Investigation Findings in Sepsis

1. Hematology (CBC)

"Thrombocytopenia, elevated prothrombin time, elevated activated partial thromboplastin time, decreased fibrinogen, and increased fibrin split products are associated with DIC and severe sepsis syndrome." - ROSEN's Emergency Medicine

2. Coagulation Profile

• PT/aPTT: Elevated (prolonged) - coagulation factor consumption
• Fibrinogen: Decreased - consumed in DIC
• D-dimer / Fibrin split products (FSP): Elevated - indicating fibrinolysis
• These findings together suggest Disseminated Intravascular Coagulation (DIC), a serious complication of severe sepsis

3. Blood Chemistry (Metabolic Panel)

• Bicarbonate: Low - indicates metabolic acidosis and inadequate perfusion
• Anion gap: Elevated - typically from lactic acidosis; DKA must be excluded
• Serum creatinine / eGFR: Elevated / reduced - signals acute kidney injury (organ failure marker, worse prognosis)
• Bilirubin: Elevated - suggests hepatic dysfunction; elevated direct bilirubin may point to a biliary source of sepsis
• Liver enzymes (ALT, AST, ALP): Elevated in hepatic involvement
• Lipase: Elevated if pancreatitis is the underlying cause of SIRS/sepsis
• Calcium, Magnesium, Phosphorus: Should be checked; often depleted

4. Lactate

• Serum lactate >2 mmol/L: Marker of tissue hypoperfusion, even without overt hypotension ("cryptic shock")
• Lactate >4 mmol/L: Meets criteria for septic shock and carries ~28% mortality
• Mortality correlation (ROSEN's):
  • Lactate 0-2.5 mg/dL → ~5% mortality
  • Lactate 2.5-4.0 mg/dL → ~9% mortality
  • Lactate >4.0 mg/dL → ~28% mortality
• Serial lactate measurements are used to assess treatment response

5. Inflammatory Biomarkers

• C-Reactive Protein (CRP): Elevated - acute-phase reactant, non-specific
• Procalcitonin (PCT): Elevated - more specific for bacterial sepsis; primarily useful for serial monitoring and antibiotic stewardship (guiding de-escalation)
• Presepsin: Emerging biomarker - a 2025 meta-analysis (PMID: 40839596) confirms diagnostic value across neonates, children, and adults
• Platelet parameters: A 2025 systematic review (PMID: 41225524) identifies thrombocytopenia and MPV changes as potential sepsis biomarkers
• Neuron-specific enolase (NSE): Elevated in sepsis-associated encephalopathy per a 2024 meta-analysis (PMID: 39039544)

6. Blood Gas (ABG/VBG)

• Metabolic acidosis - low pH, low HCO3, compensatory low pCO2
• Elevated lactate on blood gas
• Hypoxemia (low PaO2) - if ARDS is developing
• ABG helps classify acid-base disturbances and assess respiratory compensation

7. Microbiology / Cultures

• Blood cultures x 2 (peripheral): Should be collected before starting antibiotics; yield is 30-40% in confirmed sepsis (only 5-10% in undifferentiated ED presentations)
• Urine culture and urinalysis: Essential - especially in elderly patients; may show pyuria, bacteriuria
• Sputum culture: If respiratory source suspected
• Wound / abscess cultures: Site-specific sampling
• CSF culture and Gram stain: If meningitis suspected
• Gram stain results guide initial empirical therapy

8. Imaging

• Chest X-ray: Look for pneumonia, pulmonary infiltrates (ARDS pattern), pleural effusion
• CT scan (abdomen/pelvis/chest): Identify occult source - abscess, perforation, cholecystitis
• Ultrasound (POCUS): Assess fluid status, cardiac function, identify collections

9. Urinalysis

• Pyuria, bacteriuria, nitrites - suggest urinary source
• Important in older patients who may lack localizing urinary symptoms

10. Organ Dysfunction Markers (SOFA Score Components)

Summary Box: Initial Sepsis Work-up

• CBC, BMP, LFTs, ABG
• Serum lactate
• ± Procalcitonin
• Peripheral blood cultures x 2 (before antibiotics)
• Urinalysis + urine culture
• Chest X-ray ± CT / Ultrasound

