Haemolytic uraemic syndrome and thrombotic microangiopathy

• Thrombotic microangiopathy is a pattern in which platelet-rich thrombi form in small vessels. Passing red cells are sheared into fragments, platelets are consumed, and organs are ischaemic, so the result is a triad of anaemia, thrombocytopenia, and end-organ injury.
• Haemolytic uraemic syndrome is that pattern with the kidney as the main target. The common acquired form follows Shiga toxin-producing Escherichia coli infection, usually in children, and is usually self-limited. A rarer, complement-mediated form, atypical HUS, can strike at any age and relapse unless complement is blocked.
• The same microangiopathy with severe ADAMTS13 deficiency is thrombotic thrombocytopenic purpura. TTP and HUS look alike in the first hours, so every suspected case needs an ADAMTS13 assay and a STEC work-up, not guesswork.
• In atypical HUS, the standard treatment is a complement 5 inhibitor; kidneys recover better the sooner it is started. By contrast, STEC-HUS is treated supportively, with fluids, electrolytes, and renal replacement when needed; antibiotics are generally avoided.
• Platelet counts are low but are usually not replaced unless there is significant bleeding, because transfusion can add fuel to thrombus formation.

By the end of this page you should be able to:

1. Define thrombotic microangiopathy and explain how it produces microangiopathic haemolytic anaemia, thrombocytopenia, and renal injury.
2. Distinguish STEC-HUS from complement-mediated atypical HUS in pathophysiology, typical patient, and treatment.
3. Contrast HUS with TTP using the ADAMTS13 axis, organ pattern, and emergency treatment.
4. Work through the first-line investigations of a thrombotic microangiopathy and interpret a low ADAMTS13 result.
5. Outline the safe use of a C5 inhibitor in atypical HUS, including vaccination, acute dosing, and monitoring after stopping.
6. Adapt management when complement inhibitors, genetic testing, or renal replacement therapy are not available.

HUS is thrombotic microangiopathy in which the renal microcirculation dominates, although brain, gut, and other organs can also be affected. Three broad categories are useful at the bedside.

• STEC-HUS (often called typical or diarrhoea-associated HUS): endothelial injury driven by Shiga toxin from Shiga toxin-producing E. coli. It usually follows the diarrhoeal phase.
• Atypical HUS: complement-mediated TMA arising from genetic or acquired dysregulation of the alternative complement pathway, with an acute kidney injury. The term is now used for complement-mediated disease, not simply for "HUS without diarrhoea". ^[2]
• Secondary TMA: TMA associated with triggers or underlying conditions such as pregnancy, malignant hypertension, autoimmune disease, drug exposure, infection, haematopoietic stem cell or solid organ transplantation, or malignancy. In many such cases complement is amplified, and atypical HUS may be unmasked. ^[1]

The final diagnosis in an adult with new TMA often depends on the trigger story plus laboratory exclusion of TTP and STEC-HUS. A useful way to think about it is that TMA is the phenotype and the cause is the diagnosis.

In health, complement is controlled by regulators (factor H, factor I, membrane cofactor protein/CD46, thrombomodulin) and activated by effectors (factor B, C3). In atypical HUS, a regulator is defective or an effector is overactive, so a trigger sets off uncontrolled alternative-pathway activation. Endothelial deposition of C5b-9 (the membrane attack complex) and C5a then activate platelets, recruit neutrophils, injure endothelium, and start microthrombosis. ^[1] That is why drugs that bind C5 stop the process.

TTP is the same microangiopathic pattern, but the driver is severe deficiency of ADAMTS13, the von Willebrand factor (VWF)-cleaving protease. Uncleaved ultra-large VWF multimers tether platelets to endothelium and cause platelet-rich aggregates in vessels. TTP therefore also produces fragmentation and thrombocytopenia, though neurological features and renal impairment vary. TTP is immune-mediated when anti-ADAMTS13 autoantibodies are present, and congenital when there is an ADAMTS13 gene abnormality (Upshaw-Schulman syndrome). ^[2]

