Atypical uremic hemolytic syndrome
A subdiagnosed entity?
Keywords:
HEMOLYTIC-UREMIC SYNDROME, THROMBOTIC MICROANGIOPATHIES, PLASMA EXCHANGEAbstract
Thrombotic microangiopathy (MAT) is an anatomo-pathological condition characterized by a lesion in the arterial wall with parietal thickening, edema and endothelial cells detached from the basement membrane. Clinically it is seen as a hemolytic microangiopathic anaemia, microvascular occlusion due to platelete count and thrombocytopenia. It could be a consequence of a primary alteration in the complex system that regulates the relationship between the endothelio and coagulation or occur within the context of a systemic alteration. Thrombotic thrombocytopenic purpura (PPT) and hemolytic uremic syndrome (HUS) are two phenotypes of the disease. Availability of therapeutic tools calls for the fast acknowledgement of this pathogenic mechanism to start up early therapeutic. The study presents two cases of atypical HUS and based on that reviews the main diagnostic, therapeutic and prognostic aspects.
References
(1) Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int 2001; 60(3):831-46.
(2) George JN, Gilcher RO, Smith JW, Chandler L, Duvall D, Ellis C. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: diagnosis and management. J Clin Apher 1998; 13(3):120-5.
(3) George JN, Vesely SK. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: diagnosis and treatment. Cleve Clin J Med 2001; 68(10):857-8, 860, 863-4.
(4) George JN, Vesely SK, Terrell DR. The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) Registry: a community perspective of patients with clinically diagnosed TTP-HUS. Semin Hematol 2004; 41(1):60-7.
(5) Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, 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; 325(6):393-7.
(6) George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116(20):4060-9.
(7) George JN. Clinical practice: thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354(18):1927-35.
(8) Gadea M del P, Varela G, Bernadá M, Sirok A, Mota MI, Sabelli R, et al. Primer aislamiento en Uruguay de Escherichia coli productora de toxina Shiga del serotipo O157:H7 en una niña con síndrome urémico hemolítico. Rev Méd Urug 2004; 20(1):79–81.
(9) Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005; 16(4):1035-50.
(10) Frank C, Werber D, Cramer JP, Askar M, Faber M, an der Heiden M, et al; HUS Investigation Team. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med 2011; 365(19):1771-80.
(11) Kielstein JT, Beutel G, Fleig S, Steinhoff J, Meyer TN, Hafer C, et al; Collaborators of the DGfN STEC-HUS registry. Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin-producing E. coli O104:H4 induced haemolytic-uraemic syndrome: an analysis of the German STEC-HUS registry. Nephrol Dial Transplant 2012; 27(10):3807-15.
(12) Braune SA, Wichmann D, von Heinz MC, Nierhaus A, Becker H, Meyer TN, et al. Clinical features of critically ill patients with Shiga toxin-induced hemolytic uremic syndrome. Crit Care Med 2013; 41(7):1702-10.
(13) Noris M, Mescia F, Remuzzi G. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol 2012; 8(11):622-33.
(14) Noris M, Remuzzi G. Genetics and genetic testing in hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. Semin Nephrol 2010; 30(4):395-408.
(15) Noris M, Remuzzi G. Complement factor h gene abnormalities in haemolytic uraemic syndrome: from point mutations to hybrid gene. PLoS Med 2006; 3(10):e432. Disponible en: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626557/pdf/pmed.0030432.pdf. Consulta: marzo 2014.
(16) Noris M, Remuzzi G. Genetic abnormalities of complement regulators in hemolytic uremic syndrome: how do they affect patient management? Nat Clin Pract Nephrol 2005; 1(1):2-3.
(17) Noris M, Remuzzi G. Are HUS and TTP genetically determined? Kidney Int 1998; 53(4):1085-6.
(18) Noris M, Bresin E, Mele C, Remuzzi G. Atypical Hemolytic-Uremic Syndrome: 2007 Nov 16 updated 2013 Aug 08. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Smith RJH, et al, eds. GeneReviews® Internet. Seattle (WA): University of Washington, Seattle; 1993-2014. Disponible en: http://www.ncbi.nlm.nih.gov/books/NBK1367/. Consulta: marzo 2014.
