Microangiopatías trombóticas primarias: una revisión narrativa

Palabras clave: microangiopatías trombóticas, púrpura trombocitopénica trombótica, síndrome hemolítico urémico, síndrome hemolítico urémico atípico, anemia hemolítica, trombocitopenia.

Resumen

La microangiopatía trombótica (MAT) es un síndrome donde hay formación de microtrombos en la circulación que llevan a anemia hemolítica microangiopática (AHMA) y trombocitopenia con falla multiorgánica, debido a la isquemia de los tejidos. Las MAT pueden ser primarias sin causa subyacente asociada, como la púrpura trombocitopénica trombótica debida a deficiencia de la enzima ADAMTS13, el síndrome hemolítico urémico debido a la toxina Shiga de Escherichia coli enterohemorrágica, y la MAT producida por alteraciones en la regulación del complemento. Adicionalmente, pueden ser secundarias a enfermedades malignas, infecciosas, metabólicas, autoinmunes o inducidas por el embarazo. Estas patologías requieren diagnóstico y tratamiento oportunos debido a que tienen alta morbimortalidad y se asocian a complicaciones que incluyen enfermedad renal, alteraciones neurológicas como convulsiones, accidente cerebrovascular, coma y muerte. El tratamiento es multidisciplinario y se enfoca en el soporte hemodinámico, transfusional y en el manejo de la etiología cuando esta es identificada. La siguiente revisión pretende explicar de forma clara y precisa los aspectos generales de las MAT primarias.

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Biografía del autor/a

Natalia Henao-Piedrahita, Fundación Universitaria San Martín

Médica General, Fundación Universitaria San Martín. Sabaneta, Colombia.

Referencias bibliográficas

Moschcowitz E. An acute febrile pleiochromic anemia with hyaline thrombosis of the terminal arterioles and capillaries; an undescribed disease. Am J Med 1952;13:567-569. https://doi.org/10.1016/0002-9343(52)90022-3.

Contreras E, De la Rubia J, del Río-Garma J, Díaz-Ricart M, García-Gala JM, Lozano M. Guía diagnóstica y terapéutica de las microangiopatías trombóticas del Grupo Español de Aféresis. Med Clin 2015;144:e1-e13. https://doi.org/10.1016/j.medcli.2014.09.013.

Arnold DM, Patriquin CJ, Nazy I. Thrombotic microangiopathies: a general approach to diagnosis and management. CMAJ 2017;189:E153-E159. https://doi.org/10.1503/cmaj.160142.

Radhakrishnan J. Anticomplement therapies in “secondary thrombotic microangiopathies”: ready for prime time? Kidney Int 2019;96:833-835. https://doi.org/10.1016/j.kint.2019.08.005.

George JN, Nester CM. Syndromes of thrombotic microangiopathy. N Engl J Med 2014;371:654-666. https://doi.org/10.1056/NEJMra1312353.

Moake JL. Thrombotic microangiopathies. N Engl J Med 2002;347:589-600. https://doi.org/10.1056/NEJMra020528.

Romero S, Sempere A, Gómez-Seguí I, Román E, Moret A, Jannone R, et al. Guía práctica de tratamiento urgente de la microangiopatía trombótica. Med Clin 2018;151:123.e121-123.e129. https://doi.org/https://doi.org/10.1016/j.medcli.2018.01.013.

George JN, Nester CM. Approach to the patient with suspected TTP, HUS, or other thrombotic microangiopathy (TMA). Massachusetts, Estados Unidos: Wolters Kluwer Health; 2019. Acceso 20 de agosto de 2020. Disponible en https://www.uptodate.com/contents/approach-to-the-patient-with-suspected-ttp-hus-or-other-thrombotic-microangiopathy-tma#H16673902.

Nokes T, George JN, Vesely SK, Awab A. Pulmonary involvement in patients with thrombotic thrombocytopenic purpura. Eur J Haematol 2014;92:156-163. https://doi.org/10.1111/ejh.12222.

Blasco-Pelicano M, Guillé E, Quintana L, Garcia-Herrera A, Piñeiro G, Poch E, et al. Thrombotic microangiopathies assessment: mind the complement. Clin Kidney J 2020;2020:sfaa195. https://doi.org/10.1093/ckj/sfaa195.