The single most useful laboratory separator is the ADAMTS13 activity assay: activity under 10 per cent supports TTP. ^[2][1] HUS is not defined by ADAMTS13 deficiency, although an ADAMTS13 assay must still be sent for every suspected case so that TTP is not missed. ^[1]

On the kidney side this is a small-vessel disease. Glomerular and arteriolar endothelium swells and detaches, the lumen narrows with platelet-rich fibrin plugs, and the downstream tubule can be ischaemic. The blood film shows red cell fragments (schistocytes) as evidence of mechanical damage. In atypical HUS, a kidney biopsy is usually unnecessary before treatment; it may be useful later when the diagnosis remains unclear or when a trigger such as IgA vasculitis or C3 glomerulopathy is suspected. ^[1]

Thrombotic microangiopathy overall is uncommon and is best understood as a presentation. For TTP itself, clinically diagnosed disease has been estimated at 4 to 11 new cases per million people per year; one group using an ADAMTS13 activity under 5 per cent criterion reported 1.74 per million. Women are affected more often than men, and presentation spans adolescence to later adult life. ^[2]

• STEC-HUS is largely a disease of children and usually follows food- and water-borne transmission. Outbreaks are described in schools, child-care settings, and in association with undercooked meat or unpasteurised products.
• Atypical HUS is rare and can arise at any age, including in the first year of life and in late adult life. It is often triggered. Inherited or acquired complement abnormalities are found in many (though not all) families, and triggers convert a silent predisposition into overt disease. ^[1]
• Pneumococcal HUS occurs mainly in young children with invasive Streptococcus pneumoniae infection, because bacterial neuraminidase exposes the T antigen on red cells. It is uncommon but important in a sick febrile child. ^[2]

The trigger is infection with Shiga toxin 1 and/or 2-producing E. coli (enterohaemorrhagic E. coli), most famously serotype O157:H7, but non-O157 strains account for an increasing share of disease. Other Shiga-toxin producers are reported occasionally. The toxin injures renal and other endothelium through binding to globotriaosylceramide receptors, activates complement, and causes protein synthesis arrest in affected cells. Children have a higher receptor density in the kidney, which contributes to their susceptibility, and diarrhoea may be bloody. ^[1] The clinically useful prevention is avoiding the exposure.

Predisposition is the rule. The genetic panel for aHUS includes complement factor H (CFH), complement factor H-related (CFHR) proteins 1 to 5, complement factor I (CFI), CD46 (membrane cofactor protein, MCP), C3, complement factor B (CFB), thrombomodulin, and diacylglycerol kinase epsilon. Anti-factor H autoantibodies, often with a deletion in CFHR1/3, are another acquired cause. In routine practice up to half of cases have no identifiable pathogenic variant, so a negative genetic result never excludes atypical HUS. ^[1]

A trigger is needed in many patients: severe hypertension, pregnancy or the postpartum period, infection (including STEC itself, influenza, and other infections), autoimmune disease (systemic lupus erythematosus, catastrophic antiphospholipid syndrome, scleroderma renal crisis), drugs (for example calcineurin inhibitors, anti-VEGF agents, quinine), cancer, bone marrow or solid organ transplantation, and acute severe illness. ^[1] These may unmask, co-exist with, or be secondary to complement-mediated disease. Whenever a TMA looks "triggered", the correct response is to treat the trigger and, if TMA persists, to reconsider atypical HUS. ^[1]

The toxin reaches the renal microcirculation after intestinal infection. It binds endothelial receptors, is internalised, and shuts down protein synthesis; endothelial damage, platelet adhesion, and microthrombosis follow, with complement activation amplifying the injury. The result is endothelial swelling in glomeruli, microthrombi in capillaries, and a drop in filtration, so acute kidney injury, hypertension, and fluid-electrolyte disturbance dominate. Red cells passing through thrombosed vessels fragment, giving haemolysis and a falling haemoglobin. Platelet counts fall because platelets are consumed, often to very low levels. ^[1] The brain can be involved, presenting as irritability, seizures, or stroke-like features, particularly in young children.

