Cerebral Infarction in Immune Thrombotic Thrombocytopenic Purpura Is Associated with Old Age, Hypertension, Smoking, and Anti-ADAMTS13 Ig, But Not with Mortality

Raima Memon; Jingrui Sui; Chen Lin; X. Long Zheng

doi:10.1055/s-0040-1722610

TH Open, Inhaltsverzeichnis

CC BY 4.0 · TH Open 2021; 05(01): e1-e7
DOI: 10.1055/s-0040-1722610

Original Article

Cerebral Infarction in Immune Thrombotic Thrombocytopenic Purpura Is Associated with Old Age, Hypertension, Smoking, and Anti-ADAMTS13 Ig, But Not with Mortality

Raima Memon

¹Division of Laboratory Medicine, Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, United States

,

Jingrui Sui

¹Division of Laboratory Medicine, Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, United States

,

Chen Lin

²Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, United States

,

X. Long Zheng

¹Division of Laboratory Medicine, Department of Pathology, The University of Alabama at Birmingham, Birmingham, Alabama, United States

³Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States

› Institutsangaben

Abstract

Background Neurological involvement is common in patients with immune thrombotic thrombocytopenic purpura (iTTP), but the frequency, risk factors, and outcomes of these with imaging-confirmed stroke in iTTP are not known.

Methods We selected 66 out of 109 iTTP patients with neurological signs and symptoms and reviewed their CT/MRI (computed tomography/magnetic resonance imaging) findings for the evidence of stroke and other clinical information in Alabama TTP Registry.

Results Of these, 52 (78.8%) had their CT/MRI done on admission in whom 22 (42.3%) were positive for multiple acute or chronic infarcts. The patients with image-confirmed ischemic stroke were older, and appeared to be associated with a history of hypertension and smoking. Additionally, patients with imaging-confirmed stroke showed higher plasma concentrations of anti-ADAMTS13 IgG than those without stroke. More interestingly, there was no statistically significant difference in the rate of exacerbation and 60-day mortality between those with and without stroke.

Conclusion Ischemic cerebral infarcts are common findings in brain imaging studies of patients with acute iTTP; old age, chronic hypertension, and smoking, as well as high plasma concentrations of anti-ADAMTS13 IgG may be the potential risk factors for cerebral infarction in these patients. The presence of image-confirmed ischemic stroke, however, does not predict exacerbation and 60-day mortality, although the long-term effect of such ischemic brain damage on cognitive function and quality of life remains to be determined.

Keywords

thrombotic thrombocytopenic purpura - inflammatory mediators - ADAMS/ADAMTS13 - von Willebrand factor - cerebrovascular disease - autoimmune diseases - autoantibodies

