Multiple major morbidities and increased mortality during long-term follow-up after recovery from thrombotic thrombocytopenic purpura

Abstract

Key Points• After recovering from TTP, the prevalence of hypertension, depression, and systemic lupus erythematosus and risk of death are increased.• TTP may be a more chronic disorder rather than a disorder of acute episodes and complete recovery.Recovery from acute episodes of thrombotic thrombocytopenic purpura (TTP) appears complete except for minor cognitive abnormalities and risk for relapse. The Oklahoma TTP-HUS (hemolytic uremic syndrome) Registry enrolled 70 consecutive patients from 1995 to 2011 with ADAMTS13 activity <10% at their initial episode; 57 survived, with follow-up through 2012. The prevalence of body mass index (BMI), glomerular filtration rate (GFR), urine albumin/creatinine ratio (ACR), hypertension, major depression, systemic lupus erythematosus (SLE), and risk of death were compared with expected values based on the US reference population. At initial diagnosis, 57 survivors had a median age of 39 years; 45 (79%) were women; 21 (37%) were black; BMI and prevalence of SLE (7%) were greater (P < .001) than expected; prevalence of hypertension (19%; P 5 .463) was not different. GFR (P = .397) and ACR (P = .793) were not different from expected values. In 2011-2012, prevalence of hypertension (40% vs 23%; P 5 .013) and major depression (19% vs 6%; P 5 .005) was greater than expected values. Eleven patients (19%) have died, a proportion greater than expected compared with US and Oklahoma reference populations (P < .05). TTP survivors may have greater risk for poor health and premature death. (Blood. 2013;122(12):2023-2029 Continuing Medical Education online This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and the American Society of Hematology. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http://www.medscape.org/journal/blood; and (4) view/print certificate. For CME questions, see page 2142. Disclosures Johanna A. Kremer Hovinga, Bernhard Lämmle, and James N. George are consultants for Baxter, Inc. for the development of rADAMTS13 as a potential treatment of thrombotic thrombocytopenic purpura (TTP). James N. George is a consultant for Alexion, Inc. for eculizumab as treatment of aHUS. The Associate Editor Leslie V. Parise has served as an advisor or consultant for Bayer, BD Technologies, Biogen, and the Blood Research Institute of Wisconsin; has received gran...

Clinical importance of ADAMTS13 activity during remission in patients with acquired thrombotic thrombocytopenic purpura

“…For comparisons at other remission ADAMTS13 activity levels, the hazard ratio for relapse was not significant. Other morbidities that may occur after recovery from TTP (hypertension, chronic kidney disease, depression, minor cognitive impairment, and death) 10,11 did not appear to be related to remission ADAMTS13 activity (supplemental Table 2). …”

“…[6][7][8] The use of PEGf in SCN has been reported only in single patients and in retrospective cohorts with limited pharmacokinetic analysis. [9][10][11][12] One limitation might derive from severe skin and lung toxicities, which were mainly observed in patients with cyclic neutropenia or glycogen storage disease type Ib but not in classical SCN. 9 In this study, we describe the long-term outcome of PEGf treatment in children with SCN who were poorly compliant to classical G-CSF (filgrastim).…”

Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura

“…3 These microthrombi cause tissue ischemia and organ dysfunction (commonly involving the brain, heart, and kidneys), resulting in early death 4,5 or in long-term complications, such as cognitive deficits, depression, and arterial hypertension, and a shortened life expectancy. [6][7][8][9][10] Treatment of acquired TTP consists of rapid initiation of plasma exchange to remove autoantibodies and ultralarge von Willebrand factor multimers and to replenish ADAMTS13. Immunosuppressive therapy (e.g., glucocorticoids and rituximab) 1,11 inhibits autoantibody formation.…”

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“…In addition, at least one‐half of patients if not more will be at risk for future relapse of the disease 8, 9, 10, 11. Patients that are diagnosed with TTP, even if only one acute episode in the distant past are prone to long‐term complications that include hypertension, depression, headaches, and neurocognitive impairment 12, 13, 14, 15. These complications can lead to significant morbidity and are associated with a decreased life expectancy.…”