Loss-of-function in a regulator (factor H, factor I, MCP, thrombomodulin) or gain-of-function in an effector (C3, factor B) removes control of the alternative pathway. A trigger then produces unchecked C5 cleavage, C5a and membrane attack complex deposition on endothelium, platelet activation, and thrombosis. The platelet-rich microthrombi cause both the blood abnormalities and the renal presentation. ^[1] Because the process is biological and systemic, merely supporting the kidney does not turn it off, which is why a C5 inhibitor is used.

• Microangiopathic haemolytic anaemia: red cells are physically fragmented by thrombi, giving schistocytes, high lactate dehydrogenase, undetectable haptoglobin, and a raised indirect bilirubin. Coombs testing is negative, which separates this from autoimmune haemolysis.
• Thrombocytopenia: platelets are consumed in microthrombi, not destroyed in the reticuloendothelial system as in immune thrombocytopenia.
• Renal injury: glomerular microthrombosis drops filtration and may produce hypertension, haematuria, proteinuria, and oliguria or anuria.
• Neurological features: headache, confusion, seizure, or stroke reflect cerebral micro-ischaemia; these are more prominent and fluctuating in TTP but can occur in HUS.
• Gastrointestinal symptoms: STEC-HUS is often preceded by abdominal pain and diarrhoea, sometimes bloody; in both forms, gut ischaemia can cause pain and diarrhoea.

Ask for a timeline that separates triggers from symptoms:

• Infection: watery or bloody diarrhoea, or a febrile illness, in the days before the onset of pallor, oliguria, or oedema. For STEC, ask about food exposures and contacts. ^[4]
• Neurology: headache, irritability, confusion, visual disturbance, seizure, weakness, or focal deficit. Fluctuation in these symptoms is characteristic of the microangiopathic process.
• Bleeding and bruising: epistaxis, purpura, melaena, haematuria; ask about any new medication (including myelosuppressive drugs and oral contraceptive pills).
• Pregnancy and postpartum: symptoms within the antenatal, peripartum, or postpartum window.
• Family history: previous episodes, renal failure in relatives, or pregnancy losses that could be HUS; relevant in atypical HUS. ^[1]
• Past history: hypertension, kidney disease, transplant, autoimmune disease, cancer.

• General appearance: pallor, tachycardia, and signs of volume overload or dehydration. A child with STEC-HUS may look dry after diarrhoea but still develop hypertension as renal function falls.
• Blood pressure: often raised; measure in all limbs if possible and look for the retinal and cardiac signs of accelerated hypertension. ^[1]
• Neurological: level of consciousness, cranial nerves, tone, power, speech; small fluctuating deficits are typical.
• Abdomen: tenderness or colic consistent with gut ischaemia; hepatosplenomegaly is not a feature of HUS (it points towards other diagnoses such as haemolytic anaemias or marrow disease).
• Skin: petechiae or bruising, but purpura may be surprisingly limited given the platelet count.
• Kidney focus: oliguria, anuria, oedema, and uraemic signs (nausea, encephalopathy) as the disease progresses.

• Anaemia with fragmented cells. Schistocytes over 1 per cent of red cells (in the absence of other severe shape abnormalities) are a robust indicator of thrombotic microangiopathy. ^[2]
• Thrombocytopenia: platelet counts are often very low; one guideline gives 10 to 30 x 10^9 per litre as a typical range in TTP cohorts. ^[2]
• In TTP, haemoglobin is typically 8 to 10 g per dL in overseas cohorts, and 7.3 g per dL was reported as a median in Japanese patients. ^[2]
• LDH high and haptoglobin low or absent; indirect bilirubin raised; direct Coombs negative.
• Renal panel: urea and creatinine raised, potassium and acid-base disturbed, urinalysis showing protein and blood. In uncomplicated TTP the creatinine is usually under 2 mg per dL (about 177 micromol per litre), whereas severe acute renal failure requiring early dialysis points to HUS. ^[2][1]
• PT and APTT normal, fibrinogen normal, and only mild elevation of D-dimer in TMA (helps to separate TMA from DIC). ^[2]
• Neurological involvement was reported in 79 per cent of Japanese TTP patients and about 50 per cent in several overseas TTP series, while fever is documented in roughly 30 to 72 per cent. ^[2]

The list of TMA mimics is long and dangerous. Always check ADAMTS13 and STEC early, and do not allow a "trigger" to close the diagnosis.

