Key Clinical Formulas & Scores
Sensitivity = TP / (TP + FN) β proportion of true positives correctly identified
Specificity = TN / (TN + FP) β proportion of true negatives correctly identified
PPV (Positive Predictive Value) = TP / (TP + FP) β probability that positive test = true disease
NPV (Negative Predictive Value) = TN / (TN + FN) β probability that negative test = no disease
PPV and NPV are prevalence-dependent; sensitivity and specificity are not
LR+ = Sensitivity / (1 - Specificity) β probability of positive test in diseased vs non-diseased
LR- = (1 - Sensitivity) / Specificity β probability of negative test in diseased vs non-diseased
LR+ >10: large increase in probability of disease
LR+ 5-10: moderate increase
LR+ 2-5: small increase
LR- <0.1: large decrease in probability
LR- 0.1-0.2: moderate decrease
Post-test probability = (Pre-test probability Γ LR) / [(Pre-test probability Γ LR) + (1 - Pre-test probability)]
AG = NaβΊ - (Clβ» + HCOββ») = 8-12 mEq/L (normal)
Elevated AG: MUDPILES (Methanol, Uremia, DKA, Propylene glycol, INH/Iron, Lactic acidosis, Ethylene glycol, Salicylates)
Osmolal gap = Measured osmolality - Calculated osmolality
Calculated osmolality = 2[Na] + Glucose/18 + BUN/2.8 + EtOH/4.6
Osmolal gap >10: toxic alcohol ingestion (methanol, ethylene glycol)
Reticulocyte % Γ (Patient Hct / Normal Hct) = Corrected retic count
Reticulocyte production index (RPI) = Corrected retic % / Maturation correction factor
RPI <2: hypoproliferative anemia (bone marrow failure, nutritional deficiency, anemia of chronic disease)
RPI >3: appropriate bone marrow response (blood loss, hemolysis)
Absolute retic count = Retic % Γ RBC count (normal 25,000-75,000/ΞΌL)
PT (Prothrombin Time): extrinsic + common pathway (Factors VII, X, V, II, I). Normal 11-13.5 sec. Monitor warfarin (INR)
aPTT: intrinsic + common pathway (Factors XII, XI, IX, VIII, X, V, II, I). Normal 25-35 sec. Monitor heparin
Thrombin Time: fibrinogen β fibrin. Normal 14-19 sec. Detects hypofibrinogenemia, DIC, direct thrombin inhibitors
D-dimimer: fibrin degradation product. Negative excludes PE/DVT in low-risk patients (age-adjusted: age Γ 10 if >50)
Mixing study: corrects = factor deficiency; does not correct = inhibitor (lupus anticoagulant, specific factor inhibitor)
Core Concepts
Quality Control in the Clinical Laboratory
Westgard Rules: 1-2s (warning), 1-3s (reject), 2-2s (reject), R-4s (reject), 4-1s (reject), 10-X (reject). Levey-Jennings charts: visualize QC data over time. Six Sigma: measures process capability (Ο 6 = 3.4 defects per million). Sigma metric = (TEa - bias) / CV. CLIA '88: Clinical Laboratory Improvement Amendments β federal regulatory standards. CAP accreditation: College of American Pathologists proficiency testing. Point-of-care testing (POCT): requires competency assessment, connectivity to LIS, and quality oversight.
Hematology: CBC Interpretation
Complete Blood Count components: RBC count, hemoglobin, hematocrit, MCV, MCH, MCHC, RDW, reticulocyte count, WBC count with differential, platelet count. Anemia classification by MCV: microcytic (<80), normocytic (80-100), macrocytic (>100). Leukocytosis: neutrophilia (bacterial infection, stress, inflammation), lymphocytosis (viral infection), eosinophilia (allergy, parasites, malignancy), monocytosis (chronic infection, autoimmune). Thrombocytopenia: decreased production (bone marrow failure), increased destruction (ITP, TTP, DIC), sequestration (hypersplenism). Peripheral smear review confirms automated flags.