(19) Noris M, Ruggenenti P, Perna A, Orisio S, Caprioli J, Skerka C, et al. Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities. Italian Registry of Familial and Recurrent Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura. J Am Soc Nephrol 1999; 10(2):281-93.
(20) Remuzzi G, Ruggenenti P, Colledan M, Gridelli B, Bertani A, Bettinaglio P, et al. Hemolytic uremic syndrome: a fatal outcome after kidney and liver transplantation performed to correct factor h gene mutation. Am J Transplant 2005; 5(5):1146-50.
(21) Lemaire M, Frémeaux-Bacchi V, Schaefer F, Choi M, Tang WH, Le Quintrec M, et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet 2013; 45(5):531–6. Disponible en: http://www. ncbi. nlm.nih.gov/pmc/articles/PMC3719402/ pdf/nihms-474970. pdf. Consulta: marzo 2014.
(22) Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361(17):1676-87.
(23) Constantinescu AR, Bitzan M, Weiss LS, Christen E, Kaplan BS, Cnaan A, et al. Non-enteropathic hemolytic uremic syndrome: causes and short-term course. Am J Kidney Dis 2004; 43(6):976-82.
(24) Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, Carreras L, Aller Arranz E, Abarrategui Garrido C, et al. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci U S A 2007; 104(1):240–5. Disponible en: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1765442/ pdf/zpq240.pdf. Consulta: marzo 2014.
(25) Kavanagh D, Kemp EJ, Mayland E, Winney RJ, Duffield JS, Warwick G, et al. Mutations in complement factor I predispose to development of atypical hemolytic uremic syndrome. J Am Soc Nephrol 2005; 16(7):2150-5.
(26) Campistol Plana JM, Arias M, Ariceta Iraola G, Blasco M, Espinosa M, Grinyó JM, et al. Actualización en síndrome hemolítico urémico atípico: diagnóstico y tratamiento. Documento de consenso. Nefrología 2013; 33(1):27–45. Disponible en: http://www.revistanefrologia.com/revistas/P1-E547/P1-E547-S3861-A11781.pdf. Consulta: marzo 2014.
(27) Cameron JS, Vick R. Letter: Plasma-C3 in haemolytic-uraemic syndrome and thrombotic thrombocytopenic purpura. Lancet 1973; 2(7835):975.
(28) Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey MA, Ngo S, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 2013; 8(4):554-62.
(29) Wada H, Wakita Y, Nakase T, Shimura M, Hiyoyama K, Nagaya S, et al. Increased plasma-soluble fibrin monomer levels in patients with disseminated intravascular coagulation. Am J Hematol 1996; 51(4):255-60.
(30) von Baeyer H. Plasmapheresis in thrombotic microangiopathy-associated syndromes: review of outcome data derived from clinical trials and open studies. Ther Apher 2002; 6(4):320-8.
(31) Kremer Hovinga JA, Vesely SK, Terrell DR, Lämmle B, George JN. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 2010; 115(8):1500-11.
(32) Moake JL. Thrombotic microangiopathies. N Engl J Med 2002; 347(8):589-600.
(33) 33. Rizvi MA, Vesely SK, George JN, Chandler L, Duvall D, Smith JW, et al. Complications of plasma exchange in 71 consecutive patients treated for clinically suspected thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome. Transfusion 2000; 40(8):896-901.
(34) Nguyen L, Terrell DR, Duvall D, Vesely SK, George JN. Complications of plasma exchange in patients treated for thrombotic thrombocytopenic purpura. IV. An additional study of 43 consecutive patients, 2005 to 2008. Transfusion 2009; 49(2):392-4.
(35) Balduini CL, Gugliotta L, Luppi M, Laurenti L, Klersy C, Pieresca C, et al; Italian TTP Study Group. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol 2010; 89(6):591-6.
(36) George JN, Woodson RD, Kiss JE, Kojouri K, Vesely SK. Rituximab therapy for thrombotic thrombocytopenic purpura: a proposed study of the Transfusion Medicine/Hemostasis Clinical Trials Network with a systematic review of rituximab therapy for immune-mediated disorders. J Clin Apher 2006; 21(1):49-56.
