University of Wisconsin Hematology

TTP, HUS and related disorders

TTP

General, pathophysiology

  1. Sadler JE. Pathyophysiology of thrombotic thrombocytopenic purpura. Blood 2017;130:1181
  2. Hovinga et al. Pathophysiology of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. J Thromb Haemost 2018;16:618
  3. Schmidt et al. Complement and the prothrombotic state. Blood 2022;139:1972
  4. Joly et al. Thrombotic thrombocytopenic purpura. Blood 2017;129:2836
  5. Zheng et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost 2020;18:2486
  6. Zheng et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost 2020;18:2496
  7. Zheng et al. Good practice statements (GPS) for the clinical care of patients with thrombotic thrombocytopenic purpura. J Thromb Haemost 2020;18:2503
  8. Shaha et al. Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics. J Thromb Haemost 2017;15:1889
  9. Deshpande et al. Rapid ADAMTS13 activity assays for thrombotic thrombocytopenic purpura: a systematic review and meta-analysis. Blood 2025;146:233
  10. Crawley and Scully. Thrombotic thrombocytopenic purpura: basic pathophysiology and therapeutic strategies. Hematology 2013:292
  11. George and Nester. Syndromes of thrombotic microangiopathy. NEJM 2014;371:654
  12. George JN. The remarkable diversity of thrombotic thrombocytopenic purpura: a perspective. Blood Adv 2018;2:1510
  13. Prevel et al. Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival. Blood 2019;134:2209(Delayed diagnosis, higher mortality)
  14. Scully et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost 2017;15:312(DDX of TMA)
  15. Bendapudi et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol 2017;4:e157(Link to score)
  16. Sadler JE. Thrombotic Thrombocytopenic Purpura: A Moving Target. Hematology 2006;415
  17. Mariotte et al. Epidemiology and pathophysiology of adulthood-onset thrombotic microangiopathy with severe ADAMTS13 deficiency (thrombotic thrombocytopenic purpura): a cross-sectional analysis of the French national registry for thrombotic microangiopathy. Lancet Haematol 2016;3:e237(Many patients with severe ADAMTS13 deficiency and TTP had non-autoimmune disease associated with infection, cancer, transplantation, drugs, HIV; high incidence of inherited deficiency in OB cases)
  18. Joly et al. Child-onset and adolescent-onset acquired thrombotic thrombocytopenic purpura with severe ADAMTS13 deficiency: a cohort study of the French national registry for thrombotic microangiopathy. Lancet Haematol 2016;3:e537(< 10% of children with TMA have severe ADAMTS-13 deficiency; about a third of those have congenital deficiency)
  19. Grall et al. Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre. Am J Hematol 2017;92:381
  20. Le Besnerais et al. Assessment of endothelial damage and cardiac injury in a mouse model mimicking thrombotic thrombocytopenic purpura. J Thromb Haemost 2016;14:1917
  21. Alwan et al. Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura. Blood 2017;130:466(Elevated troponin at presentation associated with sixfold higher mortality)
  22. Jiang et al. Pregancy outcomes following recovery from acquired thrombotic thrombocytopenic purpura. Blood 2014;123:1674
  23. Scully et al. Thrombotic thrombocytopenic purpura and pregnancy: presentation, management, and subsequent pregnancy outcomes. Blood 2014;124:211(TTP presenting during pregnancy is often due to previously undiagnosed congenital ADAMTS13 deficiency)
  24. Deford et al. Multiple major morbidities and increased mortality during long-term follow-up after recovery from thrombotic thrombocytopenic purpura. Blood 2013;122:2023
  25. Chaturvedi et al. Silent cerebral infarction during immune TTP remission: prevalence, predictors, and impact on cognition. Blood 2023;142:326 (Lower ADAMTS13 levels in remission associated with higher stroke risk)
  26. Zafrani et al. Acute renal failure is prevalent in patients with thrombotic thrombocytopenic purpura associated with low plasma ADAMTS13 activity. J Thromb Haemost 2015;13:380(25% of patients in this retrospective series required renal replacement Rx)

