Synopsis
Recognise microangiopathic haemolysis with thrombocytopenia as an emergency, obtain decisive samples without delaying therapy, and separate TTP, STEC-HUS, complement-mediated HUS and secondary thrombotic microangiopathies.
- Thrombotic microangiopathy is a clinicopathological syndrome of small-vessel endothelial injury, microangiopathic haemolytic anaemia, thrombocytopenia and organ ischaemia; it is not a final aetiological diagnosis.
- The laboratory pattern is falling haemoglobin and platelets, schistocytes, raised LDH and indirect bilirubin, reticulocytosis and low haptoglobin. The direct antiglobulin test is usually negative and coagulation may be relatively preserved in TTP.
- Do not wait for the historical pentad of fever, neurological change, renal impairment, anaemia and thrombocytopenia. Many patients have only MAHA and thrombocytopenia when life-saving treatment should start.
- Immune TTP results from severe ADAMTS13 deficiency, generally activity below 10 IU/dL, caused by an autoantibody; congenital TTP has severe deficiency without inhibitor and pathogenic ADAMTS13 variants.
- Take ADAMTS13 activity and inhibitor samples before plasma infusion or exchange whenever possible, but never postpone urgent plasma exchange when clinical probability is high.
- Acute immune TTP is managed in a designated regional centre with daily plasma exchange, corticosteroid immunosuppression, caplacizumab and usually early rituximab under the current specialist protocol.
- STEC-HUS typically follows bloody diarrhoea, especially in children, and is managed with meticulous supportive renal care, stool Shiga-toxin testing and public-health notification; antibiotics and antimotility drugs are not routine treatment.
- Complement-mediated HUS is considered after urgent exclusion of severe ADAMTS13 deficiency, STEC and a compelling secondary cause. Complement levels can be normal, so a normal C3 does not exclude it.
- Pregnancy, malignant hypertension, transplantation, drugs, autoimmune disease, cancer, infection and DIC can produce secondary TMA; removing or treating the driver is essential and TTP can still coexist.
- Avoid prophylactic platelet transfusion in TTP because additional platelets may feed microvascular thrombosis; reserve it for life-threatening bleeding or an essential high-risk procedure after specialist advice.
Key red flags
Anaemia, thrombocytopenia and fragmented red cells occur with high LDH, low haptoglobin, indirect hyperbilirubinaemia and a marrow reticulocyte response. Severe hypertension and mechanical valves can mimic parts of this pattern.
Fluctuating confusion, headache, seizure, focal deficit, chest pain or abdominal symptoms accompany marked thrombocytopenia and MAHA, often with less severe renal failure than HUS, but no single feature safely excludes it.
Abdominal cramps and usually bloody diarrhoea precede pallor, bruising, reduced urine, oedema or hypertension by several days, most characteristically in a child but also in vulnerable adults.
Severe or persistent renal TMA occurs without severe ADAMTS13 deficiency or confirmed STEC, sometimes triggered by infection, surgery or pregnancy and sometimes with a personal or family history of recurrence.
Thrombocytopenia, haemolysis, hypertension, liver injury or AKI develops antenatally or postpartum. TTP, complement-mediated HUS, pre-eclampsia and HELLP overlap and need immediate obstetric-haematology-renal assessment.
The syndrome follows calcineurin or VEGF-pathway drugs, transplant, cancer, systemic autoimmunity, malignant hypertension, severe infection or DIC; the trigger pattern guides treatment but does not negate urgent ADAMTS13 testing.
Investigation priorities
Demonstrate thrombocytopenia and non-immune red-cell fragmentation quickly and trend severity.
Management branches
MAHA and thrombocytopenia have no immediately dominant alternative, especially with cerebral or cardiac features.
- Send citrate plasma for ADAMTS13 activity and inhibitor before any plasma if this causes no delay, plus urgent haemolysis, renal, coagulation, troponin and infection tests.
- Contact the designated regional TTP centre immediately and begin daily plasma exchange, corticosteroid and caplacizumab treatment under its protocol while arranging monitored transfer.
- Add early B-cell-directed immunosuppression as directed, trend platelets, LDH and organ injury, and revise the pathway promptly when ADAMTS13 and causal results return.