evaluates specific clotting factors (VIII, IX, XI, XII), and can be useful in diagnosis of hemophilias

• Establishing a baseline for coagulopathies or bleeding patients

• Monitoring patients on heparin.

• Highly sensitive for coagulopathy therefore often best initial test but non-specific.

#### Arterial Blood Gas (ABG)/Venous Blood Gas (VBG)

• Can be helpful in critically ill patients with suspected acid-base disturbances and to evaluate for hypoxemia.

• In situations where the knowledge of the pO2 is not critical, a VBG is often less painful for the patient to obtain and provides almost the same information as an ABG.

• Included values are pH, pCO2, HCO3- and pO2 in the case of the ABG.

• Reference levels –

• pH (7.35 - 7.45)

• paCO2 (35 - 45 mmHg)

• paO2 (80 - 100 mmHg)

• HCO3- (22-26 mEq/L)

• Interpretation is beyond the scope of the brief overview here.

#### β-HCG (Pregnancy test/Preg) (Cost – \$35)

• Used in evaluating women where pregnancy is suspected or if the presence of a pregnancy would change the management or work-up for the patient. Consideration should be made to use a urine pregnancy test when only a qualitative answer is necessary as it is much cheaper.  Quantitative serum β

• HCG concentrations can be helpful in the work-up of early pregnancy, ectopic pregnancy, molar pregnancy, or after miscarriage.

• Will begin to appear in blood and urine as early as 10 days from conception.

• Reference level (β-hCG levels are expected to double every 2-3 days for the first 4 weeks of the pregnancy, and every 96 hours after 6 weeks until 10 weeks gestation).

• Low β-hCG: Failure to double in 48—72 hours suggests ectopic pregnancy or abnormal intrauterine pregnancy

• High β-hCG: Gestational trophoblastic neoplasms (e.g. choriocarcinoma, hydatidiform mole)

• A detectable β-hCG in a male is suggestive of a malignancy and warrants further investigation.

#### Urinalysis (UA) (Cost – \$22)

• UA – Urinalysis tests for Glucose, ketones, specific gravity, protein, myoglobin (not hemoglobin), RBC, WBC, Casts, and cellular/bacterial byproducts.

• A combination of nitrates, leukocyte esterase, WBC, and bacteria indicate urinary tract infection

• Bacteria, any amount in clean sample; high specificity but low sensitivity

• Leukocyte esterase, positive = pyuria (WBC present in urine); high sensitivity, low specificity

• WBC, >10 = pyuria; high sensitivity, low specificity

• Nitrite, positive = presence of bacteria that reduce nitrate; high specificity, low sensitivity

• Epithelial cells, <5 = clean sample, higher = sample contaminated via skin flora.

• Interpretation of results for acute infection in patients with chronic indwelling catheters is difficult as the catheters can be colonized by bateria; a urine culture and sensitivities is recommended in this situation as well as correlation with patient’s symptoms.

#### Urine Toxicology (UTox) (Cost – \$129)

• Common drugs screened for include amphetamines, cocaine, benzodiazepines, barbiturates, opiates, marijuana, and PCP

• Careful interpretation of this test is required. For example, the presence of benzodiazepines in the urine of a patient does not preclude the presence of another, much more serious, cause of altered mental status requiring further work-up and intervention. Patients who abuse varying substances have a much higher risk of concurrent serious medical comorbidities and trauma.

• Cutoff points defining positive and negative tests are arbitrary, chosen to maximize sensitivity and specificity rather than correlate with degree of impairment/toxicity

• Urine with drug levels below the cutoff will be reported as negative, even though the drug may be present in the system

• Most drugs typically detectable up to 3 days after use, although this varies (e.g. benzodiazepines and barbiturates can be present for up to 6 weeks after heavy use and up to 11 weeks with marijuana)

• Test further limited by many false-negatives and false-positives

• Pearl: Don’t anchor on a diagnosis based on the results of the urine drugs screen, try to identify the toxidrome!

#### Fecal Occult Blood Test (FOBT) (Cost – \$57)

• Used to detect occult (NOT clinically apparent) blood presence in stool. Rectal bleeding per patient history or a grossly bloody rectal exam do not need a FOBT. Very useful in undifferentiated new anemia work-up, particularly in elderly patients or poor historians.

• 2 main tests:

• Detect heme (cheap, less sensitive and specific, fast)

• Guaiac-based: detect pseudoperoxidase in heme (e.g. Hemoccult, Hemoccult SENSA)

• Detect globin (expensive, more sensitive and specific, slow)

• Immunochemical tests to detect globin. Ag-Ab reaction specific for human Hb. Do not react with animal Hb or peroxide-containing foods

• False negative:

• Proximal GI lesions allow degradation of heme, not allowing oxidation

• >250mg/day of Vitamin C or other antioxidants (reducing agents interfere with guaiac oxidation)

• Antacids

• False positive:

• Mb/Hb in red meat

• Peroxidase-rich raw vegetables and fruits if tested immediately after collection (turnips, horseradish, artichokes, mushrooms, radishes, broccoli, beets, apples, oranges, bananas, pears, grapes)

### Pearls and Pitfalls

• Before ordering a test, think about how you will utilize the result. Knowing what your next step will be will prevent you from falling into the trap of ordering more tests simply to justify an unexpected result.

• Interpret results in the context of others. For example, a serum sodium level of 122 mmol/L in an altered patient means something different if the serum glucose is also 500 mg/dL.

• Be sure to review your patient’s prior laboratory test results. A serum creatinine of 1.19 mg/dL may not flag as abnormal, but it certainly is such if two days ago it was 0.80 mg/dL.

• Remember, every additional test ordered is another sample needing collection. Be sure to involve your nurses and technicians in your decision making to avoid “nickel and diming”.

### Case Study Resolution

After a discussion with the medical student on the pretest probability of a disease warranting a blood draw in a patient with an isolated hand injury, you and the medical student agree that this patient would not benefit from any laboratory testing. The patient is relieved because he will not be stuck with a needle and is not going to have to pay for unnecessary laboratory studies.

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