Laboratory Testing for Non-Specific Symptoms
For patients presenting with non-specific symptoms, routine laboratory testing should be avoided unless specific clinical features suggest an underlying disease process that would be confirmed or excluded by testing. The most appropriate approach is to perform targeted testing only when the history and physical examination raise diagnostic suspicion for a specific condition 1, 2.
When Laboratory Testing is NOT Indicated
In the absence of fever, leukocytosis, left shift, or specific clinical manifestations of focal infection, additional diagnostic tests are not indicated due to low potential yield 1. This principle applies broadly to non-specific symptoms where no clear diagnostic hypothesis exists.
The most frequent cause of abnormal test results in screening scenarios is physiologic variation or laboratory variation, not underlying disease 2. Ordering tests without diagnostic suspicion leads to false-positive results that trigger unnecessary follow-up testing and patient anxiety.
Tests should only be performed if they have reasonable diagnostic yield, are of low risk and cost, and will actually change patient management 1. If a test result will not alter your treatment strategy, there is little justification for ordering it.
When Laboratory Testing IS Indicated
For Suspected Infection
Complete blood count with differential should be performed within 12-24 hours of symptom onset (or sooner if seriously ill) when bacterial infection is suspected 1. This recommendation applies specifically when clinical features suggest infection:
- An elevated WBC count (≥14,000 cells/mm³) or left shift (≥6% band neutrophils or total band count ≥1,500 cells/mm³) warrants careful assessment for bacterial infection, with or without fever 1
- The presence of elevated total band count (≥1,500 cells/mm³) has the highest likelihood ratio (14.5) for detecting documented bacterial infection 1
- Left shift (≥6% band neutrophils) has a likelihood ratio of 4.7 for bacterial infection 1
For Specific Symptom Patterns
The testing approach should be guided by the specific constellation of symptoms:
For suspected COVID-19 in symptomatic patients, standard NAAT (rapid RT-PCR or laboratory-based NAAT) is preferred over rapid antigen testing 1. However, if NAAT is unavailable or results will be delayed more than 1 day, rapid antigen testing is acceptable 1.
For patients with suspected systemic infection or sepsis, obtain complete blood count, serum creatinine and electrolytes, inflammatory markers (C-reactive protein, procalcitonin), and blood gas analysis 1. Additionally, check serum glucose, hemoglobin A1c, and urine ketones to investigate undetected diabetes mellitus 1.
Clinical Decision-Making Framework
Step 1: Establish Pre-Test Probability
- Use history and physical examination to estimate the initial probability of disease 3
- When pre-test probability is high, order tests with high specificity to confirm the diagnosis 3
- When pre-test probability is low, order tests with high sensitivity to exclude disease 3
Step 2: Target Testing to Diagnostic Hypotheses
- Only order tests that will confirm or exclude a specific diagnostic suspicion raised during history and physical examination 2, 3
- Avoid "shotgun" approaches with multiple screening tests in the absence of clinical suspicion 2
Step 3: Interpret Abnormal Results Cautiously
- When abnormal results are obtained from screening tests ordered without diagnostic suspicion, search for correlating signs and symptoms 2
- In the absence of evidence indicating underlying disease, follow-up testing is usually unnecessary 2
Common Pitfalls to Avoid
Do not order urinalysis and urine cultures for asymptomatic patients 1. Testing should be reserved for those with acute onset of UTI-associated symptoms (fever, dysuria, gross hematuria, new or worsening urinary incontinence).
Do not order routine imaging or tumor markers in asymptomatic patients for disease screening 1. These tests have not been shown to improve survival outcomes or quality of life and have significant false-positive rates.
Avoid ordering tests simply because they are "routine" or part of a standard panel 1, 2. Each test should have a specific clinical indication.
Do not pursue extensive workups for single abnormal values in otherwise asymptomatic patients without correlating clinical findings 2.
Special Populations
For elderly patients in long-term care facilities with suspected infection, the threshold for CBC testing is lower given their atypical presentations 1. However, the same principle applies: testing should be guided by clinical suspicion rather than performed routinely.