Thrombotic Microangiopathy
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Direct answer
Schistocytes on the film, a falling platelet count and a rising creatinine define the thrombotic microangiopathies, a family that splits three ways at the bedside: thrombotic thrombocytopenic purpura, where ADAMTS13 activity below 10 per cent lets ultra-large von Willebrand multimers shear platelets and plasma exchange is a minutes-count emergency; Shiga toxin haemolytic uraemic syndrome, where children follow bloody diarrhoea into a self-supporting illness that antibiotics may worsen; and atypical HUS, a complement dysregulation disease that owns the severe kidney injury and answers to eculizumab. Two discriminators do most of the diagnostic work — the ADAMTS13 assay, and whether the kidney or the brain bears the brunt.
What you must remember
- TTP: ADAMTS13 severe deficiency below 10 IU/dL — autoimmune in adults, congenital in Upshaw–Schulman syndrome; neurological signs dominate, kidney injury is characteristically mild, and untreated mortality approaches 90 per cent while exchange plus steroids rescue more than 80 per cent.
- Exchange details: daily plasma exchange started on suspicion, not after confirmation; plasma infusion is acceptable while arranging it; caplacizumab, the anti-von Willebrand nanobody, blocks the platelet adhesion directly.
- STEC-HUS: Escherichia coli O157:H7 and Shiga toxin; children with bloody diarrhoea; antibiotics and antimotility agents may worsen outcomes; care is supportive — exchange and eculizumab are not indicated.
- aHUS: complement factor H, factor I, MCP, C3 mutations or anti-factor H antibodies; C3 often low; ADAMTS13 normal; eculizumab — the anti-C5 monoclonal — is the therapy, with meningococcal vaccination before or alongside.
- Indian paediatric nuance: anti-factor H antibody-mediated HUS is reported commonly in Indian children, adding plasmapheresis and rituximab to eculizumab and making antibody testing part of the domestic work-up.
- Secondary TMA: pregnancy and postpartum states, calcineurin inhibitors, VEGF inhibitors such as bevacizumab, gemcitabine, malignant hypertension, antiphospholipid syndrome and HIV — removing the trigger is the treatment.
- Biopsy signature: arteriolar fibrin thrombi, mucoid intimal hyperplasia and double-contour basement membranes with scant immune deposits.
- Platelet rule: do not transfuse platelets in TTP unless life-threatening bleeding — you are feeding the fire.
Where the examiner hunts
The favourite trap is the creatinine: "TTP with a creatinine of 7" should make you distrust the label, because severe kidney injury belongs to HUS, malignant hypertension and drug TMA — the exam wants you to re-examine the diagnosis, not double the exchange. The second is the sequencing question: plasma first or assay first? Plasma therapy starts on suspicion; the assay follows and neither waits for the other. The third is the Indian framing — the child with HUS in Indian practice deserves anti-factor H antibody testing, since antibody-positive disease is treated with plasmapheresis and rituximab alongside eculizumab, a combination Western textbooks underemphasise. And the vaccination question, meningococcal cover before eculizumab, remains the single most reliable one-mark item in this territory.
Frequently asked questions
What ADAMTS13 level defines TTP?
Activity below 10 IU/dL — severe deficiency; levels above 10 per cent point instead toward HUS, atypical HUS or secondary TMA.
Why must plasma exchange never be delayed?
Untreated TTP carries mortality near 90 per cent; exchange plus corticosteroids — and now caplacizumab — reduce it dramatically, and the assay takes days.
How is Shiga toxin HUS managed?
Supportively — fluids, electrolytes, dialysis and transfusion as needed; antibiotics and antimotility agents may aggravate disease.
What must precede eculizumab?
Meningococcal vaccination (with antibiotics bridging if therapy cannot wait), because C5 blockade removes terminal complement defence.
What is anti-factor H antibody HUS?
An atypical HUS subtype driven by autoantibodies, reported frequently in Indian children, treated with plasmapheresis and rituximab in addition to complement blockade.
Which drugs and states cause secondary TMA?
Calcineurin inhibitors, VEGF-pathway inhibitors, gemcitabine, malignant hypertension, pregnancy and postpartum states, antiphospholipid syndrome and HIV.