Treatment

  1. Zheng. The standard of care for immune thrombotic thrombocytopenic purpura today. J Thromb Haemost 2021;19:1864
  2. Scully et al. Impact of new medications on the treatment of immune TTP. Blood 2025;145:1353
  3. Doyle et al. Long-term risk of relapse in immune-mediated thrombotic thrombocytopenic purpura and the role of anti-CD20 therapy. Blood 2023;141:285 (Pre-emptive anti-CD20 treatment to keep ADAMTS13 > 20% prevents 96% of relapses)
  4. Akwaa et al. How I treat immune-mediated thrombotic thrombocytopenic purpura after hospital discharge. Blood 2022;140:438
  5. Ferrari and Peyvandi. How I treat thrombotic thrombocytopenic purpura in pregnancy. Blood 2020;136:2125
  6. Rock et al. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. NEJM 1991; 325:393
  7. Hayward et al. Treatment outcomes in patients with adult thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Arch Intern Med 1994;154:982
  8. Lim et al. The role of rituximab in the management of patients with acquired thrombotic thrombocytopenic purpura. Blood 2015;125:1526
  9. Scully et al. A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood 2011;118:1746 (Quicker response, lower relapse rate, no apparent complications with rituximab vs hist. controls)
  10. Fakhouri et al. Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases. Blood 2005;106:1932
  11. Westwood et al. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost 2013;11:481
  12. Zwicker et al. Adjuvant low-dose rituximab and plasma exchange for acquired TTP. Blood 2019;134:1108 (100 mg of rituximab weekly x 4 appears effective)
  13. Page et al. Rituximab reduces risk for relapse in patients with thrombotic thrombocytopenic purpura. Blood 2016;127:3092(With editorial)
  14. Chaturvedi et al. Race, rituximab, and relapse in TTP. Blood 2022;140:1335 (Black patients relapse more quickly following rituximab therapy)
  15. Hie et al. Preemptive rituximab infusions after remission efficiently prevent relapses in acquired thrombotic thrombocytopenic purpura. Blood 2014;124:204(Rituximab given to patients with persistently low ADAMTS13 levels)
  16. Jestin et al. Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura. Blood 2018;132:2143
  17. Cataland et al. Cyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura. Blood Adv 2017;1:2075(Prednisone more effective in suppressing autoantibody production)
  18. Tersteeg et al. Plasmin Cleavage of von Willebrand Factor as an Emergency Bypass for ADAMTS13 Deficiency in Thrombotic Microangiopathy. Circulation 2014;129:1320(Proposes that thrombolytic agents may be useful in treatment of TTP; with editorial)
  19. Peyvandi et al. Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura. NEJM 2016;374:511(Anti-VWF nanobody induced faster resolution of TTP, with some increase in bleeding; see also subsequent letter to editor)
  20. Peyvandi et al. Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 2017;15:1448(Caplacizumab treatment associated with 75% reduction in major thrombotic events or death)
  21. Scully et al. Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura. NEJM 2019;380:335(Caplacizumab treatment resulted in faster resoluution of thrombocytopenia and fewer adverse events, including death, than placebo)
  22. Dutt et al. Real-world experience with caplacizumab in the management of acute TTP. Blood 2021;137:1731
  23. Kühne et al. Alternate-day dosing of caplacizumab for immune-mediated thrombotic thrombocytopenic purpura. J Thromb Haemost 2022;20:951(Alternate day dosing appears safe after 3-4 weeks of daily treatment)
  24. Coppo et al. A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP. Blood 2021;137:733
  25. Schofield et al. Intracranial hemorrhage in immune thrombotic thrombocytopenic purpura treated with caplacizumab. J Thromb Haemost 2021;19:1922
  26. Prasannan et al. Delayed normalization of ADAMTS13 activity in acute thrombotic thrombocytopenic purpura in the caplacizumab era. Blood 2023;141:2208 (6-fold higher rate of ADAMTS13 less than 10% in caplacizumab treated patients)
  27. Mazepa et al. How targeted therapy disrupts the treatment paradigm for acquired TTP: the risks, benefits, and unknowns. Blood 2019;134:415
  28. Scully et al. Long-term follow-up of patients treated with caplacizumab and safety and efficacy of repeat caplacizumab use: Post-HERCULES study. J Thromb Haemost 2022;20:2810
  29. Völker et al. Impact of first-line use of caplacizumab on treatment outcomes in immune thrombotic thrombocytopenic purpura. J Thromb Haemost 2023;21:559 (Modest improvement in survival vs historical controls)
  30. Kühne et al. Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange. Blood 2024;144:1488
  31. Mingot-Castellano et al. ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapy. Blood 2024;143:1807 (Given early, capla shortens duration of PEX treatment but doesn’t eliminate requirement for immunosuppression)
  32. Patriquin et al. Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura. Br J Haem 2016;173:779 (5/6 patients had CR)
  33. Ratnasingam et al. Bortezomib-based antibody depletion for refractory autoimmune hematological diseases. Blood Adv 2016;1:31 (Bortezomib effective in a variety of autoimmune conditions including AIHA, acquired factor VIII inhibitor, and TTP)
  34. Giannotta et al. Bortezomib for rituximab-refractory immune-mediated thrombotic thrombocytopenic purpura in the caplacizumab era: an Italian multicenter study. J Thromb Haemost 2025;23:704
  35. Crowther et al. Splenectomy done during hematologic remission to prevent relapse in patients with thrombotic thrombocytopenic purpura. Ann Intern Med 1996;125:294
  36. Crowley et al. Ofatumumab for TTP in a Patient with Anaphylaxis Associated with Rituximab (letter). NEJM 2018;378:92
  37. Bendapudi et al. Recombinant ADAMTS13 for Immune Thrombotic Thrombocytopenic Purpura. NEJM 2024;390:1690
  38. George et al. Management of thrombotic thrombocytopenic purpura without plasma exchange: the Jehovah’s Witness experience. Blood Adv 2017;1:2161
  39. Arcudi et al. Prevention of relapse in patients with acquired thrombotic thrombocytopenic purpura undergoing elective surgery: a case series, J Thromb Haemost 2019; 17:492
  40. Upreti et al. Reduced ADAMTS13 activity during TTP remission is associated with stroke in TTP survivors. Blood 2019;134:1037

