Thrombotic microangiopathies

Stratton J, Warwicker P, Watkins S, Farrington K. Desmopressin may be hazardous in thrombotic microangiopathy. Nephrol Dial Transplant 2001 16(l) 161-2. 

Moake JL, BynesJJ. Thrombotic microangiopathies associated with drugs and bone marrow transplantation. Hematol Oncol Clin North Am 1996 10 485 197. 

Viale P Pagani L, Alberici F Clinical features and prognostic factors of HIV-associated thrombotic microangiopathies. Eur J Haematol 1998 60 262-263. 

In one case acute hepatitis and thrombotic microangiopathy occurred simultaneously (204). 

The authors noted that thrombotic microangiopathy due to cocaine is fairly rare. Its pathogenesis is unclear, possible mechanisms being an immune reaction or direct damage to the vascular endothelium. Cocaine-induced acute hepatitis has been linked to several toxic metabolites, including norcocaine and N-hydroxynorcocaine, which are produced by cytochrome P450 enzymes. 

Balaguer F, Fernandez J. Cocaine-induced acute hepatitis and thrombotic microangiopathy. JAMA 2005 293 797-8. 

Cyclosporine is a macrolide antibiotic and has been used as an immunosuppressive agent. Cyclosporine can cause both renal and nonrenal toxicity. Clinically renal toxicity consists of four discrete syndromes which include acute reversible renal functional impairment, delayed renal allograft function, acute vasculopathy, and chronic nephropathy with interstitial fibrosis. Proximal tubular epithelium is uniquely sensitive to the toxic effect. The toxic effect is characterized by isometric cytoplasmic vacuolations (several small equally sized vacuoles in cytoplasm), necrosis with or without subsequent mineralization, inclusion bodies (giant mitochondria), and giant lysosomes. Acute vasculopathy consists of vacuolization of the arteriolar smooth muscles and endothelial cells leading to necrosis. In some cases, thrombotic microangiopathy develops, characterized by thrombosis of the renal micro vasculature. Long-term treatment with cyclosporine results in chronic nephropathy with interstitial fibrosis (Chamey et al., 2004). 

Ciclosporin-associated thrombotic microangiopathy occurs in 3-14% of patients with a renal transplant and can cause allograft loss. Renal impairment, reflected by an increase in serum creatinine concentration, is often the only change found, and hemolysis is not always present. Plasmapheresis has been used to treat this com-phcation (71). 

A 47-year-old multiparous Hispanic woman received a living-unrelated kidney transplant for end-stage renal disease secondary to polycystic kidney disease. On the day of transplantation she received intravenous daclizumab 1 mg/kg plus methylprednisolone 300 mg and mycophenolate mofetil 3 g/day, and on day 3 ciclosporin emulsion 4 mg/kg/day. On day 8 she developed thrombotic microangiopathy without evidence of rejection. Ciclosporin was withdrawn. Plasmapheresis with fresh frozen plasma was started. Daclizumab on day 14 was postponed for 24 hours and plasmapheresis was stopped to avoid clearance of daclizumab. Thereafter she was given tacrolimus, without recurrence of hemolysis. 

Hemolytic-uremic syndrome, with histological findings of thrombotic microangiopathy and possible evolution to graft loss or death, is another instance of very severe acute nephrotoxicity (SED-13, 1125). It usually occurs at between the second and fourth weeks after transplant, with associated fever, thrombocytopenia, erythrocyte fragmentation, neurotoxicity, and renal impairment. Uncommon clinical features have been reported. 

Trimarchi H, Freixas E, Rabinovich O, Schropp J, Pereyra H, Bullorsky E. Cyclosporine-associated thrombotic microangiopathy during daclizumab induction a suggested therapeutic approach. Nephron 2001 87(4) 361-4. 

Wiener Y, Nakhleh RE, Lee MW, Escobar FS, Venkat KK, Kupin WL, Mozes MF. Prognostic factors and early resumption of cyclosporin A in renal allograft recipients with thrombotic microangiopathy and hemolytic uremic syndrome. (Tin Transplant 1997 ll(3) 157-62. 

Zarifian A, Meleg-Smith S, O donovan R, Tesi RJ, Batuman V. Cyclosporine-associated thrombotic microangiopathy in renal allografts. Kidney Int 1999 55(6) 2457-66. 

Humphreys BD, Sharman JP, Henderson JM, Clark JW, Marks PW, Rennke HG, Zhu AX, Magee CC. Gemcitabine-associated thrombotic microangiopathy. Cancer 2004 100(12) 2664-70. 

A review of 15 other available reports of renal insufficiency and proteinuria in patients with chronic myeloid leukemia or other malignancies confirmed that the histological spectrum of renal lesions associated with interferon alfa is varied, and includes membranous glomerulonephritis, minimal change glomerulonephritis, acute interstitial nephritis, hemolytic-uremic sjmdrome, and thrombotic microangiopathy. Renal comphcations were reversible in nine patients three patients had persistent proteinuria, and four had persistent renal dysfunction, of whom three required chronic hemodialysis. Two-thirds of the patients developed renal comphcations within 1 month of treatment with interferon alfa, and one-third had received a relatively low dosage of interferon alfa (9-15 MU/week). 

Two patients treated with pegylated interferon alfa-2b and ribavirin developed cutaneous thrombotic microangiopathy (302). 

Honda K, Ando A, Endo M, Shimizu K, Higashihara M, Nitta K, Nihei H. Thrombotic microangiopathy associated with alpha-interferon therapy for chronic myelocytic leukemia. Am J Kidney Dis 1997 30(l) 123-30. 

Ravandi-Kashani F, Cortes J, Talpaz M, Kantaqian HM. Thrombotic microangiopathy associated with interferon therapy for patients with chronic myelogenous leukemia coincidence or true side effect Cancer 1999 85(12) 2583-8. 

Vacher-Coponat H, Opris A, Daniel L, Harle JR, Veit V, Olmer M. Thrombotic microangiopathy in a patient with chronic myelocytic leukaemia treated with alpha-interferon. Nephrol Dial Transplant 1999 14(10) 2469-71. 

Zuber J, Martinez F, Droz D, Oksenhendler E, Legendre C, Groupe D Etude Des Nephrologues DTle-de-France (GENIF). Alpha-interferon-associated thrombotic microangiopathy a clinicopathologic study of 8 patients and review of the literature. Medicine (Baltimore) 2002 81(4) 321-31. 

Creput C, Auffret N, Samuel D, Jian R, Hill G, Nochy D. Cutaneous thrombotic microangiopathy during treatment with alpha-interferon for chronic hepatitis C. J Hepatol 2002 37(6) 871-2. 

Lecornu-Heuze L, Ducloux D, Rebibou JM, Martin L, Billerey C, Chalopin JM. Mycophenolate mofetil in cyclosporin-associated thrombotic microangiopathy. Nephrol Dial Transplant 1998 13(12) 3212-13. 

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