Eskazan AE, Salihoglu A. Treatment and outcome of primary and secondary thrombotic microangiopathies. Am J Nephrol 2015;41:427-428. https://doi.org/10.1159/000437002.

Kremer Hovinga JA, Coppo P, Lämmle B, Moake JL, Miyata T, Vanhoorelbeke K. Thrombotic thrombocytopenic purpura. Nat Rev Dis Primers 2017;3:17020. https://doi.org/10.1038/nrdp.2017.20.

Joly BS, Coppo P, Veyradier A. An update on pathogenesis and diagnosis of thrombotic thrombocytopenic purpura. Expert Rev Hematol 2019;12:383-395. https://doi.org/10.1080/17474086.2019.1611423.

Shatzel JJ, Taylor JA. Syndromes of thrombotic microangiopathy. Med Clin North Am 2017;101:395-415. https://doi.org/10.1016/j.mcna.2016.09.010.

George JN. Thrombotic microangiopathy (TMA). Platelets on the Web. Oklahoma, USA: University of Oklahoma Health Sciences Center; 2007. Acceso 5 de agosto de 2020. Disponible en https://www.ouhsc.edu/platelets/TMA.htm.

Reese JA, Muthurajah DS, Kremer Hovinga JA, Vesely SK, Terrell DR, George JN. Children and adults with thrombotic thrombocytopenic purpura associated with severe, acquired Adamts13 deficiency: comparison of incidence, demographic and clinical features. Pediatr Blood Cancer 2013;60:1676-1682. https://doi.org/10.1002/pbc.24612.

Terrell DR, Williams LA, Vesely SK, Lämmle B, Hovinga JA, George JN. The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J Thromb Haemost 2005;3:1432-1436. https://doi.org/10.1111/j.1538-7836.2005.01436.x.

Terrell DR, Vesely SK, Kremer Hovinga JA, Lämmle B, George JN. Different disparities of gender and race among the thrombotic thrombocytopenic purpura and hemolytic-uremic syndromes. Am J Hematol 2010;85:844-847. https://doi.org/10.1002/ajh.21833.

Moake JL, Rudy CK, Troll JH, Weinstein MJ, Colannino NM, Azocar J, et al. Unusually large plasma factor VIII:von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Engl J Med 1982;307:1432-1435. https://doi.org/10.1056/nejm198212023072306.

Asada Y, Sumiyoshi A, Hayashi T, Suzumiya J, Kaketani K. Immunohistochemistry of vascular lesion in thrombotic thrombocytopenic purpura, with special reference to factor VIII related antigen. Thromb Res 1985;38:469-479. https://doi.org/10.1016/0049-3848(85)90180-x.

Vacca VM, Jr. Acquired autoimmune thrombotic thrombocytopenic purpura. Nursing 2019;49:22-29. https://doi.org/10.1097/01.NURSE.0000549721.69197.4d.

Moake JL, Turner NA, Stathopoulos NA, Nolasco LH, Hellums JD. Involvement of large plasma von Willebrand factor (vWF) multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation. J Clin Invest 1986;78:1456-1461. https://doi.org/10.1172/jci112736.

Zander CB, Cao W, Zheng XL. ADAMTS13 and von Willebrand factor interactions. Curr Opin Hematol 2015;22:452-459. https://doi.org/10.1097/moh.0000000000000169.

Furlan M, Robles R, Galbusera M, Remuzzi G, Kyrle PA, Brenner B, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med 1998;339:1578-1584. https://doi.org/10.1056/nejm199811263392202.

Blombery P, Scully M. Management of thrombotic thrombocytopenic purpura: current perspectives. J Blood Med 2014;5:15-23. https://doi.org/10.2147/jbm.S46458.

Kappler S, Ronan-Bentle S, Graham A. Thrombotic microangiopathies (TTP, HUS, HELLP). Hematol Oncol Clin North Am 2017;31:1081-1103. https://doi.org/10.1016/j.hoc.2017.08.010.