(2) George JN, Gilcher RO, Smith JW, Chandler L, Duvall D, Ellis C. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: diagnosis and management. J Clin Apher 1998; 13(3):120-5.
(3) George JN, Vesely SK. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: diagnosis and treatment. Cleve Clin J Med 2001; 68(10):857-8, 860, 863-4.
(4) George JN, Vesely SK, Terrell DR. The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) Registry: a community perspective of patients with clinically diagnosed TTP-HUS. Semin Hematol 2004; 41(1):60-7.
(5) Rock GA, Shumak KH, Buskard NA, Blanchette VS, Kelton JG, Nair RC, 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; 325(6):393-7.
(6) George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010; 116(20):4060-9.
(7) George JN. Clinical practice: thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354(18):1927-35.
(8) Gadea M del P, Varela G, Bernadá M, Sirok A, Mota MI, Sabelli R, et al. Primer aislamiento en Uruguay de Escherichia coli productora de toxina Shiga del serotipo O157:H7 en una niña con síndrome urémico hemolítico. Rev Méd Urug 2004; 20(1):79–81.
(9) Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005; 16(4):1035-50.
(10) Frank C, Werber D, Cramer JP, Askar M, Faber M, an der Heiden M, et al; HUS Investigation Team. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med 2011; 365(19):1771-80.
(11) Kielstein JT, Beutel G, Fleig S, Steinhoff J, Meyer TN, Hafer C, et al; Collaborators of the DGfN STEC-HUS registry. Best supportive care and therapeutic plasma exchange with or without eculizumab in Shiga-toxin-producing E. coli O104:H4 induced haemolytic-uraemic syndrome: an analysis of the German STEC-HUS registry. Nephrol Dial Transplant 2012; 27(10):3807-15.
(12) Braune SA, Wichmann D, von Heinz MC, Nierhaus A, Becker H, Meyer TN, et al. Clinical features of critically ill patients with Shiga toxin-induced hemolytic uremic syndrome. Crit Care Med 2013; 41(7):1702-10.
(13) Noris M, Mescia F, Remuzzi G. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol 2012; 8(11):622-33.
(14) Noris M, Remuzzi G. Genetics and genetic testing in hemolytic uremic syndrome/thrombotic thrombocytopenic purpura. Semin Nephrol 2010; 30(4):395-408.
(15) Noris M, Remuzzi G. Complement factor h gene abnormalities in haemolytic uraemic syndrome: from point mutations to hybrid gene. PLoS Med 2006; 3(10):e432. Disponible en: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1626557/pdf/pmed.0030432.pdf. Consulta: marzo 2014.
(16) Noris M, Remuzzi G. Genetic abnormalities of complement regulators in hemolytic uremic syndrome: how do they affect patient management? Nat Clin Pract Nephrol 2005; 1(1):2-3.
(17) Noris M, Remuzzi G. Are HUS and TTP genetically determined? Kidney Int 1998; 53(4):1085-6.
(18) Noris M, Bresin E, Mele C, Remuzzi G. Atypical Hemolytic-Uremic Syndrome: 2007 Nov 16 updated 2013 Aug 08. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Smith RJH, et al, eds. GeneReviews® Internet. Seattle (WA): University of Washington, Seattle; 1993-2014. Disponible en: http://www.ncbi.nlm.nih.gov/books/NBK1367/. Consulta: marzo 2014.
(19) Noris M, Ruggenenti P, Perna A, Orisio S, Caprioli J, Skerka C, et al. Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities. Italian Registry of Familial and Recurrent Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Purpura. J Am Soc Nephrol 1999; 10(2):281-93.
(20) Remuzzi G, Ruggenenti P, Colledan M, Gridelli B, Bertani A, Bettinaglio P, et al. Hemolytic uremic syndrome: a fatal outcome after kidney and liver transplantation performed to correct factor h gene mutation. Am J Transplant 2005; 5(5):1146-50.
(21) Lemaire M, Frémeaux-Bacchi V, Schaefer F, Choi M, Tang WH, Le Quintrec M, et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet 2013; 45(5):531–6. Disponible en: http://www. ncbi. nlm.nih.gov/pmc/articles/PMC3719402/ pdf/nihms-474970. pdf. Consulta: marzo 2014.