• Full blood count, blood film for schistocytes (quantify), reticulocyte count.
• Clotting screen (PT, APTT, fibrinogen, D-dimer) to exclude DIC.
• Direct antiglobulin (Coombs) test.
• Renal function, electrolytes, acid-base; urinalysis for protein and blood.
• Lactate dehydrogenase, haptoglobin, indirect bilirubin.
• Stool culture, Shiga toxin PCR, and/or serology for anti-STEC antibody for STEC-HUS. ^[1]
• ADAMTS13 activity (and inhibitor) before starting plasma, where possible.
• Complement C3 and C4, and, when clinically available, factor H, factor I levels, anti-factor H antibodies.
• Infection screen tailored to the trigger (for example blood cultures, SARS-CoV-2/influenza testing in season).
• Baseline assessment for C5 inhibitor therapy (vaccination status, infection).

• ADAMTS13 activity, clinical prediction scores (French score high risk at 2 points, PLASMIC score 6 to 7 points), and, if sepsis is a possibility, blood culture. ^[1]
• STEC serotype confirmation by culture and non-culture methods. ^[1]
• Genetic panel for aHUS (CFH, CFHR1-5, CFI, CD46, C3, CFB, thrombomodulin, DGKE) and anti-factor H antibodies when aHUS is suspected. ^[1]
• Kidney biopsy only if the diagnosis remains uncertain and the risk is acceptable (for example IgA-associated TMA or C3 glomerulopathy). ^[1]
• Pregnancy testing when relevant; autoimmune serology when suspected.

Asia-Pacific expert data provide PLASMIC, French, and modified versions that add proteinuria (modified score raised thresholds) to predict severe ADAMTS13 deficiency. A high-risk PLASMIC score is 6 to 7 (modified 7), and a high-risk French score is 2 (modified 3). ^[1] TTP probability data from the Japanese guideline quote 62 to 82 per cent for PLASMIC scores 6 to 7 and 94 per cent for a French score of 2. ^[2] These are not substitutes for the assay but are used when the assay takes days.

At the bedside the diagnosis is based on the triad and on exclusion. Use the following anchors.

• TMA: microangiopathic anaemia plus thrombocytopenia plus end-organ ischaemia, most commonly renal. ^[1]
• TTP: the same triad with ADAMTS13 activity under 10 per cent. ^[2][1]
• STEC-HUS: TMA plus evidence of STEC infection, usually after bloody diarrhoea. ^[1]
• Atypical HUS: TMA without TTP or STEC-HUS, with a complement-mediated cause or trigger, treated as possible aHUS and confirmed when needed by genetics or autoantibodies. ^[1]
• Low C3 with a normal C4 is suggestive of alternative-pathway activation, although not all patients with atypical HUS have it. ^[1]

Severity is clinical. Rising creatinine, oliguria, refractory hypertension, neurological change, need for dialysis, or a falling platelet or haemoglobin while other causes are excluded mean urgent escalation. A child with STEC-HUS and even mild neurological symptoms needs neurological monitoring, and a rise in creatinine in any patient with MAHA is enough to treat urgently while testing proceeds.

Stabilise the patient while tests are run. Focus on what changes outcome: oxygen, perfusion, blood pressure control, electrolyte correction, and planning for renal replacement.

• Assess and correct volume status carefully; HUS patients can be dehydrated after diarrhoea but can also be fluid-overloaded once oliguric.
• Correct hyperkalaemia, acidosis, and other electrolyte problems; pay attention to hyponatraemia and seizure risk in children.
• Start renal replacement therapy when clinically indicated (urea, potassium, fluid, acid-base, or uraemic symptoms), with dialysis modality chosen by local team and age.
• Avoid routine antiplatelet or anticoagulant therapy: the thrombi are platelet-rich and anticoagulation does not dissolve them.
• Be cautious with red cell transfusion; transfuse for symptomatic anaemia, but platelet transfusion is usually reserved for active bleeding or before an invasive procedure.
• Control severe hypertension because accelerated hypertension both triggers and mimics TMA. ^[1]

