ESPN 50th Annual Meeting

ESPN 2017


 
Thrombotic microangiopathy in the frame of systemic diseases: four cases from pediatric clinical practice
Alejandra Rosales 1 Alvaro Madrid 1 Marina Muñoz 1 Jesus Quintero 1 Laura Alonso 1 Sara Chocron 1 Santiago Rodriguez de Cordoba 2 Gema Ariceta 1

1- HOSPITAL UNIVERSITARIO VALL DHEBRON, Barcelona, Spain
2- Consejo Superior de Investigaciones Científicas, Madrid, Spain
 
Introduction:

 Thrombotic microangiopathies result from the interaction between predisposing factors and triggering events. 

Material and methods:

 We present four pediatric cases with unusual forms of thrombotic microangiopathy in the frame of systemic diseases.

Results:

 Case 1: 5 years old, acute pancreatitis with complement activation and HUS-triad (hemolytic anemia, thrombocytopenia and acute renal failure). Early treatment with Eculizumab results in rapid hematological and renal remission. MRI shows anatomic variant (pancreas divisum) associated to high risk of spontaneous pancreatitis. Recurrence of pancreatitis under treatment with Eculizumab, with no signs of TMA.  Genetic analysis shows risk haplotypes in CHF, MCP and CFHR3-CFHR1 deletion. Pancreatitis triggered aHUS or vice versa?

Case 2: 2 years old, acute myeloid leukemia M5, after haploidentical BMT, complete chimerism. After BMT develops transfusion-dependent anemia, malignant hypertension and proteinuria. Transitory stabilization after suspension of cyclosporine. Progressive disease with two-fold increase of creatinine, renal biopsy shows TMA. Under treatment with Eculizumab normalization of blood pressure and renal function, no proteinuria. Hemoglobin recovery, no need for transfusions. Material for genetic testing from saliva (blood cells from donor), result pending.

Case 3: 15 years old, previously healthy, presents with cholestasis and HUS-triad. Ocular evaluation shows Keyser-Fleischer Ring. Copper in urine and low ceruloplasmin confirm diagnosis of Wilson’s disease. Hemolytic anemia only better under treatment with Trientine. Progressive recovery of hemoglobin and renal function. Marked complement activation, CFB-Antibodies and CFHR5 variant.

Case 4: 10 years old, Wilson’s disease. 3 years after liver transplantation presents HUS-triad in the frame of viral infection. Recovery after suspension of treatment with Tacrolimus and Everolimus. Carrier of CHR1 and 3 homozygous deletions.

Conclusions:

 This cases picture the relevance of considering TMA in non-aHUS related diseases in which complement activation and endothelial damage may be trigger or consequence of complement activation. The relevance of complement gene polymorphisms as TMA predisposing condition is not yet well understood.