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Haematologica 2019 Volume 104(1):166-175
Platelet Biology & its Disorders
Clinical factors and biomarkers predict outcome in patients with immune-mediated thrombotic thrombocytopenic purpura
Elizabeth M. Staley,†1 Wenjing Cao,†1 Huy P. Pham,2 Chong H. Kim,3 Nicole K. Kocher,1 Lucy Zheng,1 Radhika Gangaraju,4 Robin G. Lorenz,1 Lance A. Williams,1 Marisa B. Marques1 and X. Long Zheng1§
1Division of Laboratory Medicine, Department of Pathology, The University of Alabama
at Birmingham, AL; 2Department of Pathology, Keck School of Medicine of the University
3
of Southern California, Los Angeles, CA; Department of Clinical Pharmacy, University of
Colorado Anschutz Medical Campus, Aurora, CO and 4Division of Hematology and Oncology, Department of Medicine, The University of Alabama at Birmingham, AL, USA
EMS and WC Contributed equally to this work.
ABSTRACT
Immune-mediated thrombotic thrombocytopenic purpura is charac- terized by severe thrombocytopenia and microangiopathic hemolytic anemia. It is primarily caused by immunoglobin G type autoantibod- ies against ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. However, reliable markers predictive of patient out- comes are yet to be identified. Seventy-three unique patients with a con- firmed diagnosis of immune-mediated thrombotic thrombocytopenic purpura between April 2006 and December 2017 were enrolled from the Univeristy of Alabama at Birmingham Medical Center. Clinical informa- tion, laboratory values, and a panel of special biomarkers were collected and/or determined. The results demonstrated that the biomarkers asso- ciated with endothelial injury (e.g., von Willebrand factor antigen and collagen-binding activity), acute inflammation (e.g., human neutrophil peptides 1-3 and histone/deoxyribonucleic acid complexes), and activa- tion of the complement alternative pathway (e.g., factors Bb and iC3b) were all significantly increased in patients with acute immune-mediated thrombotic thrombocytopenic purpura compared to those in the healthy controls. Moreover, failure to normalize platelet counts within 7 days or failure to markedly reduce serum lactate dehydrogenase by day 5, low total serum protein or albumin, and high serum troponin levels were also predictive of mortality, as were the prolonged activated partial thrombo- plastin time, high fibrinogen, and elevated serum lactate dehydrogenase, Bb, and sC5b-9 on admission. These results may help to stratify patients for more intensive management. The findings may also provide a frame- work for future multicenter studies to identify valuable prognostic mark- ers for immune-mediated thrombotic thrombocytopenic purpura.
Introduction
Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, but life- threatening, hematologic disorder.1,2 It is characterized by severe thrombocytopenia and microangiopathic hemolytic anemia (MAHA), with or without end organ dam- age. The underlying pathophysiology of iTTP is a functional deficiency of plasma ADAMTS13 activity, resulting from autoantibodies targeting plasma ADAMTS13, a metalloprotease that cleaves von Willebrand factor (VWF).3-5 Therapeutic plasma exchange (TPE) remains the standard of care, in conjunction with immunosuppres- sive therapies that include corticosteroids and rituximab to inhibit acute inflamma- tion and autoantibody production.1,6 However, an in-hospital mortality rate remains as high as ~20%7,8 or less than 10% following the introduction of a novel therapy caplacizumab, an anti-VWF nanobody;9 nearly 30% of surviving patients may expe- rience disease exacerbation10 and/or relapse.7 Currently, clinical factors and biomark- ers predictive of clinical course/outcome are scanty, and their predictive values have yet to be established in diverse patient populations.
Correspondence:
xzheng@uabmc.edu or longzheng01@gmail.com
Received: May 23, 2018. Accepted: August 23, 2018. Pre-published: August 31, 2018.
doi:10.3324/haematol.2018.198275
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/1/166
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