Abstract

INTRODUCTION:

The atypical hemolytic uremic syndrom (aHUS) is a rare disease especially seen in childhood. It can be differentiated from HUS with the absence of diarrhea history in the prodromal phase. Although the disease is rarely seen in children, it is even rarer in adults and is usually misdiagnosed as TTP (thrombotic thrombocytic purpura). The most prominent differential findings of the disease compared to TTP, are the development of chronic renal failure requiring hemodialysis and persistant hypertension attacks. Plasmapheresis and hemodialysis has been the choice of therapy for a long time until Eculizumab. In this abstract we will report 20 cases of aHUS that are treated with Eculizumab in our clinic.

MATERIALS AND METHOD:

Plasma samples of the patients were analysed for the ADAMTS13 activity and inhibitor levels before plasmapheresis. One patient out of 20 responded to plasmapheresis treatment in one week and started to be followed on out – patient clinic without any further medication, of the remaining 19 were planned to be given Eculizumab therapy. All of of the patients were vaccinated for Neisseria meningitides, Pneumococcus and Hemophilus influenza type B prior to 2 weeks of initiation of Eculizumab. We used antibacterial prophylaxis with amoxicillin – clavulanic acid in patients requiring urgent Eculizumab. Eculizumab was administered 900mg/day for 4 weeks and dosage was elevated to 1.200 mg/day in week 5, then 1.200 mg/day every other week as maintenance therapy. The response to therapy was evaluated by the fragmentation level in the peripheral blood samples, blood cell counts, serum LDH, reticulocytes ratio, creatinine levels and proteinuria.

FINDINGS AND RESULTS:

We enrolled 20 subjects to our study who were diagnosed as aHUS and followed in our clinic since 2012. Seventeen of the 20 patients were female and the median age was 37,5 years (ranging from 23 – 80). One of the patients responded to plasmapheresis treatment and no further medication was needed. Of the remaining 19 patients eculizumab treatment was planned. However two of them died due to acute respiratory distress prior to therapy in intensive care unit. Three of the 17 patients were diagnosed with aHUS recently (in one month) and they are currently on the induction phase of eculizumab.

Fourteen of our patients are using Eculizumab for 2 to 26 months (median 8 months). One of them has been diagnosed during pregnancy and eculizumab treatment was started immediately. She had a successful delivery with preserved renal functions. Four patients did not require hemodialysis at the time of diagnosis. While four of the patients who were on dialysis, dialysis requirements were gradually decreased and was stopped in median 10 months (in 4 to 13 months). The remaining eight patients who were on eculizumab in median 2.5 months still require dialysis. 8 patient who had been on eculizumab therapy in median 2,5 months (in 1 to 7 months) still on dialysis. We terminated eculizumab therapy in patient after 13 months due to full clinical and laboratory improvement. We lost one of our patient due to severe respiratory failure in her third month of therapy.

DISCUSSION AND CONCLUSION:

Although aHUS is quite a well – established clinical presentation in childhood it is extremely rare in adults without settled diagnostic criteria and serologic features. The clinical outcome is unfavorable in this group with death rates as high as 25% during the acute phase and up to 50% of cases progressing to end-stage renal failure. It is confirmed that progress in intensive care and dialysis opportunity has contributed to the decrease of mortality. Death rate was 15% in our cohort but it would be higher without awareness of the syndrome. Even in induction period of the therapy, both clinical and laboratory findings were improved significantly with eculizumab. Renal functions were restored in nine of the 17 patients. Eculizumab has changed the future perspectives of patients with aHUS and both FDA and the EMA have approved it as life-long treatment. But, there are still some unresolved issues about the follow-up such as the optimal duration of eculizumab treatment and whether it can be stopped or how to stop the therapy. All these questions can be resolved with the data from large international prospective cohort studies.

Disclosures

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.

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