The evidence base for specific therapy in STEC-HUS is weak. Fluids, nutrition, dialysis, and careful blood pressure control are the backbone. Antibiotics are generally avoided because of the possible increased risk of HUS, and this was the basis of the prescribing guideline used in large US series (STEC guideline adherence defined by withholding antibiotics and antimotility agents; 76 per cent adherence). ^[4] If prescribing is unavoidable (for example after a surgical abdomen), the choice should follow local microbiology and specialist advice rather than an automatic "cover everything" habit. In some regions, plasma exchange is used in severe cases, but it is not established as standard for STEC-HUS in the sources used here. Supportive care should always be started while TTP and atypical HUS are being excluded.

TTP is a haematology emergency. The iTTP pathway (Japanese 2023 TTP guideline) starts with daily plasma exchange with fresh frozen plasma at 1.0 to 1.5 times circulating plasma volume, because plasma restores ADAMTS13, removes inhibitor, and clears ultra-large VWF multimers. Plasma infusion rather than exchange is not preferred. ^[2] Caplacizumab, a nanobody against the VWF A1 domain, was approved in Japan in September 2022 and reduced iTTP mortality in controlled double-blind trials. ^[2] Rituximab is used to suppress autoantibody production in repeated or refractory immune TTP. Corticosteroids are used alongside plasma exchange to suppress autoantibody production. ^[2] In congenital TTP, treatment is periodic fresh frozen plasma to replace ADAMTS13, not plasma exchange.

This is why the renal reader needs TTP in their differential: giving a C5 inhibitor to undiagnosed TTP would lose hours. The opposite is also true: TTP cannot be "sorted" by eculizumab.

Atypical HUS is the place where complement inhibition changes the disease. In adult kidney practice the usual drug is a terminal complement inhibitor. Eculizumab, from the Soliris label, is given intravenously: 900 mg weekly for the first 4 weeks, then 1,200 mg for the fifth dose one week later, then 1,200 mg every 2 weeks thereafter. In children dosing follows body weight, from 300 mg in the smallest infants to the adult schedule at 40 kg and above. ^[3] NICE highly specialised technologies guidance supports eculizumab for atypical HUS in adults and children (NICE HST1, published 2015, subject to the NHS commercial agreement and the managed access scheme). ^[5]

Acute practical steps:

• Start as soon as atypical HUS is diagnosed, and within 3 to 5 days (or earlier) from the time TMA was first recognised, if the diagnosis is suspected. ^[1]
• In pregnancy-associated cases, initiation upon clinical suspicion within 24 hours is associated with better kidney recovery. ^[1]
• Complete or update meningococcal vaccination at least 2 weeks before the first dose. If urgent treatment is required, give antibacterial prophylaxis and vaccinate as soon as feasible. ^[3]
• SOLIRIS is contraindicated for initiation in the presence of unresolved serious Neisseria meningitidis infection. ^[3]
• Supplemental dosing is required with each plasma exchange, plasmapheresis, fresh frozen plasma infusion, or IVIg cycle. ^[3]
• Treat the trigger at the same time (control blood pressure, manage autoimmune disease, withdraw offending drug, treat infection, manage pregnancy).

Duration and stopping:

• Continue an initial treatment course for about 6 months, focusing on complete haematological and renal response, and at least 3 months after stabilisation or recovery of kidney function. ^[1]
• There is no global consensus on how long to continue. Discontinuing after 6 months can be considered using individual risk (complement gene variants, prior relapse, severity of extra-renal disease, anti-factor H antibodies, age at onset, transplant status). ^[1]
• On stopping, monitor for at least 12 weeks for TMA recurrence; label-listed warning signs include change in mental status, seizures, angina, dyspnoea, or thrombosis, and a fall in platelet count by 25 per cent or more, or a 25 per cent rise in creatinine or LDH compared with on-treatment nadir. ^[3] Before stopping, be sure that re-treatment can be started quickly.
• Patients can be advised to self-monitor with home urine dipsticks and report symptoms promptly, particularly after infections, vaccinations, surgery, or pregnancy. ^[1]

