IA made substantial contribution to conception and design, acquisition of data, analysis and interpretation of data

IA made substantial contribution to conception and design, acquisition of data, analysis and interpretation of data. microangiopathy manifestations were inhibited and renal and cardiac function restored, with no need for other invasive treatments. Conclusions Establishing the diagnosis of atypical hemolytic uremic syndrome in patients presenting with thrombotic microangiopathy is challenging since common symptoms are shared with other conditions like Shiga toxin-producing hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. The described case illustrates the complexity and importance of rapid diagnosis in a rare disease and the need for appropriate and specific treatment for best long-term outcomes. Introduction Thrombotic microangiopathy (TMA) can be a manifestation of several medical conditions, like connective tissue diseases, malignancy and posttransplantation. However, TMA manifestations dominate and characterize diseases like thrombotic thrombocytopenic purpura (TTP), atypical hemolytic uremic syndrome (aHUS) and Shiga toxin-producing hemolytic uremic syndrome (STEC-HUS), thus making differential diagnosis of TMA difficult. Both STEC-HUS and aHUS are characterized by hemolytic anemia, thrombocytopenia and organ failure. STEC-HUS is more common in children and is associated with a prior infection from STEC and presence of Shiga toxin causing endothelial damage and complement activation [1]. aHUS is characterized by genetic hyperactivation of the alternative complement pathway and can present in both children and adults [2-4]. A genetic PLpro inhibitor mutation in complement regulatory genes has been identified in approximately 60 percent of patients with aHUS [3,5,6]. Dysregulation of the complement system leads to endothelial, neutrophil and platelet activation causing TMA associated with hemolytic anemia and thrombocytopenia, which in turn may cause severe organ damage in multiple vital organs [7]. TTP is another form of TMA associated with severe ADAMTS13 deficiency. ADAMTS13 is an enzyme that cleaves the ultralarge von Willebrand factor multimers that can form in plasma during shear stress causing platelet aggregation and thrombosis. Management of TMA often involves plasma exchange and/or plasma infusion (PE/PI) in an attempt to remove mutant forms and restore functional proteins. It seems to be effective in the management of TTP [8], however, outcomes are still poor in aHUS and a large percentage of patients still progresses to end-stage renal disease (ESRD) or die at first clinical manifestation of TMA [3,5,6,9]. Eculizumab is a humanized monoclonal antibody that binds to complement component C5 inhibiting its cleavage to C5a and C5b, inhibiting complement-mediated TMA in patients with aHUS [10]. Since its introduction in aHUS treatment, eculizumab has exhibited improved outcomes compared to plasma exchange (PE) in prospective clinical trials and in several published cases [10-15]. Eculizumab Rabbit Polyclonal to F2RL2 has been PLpro inhibitor approved for the treatment of aHUS and is well tolerated [5,12,16]. We present the case of a young woman of Hellenic origin who presented PLpro inhibitor with signs and symptoms of TMA following a preeclampsia-induced premature delivery. Our patient was initially managed with PE and dialysis, but TMA multiorgan manifestations persisted and improved only upon chronic eculizumab treatment. Case presentation A 31-week-pregnant young woman of Hellenic origin (age 23), free of previous medical history, was admitted in January 2011 for an urgent cesarean section due to preeclampsia presenting with nephrotic-range proteinuria (7gr/24hrs), increased blood pressure (180/100mmHg) and edema. Five days post-cesarean section, she presented hemolytic anemia, thrombocytopenia, renal impairment, tonicoclonic seizures, and hypertensive crisis. Schistocytes were detected on her peripheral blood smear, while elevated lactate dehydrogenase (LDH) 3254IU/L (laboratory normal range (LNR): 208 to 408IU/L), total bilirubin (TBIL) 4.2mg/dL (LNR: 0.3 to 1 1.2mg/dL) and serum creatinine 4.9mg/dL (LNR: 0.67 to 1 1.17mg/dL), as well as decreased platelet count (PLT: 40109/L) (LNR: 150 to 480109/L) were recorded. Intensive PE treatment was initiated (twice daily for 22 PLpro inhibitor days), in parallel with dialysis for volume and uremia control. Following PE and dialysis her clinical condition transiently improved (serum creatinine: 2.8mg/dL, LDH: 605IU/L, PLT: 141109/L). Approximately four months later, in June.