Childhood Kidney Diseases

Korean Society of Pediatric Nephrology (대한소아신장학회)
권호 표지
DOI QR코드

DOI QR Code

Pathology of Thrombotic Microangiopathy

혈전성 미세혈관병증의 병리

  • Sol, Mee Young (Department of Pathology, Pusan National University Yangsan Hospital)
  • 설미영 (부산대학교 양산병원 병리과)
  • Received : 2013.03.12
  • Accepted : 2013.03.26
  • Published : 2013.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Thrombotic microangiopathy (TMA) is a microvascular thrombotic lesion caused by endothelial injury and subsequent formation of platelet rich thrombus. TMA is first described as a classical pathologic feature of HUS/TTP. Renal biopsy finding of TMA represents kidney involvement of HUS/TTP as well as other diseases such as malignant hypertension, drug toxicity, eclampsia, pre-eclampsia, and several systemic infections. Autoimmune diseases and transplant kidney sometime also have TMA. It is needed to consider a complete autoimmune work-up of patients presenting with TMA including tests for ANA, ANCA, and ADAMTS13 inhibitory antibodies, because there are several reports of association with TMA in patients of SLE, anti-phospholipid syndrome, and ANCA-associated vasculitis.

사구체에 면역글로불린은 음성이면서 C3 만 침착되는 경우, 다른 원인이 없는 경우 C3GN을 의심하여야 한다. 광학현미경으로는 세포의 증식이 있는 경우와 없는 경우가 있지만, 전자현미경으로는 EDD가 내피세포 밑으로 혹은 메산지움 등에 침착함을 확인하여야 한다. 대체보체경로의 조절이상이 원인임으로 혈청 C3 치를 비롯하여 CFH, CFI, CFB 등을 측정하여야 하며, C3 nephritic factor, antifactor H 자가항체 등을 조사하는 것이 필요하다. 보체 조절이상을 일으키는 유전자 돌연변이를 조사해 보아야 한다. 예후는 안정적이지만, 치료는 대증적이다. 이론적으로 보체의 활성화를 저지하는 약으로 가능할 것으로 생각되며, C5 항체인 eculizumab으로 치유된 보고도 있다.

