Long-term outcomes of health-related quality of life following diverse thrombotic microangiopathy syndromes
Authors: Evaren E. Page, Yang Jiang, Deirdra R. Terrell, Sara K. Vesely, James N. George
Journal: American Journal of Hematology (2016)

To the Editor: Patient-reported outcomes reflecting health-related quality-of-life (HRQOL) are increasingly important in patient care. Among the patients enrolled in the Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) Registry, we have previously focused on patients with acquired TTP, documenting increased frequency of major depression and progressive cognitive impairment during long-term follow-up 1, 2. However patients with acquired TTP represent only 23% of patients who have been enrolled in the Registry 1. The enrollment criterion is the request for plasma exchange treatment for treatment of patients with an initial clinical diagnosis of TTP or HUS. In this study, we assessed HRQOL using the Short Form-36 (SF-36), a widely used health survey 3, during long-term follow-up in three groups of Registry patients in addition to TTP: pregnancy-associated syndromes, patients presenting with bloody diarrhea, and patients with quinine-induced thrombotic microangiopathy (TMA). Consecutive patients from 1995, when routine ADAMTS13 measurements began 1 through 2013 (to allow two year follow-up) who were ≥18 years old (therefore eligible for SF-36 assessments 3) were evaluated. Patients who had two or more HRQOL assessments, an “initial” assessment ≥12 months following recovery and the most recent (“final”) assessment ≥12 months following the initial assessment, were selected. Both assessments must have preceded the occurrence of a relapse; therefore all assessments follow only one acute episode. Sixty-seven patients were selected: TTP (34 patients), pregnancy (10 patients), bloody diarrhea prodrome (11 patients), and quinine-induced TMA (12 patients). TTP was defined by ADAMTS13 activity <10%; patients in the other three categories had ADAMTS13 activity >20%. The patients’ demographic and clinical features are summarized in Supporting Information Table I. All patients had microangiopathic hemolytic anemia and thrombocytopenia; most patients had severe neurologic abnormalities; many patients with a bloody diarrhea prodrome and quinine-induced TMA had severe acute kidney injury. Among the 10 women with pregnancy-related syndromes, six had preeclampsia with severe features, two had placental abruption with hemorrhage and disseminated intravascular coagulation, one had sepsis, and one had postpartum acute kidney injury. Among the 11 patients who presented with a bloody diarrhea prodrome, only two had positive stool cultures for E. coli O157:H7. The 12 patients with quinine-induced TMA all had definite evidence for quinine as the etiology of TMA, defined by repeated episodes with repeated quinine exposure and/or documentation of quinine-dependent antibodies reactive with platelets and/or neutrophils 4. The median initial HRQOL assessments for the four patient groups were 1.3–2.1 years after the initial episode; the median final HRQOL assessments were 6.1–8.4 years after the initial HRQOL. The HRQOL scores for patients with pregnancy-related syndromes were not different from US population norms for both the mental and physical summary measures and for both the initial and final assessments. The other three patient groups all had impaired HRQOL. For patients with TTP and quinine-mediated TMA, physical summary measures were significantly less than US population norms for both the initial and final assessments, and mental summary measures were significantly less than US population norms for the final assessments. For the patients with a bloody diarrhea prodrome, physical summary measures were significantly less than US population norms for both the initial and final assessments but the mental summary measures were not different from US population norms. TTP patients had significantly lower mental summary measures at the time of their final measurement compared to their initial measurement. Their physical summary measures were not different across 1.1–16.4 years (median, 6.1 years). HRQOL for the other three groups of patients did not change significantly from the initial to final measurements. The goal of this study was to measure long-term outcomes of HRQOL in diverse syndromes of TMA 5. We anticipated that TTP patients would have lower than normal HRQOL following recovery based on our previous observations 1, 2. The significant decline of mental component summary measures of the TTP patients was consistent with our previously documented progression of minor cognitive impairment 2. We had not previously focused on long-term HRQOL outcomes in the other three syndromes. Patients with quinine-induced TMA had decreased HRQOL similar to patients with TTP, although they did not demonstrate significant worsening of HRQOL across 7.1 years. Patients with a prodrome of bloody diarrhea and suspected Shiga toxin-induced HUS had decreased physical component summary scores at both their initial and final assessments. These data suggest that patients with quinine-induced TMA and adults with possible Shiga toxin-induced HUS, similar to patients with TTP, require careful long-term management following recovery. To provide the context for our observations, we systematically searched for and reviewed published reports describing HRQOL more than one year following recovery from each of these four categories of TMA syndromes. Only five articles were identified; they are described with their citations in Supporting Information Table II. Two previous reports described abnormalities of HRQOL following recovery from TTP; however, patients without documented ADAMTS13 deficiency were included in both reports. Two reports described QOL following pregnancy-related syndromes. One report described impaired vision-related QOL following eclampsia. The other report described impaired HRQOL following preeclampsia and related syndromes, but the method of patient recruitment may have allowed bias for selection of more severely affected patients. One report described decreased mental components of HRQOL following Shiga toxin-induced hemorrhagic colitis and HUS. These five reports had significant differences in patient identification, selection, and severity from our patients. No articles describing HRQOL following recovery from quinine-induced TMA were identified. In contrast to the previously published reports, our patients were all enrolled at the time of their initial clinical diagnosis of TTP or HUS; they had similar clinical features but distinct etiologies. Patients with pregnancy-related syndromes had no significant abnormalities of HRQOL following recovery, an observation distinctly different from the long-term HRQOL abnormalities in the other three groups of patients. Patients with TTP have multiple progressive morbidities following recovery 1, 2. These morbidities are reflected in the data documenting progressive abnormalities of HRQOL with long-term follow-up. Patients who presented with a bloody diarrhea prodrome or who had quinine-induced TMA also had significant impairment of HRQOL with long-term follow-up. These data emphasize the requirement for continued careful observations and management following recovery for these patients. Evaren E. Page,1,2 Yang Jiang2, Deirdra R. Terrell,1 Sara K. Vesely1,James N. George1,2* 1Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; 2Hematology-Oncology Section, Department of Medicine, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma Additional Supporting Information may be found in the online version of this article. Supporting Table 1 Supporting Table 2 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.