Thrombotic microangiopathy: TTP, HUS, and aHUS in ICU

Also known as Thrombotic thrombocytopenic purpura · TTP · Haemolytic uraemic syndrome · HUS · Atypical HUS · aHUS · Thrombotic microangiopathy · TMA · Upshaw-Schulman syndrome · Congenital TTP · STEC-HUS · Shiga toxin HUS · Complement-mediated TMA · PLASMIC score · Caplacizumab · Eculizumab · ADAMTS13 deficiency

Thrombotic microangiopathy (TMA): microvascular platelet-rich thrombi → thrombocytopenia + microangiopathic haemolytic anaemia (MAHA) + organ ischaemia. THREE main types: (1) TTP (thrombotic thrombocytopenic purpura): ADAMTS13 deficiency (congenital or autoantibody) → unprocessed ultra-large vWF multimers → platelet microthrombi. Neurological + cardiac predominant. Treatment: PLASMA EXCHANGE (life-saving) + steroids + caplacizumab. (2) HUS (haemolytic uraemic syndrome): Shiga toxin-producing E. coli (STEC — O157:H7) → endothelial damage → renal predominant. Treatment: supportive (no antibiotics, no plasma exchange). (3) aHUS (atypical HUS): complement dysregulation → renal predominant. Treatment: eculizumab (complement inhibitor).

high29 referencesUpdated 26 July 202641 min readSource-verified · Sept 2026

Checked against its sources on 3 Sept 2026

Practise this topic

8 MCQs

The one-line answer

A thrombotic microangiopathy is thrombocytopenia plus microangiopathic haemolytic anaemia plus organ ischaemia, with a normal coagulation screen — schistocytes on the film, high LDH, low haptoglobin, and a PT, aPTT and fibrinogen that are all normal. Then it forks three ways. TTP (severe ADAMTS13 deficiency, ≤10 per cent of normal) gets plasma exchange within four to eight hours, plus corticosteroids — a strong ISTH recommendation — with caplacizumab added when ADAMTS13 results are expected within 72 hours. STEC-HUS (bloody diarrhoea, kidney-dominant) is supportive — avoid fluoroquinolones and trimethoprim, which upregulate Shiga toxin genes; exchange is not indicated routinely. aHUS (complement-driven, kidney-dominant) gets eculizumab, with mandatory meningococcal risk mitigation. Start the exchange on suspicion; never wait for the ADAMTS13 to come back.

^[23] ^[41] ^[15] ^[28] ^[22] ^[38]

Meet the patient

A 32-year-old woman is readmitted six days after an uncomplicated delivery, with fluctuating confusion she keeps apologising for, a nosebleed that will not stop, and bruising she cannot explain. Her platelets are 14, her haemoglobin has halved in a week, and the blood film is scattered with schistocytes. Her INR, aPTT and fibrinogen are all normal.^[23] ^[40]

Two questions decide her next four hours, and they decide every TMA: is the coagulation screen normal? (it is, so this is shear rather than consumption) and which organ is failing first? (her brain is fluctuating, so treat her as TTP until the ADAMTS13 returns). Hold those two answers and the whole topic resolves.^[23] ^[26]