Keywords

References

  1. Jenette JC, Olson JL, Schwartz MM, Silva FG. Heptinstall's pathology of the kidney 6th ed. Philadelphia: Lippincott Williams & Wilkins. 2007;533-4 and 711-9.
  2. Symmers WSC. Thrombotic microangiopathic hemolytic anemia(thrombotic microangiopathy). Br Med J 1952;2:897-903. https://doi.org/10.1136/bmj.2.4790.897
  3. Gasser C, Gautier E, Steck A, Siebenmann Re, Oechslin R. Hamolytisch-uamische syndrome:Bilaterale Nierenrinden-nekrosen bei akuten erworbenen hamolytischen Anamien. Schweia Med Wochenschr 1955;85:905-9.
  4. Habib R, Mathieu H, Royer P. Maladie thrombotique arteriolecapillaire du rein chez l'enf ant. Rev Fr Etud Clin Biol 1958; 3:891-4.
  5. Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int 2001;60:831-46. https://doi.org/10.1046/j.1523-1755.2001.060003831.x
  6. Benz K, Amann K. Thrombotic microangiopathy: new insights. Curr Opin Nephrol Hypertens 2010;19:242-7. https://doi.org/10.1097/MNH.0b013e3283378f25
  7. Brunskill SJ, Tusold A, Benjamin S, Stanworth SJ, Murphy MF. A systematic review of randomized controlled trials for plasma exchange in the treatment of thrombotic thrombocytopenic purpura. Transfus Med 2007:17;17-35.
  8. Nachman PH, Glassock RJ. Glomerular, vascular, and tubulointerstitial diseases. NephSAP 2008;7:185-9.
  9. Nathanson S, Kwon T, Elmaleh M, Charbit M, Launay EA, Harambat J, et al. Acute neurological involvement in diar-rhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol 2010;5:1218-28. https://doi.org/10.2215/CJN.08921209
  10. Espinosa G, Buccirelli S, Cervera R, Lozano M, Reverter J-C, de la Red G, et al. Thrombotic microangiopathic hemolytic anemia and antiphospholipid antibodies. Ann Rheum Dis 2004;63:730-6. https://doi.org/10.1136/ard.2003.007245
  11. Shibagaki Y, Fujita T. Thrombotic microangiopathy in malignant hypertension and hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura(TTP): can we differentiate one from the other?. Hypertens Res 2005;28:89-95. https://doi.org/10.1291/hypres.28.89
  12. McMinn JR, George JN. Evaluation of women with clinically suspected thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy. J Clin Apheresis. 2001; 16:202-9. https://doi.org/10.1002/jca.10005
  13. Mannucci PM, Canciani MT. Forza I, Lussana F, Lattuada A, Rossi E. Changes in health and disease of the metalloproteinase that cleaves von Willebrand factor. Blood 2001;98: 2730-5. https://doi.org/10.1182/blood.V98.9.2730
  14. Furlan M, Lammle B. Aetology and pathogenesis of throm-botic thrombocytopenic purpura and hemolytic uremic syndrome. The role of von Willebrand factor-cleaving protease. Best Pract Res Clin Haematol 2001;14:437-54. https://doi.org/10.1053/beha.2001.0142
  15. Dragon-Durey M-A, Freneaux-Bacchi V, Loirat C, Blouin J, Niaudet P, Deschenes G. Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: Report and genetic analysis of 16 cases. J Am Soc nephrol 2004;15:787-95. https://doi.org/10.1097/01.ASN.0000115702.28859.A7
  16. Li PK, Lai FM, Tam JS, Lai KN. Acute renal failure due to postpartum hemolytic uremic syndrome. Aus N Z J Obstet Gynecol 1988;28:228-30. https://doi.org/10.1111/j.1479-828X.1988.tb01670.x
  17. Kniaz D, Eisenberg GM, Elrad H, Johnson CA, Valatis J, Breqman H. Postpartum hemolytic uremic syndrome associated with antiphospholipid antibodies: A case report and review of the literature. Am J Nephrol 1992;12:126-33. https://doi.org/10.1159/000168432
  18. Murgo AJ. Cancer and chemotherapy-associated thrmobotic microangiopathy, in Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura, Kaplan BS, Trom-peter RS, Moake JL, editors. New York; Marcel Dekker, Inc., 1992:271.
  19. Remuzzi G, Bertani T. Renal vascular and thrombotic effects of cyclosporine. Am J Kidney Dis 1989;13:261-72. https://doi.org/10.1016/S0272-6386(89)80032-0
  20. Eremia V, Jefferson JA, Kowalewska JL, Hochster H, Haas M, Wisstuch J. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008:358;1129-36. https://doi.org/10.1056/NEJMoa0707330
  21. Gurevich F, perazella MA. Renal effects of angiogenesis therapy: update for the internist. Am J Med 2009:122;322-8.
  22. Zakarija A, Kwaan HC, Moake JL, Bandarenko N, Pandey DK, McKoy JM, et al. Ticlopidine and clopidogrel-associated thrombotic thrombocytopenic purpura(TTP); review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989-2008). Kidney Int Suppl 2009;112;S20-S24.
  23. Gottschall JL, Elliot W, Lianos E, McFarland JG, Wolfmeyer K, Aster RH. Quinine induced immune thrombocytopenia associated with hemolytic uremic syndrome: A new clinical entity. Blood 1991;77;306-10.
