What is the best course of action for a 14-year-old adolescent patient with thrombocytopenia, increasing indirect bilirubin, impaired renal function, and hypertension?

Atypical Hemolytic Uremic Syndrome (aHUS) - Immediate Management Required

This 14-year-old patient presents with the classic triad of thrombotic microangiopathy (TMA): thrombocytopenia, hemolytic anemia (indicated by rising indirect bilirubin), and acute kidney injury (rising creatinine with hypertension), which strongly suggests atypical hemolytic uremic syndrome (aHUS) or thrombotic thrombocytopenic purpura (TTP) and requires immediate hematology consultation and urgent diagnostic workup before initiating treatment. 1, 2

Immediate Diagnostic Priorities

Critical laboratory tests must be obtained emergently:

• ADAMTS13 activity level and inhibitor titer - This is the single most important test to distinguish TTP from aHUS, though treatment should NOT be delayed awaiting results 1, 2
• Peripheral blood smear - Confirm presence of schistocytes (>1% supports TMA diagnosis, though absence doesn't exclude it) 1, 2
• Haptoglobin, LDH, and reticulocyte count - To confirm microangiopathic hemolysis 1, 2
• Direct Coombs test - Must be negative to confirm non-immune hemolysis 1
• Stool culture for Shiga toxin-producing E. coli (STEC) - Essential to exclude STEC-HUS, though the absence of diarrhea or short diarrheal period before TMA onset favors aHUS 1
• Comprehensive metabolic panel and coagulation studies (PT, aPTT, fibrinogen) - To assess organ function and exclude DIC 2, 3

Immediate Treatment Algorithm

If ADAMTS13 Activity <10% (TTP Suspected):

Initiate therapeutic plasma exchange (TPE) immediately with corticosteroids and rituximab without delay, as mortality increases significantly with treatment delays 2

• Methylprednisolone 1 g IV daily for 3 days, with first dose given immediately after first TPE session 2
• Transition to prednisone 1-2 mg/kg/day after initial high-dose therapy 2
• Rituximab should be offered as part of initial therapy 2
• Consider caplacizumab for severe ADAMTS13 deficiency with elevated inhibitor 2

If ADAMTS13 Activity >10% (aHUS Suspected):

Blood pressure control is the cornerstone of initial management, as malignant hypertension-induced TMA responds to antihypertensive therapy alone 4, 5

• Initiate aggressive antihypertensive therapy immediately - target blood pressure <90th percentile for age, sex, and height (or <130/80 mmHg in adolescents ≥13 years) 1
• ACE inhibitors or angiotensin receptor blockers are first-line for hypertension with renal involvement 1
• However, in females of childbearing age, provide reproductive counseling as ACE inhibitors/ARBs are teratogenic and should be avoided without reliable contraception 1
• Consider complement blockade with eculizumab for confirmed aHUS, particularly if genetic testing reveals complement pathway mutations 1, 6

Critical Management Considerations

Avoid platelet transfusions unless life-threatening hemorrhage occurs, as they may worsen thrombosis in TMA 2

For severe bleeding with platelet count <10,000/μL:

• Platelet transfusion immediately 3
• Fresh frozen plasma if coagulation studies prolonged 3
• IV methylprednisolone 30 mg/kg/day 3
• IVIg 0.8-1 g/kg as single dose 3

Distinguishing Features Favoring aHUS Over TTP

The clinical presentation helps differentiate these conditions before ADAMTS13 results return 1, 5:

• Prominent renal dysfunction with rising creatinine and hypertension strongly favors aHUS or malignant hypertension-induced TMA over TTP 5
• Relatively modest thrombocytopenia (compared to severe thrombocytopenia in TTP) 5
• Absence of severe neurological symptoms (neurological involvement occurs in only 10-20% of aHUS cases) 1
• Age at presentation - aHUS can occur at any age, and higher mortality occurs in children than adults 1

Genetic and Secondary Causes to Consider

In adolescents, investigate for complement-unrelated genes and secondary causes: 1

• Complement pathway genetic testing (CFH, CFI, CFB, C3, MCP, THBD) 1
• Drug exposure history (certain medications can trigger TMA) 2
• Exclude systemic lupus erythematosus and other autoimmune conditions 2

Renal Support and Monitoring

Initiate hemodialysis if indicated by severe uremia, hyperkalemia, volume overload, or metabolic acidosis 4, 6

Daily monitoring requirements during acute phase: 2

• Platelet count, hemoglobin, LDH
• Renal function (creatinine, urine output)
• Blood pressure measurements
• Clinical assessment for bleeding or neurological changes

Common Pitfalls to Avoid

Do not delay treatment while awaiting complete diagnostic workup if severe bleeding is present - give platelets, FFP, and consider IVIg/steroids emergently 3

Do not assume isolated immune thrombocytopenia (ITP) when thrombocytopenia presents with rising creatinine and indirect bilirubin - this triad mandates exclusion of TMA 1, 3

Do not combine two RAS blockers (ACE inhibitor and ARB) for hypertension management 1

Monitor for hemolysis if using anti-D immunoglobulin - avoid in patients with evidence of autoimmune hemolysis or decreased hemoglobin due to bleeding 1