Abstract
TTP is a rare condition of microangiopathic hemolytic anemia and thrombocytopenia with a reported incidence of 4 cases per million people. Untreated mortality is reported to be as high as 90%; plasma exchange (PLEX) has significantly reduced this to 28%. Given the heterogeneity in presentation and severity at diagnosis, there is a wide range of practice with regards to exchanges, management of refractory disease and relapse. The British Committee for Standards in Hematology (BCSH) released clinical guidelines first in 2003, updated in 2012 outlining evidence based approach to practice. Our goal was to examine clinical practices and effect on outcomes at our tertiary centre during 2005-2010, between release of the first and second edition guidelines.
Patients were retrospectively identified by searching for the TTP diagnostic code with admission dates between 2005-2010. They were excluded if they were not primarily treated in Calgary, or their thrombotic microangiopathy (TMA) was felt to be due to another diagnosis.
Thirty eight patients were identified, with an average age of 48.8 years, and mostly female (men=8 patients, 21%). Ten patients were excluded for alternate diagnoses or main treatment outside Calgary. TTP was classified as primary in 15/45 (39%), and in 33 patients (87%) this was their first episode. Secondary causes included underlying autoimmune disease (24% of patients), malignancy (16% of patients), and pregnancy (4% of patients). 4% of patients were receiving active chemotherapy at the time of diagnosis of TTP. ADAMTS13 level and inhibitor (antibodies) were only examined in 10 cases (26%), and reported in fewer. Measurement of antigen, activity and inhibitors is strongly emphasized in the literature for accurate diagnosis of TTP compared with hemolytic uremic syndrome (HUS), other TMA or congenital TTP, and this was underutilized in this tertiary centre likely due to laboratory availability.
Duration in hospital was often long, with an average of 29 days. This is likely due to the frequency of refractory disease, seen in more than half of patients (23/38, 61%). 24% of cases were fatal; this result is consistent with previously reported mortality rates in the era of PLEX. 5 of 9 fatalities were associated with malignancy where there is felt to be no benefit from PLEX, although interestingly 2 patients with malignancy received 5 to 7 days of PLEX, recovered and were discharged from hospital. Two fatalities had a delay of 48 hours or more to initiation of PLEX through misdiagnosis, one developed severe neurologic symptoms during line placement and the other presented atypically with hematuria. The most common complications of TTP included bleeding (16 patients, 42%), neurologic changes without stroke (16 patients, 42%), requirement for hemodialysis (9 patients, 24%), and radiologically identified stroke (6 patients, 16%).
35 patients (92%) received PLEX, and the average number of days on PLEX was 16. Twice daily exchange at initiation or exacerbation was common (29%), as were tapers (60%), although literature now suggests tapering does not reduce relapses. Steroids are recommended in most cases for immunosuppression; only 21 of our patients (55%) received these in hospital. Secondary immunosuppression was occasionally instituted in refractory or relapsing cases including cyclophosphamide (13 patients, 34%), rituximab (5 patients, 13%), mycophenolate mofetil and vincristine (1 patient each, 3%). Rituximab is now routinely used in initial treatment to decrease relapses, for refractory disease, and occasionally as prophylaxis with low ADAMTS13 in asymptomatic patients, and other agents generally recommended against given its efficacy and safety, but this was not standardized in our group.
Limitations for this project include small patient numbers, the change in definitions of HUS, TMA and TTP over time, and the retrospective nature of patient selection and data collection.
In summary, diagnostic and treatment strategies for TTP have become significantly more standardized in the past 10 years. A protocolized strategy for initial investigations, PLEX and immunosuppressive therapies in line with previously published guidelines would be useful in our institution, potentially reduce relapses and improve rapidity of patient response, however our mortality statistics appear similar to those previously published.
Disclosures
No relevant conflicts of interest to declare.
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