Clinical Findings in Sepsis

Definitions and Diagnostic Criteria

• Temperature >38°C or <36°C
• Heart rate >90 beats/min
• Respiratory rate >20 breaths/min or PaCO2 <32 mmHg
• WBC >12,000/µL, <4,000/µL, or >10% bands

General / Systemic Signs

Organ-Specific Clinical Findings

1. Cardiovascular (25% develop shock; 50% have myocardial dysfunction)

• Tachycardia
• Hypotension (SBP <90 mmHg or ≥40 mmHg drop from baseline)
• Skin mottling - patchy violaceous discolouration, especially on knees
• Prolonged capillary refill (>2 seconds)
• Oliguria - reduced organ perfusion
• Altered mental status from cerebral hypoperfusion
• Early sepsis: warm, flushed skin (vasodilation, high cardiac output)
• Late/septic shock: cold, clammy skin (vasoconstriction, falling output)

2. Neurological (54% develop encephalopathy)

• Altered consciousness - confusion, disorientation, agitation
• Delirium - hyperactive or hypoactive
• Reduced cognition and attention
• Coma in severe cases
• Seizures, stroke, or meningitis may occur as complications (require further evaluation with EEG, brain imaging, LP)

3. Respiratory (7% develop ARDS)

• Tachypnoea and increased work of breathing
• Hypoxia - dyspnoea, cyanosis, SpO2 <90%
• Bilateral pulmonary infiltrates if ARDS develops (PaO2/FiO2 <300)
• Crackles on auscultation

4. Renal (67% develop acute kidney injury - most common organ affected)

• Oliguria (<0.5 mL/kg/hr) or anuria
• Peripheral oedema from fluid retention
• Biochemical: rising creatinine, BUN, hyperkalemia, proteinuria

5. Gastrointestinal / Hepatic

• Jaundice - hepatic dysfunction, elevated bilirubin
• Abdominal pain, distension, ileus
• Nausea, vomiting
• GI bleeding (stress ulceration)

6. Haematological / Skin

• Petechiae and purpura - thrombocytopenia and DIC
• Ecchymoses and bleeding from venepuncture sites - DIC
• Skin mottling (livedo reticularis)
• Purpura fulminans in meningococcal sepsis - rapidly spreading necrotic purpuric lesions

Progression: Early vs Late Sepsis

Quick Reference: SOFA Score (Organ Dysfunction Criteria)

bedside Screening: qSOFA

• Altered mentation (GCS <15)
• Respiratory rate ≥22/min
• Systolic BP ≤100 mmHg

TLC of 12,500/mm³ - Interpretation in Sepsis

Normal Reference Range

• Normal TLC: 4,000 - 11,000 cells/mm³
• TLC of 12,500 = mildly elevated → Leukocytosis

Significance in Sepsis

• Temperature >38°C or <36°C
• Heart rate >90 bpm
• Respiratory rate >20 breaths/min
• WBC >12,000 or <4,000 or >10% bands ← this patient meets this

How to Interpret 12,500 in Context

1. Early sepsis or a mild systemic inflammatory response
2. Localised bacterial infection without systemic spread
3. Physiological stress (surgery, trauma, steroids, exercise)
4. Viral infection (can cause mild leukocytosis)

Important Caveats (from ROSEN's Emergency Medicine)

• Leukocytosis is insensitive and non-specific for sepsis - its absence does not rule out sepsis, and its presence does not confirm it
• The degree of leukocytosis does not reliably correlate with severity of infection
• Leukopenia (<4,000) in sepsis is actually a worse prognostic sign than leukocytosis, indicating bone marrow suppression from overwhelming infection
• Always look at the differential count alongside the total:
  • Neutrophilia with bandemia (>10% bands) = more specific for bacterial infection
  • Lymphopenia alongside leukocytosis = common in sepsis, associated with immune dysregulation
  • Left shift (immature granulocytes) = bone marrow responding to demand

Bottom Line

• Satisfies the WBC SIRS criterion (>12,000)
• Represents mild leukocytosis - consistent with but not diagnostic of sepsis
• Must be interpreted alongside clinical features, other SIRS criteria, lactate, procalcitonin, and cultures
• A normal or low WBC in an unwell patient would actually be more concerning