ADAMTS-13

  1. Masias and Cataland. The role of ADAMTS13 testing in the diagnosis and management of thrombotic microangiopathies and thrombosis. Blood 2018;132:903
  2. Sadler E. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. Blood 2008;112:11
  3. Furlan et al. Von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. NEJM 1998;339:1578.
  4. Tsai and Lian. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. NEJM 1998;339:1585
  5. Hassan et al. The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry. Br J Haem 2015;171:830
  6. Banno et al. Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura. Blood 2006;107:3161 (In mice)
  7. Feys et al. Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papio ursinus). Blood 2010;116:2005
  8. Hovinga et al. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 2010;115:1500(Low ADAMTS13 activity associated with higher relapse rate; some patients did not relapse despite persistently low levels)
  9. Alwan et al. Presenting ADAMTS13 antibody and antigen levels predict prognosis in immune-mediated thrombotic thrombocytopenic purpura. Blood 2017;130:466
  10. Rieger et al. ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases. Blood 2005;106:1262  (ELISA assay for ADAMTS-13 antibodies)
  11. Zheng et al. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura.  Blood 2004;103:4043
  12. Coppo et al. Prognostic value of inhibitory anti-ADAMTS13 antibodies in adult-acquired thrombotic thrombocytopenic purpura. Br JHaematol 2006;132:66
  13. Starke et al. The clinical utility of ADAMTS13 activity, antigen and autoantibody assays in thrombotic thrombocytopenic purpura. Br JHaematol 2007;136:649
  14. Jin et al. Relationship between ADAMTS13 activity in clinical remission and the risk of TTP relapse. Br JHaematol 2008;141:651(Low ADAMTS13 level, younger age associated with higher relapse rate)
  15. Page et al. Clinical importance of ADAMTS13 activity during remission in patients with acquired thrombotic thrombocytopenic purpura (letter). Blood 2016;128:2175(Levels may fluctuate dramatically during remission without clinical relapse)
  16. Mannucci and Peyvandi. TTP and ADAMTS13: when is testing appropriate? Hematology 2007:121
  17. Fakhouri et al. Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases. Blood 2005;106:1932
  18. Nolasco et al. Hemolytic uremic syndrome–associated Shiga toxins promote endothelial-cell secretion and impair ADAMTS13 cleavage of unusually large von Willebrand factor multimers. Blood 2005;106:4199
  19. Chauhan et al. The combined roles of ADAMTS13 and VWF in murine models of TTP, endotoxemia, and thrombosis. Blood 2008;111:3452.(VWF mediates thrombocytopenia in ADAMTS-13 deficiency but not endotoxemia)
  20. Sonneveld et al. Low ADAMTS13 activity is associated with an increased risk of ischemic stroke. Blood 2015;126:2739
  21. Maino et al. Plasma ADAMTS-13 levels and the risk of myocardial infarction: an individual patient data meta-analysis. J Thromb Haemost 2015;13:1396(Very low ADAMTS13 levels associated with high risk of MI)
  22. Levi et al. The role of ADAMTS‐13 in the coagulopathy of sepsis. J Thromb Haemost 2018;16:646
  23. Xu et al. ADAMTS13 controls vascular remodeling by modifying VWF reactivity during stroke recovery. Blood 2017;130:11