  24. Fine DM, Fogo AB, Alpers CE. Thrombotic microangiopathy and other glomerular disorders in the HIV-infected patient. Semin Nephrol 2008:28;545-55. https://doi.org/10.1016/j.semnephrol.2008.08.007
  25. Matsuyama T, Kuwana M, Matsumoto M, Isonishi A, Inokuma S, Fujimura Y. Heterogeneous pathogenic processes of thrombotic microangiopathies in patients with connective tissue diseases. Thromb Haematol 2009:102;371-8.
  26. Park YA, Waldrum MR, Marques MB. Platelet count and prothrombin time help distinguish thrombotic thrmobocytopenic purpura-hemolytic uremic syndrome from disseminated intravascular coagulation in adults. Am J Clin Pathol 2010; 133:460-5. https://doi.org/10.1309/AJCPPNF63FLIORCI
  27. Satoskar AA, Pelletier R, Adams P, Nadasdy GM, Brodsy S, Pesavento T. De novo thrombotic microangiopapthy in renal allograft biopsies-role of antibody-mediated rejection. Am J Transplant 2010;10:1804-11. https://doi.org/10.1111/j.1600-6143.2010.03178.x
  28. Ashman N, Chapagain A, Dobbie H, Raffery MJ, Sheaff MT, Yagoob NM. Belatacept as maintenance immunosuppression for postrenal transplant de novo drug-induced thrombocytic microangiopathy. Am J transplant 2009:9:424-7. https://doi.org/10.1111/j.1600-6143.2008.02482.x
  29. Baid S, Pascual M, Williams WW Jr, Tolkoff-Rubin N, Johnson SM, Collins B. Renal thrombotic microangiopathy associated with anticardiolipin antibodies in hepatitis C-positive renal allograft recipients. J Am Soc Nepprol 1999;10:146-53.
  30. Gallay BJ, Alpers CE, Davis CL, Schultz MF, Johnson RJ. Glomerulonephritis in renal allografts associated with hepatitis C infection: a possible relationship with transplant glomerulopathy in two cases. Am J Kidney Dis 1995;26:662-7. https://doi.org/10.1016/0272-6386(95)90606-1
  31. Cosio FG, Roche Z, Agarwal A, Falkenhain ME, Sedmak DD, Ferguson RM. Prevalence of hepatitis C in patients with idiopathic glomerulopathies in native and transplant kidneys. Am J Kidney Dis 1996;28:752-8. https://doi.org/10.1016/S0272-6386(96)90260-7
  32. Chansirikulchai S, Myerson D, Guthrie KA, McDonald GB, Alpers CE, Hingorani SR. Renal thrombotic microangiopathy after hematopoietic cell transplant: role of GVHD in pathogenesis. Clin J Am Soc Nephrol 2009:4;345-53. https://doi.org/10.2215/CJN.02070508
  33. Kwok SK, Ju JH, Cho CS, Kim HY, Park SH. Thrombotic thrombocytopenic purpura in systemic lupus erythema-tosus: risk factors and clinical outcome: a single center study. Lupus 2009;18:16-21. https://doi.org/10.1177/0961203308094360
  34. Nesher G, Hanna VE, Moore TL, Hersh M, Osborn TG. Thrombotic microangiopathic hemolytic anemia in systemic lupus erythematosus. Semin Arthritis Rheum 1994;24:165-72. https://doi.org/10.1016/0049-0172(94)90072-8
  35. Hamasaki K, Miura T, Kanda H, Kubo K, Setoguchi K, Satoh T, et al. Systemic lupus erythematosus and thrombotic thrombocytopenic purpura: a case report and literature review. Clin Rheumatol 2003;22:355-8. https://doi.org/10.1007/s10067-003-0742-1
  36. Lansigan F, Isufi I, Tagoe CE. Microangiopathic haemolytic anaemia resembling thrombotic thrombocytopenic purpura in systemic lupus erythematosus: the role of ADAMTS13. Rheumatology 2011;50:824-9. https://doi.org/10.1093/rheumatology/keq395
  37. Watanabe H, Kitagawa W, Suzuki K, Yoshino M, Aoyama R, Miura N, et al. Thrombotic thrombocytopenic purpura in a patient with rapidly progressive glomerulonephritis with both anti-glomerular basement membrane antibodies and myeloperoxidase anti-neutrophil cytoplasmic antibodies. Clin Exp Nephrol 2010;14:598-601. https://doi.org/10.1007/s10157-010-0312-1
  38. Asamiya Y, Moriyama T, Takano M, Iwasaki C, Kimura K, Ando Y, et al. Successful treatment with Rituximab in a patient with TTP secondary to severe ANCA-associated vasculitis. Inter Med 2010;49;1589-91.
  39. Agrawal V, Vaidya CK, Ye J, Freeman J, McKiernan C, Blier PR, et al. Concomitant thrombotic thrombocytopenic purpura and ANCA-associated vasculitis in an adolescent. Pediatr Nephrol 2011;26;1317-20. https://doi.org/10.1007/s00467-011-1862-5
  40. Noda S, Ogura M, Tsutsumi A, Udagawa T, Kamei K, Matsuoka K, et al. Thrombotic microangiopathy due to multiple autoantibodies related to antiphospholipid syndrome. Pediatr Nephrol 2012:27;681-5. https://doi.org/10.1007/s00467-011-2085-5

Cited by

  1. A Case of Rheumatoid Arthritis Accompanied by Thrombotic Thrombocytopenic Purpura vol.89, pp.1, 2013, https://doi.org/10.3904/kjm.2015.89.1.122