Clinical Cases in Pharmacology Clinical Cases  ·  Nephrology Vol. II  ·  Glomerular and Vascular Disorders  ·  Atypical HUS
Nephrology Vol. I: Glomerular and Vascular Disorders, Case 0010 — Glomerular and Vascular Disorders

Postpartum Atypical HUS: Eculizumab Now, or Plasma Exchange While Confirming It

A single patient, three weeks postpartum, with a working diagnosis of atypical HUS and a genetic panel still pending. The disagreement is whether to commit to complement inhibition on clinical suspicion alone or start with the older, cheaper therapy while confirmation is awaited.

Abbreviations, terms, and other agents mentioned in this case aHUS — atypical hemolytic uremic syndrome  ·  ADAMTS13 — a von Willebrand factor-cleaving protease; normal activity distinguishes aHUS from TTP  ·  PLEX — plasma exchange  ·  TMA — thrombotic microangiopathy
Presentation

Sophia L. delivered her first child three weeks ago without complication — a healthy birth, an uneventful recovery she was just starting to feel like herself after, when new fatigue and swelling sent her back to the emergency department instead of to a pediatrician's office. Her platelets came back at 38,000, schistocytes were on the smear, and her creatinine was climbing from a normal pre-pregnancy baseline. Her ADAMTS13 activity, checked immediately given the platelet count, came back at 62% — normal, which rules out TTP and leaves atypical HUS as the working diagnosis, precisely the complement-dysregulation disease pregnancy and the postpartum period are recognized triggers for.

A complement genetic panel was sent the day of admission, but results won't return for a week to ten days — a timeline that has nothing to do with how fast her kidneys are declining right now. Eculizumab's efficacy in aHUS rests on real prospective trial data, not case-series inference, and has become the standard first-line approach over plasma exchange specifically because aHUS can progress to irreversible renal injury, and in some cases extra-renal thrombotic microangiopathy, faster than a genetic panel can confirm the diagnosis. Plasma exchange has its own real history here — it was the standard before eculizumab existed, it's markedly cheaper, and a recognized subset of postpartum aHUS does respond to it, which is part of why simply defaulting to the newer, more expensive drug for every suspected case isn't obviously the only reasonable path. What her case adds that a generic aHUS presentation wouldn't is the postpartum trigger itself: pregnancy is one of the best-recognized precipitants for complement dysregulation to become clinically apparent, which makes an underlying pathogenic complement variant more likely in her specifically than in an aHUS presentation without an obvious trigger. Her creatinine, checked twice in the twelve hours since admission, has already moved from 2.1 to 2.6 — a real, measured slope, not a single alarming number that might settle on its own, and the kind of trajectory the team is reading as evidence this is actively progressing rather than a process that has already found its floor.

Sophia L. · 26 3 weeks postpartum, admitted overnight
History
Uncomplicated vaginal delivery 3 weeks ago, no prior renal or hematologic disease
Labs
Platelets 38,000, schistocytes on smear, LDH 890
ADAMTS13 activity
62% (normal, rules out TTP)
Creatinine
2.6 mg/dL, rising from a normal baseline
Complement genetic panel
Sent, results pending (7-10 day turnaround)
Blood pressure
168/104, new since admission

On the joint nephrology-obstetric medicine consult, hospital day 1

Nephrologist (eculizumab now) Opening

Her creatinine is already climbing from a normal baseline, and the genetic panel won't be back for a week or more. aHUS can cause irreversible renal injury faster than that. Eculizumab has real prospective trial data behind it — I'd start it now rather than wait for confirmation that may come too late to matter.

Hematologist (PLEX-first) Response

I'm not disputing the urgency, but plasma exchange has a long track record here too, it's substantially cheaper, and there's a real, recognized subset of postpartum thrombotic microangiopathy that responds to PLEX specifically. I'd rather start there and reserve eculizumab for confirmed disease or clear PLEX non-response than commit to the costlier option first.

Treating this as 'start the cheap option and escalate if it fails' assumes we'll catch non-response in time — with aHUS, that assumption is exactly what the trial data argue against.

Clinical Pharmacologist (eculizumab in parallel) Final

I don't think this actually has to be sequential either way. Her genetic and functional complement workup is already underway — we don't have to choose between waiting for it and ignoring it. What I'd add is this: postpartum onset isn't incidental context, it's diagnostic information. Pregnancy is one of the best-established triggers for an underlying complement-regulatory defect to become clinically apparent, which raises the probability she has a genuine pathogenic variant well above a generic aHUS presentation without a clear trigger.

That's reason to treat her more, not less, aggressively from the start — eculizumab now, workup continuing in parallel, rather than a stepwise PLEX-first sequence built for lower-probability cases than hers.

Regimen selected
Eculizumab
Terminal Complement C5 Inhibitor · Weekly induction dosing
Started immediately on clinical suspicion, given the trial-demonstrated urgency of early complement blockade and her postpartum trigger raising pretest probability.
Plasma Exchange — Not Adopted as First Step
Extracorporeal Therapy · Considered, deferred
A real, established option, but not chosen as the initial approach given the diagnostic weight her postpartum trigger carries.
Where this was left

Agreed: start eculizumab immediately, meningococcal vaccination given per protocol, complement genetic panel and functional workup continuing in parallel rather than gating treatment. Platelet count, LDH, and creatinine rechecked daily.

The PLEX-first position wasn't dismissed as wrong in general — plasma exchange remains the explicit fallback if eculizumab response is inadequate, and everyone agreed her postpartum trigger specifically, not aHUS presentations broadly, was what tipped the balance toward immediate complement blockade.

Educational content only — a composite teaching case, not a real patient encounter or a substitute for clinical guidance. About These Cases →