Congenital TTP (Upshaw-Shulman syndrome)

  1. Hovinga and George. Hereditary thrombotic thrombocytopenic purpura. NEJM 2019;381:1653
  2. Alwan et al. Characterization and treatment of congenital thrombotic thrombocytopenic purpura. Blood 2019;133:1644
  3. Borogovac et al. Prevalence of neuropsychiatric symptoms and stroke in patients with hereditary thrombotic thrombocytopenic purpura. Blood 2022;140:785
  4. Scully et al. Recombinant ADAMTS-13: first-in-human pharmacokinetics and safety in congenital thrombotic thrombocytopenic purpura. Blood 2017;130:2055
  5. Asmis et al. Recombinant ADAMTS13 for Hereditary Thrombotic Thrombocytopenic Purpura. NEJM 2022;387:2356
  6. Scully et al. Recombinant ADAMTS13 in Congenital Thrombotic Thrombocytopenic Purpura. NEJM 2024;390:1584
  7. Taylor et al. Pharmacokinetics of plasma infusion in congenital thrombotic thrombocytopenic purpura. J Thromb Haemost 2019;17:88(Median ADAMTS-13 half-life 130 hours, range 83-190; suggests treatment needed every 4-10 days)
  8. Moatti-Cohen et al. Unexpected frequency of Upshaw-Schulman syndrome in pregnancy-onset thrombotic thrombocytopenic purpura. Blood 2012;119:5888
  9. Tarasco et al. Annual incidence and severity of acute episodes in hereditary thrombotic thrombocytopenic purpura. Blood 2021;137:3563(Episode decrease with age after age 10)
  10. Borogovic et al. Morbidities and mortality in patients with hereditary thrombotic thrombocytopenic purpura. Blood Adv 2022;6:750

HUS

  1. Michael et al. Haemolytic uraemic syndrome. Lancet 2022;400:1722
  2. Jokiranta TS. HUS and atypical HUS. Blood 2017;129:2847
  3. Hovinga et al. Pathophysiology of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. J Thromb Haemost 2018;16:618
  4. George and Nester. Syndromes of thrombotic microangiopathy. NEJM 2014;371:654
  5. Lizewski and Atkinson. Too Much of a Good Thing at the Site of Tissue Injury: The Instructive Example of the Complement System Predisposing to Thrombotic Microangiopathy. Hematology 2011: 9
  6. Conway EM. HUS and the case for complement. Blood 2015;126:2085
  7. Phillips et al. The role of ADAMTS-13 activity and complement mutational analysis in differentiating acute thrombotic microangiopathies. J Thromb Haemost 2016;14:175(Platelet count and creatinine not adequate to distinguish aHUS from TTP; complelement mutation analysis recommended in TMA patients with ADAMTS13 > 10%)
  8. Freedman et al. Shiga Toxin–Producing Escherichia coli and the Hemolytic–Uremic Syndrome. NEJM 2023;389:1402
  9. Su and Brandt. Escherichia coli O157:H7 infection in humans. Ann Intern Med 1995;123:698
  10. Lapeyraque et al. Eculizumab in severe Shiga-toxin-associated HUS (letter). NEJM 2011;364:2561
  11. Brocklebank et al. Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: an observational cohort study. Blood 2023;142:1371
  12. Nitschke et al. Association Between Azithromycin Therapy and Duration of Bacterial Shedding Among Patients With Shiga Toxin–Producing Enteroaggregative Escherichia coli O104:H4. JAMA 2012;307:1046(Antibiotic treatment associated with lower frequency of long-term bacterial carriage)
  13. Caprioli et al. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood 2006;108:1267
  14. Kavanagh and Goodship. Atypical Hemolytic Uremic Syndrome, Genetic Basis, and Clinical Manifestations. Hematology 2011;15
  15. Noris and Remuzzi. Atypical hemolytic-uremic syndrome. NEJM 2009;361:1676
  16. Fakhouri et al. How I diagnose and treat atypical hemolytic uremic syndrome. Blood 2023;141:984
  17. Fang et al. Membrane cofactor protein mutations in atypical hemolytic uremic syndrome (aHUS), fatal Stx-HUS, C3 glomerulonephritis, and the HELLP syndrome. Blood 2008;111:624
  18. Fakhouri et al. Factor H, membrane cofactor protein, and factor I mutations in patients with hemolysis, elevated liver enzymes, and low platelet count syndrome. Blood 2008;112:4542(Mutations found in 4/11 patients)
  19. Frémeaux-Bacchi et al. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood 2008;112:4948
  20. Roumenina et al. Hyperfunctional C3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome. Blood 2009;114:2837
  21. Delvaeye et al. Thrombomodulin Mutations in Atypical Hemolytic–Uremic Syndrome. NEJM 2009;361:345
  22. Roumenina et al. A prevalent C3 mutation in aHUS patients causes a direct C3 convertase gain of function. Blood 2012;119:4182
  23. Legendre et al. Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic–Uremic Syndrome. NEJM 2013;368:2169
  24. Cofiell et al. Eculizumab reduces complement activation, inflammation, endothelial damage, thrombosis, and renal injury markers in aHUS. Blood 2015;125:3253
  25. Noris et al. Dynamics of complement activation in aHUS and how to monitor eculizumab therapy. Blood 2014;124:1715(In vitro complement deposition assays correlated with treatment response, could be used to titrate drug dose)
  26. Cataland et al. Biomarkers of terminal complement activation confirm the diagnosis of aHUS and differentiate aHUS from TTP. Blood 2014;123: 3733
  27. Cole et al. Complement biosensors identify a classical pathway stimulus in complement-mediated thrombotic microangiopathy. Blood 2024;144:2528 (Suggests activation of classical pathway by IgM is the trigger for aHUS, and that alternative pathway regulatory defects are secondary contributors)
  28. Feng et al. Partial ADAMTS13 deficiency in atypical hemolytic uremic syndrome. Blood 2013;122:1487 (Found concomitant with complement gene mutations in many patients)
  29. Merrill et al. Eculizumab cessation in atypical hemolytic uremic syndrome. Blood 2017;130:368 (3 of 15 of patients relapsed after treatment cessation)
  30. Fakhouri et al. Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study. Blood 2021;137:2438 (“Reasonable and safe” in most cases, except with certain rare complement gene variants)