Clinical Chemistry: Critical Values
Critical values requiring immediate physician notification: Potassium <2.5 or >6.5 mEq/L, Glucose <40 or >500 mg/dL, Sodium <120 or >160 mEq/L, Calcium <6.5 or >13 mg/dL, pH <7.20 or >7.60, pCO2 <20 or >70 mmHg, Troponin (elevated above reference), Hemoglobin <7 or >20 g/dL, Platelets <20,000 or >1,000,000/ΞΌL, WBC <1,000 or >50,000/ΞΌL. Turnaround time (TAT): stat tests <60 minutes, routine tests same day. Delta check: significant change from previous value β verifies result validity or indicates acute change.
Clinical Case Studies
Case 1: Diagnostic Test Interpretation β Troponin
Scenario: 60-year-old male with chest pain. Troponin I 0.04 ng/mL (reference <0.04). Pre-test probability of ACS: intermediate (50%). Test sensitivity 90%, specificity 85%.
Analysis: LR+ = 0.90/(1-0.85) = 6. Pre-test odds = 0.50/(1-0.50) = 1.0. Post-test odds = 1.0 Γ 6 = 6.0. Post-test probability = 6/(1+6) = 85.7%. Interpretation: A positive troponin in this patient significantly increases probability of ACS β admit for further evaluation. Note: single troponin elevation does not distinguish Type 1 (plaque rupture) from Type 2 (demand ischemia) MI.
Case 2: Hemolysis β Spurious Results
Scenario: 35-year-old female, blood draw reported as "hemolyzed." Results: K 7.8 mEq/L, LDH 1,200 U/L, AST 180 U/L, Hgb 6.5 g/dL, haptoglobin <10 mg/dL. Peripheral smear shows schistocytes.
Analysis: Hemolysis causes spurious elevation of intracellular elements: K, LDH, AST, phosphate. True in vivo hemolysis supported by: low haptoglobin, elevated indirect bilirubin, schistocytes on smear, increased reticulocyte count. However, the degree of potassium elevation (7.8) is disproportionate to hemolysis β consider mixed picture or specimen issue. Repeat draw with proper technique (avoid small gauge, vigorous mixing, ice transport if needed). Correlate clinically.
Case 3: Coagulopathy β Mixing Study
Scenario: 50-year-old male, prolonged aPTT (85 sec), PT 14 sec (normal). No bleeding history. Patient on no anticoagulants. Mixing study: aPTT corrects to 30 sec (1:1 mix with normal plasma).
Analysis: aPTT correction with mixing study indicates factor deficiency (not inhibitor). Isolated aPTT prolongation with normal PT suggests intrinsic pathway deficiency: Factor VIII (Hemophilia A), IX (Hemophilia B), XI, or XII. Next steps: factor assays (VIII, IX, XI, XII). von Willebrand disease can also cause prolonged aPTT (vWF stabilizes Factor VIII). Factor XII deficiency causes prolonged aPTT but NO bleeding tendency (contact activation defect). Lupus anticoagulant would NOT correct with mixing study (or correct partially with immediate correction but prolong on incubation).
Practice Questions
A: PPV = (Sens Γ Prev) / [(Sens Γ Prev) + ((1-Spec) Γ (1-Prev))] = (0.95 Γ 0.10) / [(0.95 Γ 0.10) + (0.10 Γ 0.90)] = 0.095 / (0.095 + 0.090) = 0.095/0.185 = 51.4%. Even with good sensitivity and specificity, PPV is modest at low prevalence.
A: 1-3s rule β REJECT run. This indicates random error or systematic shift. Investigate cause before reporting patient results.
A: Iron deficiency anemia (microcytic, hypochromic): low MCV, low ferritin (<30 = diagnostic), high TIBC, low transferrin saturation (<15%). Confirmatory: response to iron therapy (reticulocyte count rises in 7-10 days, Hgb rises in 2-4 weeks).
A: Negative D-dimer in low pre-test probability patient effectively excludes PE (NPV >95%). No imaging needed. For patients >50, use age-adjusted cutoff: age Γ 10 ng/mL (e.g., 60-year-old: <600 ng/mL).
A: STAT tests should result within 60 minutes of specimen receipt in the laboratory. Troponin is a critical value when significantly elevated β immediate physician notification required. Serial troponins at 0, 3, 6 hours improve sensitivity for MI diagnosis.