Volltext

Referenzen

References
1 Moake JL. Thrombotic thrombocytopenic purpura: the systemic clumping “plague”. Annu Rev Med 2002; 53: 75-88
2 Zheng XL, Sadler JE. Pathogenesis of thrombotic microangiopathies. Annu Rev Pathol 2008; 3: 249-277
3 Terrell DR, Williams LA, Vesely SK, Lämmle B, Hovinga JA, George JN. The incidence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: all patients, idiopathic patients, and patients with severe ADAMTS-13 deficiency. J Thromb Haemost 2005; 3 (07) 1432-1436
4 Staley EM, Cao W, Pham HP. et al. Clinical factors and biomarkers predict outcome in patients with immune-mediated thrombotic thrombocytopenic purpura. Haematologica 2019; 104 (01) 166-175
5 Rinkel GJ, Wijdicks EF, Hené RJ. Stroke in relapsing thrombotic thrombocytopenic purpura. Stroke 1991; 22 (08) 1087-1089
6 Downes KA, Yomtovian R, Tsai HM, Silver B, Rutherford C, Sarode R. Relapsed thrombotic thrombocytopenic purpura presenting as an acute cerebrovascular accident. J Clin Apher 2004; 19 (02) 86-89
7 Boattini M, Procaccianti G. Stroke due to typical thrombotic thrombocytopenic purpura treated successfully with intravenous thrombolysis and therapeutic plasma exchange. BMJ Case Rep 2013; 2013: bcr2012008426
8 Wiernek SL, Jiang B, Gustafson GM, Dai X. Cardiac implications of thrombotic thrombocytopenic purpura. World J Cardiol 2018; 10 (12) 254-266
9 Benhamou Y, Boelle PY, Baudin B. et al; Reference Center for Thrombotic Microangiopathies, Experience of the French Thrombotic Microangiopathies Reference Center. Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. J Thromb Haemost 2015; 13 (02) 293-302
10 Atreya AR, Arora S, Sivalingam SK, Giugliano GR. ST segment elevation myocardial infarction as a presenting feature of thrombotic thrombocytopenic purpura. J Cardiovasc Dis Res 2012; 3 (02) 167-169
11 Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med 1991; 325 (06) 398-403
12 Zheng XL, Kaufman RM, Goodnough LT, Sadler JE. Effect of plasma exchange on plasma ADAMTS13 metalloprotease activity, inhibitor level, and clinical outcome in patients with idiopathic and nonidiopathic thrombotic thrombocytopenic purpura. Blood 2004; 103 (11) 4043-4049
13 Page EE, Kremer Hovinga JA, Terrell DR, Vesely SK, George JN. Thrombotic thrombocytopenic purpura: diagnostic criteria, clinical features, and long-term outcomes from 1995 through 2015. Blood Adv 2017; 1 (10) 590-600
14 Nunez Zuno JA, Khaddour K. Thrombotic Thrombocytopenic Purpura Evaluation and Management. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2020
15 Scully M, Cataland S, Coppo P. et al; International Working Group for Thrombotic Thrombocytopenic Purpura. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost 2017; 15 (02) 312-322
16 Scully M, Hunt BJ, Benjamin S. et al; British Committee for Standards in Haematology. Guidelines on the diagnosis and management of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies. Br J Haematol 2012; 158 (03) 323-335
17 Saha M, McDaniel JK, Zheng XL. Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics. J Thromb Haemost 2017; 15 (10) 1889-1900
18 Zheng XL, Vesely SK, Cataland SR. et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost 2020; 18 (10) 2486-2495
19 Zheng XL. ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura. Annu Rev Med 2015; 66: 211-225
20 Lämmle B, Kremer Hovinga JA, Alberio L. Thrombotic thrombocytopenic purpura. J Thromb Haemost 2005; 3 (08) 1663-1675
21 Furlan M, Robles R, Lämmle B. Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis. Blood 1996; 87 (10) 4223-4234
22 Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 1998; 339 (22) 1585-1594
23 Rock GA, Shumak KH, Buskard NA. et al; Canadian Apheresis Study Group. Comparison of plasma exchange with plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Engl J Med 1991; 325 (06) 393-397
24 Burrus TM, Wijdicks EF, Rabinstein AA. Brain lesions are most often reversible in acute thrombotic thrombocytopenic purpura. Neurology 2009; 73 (01) 66-70
25 Fugate JE, Claassen DO, Cloft HJ, Kallmes DF, Kozak OS, Rabinstein AA. Posterior reversible encephalopathy syndrome: associated clinical and radiologic findings. Mayo Clin Proc 2010; 85 (05) 427-432
26 Rock G. Plasma exchange in the management of thrombotic thrombocytopenic purpura. Vox Sang 2002; 83 (Suppl. 01) 141-143
27 Peyvandi F, Scully M, Kremer Hovinga JA. et al; TITAN Investigators. Caplacizumab for acquired thrombotic thrombocytopenic purpura. N Engl J Med 2016; 374 (06) 511-522