Genetic testing and family management:

• A genetic panel is recommended in severe or complicated TMA, in confirmed aHUS, before transplantation, and when aHUS is suspected. ^[1]
• Involvement of an experienced geneticist and genetic counsellor is recommended, because interpreting the variants is complex. ^[1]
• For pregnant women with suspected aHUS, C5 inhibitor data are reassuring (eculizumab in pregnancy, with no detection in breast milk and no documented complement effect on the newborn in the available observations). ^[1]
• For transplant patients, eculizumab prophylaxis reduces recurrence and timely use improves graft survival, although the optimal maintenance duration remains uncertain. Live related donation is usually not considered, whatever the genetic result. ^[1]

Historically some patients with atypical HUS were treated with plasma exchange, but the preferred treatment is C5 inhibition when available. In atypical HUS, plasma exchange may still be used while the diagnosis is uncertain, in very early disease, when C5 inhibitors are unavailable, or for anti-factor H autoantibody clearance. The same applies to complement-mediated TMA triggered by autoimmunity. For anti-factor H antibody disease, plasma exchange plus immunosuppression is a targeted option. This division is the practical cross-check with haematology practice.

• Renal failure, acute or chronic, sometimes requiring permanent dialysis; hypertension in many.
• Neurological injury: seizure, encephalopathy, infarction.
• Gut ischaemia: colitis, rectal bleeding, even bowel ischaemia or perforation.
• Cardiac involvement: myocardial ischaemia and arrhythmia are described in severe microangiopathy.
• Treatment complications: meningococcal and other encapsulated bacterial infections with complement inhibition; bleeding or other complications of plasma exchange; transfusion-related problems.
• Relapse, particularly of atypical HUS after C5 inhibitor withdrawal; repeated HUS can lead to chronic kidney disease. ^[1]
• Transplant recurrence of atypical HUS, especially with CFH variants.

Historically, untreated or poorly treated atypical HUS had a high risk of death and end-stage kidney disease, particularly in children and with relapsing forms. With C5 inhibitors, kidney recovery is more common the earlier treatment starts, but outcomes vary with the exact complement variant, the trigger, and the time to treatment. ^[1] STEC-HUS is usually reversible with supportive care, though the neurological form and need for dialysis worsen prognosis; some children are left with chronic kidney disease or hypertension. The presence of even mild neurological symptoms in STEC-HUS should be treated as high-risk. The lack of a validated predictor of relapse after stopping C5 inhibitors is a continuing source of uncertainty, and explains why stopping criteria are clinical rather than laboratory-driven.

• Food safety: avoid undercooked meat, unpasteurised milk and cheese, and cross-contamination; and wash fruits and vegetables. ^[4]
• Water and hygiene: attention during outbreaks in schools and child-care settings.
• Meningococcal vaccination and maintenance of vaccination status for anyone starting C5 inhibitor therapy. ^[3]
• Genetic counselling and family testing in atypical HUS, particularly for transplant decisions and reproductive counselling.
• Screening of relatives is not routine; cascade testing after a known pathogenic variant, and clinical advice on pregnancy and contraception, are more realistic offers. ^[1]
• For the household of an STEC case, ensure hand hygiene and seek testing if symptoms develop.

STEC-HUS is the dominant thrombotic microangiopathy of childhood. Children often present with bloody diarrhoea, pallor, and oliguria, then hypertension and neurological features. Fluid management has to balance dehydration with oliguric fluid overload. Treatment is supportive, with dialysis when indicated, neurological monitoring, and specialist paediatric nephrology and haematology input. ^[1] Pneumococcal HUS should be considered in any febrile child with HUS and respiratory infection. ^[2]

Pregnancy or its complications can trigger TMA and atypical HUS, usually in a woman with an underlying complement variant, but also in women without identifiable abnormalities. ^[1] The differential includes TTP, pre-eclampsia, HELLP syndrome, and other secondary TMAs. TTP and severe pre-eclampsia/HELLP are more common in the second and third trimesters; peripartum or postpartum TMA suggests complement-mediated atypical HUS, although pregnancy-associated aHUS can occur in any trimester. ^[1] Complement variants are reported in 41 to 56 per cent of pregnant women with aHUS, mainly CFH. ^[1] Kidney outcomes are better with C5 inhibitor treatment. Ideally start within 24 hours when atypical HUS is suspected, and eculizumab appears safe in pregnancy with no detection in breast milk in the available observations. ^[1] Management requires obstetric, nephrology, and haematology teams.

