Diagnostic Procedures Flashcards

A 58-year-old patient on warfarin presents with an INR of 1.8 (target 2.0–3.0). The prescriber suspects non-adherence but the patient insists they have been compliant. Which laboratory finding would most strongly suggest a pharmacokinetic drug interaction rather than non-adherence as the cause of the subtherapeutic INR?

Answer: A recent doubling of serum cholestyramine co-administration documented in the medication list

Cholestyramine (a bile acid sequestrant) binds warfarin in the GI tract and significantly reduces its absorption, lowering the INR despite patient adherence. This represents a documented pharmacokinetic interaction at the absorption level. Serum albumin changes would affect protein binding but rarely reduce INR to this extent acutely. VKORC1 variants affect pharmacodynamics (warfarin sensitivity at initiation) rather than explaining a sudden drop in a previously stable patient. Thrombocytopenia would not explain a low INR.

During therapeutic drug monitoring (TDM) of vancomycin using AUC-guided dosing, a patient's calculated AUC₀₋₂₄ is 520 mg·h/L. The current regimen is 1250 mg IV q12h. The MIC of the isolated MRSA strain is 1 mg/L. Which is the most pharmacodynamically appropriate interpretation?

Answer: The regimen is supratherapeutic; dose reduction is warranted to minimize nephrotoxicity risk while maintaining efficacy

Current ASHP/IDSA/SIDP guidelines recommend an AUC/MIC target of 400–600 mg·h/L for serious MRSA infections. An AUC₀₋₂₄ of 520 mg·h/L with an MIC of 1 mg/L yields an AUC/MIC of 520, which falls within the therapeutic window. However, values above 600 are associated with significantly increased nephrotoxicity without additional efficacy gain. At 520 the patient is within range but approaching the upper limit — the regimen is currently acceptable but the prescriber should monitor renal function closely; dose reduction is not yet warranted. The most precise interpretation is that the regimen is within target, making option A the closest, but option B reflects the nuanced clinical concern. Re-reading: AUC/MIC = 520/1 = 520, which IS within 400–600 — option A states it correctly. Option B recommends unnecessary dose reduction. The correct answer is A.

A 72-year-old woman with CKD stage 3b (eGFR 38 mL/min/1.73m²) is being evaluated for iron-deficiency anemia. Her ferritin is 95 µg/L and transferrin saturation (TSAT) is 17%. Hemoglobin is 98 g/L. She is not on erythropoiesis-stimulating agents (ESAs). Which interpretation of these iron indices is most accurate in the context of CKD?

Answer: Ferritin ≥100 µg/L is required to exclude absolute iron deficiency in CKD, and TSAT <20% suggests functional iron deficiency coexisting with the anemia of CKD

In CKD, ferritin is an acute-phase reactant and is often falsely elevated relative to true iron stores. KDIGO guidelines use thresholds of ferritin <500 µg/L AND TSAT <30% as parameters where IV iron supplementation can be trialed. A ferritin of 95 µg/L does not rule out iron deficiency in CKD, especially paired with a TSAT of 17% (<20%), which indicates functional iron deficiency — insufficient iron delivery to erythroid precursors relative to demand. Option A is incomplete. Option C applies general population reference ranges inappropriately to CKD. Option D is incorrect; ferritin of 95 µg/L does not represent iron overload.

A pharmacist reviewing a requisition for a HER2 immunohistochemistry (IHC) test notices the result is reported as 2+ (equivocal). The oncologist asks the pharmacist to advise on next steps before initiating trastuzumab therapy. What is the most appropriate recommendation?

Answer: Proceed to fluorescence in situ hybridization (FISH) to determine HER2 gene amplification status before initiating trastuzumab

Per ASCO/CAP guidelines, an IHC result of 2+ is equivocal and must be reflexed to FISH (or another in situ hybridization method) to determine whether true HER2 gene amplification is present. IHC 3+ (strong complete membrane staining in >10% of cells) is required for direct HER2-positive classification. Trastuzumab should only be initiated once HER2 positivity is confirmed, as the drug offers no benefit — and carries cardiotoxicity risk — in HER2-negative tumours. Empirical initiation or repeating IHC alone are not guideline-concordant steps for an equivocal result.

A 45-year-old male presents for monitoring of lithium therapy (bipolar I, maintenance). His serum lithium level drawn 10 hours post-dose is 0.95 mmol/L. He reports mild fine tremor and increased thirst. Serum creatinine is elevated compared to his baseline 6 months ago (baseline 82 µmol/L, now 108 µmol/L). Which is the most clinically significant concern raised by these combined findings?

Answer: The creatinine rise suggests early lithium-induced nephrotoxicity, warranting reassessment of the lithium regimen independent of the current level

A 32% rise in serum creatinine from baseline (82 → 108 µmol/L) in a patient on long-term lithium is a clinically significant signal of nephrotoxicity, a well-documented and potentially irreversible adverse effect of chronic lithium use. Even though the lithium level at 0.95 mmol/L falls within the typical maintenance range (0.6–1.2 mmol/L), cumulative nephrotoxicity is related to duration and exposure rather than acute supratherapeutic levels. This warrants a nephrology review and serious consideration of lithium alternatives. Option A is incorrect — 0.95 mmol/L is within range. Option B is relevant (standard sampling is 12 hours post-dose) but the 10-hour level would be slightly higher than a true trough, not dramatically different. Option D dismisses a clinically meaningful renal trend.

A patient with suspected Clostridioides difficile infection (CDI) has a positive glutamate dehydrogenase (GDH) antigen test but a negative toxin immunoassay (EIA). The treating team asks the pharmacist to interpret this result and recommend a testing pathway. What is the most appropriate response?

Answer: The discordant result requires reflex nucleic acid amplification testing (NAAT) to differentiate C. difficile colonization from toxigenic CDI before initiating therapy

Current IDSA/SHEA guidelines recommend a two- or three-step algorithm for CDI diagnosis. GDH detects the C. difficile antigen (present in both toxigenic and non-toxigenic strains) with high sensitivity but low specificity — a positive GDH confirms the organism is present. The toxin EIA is specific but has limited sensitivity (~60–70%), meaning false negatives occur. A GDH+/toxin EIA– result is discordant and should reflexively be tested by NAAT (PCR), which detects the toxin gene (tcdB) with high sensitivity and specificity. A positive NAAT in this context suggests toxin-producing C. difficile; however, clinical context (symptoms, WBC, frequency of stools) must guide the final treatment decision to avoid over-treating asymptomatic colonizers. Option A ignores the known limitations of toxin EIA. Option C is not guideline-concordant. Option D relies on GDH, which is not specific for toxigenic strains.