28 Scully M, Cataland SR, Peyvandi F. et al; HERCULES Investigators. Caplacizumab treatment for acquired thrombotic thrombocytopenic purpura. N Engl J Med 2019; 380 (04) 335-346
29 Zheng XL, Vesely SK, Cataland SR. et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost 2020; 18 (10) 2496-2502
30 Jestin M, Benhamou Y, Schelpe AS. et al; French Thrombotic Microangiopathies Reference Center. Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura. Blood 2018; 132 (20) 2143-2153
31 Westwood JP, Thomas M, Alwan F. et al. Rituximab prophylaxis to prevent thrombotic thrombocytopenic purpura relapse: outcome and evaluation of dosing regimens. Blood Adv 2017; 1 (15) 1159-1166
32 Westwood JP, Webster H, McGuckin S, McDonald V, Machin SJ, Scully M. Rituximab for thrombotic thrombocytopenic purpura: benefit of early administration during acute episodes and use of prophylaxis to prevent relapse. J Thromb Haemost 2013; 11 (03) 481-490
33 Froissart A, Buffet M, Veyradier A. et al; French Thrombotic Microangiopathies Reference Center, Experience of the French Thrombotic Microangiopathies Reference Center. Efficacy and safety of first-line rituximab in severe, acquired thrombotic thrombocytopenic purpura with a suboptimal response to plasma exchange. Crit Care Med 2012; 40 (01) 104-111
34 Schleinitz N, Ebbo M, Mazodier K. et al. Rituximab as preventive therapy of a clinical relapse in TTP with ADAMTS13 inhibitor. Am J Hematol 2007; 82 (05) 417-418
35 Bresin E, Gastoldi S, Daina E. et al. Rituximab as pre-emptive treatment in patients with thrombotic thrombocytopenic purpura and evidence of anti-ADAMTS13 autoantibodies. Thromb Haemost 2009; 101 (02) 233-238
36 Scully M, McDonald V, Cavenagh J. et al. A phase 2 study of the safety and efficacy of rituximab with plasma exchange in acute acquired thrombotic thrombocytopenic purpura. Blood 2011; 118 (07) 1746-1753
37 Montoya RC, Poiesz BJ. Rituximab as prophylaxis in chronic relapsing thrombotic thrombocytopenic purpura: a case report and review of the literature. Blood Coagul Fibrinolysis 2012; 23 (04) 338-341
38 Sui J, Cao W, Halkidis K. et al. Longitudinal assessments of plasma ADAMTS13 biomarkers predict recurrence of immune thrombotic thrombocytopenic purpura. Blood Adv 2019; 3 (24) 4177-4186
39 Martino S, Jamme M, Deligny C. et al; French Reference Center for Thrombotic Microangiopathies. Thrombotic thrombocytopenic purpura in Black People: impact of ethnicity on survival and genetic risk factors. PLoS One 2016; 11 (07) e0156679
40 Terrell DR, Motto DG, Kremer Hovinga JA, Lämmle B, George JN, Vesely SK. Blood group O and black race are independent risk factors for thrombotic thrombocytopenic purpura associated with severe ADAMTS13 deficiency. Transfusion 2011; 51 (10) 2237-2243
41 van den Born BJ, van der Hoeven NV, Groot E. et al. Association between thrombotic microangiopathy and reduced ADAMTS13 activity in malignant hypertension. Hypertension 2008; 51 (04) 862-866
42 van den Born BJ, Honnebier UP, Koopmans RP, van Montfrans GA. Microangiopathic hemolysis and renal failure in malignant hypertension. Hypertension 2005; 45 (02) 246-251
43 Chaturvedi S, Carcioppolo D, Zhang L, McCrae KR. Management and outcomes for patients with TTP: analysis of 100 cases at a single institution. Am J Hematol 2013; 88 (07) 560-565
44 Chaturvedi S, Bhatia N. Predictors of survival in thrombotic thrombocytopenic purpura. Haematologica 2013; 98 (05) e58
45 Ferrari S, Scheiflinger F, Rieger M. et al; French Clinical and Biological Network on Adult Thrombotic Microangiopathies. Prognostic value of anti-ADAMTS 13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS 13 activity. Blood 2007; 109 (07) 2815-2822
46 Cao WJ, Pham HP, Williams LA. et al. Increased plasma levels of human neutrophil peptides (HNPs) and complement activation markers in patients with acquired thrombotic thrombocytopenic purpura (TTP). Blood 2015; 126: 1147
47 Fuchs TA, Kremer Hovinga JA, Schatzberg D, Wagner DD, Lämmle B. Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies. Blood 2012; 120 (06) 1157-1164
48 Lin C, Memon RA, Sui J, Zheng XL. Identification of biomarkers in patients with thrombotic thrombocytopenic purpura presenting with large and small ischemic strokes. Cerebrovas Dis EXTRA 2020. In press
49 Sui J, Lu RN, Halkidis K. et al. Plasma levels of S100A8/A9, histone/DNA complexes, and cell-free DNA are associated with mortality in patients with immune thrombotic thrombocytopenic purpura. Thromb Haemost 2020; (e-pub ahead of print)