Older patients have more triggers (malignancy, drugs, hypertension, vascular disease) and may look toxic rather than have a diarrhoeal prodrome. Excluding secondary TMA and cancer is usually necessary before settling on atypical or primary TMA. Complement inhibitors are still appropriate when a complement-mediated disorder is present, and reinfection and sepsis risk with meningococcal vaccination must be managed carefully.

Calcineurin inhibitors, VEGF inhibitors, interferons, and anti-cancer therapies can all cause TMA. Drug withdrawal, blood pressure control, and suppression of autoimmunity (when relevant) come first; C5 inhibitors are considered for refractory complement amplification. Transplant-associated TMA in children and adults often requires reduction of immunosuppression, plasma or C5 inhibition, and specialist haematology input. ^[1]

• The single most helpful test is the blood film: fragment cells in the setting of thrombocytopenia and renal injury make TMA.
• Send ADAMTS13 and STEC testing when possible, but start clinical management without waiting.
• If eculizumab is unavailable, the alternatives are plasma exchange (where feasible), aggressive supportive care, and early referral. Anti-factor H antibody disease benefits from plasma exchange plus immunosuppression where that expertise exists.
• Vaccination may be delayed or unavailable; in the absence of vaccine, prolonged antibiotic prophylaxis while on complement inhibition is sometimes used, set against local risk. ^[1][3]
• Dialysis access is often the limiting step. Peritoneal dialysis can be life-saving for children, and nephrology outreach can support local teams.
• The higher incidence of infection-related triggers and late presentation mean outcomes depend heavily on early recognition and safe transfer.

• Thrombotic microangiopathy is a pattern, not a diagnosis: microangiopathic haemolysis, thrombocytopenia, and end-organ ischaemia.
• HUS is the TMA of the renal microcirculation; it is either STEC-associated or complement-mediated atypical HUS.
• STEC-HUS causes an epidemic, child-predominant disease that is treated supportively; antibiotics are generally avoided because they may increase HUS risk. ^[4]
• Atypical HUS is complement-mediated, is triggered rather than caused de novo by the trigger, and responds to C5 inhibition. ^[1]
• Exclude TTP in every case by an ADAMTS13 assay (activity under 10 per cent defines TTP). ^[2][1]
• The PLASMIC and French scores (with modified versions adding proteinuria) predict severe ADAMTS13 deficiency when the assay is delayed. ^[1][2]
• C5 inhibitor therapy for atypical HUS should start within 3 to 5 days or earlier, and within about 24 hours in pregnancy-associated disease when possible. ^[1]
• Eculizumab adult aHUS schedule: 900 mg weekly for 4 weeks, then 1,200 mg at week 5, then 1,200 mg every 2 weeks. ^[3]
• Complete or update meningococcal vaccination at least 2 weeks before the first dose; if urgent treatment is required, give prophylaxis and vaccinate as soon as feasible. ^[3]
• Atypical HUS genetic testing covers CFH, CFHR1-5, CFI, CD46, C3, CFB, thrombomodulin, and DGKE, but a negative result does not exclude disease. ^[1]
• Initial treatment is usually continued for about 6 months; stopping later requires 12 weeks of biochemical follow-up. ^[1][3]
• Platelet transfusion is generally reserved for bleeding; normal PT/APTT and fibrinogen separate TMA from DIC. ^[2]
• Triggers in atypical HUS include pregnancy, malignant hypertension, autoimmunity, drugs, infection, and transplantation. ^[1]

Related pages on the site: the haematology counterpart on thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome; autoimmune haemolytic anaemia; disseminated intravascular coagulation; acute kidney injury; and severe hypertension. These are named here in plain text because cross-links will be added as the renal and haematology sections are completed.