What is the most likely diagnosis and recommended emergent management for a postpartum woman with chronic hemolysis (daily lysed blood for 6 months), prior obstetric complications suggestive of missed thrombotic microangiopathy, acute hypertension and hematuria during labor, and new severe neuro‑psychiatric symptoms?

Postpartum Thrombotic Microangiopathy (TMA) with Chronic Hemolysis

This patient most likely has complement-mediated atypical hemolytic uremic syndrome (aHUS) that was triggered by pregnancy 4 years ago and has remained undiagnosed, with ongoing chronic hemolysis and severe neuropsychiatric sequelae requiring urgent hematology/nephrology consultation, ADAMTS13 testing to exclude TTP, complement studies, and consideration for eculizumab therapy. 1, 2

Diagnostic Reasoning

Evidence Supporting Missed Pregnancy-Associated TMA

The obstetric history 4 years ago demonstrates classic features of acute TMA during labor 1, 3:

• Acute hypertensive crisis during labor (BP 135/108 during pushing after lifetime normotension) indicates autoregulation failure and endothelial injury 4
• Hematuria with bloody urine during active labor suggests acute kidney injury from microvascular thrombosis 1, 2
• Excessive blood loss (650mL without stage 2/3 bleeding) indicates consumptive coagulopathy 3
• Postpartum hypertensive emergency (140/110 at 1 month) with persistent headache indicates ongoing TMA rather than resolving preeclampsia 4

Chronic Hemolysis Pattern

Daily lysed blood specimens for 6+ months with prior nucleated RBCs (1.5 years ago) definitively indicates ongoing microangiopathic hemolysis 4. This chronic pattern distinguishes complement-mediated aHUS from acute TTP or pregnancy-limited HELLP syndrome, both of which resolve after delivery 1, 2.

Neuropsychiatric Manifestations as TMA Sequelae

The severe psychiatric symptoms (OCD, paranoia, rage, hypersexuality, panic) developing immediately postpartum represent chronic brain injury from microvascular ischemia 4:

• Hypertensive encephalopathy causes seizures, lethargy, and altered mental status acutely 4
• Chronic cerebral microvascular injury can manifest as psychiatric symptoms 4
• The dramatic response to progesterone (not SSRIs) suggests hormonal modulation of complement activation rather than primary psychiatric disease 1

Emergent Diagnostic Workup Required

Rule Out TTP Immediately

ADAMTS13 activity must be measured urgently (before any plasma therapy) because TTP requires plasma exchange while aHUS requires complement blockade—opposite treatments 1, 3, 2:

• ADAMTS13 activity <10% confirms TTP 1, 2
• ADAMTS13 activity >10% excludes TTP and supports aHUS diagnosis 1, 3

Confirm Active TMA

Obtain these laboratory studies immediately 4, 1:

• Complete blood count with peripheral smear looking for schistocytes (fragmented RBCs) 4
• Lactate dehydrogenase (LDH) elevated in hemolysis 4, 1
• Haptoglobin unmeasurable in hemolysis 4
• Platelet count typically low in active TMA 1, 2
• Serum creatinine and urinalysis to assess kidney injury 4
• Direct Coombs test negative in TMA (distinguishes from autoimmune hemolysis) 4

Complement Studies for aHUS

If ADAMTS13 >10%, send complement workup 1, 5:

• C3, C4, CH50 levels
• Anti-complement factor H antibodies
• Genetic testing for complement regulatory protein mutations (CFH, CFI, MCP, CFB, C3)

Emergent Management Algorithm

If ADAMTS13 <10% (TTP Diagnosis)

Initiate plasma exchange immediately (twice daily initially) 1, 2. Do not delay for genetic results.

If ADAMTS13 >10% and Progressive Kidney Injury (aHUS Diagnosis)

Eculizumab (complement C5 inhibitor) is the definitive treatment 6, 5:

• Meningococcal vaccination required at least 2 weeks before first dose per REMS program, OR start prophylactic antibiotics if treatment cannot be delayed 6
• Loading dose: 900mg IV weekly × 4 weeks 6, 5
• Maintenance: 1200mg IV at week 5, then every 2 weeks 6, 5
• Treatment is typically lifelong because discontinuation causes TMA relapse in most patients 6, 5

If Diagnosis Uncertain

Plasma exchange can be initiated empirically while awaiting ADAMTS13 results, as it treats TTP and provides temporary benefit in aHUS 1, 3, 2. However, plasma exchange alone is insufficient for aHUS—65% of patients progress to dialysis or death without complement blockade 5.

Blood Pressure Management

Current hypertension likely represents chronic kidney injury from TMA rather than primary hypertensive emergency 4:

• Target BP <140/90 mmHg 4, 7
• Continue labetalol and nifedipine (both safe for breastfeeding) 4, 7
• ACE inhibitors can be added postpartum and are breastfeeding-compatible 4, 8
• Avoid aggressive BP reduction (>25% MAP decrease) which can worsen organ perfusion 4

Critical Pitfalls to Avoid

Do not assume psychiatric symptoms are primary mental illness—they represent organic brain injury from chronic microvascular ischemia requiring TMA treatment, not just psychotropic medications 4, 1.

Do not attribute chronic hemolysis to laboratory artifact—daily lysed specimens over 6 months indicates true intravascular hemolysis requiring investigation 4.

Do not delay eculizumab if aHUS is diagnosed—every day without complement blockade allows progressive irreversible organ damage 6, 5. The dramatic improvement seen in case reports (renal function restoration, hemolysis cessation) occurs only with prompt treatment 5.

Do not stop eculizumab once started—even brief treatment interruptions cause immediate TMA relapse 6, 5.

Prognosis with Treatment

With eculizumab therapy for aHUS, expect 5:

• Cessation of hemolysis within days to weeks
• Improvement in kidney function (though some chronic damage may be irreversible)
• Stabilization of neurologic symptoms
• Potential improvement in psychiatric manifestations as cerebral perfusion improves

Without treatment, progression to end-stage renal disease requiring dialysis occurs in 65% of aHUS patients 5.