(22) Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361(17):1676-87.
(23) Constantinescu AR, Bitzan M, Weiss LS, Christen E, Kaplan BS, Cnaan A, et al. Non-enteropathic hemolytic uremic syndrome: causes and short-term course. Am J Kidney Dis 2004; 43(6):976-82.
(24) Goicoechea de Jorge E, Harris CL, Esparza-Gordillo J, Carreras L, Aller Arranz E, Abarrategui Garrido C, et al. Gain-of-function mutations in complement factor B are associated with atypical hemolytic uremic syndrome. Proc Natl Acad Sci U S A 2007; 104(1):240–5. Disponible en: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1765442/ pdf/zpq240.pdf. Consulta: marzo 2014.
(25) Kavanagh D, Kemp EJ, Mayland E, Winney RJ, Duffield JS, Warwick G, et al. Mutations in complement factor I predispose to development of atypical hemolytic uremic syndrome. J Am Soc Nephrol 2005; 16(7):2150-5.
(26) Campistol Plana JM, Arias M, Ariceta Iraola G, Blasco M, Espinosa M, Grinyó JM, et al. Actualización en síndrome hemolítico urémico atípico: diagnóstico y tratamiento. Documento de consenso. Nefrología 2013; 33(1):27–45. Disponible en: http://www.revistanefrologia.com/revistas/P1-E547/P1-E547-S3861-A11781.pdf. Consulta: marzo 2014.
(27) Cameron JS, Vick R. Letter: Plasma-C3 in haemolytic-uraemic syndrome and thrombotic thrombocytopenic purpura. Lancet 1973; 2(7835):975.
(28) Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey MA, Ngo S, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 2013; 8(4):554-62.
(29) Wada H, Wakita Y, Nakase T, Shimura M, Hiyoyama K, Nagaya S, et al. Increased plasma-soluble fibrin monomer levels in patients with disseminated intravascular coagulation. Am J Hematol 1996; 51(4):255-60.
(30) von Baeyer H. Plasmapheresis in thrombotic microangiopathy-associated syndromes: review of outcome data derived from clinical trials and open studies. Ther Apher 2002; 6(4):320-8.
(31) Kremer Hovinga JA, Vesely SK, Terrell DR, Lämmle B, George JN. Survival and relapse in patients with thrombotic thrombocytopenic purpura. Blood 2010; 115(8):1500-11.
(32) Moake JL. Thrombotic microangiopathies. N Engl J Med 2002; 347(8):589-600.
(33) 33. Rizvi MA, Vesely SK, George JN, Chandler L, Duvall D, Smith JW, et al. Complications of plasma exchange in 71 consecutive patients treated for clinically suspected thrombotic thrombocytopenic purpura-hemolytic-uremic syndrome. Transfusion 2000; 40(8):896-901.
(34) Nguyen L, Terrell DR, Duvall D, Vesely SK, George JN. Complications of plasma exchange in patients treated for thrombotic thrombocytopenic purpura. IV. An additional study of 43 consecutive patients, 2005 to 2008. Transfusion 2009; 49(2):392-4.
(35) Balduini CL, Gugliotta L, Luppi M, Laurenti L, Klersy C, Pieresca C, et al; Italian TTP Study Group. High versus standard dose methylprednisolone in the acute phase of idiopathic thrombotic thrombocytopenic purpura: a randomized study. Ann Hematol 2010; 89(6):591-6.
(36) George JN, Woodson RD, Kiss JE, Kojouri K, Vesely SK. Rituximab therapy for thrombotic thrombocytopenic purpura: a proposed study of the Transfusion Medicine/Hemostasis Clinical Trials Network with a systematic review of rituximab therapy for immune-mediated disorders. J Clin Apher 2006; 21(1):49-56.
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Published
2014-03-31
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1.
Silvariño R, Pérez G, Canzani O, Larre Borges P, Acosta N, Noboa Óscar. Atypical uremic hemolytic syndrome: A subdiagnosed entity?. Rev. Méd. Urug. [Internet]. 2014 Mar. 31 [cited 2024 Nov. 24];30(1):56-64. Available from: https://revista.rmu.org.uy/index.php/rmu/article/view/260
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