Griffin D, Al-Nouri ZL, Muthurajah D, Ross JR, Ballard RB, Terrell DR, et al. First symptoms in patients with thrombotic thrombocytopenic purpura: what are they and when do they occur? Transfusion 2013;53:235-237. https://doi.org/10.1111/j.1537-2995.2012.03934.x.

George JN. How I treat patients with thrombotic thrombocytopenic purpura: 2010. Blood 2010;116:4060-4069. https://doi.org/10.1182/blood-2010-07-271445.

Vesely SK, George JN, Lämmle B, Studt JD, Alberio L, El-Harake MA, et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blood 2003;102:60-68. https://doi.org/10.1182/blood-2003-01-0193.

Brocklebank V, Wood KM, Kavanagh D. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol 2018;13:300-317. https://doi.org/10.2215/cjn.00620117.

Bendapudi PK, Hurwitz S, Fry A, Marques MB, Waldo SW, Li 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;4:e157-e164. https://doi.org/10.1016/s2352-3026(17)30026-1.

George JN. Systemic malignancies as a cause of unexpected microangiopathic hemolytic anemia and thrombocytopenia. Oncology 2011;25:908-914.

Furlan M, Robles R, Morselli B, Sandoz P, Lämmle B. Recovery and half-life of von Willebrand factor-cleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura. Thromb Haemost 1999;81:8-13.

Zheng XL, Vesely SK, Cataland SR, Coppo P, Geldziler B, Iorio A, et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost 2020;18:2496-2502. https://doi.org/10.1111/jth.15010.

Scully M, Hunt BJ, Benjamin S, Liesner R, Rose P, Peyvandi F, et al. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol 2012;158:323-335. https://doi.org/10.1111/j.1365-2141.2012.09167.x.

Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Writing Committee of the American Society for Apheresis: The seventh special issue. J Clin Apher 2016;31:149-162. https://doi.org/10.1002/jca.21470.

Scully M, Cataland S, Coppo P, de la Rubia J, Friedman KD, Kremer Hovinga J, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost 2017;15:312-322. https://doi.org/10.1111/jth.13571.

Wang HX, Han B, Zhao YY, Kou L, Guo LL, Sun TW, et al. Serum D-dimer as a potential new biomarker for prognosis in patients with thrombotic thrombocytopenic purpura. Medicine (Baltimore) 2020;99:e19563. https://doi.org/10.1097/md.0000000000019563.

Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R. [Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia]. Schweiz Med Wochenschr 1955;85:905-909.

Fakhouri F, Zuber J, Frémeaux-Bacchi V, Loirat C. Haemolytic uraemic syndrome. Lancet 2017;390:681-696. https://doi.org/10.1016/s0140-6736(17)30062-4.

Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet 2005;365:1073-1086. https://doi.org/10.1016/s0140-6736(05)71144-2.

Witham PK, Yamashiro CT, Livak KJ, Batt CA. A PCR-based assay for the detection of Escherichia coli Shiga-like toxin genes in ground beef. Appl Environ Microbiol 1996;62:1347-1353. https://doi.org/10.1128/aem.62.4.1347-1353.1996.

Bell BP, Goldoft M, Griffin PM, Davis MA, Gordon DC, Tarr PI, et al. A multistate outbreak of Escherichia coli O157:H7-associated bloody diarrhea and hemolytic uremic syndrome from hamburgers. The Washington experience. Jama 1994;272:1349-1353.

Buchholz U, Bernard H, Werber D, Böhmer MM, Remschmidt C, Wilking H, et al. German outbreak of Escherichia coli O104:H4 associated with sprouts. N Engl J Med 2011;365:1763-1770. https://doi.org/10.1056/NEJMoa1106482.

Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005;16:1035-1050. https://doi.org/10.1681/asn.2004100861.

Cody EM, Dixon BP. Hemolytic uremic syndrome. Pediatr Clin North Am 2019;66:235-246. https://doi.org/10.1016/j.pcl.2018.09.011.

