What is the most likely diagnosis and immediate management for an adult with leukocytosis (white blood cell count 13.5 ×10⁹/L), microcytic anemia (mean corpuscular volume 72 fL), normal sodium (141 mmol/L) and potassium (4.8 mmol/L), impaired renal function (creatinine 3.2 mg/dL, blood urea nitrogen 17 mg/dL), and mild hyperbilirubinemia (total bilirubin 3 mg/dL)?

Acute Kidney Injury with Hemolytic Anemia and Sepsis

This patient requires immediate evaluation for sepsis with organ dysfunction and hemolytic uremic syndrome (HUS) or thrombotic microangiopathy (TMA), followed by urgent nephrology consultation and consideration of plasma exchange if TMA is confirmed.

Immediate Clinical Assessment

The laboratory constellation points to a life-threatening syndrome requiring urgent intervention:

• Severe renal dysfunction (creatinine 3.2 mg/dL) meets criteria for acute kidney injury and severe sepsis 1
• Microcytic anemia (MCV 72 fL) with mild leukocytosis (WBC 13.5 × 10⁹/L) suggests either chronic iron deficiency with superimposed acute illness or microangiopathic hemolysis 1
• Hyperbilirubinemia (bilirubin 3 mg/dL) indicates hemolysis, hepatic dysfunction, or both 1
• Normal electrolytes (sodium 141, potassium 4.8) argue against severe tumor lysis syndrome but do not exclude it 1

Diagnostic Priority: Rule Out Thrombotic Microangiopathy

The triad of anemia, renal failure, and hyperbilirubinemia mandates immediate evaluation for TMA/HUS:

• Obtain peripheral blood smear urgently to assess for schistocytes (>1% supports TMA diagnosis, though absence does not exclude it) 1
• Measure haptoglobin, LDH, and indirect bilirubin to confirm microangiopathic hemolysis 1
• Check platelet count immediately—thrombocytopenia (<150,000/mm³ or 25% reduction) is a cardinal feature of TMA 1
• Order ADAMTS13 activity stat to differentiate thrombotic thrombocytopenic purpura (TTP, activity <10%) from HUS 1
• Send stool for Shiga toxin/VTEC if any history of diarrhea, even brief 1

The combination of renal dysfunction (creatinine >2.0 mg/dL), bilirubin >2 mg/dL, and leukocytosis >12 × 10⁹/L meets criteria for severe sepsis with organ dysfunction 1. However, TMA can mimic sepsis and requires plasma exchange rather than antibiotics alone 1.

Concurrent Evaluation for Sepsis

While awaiting TMA workup results:

• Obtain blood cultures, urinalysis, and chest X-ray to identify infection source 1
• Measure procalcitonin and C-reactive protein—values >2 SD above normal support sepsis 1
• Check coagulation studies (INR, aPTT)—INR >1.5 or aPTT >60 seconds indicates coagulopathy consistent with severe sepsis 1
• Assess for hypotension or lactate elevation—these define septic shock requiring immediate fluid resuscitation 1

Differential Diagnosis Framework

If Schistocytes Present + Thrombocytopenia + Hemolysis Confirmed:

Atypical HUS (complement-mediated TMA) is most likely 1:

• Neurologic involvement occurs in only 10–20% of aHUS cases, so absence of CNS symptoms does not exclude it 1
• Initiate plasma exchange immediately while awaiting ADAMTS13 results 1
• Consult nephrology urgently for potential eculizumab therapy 1
• Genetic testing for complement pathway mutations should follow stabilization 1

If Microcytosis Without Hemolysis:

Chronic iron deficiency with superimposed acute illness is the diagnosis 2, 3:

• MCV 72 fL with elevated RDW (if available) strongly suggests iron deficiency 2
• Measure serum ferritin, transferrin saturation, and iron studies 2
• Ferritin <30 µg/L confirms iron deficiency; <45 µg/L is optimal threshold in practice 2
• Investigate for GI blood loss (most common cause in adults) once stabilized 2
• The acute kidney injury likely represents sepsis-induced acute tubular necrosis rather than hemolytic-uremic syndrome 1

Immediate Management Algorithm

Step 1: Stabilize and Resuscitate

• Aggressive IV fluid resuscitation (crystalloid boluses) if hypotensive or lactate elevated 1
• Avoid red cell transfusion until TMA is excluded—transfusion can worsen microvascular thrombosis 1
• Maintain urine output >0.5 mL/kg/hr with fluids; avoid nephrotoxic agents 1

Step 2: Empiric Antimicrobial Therapy

• Start broad-spectrum antibiotics immediately if sepsis suspected (do not delay for culture results) 1
• Cover gram-negative and gram-positive organisms based on likely source 1

Step 3: Nephrology Consultation

• Urgent consultation required for creatinine 3.2 mg/dL with unclear etiology 1
• Discuss need for renal replacement therapy if oliguria develops or potassium rises 1

Step 4: Hematology Consultation if TMA Suspected

• Plasma exchange should begin within 4–8 hours if TMA cannot be excluded 1
• Do not wait for ADAMTS13 results to initiate plasma exchange in critically ill patients 1

Critical Pitfalls to Avoid

• Do not assume microcytic anemia is simply iron deficiency in the setting of acute renal failure and hyperbilirubinemia—hemolysis must be excluded 1, 2
• Do not delay plasma exchange if TMA is possible—mortality approaches 90% without treatment 1
• Do not attribute hyperbilirubinemia to liver disease alone—indirect hyperbilirubinemia suggests hemolysis 1
• Do not overlook combined pathology—sepsis and TMA can coexist, and both require specific treatment 1
• Do not transfuse platelets in TMA unless life-threatening bleeding occurs—transfusion may worsen thrombosis 1

Monitoring and Follow-Up

• Repeat CBC, creatinine, and LDH every 6–12 hours during acute phase 1
• Monitor for neurologic symptoms (seizures, altered mental status, focal deficits)—these indicate CNS involvement requiring brain MRI 1
• Track urine output hourly—oliguria (<0.5 mL/kg/hr for >2 hours) indicates worsening renal function 1
• Serial blood smears to assess schistocyte burden if TMA confirmed 1

The key decision point is whether this represents sepsis with acute tubular necrosis versus TMA with renal involvement—the peripheral smear, platelet count, and hemolysis markers will differentiate these within hours and determine whether plasma exchange is needed 1.