# Thrombotic Microangiopathy

> Thrombotic microangiopathy in NEET-PG Pathology: TTP ADAMTS13, shiga-toxin HUS, atypical complement HUS, schistocytes and DIC exclusion.

- Canonical URL: https://prepelephant.com/topics/neet-pg/pathology/thrombotic-microangiopathy-pathology
- Exam / course: NEET-PG · Subject: Pathology
- Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team
- First published: 2026-10-02
- Last updated: 2026-10-02
- How to cite: "Thrombotic Microangiopathy", PrepElephant, https://prepelephant.com/topics/neet-pg/pathology/thrombotic-microangiopathy-pathology

## Direct answer

Microangiopathic haemolysis with thrombocytopenia and a normal INR defines the thrombotic microangiopathies — TTP and the haemolytic uraemic syndromes — in which platelet-rich microthromi occlude arterioles and capillaries while coagulation is spared, separating them from DIC at the laboratory bench. Thrombotic thrombocytopenic purpura follows severe ADAMTS13 deficiency (activity under 10 per cent): ultra-large von Willebrand factor multimers accumulate and shred passing erythrocytes, producing the pentad of thrombocytopenia, microangiopathic haemolysis, neurologic signs, renal impairment and fever. Typical HUS follows shiga toxin-producing Escherichia coli (O157:H7) dysentery damaging glomerular endothelium, with children dominant and renal failure prominent; atypical HUS arises from complement dysregulation (factor H or I mutations, anti-factor H antibodies) and responds to eculizumab. Plasma exchange saves TTP; supportive care and dialysis carry typical HUS.

## What you must remember

- **Core laboratory triad:** schistocytes and helmet cells on the smear, thrombocytopenia, and a normal or near-normal PT/INR with normal D-dimer rise — DIC shows the opposite coagulation pattern.
- **TTP mechanism:** acquired autoantibody (or rare congenital Upshaw-Schulman syndrome) against ADAMTS13, the metalloprotease that cleaves ultra-large vWF multimers; activity under 10 per cent is diagnostic; platelet count is often below 20,000 with neurologic features fluctuating from headache to seizures.
- **Typical (STEC) HUS:** shiga toxin (Stx1, Stx2) from Escherichia coli O157:H7 (undercooked beef, unpasteurised milk, and person-to-person spread) binds Gb3 receptors on glomerular endothelium; prodromal bloody diarrhoea, then oliguria, hypertension and haemolysis; children under five and the elderly (with higher mortality) at risk; antibiotics and antimotility drugs may worsen outcomes.
- **Atypical HUS:** complement-mediated, from factor H or I deficiency, membrane cofactor abnormalities or anti-factor H antibodies; no diarrhoea prodrome, relapsing course, family history; eculizumab (anti-C5) transformed outcomes, and unchecked disease progresses to end-stage renal disease.
- **Secondary causes:** pregnancy, malignant hypertension, lupus, antiphospholipid syndrome, calcineurin inhibitors, quinine, clopidogrel, ticlopidine, HIV and cobalamin C deficiency — the exam's drug-and-disease list.
- **Treatment mapping:** TTP — urgent plasma exchange with corticosteroids (and caplacizumab, an anti-vWF nanobody, where available); typical HUS — supportive with dialysis, no exchange; atypical HUS — eculizumab with meningococcal vaccination.
- **Untreated TTP mortality:** historically near-universal before plasma exchange; suspected TTP gets exchange before ADAMTS13 results return — treatment starts on suspicion.
- **Indian context:** STEC HUS is reported less often than shigella-associated HUS in Indian series, and typhoid, malaria and dengue dominate the broader fever-with-haemolysis differential — but the schistocyte smear and INR check apply regardless of the local pathogen list.

## TTP versus HUS versus DIC in one reasoned pass

A 28-year-old pregnant woman has confusion, pallor and petechiae: haemoglobin 7, platelets 15,000, LDH over 1500, creatinine mildly raised, INR normal, smear full of schistocytes. Normal coagulation excludes DIC; prominent neurology with mild renal injury favours TTP over HUS; pregnancy is a classic trigger. Start plasma exchange immediately and send ADAMTS13 — the test confirms later, treatment cannot wait. Contrast a four-year-old with five days of bloody diarrhoea, now pale, oliguric and hypertensive with the same schistocyte picture but marked azotaemia: STEC HUS — fluids carefully managed, dialysis as needed, no antibiotics, no exchange; most children recover renal function, unlike atypical HUS. A third patient, an adult with recurrent episodes and a family history of renal failure without diarrhoea, fits atypical HUS: complement studies and eculizumab. Finally the DIC patient — sepsis or obstetric catastrophe — shows prolonged PT and aPTT, low fibrinogen, raised D-dimers, and bleeding with oozing puncta: the coagulation profile, not the smear, sorts them out.

## Where candidates slip

The first slip is waiting for ADAMTS13 before treating: suspected TTP is a medical emergency in which plasma exchange starts on clinical grounds, since assays take days. Second, antibiotics in STEC HUS — candidates reflexively treat bloody diarrhoea, but antibiotics and antimotility agents may increase toxin release and HUS risk; management is supportive. Third, using the pentad as a gate: full pentads are rare; the dyad of schistocytic haemolysis plus thrombocytopenia with normal coagulation is enough to act. Fourth, forgetting secondary TMA: a hypertensive emergency or antiphospholipid syndrome can produce an identical smear, and treating the trigger matters as much as exchange. Fifth, eculizumab requires meningococcal vaccination before or alongside therapy — an exam-tested safety pairing.

## Frequently asked questions

### What distinguishes TMA from DIC in the laboratory?

Both show microangiopathic haemolysis and thrombocytopenia, but TMA keeps PT, aPTT and fibrinogen normal with modest D-dimer, whereas DIC prolongs coagulation times, consumes fibrinogen and markedly raises D-dimers.

### What causes thrombotic thrombocytopenic purpura?

Severe deficiency of ADAMTS13 (under 10 per cent activity), usually from autoantibodies, leaving uncleaved ultra-large von Willebrand factor multimers that aggregate platelets in microvasculature.

### How does shiga toxin cause haemolytic uraemic syndrome?

Toxin from STEC binds Gb3 receptors on glomerular and renal tubular endothelium, causing endothelial injury and platelet-fibrin microthrombi, haemolysis and acute kidney injury after bloody diarrhoea.

### Why is plasma exchange urgent in suspected TTP?

Untreated TTP carries historically very high mortality, and exchange replaces the missing ADAMTS13 while removing the autoantibody — outcomes depend on starting before confirmatory results.

### What is atypical HUS and its specific therapy?

Complement-mediated TMA from factor H or I mutations, complement regulatory defects or anti-factor H antibodies, treated with the anti-C5 monoclonal antibody eculizumab alongside meningococcal vaccination.