References29Show

[14]Zheng XL, Al-Housni Z, Cataland SR, et al. 2025 focused update of the 2020 ISTH guidelines for management of thrombotic thrombocytopenic purpura J Thromb Haemost, 2025.PMID 40533296
[15]Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura J Thromb Haemost, 2020.PMID 32914582
[16]Scully M, Cataland SR, Peyvandi F, et al. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura N Engl J Med, 2019.PMID 30625070
[17]Peyvandi F, Scully M, Kremer Hovinga JA, et al. Caplacizumab for acquired thrombotic thrombocytopenic purpura N Engl J Med, 2016.PMID 26863353
[18]Peyvandi F, Cataland S, Scully M, et al. Caplacizumab prevents refractoriness and mortality in acquired thrombotic thrombocytopenic purpura: integrated analysis Blood Adv, 2021.PMID 33881463
[19]Bendapudi PK, Hurwitz S, Fry A, et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study Lancet Haematol, 2017.PMID 28259520
[20]Li A, Khalighi PR, Wu Q, et al. External validation of the PLASMIC score: a clinical prediction tool for thrombotic thrombocytopenic purpura diagnosis and treatment J Thromb Haemost, 2018.PMID 29064619
[21]Rock GA, Shumak KH, Buskard NA, et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. Canadian Apheresis Study Group N Engl J Med, 1991.PMID 2062330
[22]Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome N Engl J Med, 2013.PMID 23738544
[23]Fox LC, Cohney SJ, Kausman JY, et al. Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand Intern Med J, 2018.PMID 29582550
[24]Abou-Ismail MY, Kapoor S, Citla Sridhar D, et al. Thrombotic microangiopathies: An illustrated review Res Pract Thromb Haemost, 2022.PMID 35615754
[25]Park YA, Waldrum MR, Marques MB Platelet count and prothrombin time help distinguish thrombotic thrombocytopenic purpura-hemolytic uremic syndrome from disseminated intravascular coagulation in adults Am J Clin Pathol, 2010.PMID 20154285
[26]Sakai K, Wada H, Nakatsuka Y, et al. Characteristics behaviors of coagulation and fibrinolysis markers in acquired thrombotic thrombocytopenic purpura J Intensive Care Med, 2021.PMID 31964209
[27]Safdar N, Said A, Gangnon RE, et al. Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 enteritis: a meta-analysis JAMA, 2002.PMID 12190370
[28]Kimmitt PT, Harwood CR, Barer MR Toxin gene expression by shiga toxin-producing Escherichia coli: the role of antibiotics and the bacterial SOS response Emerg Infect Dis, 2000.PMID 10998375
[29]Mazzierli T, Allegretta F, Maffini E, et al. Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management Front Pharmacol, 2022.PMID 36699080
[30]Kavanagh D, Goodship TH, Richards A Atypical hemolytic uremic syndrome Semin Nephrol, 2013.PMID 24161037
[31]Borogovac A, Reese JA, Gupta S, et al. Morbidities and mortality in patients with hereditary thrombotic thrombocytopenic purpura Blood Adv, 2022.PMID 34807988
[32]Jestin M, Benhamou Y, Schelpe AS, et al. Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura Blood, 2018.PMID 30201758
[33]Hie M, Gay J, Galicier L, et al. Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura Blood, 2014.PMID 24869941
[34]Zununi Vahed S, Rahbar Saadat Y, Ardalan M Thrombotic microangiopathy during pregnancy Microvasc Res, 2021.PMID 34252400
[35]George JN, Vesely SK, Terrell DR, et al. The Oklahoma Thrombotic Thrombocytopenic Purpura-haemolytic Uraemic Syndrome Registry. A model for clinical research, education and patient care Hamostaseologie, 2013.PMID 23364684
[36]Vesely SK Life after acquired thrombotic thrombocytopenic purpura: morbidity, mortality, and risks during pregnancy J Thromb Haemost, 2015.PMID 26149027
[37]Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children Pediatr Nephrol, 2016.PMID 25859752
[38]Menne J, Delmas Y, Fakhouri F, et al. Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study BMC Nephrol, 2019.PMID 30971227
[39]Tun NM, Villani GM Efficacy of rituximab in acute refractory or chronic relapsing non-familial idiopathic thrombotic thrombocytopenic purpura: a systematic review with pooled data analysis J Thromb Thrombolysis, 2012.PMID 22547089
[40]Moatti-Cohen M, Garrec C, Wolf M, et al. Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura Blood, 2012.PMID 22547583
[41]Zheng XL, Vesely SK, Cataland SR, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura J Thromb Haemost, 2020.PMID 32914526
[42]Swisher KK, Terrell DR, Vesely SK, et al. Clinical outcomes after platelet transfusions in patients with thrombotic thrombocytopenic purpura Transfusion, 2009.PMID 19210323