Other thrombotic microangiopathies

  1. Doreille et al. How I treat thrombotic microangiopathy in the era of rapid genomics. Blood 2023;141:147
  2. Masias et al. None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood 2017;129:2857
  3. George and Nester. Syndromes of thrombotic microangiopathy. NEJM 2014;371:654
  4. Al-Nouri et al. Drug-induced thrombotic microangiopathy: a systematic review of published reports. Blood 2015;125:616
  5. Reese et al. Drug-induced thrombotic microangiopathy: Experience of the Oklahoma registry and the BloodCenter of Wisconsin. Am J Hematol 2015;90:406
  6. Thomas and Scully. How I treat microangiopathic hemolytic anemia in patients with cancer. Blood 2021; 137:1310
  7. Jodele et al. The genetic fingerprint of susceptibility for transplant-associated thrombotic microangiopathy. Blood 2016;127:989(Complement gene variants and upregulation of complement pathways associated with TMA after HSCT)
  8. Eremina et al. VEGF inhibition and renal thrombotic microangiopathy. NEJM 2008;358:1129(HUS caused by bevacizumab)
  9. Park et al. Complement-mediated thrombotic microangiopathy associated with lupus nephritis. Blood Adv 2018;2:2090
  10. Henderson et al. Low-Dose Aspirin for Prevention of Morbidity and Mortality From Preeclampsia: A Systematic Evidence Review for the U.S. Preventive Services Task Force. Ann Intern Med 2014;160:695(Modest reduction in risk for adverse outcomes with ASA, no apparent adverse effects)
  11. Rolnik et al. Aspirin versus Placebo in Pregnancies at High Risk for Preterm Preeclampsia. NEJM 2017;377:613 (Preeclampsia incidence reduced from 4.3% to 1.6% with 150 mg/d ASA; with editorial)
  12. Peyvandi et al. Thrombotic microangiopathy without renal involvement: two novel mutations in complement-regulator genes. J Thromb Haemost 2016;14:340
  13. Kavanagh et al. Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature. Blood 2016;128:2824
  14. Hunt et al. A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER. Blood 2017;129:896
  15. Warkentin T. Ischemic limb gangrene with pulses. NEJM 2015;373:642