Karpac CA, Li X, Terrell DR, Kremer Hovinga JA, Lämmle B, Vesely SK, et al. Sporadic bloody diarrhoea-associated thrombotic thrombocytopenic purpura-haemolytic uraemic syndrome: an adult and paediatric comparison. Br J Haematol 2008;141:696-707. https://doi.org/10.1111/j.1365-2141.2008.07116.x.

Manrique-Caballero CL, Peerapornratana S, Formeck C, Del Rio-Pertuz G, Gomez Danies H, Kellum JA. Typical and atypical hemolytic uremic syndrome in the critically ill. Crit Care Clin 2020;36:333-356. https://doi.org/10.1016/j.ccc.2019.11.004.

Spinale JM, Ruebner RL, Copelovitch L, Kaplan BS. Long-term outcomes of Shiga toxin hemolytic uremic syndrome. Pediatr Nephrol 2013;28:2097-2105. https://doi.org/10.1007/s00467-012-2383-6.

Garg AX, Suri RS, Barrowman N, Rehman F, Matsell D, Rosas-Arellano MP, et al. Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression. Jama 2003;290:1360-1370. https://doi.org/10.1001/jama.290.10.1360.

Taylor CM, Machin S, Wigmore SJ, Goodship TH. Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom. Br J Haematol 2010;148:37-47. https://doi.org/10.1111/j.1365-2141.2009.07916.x.

Geerdink LM, Westra D, van Wijk JA, Dorresteijn EM, Lilien MR, Davin JC, et al. Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics. Pediatr Nephrol 2012;27:1283-1291. https://doi.org/10.1007/s00467-012-2131-y.

Hofer J, Janecke AR, Zimmerhackl LB, Riedl M, Rosales A, Giner T, et al. Complement factor H-related protein 1 deficiency and factor H antibodies in pediatric patients with atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 2013;8:407-415. https://doi.org/10.2215/cjn.01260212.

Licht C, Ardissino G, Ariceta G, Cohen D, Cole JA, Gasteyger C, et al. The global aHUS registry: methodology and initial patient characteristics. BMC Nephrol 2015;16:207. https://doi.org/10.1186/s12882-015-0195-1.

Makou E, Herbert AP, Barlow PN. Functional anatomy of complement factor H. Biochemistry 2013;52:3949-3962. https://doi.org/10.1021/bi4003452.

Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 2010;5:1844-1859. https://doi.org/10.2215/cjn.02210310.

Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA, Macher MA, Niaudet P, Guest G, et al. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 2007;18:2392-2400. https://doi.org/10.1681/asn.2006080811.

Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Frémeaux-Bacchi V, Kavanagh D, et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney disease: Improving global outcomes" (KDIGO) Controversies Conference. Kidney Int 2017;91:539-551. https://doi.org/10.1016/j.kint.2016.10.005.

Cataland SR, Holers VM, Geyer S, Yang S, Wu HM. Biomarkers of terminal complement activation confirm the diagnosis of aHUS and differentiate aHUS from TTP. Blood 2014;123:3733-3738. https://doi.org/10.1182/blood-2013-12-547067.

Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009;361:1676-1687. https://doi.org/10.1056/NEJMra0902814.

Masias C, Vasu S, Cataland SR. None of the above: thrombotic microangiopathy beyond TTP and HUS. Blood 2017;129:2857-2863. https://doi.org/10.1182/blood-2016-11-743104.

Gordon CE, Chitalia VC, Sloan JM, Salant DJ, Coleman DL, Quillen K, et al. Thrombotic microangiopathy: A multidisciplinary team approach. Am J Kidney Dis 2017;70:715-721. https://doi.org/10.1053/j.ajkd.2017.05.017.

Bittencourt CE, Ha JP, Maitta RW. Re-examination of 30-day survival and relapse rates in patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. PLoS One 2015;10:e0127744. https://doi.org/10.1371/journal.pone.0127744.

Cómo citar
1.
Henao-Piedrahita N. Microangiopatías trombóticas primarias: una revisión narrativa. Med. Lab. [Internet]. 5 de abril de 2021 [citado 21 de abril de 2021];25(2):485-99. Disponible en: https://medicinaylaboratorio.com/index.php/myl/article/view/432
Publicado
2021-04-05
Sección
Artículos de revisión
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